AccessPoint from IMS Health

AccessPointNews, views and insights from leading experts in RWE and HEOR

VOLUME 4, ISSUE 8MAY 2014

IMS REAL-WORLD EVIDENCE SOLUTIONS ANDHEALTH ECONOMICS & OUTCOMES RESEARCH

New gateways to real-world data

Scandinavia leads the way

Research data selectionAccounting for disparities is key

Oncology poised forevidence transformation

Payment by useFinding a path to broader access

High-value targeted therapies Accessing emerging markets

Oncology Special EditionInnovation demands RWE evolution

WelcomeI hope you find our latest edition of AccessPoint informative andthought provoking. As always, we explore dynamics shaping theHEOR, safety and RWE landscape. Our decision to dedicate theentire issue to oncology reflects both its importance acrosshealthcare stakeholders and the recent, rapid innovations. We are entering a time of greater insight – and hope – about theprogress being made towards a cure for cancer. Our explorationhas highlighted four themes

• Recent innovations signal a need to evolve and tailor RWE.Oncology outcomes research is delivering a deeperunderstanding of cancer and demonstrable impact. But asdrug development broadens in developed and emergingmarkets such as Asia, and the scrutiny of value intensifies, we explore the need for new measures and tailored approaches.

• Data access is expanding RWE but focused application is key.Robust, longitudinal, linked real-world data is helping tocomplete evidenced-based patient pathways. The potential ofScandinavia as a global platform, pan-European collaborativeinitiatives, and creation of data pools from US oncologypractices, are optimizing resources for improved outcomesresearch in cancer. But our comparison of linked datasetsreinforces the need for a discerning approach to data selection.

• Methodologies are uniquely evolving in oncology. Unique demands on evidence requirements in oncology aredriving innovative methods for demonstrating economicimpact. Examples include adaptive approaches to modelingcost-effectiveness and budget impact, and the developmentof disease-specific co-morbidity scales in blood borne cancers.

• Emerging potential for RWE can further extend its value.Despite recent advancements many areas of research remainunderserved, positioning the market for significantlyexpanded use of RWE. It can support optimal drug utilization,inform efficacy on an ongoing basis, and broaden access tonew cancer treatments by enabling innovative contractingbased on differential patient value.

At IMS Health we are passionate about improving patientoutcomes and advancing healthcare and hope our insights willhelp to accelerate further innovations in cancer.

Jon ResnickVice President and General Manager Real-World Evidence SolutionsIMS [email protected]

AccessPoint is published twice yearly by the IMS Real-World Evidence (RWE) Solutions and Health Economics & Outcomes Research (HEOR) team. VOLUME 4, ISSUE 8. PUbLISHEd MAY 2014.

IMS HEALTH 210 Pentonville Road, London N1 9JY, UK Tel: +44 (0) 20 3075 4800 • www.imshealth.com/[email protected]

©2014 IMS Health Incorporated and its affiliates. All rights reserved.Trademarks are registered in the United States and in various other countries.

IMS REAL-WORLD EVIDENCE SOLUTIONS & HEOR

“We are entering a time of greater insight – and hope – about theprogress being made towards a cure for cancer.”

ACCESSPOINT • VOLUME 4 ISSUE 8 PAGE 1

Recent innovations signal a need to evolve and tailor RWETrends in cancer care and global implications page 8Evidence-based insights in oncology page 14High-value oncology targeted therapies in Asia Pacific page 46

RWE is expanding but focused application is keyTransforming oncology outcomes research in Sweden page 21Future access to innovative oncology drugs in the EU page 32Research questions drive data selection page 40

Methodologies are uniquely evolving in oncologyUnderstanding treatment patterns in prostate cancer page 36Economic modeling for hematological cancers in Latin America page 56Developing disease-specific scales for leukemia page 59

Emerging potential for RWE can further extend its valuePayment by use: Achieving a new value paradigm for oncology page 26Drug utilization in oncology page 51Connecting advancements to strengthen decision making page 7

NEWS2 IMS INSTITUTE ANALYZES TRENDS

3 ONCOLOGY HEADS R&D PIPELINE

4 POST-AUTHORIZATION EFFICACY

5 NEW INSIGHTS INTO PATIENT JOURNEY

7 STRENGTHENING DECISION MAkING

PROJECT FOCUS56 HEMATOLOGICAL CANCERS

Demonstrating value in Latin America59 CHRONIC LYMPHOCYTIC LEUkEMIA

Understanding the burden of co-morbidities

IMS RWES & HEOR OVERVIEW62 ENABLING YOUR REAL-WORLD SUCCESS

Solutions, locations and expertise

AccessPointNews, views and insights from leading experts in RWE and HEOR

PAGE 2 IMS REAL-WORLD EVIDENCE SOLUTIONS & HEOR

NEWS | IMS INSTITUTE INSIGHTS

IMS Institute for Healthcare Informatics brings oncology to the forefront of its latestresearch with unique insights into market trends

Cancer innovation heads new analyses onhealthcare dynamics globally

The IMS Institute for Healthcare Informatics hasconducted and published a wide range ofgroundbreaking research derived from granularanalysis of information. Addressing key issues inhealthcare and the use of medicines, it continuesto enlighten with unique insights.

SPOTLIGHT ON ONCOLOGYGlobal marketThe Institute’s latest report, “Innovation in cancer care andimplications for health systems: Global oncology trendreport” offers the most comprehensive review of currenttrends in the oncology market. Published in May, 2014, itconsiders the state of innovation in therapeutics, measuresof the value of treating cancer, pricing dynamics and, in theUS, changes that are impacting the delivery of medicines inthis area. It also assesses the potential for biosimilars toreshape the oncology market. Among its key findings are:

• Moderation of global market growth for oncologyspending

• More targeted innovation in cancer therapies • Increased payer scrutiny of pricing and the value of

treatments • Growing impact of biosimilars and non-original biologics

“Oncology is bringing higher levels of uncertainty to healthsystems across the globe – both in terms of the nature and rateof innovative treatments, and levels of reimbursement forpatient care. The reality is that countries struggle to bringtogether the right combination of preventive measures andclinical interventions, including vaccines, diagnostics andtherapeutics.”

Advancing oncology in IndiaComplementing the broader cancer report, a recent studyfrom the IMS Institute in India, “Defeating India’s silentkiller: The fight to diagnose and treat cervical cancer”,brings a perspective on key aspects relating to diseaseburden, screening, diagnosis and treatment of this common but preventable cancer, sharing learnings fromother countries and providing recommendations foreffective control.

“India accounts for nearly one-third of global cervical cancer deaths, despite the fact that it is one of the fewcarcinomas that are preventable and curable to a large extent.The IMS Institute India believes there is an urgent need to strengthen the existing health systems in orderto improve accessibility to primary and secondary preventionand screening measures.”

HEALTHCARE SPENDING, TECHNOLOGY ANDSOCIAL MEDIA Other recent topics covered by the Institute include:

• Medicine use and shifting costs of healthcare(April, 2014). The first view of total system spending onmedicines in the US in 2013, with a focus on theutilization of key healthcare services, patient costs formedicines and shift in the types of employer-providedinsurance.

• Riding the information technology wave in lifesciences (March, 2014). An outlook on how the currenttechnology wave – defined in terms of cloud-basedstorage, new applications, systems integration andembedded analytics – will be harnessed by life sciencescompanies in their commercialization activities and whythis is necessary for them to succeed in bringinginnovative diagnostic and treatment options to patients.

• Engaging patients through social media (January, 2014).A review of the impact of social media on the use of medicines, including the role that pharmaceuticalmanufacturers are playing in leveraging social mediaplatforms as part of their business model.

Copies of these reports and other insights are availablefrom the IMS Institute website at www.theimsinstitute.org,together with further information on its extensive rangeof research activities.

Innovation in cancer caresee our R&D report on page 3 and Insights feature on page 8to discover more findings from the IMS Institute cancertrends report.


R&D TRENDS IN ONCOLOGY | NEWS

Oncology dominates R&d pipeline but reportuncovers key shifts

New dynamics are changing the focus of drug development activities in cancer

Immunology therapy has become a strong area ofrecent investment, based on current success in clinicaltrials and a promising outlook.

• Clustering of innovation around cancer types.Advances in underlying science have led to innovationclusters around certain cancer types as new moleculartargets have been identified. This has been witnessed bythe recent developments in therapies for metastaticmelanoma, prostate cancer and lung cancer.

• An R&D focus on factors other than prevalence.Currently, much of the late-stage pipeline is centered onhigher prevalence tumors, such as breast, lung andcolorectal cancer (Figure 1). However, another key driverof innovation is unmet needs which are not always tiedto prevalence; tumor types with lower prevalence, suchas ovarian, leukemia, stomach and liver cancers also arebeing actively pursued.

• Growing number of accelerated approvals. After aninnovation slowdown through 2008, the oncologypipeline has increased with more accelerated approvals;cancer products comprise 34% of Breakthrough Therapy Designations (BTDs), a fast-track processallowing investigational agents to receive FDA approvalas early as 3 months ahead of schedule. Together with anew Uk Early Access to Medicines program, this couldplay a significant role in accelerating oncology drugdevelopment and approval in the future.

A copy of the full report,published May, 2014, is availableto download at the Institutewebsite www.theimsinstitute.org

Source: IMS R&D Focus, Globocan

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FIGURE 1: PHASE III TRIALS BY CANCER TYPE AND 5-YEAR DISEASE PREVALENCE

After several years of significant innovation,oncology still represents the largest area of drugdevelopment according to a new report from the IMS Institute for Healthcare Informatics. There are nearly 2,000 products for cancer in thepipeline – four times the number of the nextlargest therapeutic class. However, despite thehigh level of pharma investment, fewer of these drugs are progressing to phase II and III,underscoring the challenges of achievingsuccessful results in the clinic. The comprehensive evaluation of current market trends inoncology, “Innovation in cancer care and implicationsfor health systems: Global oncology trend report”, notesthat while 22 new molecular entities (NMEs) for cancer havebeen launched over the past two years, the high failure rate and increasing competition make it risky and expensiveto bring new cancer therapies to patients. Among some ofthe report’s key findings in this area are:

• Increasingly targeted nature of innovation in cancertherapies. The research pipeline is overwhelminglypopulated with targeted therapies which havedramatically increased their share of the oncologymarket in the past ten years. This reflects a clear shiftaway from biologics; the majority of NMEs approved in cancer over the last decade have been non biologics.

Innovation in cancer careSee our insights feature on page 8 to discover morefindings from the IMS Institutecancer trends report.

NEWS | POST-AUTHORIZATION EFFICACY

continued opposite


Partnership initiatives accelerate move towardscontinuous monitoring of efficacy and safety

IMS Health/ENCePP collaboration informs and shapes policy debate to advancepharmacovigilance in Europe

Reinforcing a commitment to promotingexcellence in pharmacoepidemiological andpharmacovigilance (PV) research, IMS Health hasbeen working with leading scientific network,ENCePP,1 on initiatives to further strengthenEurope’s comprehensive legislation for drugsafety monitoring. The company partners withENCePP to develop and disseminate standardsin this area and is a member of the ENCePP-HTAworking group established in collaboration with EUnetHTA.2 Recommendations arising fromthis collaboration are helping to guide regionalpolicy on post-authorization efficacy studies(PAES) and to facilitate their more efficientimplementation.

DELEGATED ACTProviding direction on PAES Europe’s well-established and highly respected regulatoryframework for PV, reformalized by new laws andguidelines in 2010 and 2012, has been recentlyaugmented by the adoption of a delegated act (DelegatedRegulation (EU) No 357/2014). Effective from 30 April,2014, this clarifies the circumstances in which post-authorization efficacy studies (PAES) may be required byregulatory authorities. PAES are studies conducted after a drug has beenapproved to gather additional information on efficacy.They can be requested when questions exist that can onlybe addressed once a product is in real-world use or whenthey arise post-authorization.3 Increased emphasis onPAES reflects growing recognition that while safety is the

principal focus of PV, any new information or signalsdetected could potentially affect a product’s overallbenefit:risk balance.4

The enactment follows a period of extensive publicconsultation by the European Commission to gatherstakeholder views, including those of industryassociations, manufacturers, public institutions, andacademia and healthcare professionals. Input provided byENCePP, in response to the request for feedback, was ledand coordinated by IMS Health as part of the ENCePP-HTAworking group. Their recommendations and advice, whichincluded accounting for the requirements of HTA bodies,establishing a common standard for PAES, and ensuringdissemination of study results, has helped to shape, andis reflected in, the final version of the Act.

Identifying potential for efficiencies in post-authorization research The new legislation marks a key step forward in thecontinuous assessment of both efficacy and safety ineveryday practice in Europe through the use of PAES andPASS (post-authorization safety studies) to ensure that anyunintended harmful effects of a medicine do not offset itsintended clinical benefits. Further supporting policy progress in this area, IMS Health,as a member of the ENePP-HTA working group, recentlyjoined representatives from the European MedicinesAgency (EMA), the French Haute Autorité de Santé(HAS) and the University of Bordeaux, to lead a workshop exploring the potential benefits of increased regulatory/HTA agency collaboration in post-authorization studies.5 This is increasingly valid giventhe overlap in their requirements for this research. Heldduring the ISPOR 16th Annual European Congress in Dublin in November, 2013, the workshop consideredcollaborative opportunities to avoid duplication of

1 European Network of Centres for Pharmacoepidemiology and Pharmacovigilance 2 European network for Health Technology Assessment 3 Specifications for additional efficacy studies for medicines published in the Official Journal of the EU http://www.ema.europa.eu4 http://ec.europa.eu/health/files/pharmacovigilance/2013_pc_paes/summary_public_consultation.pdf5 Post-authorisation studies in Europe: Bridging the gap between regulatory and health technology assessment (HTA) stakeholder needs for additional evidence. ISPOR

16th Annual European Congress, Dublin, Ireland, 4 November, 2013


IMS HEALTH AND PYGARGUS | NEWS

Scandinavia opens gateway to understanding the entire treatment journey

Marking a new milestone in helping healthcaredecision makers identify, link and interpret real-world outcomes in near real time, IMS Healthrecently announced the acquisition of Pygargus AB,a leading independent Scandinavian life scienceconsultancy specializing in RWE. The move provides researchers with customized access touniquely robust and granular anonymous patient-level data.With a history of 20 years, this data enables a comprehensiveunderstanding of the patient treatment pathway andempowers unique RWE insights when linked to national anddisease-specific registries. Generated from Sweden and thebroader Nordic region, it can also inform science anddecision making globally with coverage across all diseaseareas, led by cancer.Traditionally, the disconnected nature of healthcare dataacross various sites of service delivery has limited thepotential of outcomes research to deliver meaningful,

holistic insights. In oncology, this challenge has beenmagnified by the scarcity of credible, long-term datafollowing-up patients and their treatment experience over time. In this respect, the Nordic region is exceptionally well-placedas a setting for real-world data, with several key advantagescompared to other research environments:

• Well-structured public healthcare

• Long established high-quality EMRs

• National registry environment

• Mature regulatory research framework

REAL-WORLD INSIGHTSThe new offering combines IMS Health’s market-leadingcapabilities in RWE with proprietary technology developedby Pygargus for extracting and integrating patient-anonymous information from such sources as EMR, healthregistries and claims databases (Figure 1, overleaf ).

continued from previous page

research effort and stimulate more effective use ofresources. These included the possibility of centering suchinitiatives on work packages being developed byEUnetHTA and ENCePP as a means of ensuring that thescope and design of additional studies are sufficient tomeet the needs of both regulators and HTA bodies.

MOVING FORWARD The concepts discussed at this initial workshop are beingcarried forward for further exploration at a workshop to beheld during the 30th Annual Meeting of ISPE later in 2014.This will consider examples of initiatives that are ongoingin the EU and Asia to bridge gaps between regulatory andHTA requirements, and the potential for globalharmonization of methodological standards in post-authorization studies.

For further information on IMS Health capabilities indeveloping combined strategies for safety and HTA or forclarification on PAES, please email Massoud Toussi [email protected]

Find out moreDelegated Acthttp://www.ema.europa.eu

Public Consultationhttp://ec.europa.eu/health/files/pharmacovigilance/2013_pc_paes/summary_public_consultation.pdf

ENCePP responsehttp://ec.europa.eu/health/files/pharmacovigilance/2013_pc_paes/encepp.pdf

ISPOR workshop W31 on post-authorization studies http://www.ispor.org/Events/EventInformation.aspx?eventid=42&p=127

continued on next page


NEWS | IMS HEALTH AND PYGARGUS

Scandinavia opens gateway to understanding the entire treatment journey continued from previous page

COMPLETING THE CANCER PATIENT PATHWAYSpecifically in oncology, the Nordics are a key source ofqualitative patient-level health information on diseasediagnosis and management. The region has a 10-year historyof EMRs and long established National Cancer Registries.Sweden, for example, has more than 20 robust, tumor-specific registries available for oncology research in cancerssuch as breast, gynecological, hematological, lung andprostate. These include complementary health informationaround the time of diagnosis and during disease progression.Covering all diagnosed cases of cancer over more than 50years, the data can be linked via unique patient identifiersfrom birth to death. By connecting patient attributes totherapies and outcomes, this high-quality linked datasetdelivers the deepest granularity in oncology observed in anysingle European market, to inform global research in moreinnovative and streamlined ways. The complete pathway isenabled with information that includes:• Co-morbidities• Surgical procedures & other measures• Socio-economic variables • Metastasis development (or progression of

cancer/tumor)• Death (and underlying cause)• Hospitalizations (length of stay, etc)• Medical treatments• Family disease history• Patient histology

• Tumor characteristics (TNM, staging information)• All laboratory test results• Risk factors & performance status

REAL-WORLD IMPACTPygargus has a history of developing and contributing tolarge-scale, scientifically credible epidemiology andoutcomes studies which rely on a complete view of thepatient journey, to meet specific needs in epidemiology,outcomes research and pharmacovigilance across a rangeof disease areas. Some of these have led to breakthroughresearch. Recent cohorts from executed studies haveextracted anonymous patient-level health informationrelated to 1.6 million patients with cardiovascular disease,approximately 90,000 patients with diabetes, andapproximately 7,000 patients with prostate cancer.The acquisition adds to IMS Health’s deep outcomesresearch expertise and scalable RWE platform supporting abroad range of applications, from epidemiological studiesand comparative effectiveness and safety research, tocommercial analytics.

For further information on the IMS Health/Pygargus RWEplatform and opportunities to efficiently link and analyzecomplex datasets in oncology and other disease areas inScandinavia, please email Patrik Sobocki [email protected]

ecords data R

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Tailored study database Tailored study database Tailored study database

FIGURE 1: TAILORED DATABASE USING CUSTOMIZED EXTRACTION PROGRAM


IMS HEALTH AT ISPOR | NEWS

Unprecedented developments in the magnitude,reach and availability of real-world data arecreating new opportunities for HEOR to supportfaster, more efficient decision making. Butalongside the potential there are significantchallenges in deriving the maximum value.These and other advancements impacting technologyassessments drove the topics of debate at the ISPOR 16thAnnual European Congress in November, 2013. More than3,800 participants gathered in Dublin to consider progresstowards “Finding the Right Pieces for the Health CareDecision-Making Puzzle” and discover the latest researchfrom more than 1,800 podium and poster presentations.

INTERSECTION OF RWE AND HEALTH ECONOMICS Leading an extensive range of IMS Health activities at ISPORwas the IMS Health Symposium,“The intersection of healtheconomics and real-world evidence: Validatinghealthcare decision making.” The panel included seniorindustry guest speakers Dr Melvin Olson, Global Head ofHEOR for Neuroscience and Ophthalmology at Novartis;and Dr Patrik Sobocki, CEO at Pygargus AB; and IMS Healthexperts, Dr Jacco keja and Dr Mark Lamotte. The session offered insights into the importance of RWE andits potential to bring about a step change in traditionalapproaches to health economics. Referencing case studyexamples in cancer and cardiovascular disease, thepresentations explored:

• Role of RWE in validating healthcare decision making

• Current gaps in RWE use from an industry perspective

• Power of high quality patient-level Nordic data

• Synergies between RWE and health economics

• Potential for improved economic modeling using RWEAmong the key outputs from the discussion were:

• RWE has potential but perceptions must change.The goal of health economics is to present and projectreal-world effectiveness in an economic framework,allowing informed decision making for cost-effectiveresource allocation. Heath economic and outcomesresearchers have for too long relied on internal validityand clinical trial data. RWE allows for better estimatesof transition rates and probabilities, enabling a move

ISPOR congress explores stimulants of change in the adoption of new healthcare technologies

Connecting advancements in RWE to strengthen healthcare decision making

from effectiveness projection to effectivenessmeasurement. However, perceptions ofobservational research must change in ways thatbuild the reputation and practical application of RWE.

• RWE boundaries must be expanded and standardsestablished. Despite its growing importance, RWE isnot being applied creatively or strategically; it is timeto challenge just how it could and should be used.The RWE strategy of the future should be acomprehensive plan across the lifecycle usingevidence from multiple sources with a focus onestablishing partnerships, involving kOLs, and onimproving internal awareness and communication aswell as external awareness and education.

• RWE generation needs to start early and build overtime. Evidence platforms (data marts) are a keyenabler, allowing the creation of larger, morepowerful datasets and more cost-effective access,based on housing and linking multiple data sources(eg, pharmacy and claims, hospital, EMRs, RCTs,observational research, PRO studies).

• RWE needs can be uniquely met in the Nordics.Scandinavia brings the opportunity to link real-timeanonymous patient-level data for the creation ofdatasets to answer multiple research questions. The combination of data from EMRs with registriesallows a complete picture of the patient in terms ofclinical measures and demographics. Examples existof its tangible impact on pre-launch activities and ininforming economic models.

• RWE can drive true cost-effectiveness models.Health economic modelers need to become moreaware of what RWE data is available and where it canbe found, instead of relying solely on data fromclinical trials or the literature more generally. Thismeans breaking down silos and doing more thanbefore to build a model that incorporates allavailable data. This will make it possible to movemore and more away from a cost-efficacy modeltowards a real cost-effectiveness model.

Proceedings of the symposium can be obtained from Angelika Boucsein [email protected]

Page 1 IMS HEALTH ECONOMICS AND OUTCOMES RESEARCH

INSIGHTS | RWE TRENDS

Cancer is a leading priority for health systems globally, and stakeholderscontinue to seek the right combination of measures to assess treatments andinvestments. A recent comprehensive study of trends, innovation and spend inoncology, from the IMS Institute for Healthcare Informatics, provides a stepforward in that search.

Kjel Johnson, PHARM.D, BCPS, FCCP, FAMCP is Vice President Global Oncology, IMS [email protected]

The author


OUTCOMES - Issue 1 Page 1

RWE TRENDS | INSIGHTS

Implications for global healthcare systemsThe IMS Institute, in collaboration with an external advisory board, undertook acomprehensive evaluation of current market trends for cancer medicines. LeveragingIMS Health databases, analytics platforms and forecasting tools, as well as publishedliterature, the study included a review of innovation in therapeutics, measures of thevalue of treating cancer and pricing dynamics globally. It also analyzed dynamicsimpacting the delivery of oncology medicines in the US specifically. This articlehighlights several of its key findings, including the changes in oncology spendoccurring in parallel to evolving innovations in treatment.

