Managing Patient Reported Outcomes

Francesca MartinelliQoL Department, EORTC HQ

Brussels, Belgium

MedicReS Good Clinical Research CME June 7-8 2013 | Istanbul Turkey

A bit of history

• 1962: Groupe Européen de Chimiothérapie Anticancéreuse (GECA), founded by Henry Tagnon.

• Idea: multidisciplinary approach and international cooperation in clinical research in Europe.

A bit of history

• 1968: European Organisation for Research and Treatment of Cancer (EORTC)

• Network and a coordinating scientific and operational infrastructure based in Brussels.

Quality of Life (QoL)

Wilson and Cleary, JAMA 1995;273(1): 59-65

The early years of QoL in the EORTC

• QoL was a new concept for clinical groups• Scepticism was high• No robust standardized measure was available• Only a few translations were available• Only a few modules were available• Investigators debated the added value of QoL• Few studies worldwide had shown the added value

of QoL• Consequently, QoL was a challenge

A bit more of history

• 1980: Quality of Life Group (QLG)• Aim:• to advise the EORTC Headquarters and the various

cooperative groups on the design, implementation and analysis of QoL studies

• Different countries• Broad range of professionals

• http://groups.eortc.be/qol/

A bit more of history

• 1993: Quality of Life Department (QLD)• Aims:• to evaluate the importance of various factors that

improve the QoL of cancer patients• to supervise the evaluation of QoL in selected cancer

clinical trials• to encourage physicians to pay greater attention to

quality of life factors in the treatment of cancer by stimulating, enhancing and coordinating the evaluation of quality of life in cancer clinical trials

• To focus on clinical groups with a clear QoL related research agenda and committed investigators

• To centralize and professionalize QoL input to clinical groups

• To identify a local coordinator for the QoL component of a trial

• To monitor compliance• To provide regular feedbacks to the local centers

Lessons learned (1)

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• To make QoL assessment a mandatory part of trials• To include baseline QoL in the eligibility criteria• To have clear stopping rules linked to the QoL

component of trials

Lessons learned (2)

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PubMed searches

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• Module development– QLQ-C30– modules– IN-PATSAT32– QLQ-C15-PAL– …

• Field studies• Translations• Clinical trials

QLG today: activities

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QLG

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• Data management• Data Repository project• Dissemination of the EORTC QoL instruments• Translations• Protocols• Statistical research

QLD today: activities

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QLD

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QLQ-C30

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More than 85 available translations

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Global health status / QoL: Symptom scales / single items:Global health status / QoL Fatigue

Nausea and vomiting

Functioning scales: Pain

Physical functioning DyspnoeaRole functioning InsomniaEmotional functioning Appetite lossCognitive functioning ConstipationSocial functioning Diarrhoea

Financial difficulties

Structure

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Bone metastases (QLQ-BM22) Hepatocellular carcinoma (QLQ-HCC18)Brain (QLQ-BN20) Information (QLQ-INFO25)Breast (QLQ-BR23) Lung (QLQ-LC13)Cervical (QLQ-CX24) Multiple myeloma (QLQ-MY20)Colorectal (QLQ-CR29) Oesophageal (QLQ-OES18)Colorectal liver metastases (QLQ-LMC21) Oesophago-Gastric (QLQ-OG25)Endometrial (QLQ-EN24) Ovarian (QLQ-OV28)Gastric (QLQ-STO22) Prostate (QLQ-PR25)Head & Neck (QLQ-H&N35)

Validated modules

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QLQ-BR23

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QLQ-INFO25

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Carcinoid / Neuroendocrine tumours Oral healthCholangiocarcinoma and Gallbladder cancer PancreaticChronic lymphocytic leukaemia Peripheral neuropathyElderly cancer patients Radiation proctitisCancer related fatigue Spiritual wellbeingHigh dose chemotherapy Superficial bladderMuscle invasive bladder TesticularOphthalmic

Modules in development (1)

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Children and adolescents Chronic myeloid leukaemicSpinal cord compression Nasopharyngeal carcinomaPleural effusion Breast reconstructionUpdate of the QLQ-LC13 Update of the QLQ-H&N35Cancer cachexia and nutritional status Lymphoma and CLLVulvaMelanoma

