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IAS 2013 - Symposium Health-Related Quality of Life Why and how ? Pr Olivier CHASSANY Patient-Reported Outcomes Research Unit, University Paris 7 & Hôpital.

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Presentation on theme: "IAS 2013 - Symposium Health-Related Quality of Life Why and how ? Pr Olivier CHASSANY Patient-Reported Outcomes Research Unit, University Paris 7 & Hôpital."— Presentation transcript:

1 IAS 2013 - Symposium Health-Related Quality of Life Why and how ? Pr Olivier CHASSANY Patient-Reported Outcomes Research Unit, University Paris 7 & Hôpital Saint-Louis

2 Health : "A state of complete physical, mental, and social well-being not merely the absence of disease” (World Health Organization (WHO) 1948) “The value assigned to duration of life as modified by the impairments, functional states, perceptions and social opportunities that are influenced by disease, injury, treatment, or policy” (Pr Donald Patrick, Seattle, USA) Assessment of HRQL is: Subjective (patient’s perception) Self-reported in most conditions Multidimensional Health-Related Quality of Life (HRQL) - Definition

3 FDA & EMA Guidance on assessment of PRO/HRQL in clinical trials of drugs 2006 http://www.ema.europa.eu/docs/en_GB/d ocument_library/Scientific_guideline/2009/ 09/WC500003637.pdf 2009 http://www.fda.gov/downloads/Drugs/Guidance ComplianceRegulatoryInformation/Guidances/ UCM193282.pdf PROHRQL FDA

4 Why should we measure the perception of patients in clinical trials ? Changes in the therapeutic targets in the growing context of chronic diseases and palliative treatment in a rising old population Cancer HIV/AIDS Heart failure Parkinson’s disease Alzheimer’s disease Asthma COPD Osteoarthritis Diabetes … Nowadays, therapeutic benefits : rarely curative, or prolonging survival, but improving symptoms and functional status, and thus preserving or restoring HRQL Availability of PRO questionnaires correctly validated and translated for many diseases / conditions

5 1.“Objective” markers versus PROs 2.Clinician-Reported Outcomes and proxies/caregivers versus PROs 3.Between PROs What is the agreement between different perspectives ?

6 “Objective” measure Exercise test versus physical functioning, r = 0.40 “Subjective” measure Wiklund I et al. Clin Cardiol 1991. Slide presented with the authorization of Pr Ingela Wiklund “Objective” marker versus PRO © Pr Ingela Wiklund

7 Patients 39.0 ± 24.9 (n=232) GPs 30.4 ± 21.0 (n=307) Difference 8.6 (28%) Correlation Kw = 0.31 (n=232) Clinicians underestimate pain severity (Irritable Bowel Syndrome - IBS) All values under the equality line indicate GP underestimation of pain by GPs Pain values ranged between 0 (no pain) and 100 (severe pain) Chassany O, Duracinsky M, et al. Discrepancies between PROs and Clinician-Reported Outcomes in chronic venous disease, irritable bowel syndrome, and peripheral arterial occlusive disease. Value in Health 2006.

8 Bendtsen P. Measuring health-related quality of life in patients with chronic obstructive pulmonary disease in a routine hospital setting: Feasibility and perceived value. Health Qual Life Outcomes. 2003 Patients' perception adds an information that is not captured by physicians or “objective” markers

9 The impact on HRQL is not always foreseeable and is not systematically correlated with the severity of the disease as perceived by the medical community Good HRQL Bad HRQL Patrick D, Erickson P. Health status and health policy. Quality of life in health care evaluation and resource allocation. Oxford University Press, 1993.