ONCOLOGY SPENDING Although oncology spending has increased consistently over the past few years, the trend has moderated. Cancer spend has increased over the past decade to reach $91bn in 2013. The advent of targeted therapies marked aninitial upsurge in the early 2000s, followed by slowing growth rates. A series of successful launches in 2012 and 2013created a more recent uptick, reflecting innovations in previously underserved tumor types, such as castration-resistantprostate cancer (CRPC) and metastatic melanoma (Figure 1). Nevertheless, current trends demonstrate a compoundannual growth rate (CAGR) for the overall oncology class (including supportive care) of 5.4% worldwide. For Europespecifically – where stringent regulatory processes may dampen approvals and utilization – it is less than 5%. In the US,despite less stringent reviews, it is only 3.5%.

Innovation in cancer care


Oncology Market Dynamics in Key Markets

FIGURE 1: GLOBAL ONCOLOGY MARKET DYNAMICS 2003-2013




To provide a truly comprehensive evaluation of oncology spend, both therapeutic oncology and supportive care agentswere included in the analysis. It also included generic and branded utilization.

As the report demonstrates, total spend reflects more than drug pricing alone, notably the distribution channel in the US.Specifically, the physician office is generally the most economical infusion setting in the US for all stakeholders involved,but administration in the hospital outpatient setting is increasing despite being more costly than all other channels.

Furthermore, from a real-world perspective, oncology is not practiced in a vacuum and oncologics are seldom used underperfect conditions in realization of their estimated costs. Instead, a disparity between ideal utilization (>85% of the approveddose) and actual utilization is driven by factors such as dose intensity, patient tolerance and affordability to the patient.

Inadequate relative dose intensity (RDI) can impact the cost of care by significantly diminishing an agent’s potential forimproved outcomes.1,2 Represented by the amount of drug administered per unit of time, expressed as the fraction of thatused in the standard regimen, an RDI of <85% in clinical practice essentially provides placebo-level effectiveness at nearly thesame cost.1,2 This phenomenon exists independently of drug pricing and is unfortunately common in real-world scenarios.3

PIPELINE FRUITIONLandmark discoveries have helped foster an abundant cancer pipeline but failure rates remain high. The R&D drug pipeline is overwhelmingly populated by oncology therapies, with nearly 30% of the 6,357 activeproducts to date seeking a cancer-related indication. A record 11 NMEs were approved globally in oncology in 2012followed by 10 approvals in 2013. However, only ~10% of investigational agents that continue on to late-stagedevelopment receive eventual approval (Figure 2).

These launches reflect the trend toward waves of therapies being introduced by cancer type, such as the clusters of approvalsfor renal cell carcinoma a few years ago and in metastatic melanoma and CRPC more recently. When a new pathway ormolecular target for treating a particular tumor is identified, numerous manufacturers often choose to exploit the pathway indeveloping new therapeutics. Thus, following the approval and hugely successful launch of Yervoy (ipilimumab) formetastatic melanoma in 2011, it was not surprising to see a host of other agents with similar indications either approved(Zelboraf (vemurafenib); Mekinist (trametinib); Tafinlar (dabrafenib)) or nearing approval in late-stage clinical trials.

FIGURE 2: CHARACTERIZATION OF THE ONCOLOGY-SPECIFIC SHARE OF THE ACTIVE DRUG PIPELINE

1 Bonadonna G, Zambetti M, Valagussa P, et al. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: The results of 20 years of follow-up. N Engl J Med, 1995; 332:901–906

2 kwak LW, Halpern J, Olshen RA, Horning SJ. Prognostic significance of actual dose intensity in diffuse large-cell lymphoma: Results of a tree-structured survival analysis. J Clin Oncol, 1990; 8:963–977

3 Johnson k. The most costly chemotherapy today. Managed Care Oncol, 2008; 3(4):5-6



LAUNCH SUCCESSLaunch success is often influenced by payer perception of unmet need as much as by specific outcomes data andindividual drug pricing. Oncology launches over the past four years have differed substantially in their success. While Avastin (bevacizumab),launched a decade ago, is largely considered to be the most successful cancer drug launch of all time, Zytiga(abiraterone) is following a similar trajectory. Yervoy (ipilimumab) is keeping pace with the successful launches ofGlivec/Gleevec (imatinib) and Erbitux (cetuximab) some time ago. Conversely, several recent launches have been farsmaller, having achieved ≤$10mn per month in global sales (Figure 3).

Interestingly, some of the products from this latter group offered significant improvements in overall survival (OS) orprogression-free survival (PFS). A key factor driving the differential success of these launches is payer perception oftherapeutic need. While it may seem counterintuitive for a new product treating a relatively limited available patientpopulation (eg, multiple myeloma) to surpass those targeting a larger one (eg, colorectal cancer), perceived unmetneed on the part of payers may trump a larger available patient population given the numerous therapeutic optionsalready available.4

PAYER SCRUTINYPayers are increasingly looking for ways to define the value of meaningful clinical outcomes, with a trendtoward increased management interventions for certain cancer therapies.The American Society of Clinical Oncology (ASCO) recently released a report compiling the input of experts on fourtumors – pancreatic, lung, breast and colon – in defining the expected outcomes for deeming a particular therapyeffective.5 For each of these tumors, a range of between 3 and 6 months improvement in overall survival (OS) wasselected as the primary endpoint (Table 1, overleaf ). However, it was noted that this would not necessarily diminish thevalue of PFS and other surrogate endpoints in certain clinical situations.5


Pomalyst-2013 Xo!go-2013, Zelboraf-2011 Xalkori-2011, Zaltrap-2012, Stivarga-2012, Iclusig-2013, Jaka!-2011, Adcetris-2011

5

FIGURE 3: SELECTED US ONCOLOGY LAUNCHES ON A 3-MONTH ROLLING AVERAGE IN FIRST 24 MONTHS SINCE LAUNCH US$MN

4 Lux W, kontos N. Adapting to new market realities: Achieving launch excellence in oncology. IMS Health White Paper, 20115 Ellis LM, et al. American Society of Clinical Oncology perspective: Raising the bar for clinical trials by defining clinically meaningful outcomes. J Clin Oncol, 2014;

Mar 17:epub ahead of print 10.1200/JCO.2013.53.8009.


With multiple treatment options for various cancer types, coupled with increasing financial pressures across alltherapeutic classes, payers and physicians are likely to look hard at the relative value of new launches and ultimatelycould reference these or similar guidelines in making coverage and treatment decisions. Although agents withrelatively slight improvements in OS and PFS may be approved for use on the basis of other criteria, such as improvedquality of life, the signs point to a future of more rigorous evaluations in oncology.

The rise of more restrictive coverage and utilization criteria would not be surprising given the cost of modern-dayoncologics. In Europe, health technology assessments have already become more stringent. In the US, according to arecent benchmarking survey of pharmacy benefit trends, over 90% of healthcare plans with a medical formulary reportthe use of prior authorization for high-cost injectable drugs such as those to treat cancer.6

PATIENT OUT-OF-POCKET COSTS IN THE USFinancial pressures on patients following recent legislation have the potential to impact cancer care in the US. The number of medical oncologists in the US continues to grow while the nature of medical practices is changing. Therehas been a 24% increase in the number of oncology practices acquired by a hospital and a 21% increase in the number ofoncology practices that have closed; concurrently, the size of remaining oncology practices has grown as groups ofproviders aggregate7 to mitigate increasing financial constraints resulting in part from the Affordable Care Act (ACA).

One particular change is the ACA’s expansion of 340B eligibility. By design, the 340B Drug Pricing Program is intended toenable healthcare organizations that care for underserved patients to purchase outpatient drugs at discounted prices(~51% of average wholesale price; AWP). However, while uncompensated care as a percentage of total hospital expenseshas remained unchanged over the past decade, the percentage of hospital drug purchases through 340B pricing hasincreased dramatically to 25% in 2013. One factor may be the ACA’s expanded eligibility to participate in this program.

This arrangement can encourage the referral of cancer drug infusions to the facility outpatient setting from theoncologist’s office, where the hospital can purchase the drug at a significant discount and yet charge a premium topayers for hospital-based administration. In fact, the average cost increase to payers for a patient to receive a cancerdrug in the hospital versus the physician’s office was found to be 189% for a set of frequently used therapies (Figure 4).


Primary End Point Secondary End Point

Cancer typei Patient population Current baseline median OS (months)

Improvement over current OS that would be clinically meaningful (months)

Target HRs Improvement in 1 year survival rate(%)

Improvement in PFS (months)

Pancreatic Cancer FOLFIRINOX-eligible patents 10 to 11 4 to 5 0.67 to 0.69 48 to 63 4 to 5

Pancreatic Cancer Gemcitabine or gemcitabine/hab-pac itaxel-eligible patients

8 to 9 , 3 to 4 0.6 to 0.75 35 to 50 3 to 4

Lung Cancer Nonsquamous cell carcinoma 13 3.25 to 4 0.76 to 0.8 53 to 61 4

Lung Cancer Squamous cell carcinoma 10 2.5 to 3 0.77 to 0.8 44 to 53 3

Breast Cancer Metastatic triple negative, previously untr ated for metastatic disease

18 , 4.5 to 6 0.75 to 0.8 63 to 71 4

Colon Cancer Disease progression with all prior therapies (or not a candidate for standard second or third-line options)

4 to 6 3 to 5 0.67 to 0.67 25 to 36 3 to 5

Abbreviations: FOLFIRINOX, leucovori uracil, irinotecan and oxaliplatin; HR , hazard ratio; OS, overall survival; PFS, progression-free survivalSource: i. Ellis LM, et al. J Clin Oncol. 2014; Mar 17:epub ahead of print 10.1200/JCO.2013.53.8009, ii. Conroy T, et al. N Engl J Med 2011;364:1817-1825.iii. Kindler HL, et al. Lancet Oncol. 2011;12:256-262. iv.. DD, et al. N Engl J Med. 2013;369: 1691-1703. v. Porter ME. N Engl J Med. 2010;363:2477-2481. vi. Rossi A, et al. J Clin Oncol. 2012;30:1692-1698. vii. O’Shaughnessy, et al. Oncologist. 2012;17:476-484. viii. Cortazar P, et al. J Clin Oncol. 2012; 30:1705-1711. ix. Grothey A, et al. Lancet. 2013;381:303-312.

TABLE 1: ASCO-RECOMMENDED TARGETS FOR MEANINGFUL CLINICAL TRIAL OUTCOMES.5

6 Magellan Rx Management 2013 Medical Pharmacy Trend Report, May 2014. Available at: http://www.magellanrxinsights.com/ 7 Community Oncology Alliance (COA) Practice Impact Report, 2012, 2013


Patients pay a portion of these increased costs, with an average $134 increase in out-of-pocket cost per dose ofchemotherapy. Considering that they frequently receive several infusions in one visit, even a seemingly minimalincreased cost per dose may be immediately compounded depending on the number of therapies in a particulartherapeutic regimen. This increased spend should inform patient affordability discussions given that the total out-of-pocket cost for a cancer patient today is approximately $9,000 annually.

An implication of these cost increases to the patient is therapeutic adherence since literature shows that even modestincreases in co-pay amounts can result in measurable reductions in adherence.8,9 Furthermore, as therapeuticadherence decreases, the cost of care may actually increase, with approximately $8,000 per year higher costs for non-adherent patients in a recent evaluation of early-stage ER+/PR+ breast cancer patients.10 In this manner, recent changesto the US healthcare system may ultimately have unintended consequences on the quality and cost of American carefor cancer patients.

CONCLUSION Oncology innovation, outcomes and spend are all important elements to consider in developing appropriate measuresto assess treatments and investments. This Institute report provides a uniquely comprehensive study in an emergingworld of data and evidence developed to inform those decisions.


FIGURE 4: HOSPITAL OUTPATIENT COSTS COMPARED TO PHYSICIAN OFFICE COSTS

This article is based on findings presented in “Innovation in cancer care and implications for health systems: Globaloncology trend report” published by the IMS Institute for Healthcare Informatics in May, 2014. Further analyses and insightscan be found in the full report which is available to download at www.theimsinstitute.org

The IMS Institute for Healthcare Informatics leverages collaborative relationships in the public and private sectors tostrengthen the vital role of information in advancing healthcare globally. Its mission is to provide key policy setters anddecision makers in the global health sector with unique and transformational insights into healthcare dynamics derived from granular analysis of information.

8 Bach PB. Limits on Medicare's ability to control rising spending on cancer drugs. N Engl J Med, 2009; 360:626-633 9 Eaddy MT, Cook CL, O’Day k, Burch SP, Cantrell CR. How patient cost-sharing trends affect adherence and outcomes: A literature review. PT 2012, Jan; 37(1):45-5510 Neugut AI, et al. Association between prescription co-payment amount and compliance with adjuvant hormonal therapy in women with early-stage breast cancer.

J Clin Oncol, 2011; 29:2534-2542



Oncology outcomes research, for many years limited to snapshots of patientexperiences, is starting to deliver a much deeper understanding of cancer andits treatment based on insights into the entire patient pathway. As continuedinnovation in data access and linkage transforms the potential of real-worldevidence in oncology, the market is set for significant growth in its use. Already, its expanding value is yielding impressive results globally but, as anindustry perspective reveals, the full possibilities have yet to be realized.

Chirag Ghai, MBA is Director RWE Solutions & HEOR, IMS [email protected]

The author



The journey is only just beginningHistorically, inadequate access to anonymous patient-level oncology data outside of randomized clinical trials has posed challenges in developing research andcommercial insights. Although traditional oncology real-world databases wereavailable, they existed in silos. In the absence of data management techniques therewas no means of integrating these data sources and they were thus not a truelearning healthcare system.1 They also lacked depth, missing elements that arecritical to providing meaningful insights in oncology, such as mortality, tumorinformation and progression status. Thus, while researchers could develop snapshots of patient experiences, they were unable to illustrate a near real-timeand comprehensive view of the patient journey. As a result, real-world evidence (RWE) in oncology has primarily beenused as a tool for value and safety demonstration, with a host of broader applications remaining unaddressed.

RECENT INNOVATIONS ACCELERATING POTENTIAL OF ONCOLOGY RWE The advent of the HITECH act in 2006 dramatically accelerated oncology RWE. Health IT (HIT) changes have opened up access to broad and deep patient-level data assets2 and data management, making it possible to link real-worldoncology patient-level data3 (Figure 1, overleaf ). This provides a capability to build longitudinal patient journeys tofollow populations across different types of cancers. For example, the proliferation of EMRs through oncology practices makes clinically rich data available for linkage to gold-standard databases such as health plan claims, pharmacy and socio-demographics.3 Patient mortality information, when linked to medical and pharmacy claims and clinicalattributes in oncology EMRs, provides insights on survival patterns of patients diagnosed at different cancer stages.

Through access to integrated data, bio-pharma most commonly generates oncology RWE for disease burden, line oftherapy, risk stratification and clinical profiling studies. But they are not alone – payers and providers are also usingoncology RWE. Payers, for example, are establishing evidence-based oncology treatment pathways aimed ateliminating unnecessary medical interventions and promoting cost-effective treatments.4 Providers, meanwhile, are generating insights such as tracking of hospital treatment trends and patient care evaluation.5

Thus, by linking patient characteristics to treatment options and outcomes, a broad and deep real-world oncologydatabase can enable answers to more complex questions at the product and disease level.

Evidence-based insights in oncology


1 Institute of Medicine (IOM). Delivering High Quality Cancer Care: Charting a New Course for a System in Crisis. Washington DC: The National Academies Press, 20132 Health Plan and Medical Claims, Hospital CDM, Specialty pharmacy, oncology registers, tumor banks and socio-demographic information, Electronic Medical Records(EMRs) ASCO and the National Cancer Institute have been spearheading initiatives for oncology practices to implement EMRs to interconnect oncology practices

3 American Society of Clinical Oncology. Shaping the Future of Oncology: Envisioning Cancer Care in 2030. Outcomes of the ASCO Board of Directors Strategic Planningand Visioning Process, 2011-2012

4 NICE provides a useful specialists access to a host of cancer pathway recommendations. http://pathways.nice.org.uk/5 Banner Health’s Oncology Hospital, Fairbanks Memorial, maintains a Tumor Registry, under the medical direction of the Cancer Committee, comprising clinical data on allcancer patients seen at FMH



MARKET POISED FOR DRAMATIC EXPANSION OF RWE IN ONCOLOGYThe increasing availability of RWE in oncology is moving stakeholders towards a data-driven approach in cancerresearch and commercial engagement.

Supply-side On the supply side, several factors will enrich oncology with new real-world data. Aided by IT advances, the collectionand sharing of biospecimens will support molecular-based cancer. The move away from a one-size-fits-most approachin oncology will result in oncology RWE initiatives integrating and mining genomic (sequencing), proteomic, clinical,imaging and financial data, thereby expanding interrogation and analytics to include dozens of variables.6

Patient-initiated data is likely to be another new source, with patient-friendly HIT interfaces positioning the patient asan active participant in the RWE exchange. For example, real-time connections with oncologists will allow patients toreport their health status, side-effects and other experiences as they happen.

Demand-sideEven with such supply-side advances, demand for oncology RWE is likely to outpace supply (Figure 2) especially incases where a deep understanding of the patient is lacking. For example, in blood-borne cancers it is difficult toperform analyses on lines of therapy or pre- versus post-relapse based on therapy sequences, since almost every(lymphoma, myeloma and leukemia) course involves administration of the same product. A very detailed combinationof lab results is required to confirm whether patient cohorts are consistent with a particular clinical pathway.Consequently, data mining capabilities are required to tap into the clinical notes (or unstructured data within EMRs) toextract the insights required.7

FIGURE 1: UNIQUE POSSIBILITIES IN ONCOLOGY LINKED DATA

6 http://www.upmc.com/media/NewsReleases/20137 IMS Health HEOR expertise: Vernon Schabert



RWE demand is a function of two sources: the first is pull for RWE among stakeholders external to bio-pharma such asnational and private payer systems, regulatory agencies and provider systems for decision making; the second is theevolving application and user-set expansion to commercial stakeholders within bio-pharma such as brand managers,market access experts, sales teams, market researchers and forecasters.

Externally, RWE application for payers will move beyond monitoring appropriate product usage to meet needs aroundproduct pricing and access decisions. For example, payers will increasingly demand that data be used to match patientswith specific treatments to improve outcomes in key populations and incentivize pathway prescribing. Payer-developed clinical guidelines have the potential of being transformed into living, evolving documents that are notreliant on clinical trials and expert analyses. In Europe, RWE may enable HTA dialogue to identify critical researchquestions that have not been adequately answered in the past, as well as address study variability due to quicklychanging treatment options. Its ability to do so is in providing the types of patient sample sizes and follow-up timesrequired to measure overall survival (OS) rates – HTAs choice of endpoint.8

Beyond payers, hospitals and care delivery settings will also actively participate in RWE exchange. In hospitals and newcare delivery settings,9 decision makers such as administrators will ascertain product value by seeking insights frompublished evidence. Through the aggregation and analysis of data from patient experiences in real time, integratedoncology RWE systems will predict and identify trends and associations between hosts of variables and generate newhypotheses. Physicians and researchers will evaluate those hypotheses and determine which lead to improved care inreal-world settings. RWE opportunities for new stakeholder engagement vehicles will also include value-added servicessuch as embedding routinized quality measurement and improvements in oncologist practices and sites of care.

FIGURE 2: ONCOLOGY RWE DEMAND AND SUPPLY EVOLUTION


8 Overcoming Incomplete Evidence Network and Heterogeneity Issues with Simulated Treatment Comparisons. Workshop at ISPOR 16th Annual European Congress,Dublin, Ireland, 2-6 November, 2013

9 Care process data includes high tech imaging guidelines, radiation therapy “pathways”, chemotherapy regimen compliance



Internally, within bio-pharma, RWE in oncology has been under the purview of health economics and outcomesresearchers and epidemiologists. Now, bio-pharma is expected to drive adoption of RWE capabilities to address a rangeof commercial applications. Those organizations that understand the breadth and depth of RWE uses (Figure 3) willexpand adoption to a commercial audience and embrace new ways to engage with stakeholders on addressing morecomplex questions.

RWE can improve a host of tactics such as physician targeting, detailing, promotional activities, rep visits. However, thereal source of value will be in shaping launch strategies and targeted marketing campaigns, and understanding patientpathways and flows for commercial planning. Lessons learned from bio-pharma oncology commercial teams indicatethat winners will lever RWE in areas such as key opinion leader and patient advocacy engagement, messaging (lifeextending versus symptom reducing), compendia diagnostics, and physician and patient segmentation. For example,projecting patient-level data nationally provides a far more granular and clinically-oriented perspective in market sizingand forecasting as compared to traditional methods.

Going forward, as bio-pharma seeks deeper levels of oncology evidence, it will be critical for HEOR, epidemiology and commercial functions to collaborate as a collective, given the unique scientific and commercial insights that eacharea brings.

The increasing availability of RWE in oncology is moving stakeholders towards adata-driven approach in cancer research and commercial engagement.

FIGURE 3: TRENDS IN RWE APPLICATION

Note: Not an exhaustive list of oncology RWE applications



THE EXPANDING VALUE OF RWE IN ONCOLOGY – AN INDUSTRY PERSPECTIVE

INTERVIEW WITH ALEX LIEDE, PHD

Alex Liede is Director, Center for Observational Research at Amgen and heads the company’s industry-leadingoncology evidence platform partnership for commercial and research insights. IMS Health has been working withAmgen on this evidence platform for over six years. Alex holds a PhD in Genetic Epidemiology from the University ofToronto and is currently in his 10th year at Amgen. Here he shares his perspective on the evolution and practicalapplication of RWE in oncology and why its full potential has yet to be realized.

Q: Why did Amgen build an RWE capability in oncology?AL: We realized that RWE would be a tremendous asset in oncology, especially as we engaged with scientificand regulatory stakeholders. The overall understanding of cancer patients in real-life settings used to be verylimited because of isolated datasets, and claims databases did not provide a sufficient level of detail (eg,laboratory values). And we saw how incomplete pictures of that patient experience could lead to poor decisions.We therefore committed to building a better fact base about oncology by increasing not only the amount ofreal-world data but also data linkable to additional sources to build a more comprehensive picture. Amgen’soncology evidence platform represents an oncology EMR database that is linkable to several additional dataassets within IMS Health in a HIPAA-compliant manner. In 2014, we are building further collaborations withacademic institutions and other third-party research partners to develop studies and glean additional insights.

