How to Design Effective

and Efficient

Real World Trials

Todd Berner MDExecutive Medical Director, UrologyAstellas Scientific & Medical Affairs, Inc.October 23, 2014

Muller RW, ECRI Institute Conference 11.28.2012

Providers Assuming Risk:

• Nationwide, about 120 provider-sponsored health plans are owned by hospitals or health systems or are in the process of applying for a license to own health plans

• Few provider-owned health plans participate in exchanges

• About 15% of hospitals had PPOs, 13% HMOs and 5% fee-for-service products in 2011, with percentages relatively flat over a decade, according to AHA’s latest data

Health Plan Week August 19, 2013 Volume 23 Issue 28

There are limitations for smaller provider organizations in taking full risk and

becoming an insurance plan, “because you need large numbers in terms of how

capitated rates are set.”

Transforming Care Delivery

Transformation of Care

Accountable

Care

Payment

Models

Health Coach

Primary Care

Snyder R, ECRI Institute Annual Conference Nov 28,2012

EMR

Best Practices

Listening to the Patient Voice in Research

PCORI Determinants of Success in Involving Patient’s in Research

Are we producing high-quality, timely, useful, trustworthy information?

Is the information we produce being used?Are other (funders of) researchers following our

lead?

Efficacy

7

Real World Evidence

Effectiveness

Value Information= Valued Information• Generate valued information regarding cost-

effectiveness useful to payers and/or policy makers• Real World Evidence Development

• Follows from clinical findings, real-world observations

– Retrospective data studies– Models of care– Prospective observations– Measures of Patient Experience(PROs)

“Value is in the eyes of the Beholder”

Value Evidence Generation

Effectiveness Efficacy

Adherence

Individual Patient

Characteristics

Tolerability

Access

Hypothesis

Question

Methodology

Data Generation

Using Evidence to Inform Development of Clinical Trials

• Retrospective Claims and Medical Records Database Analysis• Analysis of treatment patterns and utilization• Analysis of prevalence and population trends• Burden of Illness• Adherence and persistence assessments• Economic and resource utilization• Effectiveness studies and outcomes analysis• Pharmacoepidemiology

• Prospective Research• Patient Reported Outcomes• Treatment patterns and resource utilization• Quality of Life• Productivity

RWE within the product lifecycle

Pre-launch Product Launch 1 yr post-launch 2+ yrs post-launch

Market Shaping• Burden of

Illness• Gaps in

Care

• RCT on-label communication• Establish

place in treatment

• Analysis of clinical trial subpopulations

• Economic evaluations

• Budget impact• CE using RCT data• PRO Measures of

Patient Experience

RWD generation• Adherence/ persistence• Healthcare

Resource Utilization

• Clinical Outcomes• Patient

Satisfaction

Real World Evidence:Efficacy vs. Effectiveness

Example- Conditions with significant patient subjective symptom

outcome measures (OAB, IBD, migraine)• RCT data

Extremely high placebo response ratesDifficult to show efficacy for drug compared to placeboIt is essentially all non-pharmacologic therapy compared to

non-pharmacologic therapy + drug• Real World data

All of the behavioral, non-pharmacologic intervention associated with the RCT moves over to the drug side of the ledger

This becomes a comparison of activated, engaged Rx recipients vs. those with just an Rx

Inception Point:The ‘Representativeness’ Issue

Robert M. Califf, MDConsiderations in Designing Acute

Decompensated Heart Failure Clinical Trials

Pragmatic Clinical Trials

Brass EP Clin Pharmacol Ther 2010

How much could we save if RWE replaced just a single clinical trial?