Modules in development (2)

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• QLQ-C15-PAL– to assess the quality of life of palliative cancer care

patients

• IN-PATSAT32– to measure patients’ appraisal of hospital doctors

and nurses, as well as aspects of care organisation and services

Additional questionnaires

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• Aims:– to store information about the development of

module items and the wording and translation of the various items and subscales

– to store information about results from pre-testing and field-testing

– to compare items and subscales in new modules with those that are already approved

– to speed up item construction– to act as a data bank for items to be used in ad

hoc questionnaires

Other activities: the Item Bank

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• CAT (Computerized Adaptive Testing)– clinical trials– daily oncology practice– remote monitoring

• CHES

Other activities: the future is electronic!

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• EORTC holds a wealth of data on patient psychosocial / QoL issues.

• Imperative to tap into this wealth to help patients, clinicians and governments make informed choices about cancer care.

• The QLD has developed Patient Reported Outcomes and Behavioural Evidence (PROBE), a research program, compiling a series of broad-based research questions, analysis presentation and dissemination of key-psychosocial / QoL findings in symposium and consensus-developed statements.

Other activities: the PROBE project

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• QoL assessment mandatory in all participating centers for trials with a QoL endpoint

• Guidelines and templates for key QoL paragraphs (design, measures, analysis plan) of clinical trial protocols

• Standard procedures for monitoring compliance • Minimal level of compliance now set before

reviewing closure of study• Standardized analysis plans for examining missing

data patterns and for group comparisons over time• Guidelines

Need of standardization

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Joint EORTC Brain Tumour Group/Radiotherapy Group and NCIC CTG phase III randomised

controlled trial evaluating QoL in glioblastomapatients

M Taphoorn, R Stupp, D Osoba, J Curschmann, R Kortmann, MJ van den Bent, W Mason, C Coens, E Eisenhauer, A Bottomley. Lancet Oncol, 2005; 6: 937-44

Impact on clinical practice

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Background

• Glioblastoma (GBM) is the most common primary brain tumor

• Treatment:– adjuvant chemotherapy following radiotherapy (RT)

has been an issue of debate for years – surgery: biopsy and / or resection– focal RT

• Prognosis:– Median survival: 9 - 12 months, limited data on QoL

• New oral treatment to be evaluated: Temozolomide(TMZ)

• 573 newly diagnosed GBM patients, median age 56– standard (RT only): 286– experimental (RT/TMZ): 287

• QoL assessments– Baseline compliance was over 86%, and over 80% at all assessment points.

• Pre-selection of 7 scales– QLQ-C30: global health status / QoL, fatigue, insomnia, social and

emotional functioning– QLQ-BN20: communication deficit, future uncertainty

• Hypothesis: – QoL may deteriorate more severely during intense treatment (RT + TMZ)

compared to standard (RT). – QoL will improve more slowly following RT + TMZ compared to RT alone.

Patients and methods

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Global QoL scale over time

Social Functioning over time

Future Uncertainty over time

QoL results results

Conclusions

• No negative impact of concomitant / adjuvant TMZ on QoLduring treatment

• No decrease / slight improvement in QoL during first year following treatment

• RT with concomitant and adjuvant TMZ:– more effective than standard treatment– safe– no detrimental effect on QoL

• While some argue that the survival benefit is not huge (e.g. 2 ½ months) we can say that it is, also the quality of survival is important.

• Now this is a standard of care in GMB

Key lessons learned... (1)

• Focus on clinical trials with the largest potential QoLpayoff.

• Pre-select the most clinically important endpoints.• Educate the collaborators, providing guidelines and

training opportunities; hold QoL planning meetings.• Monitor QoL compliance continuously, and provide

timely feedback.• Follow a predetermined analysis plan, including

detailed evaluation of patterns of missing data.

• Provide guidelines for interpreting the clinical significance of results (e.g., 10 point change).

• Require that groups with poor performance in assessing QoL outcomes evaluate source of problems and justify logic of any further investment in QoLinvestigations.

• Always budget costs of QoL component of trials.• Centralize QoL activities (planning, data collection

monitoring, analysis) to enhance efficiency and quality of work done.

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Key lessons learned... (2)

Thank you for your attention

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