CASE STUDYScaling RWE to reach main opportunity areas and bio-pharma functions10

Challenge: One company started its RWE journey by creating an integrated evidence platform in response tovalue and safety demonstration challenges. When the FDA questioned the appropriate use of a $1 bn oncologyproduct, up to $500 mn of revenue was placed at risk due to potential label changes. Approach: The company realized that the FDA was basing its decisions on an incomplete picture of currenttreatments, with the potential for misperceptions that could affect the entire oncology franchise. Its response wasto develop the broadest RWE platform at the time, enabling a variety of insights to inform discussions with amultitude of stakeholders. Impact: With the RWE platform in place, the company successfully defended the FDA challenge, justifying theinitial investment. It was also able to counter misleading academic-led publications in high profile forums such asthe New England Journal of Medicine. Moreover, it could rebut each one in as little as two weeks.Incremental benefits: Once the company saw the power of RWE insights, it continued to invest in the platformbeyond value and safety demonstration. Commercial leaders acquainted with RWE capabilities started tosystematically lever detailed patient pathways to understand product use, identify patterns of under-diagnosis andunder-treatment and shape highly targeted marketing campaigns. These campaigns nearly doubled brand growth.Over time, RWE became the company’s currency and competitive advantage for engaging health systems, withgranular forecasting and disease progression models levered by a series of medical center partners for their ownservice planning. For the first time in the industry, it effectively developed a closed-loop system to use insights toengage and improve patient pathways. Future outlook: For this company and its multi-year RWE investment, the opportunities continue to expand. Forexample, it recently added tissue sampling to its data platform to enable step changes across clinical development(eg, improving sample size for biomarkers and phase II development).

10 Hughes B, kessler M. Breaking New Ground in RWE Value: How Some Pharmacos are Poised to Realize a $1 Billion Opportunity. IMS Health White Paper, 2014




Q: How have you seen RWE evolve in oncology?AL: RWE is not a new concept and it has been in place since the early days of epidemiology in medicine. But wenow benefit from the near real-time nature of RWE as compared to the past where insights relied on data sourcesthat were not refreshed periodically. Consequently, the evidence generated was potentially outdated and notreflective of current patient care in oncology. Now there is very little lag time associated with the data that ismined, such as data from EMRs.

Q: What does this evolution mean in terms of the use of RWE?AL: We have seen a strong ramp-up in the demand for these real-life insights now that the information isavailable to inform internal decisions as well as external interactions. Externally, RWE is becoming a moreconsistent baseline to inform decisions. Clinicians and payers are more willing to use it. We work with academicmedical centers to jointly shape publications with experts and further validate real-world oncology data. This way,we can jointly develop evidence to address questions that customers and regulators may have after productlaunch.

Internally, the applications are broad. In clinical development, we now better understand the patient experiencein the clinical setting from how they are diagnosed to how they are treated. We know more about them, such asthe age distribution of certain cancers. After launch, RWE helps us understand more about the patients as well aswhat happens to them during and after treatment. For us, it means thinking about market share in a moremeaningful, patient-centric way. We also better understand persistence on therapy and some of thecharacteristics of non-persistent patients to help us identify ways to better deliver our value to patients andpayers.

Q: Can you provide a recent example of how RWE enabled a better outcome for Amgen?AL: We recently used RWE to build the case for orphan drug status for an oncology agent. The agent was beingprepared for review with the FDA and we were seeking a new orphan drug indication (hypercalcemia ofmalignancy or HCM). To do this, we used RWE for understanding how many patients in a specific year experiencedHCM. By examining EMR data linked with claims data we were able to estimate the proportion and prevalence forpatients who experienced high calcium values after a cancer diagnosis – we could never have estimated thepopulation size so accurately without access to calcium laboratory data. The FDA granted the agent orphan drugdesignation for the regulatory filing. This was a big achievement in that we successfully demonstrated to the FDAthat the oncology EMR data represents a robust evidence platform, representative of cancer care in the US.

Q: Building on the success of linking EMRs and claims, what are some next generation data sources thatwould be valuable for oncology RWE?AL: There are two areas that come to mind: the first is bringing in biomarker and genetic data. As an example,determining and demonstrating how many patients have a genetic marker associated with improved response toa therapy would provide a viable path to bringing a product to market; the second area is patient-reportedoutcomes where it would be valuable to capture outcomes such as pain scores.

Q: Would you say we are at the beginning of the journey for oncology RWE generation?AL: Yes. We now need a focused RWE approach since there are so many sources emanating oncology data. Thefull potential would include expansion to social media, consumer databases and non health-related behaviors.Even existing data sources such EMRs are generating new, ever expanding data as new measures are recordedfrom patient visits such as chemotherapy and follow-up. Much expertise is required to understand the privacy,regulatory and legal aspects.

2.Understanding of free text


DATA LINkAGE | INSIGHTS

At a time of concentrated pressure on evidence demands in oncology, the Scandinavian region offers unique potential for RWE generation. With a population base of more than 25 million, a history of extensive datacollection, and the ability to link data at the patient level, it enables unparalleledinsights into the entire cancer treatment journey and outcomes related to themanagement of the disease.

Patrik Sobocki, PHD, MSC is Senior Principal RWE Solutions & HEOR, IMS [email protected]

The author

Transforming oncology outcomesresearch through data linkage in Sweden

A unique real-world lens on the entire patient journey Oncology presents one of the most complex and challenging disease areas foroutcomes research, not least due to limited and heterogeneous data, significant gapsacross relevant care settings, and lack of robust longitudinal information to allow anunderstanding over time. Yet, more than ever, it is reliant on RWE, reflecting increased product scrutiny by regulators and payers but also growinguse by medical oncologists, a majority of whom have reported considering RWE in their recommendations for treatment.1

At the same time, oncology has one of the richest R&D pipelines, exploring new molecules and therapeutic approachesand extended indications for existing agents across a range of different cancers. These include breast, lung and prostatecancer (PC) as well as less common tumor types such as ovarian, stomach and liver,2 which bring their own challengesfor understanding epidemiology and generating RWE.

As these trends continue, and science drives further growth in innovative new oncologics, the ability to overcome datalimitations and maximize the value of existing resources will be key to ensuring more effective, efficient and insightfuloutcomes research in support of optimal patient care.

NEW OPPORTUNITIES In the growing global search for credible real-world oncology data, the Scandinavian region is unrivalled inopportunities to generate RWE, reflecting the well-structured public healthcare of Sweden, Norway and Denmark, theirlong established high-quality EMRs, national and disease-specific registries, and a mature regulatory framework forclinical research.

Rich, longitudinal EMR and registry data The combination of EMRs and National Cancer Registries, the oldest of which (Denmark) has been collecting data since1942, makes Scandinavian data a source of qualitative, patient-level health information on oncology diagnosis andmanagement in a system of high-quality care. Sweden in particular, rated as the most advanced country inimplementing value-based healthcare,3 has a 20-year history of quality patient-centric EMR data entry, with 100%coverage providing integrated information on both primary and specialist care. This compares to around 50%-100%coverage in EU (varying by country) and around 50%+ in North America. Uniquely, it enables access to EMR data formore than 5 million lives in the region, including patient information, diagnosis, side-effects, physician visits, lab tests,prescriptions and mortality (Figure 1).

Transforming oncology outcomesresearch through data linkage in Sweden

INSIGHTS | DATA LINkAGE


1 87% of oncologists consider ‘real-world’ evidence when recommending treatment. 13 April, 2013. Accessed 3 May 2014 at http://social.eyeforpharma.com/market-access/oncologists-consider-real-world-evidence-rwe-decision-making

2 Innovation in cancer care and implications for health systems: Global oncology trend report. IMS Institute for Healthcare Informatics, May, 2014 3 Progress toward Value-Based Health Care: Lessons from 12 countries, BCG, June 2012. Available at: http://www.bcg.com/



Sweden is also a pioneer in building national, quality health registries in various disease areas and now has more than100, many with a history of over 15 years. Based on a system of mandatory reporting, the Swedish Cancer Registry,established in 1958, records every case of newly diagnosed cancer across the entire population, registeringapproximately 50,000 malignant cases of cancer each year. Containing patient, medical and follow-up data, it is notedfor its high level of completeness.4 In addition, more than 20 robust, tumor-specific registries are also available forresearch. Covering leading tumor types such as breast, colorectal, lung and prostate, as well as a range of less commoncancers (eg, acute lymphoblastic leukemia, chronic myeloid leukemia, multiple myeloma) these include additionalcomplementary health information around the time of diagnosis and during disease progression. All the Nordicnational cancer registries achieve almost 100% coverage, from sources that include physicians, hospitals, and patients.5

Increasingly recognized for their value in driving quality improvements in healthcare,6 the use of these diseaseregistries has been linked both to enhanced health outcomes as well as reduced healthcare costs.7 Sweden has beenshown to have among the best 5-year survival rates for cancer in Europe among countries studied.8,9

Unique opportunities for database linkage The exceptional potential of patient-level cancer data for RWE generation in Scandinavia lies in the unique opportunityfor linking databases at individual patient level, permitted by regulations for research purposes and enabled by theexistence of a unique personal identification (Social Security) number in each country (Figure 2, overleaf ).

The integration of EMR data and information from national and disease-specific registries enables unparalleled accessto real-time, longitudinal population-based data for more than 25 million people, delivering the deepest granularity inoncology seen in a single European market.

H

H

Age, gender, vitals

• Comorbid condition

P

FIGURE 1: LONGITUDINAL DATA FROM EMRS IN SCANDINAVIA

4 Barlow L, Westergren k, Holmberg L, Talbäck M. The completeness of the Swedish Cancer Register: A sample survey for year 1998. Acta Oncol. 2009; 48(1):27-33. Accessed4 May, 2014 at: http://www.ncbi.nlm.nih.gov/pubmed/18767000

5 Møller B, Fekjaer H, Hakulinen T, et al. Prediction of cancer incidence in the Nordic countries up to the year 2020. Eur J Cancer Prev, 2002 Jun; 11 Suppl 1:S1-966 Fine-Tuning Health Care – improved outcomes and cost efficiency using quality registries. Accessed 4 May, 2014 at: www.government.se/qualityregistries7 Larsson S, Laywer P, Garellick G, Lindahl B, Lundström M. Use Of 13 Disease Registries In 5 Countries Demonstrates The Potential To Use Outcome Data To Improve Health

Care’s Value. Health Affairs, 2012, Jan; 31(1):220-7. Accessed 4 May, 2014 at: http://content.healthaffairs.org/content/early/2011/12/06/hlthaff.2011.0762.full8 Berrino F, Verdecchia A, Michel Lutz J, et al. Comparative cancer survival information in Europe. European Journal of Cancer, 2009, April; 45(6):901-89 De Angelis R, Sant M, Coleman MP, et al. Cancer survival in Europe 1999-2007 by country and age: Results of EUROCARE-5 – a population-based study. The Lancet, 2014,

Jan; 15(1):23-34



INSIGHTS | DATA LINkAGE

Using this data, oncology researchers can build acomplete patient pathway with information thatincludes:

• Co-morbidities

• Surgical procedures & other measures

• Socio-economic variables

• Metastasis development (or progression of cancer/tumor)

• Death (and underlying cause)

• Hospitalizations (length of stay, etc)

• Medical treatments

• Family disease history

• Patient histology

• Tumor characteristics (TNM, staging information)

• All laboratory test results

• Risk factors & performance status

Robust, comprehensive databasesThe possibility to extract and integrate high-quality, anonymous patient-level data from EMRs and registries inScandinavia enables the development of robust, comprehensive tailored databases to meet specific needs inepidemiology, outcomes research and pharmacovigilance. Leveraging a unique software program (Pygargus CXP) forextracting large volumes of data, this involves a detailed process of study design and approval, data collection andmapping, and linkage and management (Figure 3).

H

H

FIGURE 2: OPPORTUNITIES FOR DATABASE LINKAGE

H

H

Tumor staging

• Performance status

P

FIGURE 3: CUSTOMIZED DATABASE USING CUSTOMIZED EXTRACTION PROGRAM



Through the linkage of patient characteristics to therapies and outcomes, the Scandinavian dataset offers a powerfulplatform for developing highly-powered, large-scale epidemiological and outcomes research studies. Databases builtfrom this resource have supported global research with real-world insights addressing a range of questions aroundcomparative effectiveness, pharmacovigilance, epidemiology and clinical outcomes. The following case study providesa practical application of the process and potential in PC.

CASE STUDYMeasuring outcomes of prostate cancer patients to define high risk and inform optimal managementBackground: PC is the second most common cancer diagnosed in men and the sixth leading cause of cancerdeath in men.10 In Sweden, an observed increase in the incidence of the disease has been attributed to extensiveuse of serum prostate-specific antigen (PSA) testing, with most new cases diagnosed as non-metastatic. In apercentage of men treated with curative intent the disease will recur, as evidenced by an increase in serum PSA inthe absence of metastases. Responses to the current standard of care for recurrence are typically not durable, withnearly all patients ultimately progressing to castration-resistant disease (CRPC). The purpose of this retrospectivecohort study was to identify the clinical course of PC in Sweden with a view to characterizing patients at particularrisk of CRPC and other metastases, given the significant and growing burden of the disease and the absence ofexisting documented evidence, especially on the impact of time-varying factors such as PSA values.

Approach: The study was based on longitudinal EMR data from eight Swedish outpatient urology clinics (wherePC patients are predominantly seen) linked to national registry data in the country, which enabled a study cohortof more than 7,000 patients. Data was extracted and linked using Pygargus’ unique proprietary CustomizedeXtraction Program (CXP) on an anonymous basis through the use of a unique study id in place of personal idnumbers. The value of EMR was demonstrated in the type of information needed, which was otherwise notavailable, for this type of study. Specifically, EMRs provided PSA laboratory data, treatment details, as well asinformation on patient characteristics. The Swedish National Patient Register enabled tracking of patients whotransitioned from the urology clinics to hospital-based oncology clinics, and the retrieval of information onmetastatic diagnoses, co-morbidities and orchiectomies. Finally, the linkage of EMR data to the National Register of Cause of Death allowed for estimates of overall survival and incidence of death.

Benefits: Presented at ICPE 2013 (the International Congress on Pharmacoepidemiology, Montreal, Canada) andwith a manuscript accepted for publication in a peer-reviewed medical journal (Cancer Epidemiology), thisbreakthrough study described the disease progress and key predictors of outcomes. Based on the longitudinalcapture of medical and demographic data and patterns of treatment and diagnosis in real-world clinical practice, it enabled the first insights into the clinical course of PC in a focused patient population treated with androgen-deprivation therapies. Its unique ability to examine PSA values over time was critical to understanding riskdeterminants such as PSA doubling time for developing metastases and informing optimal management of the disease.

CONCLUSIONThe Scandinavian region represents a strong and compelling environment for RWE research in cancer, based on a longhistory of collecting oncology-specific health information in EMRs and national population-based health registers. By combining population-based anonymous patient-level health information from EMRs with health register data,powerful research programs can be developed to inform research questions that are difficult to answer anywhere else.

10 Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA: Cancer J Clin, 2011; 61(2):69-90

Continued innovation in oncology is driving higher-cost, multi-line drugregimes. The emergence of novel products, with multiple indications andsignificant budget impact, is placing the existing ‘one product, one price’ systemunder increasing pressure. A bold move towards differential pricing, reflectingthe value of a drug in a specific setting, could play a key role in helping payersmanage finite resources, while rewarding innovation, broadening access andcreating opportunities for improved outcomes.

The authors

Ashley Woolmore, D.CLIN.PSYCH is Senior Principal RWE Solutions, IMS [email protected]

Daniel Simpson, M.BIOCHEM is Senior Principal RWE Solutions, IMS [email protected]

Page 1 IMS HEALTH ECONOMICS AND OUTCOMES RESEARCH

INSIGHTS | PAYMENT BY USE


Achieving a new value paradigm for oncology Built on years of price tolerance and high willingness to pay for even relativelymarginal benefits, in line with national priorities for cancer and public support, theoncology sector has fostered and rewarded some of the most expensive specialtymedicines available. In Europe, and signaled elsewhere, there is a perceived need toclosely manage patient access and thereby the growing budget impact of new agents.Compounding affordability issues is the emergence of sequential or combination multi-drug regimes. Despite majorbreakthroughs in targeted therapy, these are seen to offer “the best route – and quite possibly the only way forward –to overcome the enormous problem of genetic complexity and heterogeneity of human cancer.”1 The situation will onlyintensify as more new treatments target multiple tumor types, leading to higher scrutiny of exactly how a drug is beingused. Today, in Europe, 50% of leading oncologics are already licensed for more than one cancer; by 2019, over 80% areanticipated to have multiple indications (Figure 1).

Payment by use

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PAYMENT BY USE | INSIGHTS



FIGURE 1: IN EUROPE, MORE THAN 80% OF LEADING ONCOLOGICS WILL HAVE MULTIPLE INDICATIONS BY 2019



GROWING DIVISION BETWEEN PRICE AND VALUECurrently, the architecture for setting prices in the pharmaceutical industry in a given country is product-centric: oneprice for one product (be that pack or ‘mg per vial’). There is a growing mismatch between offering a single price andthe value delivered by increasingly complex oncologics in different usage situations.

For example, a product launched initially in one indication may well be priced at a payer-acceptable level given its clinicalvalue or cost-effectiveness for that use. However, when subsequently expanded into another tumor type, where itsimpact on overall survival could be lower, it may not. Maintaining the price of the first indication will prohibit access forthe second; reducing it will diminish the revenue potential proportionate to its established cost-effectiveness or value.

Failure to address these issues now will accelerate the move toward measures for managing affordability: draconianpricing restrictions; usage according to prioritized cohorts (sub-populations); consideration of cost-capping; andexploration of options for third-party payments (insurer solutions/co-pays), leaving patients struggling to access drugsthat could potentially improve their survival.

LIMITED SUCCESS FROM CURRENT APPROACHESTo date, attempts to tackle the rising price demands from pharma for oncology drugs have centered on guidelines andgovernance of use, including relegating innovative products to later lines of therapy. Usage agreements have typicallyinvolved either imposing financial limits on products by patient or volume (unit or revenue), or restrictingreimbursement to sub-populations with specific characteristics associated with improved outcomes.

Whilst pharma companies have attempted to put in place innovative contracting and pricing schemes to impact thenet price paid by payers,2 they have tended to be point solutions from individual manufacturers for individual products.These measures have so far met with limited success – certainly no global or European standard has emerged as a clearsolution that meets both the needs of payers and suppliers to healthcare.

PAYMENT BY USEOne potential solution would be a move towards a differential pricing system that allows an effective price to be paid asa function of actual product use (eg, line of therapy, combination, tumor type). This permits a closer alignment of thevalue delivered with price. Payment by Use (PbyU) allows a more logical reflection of value, particularly in the case ofhigh-price products where the conditions of use vary (see panel on page 31).

Necessary but not sufficientPrice setting in oncology is complex and beyond the scope of this paper. Critically, however, one of the key barriers toachieving a more elegant solution has been a failure to recognize the core capability required to underpin moreinnovative approaches: a real-time (or rather, regular and consistent) understanding of exactly how oncology productsare being used in clinical practice, by line of therapy, tumor type and dosage. Only with both of these building blocks inplace is the move towards a new form of performance or outcomes-based scheme realizable (Figure 2). As the necessary(but not sufficient) first step on the journey, PbyU would establish the foundational knowledge base on which to buildmore adapted pricing schemes.

FIGURE 2: BUILDING BLOCKS UNDERPINNING INNOVATIVE CONTRACTING IN ONCOLOGY

Pricing strategy (list and net) Accurate patient-level use information

Payment by use

Enables

Today

Future Payment by performance

+Payment by use (PbyU) is the foundation for payment by performance (PbP). Accurate patient-level information is afundamental requirement for both.

Payment as a function of USE(eg, tumor type, line of therapy, mono/combo)

Payment as a function of OUTCOME(eg, survival, PFS, recurrence)

Incorporate OUTCOME data

1

3a

3b

2



ChallengesAlready, there has been some progress towards implementing PbyU by individual actors within the industry; theapproach is actively being discussed or even piloted by a number of top ten manufacturers. However, PbyU representsa major change in paradigm. As such, several factors drive the need not for individual company initiatives but for a pan-industry approach:1. Creating a ‘win-win’ with payers2. Ensuring perceived fairness for all stakeholders3. Financing the cost of gathering and managing the data 4. Enabling independent information governance

Financial flows and incentives within the healthcare system are complex. Current payment systems are not built to copewith a PbyU type of price management scheme. A plethora of net-pricing mechanisms bring inconsistency betweenmanagement of products, while comparative value across therapy areas is difficult to distinguish due to differentpricing and market access stipulations. For example, in Italy, patients receiving Yondelis (trabectedin) are evaluatedafter two treatment cycles (six weeks) whereby the treatment cost for non-responders is refunded. Within the Uk, thecost of the drug is covered if used for more than five treatment cycles, limiting the cost to the NHS to £17,500 ($28,000)to £25,000 ($40,000) per patient. An effective PbyU infrastructure would have to be built with the system’s stakeholders,and a pan-industry initiative could represent an acceptable engagement approach.

Program system requirementsChallenges to establishing PbyU also exist in linking the necessary elements of a coordinated, trusted system.Practically, in the immediate to near term, this involves bringing together four key components:

1. Oncology dataset based on the systematic collection of healthcare and treatment information, ideally at a nationallevel, covering essentially all treated cancer patients. This would likely comprise 40 fields of data for every patienttracked in every country involved in the scheme.

2. Trusted third-party aggregator to de-identify and manage the data in a consistent manner on a secure andreliable system.

3. Clear governance of the information and rules regarding the access rights of different user types (national andlocal payers; scientific and medical community; suppliers to healthcare) with the appropriate safeguards to ensurepatient anonymity.

4. Practical application of the data based on distinct outputs for respective users to support:

a. Scientific and medical community: An understanding of clinical processes and outcomes based on real-world practice

b. Payers/suppliers: Financial transaction management based on actual use and agreed value

Core to the success of PbyU will be the level of trust in the underlying data – recognition by suppliers to healthcare of their role in helping payers better understand their investments and make more informed choices. This will meanestablishing systems to assure data accuracy, quality and validity. The most effective way of achieving this is throughfocused effort and a collaborative approach to creating a PbyU pricing infrastructure in Europe.

Realistic ambitionPowered by such a unified strategy, the development of a foundational capability linking highly robust clinical datawith information on drug consumption (Figure 3, overleaf ) is an achievable goal. The recently implemented SACT(Systemic Anti-Cancer Therapy) database in the Uk3 is a practical example of how a national, comprehensive linkeddataset of cancer patients and oncology products can be developed in order to understand real-world management ofthe condition from a clinical perspective (ie, 4a. above and not conceived for PbyU).

Done right, PbyU enables a pricing mechanism and data collection capability that responds to the need for payers toshow they have made the best use of scarce financial resources, while ensuring that innovation is rewarded andoffering outcomes improvements to patients which would otherwise be unavailable due to poor cost-effectiveness.