Cutting Edge Survey Phase IIIB/IV Clinical Trials 2011

Capturing Stakeholder Voices

Uncovering the true needs• In this changing landscape, they may not have a

clear idea • Use therapeutic expertise to generate ideas

• Build on those ideas they do have

• But this might not be enough• May need to actually work together to figure it out• Collaborative Research

The “We don’t have the bandwidth ”

Challenge

Complexities of Defining Quality

Measurement Challenges• Disparate data sources needed

• What data should be reported that will be useful to stakeholders? to achieve behavior change for patient choice for payer market decisions

• Criteria for Outcome MeasuresRisk adjustmentCapture few unintended consequences

The Joint Commission National Patient Safety Goals 2012

Quality MetricsBenefit from a focused clinical set of proven,

evidenced-based process and outcome measures that are most likely to drive quality outcomes and have utility for patientsTie to the power of payment policiesAppreciate that clinical measures not credible to

clinicians don’t get measured well, nor do they result in quality improvement

Many measures may not even contain the information needed to make QI changes

The Joint Commission National Patient Safety Goals 2012

Evidenced Based Solutions

Measurement is not the endpoint Need to find ways to improve on performance,

using tested proven solutions that are sustainable because they are imbedded into practice & are widely acceptedBring process improvement into solutionsSolutions must be customizable to settingImprovements must be measurable to know if

they work and at what cost

The Joint Commission National Patient Safety Goals 2012

Performance Improvement Research Collaborative:Blueprint

Phase I Phase II Phase III Phase IV

Research: Burden of IllnessPredictive Model

Project Phases

Recruit Health Pilot SitesDesign Change Package

Implement Change

Package in Pilots

Collect Data

Disseminate Best Practices

Learned

Analyze Align Implement Spread

Partnering to deliver improved care at a reduced cost.

Mapping the Patient Journey

Baker GR, Schwartz FHealthcare Quarterly, 8(3) May

2005.doi:10.12927/hcq.2005.17194

Patients newly initiating therapy

Index event captured by HCP InvestigatorPatient then engages with Registry and provides ePRO data

throughout the course of 12 month observation period, independent of whether they:

Remain on treatment

Switch or add on additional treatments

Change or consult with multiple providers

Naïve sites; Weighted PCP representation;Linkage to multipayer/allpayer claims data of meaningful

scale is still lacking

The Patient Journey-An Observational Registry

Phase 1

• Descriptive analysis (baseline characteristics, treatment patterns (adherence (primary and secondary), discontinuation, and switchers) and healthcare resource use.

• Identify risk factors associated with treatment patterns

Phase 2• Survey patients newly

initiated on therapy who subsequently Persist, Switch, or Discontinue

Phase 3

Primary Nonadherence within a ‘Closed’ Healthcare System

Performance Improvement within a Health System with Significant ‘excursions’ of Patient Care Outside the System• Assess treatment approaches, Explore several measures:

Compare the number of visits during which condition was: Appears in the problem list Listed as a diagnosis A drug was prescribed for the condition

Examine appropriateness of referral patterns: PCP should try at least one drug for this condition– but only one – before

referring to a specialist Referrals made without trying any drug or after prescribing more than one

will be classified as potentially inappropriate or suboptimal Subgroup analysis of referrals from the Health System’s primary care

clinic network vs others Examine the use of diagnostic testing and imaging Examine the use and documentation of validated symptom assessment tools. Compare presentation of treatment options to patients among those that we

can identify via the EHR

EMR Based Condition Specific Prompts and HCP Clinical Decision Support

National Quality Strategy--The Future of Quality MeasurementONC, AHRQ, CMS Presentation. September 14, 2012

*

EMR Based Condition Specific Prompts and HCP Clinical Decision Support

• Clinical Decision Support (CDS) Detect potential safety and quality problems and help prevent them

Detect inappropriate utilization of services, medications, and supplies

Foster the greater use of evidence-based medicine principles and guidelines

Organize, optimize and help operationalize the details of a plan of care

Help gather and present data needed to execute this plan

Ensure that the best clinical knowledge and recommendations are utilized to improve health management decisions by clinicians and patients

Osheroff JA, Pifer EA, Teich JM, et al. Improving Outcomes with Clinical Decision Support: An Implementers' Guide

Chicago: HIMSS; 2005.

What Does Good Look Like?Toward Continued Excellence

• More patient-centered care• More predictable outcomes• Low tolerance for unwarranted deviations

from the norm• Collective Mindfulness• Greater efficiencies, less waste• More appropriate/evidence based care

that meets shared expectations• Evolving “Learning” Systems

The Joint Commission National Patient Safety Goals 2012