10 24 adolescents (11-18 yrs) with CF, their mothers, and their fathers completed the Child Health Questionnaire during routine CF clinic visits at 2 urban hospitals. Correlation between adolescent vs. mother & father reports of perceived adolescent health Adolescents with cystic fibrosis: family reports of adolescent quality of life and forced expiratory volume in one second. Powers PM et al. Pediatrics 2001; 107: E70. Health ScaleMothersFathers General health0.660.57 Physical functioning0.690.31 Role/social-physical0.620.49 Bodily pain0.690.37 Role/social-emotional-0.120.24 Role/social-behavior0.480.17 Mental health0.330.48 Family activities0.45-0.09 Self-esteem0.410.65 Behavior problems0.710.66

11 Pain values ranged between 0 (no pain) and 100 (severe pain) QoL scores ranged between 0 (bad QoL) and 100 (good QoL) Patients’ perception : Pain only partially reflected HRQL (Irritable Bowel Syndrome) Patient-assessed QoL decreased as patient- assessed pain increased (r=0.71). However, patient- assessed QoL scores varied drastically for a given pain intensity, suggesting that pain intensity only partially reflected QoL.

12 4.1.2. Patient’s assessed outcome measures (cont’d) Efficacy of a new drug evaluated by patient is important when … even relatively limited extent of skin psoriasis may severely socially and psychologically disable the patient. The assessment of HRQL scales specific for psoriasis may represent an added value for a new drug in comparative clinical trials, in addition to classical efficacy/safety measures. Patient-assessed drug efficacy may be a secondary or tertiary endpoint in pivotal clinical trial. … Ideally, trials assessing psoriasis-specific HRQL should be designed to assess patient’s perspective in the evaluation of drug-effect in order to understand better the clinical significance of the benefit observed and to be sure that the administered treatment does not impact adversely on patient’s HRQL. EMA guidelines : Psoriasis : Note for Guidance CPMP/EWP/2454/02 (Nov. 2003) HRQL

13 From Pr Ingela Wiklund (UBC)

14 Chassany O, et al. Validation of a specific QoL in functional digestive disorders (FDDQL). Gut 1999; 44: 527-533 1.Physical functioning 2.Physical role functioning 3.Bodily pain 4.General health 5.Vitality 6.Social role functioning 7.Emotional role functioning 8.Mental health Sleep and diet disturbances (83%) Generic SF-36 36 items 8 domains Irritable Bowel Syndrome Functional Digestive Disorders Quality of Life (FDDQL) 43 items (8 domains) 1.Daily activities 2.Anxiety 3.Sleep 4.Diet 5.Abdominal Discomfort 6.Coping with disease 7.Control of disease 8.Stress Generic or specific questionnaire ? Importance of the content validity - A “validated” scale doesn’t imply that it is relevant for the population studied - A single item is inadequate to capture all the aspects of HRQL

15 Importance of various areas of limitations due to asthma among Harlem emergency department users (n =247) mostly Afro-american patients with a low socio- economic status and a lower compliance Content validity - Importance of the sample included during the validation process Asthma-related limitations in sexual functioning: an important but neglected area of quality of life. Meyer IH, et al. Am J Public health 2002; 92: 770-772.

16 ABCD vs Mental Component Summary (MCS) SF-12, r=0.65 Rigorous process of development & validation of HRQL & PRO questionnaires Content validity Item generation Scaling Item reduction Reproductibility Construct validity Discriminant validity Convergent validity Responsiveness Cultural adaptation Scientific Advisory Committee of the Medical Outcomes Trust. Assessing health status and quality-of-life instruments: attributes and review criteria. Qual Life Res 2002 Factorial analysis ABCD ScoreABCD score vs nb of lipodystrophy regions

17 Conceptual Framework of Patient-Reported Outcomes in Paroxysmic Nocturnial Haemoglobinluria (PNH) Cross-sectional study (n between 28 and 38) FSI: Fatigue Symptom Inventory BPI: Short form Brief Pain Inventory PSQ: Pittsburgh Sleep Quality Index STAIS: State-Trait Anxiety Inventory BDI: Beck Depression Inventory QoL: EORTC QLQ-C30 global score Anaemia Fatigue Sleep Pain Depression Anxiety QoL r = 0.241 0.452 0.419 0.589 0.644 0.786 Fatigue predicted by: Pain Sleep impairment Anxiety / depression Higgins, Stern, Penn State University