ImplicationsAs a fundamental change to the way in whichinformation is used to manage healthcare inpartnership between pharma and payers, theestablishment of a PbyU system will raise a numberof important, practical issues. For the industry as acollaborative group, the ability to execute anddeliver on its promise will require answers to somekey questions in relation to:

• Identifying the necessary capabilities andassets, and agreeing which party will beresponsible for their development

• Understanding the notion of risk in terms of theuncertain long-term implications of PbyUversus taking no action

• Determining the right starting point for thepractical implementation of PbyU with regardto product and territory, and planning how tobuild on that in phases to deliver value over thenext 2-5 years

At a broader level, there are far reachingimplications to address in terms of: incorporatingall providers/payers in a market into a singlesystem; determining the steps involved bothwithin and across different countries; running newand old systems in parallel mid-term; and workingwith payers to demonstrate the accuracy andvalue. However, PbyU is the lynchpin on the pathtowards increased integrated industry andhealthcare understanding.

CONCLUSIONThe assumption of high prices and high rewards in oncology is fast giving way to a world where money is a finitequantity, where budgets are fixed, and where there is growing moral outrage at ever higher prices. A world whereachieving product use is based not on price maximization but on ensuring the financial offer for the right product,for the right indication at an economic value that expands drug availability to a broader number of patients. Thisimplies an evolution away from the traditional pricing architecture to a model that is based on the value to theindividual cancer patient.

PbyU offers a platform for creating a more balanced delivery of value, based on commitment, collaboration and a newmodel of engagement between industry and payers, leveraging closer links with the healthcare system and a deeperunderstanding of product use and how patients can derive maximum benefit. Consistent with discussions aroundaccess to innovative medicines,4 and supported by a trusted third party, it will enable data on cancer patients and



“The principle of this scheme in essence is value-based pricing; you pay forthe value or performance of a drug. A differential pricing strategy would stillreward and encourage innovation from a pharmaceutical companyperspective, whilst managing budgets.” Payer, UK

FIGURE 3: A PBYU SYSTEM WILL REQUIRE A DATA SOURCE, TRUSTEDTHIRD-PARTY AGGREGATOR AND APPROPRIATE GOVERNANCE

Transparently governed, aggregated data will underpinmultiple useful outputs



treatment, collated at source and appropriately governed, to serve as a reliable and clinically valid foundation forpricing oncology drugs in a more flexible, evidence-based way. As a core capability that can only be built collectively, it is perhaps not of itself an element of competitive advantage but when integrated with unique products to create arelevant pricing strategy for the market it will serve as the platform for advantage through differentiation.

PbyU is bold in its demand for a consortium approach but also in the fact that while the near-term benefits to all partiesare clear, the implications downstream are less certain. However, within the context of the current unsustainabledynamics, building such a pan-European infrastructure should be a strategic priority for the healthcare industry of theregion. Based on a definitive collection of anonymous patient-level information covering cancer and its treatment, it will serve as the gateway to establishing more sophisticated, outcomes-based pricing in the future.

AcknowledgmentThis article is based on collaborative work. The authors gratefully acknowledge the contributions of Brittany Blackstone,Sarah Gardner and Craig Montgomery at IMS Health.

1 Tackling cancer’s biggest challenge: Combination treatments offer hope to overcome drug resistance. Professor Workman, Deputy Chief Executive, Institute for CancerResearch. Accessed 9 Apr 2014 at: http://www.icr.ac.uk/press/recent_featured_articles/archive_featured_article/combination_treatments/index.shtm

2 Innovation in cancer care and implications for health systems: Global oncology trend report. IMS Institute for Healthcare Informatics, May, 2014. 3 http://www.ncin.org.uk/collecting_and_using_data/data collection/chemotherapy4 Improving patient access to innovative medicines. EFPIA, March 2014. Accessed 11 May, 2014 at: http://www.efpia.eu

“Although challenging, this type of arrangement could be achievable. It issimilar to web-based registries whereby the therapy reimbursement is linkeddirectly to the registry. This method allows differential pricing, and the abilityto distinguish between indications.” Payer, Italy

WHICH PRODUCT TYPES MAY BENEFIT FROM PBYU?PbyU has particular applicability for products with:1. Differential value by indication/patient: Where the value of the drug is different in each indication, forexample in terms of: survival, cure rates, length of course (affecting economic metrics), QALY scores depending onthe sub-population.

2. Differential dosing strength or positioning by indication/patient: If the way in which the drug is takenvaries between indications then the value may differ, for example, through different dosing (strength, frequency,duration). The drug may be listed as a different line of therapy for different indications, eg, first-line for breastcancer but second-line for lung cancer.

3. Usage in combination: The value of the drug may change depending on which other drugs it is combinedwith as this can affect outcomes, reflects choices available and will have varying effects on budgets.

4. High risk of off-label or experimental use: PbyU can help to manage this risk.

5. High-cost: These drugs come under the greatest payer scrutiny, have the highest budget impact and requireinnovative differentiation vs. competitors. Candidates are those where large sums of money are potentially beingleft on the table. Setting up and managing PbyU will prohibit use in $1-10/day products, at least initially.


INSIGHTS | THERAPY ACCESS IN EU

The breadth of applications for which regulators, payers and physicians use real-world evidence (RWE) in oncology continues to expand in their efforts toprovide cancer patients with rapid and ongoing access to innovative and life-prolonging therapies.1 Looking ahead, illustrated through examples, it ispossible to see how RWE use could evolve in Europe and where opportunitiesexist for industry to play a more proactive role with these stakeholders withoutcompromising their commercial interests.

Michael Opel, PHD is Senior Consultant RWE Solutions & HEOR, IMS [email protected]

Amanda McDonell, MSC is Senior Consultant RWE Solutions & HEOR, IMS [email protected]

Karin Berger, MBA is Principal RWE Solutions & HEOR, IMS [email protected]

The authors


Evolution and proactive application of real-world evidenceRWE provides a valuable complement to randomized controlled clinical trial (RCT)data, the gold standard of clinical evidence. RCT data is the only drug-specificevidence available prior to market authorization and hence serves as the primarydriver behind initial pricing, reimbursement and market access decisions. This principle applies, with some variation, across countries and indications. For example, in Germany the IQWiGassesses the benefit of a new medication relative to the standard of care; in France the HAS assesses the relative andoverall clinical benefit; and in England and Wales NICE distils its clinical assessment into the infamous quality-adjustedlife year (QALY).

However, stakeholders are also keenly aware that current RCTs do not provide the answers to all of their questions,often capturing surrogate rather than hard patient-relevant endpoints (eg, progression-free survival vs. overallsurvival).2 While this reflects practical trial design considerations, it leaves payers to base cost-effectiveness decisions on statistically-defined outcomes only.3 Even where trials are designed to measure outcomes, the ethical need for cross-over can make results less compelling.4,5

REAL-WORLD EVIDENCE TODAYEvidence generated in the real world, if collected and analyzed correctly, can help to answer these and otherstakeholder questions.6 Prior to market authorization, it can help to characterize disease epidemiology, treatmentparadigm and associated resource utilization. Post-market authorization it can help assess a drug’s performance outsidethe artificial RCT setting and describe any shifts in the treatment paradigm.

Today, we observe very different levels of RWE usage across these areas. Pre-market authorization, there is some RWEusage, commonly limited by the focus of the national healthcare system: in the Uk, for example, RWE describing thetreatment paradigm is used to inform cost-effectiveness calculations. In one recent submission to the ScottishMedicines Consortium (SMC ) for a breast cancer medication, the use of industry-submitted RWE successfully changedthe SMC’s perception of the standard of care. In France, while limited in use today at initial pricing and market accessdecisions, French payers have signaled some interest in using RWE to improve epidemiological assessment. While RWEis used more for post-market than pre-market authorization, payers are recognizing the importance of understanding adisease to enable more informed decisions.

Use of drug-specific RWE is already extensive and still growing post launch: pharmacovigilance is a well establishedapplication. Given unmet medical need and premium drug pricing, payer interest in RWE has been particularly high inoncology as exemplified by Italy’s complete reliance on innovative agreements in this therapeutic area. In fact,innovative pricing and market access agreements are a growing consumer of RWE insights.

THERAPY ACCESS IN EU | INSIGHTS

Future access to innovative oncologydrugs in the EU

“We focus on the primary RCT endpoint when assessing novel drugs and willcontinue to do so.“ National Payer, UK, March 2014



RWE can also be used by regulators, payers and physicians to help products:in Germany, a real-world study for remifemin (see panel, right) indicated areduction in breast cancer risk which led to the removal of a black boxwarning from the label and hence maintained access for patients.7

Across Europe, the oral formulation of vinorelbine was shown to producesubstantial time savings (Figure 1).8 Such time savings have led to a markedshift in prescribing practice.9

AN EXPANDING ROLE Going forward, the use of drug-specific RWE in the post-market authorizationsetting is likely to intensify as countries follow the example of France andreassess drug efficacy on an ongoing basis. These frequent assessments placeadditional pressure on pharmaceutical companies to develop more evidence.The need for additional evidence to support ongoing access in oncology maybe more muted than in other indications, given the ethical requirement forcontinuing drug availability. However, the complexity of drawing conclusionsbased on the diseases means that RWE must be developed carefully.

RWE is also likely to play a greater role within pharmaceutical companies to direct research efforts towards the areas ofhighest unmet need and demonstrating drug benefit for specific patient cohorts. RWE can help identify patients withparticular characteristics for further research. It can also enable better definition of RCT populations, which in turn willenhance the primary endpoint signal and thus drive access potential.

In fact, the future holds great commercial promise for RWE use to support oncologics. The mortality associated withoncologic indications commands rapid adoption post-market authorization. A recent adoption analysis of a breastcancer medication indicated a later use than indicated for 50% of patients (see panel, opposite). As such, real-worlddata can be used more extensively to monitor and drive adoption.

FIGURE 1: TIME SAVING FROM USING ORAL RATHER THAN IV VINORELBINE BY STAkEHOLDER (MINUTES)8

Patient

+85

Pharmacist

+35

Nurse

+30

Physician

+2

INSIGHTS | THERAPY ACCESS IN EU

REMIFEMIN CASE EXAMPLESituation: Standard hormonetherapy is contra-indicated forwomen with a history of breastcancer; safety of the treatmentalternative (remifemin) unclear forthis patient cohort; black boxwarning on the label.

Data & analysis: Observationalretrospective cohort study usingIMS Disease Analyzer.

Result: No increase in breast cancerrisk from remifemin treatment.

Benefit: Black box removal andcontinued access for patients.

by leading the way in understanding cancer in real-life settings, the industry canensure its relevance beyond specific products.


OPPORTUNITIES FOR INDUSTRY TO SUPPORT ACCESSIt is clear that regulators and payers are requiring more RWE and thatindustry must respond to ensure ongoing compliance. However, there arealso distinct opportunities for companies to generate RWE proactively tosupport their commercial interests:

1. Pre-market authorization

• Use epidemiology- and treatment paradigm-specific RWE to drive R&Dtowards areas of highest unmet need

• Inform RCT design and drive primary endpoint magnitude

2. Post-market authorization

• Monitor effectiveness, epidemiology, safety, changes in treatmentpatterns and compliance to help all stakeholders ensure that evolvingtreatment insight is rapidly adopted into standard practice in anequitable manner

While there are undoubtedly other opportunities for proactive use of RWE,these will allow pharmaceutical companies to better target research,improve pricing and market access potential, and drive product adoption.

RWE brings value in many ways for oncology stakeholders, both inunderstanding cancer as well as assessing potential treatments.Pharmaceutical companies should be active generators and consumers ofRWE to engage effectively with other stakeholders and continue to providemore insights into the disease. By leading the way in understanding cancerin real-life settings, the industry can ensure its relevance beyond specificproducts.

BREAST CANCER TREATMENTPARADIGM CASE EXAMPLEResearch question: Do patientsreceive a novel oncologic in theindicated line of therapy or later?

Data: Robust panel of 800physicians and >590 hospitals,with >57,000 patients/yearreported in EU5.

Result: Approximately 50% ofpatients receive the novelmedication post the indicated lineof therapy.

Benefit: Monitoring and ensuringbest practice.

1 McCabe, C. Market and patient access to new oncology products in Europe: A current, multidisciplinary perspective. Annals of Oncology, 2009; 20:403-4122 Booth C, Eisenhauer E. Progression-free survival: Meaningful or simply measurable? Journal of Clinical Oncology, 2012; 30(10):1030-33 Fleming T, Rothmann M, Lu H. Issues in using progression-free survival when evaluating oncology products. Journal of Clinical Oncology, 2009; 27(17):2874-804 Trotta F, Apolone G, Garattini S, Tafuri G. Stopping a trial early in oncology: For patients or for industry? Annals of Oncology, 2008; 19:1347-535 Chabot I, LeLorier J, Blackstein M. The challenge of conducting pharmacoeconomic evaluations in oncology using crossover trials: The example of sunitinib for

gastrointestinal stromal tumour. European Journal of Cancer, 2008; 44(7):972-76 Garrison L, Neumann P, Erickson P, Marshall D, Mullins C. Using real-world data for coverage and payment decisions: The ISPOR Real-World Data Task Force Report. Value in

Health, 2007; 10(5):326-357 Zepelin, HH. Isopropanolic black cohosh extract and recurrence-free survival after breast cancer. International Journal of Clinical Pharmacology and Therapeutics, 2007;

45 (3): 143-548 James, RD. Improving chemotherapy capacity by switching from intravenous to oral vinorelbine. European Journal of Oncology Pharmacy, 2010; 4(3):14-189 Jeynes-Ellis, A. The vision for real world data - Harnessing the opportunity in the Uk. ABPI White Paper, 2011

THERAPY ACCESS IN EU | INSIGHTS

INSIGHTS | UNDERSTANDING TREATMENT PATTERNS


The impact of new products in a therapeutic setting is highly dependent on prevailing practice and the preference of prescribing physicians. Identifying variance in patterns of treatment can thus aid understanding ofpotential parallels between markets sharing similar constraints on patientaccess. A comparison in metastatic castrate-resistant prostate cancer betweenthe Uk and selected Asian markets reveals some important considerations fornew therapeutic interventions.

Christopher King, MBA is Senior Manager Oncology, RWE Solutions & HEOR, Asia Pacific & China, IMS [email protected]

The author

UNDERSTANDING TREATMENT PATTERNS | INSIGHTS


Implications of variance between UK and AsiaSince 2010, treatment options for patients with metastatic castrate-resistant prostatecancer (mCRPC) in Western Europe have increased with the EMA approval of agentssuch as Jevtana (cabazitaxel); Zytiga (abiraterone); Xtandi (enzalutamide); Xofigo(radium Ra 223 dichloride); and Provenge (sipuleucel-T). In the Uk, where product access is determined by NICE (England/Wales) and SMC (Scotland) based on demonstratedcost-effectiveness in conjunction with overall quality of life and efficacy, patients have two of the new treatmentoptions available to them: Zytiga and the recently recommended (January, 2014), Xtandi.

In Asia, there are similar concerns around ensuring cost-effective treatments for cancer. It is therefore helpful todetermine how prescribing patterns for mCRPC have changed since the launch of Zytiga in the Uk, and to compare thecurrent situation with the treatment of mCRPC in the selected Asian markets of korea, China and Japan. This is madepossible through the use of anonymous patient-level data available in IMS Oncology Analyzer™ (OA).

COMPARING REAL-WORLD PRACTICE IN MCRPCMethod OA is a patient database, collected through a quarterly physician panel survey, which reports information on patientcase history related to treatment across all cancer types. For the purposes of this analysis, a comparison was madebetween the period before Zytiga’s launch (April 2011 to March 2012) and the most recent available data (January toDecember 2013) in korea, China, Japan and the Uk.

Results From April 2011 to March 2012, 126 castrate-resistant prostate cancer patients were collected via OA in the Uk. Asignificant portion (43%) of these patients received a regimen containing docetaxel. From January 2013 to December2013, 132 mCRPC patients were collected, of whom 34% were treated with a regimen containing docetaxel. Zytigausage in 2013 was calculated to be 33% of all mCRPC patients (see Figure 1, page 38).

By comparison, from January 2013 to December 2013:

• Korea: OA collected 35 mCRPC patients, 57% of whom were treated with a regimen containing docetaxel. This usage of docetaxel had been consistent for a two-year period.

• China: OA collected 47 mCRPC patients, 66% of whom were treated with a regimen containing docetaxel.

• Japan: OA collected 31 mCRPC patients, 23% of whom were treated with a regimen containing docetaxel. Usage of docetaxel in mCRPC patients was found to have declined in the past year, from 42% (sample of 33patients) during the period January to December 2012. This would appear to indicate that physicians are choosing to re-challenge with additional hormonal agents in favor of administering docetaxel.

Understanding treatment in metastaticcastrate-resistant prostate cancer


INSIGHTS | UNDERSTANDING TREATMENT PATTERNS


FIGURE 1: PROSTATE CANCER LANDSCAPE IN UK AND SELECTED ASIAN MARKETS

Total Prostrate Cancer PatientsUK - 100% (1,053)korea - 100% (348)China - 100% (307)Japan - 100% (624)

Stage I-IIIUK - 52% (542)

korea - 40% (138)China - 45% (132)Japan - 77% (480)

Stage IVUK - 44% (471)


Source: IMS Oncology Analyzer™, MAT Q4, 2013. Excluding trial patients

N = Patients on a L01 and L02 regimen 140 patients are unstaged

Bone metsUK - 87%

korea - 68%China - 85%Japan - 75%

Bone metsUK - 0%

korea - 0%China - 0%Japan - 0%

Castrate ResistantUK - 25% (132)korea - 17% (35)China - 28% (47)Japan - 22% (31)

N/S1

Uk - 5% (22)korea - 1% (2)China - 0% (0)Japan - 4% (5)

Unknown1

Uk - 11% (48)korea - 8% (16)

China - 15% (27)Japan - 2% (3)

Hormone SensitiveUk - 59% (269)


UK mCRPCAll lines oftherapies

TOP REGIMENSZytiga - 16%

Docetaxel/Goserelin - 10%Bicalutamide/Goserelin - 8%

Zytiga/Goserelin - 8%Docetaxel - 6%

TOP REGIMENSDocetaxel - 54%

Mitoxantrone - 14%Bicalutamide/Triptorelin - 9%Bicalutamide/Leuprorelin - 6%

Cyproterone - 6%

TOP REGIMENSDocetaxel - 38%Flutamide - 9%

Docetaxel/Flutamide - 4%Flutamide/Leuprorelin - 4%

Mitoxantrone - 4%

TOP REGIMENS Goserelin - 10%

Estramustine/Leuprorelin - 10%Bicalutamide - 6%Leuprorelin - 6%Docetaxel - 6%

korea mCRPCAll lines oftherapies

China mCRPCAll lines oftherapies

Japan mCRPCAll lines oftherapies

Total Docetaxel34%

Total Zytiga 33%

Total Docetaxel57%

Total Docetaxel66%

Total Docetaxel23%

UNDERSTANDING TREATMENT PATTERNS | INSIGHTS


FIGURE 2: STATUS OF EMA AND NICE RECOMMENDATIONS FOR RECENT MCRPC PRODUCTS

Jevtana (cabazitaxel)

Zytiga (abiraterone)

Xtandi (enzalutamide)

Xofigo (radium 223)

Provenge (sipuleucel-T)

January, 2011

July, 2011

April, 2013

September, 2013

September, 2013

None issued

June, 2012

January, 2014

None issued

None issued

Product EMA Recommendation Nice Recommendation

Variable practices revealedCurrent treatment practices for patients with mCRPC vary by country. Physicians in korea and China have a higherpreference for treating with a docetaxel-containing regimen than is the case in Japan, where there appears to be apreference to continue treating patients with hormonal therapies rather than chemotherapy agents. Furthermore, thedata suggests that docetaxel-containing regimens are most often used in third-line treatment and later.

DISCUSSIONTreatment patterns have changed significantly in the Uk since the availability of Zytiga and they are expected tocontinue evolving as new therapeutic options become available. Asian physicians would have a similarly positiveattitude to new treatment options for mCRPC but currently are unable to prescribe newer therapies due to marketaccess challenges. The way in which physicians in korea, China and Japan choose to treat their mCRPC patients in thefuture could follow a similar pattern to the Uk but ultimately this will be determined by the regulatory andreimbursement approval of new therapeutic agents.

The relative size of mCRPC in the overall cancer population in Asia is fairly small in comparison to Western markets.There is an opportunity for new mCRPC treatments to be designated as orphan drugs due to the relatively small patientpopulations and clinical superiority to currently available therapeutic options. As orphan drug status influencesregulatory and reimbursement decisions, this is a critical element of ensuring patient access to new treatments.

As the regulatory authorities in Asia determine the usage parameters for new therapies, consideration of diseasedynamics will also play a role. Incidence, prevalence and mortality in mCRPC vary greatly between Western and Asianpopulations, but also among different Asian populations. It is clear from the OA data that the difference in populationdistribution between early and metastatic disease can be substantial and this will have significant bearing on patienttreatment options. Finding the optimal sequence of therapies will differ according to patient and disease characteristicsand availability of treatments. Based on these dynamics, the most common treatment strategies will vary betweencountries and this should be accounted for in determining product positioning and messaging to physicians.

The most common treatment strategies will vary between countries and this shouldbe accounted for in determining product positioning and messaging to physicians.

The ability to link fragmented streams of data is enabling new levels of insight incancer across the continuum of care. As more is demanded of available datasources, accounting for their respective strengths and limitations is essential toaddress specific questions efficiently. A recent comparison of two linkeddatasets in the US for non-small cell lung cancer underscores the importance ofthis critical step in ensuring the best data selection for particular needs.

Rolin Wade, RPH, MS is Principal RWE Solutions & HEOR, IMS [email protected]

PAGE 40 IMS HEOR & REAL-WORLD EVIDENCE SOLUTIONSPage 1 IMS HEALTH ECONOMICS AND OUTCOMES RESEARCH

INSIGHTS | RESEARCH DATA SELECTION IN NSCLC

The authors

Chi-Chang Chen, PHD, M.PHARM is Director RWE Solutions & HEOR, IMS [email protected]

Shibani Pokras, MPH is Principal RWE Solutions & HEOR, IMS [email protected]


A comparison of real-world insights in non-small cell lung cancerLung cancer (LC) is the leading cause of cancer-related mortality globally.1 Oftendiagnosed at an advanced stage with poor prognosis, in the US alone it is responsiblefor around 159,000 deaths each year.2

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all LC. Despite the existence of several largeadministrative claims and EMR databases in the US, the ability of any one of these individually to answer real-worldresearch questions in NSCLC is limited. Increasingly, such questions require data elements that include histology andstaging at diagnosis, longitudinal treatment patterns across multiple sites of care, as well as detailed utilization and cost data.

Claims data contains information across various healthcare settings and includes detailed treatment and resourceutilization. However, it lacks the clinical data that is critical to analyzing NSCLC populations, such as stage, morphology,laboratory results and performance status. EMRs from oncologist offices, on the other hand, do provide this type ofdetail but being sourced from a single site of care, such as an oncology practice or clinic, information on hospitalizationor surgical care may be unavailable or incomplete.

