francesca martinelli medicres world congress 2013
TRANSCRIPT
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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