Thus, the fragmented data streams from individual databases have significant limitations in understanding thecomplete patient journey. One solution to this problem is the creation of a more comprehensive longitudinal patientrecord by linking data sources to one another at the individual patient level.

With this in mind, IMS Health recently explored the generation of a NSCLC comprehensive disease record (CDR) linkingthe PharMetrics Plus™ health plan claims database to the IMS Oncology EMR database. A comparison of this linkeddataset to the US National Cancer Institute SEER data (Surveillance, Epidemiology and End Results) for NSCLC, illustratesthe importance of accounting for the strengths and limitations of available data sources to best address the particularneeds of any given research question.

THE INDIVIDUAL DATABASES IMS Health linked the IMS PharMetrics Plus™ health plan claims database to the IMS Oncology EMR, as well as mortalitydata, to create the NSCLC Comprehensive Disease Record. This was compared to the SEER database. Summaries of eachdatabase are provided below.

IMS PharMetrics Plus™ health plan claims databaseThis longitudinal database comprises adjudicated claims for more than 150 million unique enrollees across the US,representing one of the largest claims databases in the US. Enrollees with both medical and pharmacy coveragerepresent more than 45 million unique lives annually. The database offers longitudinal information on outpatientdiagnoses and procedures, prescription drug use, hospital admissions, patient demographic and payer details, costsand healthcare resource use.

Research question-driven data selection

ACCESSPOINT • VOLUME 3 ISSUE 5 PAGE 41OUTCOMES - Issue 1 Page 1

RESEARCH DATA SELECTION IN NSCLC | INSIGHTS

1 GLOBOCAN 2012, Estimated cancer incidence, prevalence and mortality worldwide in 2012. Accessed 9 May, 2014 at: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx.2 American Cancer Society, Cancer Facts and Figures, 2014. Accessed 9 May, 2014 at: http://www.cancer.org/acs/groups/content/@research/documents/webcontent/acspc-

042151.pdf





IMS Oncology EMR With a history from 1997, this dataset encompasses over 500,000 cancer patients across 37 states and 550 treatingoncologists. Approximately 60,000 patients are observed every month. Data elements include: cancer staging; TNMvalues; patient demographics; clinical lab results; injectables and oral medications prescribed or administered, withdetailed dosing schedules and drug regimens; vitals; and radiation treatments, including sites radiated, and mortality.3

SEER database An authoritative source of cancer statistics, SEER collects and publishes cancer incidence and survival data in the USfrom population-based cancer registries covering approximately 28% of the population. Data elements include: patientdemographics; primary tumor site; tumor morphology and stage at diagnosis; first course of treatment; and follow-upfor vital status.4

DATABASE LINKAGE IMS Health linking technology uses a proprietary algorithm and deterministic matching method, executed through atrusted third-party leveraging a patented HIPAA-compliant de-identification process, to create a patient key. Patientswith a matching encryption key in both datasets can be assembled into a third study cohort.

DATA EXTRACTION METHODOLOGY As shown in Figure 1, the NSCLC CDR linked dataset comprised three types of linked datasets based on the followinginclusion criteria:

1. Core datasetThe approximately 500 patients included in the Core dataset have an NSCLC diagnosis in both PharMetrics Plushealth plan claims and oncology EMR. Information from both claims and oncology EMR is included for thesepatients.

3 Mortality Data from Consumer (Cx) Database: Sourced from social security death index records. IMS Health receives approximately 50% of all deaths on average throughlinkage to this consumer data.

4 When linked to Medicare data, SEER can provide insight into healthcare resource use for patients covered by Medicare, and prescription treatment details for the subsetthat has Medicare Part D coverage. This linked data typically has a two-year time lag.

FIGURE 1: NSCLC CDR FEASIBILITY COUNTS

* Counts include histologically confirmed NSCLC patients as well as patients proxied through either (1) lack of etoposide use, or (2)with pemetrexed use in history or follow-up

Offering structure Approximate patient counts (Jan 2006 – March 2013)

Core: Patients with at least 1 NSCLC diagnosis* in PharMetrics Plushealth plan claims with medical and pharmacy coverage AND in oncology EMR

Core with PharMetrics Plus: Patients with at least 1 NSCLCdiagnosis* in PharMetrics Plus health plan claims with medical andpharmacy coverage PLUS all patients available in Core offering

Comprehensive: Patients with at least 1 NSCLC diagnosis* inEITHER PharMetrics Plus health plan claims with medical andpharmacy coverage OR at least 1 NSCLC diagnosis* in EMR PLUS all patients available in Core offering

~500

~156,000

~182,000



2. Core with PharMetrics Plus datasetThis includes approximately 156,000 patients with an NSCLC diagnosis available in PharMetrics Plus health planclaims and all their claims level detail. It also includes information from oncology EMR for the subset ofapproximately 500 patients who have an NSCLC diagnosis in oncology EMR and who are also diagnosed with NSCLCin PharMetrics Plus.

3. Comprehensive dataset This includes approximately 156,000 patients with an NSCLC diagnosis in PharMetrics Plus health plan claims andapproximately 26,000 patients with an NSCLC diagnosis in oncology EMR. It also contains a subset of approximately500 patients with an NSCLC diagnosis in both datasets. Available claims and EMR data for each of these populationsvaries by whether the patient is identified in PharMetrics Plus, oncology EMR, or both. In total, the comprehensivedataset provides information on approximately 182,000 NSCLC patients.

The SEER NSCLC cohort contains pathology-confirmed NSCLC patients from 2006-2010 (152,000+ patients).

As shown in Table 1, the respective databases differ, both in their source data as well as the collection methodology,and consequently have their own particular strengths and limitations.

TABLE 1: COMPARISON OF NSCLC DATABASE ATTRIBUTES

Attributes Core dataset Core with PharMetrics Plus Comprehensive SEER*

*Age at diagnosis for SEER is 20 and higher; Years used 2006 to 2010. ICD O codes used for SEER NSCLC include bronchioloalveolar(82503); large cell carcinoma (80123); adenosquamous carcinoma (85603); non-small cell carcinoma (80463)

NSCLC Sample size

Strengths

Limitations

~500

1. Comprehensive longitudinal claims and clinical datafor all patients, beyond Medicare-eligible

2. Only 3-4 months data lag compared to 2+ years for SEER

3. Additional treatment details, such as clinical labresults and co-morbidities prior to diagnosis, enable expanded determination of risk profile

4. Allows segmentation by payer and product type5. Availability of patient out-of-pocket payments

1. Smaller sample size2. May be underpowered

for some researchquestions

1. Aged 65 and overNSCLC populationunder represented

2. Majority of patients do not have stage/morphology data

1. Sample with stage/morphologydata not as complete as SEER

2. Staging for blood cancers generallynot available

3. Not a registry – data fields are notalways populated for all patients

1. No claims datafor completeview ofoutpatient/inpatient/pharmacyutilization

2. Long data lag:2+ years

1. Generalizableto USpopulation

2. Linked to NDI/Social securityadministrationfor mortalitydata

3. Complete race/ethnicity data

In addition to 1-5 strengths of Coreand Core with PharMetrics Plus1. Capable of building cohorts

representative of both under andover 65 year population

2. Offers flexibility in cohort building/selection depending on researchquestions

3. Maximum longitudinal samplewith clinical details

~156,000 ~182,000 ~152,000




DATABASE ANALYSIS A breakdown of patient characteristics among the respective datasets is summarized in Table 2. It can be seen thatgender distribution was broadly similar across all datasets, with an even split between male and female patients in theIMS Health datasets, and a slightly higher proportion of males than females in the SEER sample (56% vs. 44%). However, notable differences can be observed between the respective populations in relation to age at diagnosis and the stage of disease at diagnosis.

Age at diagnosis Among the approximately 500 linked patients in the IMS Health Core dataset, 25% were aged 65 years and over atdiagnosis compared to 64% in the SEER population (Table 1, Figure 2). In the two additional IMS Health datasets – Corewith PharMetrics Plus and Comprehensive – the proportion of patients aged 65 years and over at diagnosis was higherthan in the linked dataset (45% and 48%, respectively). The IMS Health datasets represent a younger populationcompared to the SEER sample, reflecting the source of data being a commercially-insured population.

Stage at diagnosisAmong the approximately 500 linked patients in the IMS Health Core dataset, 47% of patients were Stage IV/metastaticat diagnosis compared to 21% in the SEER population (Table 1, Figure 3). The two IMS Health datasets, Core withPharMetrics Plus and Comprehensive, have a more representative population of patients who were metastatic atdiagnosis (31% and 30%, respectively) but have a larger portion of unknown stage.

CHOOSING THE RIGHT DATA OPTION The respective characteristics of the linked dataset and the SEER population reveal disparities that should be taken intoaccount when choosing data to answer specific research questions.

While the Core dataset is the smallest among the four comparison data options, it offers the most comprehensive datafor all patients; the Core with PharMetrics Plus dataset provides the addition of longitudinal claims data for a muchlarger sample of NSCLC patients; the Comprehensive adds all NSCLC patients from the OEMR database; finally, the SEERNSCLC sample is nationally representative in terms of age and geography for patients with pathology-confirmed NSCLCand offers the most complete mortality status data.

TABLE 2: DATABASE PATIENT CHARACTERISTICS

Core2006-2013

Core withPharMetrics Plus

2006-2013Comprehensive

2006-2013SEER*

2006-2010

*Age at diagnosis for SEER is 20 years and over

NSCLC sample size

Stage at diagnosisStage IV/MetastaticStage I to III or unknown

Age Group 18-34 years 35-44 years 45-54 years 55-64 years 65+ years

GenderFemale Male

~500

47%53%

0%2%

21%53%25%

50%50%

~156,000

31%69%

1%3%

15%35%45%

49%51%

~182,000

30%70%

1%3%

15%34%48%

49%51%

~152,000

21%79%

0%2%

10%24%64%

44%56%



Based on their respective profiles, Table 3 illustrates how the most robust and appropriate dataset may be chosendepending on the nature of the research enquiry.

CONCLUSIONSTechnology is now employed providing the ability to link diverse databases to one another and develop a longitudinal,clinically rich view of an NSCLC population. Comparisons between the IMS Health linked datasets and the SEER populationhighlight potential differences which should be considered when selecting data for specific research needs. Each databasehas its own unique set of strengths and limitations, and selection of the database should consider critical factors such asthe target populations and specific study questions of interest to ensure the optimal choice for the purpose.

FIGURE 2: AGE GROUP AT DIAGNOSIS

100%

90%

80%

70%

60%

50%

40%

30%

20%

10%

0%

FIGURE 3: STAGE AT DIAGNOSIS

18-34 years

Core Core withPharMetrics Plus

Comprehensive SEER

25%

53%

21%

2%

45%

35%

15%

3%

48%

34%

15%

3%

64%

24%

10%2%

35-44 years 45-54 years 55-64 years 65+ years

100%

90%

80%

70%

60%

50%

40%

30%

20%

10%

0%

Stage I to III or unknown

Core Core withPharMetrics Plus

Comprehensive SEER

53%

47%

69%

31%

70%

30%

79%

21%

Stage IV/Metastatic

TABLE 3: SAMPLE OF RESEARCH QUESTIONS BY DATASET

Core Core with PharMetrics Plus Comprehensive SEER

Questions requiringa comprehensiveexamination ofclinical, treatmentand economicoutcomes based onspecific tumorcharacteristics

and Research questions

are adequatelyanswered utilizing asmall patientpopulation

A medical chartreview is beingconsidered toanswer the researchquestion

Questions requiring a comprehensiveexamination of clinical, treatment and economicoutcomes based on specific tumor characteristics

and What are the treatment patterns/healthcare

resource utilization in the broad population? What are the differences in overall healthcare

costs among patients being treated bytreatment line?

How do various patient co-morbidities andpatient history affect treatment selection andoutcomes?

What types of supportive care, diagnostictesting and surgery are provided to patientswith NSCLC?

What are the utilization patterns of newtreatment modalities to the market and in whattypes of patients and by line of therapy?

All questions for Core withPharMetrics Plus

and How are clinical

lab-confirmed treatmenttoxicities (eg, anemia,neutropenia) related totreatment exposure andpatient characteristics?

What is the distribution offirst-line therapy based ontumor stage at diagnosis?

How is performance statusassociated withhospitalization?

What are the trendsin NSCLC over timesuch as incidence,prevalence andsurvival statistics?

What is thebreakdown bystage/morphologyand by race/ethnicityat diagnosis?

What is the impactof stage at diagnosisand morphologysubtype on overallsurvival?

What is the overallsurvival from theinitiation of each lineof therapy?

INSIGHTS | TARGETED THERAPIES IN EMERGING MARkETS


Significant growth in the oncology sector as a leading area of healthcareexpenditure reflects in part the rising contribution to sales of the emerging Asia Pacific markets. With their role set to expand even further, these countriesare ripe with potential but also present significant challenges for pricing andmarket access. Innovative models and collaborative initiatives that are able toaddress affordability issues will be key to unlocking opportunities for high-valueoncologics in the region.

Joe Caputo, BSC is Regional Principal RWE Solutions & HEOR, Asia Pacific, IMS [email protected]

Amkidit Afable, MBA is Principal IMS Consulting Group, Asia Pacific, IMS [email protected]

The authors

TARGETED THERAPIES IN EMERGING MARkETS | INSIGHTS


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Opportunities and challenges in emerging Asia Pacific marketsThe global pharmaceutical market is set to increase to circa $1.2 trillion in the nextfew years, with pharmerging markets1 expected to contribute double-digit growthduring the same period. This outlook is being driven by several therapeutic classesthat provide attractive growth potential, including oncology, respiratory and diabetes. The Asia Pacific region is fast becoming a major contributor to global oncology sales. A recent report on innovation incancer care by the IMS Institute for Healthcare Informatics confirms that pharmerging markets have made cancer theirfourth largest healthcare spend area and are poised for further growth.2 Some are already ahead of the curve; in China,for instance, oncology now represents the second largest therapeutic class.

These high growth rates (Figure 1) can be attributed to:

• Greater numbers of people diagnosed with cancer, driving necessary demand for more advanced and affordableoncology products in the first instance

• Increasing income and patient affordability, resulting in rising spend on expensive oncology treatment

• Expanded coverage of oncology products under public health insurance schemes, eg, korea and Taiwan haveextended coverage to include certain targeted cancer therapies such as Iressa (gefitinib)

High-value oncology targeted therapies

FIGURE 1: SALES AND GROWTH OF TOP THERAPY AREAS IN ASIA-PACIFIC REGION


1 Pharmerging countries are defined as those with >$1Bn absolute spending growth over 2013-17 and which have GDP per capita of less than $25,000 at purchasing powerparity (PPP). Tier 1: China; Tier 2: Brazil, India, Russia; Tier 3: Mexico, Turkey, Venezuela, Poland, Argentina, Saudi Arabia, Indonesia, Colombia, Thailand, Ukraine, SouthAfrica, Egypt, Romania, Algeria, Vietnam, Pakistan and Nigeria.

2 IMS Institute for Healthcare Informatics. Innovation in cancer care and implications for health systems: Global oncology trend report, May 2014

Source: IMS Health MIDAS, 2013; Top therapy areas comprise 80% of the Asia-Pacific market; MAT Q3/2008–MAT Q3/2013.


CHALLENGES WITHIN GROWING MARKETS Although at face value there is a significant opportunity provided by the growth of emerging markets, pharmacontinues to face challenges, and multinational companies (MNCs) have lost ground both to local manufacturers andgeneric competition in terms of market share. Pricing, access and regulatory challenges continue to be pain points;pricing and market access is seen as the number one issue facing the industry in the next 3-5 years according to asurvey of senior MNC executives.

Specific challenges include affordability-constrained populations with limited access and low awareness:

• Around 3.8 bn people live in Asia, the vast majority on very low income levels (Figure 2)

• High out-of-pocket (OOP) spend on medicines (often >50%)

• Healthcare spend as a % of GDP (around 2% to 6%) lags developed-world averages

• Significant gap in healthcare delivery (eg, physicians per capita below half of OECD average)

MULTINATIONAL RESPONSESMNCs are increasingly acknowledging the challenges of the emerging countries. Many are looking to innovate as analternative to implementing traditional R&D pricing models in markets that cannot generally afford the price of globalinnovation. To address affordability barriers and expand access for oncology products in emerging Asia, evidencesuggests that pharma has so far focused on applying discrete affordability-based levers, including:

• Direct price cuts/simple discounts (blanket discount on price list)• Sanofi price cuts in India. Despite the rarity of price cuts in India, Sanofi established a substantial presence

within the vinca alkaloid (L1C) class of oncology drugs after reducing the price of both 20mg and 80mgTaxotere (docetaxel) by 60% in the country. Its share of volume increased significantly as a consequenceacross both dosage strengths.

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FIGURE 2: POPULATION DISTRIBUTION ACROSS INCOME GROUPS IN REPRESENTATIVE EMERGING ASIAN COUNTRIES

Source: Based on data from: key indicators for Asia and the Pacific 2010. Asian Development Bank, August, 2010; p17




• Roche discounts for Herceptin (trastuzumab) and Avastin (bevacizumab) in Thailand. With both of thesebreast cancer products unreimbursed and patient affordability low, discounting helped Roche gain groundon non-targeted therapies such as Eloxatine (oxaliplatin) in terms of value share. After cutting the price ofAvastin by 15% and Herceptin by 40% in 2007 the company achieved value growth of more than 25%annually, reflecting increased demand and affordability.

• Volume-based patient discounts for each additional cycle or course • Roche volume discounts for Tarceva (erlotinib) in Indonesia. With Tarceva unreimbursed for non-small cell

lung cancer and patient affordability low, Roche offered patients volume-based discounts for the drug. Aspart of the scheme the company covered cycles 3 & 6 out of the total 6 cycles required for treatment, therebyincreasing the likelihood of patients completing their course. This had the impact of reducing OOP costs andincreasing loyalty to the brand.

• Patient income-based discount (income-based tiered pricing) • Patient access programs fall into this category where certain low-income segments of the population are

given access to healthcare via partnerships and co-funding arrangements between pharma, government andthe patients themselves. In China, for instance, Bayer’s Nexavar (sorafenib) is made available free to patientsfor their lifetime after they have purchased 3 months’ treatment.

Generally, such levers appear to have expanded the market and enabled MNCs to gain a competitive edge, resulting inoverall value growth. In particular, MNCs have succeeded in expanding access to a broader population base by simplycutting prices to meet relatively lower affordability and income per capita levels in the developing world.

WAY FORWARD Pricing and access plays in oncology in Asia are ripe for innovation and change. One such example is in China, where Roche has created significant buzz by partnering with Swiss Re (see panel below). The government in particularhas recently been encouraging a shift towards more pharma-private insurance partnerships to unlock access to high-cost treatments.

TARGETED THERAPIES IN EMERGING MARkETS | INSIGHTS

INNOVATIVE APPROACHES TO PRICING AND MARKET ACCESS Roche/Swiss Re partnership in China

Background. In 2010, with a large percentage of its portfolio dedicated to high-cost oncology products and facing continued affordability issues in China, Roche partnered with global reinsurance company Swiss Re toaccelerate access to innovative oncologics in the country.

Key features. In a marked shift away from traditional patient access schemes, the partnership focused onsupplementing basic government health insurance through provision of private insurance cover to China’s middle class. This included treatments for cancer which were mostly paid for OOP.

Benefits. With 6 million enrollees by 2012 and substantial growth anticipated, this groundbreaking, market-shaping approach, supported by a novel funding mechanism, significantly expanded access to the country’s rising middle class with government backing for increased participation of private insurance in healthcare coverage.

Source: Roche to boost cancer drug sales in China with Swiss Re health insurance partnership. IHS Global Insight. Accessed 9 May, 2014 at:http://www.ihs.com/zh/cn/products/global-insight/industry-economic-report.aspx?ID=1065973425

Although such non-traditional partnerships are still in their infancy, a number of shifts could potentially occur as emergingAsia and the oncology space become an even more important battleground. These are expected to include:

• Top-down, company-driven initiatives. Move towards more portfolio or company-wide driven brand-specificinitiatives (eg, access, affordability or tiered pricing implementation across the entire portfolio)

• Innovative partnerships and funding mechanisms. Establishment of creative financing (eg, micro-financingschemes; partnerships with banks and other financial institutions; collective procurement; social media drivensponsorships, etc) and/or expanding partnerships and funding to non-traditional sources (eg, high net worthindividuals; company CSRs; pseudo-government organizations; international NGOs; gaming and lotterycorporations, etc).

• Broader stakeholder engagement through emerging channels. Expansion of stakeholder engagement to takeinto consideration an increasingly complex network of influencers (eg, patients, advocacy groups, NGOs,technology companies) as well as emerging channels of influence (eg, social media, tech apps, etc).

• Linkage and leverage of new sources of RWE and new technologies. This includes the ability to mine socialmedia and will support more informed R&D, commercial strategies and outcomes (eg, use of RWE in reimbursementdecisions in korea and Thailand; Merck, UCB and Novartis partnering with PatientsLikeMe, a patient organization, togather patient views on psoriasis, epilepsy and organ transplant respectively to better inform outcomes, etc).

• Patient-centric business models. Shift from product to service and value-based offerings which provide a moreholistic and personalized solution to patients, encompassing the whole patient journey as well as thepharmaceutical value chain in totality (eg, personalized medicine: individualized and customized approach todisease management; integration of patient needs throughout the value chain, etc).

KEY TAKEAWAYS MNCs increasingly have to adopt innovative pricing and access models to compete in high-value therapeutic classes,such as oncology. Reliance on the traditional R&D cost-based pricing model is no longer an option, particularly inemerging markets where affordability is a key issue. Whilst the inflection point for innovative pricing and accesssolutions may be more of a medium- to long-term game for most MNCs, there is nevertheless a willingness to supportinnovative access initiatives that include private funding mechanisms and collaborative partnerships. By takingcalculated risks and positioning themselves as early movers, MNCs can potentially reap greater rewards over their peersand bridge the gap to expanded patient access to healthcare.


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DRUG UTILIZATION | INSIGHTS

Real-world evidence has delivered great insights in oncology but manyimportant research questions remain unanswered. As improvements in datacapture, reach and access bring larger patient numbers and depth acrosssettings of care, attention should focus on underserved areas of understandingin cancer, such as co-morbidities and thrombosis, to ensure optimal drugutilization and improved outcomes.

Jacco Keja, PHD is Senior Principal RWE Solutions & HEOR, IMS [email protected]

The authors

Birgit Ehlken, MSC is Director RWE Solutions & HEOR, IMS [email protected]

Joel Kallich, PHD is Principal, Big Health [email protected]

Drug utilization in oncology

ACCESSPOINT • VOLUME 3 ISSUE 5 PAGE 51OUTCOMES - Issue 1 Page 1ACCESSPOINT • VOLUME 4 ISSUE 8 PAGE 51

Current topics and challenges Rising healthcare costs, particularly in cancer, together with continued concernsabout safety, efficacy and quality have generated a call for more and better real-world evidence (RWE). The appropriate collection and interpretation of real-world data (RWD) is central to oncology research, treatment andcoverage/reimbursement decisions. All stakeholders need to understand the vast amount of evidence being generatedbut, more importantly, be able to translate that evidence into decisions and processes that can benefit cancer care.Appropriate use of both drugs and information can lead to enhanced outcomes for patients, reduced healthcare costs,and increased value to all stakeholders.

CURRENT STATUS RWD sources vary in their richness, quality and timeliness, and hence in their value for pharmacovigilance. In recognition of the need for improvements, regulators have been developing tools to speed up the collection of dataat the point of care, thereby enabling earlier detection of safety issues. The US Sentinel initiative is one example of asystem designed to enable higher quality and faster information on a product’s use and adverse event profile in real-world (and sometimes real-time) clinical practice, and to use this knowledge more effectively.

Epidemiological evaluations using population- or census-based approaches can help test hypotheses and defineevolving safety problems quickly. However, this requires specially trained staff and significant resources. In addition,improved tools are required to aggregate health information electronically and then leverage other technology toaccess and analyze this quickly and reliably. Although the wider adoption of EMRs and other health informationsystems will help to harness these types of opportunities, more resources are needed for making more effective,frequent use of the practical clinical data culled from real-world settings.

UNMET RESEARCH NEEDS IN ONCOLOGY The ability to gain a deeper understanding of drug utilization is highly relevant in oncology, especially given that abroad range of new treatment options are emerging. An area where there is a particular requirement for more andbetter information is the way in which co-morbidities and other patient characteristics influence diagnosis, treatmentand outcome.

Impact of patient characteristics, including co-morbiditiesSurvival patterns of cancer patients with co-morbid disease are well studied but often with compounded co-morbidityindexes. Cohort studies which dissect the interaction between disease and cancer are rare. A recent publication on alarge cohort using data from medical and administrative registries found this interaction to be substantial in breastcancer, affecting mortality (Figure 1, overleaf ).1 Understanding this interaction and improved treatment of the co-morbid diseases and breast cancer should delay death caused by this interaction.

Drug utilization in oncology

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INSIGHTS | DRUG UTILIZATION

1 Ording AG, Garne JP, Nyström PM, Frøslev T, Sørensen HT, Lash TL. Comorbid diseases interact with breast cancer to affect mortality in the first year after diagnosis –a Danish nationwide matched cohort study. PLoS One, 2013; 8(10):e76013


ACCESSPOINT • VOLUME 3 ISSUE 5 PAGE 53OUTCOMES - Issue 1 Page 1




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• Treatment patterns: Substantial co-morbid conditions also impact cancer treatment patterns. A retrospectivecohort analysis of elderly chronic lymphocytic leukemia (CLL) patients, using the linked Surveillance, Epidemiology,and End Results (SEER)-Medicare database, found that ~60% of advanced stage CLL patients are not receivingtreatment, possibly due to older age and/or a higher co-morbidity burden.2 Additional and better data on clinicaland patient decision making is needed to determine the reasons for this finding. Similarly, understanding theinteraction between disease progression and the side-effects of treatment and the way this impacts subsequentdecision making, requires better and more complete data across the patient journey through the healthcare system.

• Long-term follow up: Recent studies have found that childhood cancer survivors are at-risk for many late effects ofboth treatments and the disease, potentially requiring additional therapies to improve their quality of life andoutcomes. The results from a provincial health insurance registry and the Childhood Cancer Survivor Study indicatethat survivors of childhood, adolescent and young adult cancer have an increased likelihood of using all categoriesof antidepressants compared to their peers. This may indirectly reflect increased underlying prevalence of mentalhealth conditions among these individuals.3,4

FIGURE 1: MORTALITY RATES PER 1,000 PERSON-YEARS FOR 0–1 YEAR OF FOLLOW-UP BY CHARLSON CO-MORBIDITY INDEX (CCI) SCORESAND INDIVIDUAL DISEASES IN THIS CO-MORBIDITY INDEX.

2 Satram-Hoang S, Reyes C, Hoang kQ, Faiyaz Momin F, Skettino S. The Unmet Need in Chronic Lymphocytic Leukemia: Impact of Comorbidity Burden on TreatmentPatterns and Outcomes in Elderly Patients. Journal of Cancer Therapy, 2013; 4:1321-1329

3 Deyell RJ, Lorenzi M, Ma S, Rassekh SR, Collet JP, Spinelli JJ, McBride ML. Antidepressant use among survivors of childhood, adolescent and young adult cancer: A report ofthe Childhood, Adolescent and Young Adult Cancer Survivor (CAYACS) Research Program. Pediatr Blood Cancer, 2013; 60(5):816-22

4 Brinkman TM, Ullrich NJ, Zhang N, Green DM, Zeltzer Lk, Lommel kM, Brouwers P, Srivastava Dk, Jain N, Robison LL, krull kR. Prevalence and predictors of prescriptionpsychoactive medication use in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. J Cancer Surviv, 2013; 7(1):104-14

Source: Ording AG, Garne JP, Nyström PMW, Frøslev T, et al. (2013) Comorbid Diseases Interact with Breast Cancer to Affect Mortality inthe First Year after Diagnosis – A Danish Nationwide Matched Cohort Study. PLoS ONE 8(10): e76013. doi:10.1371/journal.pone.0076013http://www.plosone.org/article/info:doi/10.1371/journal.pone.0076013

52042032022012020-80

Baseline

CCI score 1

CCI score 2-3

CCI score ≥ 4

Myocardial infarction

Congestive heart failure

Peripheral vascular disease

Cerebrovascular disease

Dementia

Chronic pulmonary disease

Connective tissue disease

Ulcer disease

Mild liver disease

Diabetes I and II

Hemiplegia

Moderate to severe renal disease

Diabetes with end organ damage

Any tumor

Leukemia

Lymphoma

Moderate to severe liver disease

Metastatic solid tumor

AIDS

Rate per 1000 person-years

0-1 year of follow-up

Co-morbidity Breast cancer Interaction contrast

The findings of this study underscore the need for further research on the psychopharmacologic treatment ofsurvivors of childhood cancer. Characterization of medication utilization, including indication for use, dose andpolypharmacy, are important considerations for future studies. Understanding predictors of psychoactivemedication use among this patient population has the potential to inform screening and intervention practicesaffecting many childhood cancer survivors.

Research results from RWD of cancer patients with co-morbid conditions have triggered the development of clinicalguidelines – steps towards the rapid learning healthcare system for oncology that the Institute of Medicine envisionedin 2009. These have included the release of guidance by ASCO in 2012 on appropriate chemotherapy dosing for obesecancer patients; real-world studies have demonstrated that up to 40% of obese patients receive limited chemotherapydoses that are not based on actual body weight, possibly affecting treatment effectiveness for these patients.5

ThrombosisThe use of RWE in the past few years has enhanced understanding of cancer-associated thrombosis, a major cause ofmorbidity and mortality in cancer patients. By utilizing retrospective data, researchers have found high rates of clinicalevents; the most contemporary reports document rates as “unacceptably high”. With the increasing cancer prevalenceand age of the population, enhanced detection of incidental thrombosis, and the greater thrombogenicity of multi-agent chemotherapeutic regimens, a steady increase in the incidence of cancer-associated thrombosis during the past two decades has been observed.6

In particular, cisplatin-based regimens are associated with a wide range of thromboembolic complications. A databaseanalysis found that about 18% of patients receiving cisplatin-based chemotherapy experience a thromboemboticevent.7 Venous manifestations of cancer-associated thrombosis include deep vein thrombosis (DVT) and pulmonaryembolism (PE), as well as visceral or splanchnic vein thrombosis, together described as venous thromboembolism (VTE).

Cancer-associated thrombosis affects patient lives significantly. The consequences of VTE include: the need for long-term anticoagulation; a 12% annual risk of bleeding complications; up to 21% annual risk of recurrent events (even withanticoagulation); delay or discontinuation of chemotherapy; consumption of healthcare resources; and a potentialimpact on patient quality of life. Most importantly, thrombotic events are the second leading cause of death in cancerpatients (after cancer itself ) and are associated with worsened short-term and long-term survival.

The safety and efficacy of anticoagulant therapy prior to, during and post anticancer treatments has not been wellstudied. The use of EMRs in this respect has the potential to provide much information for clinicians. Further, the impactof co-morbidities, other demographic and clinical characteristics of patients, as well as other oral or intravenousmedications, can be quickly and efficiently investigated by researchers with access to large numbers of these records.

DATABASE CHALLENGES IN ONCOLOGY Databases methods offer fast and efficient access to data. Approaches to linking datasets are now underway, furtherextending their application. These differ in the US and Europe but both lead to valuable sources and major initiativesare underway to open up data. However, datasets must be of high quality and sufficient size when dealing withoncology, especially given the lower incidence numbers and the need to create different cohorts of patients withdifferent co-morbidities.

USIn the US, the usual claims data, promising volumes and particularly good access, falls short in this case due to lack ofclinical detail. EMR data, which often has the clinical detail, does not have sufficient absolute numbers and is not linkedacross different treatment settings – making it challenging to capture real-world outcomes or track utilization patterns.

5 Griggs JJ, Mangu PB, Anderson H, Balaban EP, Dignam JJ, Hryniuk WM, Morrison VA, Pini TM, Runowicz CD, Rosner GL, Shayne M, Sparreboom A, Sucheston LE, Lyman GH;American Society of Clinical Oncology. Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practiceguideline. J Clin Oncol, 2012; 30(13):1553-61

6 Lee AYY, Peterson EA. Treatment of cancer-associated thrombosis. Blood, 2013; 122:2310-23177 Moore RA, Adel N, Riedel E, et al. High incidence of thromboembolic events in patients treated with cisplatin-based chemotherapy: A large retrospective analysis. J Clin

Oncol, 2011; 29(25):3466–3473


INSIGHTS | DRUG UTILIZATION



Solutions therefore need to be built by creating integrated data platforms comprising comprehensive data acquisition,integration, warehousing and analytics to explore treatment patterns, drug utilization and clinical outcomes in the real-world setting – without compromising patient confidentiality. This has been accomplished successfully in the US throughthe creation of data pools from oncology practices and linking these to EMRs in other healthcare settings, as well as otherdatabases such as healthcare claims.

EuropeIn Europe, some of the strongest data for oncology exists in the Nordics with the possibility to link multiple differentdatasets including well-established public registries. This is often a public/private collaboration executed by thirdparties such as Pygargus (now part of IMS Health).

More fundamental approaches are undertaken pan-European with strong support by the EU. One such example is theEurocanPlatform, an EC-funded project with 28 European cancer institutions and organizations working together in aunique collaboration. The centers share infrastructures and collaborate on projects to help advance cancer research andtreatment.8 EurocanPlatform is building the necessary resources and know-how to improve cancer care from bench tobedside: basic research; early and late translational research; clinical research; epidemiological research;implementation in care; and population-based outcomes research.8 One further notable area of activity is thedevelopment of biobanks with comprehensive clinical data – a key advancement given the growth of personalizedmedicine and genomics in cancer.

Issues around safety in oncology mainly concern appropriate and off-label use of (combinations of ) drugs in relation tothe disease stage and subtypes of cancer. The recent Good Pharmacovigilance Practice (GVP)9 established a clearregulatory framework for drug safety monitoring and calls for the assessment of the effectiveness of risk minimizationmeasures (RMMs). This should include the evaluation of their implementation and outcome. Drug utilization studiesprovide simple metrics for monitoring of appropriate drug use and thus the implementation of RMMs.

CONCLUSION This is an exciting time in oncologic care with RWD increasing in frequency, duration, detail, capture rate and linkageacross disparate healthcare settings and administrative sources. As stakeholders come to better understand andleverage the data through the development of more flexible tools, its application across underserved areas of oncologyoutcomes research, such as co-morbidities and thrombosis, paves the way for real-world analyses that will help improvequality, safety and outcomes for cancer patients worldwide.

8 http://eurocanplatform.eu/9 European Medicines Agency. Good pharmacovigilance practices, 2013. http://www.ema.europa.eu/

Healthcare authorities across Latin America are generating newand growing demands for health economics and outcomesresearch to support the efficient allocation of resources andbroader access to new technologies. Owing to the diversity inpatient populations, local health practices and payer systems,economic models that are directly tailored to individualcountries are vital to understand the total cost-effectiveness andbudget impact of new therapies on the current market.

In Latin America, different payers have different perspectivesand needs: national formularies are typically focused on cost-effectiveness analysis and adaptations while stakeholders at thelocal level are primarily concerned with the immediate financialimplications of treatment through budget impact analyses. Withmore Latin American countries adopting a formal process forhealth technology assessment, the need for robust real-worldevidence and health economic data has never been greater. Forone bio-pharmaceutical manufacturer looking to launch in theregion, the ability to demonstrate product cost-effectivenesswithin the context of the country setting was pivotal to marketaccess decision making and local payer negotiations.

IDENTIFYING LONG-TERM VALUEThe company had recently attained the rights to a treatment forfirst-line chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin’s lymphoma (iNHL) in patients who had failed rituximabor a rituximab-containing regimen. The product was alreadyapproved in the US, and they now wished to launch it in LatinAmerica. CLL is the most common adult leukemia in Westernnations and patients with stage B or C disease have a lifeexpectancy of between 2-7 years. Approximately 25-30% of NHLcases are indolent, characterized by slow growth and withsurvival of around 10 years. While CLL and iNHL may notrepresent a large patient population in the Latin Americanregion, the extensive use of healthcare resources over the courseof the disease can put a large strain on healthcare systems.

To benefit patients, treatments for CLL and iNHL need todemonstrate improvements in overall survival (OS), progression-free survival (PFS) and high complete response rates. Currentlyavailable treatments in Latin America are not shown to confersubstantial clinical benefits in either condition. The product inquestion showed significant gains in OS and PFS, with a higher

Robust health economicevidence, specific to thelocal setting, is increasinglykey to market accessdecision making in theLatin American region

Demonstrating cost-effectiveness and budgetimpact in hematological cancers in Colombia and Mexico

The authorsBeth Wehler, MPH is Consultant RWE Solutions & HEOR, IMS [email protected]

David Bertwistle, PHD is Senior Consultant RWE Solutions & HEOR,IMS Health [email protected]

Julie Munakata, MS is Principal RWE Solutions & HEOR, IMS [email protected]

PROJECT FOCUS | HEMATOLOGICAL CANCERS


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FIGURE 1: SURVIVAL OUTPUTS FROM THE COHORT MODEL

complete response rate, versus its immediate comparatorin both CLL and iNHL. Longer PFS and higher responserates were expected to translate into quality of life gains,resulting in a favorable incremental cost-effectivenessratio (ICER).

The company was keen to demonstrate the clinicalbenefits of the product alongside the economicimplications of its use in CLL and iNHL in Latin America,particularly in terms of long-term cost and patientoutcomes. This information would be vital forreimbursement submissions in the region. However,differences in the healthcare systems of the two focuscountries required extensive knowledge of systemrequirements. In IMS Health they found a partner with acoordinated, global team of experts who had extensivehealth economic modeling experience. This allowed themto adapt a CLL and iNHL model in two different countries,supported by a strong network of IMS Health affiliateswith specialized local expertise.

DEVELOPING LOCAL MODELSThe goal of the models was to show the product’s cost-effectiveness in first-line CLL and iNHL in patientspreviously treated with rituximab or a rituximab-containing regimen in Colombia and Mexico. The coremodel was developed for Colombia for each indicationand was then adapted to Mexico.

Leveraging recently reported clinical trial data and arecently published CLL meta-analysis, IMS Healthdesigned partitioned survival models to capture theclinical effects, costs and quality of life outcomes forpatients with CLL and iNHL. The models for bothindications considered three health states: progression-free, progressive disease, and death.

Country-specific information included discount rates,willingness-to-pay, type and frequency of resource useand unit costs. Unit cost data for each country wascollected by the local IMS Health affiliate in each market,with micro-costing allowing for reasonable cost estimatesfor health states and adverse events.

HEMATOLOGICAL CANCERS | PROJECT FOCUS




PROJECT FOCUS | HEMATOLOGICAL CANCERS

Interviews with key opinion leaders were conducted inColombia and Mexico for each indication in order to elicitinformation about local practice for type and frequency ofresource use. Interviews were conducted in the locallanguage.

Outcomes were measured over a 25-year time horizon forCLL and a 35-year time horizon for iNHL, corresponding tolifetime horizons for each indication. key outcomesincluded ICERs for cost per life year (LY), per quality-adjusted life year (QALY) and per progression-free life year(PFLY). Extensive sensitivity analyses were conducted onall key parameters of the models. Additional modelvalidation was conducted to test model assumptionsusing cross-validation by leveraging two differentsoftware programs (Excel and TreeAge Pro). A budgetimpact model was included for each model.

SIGNIFICANT BENEFITS REVEALEDThe IMS Health analyses showed that despite the higherdrug acquisition cost the new product offered good valuefor money for both indications in both countries. Thequality of life benefit due to better response rates andlonger PFS with the new product contributed to favorableICERs below the willingness-to-pay in each country.Sensitivity analyses showed that the models were mostsensitive to estimates for OS and PFS, comparator drugprices and treatment duration (Figure 1, page 57).

The cross-validation exercise indicated that theassumptions made with the Excel model produced moreconservative, but still favorable, results versus thealternative implementation method of the TreeAge Proplatform. The most influential variables (in terms of thecost-effectiveness results) remained similar between thetwo implementation methods.

PRACTICAL TOOL FOR DECISION MAKINGThrough its work with IMS Health, the company gained adeep understanding of the value of its new product in thecontext of Latin America, based on robust healtheconomic models, cross-validated for increased rigor andconfidence in the results. These models are vital to informmarket access decision making and serve as a field tool fortheir Latin American counterparts. They are currentlybeing used in negotiations with different payers in LatinAmerican countries and seven model-related conferenceabstracts have been presented at internationalconferences, enabling the broad dissemination of thestudy findings.

The importance of collecting country-specific informationfor adaptations was demonstrated in this project by thesubstantially different results produced by the Mexicanand Colombian models for CLL. The sensitivity analysisresults from the models indicate that local resource useand cost inputs are critical to understanding theeconomic impact of a new product in these two countries.

In the controlled setting of a clinical trial, the use of specificeligibility criteria, while essential for a study’s internal validity,can leave certain patient groups under-represented in researchand development activities. This is especially true in oncology,where the particular strictness of inclusion criteria means that“only the very fittest cancer patients are enrolled.” 1 In thesecases, tools that can aid understanding of real-world patientexperience have a valid role to play in promoting improveddisease management.

CHRONIC LYMPHOCYTIC LEUKEMIAMost cases of chronic lymphocytic leukemia (CLL) are diagnosedin patients aged over 50 years, increasing the likelihood ofassociated co-morbid conditions. Potentially life threateningwhen combined with the leukemia and its aggressive treatment,these can not only decrease quality of life but also lifeexpectancy. Despite this, clinical trials in CLL have excludedpatients with co-morbidities given the high risk ofchemotherapy toxicity. Thus, the majority of CLL patients arepoorly represented in this setting and hence not considered fornew drug development.

Traditionally, the burden of co-morbidities has been measuredby the Cumulative Index Illness Rating Scale (CIRS)2, the kaplan-Feinstein index (kFI)3 and the Charlson Co-morbidityIndex (CCI)4. Although widely used to assess the presence andfrequency of co-morbidities in oncologic patients5,6 and patientswith hematologic disorders7,8, they are unspecific for CLL andother oncologic diseases. A specific scale to assess the burden ofco-morbidities in CLL would be more efficient, enabling focus oncharacteristics specific to this patient population.

DEVELOPING A DISEASE-SPECIFIC SCALEAgainst this background, IMS Health set out to develop adisease-specific scale to assess the burden of co-morbidities inpatients with cancer and, more particularly, in patients with CLL.This was not intended for use as a decision tool but as a tool tomeasure the impact of the co-morbidities, considering not onlytheir number but also their severity, to help treating physiciansto understand their significance for a given patient.

Disease-specific scales,developed with astandardized methodology,can enhance clinical practicewith a true appreciation ofreal-world patient experience

The authorsMontse Pedros, MD is Senior Consultant RWE Solutions & HEOR,IMS [email protected]

Núria Perulero, BSC is Director RWE Solutions & HEOR, IMS [email protected]

Núria Lara, MD, MSC is Senior Principal RWE Solutions & HEOR,IMS [email protected]

CHRONIC LYMPHOCYTIC LEUkEMIA | PROJECT FOCUS


Enabling understanding of co-morbidity burden inchronic lymphocytic leukemia


PROJECT FOCUS | CHRONIC LYMPHOCYTIC LEUkEMIA


MethodologyIMS Health proposed a phased approach, as shown inFigure 1 and outlined below.

1. Phase I: Literature reviewThe first phase involved a standardized literature reviewto identify any pre-existing scales for measuring co-morbidities in CLL. Using the MedLine database andpredefined search strategy, this focused on studiespublished in English or Spanish during the 10 years from1999 to 2009. All identified articles were reviewed andthose assessing co-morbidities selected for furtherevaluation. Six final papers were analyzed in depth by twoindependent reviewers and the data of interest abstractedin a standardized form (ie, presence, assessment and/orimpact of co-morbidities).2. Phase II: Securing expert consensusDuring the second phase, results from the literaturereview were discussed with an expert panel to determinethe content of the scale. Five physicians with recognizedexpertise in managing CLL were invited to participate in aconsensus meeting and agreement was reached on 19patient characteristics and co-morbidities to be includedin the scale. Some of the variables were stratified by toolscommonly used in clinical settings where these cancerpatients are managed, ie, the ECOG scale was split intofive categories (0 to 4); and the WHO Body Mass Index(BMI) calculation was used to measure obesity.

The relative weight for each category of co-morbidity wasdefined by its impact on the patient and management ofthe disease, ranging from 3: very important to 1: lessimportant. The format was also agreed with a focus onease of use. Elements included: electronic application;pull-down menus for response categories; and summaryof the results with score.

This process enabled a first draft of the scale in paperwhich was refined to implement a ‘traffic-light’ alertsystem for each item, making it easier to identify thosewith a higher score quickly (Table 1).

At the end of this phase, the second draft of the paperscale was available and the corresponding electronicversion ready for use.

3. Phase III: Pilot studyThe third phase involved assessing tool feasibility andusability by physicians treating CLL, in collaboration withthe expert panel. Data was included from 10 patientsacross five participant sites. Physicians were asked to usethe tool with data from the clinical chart of two patients,whose identity was not revealed, noting any problemsand/or suggestions regarding the format and/or contentof the scale, as well as the electronic application. This pilotconfirmed the scale’s feasibility but also highlighted theneed for certain changes, allowing development of thedefinitive version.

FIGURE 1: APPROACH TO DEVELOPING A NEW CO-MORBIDITY SCALE FOR CLL

Phase ILiterature review

To identify existing scales used in studies with patientswith the given cancer1

Phase IIMeeting with experts

To discuss the literature reviewTo set the content of the draft scale

To agree on a format for the draft scale2

Phase IIIPilot study

To assess the feasibility of the draft scale to be used in patients with thegiven cancer under real-world conditions3

Phase IVQualitative analysis

To analyze the pilot study resultsTo select the items to be included in the scale4

Phase VScale validation To assess the psychometric properties of the scale5

CHRONIC LYMPHOCYTIC LEUkEMIA | PROJECT FOCUS

4. Phase IV: Qualitative analysisNext, in order to analyze the pilot study results and selectthe items to be included in the scale, a meeting was heldto share all physician comments and suggestions. These included modifications to the classification of co-morbidities and corresponding scores, as well as to theresponse categories in some of the items, enabling thehigher accuracy of the scale. Following this process, thefinal version was available for use as an electronicapplication. Among the parameters included were:

• Creatinine clearance

• Heart disease

• Symptomatic cardiomyopathy of any cause oraffecting ejection fraction

• Coronary or ischemic heart disease• Atrial fibrillation/Arrhythmia• Valve disease• Hypertension• Bronchial disease/COPD• Smoking• Cancer (past or present)• Diabetes• Liver disease• Hepatitis (B/C)

• Obesity (BMI)

• Mental disorders (in treatment)

Scoring systemThe electronic tool includes three sections:

1. Vital and functional scale capturing age, ECOGstatus, degree of dependency (for enhancedunderstanding only)

2. Co-morbidity scale containing 10 potential co-morbidities pertaining to CLL

3. CLL alerts, including drugs that interact with treatment

Each co-morbidity is weighted (from 0-2) depending onits relevance or impact on therapeutic decisions.Response options are also weighted, with the absence ofthe co-morbidity scoring 0 points, a mild/moderate

co-morbidity scoring 1 point, and a severe co-morbidity, 2 points. The score, automatically calculated by theelectronic scale, ranges from 0 to 57 points according tothe level of severity.

NEW UNDERSTANDING OF CO-MORBIDITY IMPACTPresented at ISPOR9, the new co-morbidity scale iscurrently being used in a prospective non-interventionalmulti-centric study to assess its psychometric propertiesin terms of internal and external validity in the Spanishversion (Phase V, Figure 1). The stepwise approach to itsdevelopment and validation with real-world patients willensure and enhance its value within day-to-day clinicalpractice in CLL. It will help physicians understand theimpact of co-morbidities, support their decision makingprocess when managing CLL patients and facilitateappropriate treatment.


1 Chustecka Z. One in 5 Clinical Trials in Adult Cancer Not Completed. 29 Jan 2014. Quoting Matthew Galsky, MD, Associate Professor of Medicine, Icahn School of Medicine,Mount Sinai, New York. Accessed 2 May, 2014 at http://www.medscape.com

2 Miller MD, Paradis CF, Houck PR, Mazumdar S, Stack JA, Rifai AH, et al. Rating chronic medical illness burden in geropsychiatric practice and research: Application of theCumulative Illness Rating Scale. Psychiatry Res, 1992; 41:237-248

3 kaplan MH, Feinstein AR. The importance of classifying initial co-morbidity in evaluation the outcome of diabetes mellitus. J Chronic Dis, 1974; 27:387-4044 Charlson ME, Pompei P, Ales kL, Mackenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis,

1987; 40:373-3835 Groome PA, Rohland SL, Siemens DR, Brundage MD, Heaton J, Mackillop WJ. Assessing the impact of comorbid illnesses on death within 10 years in prostate cancer

treatment candidates. Cancer, 2011 Sep 1; 117(17):3943-526 Castro MA, Dedivitis RA, Ribeiro kC. Comorbidity measurement in patients with laryngeal squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec, 2007; 69(3):146-527 kleber M, Ihorst G, Terhorst M, koch B, Deschler B, Wäsch R, Engelhardt M. Comorbidity as a prognostic variable in multiple myeloma: Comparative evaluation of common

comorbidity scores and use of a novel MM-comorbidity score. Blood Cancer J, 2011 Sep; 1(9):e358 Timilshina N, Breunis H, Brandwein JM, Minden MD, Gupta V, O'Neill S, et al. Do quality of life or physical function at diagnosis predict short-term outcomes during

intensive chemotherapy in AML? Ann Oncol, 2014 Apr; 25(4):883-89 Carbonell F, De La Serna J, Giraldo P, Lopez A, Rios E, Perulero N, Castro-Gomez A. Development of a co-morbidity scale in patients with Chronic Lymphocytic Leukaemia

(CoLLeCT). Value in Health, 2010; 13(7):A459

TABLE 1: EXAMPLE OF THE CONTENT AND ASSESSMENT PARAMETERSOF THE CLL CO-MORBIDITY SCALE AFTER FIRST CONSENSUS MEETING

Kidney failure

Hypertension

Bronchialdisease/COPD

Smoking

Obesity (based oncalculation of BMI)

+2

+1

+2

+1

0

60-89 – Mild30-59 – Moderate15-29 – Advanced<15 – On dialysis or with

kidney failure

ControlledControlled but withdamage to target organsUncontrolled

NoneMildModerateSevere, requiring oxygen

Non-smoker1-5 cigarettes/day 6-20 cigarettes/day>20 cigarettes/day

≤25 normal weight26-≤30 overweight30-<35 obese≥35 morbid obesity

Assessment parametersCo-morbidity Weightingfactor

Enabling your real-world successIMS Health has a globally unique and powerful RWE approach to understand patientoutcomes and support successful market access. It is built off a long history in HEOR,scientific methodologies, anonymous patient-level information and cross-stakeholdercollaborations.

Our approach is designed to enable your success.

• Largest multi-disciplinary team of RWE and HEOR experts, as well as leading scientists inepidemiology, drug safety and risk management, based in 18 countries worldwide

• Credible scientific voice and deep therapy area knowledge, captured in over 2,500 publications

• Market leadership in developing and adapting robust economic models

• Most advanced capabilities in RWE management and analysis, leveraging relevant IMS Healthproprietary and other key external, third-party patient-level data assets

• Proven expertise in generating and communicating RWE to advance stakeholder engagement at all levels

• Cutting-edge technology to power scientific and commercial insights

IMS RWE SOLUTIONS & HEOR | OVERVIEW

Leadership and innovation across the RWE and HEOR spectrum


IMS REAL-WORLD

EVIDENCE SOLUTIONS

& HEOR

Analytics

Technology-Enabled

Servicesand Engagement

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Anonymous Patient-Level InformationIMS LifeLinkTM – the largest collection ofscientifically validated, anonymous patient-level data assets • Health plan claims• PharMetrics PlusTM

• Longitudinal Rx• Electronic medical records• Hospital disease• Custom data sourcing

Technology-Enabled Analytics

Analytic tools that leverage powerfultechnologies to deliver scientific andcommercial insights efficiently• data integration & linking• Platform development• data warehouse/data marts• User interface & sophisticated

analytics library• IMS Evidence 360

Outcomes Research, Epidemiology & drug Safety• Evidence generation• PRO, QoL studies• Late-phase studies• Mixed methods• database studies, CER• drug utilization studies• Comparative safety &

outcomes studies

Strategic Support• Corporate, franchise and product

RWE strategy development • Evidence plans aligned with

commercial priorities• dynamic marketing plans and

outcomes-based commercialization• Stakeholder engagement• RWE training/organizational

readiness

Market-Level Engagement• Patient journeys, market

landscapes and forecasts• Incentive compensation

approaches• Performance management

approaches • Targeted media and patient

(where allowed) engagementmodels

Health Economic Modeling& Market Access• Health economic evaluations• Core models & local

adaptations• budget impact• Indirect comparisons• Value dossiers • HTA readiness• Value communication

Generating scientifically and commercially relevant insights using novel patient-centric metrics

Services and Engagement

Global scope, local expertiseIMS RWE Solutions & HEOR experts are located in 18 countries worldwide and they have published on projects completed in more than 50 countries on all continents.

Jon Resnick, Vice President and General ManagerOne IMS drive, Plymouth Meeting, PA 19462, USA • Tel: +1 610 834 0800 • [email protected]

Dr. Michael Nelson, Senior Principal8280 Willow Oaks, Corporate drive, Suite 775, Fairfax, Virginia 22031, USA • Tel: +1 703 837 5150 • [email protected]

Dr. Jacco Keja, Senior Principal210 Pentonville Road, London N1 9JY, UK • Tel: +31 (0) 631 693 939 • [email protected]

Patrik Sobocki, Senior PrincipalSveavägen 155, SE-113 46 Stockholm, Sweden • Tel: +46 (0) 8 508 99 995 • [email protected]

Your primary contacts

NORTH AMERICAREGIONAL HEADQUARTERS11 Waterview boulevardParsippany, NJ 07054USATel: +1 973 316 4000

UNITED STATES8280 Willow Oaks Corporate drive, Suite 775Fairfax, Virginia 22031USATel: +1 703 837 5150

One IMS drivePlymouth MeetingPA 19462USATel: +1 610 834 0800

CANADA16720 Route TranscanadienneKirkland, Québec H9H 5M3CanadaTel: +1 514 428 6000

LATIN AMERICAREGIONAL HEADQUARTERSInsurgentes Sur # 23755th Floor, Col. TizapanMéxico City d.F. - C.P. 01090 MéxicoTel: +52 (55) 5062 5239

EUROPEREGIONAL HEADQUARTERS210 Pentonville RoadLondon N1 9JYUnited KingdomTel: +44 (0) 20 3075 4800

BELGIUMMedialaan 381800 VilvoordebelgiumTel: +32 2 627 3211

FRANCE29ème EtageTour Ariane5-7 Place de la Pyramide92088 La défense CedexFranceTel: +33 1 41 35 1000

GERMANYErika-Mann-Str. 580636 MünchenGermanyTel: +49 89 457912 6400

ITALYViale Certosa 220155 MilanoItalyTel: +39 02 69 78 6721

SPAINdr Ferran, 25-2708034 barcelonaSpainTel: +34 93 749 63 00

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SWITZERLANDTheaterstr. 44051 basleSwitzerlandTel: +41 61 204 5071

UNITED KINGDOM210 Pentonville RoadLondon N1 9JYUnited KingdomTel: +44 (0) 20 3075 4800

ASIA PACIFICREGIONAL HEADQUARTERS8 Cross Street #21-01/02/03Singapore 048424Tel: +65 6412 7365

AUSTRALIALevel 5, Charter Grove29-57 Christie StreetSt Leonards, NSW 2065AustraliaTelephone: +61 2 9805 6800

CHINA7/F Central TowerChina Overseas PlazaJianguomenwai Avenue, Chaoyang districtbeijing 100001ChinaTel: +86 10 8567 4255

SOUTH KOREA9F Handok building735 Yeoksam1-dongKangnam-ku Seoul135-755S. KoreaTel: +82 2 3459 7307

TAIWAN8th FloorNo 2, Tun Hwa South RoadSection 1Taipei 10506TaiwanROCTel: +886 2 2721 5337

For further information, email [email protected] or visit www.imshealth.com/rwe

IMS RWE Solutions & HEOR office locations

LOCATIONS | IMS RWE SOLUTIONS & HEOR


Expertise in depthThe IMS Health RWE Solutions & HEOR team brings unrivalled experience and specialistknowledge from industry, consulting, government and academia globally, and includesleading scientists in epidemiology, drug safety and risk management. With proven expertisein all key therapy areas, we have a track record of helping clients meet the growing demandsof an increasingly complex pharmaceutical landscape.

Yumiko Asukai, MSC• Yumi Asukai is a Principal, specializing in the development of economic models across the product lifecycle and the

interpretation of model outputs for strategic market access and value demonstration. Her expertise in this field spans from early strategic modeling through to global core cost-utility models.

• Yumi’s background includes roles at Fourth Hurdle Consulting and in healthcare and business consulting in San Franciscoand Tokyo, where she focused on comparative studies of health policies between Japan and the US complemented byanalyses of primary data. Yumi has worked extensively in the cardiovascular, oncology and respiratory disease areas andshe is part of a global modeling taskforce for COPd composed of academic and industry members.

• Yumi holds a Master's degree in Health Policy, Planning and Financing from the London School of Hygiene & TropicalMedicine and the London School of Economics, and a bachelor's degree in Political Science from Stanford University.

Our senior team

Nevzeta Bosnic, BA• Nevzeta bosnic is a Principal, focused on managing projects to meet the broad spectrum of client needs in the Canadian

pharmaceutical market.• Formerly director of Economic Consulting at brogan Inc, Nev has led many strategic consulting, policy and data analyses

for pharmaceutical clients, government bodies and academic institutions in Canada. She has extensive knowledge ofpublic and private drug plans across the country and in-depth expertise and experience on the drug reimbursement process.

• Nev holds a bachelor’s degree in business Economics from the School of Economics and business at the University ofSarajevo, bosnia-Herzegovina.

Karin Berger, MBA• Karin berger is a Principal, with a focus on RWE, PROs and cost-effectiveness evaluation analyses at a national and

international level.• Formerly Managing director of MERG (Medical Economics Research Group), an independent German organization

providing health economics services to the pharmaceutical industry, university hospitals and European Commission, Karin has more than 15 years experience in the health economics arena. She lectures at several universities, has publishedextensively in peer-reviewed journals, and regularly presents at economic and medical conferences around the world.

• Karin graduated as diplom-Kaufmann (German MbA equivalent) from the bayreuth University, Germany, with a specialfocus on health economics.

IMS RWE SOLUTIONS & HEOR | EXPERTISE


Jean-Marc Aubert, M.ENG, MSC• Jean-Marc Aubert is a Senior Principal, supporting healthcare providers, health authorities and payers.• Jean-Marc has extensive pharmaceutical experience ranging from real-world effectiveness and the regulatory process to

sales force, marketing effectiveness and brand performance. His background includes roles as a partner heading businessdevelopment in the healthcare sector at Jalma, as deputy director at CNAMTS (French National Health Insurance Fund forSalaried Workers) and as Chief of Staff of the State Secretary for Health Insurance.

• An expert in the French healthcare system, market access, commercial effectiveness, RWE and HEOR, Jean-Marc holds aMaster’s degree in Engineering and a Master of Science degree, both from École Polytechnique, France; a SpecialistPostgraduate diploma in Statistics and Economics from École Nationale de la Statistique et de l'AdministrationÉconomique (ENSAE); and a Specialist Postgraduate diploma in Economics (dEA) from École des Hautes Études enSciences Sociales (EHESS), France.

Neil Corner• Neil Corner is a Leader, RWE Solutions, supporting government, academics and the pharmaceutical industry in

understanding and delivering health outcomes data, with a focus on mHealth, integrated patient data and EMRs,including the creation of interactive electronic patient registries.

• Neil has 27 years experience in the pharmaceutical industry in the UK, US, EMEA and Canada, 16 of which were spent atJanssen Pharmaceuticals, including the post of Global Commercial Leader. Prior to joining IMS Health, where his roleshave included international franchise lead for patient and medical data, Neil led Helix Healthcare, a division of Quintiles.

• Neil is the author of several publications on EMR data validation, RWE in the Canadian market and Customer RelationshipManagement. His research and development activities currently focus on the innovative design and construction ofintegrated health data ecosystems to create outcomes in the world of big data.

Joe Caputo, BSC• Joe Caputo is Regional Principal, Asia Pacific, leveraging more than 20 years experience in the pharmaceutical sector to

help clients address the challenges of global reimbursement and market access throughout the drug developmentprogram. He has led numerous projects involving payer research, value dossiers, local market access models and HTAsubmissions.

• Joe's background includes industry roles in drug development, sales and marketing, and UK and global health outcomes,as well as consulting in health economics. He has wide-ranging knowledge of the drug development process at bothlocal and international level and a unique understanding of evidence gaps in light of reimbursement and market access requirements.

• Joe holds a bachelor's degree in Applied Statistics and Operational Research from Sheffield Hallam University, UK.

Adam Collier, MSC• Adam Collier is a Principal, with responsibility for consulting and data related to IMS Health patient-level data assets in

the UK. He has 18 years commercial experience in the UK and European healthcare industry. • Adam’s background spans pharmaceuticals, consulting and healthcare provision, allowing an unusually broad view of

the challenges inherent across the healthcare arena. He spent nine years at GlaxoSmithKline in roles within customer andtrading strategy, commercial analysis and European marketing, and two years at Accenture, where he also completed asecondment to the Medicines & Healthcare Products Regulatory Agency (MHRA) to work on their patient data assetGPRd (now CPRd). Prior to joining IMS Health, he spent several years with a private healthcare provider.

• Adam holds a Master’s degree in Chemistry from the University of Oxford.

Mitch DeKoven, MHSA• Mitch deKoven is a Principal, leading teams in a variety of projects, including value development plans, retrospective

database studies and observational surveys. • Prior to joining IMS Health, Mitch was an Associate director of Reimbursement and Market Access at ValueMedics

Research LLC. His previous roles include Manager of Reimbursement Services at United bioSource Corporation’s Center forPricing & Reimbursement, Consultant with CHPS Consulting, and Program Manager of the Center for Cancer and blooddisorders Children’s National Medical Center in Washington, dC, a position he held after completing an administrativefellowship with the Johns Hopkins Health System.

• A past president of the board of directors of the Lupus Foundation of America Greater Washington Chapter, Mitch serveson six editorial advisory boards and is a peer reviewer for a number of international healthcare journals. He has alsoauthored several articles. Mitch holds an MHSA from the University of Michigan School of Public Health and a bachelor’sdegree in Spanish from Washington University in St. Louis.

EXPERTISE | IMS RWE SOLUTIONS & HEOR


Frank-Ulrich Fricke, PHD, MSC• dr. Frank-Ulrich Fricke is a Principal at IMS Health and Professor for Health Economics, Georg-Simon-Ohm University of

Applied Sciences, Nuremberg in Germany, with a focus on health economic evaluations, market access strategies andhealth policy.

• Formerly a Managing director of Fricke & Pirk GmbH, and previously Head of Health Economics at NovartisPharmaceuticals, Frank-Ulrich has conducted health economic evaluations across a wide range of therapeutic areas,developing a wealth of experience in pricing, health affairs and health policy. As a co-founder of the NIG 21 association, hehas forged strong relationships with health economists, physicians and related researchers working in the Germanhealthcare system.

• Frank-Ulrich holds a Phd in Economics from the bayreuth University, and an MbA equivalent from the Christian-Albrechts-University, Kiel.




Benjamin Hughes, PHD, MBA, MRES, MSC• dr. ben Hughes is a Senior Principal, leading the development of the RWE service offering. He has helped many clients

in the pharmaceutical industry to articulate and implement their RWE strategies, through definition of RWE vision,business cases for RWE investments, capability roadmaps, partnerships, brand evidence reviews, HEOR functiondesign, RWE training programs and related clinical IT strategies.

• Previously head of the European RWE service line at McKinsey & Co, ben has extensive experience advising healthcarestakeholders on health informatics and RWE-related topics. This includes work on France’s electronic health recordstrategy, EMR adoption strategy for governments across Europe and Asia, data releases to support the UK’stransparency agenda, and the development of payer health analytics and RWE capabilities across countries in Europe.

• A widely published author on health informatics, ben holds a Phd in Medical Informatics from ESAdE barcelona, an MbA from HEC Paris, and Masters’ degrees in Research from ESAdE barcelona and in Physics from University College, London.

David Grant, MBA• david Grant is a Senior Principal, specializing in reimbursement and market access, environmental analysis, prospective

and retrospective data collection and communications for product support.• A co-founder and former director of Fourth Hurdle, david’s experience spans more than 10 years in health economics

and outcomes research consulting, and 15 years in the pharmaceutical industry, including roles in clinical research,new product marketing and health economics in the UK and Japan.

• david holds an MbA from the London business School and a degree in Microbiology.

Joshua Hiller, MBA• Joshua Hiller is a Senior Principal, supporting the strategic planning and development of IMS Health capabilities for

data sourcing, integration, analytics and studies. He is also currently serving as Alliance director in the company’scollaboration with AstraZeneca for the advancement of RWE.

• during a career that includes roles in market analytics, government and healthcare consulting in both the US and UK,Joshua has led a wide range of projects for clients in the pharmaceutical and biotech sector as well as industryassociations. He has extensive experience in pharmaceutical pricing, contracting, market landscape development,supply management, cross border trade, lifecycle management, competitive defense, generics market drivers andaccount management, with expertise across US and European markets.

• Joshua holds an MbA (beta Gamma Sigma) from Columbia business School, New York, and a bachelor of Sciencedegree in Mathematics from James Madison University, Virginia.

Kjel A. Johnson, PHARM.D, BCPS, FCCP, FAMCP• dr. Kjel Johnson is a Vice President, focused on developing the company’s oncology data, analytics and informatics

business across key geographies. • Kjel was previously Senior Vice President of Strategy and business development at Magellan Pharmacy Services/ICORE

Healthcare, developing comprehensive specialty management strategies and services for payers. A co-founder ofICORE, he has significant expertise in outsourcing and turn-around strategies, outcomes measures and cost reductionstrategies gained during a career that includes senior roles at deloitte Consulting, UPMC HealthPlan and CoventryHealthcare.

• Principle investigator on more than 40 clinical trials, Kjel has authored over 50 papers and founded Managed CareOncology. He lectures at the University of North Carolina and is a Fellow of the Academy of Managed Care Pharmacistsand the American College of Clinical Pharmacy. Kjel holds degrees from the University of Minnesota and he completeda post-doctoral fellowship at St. Paul Ramsey Medical Center, Minnesota. He is board Certified in Pharmacotherapy.

Jacco Keja, PHD• dr. Jacco Keja is a Senior Principal, drawing on deep expertise in global market access, operational and strategic

pricing, and health economics and outcomes research. • Jacco’s background includes four years as global head of pricing, reimbursement, health outcomes and market access

consulting services at a large clinical research organization and more than 13 years experience in the pharmaceuticalindustry, including senior-level international and global roles in strategic marketing, pricing and reimbursement andhealth economics.

• Jacco holds a Phd in biology (Neurophysiology) from Vrije Universiteit in Amsterdam, a Master's degree in Medicalbiology, and an undergraduate degree in biology, both from Utrecht. He is also visiting Professor at the Institute ofHealth Policy & Management at Erasmus University, Rotterdam.




Rob Kotchie, M.CHEM, MSC• Rob Kotchie is a Vice President, with a focus on bringing innovative solutions to clients through strategic alliances,

collaborations and the deployment of novel technology.• Previously with ZS Associates, Rob has more than 10 years consulting experience, specializing in the synthesis and

application of RWE to facilitate market access, drug uptake and the responsible use of medicines. In his former role asChief of Staff at IMS Health, he supported all operational and management activities related to execution of thecompany’s strategy, and played an integral role in its 2013 dividend recapitalizations and initial public offering in 2014.

• Rob has particular expertise in the areas of oncology, respiratory, cardiovascular and CNS and has published more than 30peer-reviewed journal articles and poster presentations. He holds a first class honors degree in Chemistry from theUniversity of Oxford and an MSC in International Health Policy from the London School of Economics.

Mark Lamotte, MD• dr. Mark Lamotte is a Senior Principal, responsible for project management and quality assurance within his team, and for

leadership of health economic modeling. • A medical doctor specialized in cardiology, Mark spent six years in clinical practice before joining Rhône-Poulenc Rorer as

Cardiovascular Medical Advisor and later becoming Project Manager and Scientific director at the belgian research organization,HEdM. He has worked on over 300 cardiovascular, pulmonary, diabetes, urology and oncology projects, incorporating expertinterviews, patient record review, modeling and report writing. Many of these projects have resulted in peer-reviewed publications.

• Mark holds an Md from the Free University of brussels (Vrije Univeristeit brussel, belgium) and is fluent in dutch, French,English and Spanish.

Joseph Kim, PHD, MPH • dr. Joe Kim is a Senior Principal, providing scientific direction in the design and analysis of observational studies across a

wide range of projects. • A trained epidemiologist and statistician, Joe has over 20 years experience in population-based research in the US and Europe.

He was previously Senior director in benefit-Risk Management at Quintiles assisting in the development of pharmacovigilancesystems, risk management plans and benefit-risk evaluation reports, and in the design of post-authorization safety studies.Prior to this, worked in epidemiology at Roche and Amgen.

• For the last 10 years, Joe has taught pharmacoepidemiology and pharmacovigilance at the London School of Hygiene &Tropical Medicine, and more recently on the MPH program at the French School of Public Health in Paris. He holds a Phd inEpidemiology from the University of Minnesota, and an MPH from the Graduate School of Public Health, San diego.

Tim Kelly, MSC, BS• Tim Kelly is a Vice President, with responsibility for the company’s RWE data assets and data architecture backbone, and

for overseeing platform delivery infrastructure and engagements to ensure at-scale, high-quality data mart deployment. He also leads the client services team supporting data and technology applications.

• Tim’s background includes two decades of life-science experience managing large-scale data warehousing, technology,and analytic applications and engagements. He has worked with many clients in the pharmaceutical and biotech sectors,leveraging deep expertise in information management and modeling, commercial operations and analytics, advancedanalytics, business intelligence, data warehousing and longitudinal analytics.

• Tim holds a Master’s degree in Management Science from Temple University, Philadelphia and a bachelor’s degree inQuantitative business Analysis from Penn State University.

Marla Kessler, MBA• Marla Kessler is a Vice President, also heads overall marketing efforts for IMS Health RWE Solutions; and is an active leader

of global RWE projects. She helps clients develop commercial strategies for products and portfolios, define evidence plansto support them, and coordinate implementation to ensure successful execution.

• Marla has 15 years strategic and business line experience gained through previous leadership roles at McKinsey &Company and Pfizer. during her career at IMS Health she has designed and led RWE boot camps to help clients buildcapabilities in this area across the broader organization, and also developed thought leadership in RWE. This includes co-authoring a major IMS Health benchmarking study exploring variations in RWE supply and demand across thepharmaceutical industry’s top markets.

• Marla holds an MbA from duke University’s Fuqua School of business in durham, North Carolina.

Claude Le Pen, PHD• dr. Claude Le Pen is a member of the strategic committee of IMS Health and Professor of Health Economics at

Paris-dauphine University, providing expert economic advisory services to the consulting practice.• A renowned economist, leading academic and respected public commentator, Claude has served as an appointed senior

member of several state commissions in the French Ministry of Health and is an expert for a number of parliamentarybodies, bringing a unique perspective and unparalleled insights into the economic evaluation of pharmaceuticaltechnologies at the highest level.

• Claude studied business Administration in HEC business School in Paris and holds a Phd in Economics from Panthéon-Sorbonne University.

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Frédérique Maurel, MS, MPH• Frédérique Maurel is a Principal, with a focus on observational research and health economics studies.• A skilled consultant and project manager, Frédérique has extensive experience in the economic evaluation of medical

technologies gained in roles at ANdEM, Medicoeconomie, and AREMIS Consultants.• Frédérique holds a Master’s degree in Economics – equivalent to an MS – and completed a post-graduate degree

equivalent to an MPH with a specialization in Health Economics at the University of Paris-dauphine (Paris IX) as well as adegree in Industrial Strategies at the Pantheon-Sorbonne University (Paris I).

Ragnar Linder, MSC• Ragnar Linder is a Principal, with more than 25 years experience in pharmaceutical marketing, sales and business development.• Co-founder of the Nordic-based consultancy and research organization, Pygargus Ab, Ragnar has worked in various senior

level industry roles. These include General Manager of Amgen Nordic Ab, director of International Marketing atAventis/Hoechst Marion Roussel, and Head of Sales & Marketing at Hoechst Pharmaceuticals Ab. He has also served on theboard of directors for several CRO and biotech companies.

• Ragnar holds a Master of Science degree in Chemical Engineering from the Royal Institute of Technology in Sweden.

Adam Lloyd, M.PHIL, BA• Adam Lloyd is a Senior Principal, with a focus on economic modeling and the global application of economic tools to

support the needs of local markets.• A co-founder and former director of Fourth Hurdle, and previously Senior Manager of Global Health Outcomes at

GlaxoWellcome, Adam has extensive experience leading economic evaluations of pre-launched and marketed products,developing submissions to NICE and the SMC, decision-analytic and Markov modeling, and in the use of health economicsin reimbursement and marketing in continental Europe.

• Adam holds a Master's degree in Economics and a bachelor's degree (Hons) in Philosophy, Politics and Economics fromthe University of Oxford.

Charles Makin, MS, MBA, MM, BS• Charles Makin is a Principal, leading value strategy development, economic evaluations and health outcomes research

studies and observational research. He has served as principal investigator on numerous US-based and global database analyses, adherence interventions, systematic literature reviews, and PRO research.

• Charles has deep insight into best practices in global research and market access. He was previously Global Head ofResearch design and Proposal development at UnitedHealth Group. He also worked as Research Operations Manager atWellPoint, leading project teams to execute HEOR projects.

• A widely published author, Charles holds a Master’s degree in Pharmacy Administration from Purdue University, Indiana,an MbA (summa cum laude) in Marketing Management and a Master’s degree in Management (summa cum laude), bothfrom Goldey beacom College, delaware, and a bachelor’s degree in Pharmacy from the University of Pune, India.

Ed Malka, PHD, MPH• dr. Ed Malka is a Principal, with a broad array of expertise in many disease states from basic science to population research.

An experienced epidemiologist, biostatistician and chemist, he is skilled in the design and analysis of complex and novelstudies to answer questions of CER and RWE studies.

• Previously Associate director, Epidemiology and Health Outcomes at PPd, Ed has held various senior research positions atRutgers University, and served as Associate Scientist at Ortho diagnostic Systems, Inc. and Assistant Professor ofEpidemiology and biostatistics at SUNY downstate Medical Center.

• Ed has a particular research interest in hypertension and wide ranging methodological expertise, from techniquesassociated with pharmacoepidemiology to those used in analyzing complex sampling designs with weighted samplingissues. He holds a Phd in Epidemiology (biostatistics specialization) and a Master of Public Health degree, both from theState University of New Jersey-New brunswick at Rutgers, and a bachelor’s degree in Chemistry from Columbia University.

Bo Lidman, MSC• bo Lidman is a Principal, with more than 30 years experience in the life sciences industry. • bo’s background spans roles in marketing, sales and business development in both start-up companies and

pharmaceutical organizations, including Upjohn Ab and Merck Sharpe & dohme Ab. He served as the General Manager ofProfdoc Ab, CPC Ab and Peritide Ab before co-founding the Nordic-based consultancy and research organization,Pygargus Ab, specializing in real-world evidence. He was most recently responsible for developing the company’s ITplatform and EMR extraction methodology.

• bo holds a Pol. Mag. (Master’s equivalent) and bachelor’s degree in business and Economics from the Institute ofPhilosophy in Marketing and Economics, Uppsala University, Sweden.

ACCESSPOINT • VOLUME 4 ISSUE 8 PAGE 69AccessPoint - Issue 3 Page 69


Julie Munakata, MS• Julie Munakata is a Principal, with a focus on global economic modeling, value development planning, and survey

data analysis.• An accomplished researcher and author of more than 25 original articles, Julie has extensive experience in managing

clinical trials, health economic studies and decision analytic modeling work, gained in senior roles at ValueMedicsResearch LLC, the VA Health Economics Resource Center and Stanford Center for Primary Care & Outcomes Research, andWyeth Pharmaceuticals.

• Julie holds an a Master's degree in Health Policy and Management from the Harvard School of Public Health and abachelor’s degree in Psychobiology from the University of California, Los Angeles.

Carl de Moor, PHD• dr. Carl de Moor is a Senior Principal, with 25 years experience in epidemiology, biostatistics and health outcomes

research in retrospective and prospective studies, clinical and patient-reported outcomes studies, economic analysis and design of registries.

• Previously VP Epidemiology North America at MAPI, Carl has also held roles as Executive director, Epidemiology & HealthOutcomes at PPd, and VP Health Outcomes and Pharmacoeconomics at Supportive Oncology Services, Inc. Prior to joiningthe industry, he was Associate Professor, department of Psychiatry at Harvard Medical School and Associate Professor,department of biostatistics at Md Anderson Cancer Center.

• Carl has authored more than 100 peer-reviewed publications, served as co-investigator or co-principal investigator onover 40 NIH funded grants and contracts, performed editorial reviews for 12 industry publications, and served as thesisand dissertation advisor to numerous graduate students. He holds a Phd in biostatistics from the University of Washingtonwith an emphasis on epidemiologic methods, and a bachelor’s degree in biology from San diego State University.

Lisa Stockwell Morris, PHD, RPH• dr. Lisa Morris is a Vice President, with global responsibility for LifeLink, the company’s suite of patient-centered insights,

and for developing patient-centered information capabilities within the US, EMEA, and Asia Pacific. • Lisa has many years experience in applying market research tools to answer a wide range of business questions, delivering

customized solutions using LRx, medical and pharmacy claims data, EMRs and other clinically-rich secondary informationsources. Previously Associate director for Health Outcomes Assessment at Wyeth-Ayerst Research, where she incorporatedhealth outcomes and economic information into drug development plans, Lisa has also held roles as a senior manager inthe Outcomes Research group at diversified Pharmaceutical Services (dPS) and United Healthcare Corporation (UHC),managing all aspects of customized health services research projects.

• A registered pharmacist, Lisa holds a doctorate in Pharmacoeconomics with an emphasis on Marketing from theUniversity of South Carolina, where she also received a bachelor’s degree in Pharmacy.


Michael Nelson, PHARM.D • dr. Michael Nelson is a Senior Principal, with particular expertise in retrospective database research, prospective

observational research, health program evaluation, and cost-effectiveness analysis.• during a career that includes leadership roles in HEOR at PharmaNet, i3 Innovus, SmithKline beecham, and

dPS/UnitedHealth Group, Mike has gained extensive experience in health information-based product development,formulary design, drug use evaluation, and disease management program design and implementation.

• A thought leader in health economics for more than 20 years, Mike holds a doctorate in Pharmacy and a bachelor ofScience degree, both from the University of Minnesota College of Pharmacy. He also served as an adjunct clinical facultymember at the University of Minnesota whilst in clinical pharmacy practice.

Joan McCormick, MBA• Joan McCormick is a Principal, leading a team providing strategic advice to companies with new products coming to

market and ongoing consultation on the rules for existing drugs post launch. • Formerly Head of Price Regulation Consulting at brogan Inc, Joan has supported many major pharmaceutical companies

with the preparation of pricing submissions to the Patented Medicine Prices Review board (PMPRb), gaining extensiveinsights into the operation of the Canadian pharmaceutical market.

• Joan holds an MbA from the University of Ottawa, Canada and a bachelor’s degree in Life Sciences from Queen’s Universityin Kingston, Canada.


Stefan Plantör, PHD, MBA, MSC• dr. Stefan Plantör is a Principal, with a focus on AMNOG-related projects, including benefit dossiers, as well as reference

price management, health economic evaluations and health policy analyses.• Stefan’s background includes roles as a researcher and five years experience in the pharmaceutical industry. He has also

served as a board member of ProGenerika, the German pharmaceutical association. Over the course of his career, Stefanhas broadened his expertise to include data analyses and decision analytic modeling, authored a number of publicationsin international journals and presented his research at major congresses.

• Stefan holds a Phd in biology from the University of Tübingen, an MbA in International Marketing from the Europeanbusiness School, Reutlingen and an a Master's degree in Microbiology from the Eberhardt-Karls-University (Tübingen).

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Patrik Sobocki, PHD, MSC • dr. Patrik Sobocki is a Senior Principal, with more than 14 years experience in RWE, HEOR and market access. • Patrik’s background spans academia, consulting and the life-science industry within RWE and HEOR, including

international management responsibilities in various senior roles. He was most recently a partner at the Nordic-basedconsultancy and research organization, Pygargus Ab, where he worked with the company’s unique methodology forgenerating population-based RWE based on anonymous patient-level data from EMR and health registers.

• Patrik has conducted numerous health economics projects, outcomes research and epidemiology studies and publishedmore than 40 articles in international peer-reviewed journals. He holds a Phd in Health Economics from the KarolinskaInstitutet, a Master’s degree in Economics and business Administration from the Stockholm School of Economics, and anAssociate Professorship at the Karolinska Institutet.

Daniel Simpson, M.BIOCHEM• daniel Simpson is a Senior Principal, with responsibility for diabetes portfolios and involvement in the UK CObIC initiative,

focused on moving healthcare commissioning towards patient-based outcome measures. He also takes a leadershipposition on commercial analytics.

• daniel has more than 18 years experience in healthcare and pharmaceutical markets. Over the course of his career he hasworked for all the top 10 pharmaceutical companies and healthcare systems in major markets, delivering insights frompatient-level data to support improved decision making on resource allocation. He previously worked in thehealthcare/pharmaceutical strategy divisions for both Accenture and the Monitor Group.

• Published in a series of conference posters and papers, dan holds a Master’s degree in biochemistry from St Anne’sCollege, University of Oxford.

Núria Lara Surinach, MD, MSC• dr. Núria Lara is a Senior Principal, with a focus on the design and coordination of local and international observational

and patient-reported outcomes studies.• A former practicing GP and clinical researcher, Núria’s experience spans roles in outcomes research at the Institute of

Public Health in barcelona and in Catalan Health Authorities, and consulting positions within the pharmaceutical andmedical device industries focusing on medical regulatory and pricing affairs, pharmacoeconomics and market access strategies.

• Núria holds an Md (specializing in Family and Community Medicine in barcelona), and a Master’s degree in Public Healthfrom the London School of Hygiene and Tropical Medicine and London School of Economics.

Patrick Svarvar, PHD• dr. Patrick Svarvar is a Principal, with more than 15 years pharmaceutical industry experience in HEOR and related

functional areas.• Patrick’s background includes Swedish/Nordic affiliate roles in HEOR and pricing at Pfizer and Schering-Plough as well as

global HEOR roles at AstraZeneca, Pfizer and Merck. Most recently, he was Executive director and Franchise Leader, GlobalHealth Outcomes at Merck. Prior to moving into the industry, he worked for a number of years in health economics andhealth services research at the Swedish Institute for Health Economics (IHE).

• Patrick has been involved in a wide range of HEOR study types across multiple therapeutic categories. He is also experienced inmarket access, health technology assessment, clinical development strategies & processes, strategic pricing & reimbursement,marketing, and payer market research. He holds a Phd in business Administration/Economics from Lund University.

Jon Resnick, MBA• Jon Resnick is a Vice President and General Manager, leading the company’s global RWE & HEOR business, including the

development of RWE strategy, offerings, collaborations and foundational technologies to meet the RWE needs ofhealthcare stakeholders.

• A former Legislative Research Assistant in Washington dC and member of the Professional Health and Social Security stafffor the US Senate Committee on Finance, Jon has 10 years consulting experience at IMS. He was most recently responsiblefor leading the European management consulting team and global HEOR business teams of 300 colleagues, advisingclients on a wide range of strategic, pricing and market access issues.

• Jon holds an MbA from the Kellogg School of Management, Northwestern University, with majors in Management andStrategy, Finance, Health Industry Management, and biotechnology.

Shibani Pokras, MPH • Shibani Pokras is a Principal, applying her outcomes research skill set in developing and marketing new data products for

commercial, academic and government researchers.• An award-winning outcomes researcher, Shibani has worked with clients in the life science industry to design analyses for

multiple research databases and convert these into novel interactive payer-ready applications. She has extensiveexperience in developing product-specific health economic value strategy informed by close interactions with managedcare payers, clinicians and scientific research.

• Shibani’s background includes roles at ValueMedics Research LLC, and a fellowship award through NovartisPharmaceuticals and the duke University Center for Clinical and Genetic Economics. Shibani holds an MPH from the YaleSchool of Public Health and Yale School of Management, and a bachelor of Science degree (Hons) in Life Sciences andbiochemistry from St. Xavier’s College in Mumbai, India.

ACCESSPOINT • VOLUME 4 ISSUE 8 PAGE 71AccessPoint - Issue 3 Page 71



Rolin Wade, RPH, MS• Ron Wade is a Principal and a recognized expert in the applications and limitations of using large retrospective datasets

and late-phase datasets for health economics and outcomes research.• Prior to joining IMS Health, Ron served as a Healthcare Executive and Principal Investigator with Cerner Research and as a

Research director at HealthCore. He also has experience generating evidence to support value messages to managedcare, government payers and public health associations, gained in leadership roles within the pharmaceutical industry.

• A widely published author with expertise in many therapy areas, Ron lectures at colleges of pharmacy and he has hadleadership roles with the American College of Clinical Pharmacy and the Academy of Managed Care Pharmacy. He is alicensed pharmacist and holds a Master's degree in Pharmaceutical Sciences from the University of the Pacific, Californiaand a bachelor of Science degree in Pharmacy.

Massoud Toussi, MD, PHD, MSC, MBA • dr. Massoud Toussi is a Principal and Medical director, applying his expertise to assure the quality of outcomes research

and pharmacovigilance. He is also the representative of IMS Health in ENCePP.• Previously head of Global Clinical Research Operations at Cegedim, Massoud has also worked with the French High

Authority for Health (HAS) and various CROs as Project Lead, Scientific Manager and Operations director. His experienceincludes drug safety reporting, natural language processing, database linkage and drug utilization studies.

• Massoud holds an Md from Mashad University in Iran, a Master's degree in Medical Informatics and CommunicationTechnology from Paris VI, a Phd in Medical Informatics from Paris XIII University, and an executive MbA from a jointprogram of Universities of Paris-dauphine and Quebec à Montreal.

Arnaud Troubat, PHARM.D, MBA, MHEM• dr. Arnaud Troubat is a Principal, with extensive consulting experience and special expertise in the development of

registration dossiers and market access strategies across a large number of therapeutic areas. • A pharmacist by training, Arnaud began his career at the French pharmaceutical industry association (LEEM). He then

spent a number of years in the pharmaceutical affairs department at ICI, leading regulatory work on registrationsubmissions and reimbursement strategies, before subsequently moving into consulting. Most recently he was director atCarré-Castan Consultants, managing a research team.

• Arnaud holds a doctor of Pharmacy degree and an MbA from IAE Paris and a Master’s degree in Health Economics andManagement from Paris-dauphine University.

Jovan Willford, MBA• Jovan Willford is a Senior Principal, supporting growth strategy, offering development and commercialization of RWE

solutions in the Asia-Pacific region. • Jovan’s background includes more than 10 years strategic advisory experience across payers, providers, life science

organizations and technology companies, including several cross-industry collaborations to advance quality and value ofcare delivery.

• Jovan holds an MbA from the Kellogg School of Management, Northwestern University, with majors in Management andStrategy, Managerial Economics and International business, and an undergraduate degree from the University of Notredame with majors in Marketing and Philosophy.

Ashley Woolmore, D.CLIN PSYCH, MBA• dr. Ashley Woolmore is a Senior Principal, with a focus on developing innovative approaches to help clients reinforce

differentiation through the integration of real-world data into strategic decision making. He has 20 years experience in thelife sciences and healthcare sector.

• Ashley leverages a uniquely diverse background in clinical, healthcare system management and life sciences strategyconsulting in senior advisory roles to support clients across developed and emerging markets on a wide set of healthcaresystem issues. His expertise includes strategy development, healthcare analytics, RWE for strategic insight, populationhealth management applications, and differentiated market access approaches.

• A thought leader with a particular interest in opportunities arising from convergence between the life sciences industryand broader healthcare system, Ashley holds a doctorate in Clinical Psychology from the University of Oxford, an MbA inStrategy from HEC in Paris, and a bachelor of Science (Hons) degree in Natural Sciences and Psychology.

Marc Tapies, MBA• Marc Tapies is a Principal, with a focus on market access, health economics and outcomes research.• Prior to his current role at IMS Health, Marc worked within the company’s wholesaler data business in Spain where he was

responsible for wholesaler panel management, design and quality control of data production and the development ofnew offerings based on wholesaler data. As Engagement Manager in the IMS Consulting team in Spain, he led projects inthe areas of commercial effectiveness, market analysis and portfolio management in the pharmaceutical industry. Marcpreviously worked for 5 years in the areas of supply chain management and information technologies.

• Marc holds an MbA from IESE business School and a degree in Industrial Engineering from Universitat Politècnica deCatalunya, Spain.

About IMS Health

IMS Health is a leading global information and technology services company providing clients in the healthcare industrywith comprehensive solutions to measure and improve their performance. By applying sophisticated analytics andproprietary application suites hosted on the IMS One intelligent cloud, the company connects more than 10 petabytes ofcomplex healthcare data on diseases, treatments, costs and outcomes to help its clients run their operations moreefficiently. Drawing on information from 100,000 suppliers, and on insights from more than 45 billion healthcaretransactions processed annually, IMS Health’s approximately 9,500 employees drive results for healthcare clients globally.Customers include pharmaceutical, consumer health and medical device manufacturers and distributors, providers,payers, government agencies, policymakers, researchers and the financial community. Additional information is available at www.imshealth.com.

©2014 IMS Health Incorporated and its affiliates. All rights reserved. Trademarks are registered in the United States and in various other countries.All trademark names are acknowledged as the property of their respective owners.

ACCESSPOINT0514

EUROPE210 Pentonville RoadLondon N1 9JYUnited kingdomTel: +44 (0) 20 3075 4800

[email protected]/rwe

THE AMERICAS8280 Willow OaksCorporate DriveSuite 775Fairfax, Virginia 22031USATel: +1 (703) 837 5150

ASIA PACIFIC8 Cross Street #21-01/02/03Singapore 048424Tel: +65 6412 7365

LATIN AMERICAInsurgentes Sur # 2375 5th FloorCol. TizapanMéxico D.F. - C.P. 01090México Tel: +52 (55) 5062 5239

IMS REAL-WORLD EVIDENCE SOLUTIONS AND HEALTH ECONOMICS & OUTCOMES RESEARCHis based in 18 countries worldwide with regional headquarters in:

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