18 Fatigue Symptom Inventory Rate how much of the day, on average, you felt fatigued in the past week St-George Respiratory Questionnaire (50 items) Over the last year, in an average week, how many good days (with little chest trouble) have you had Fatigue symptom inventory Understanding of items must be checked with patients

19 Interpretation of HRQL & PRO results ? Zafirlukast improves asthma symptoms and HRQL in patients with moderate reversible airflow obstruction. Nathan RA et al. J Allergy Clin Immunol 1998. Marquis P, Chassany O, Abetz L. A comprehensive strategy for the interpretation of quality of life data based on existing methods. Value in Health 2004 ; 7 : 93-104. What does mean this HRQL difference ? Active treatment vs Placebo p Daytime symptoms (0 to 3) - 0.14< 0.001 Nighttime awakening (per wk) - 0.63< 0.001 beta2 agonist use (puffs/day) - 0.64< 0.001 FEV10.050.331 Morning PEF (BL : 362) + 13,1 L/min< 0.001 Evening PEF (BL : 398) + 11,5 L/min< 0.001 Global AQLQ score (BL : 4.28, range score 1-7) + 0.260.004

20 How to interpret PRO – HRQL results when relevance is not obvious ? How to interpret PRO – HRQL results when relevance is not obvious ? Mean score difference ± SD (p < 0.05) between 2 groups MID Minimal Important Difference Responders (%) NNT Number Needed to Treat Effect Size Anchor-based Distribution- based Population- based Relate changes on a HRQL measure to known population norms Differences or changes for HRQL are inevitably smaller that for other endpoints (e.g. symptoms) being an indirect measure of the disease But different interpretations will not save a small mean difference between groups

21 Minimal Clinically Important Difference (MID) Smallest difference in measure patients perceive as beneficial, and would mandate, in the absence of troublesome side effects and excessive cost, a change in patient’s management. Difference on HRQL corresponding to smallest change in status that shareholders (patients, clinicians,...) consider important Patrick DL, Erickson P: Health Status and Health Policy. Oxford University Press. New York 1993. pp 422-3 Jaeschke R, Singer J, Guyatt GH: Measurement of health status - ascertaining the minimal clinically important difference. Controlled Clinical Trials. 1989; 10:407:415

22 Minimal Important Difference (MID) Mapping Changes in PROs scores to a single question Guyatt GH, Juniper EF. Several publications * Overall, has there been any change in your shortness of breath during your daily activities since the last time you saw us ? Answer to the GLOBAL RATING change from -7 to +7* WorseBetter Interpretation of change Mean change in HRQL scale (range 1-7) A very great deal- 7+ 7Large1.5 A great deal A good deal Moderately - 6 - 5 - 4 + 6 + 5 + 4 Moderate1.0 Somewhat A little - 3 - 2 + 3 + 2 Small 0.5 Almost the same- 1+ 1 About the same

23 23 Minimal Important Difference (MID) Comparison between groups Definition of responders Comparison of 2 means Comparison of 2 percentages AQLQ (Asthma) [1-7] 0.5 Improvement higher than 0.5 (depends on baseline value) Number Needed To Treat (NNT) When defining a meaningful change on an individual patient basis (i.e. a responder), that definition is larger than the MID for group mean comparison Not the same

24 24 Minimal Important Difference (MID) Comparison between groups Definition of responders Comparison of 2 means Comparison of 2 percentages PAIN (Osteoarthritis) VAS (0-100) 10-20% 10-15 mm (VAS) 30-50% decrease vs. baseline or value < 30 mm Number Needed To Treat (NNT) When defining a meaningful change on an individual patient basis (i.e. a responder), that definition is larger than the MID for group mean comparison Not the same

25 Adjunctive treatment of partial-onset seizures in patients with epilepsy ≥ 12 years European Approval (07/2012) Fycompa (perampanel) Clear dose response for adverse events, captured by global assessments European public assessment report (EPAR) - http://www.ema.europa.eu * Much or very much improved CGIC - Clinical Global Impression of Change PGIC - Patient Global Impression of Change

26 “The benefit on patients’ survival seen in the study was very limited and it did not outweigh the risk associated with the combination of erlotinib and gemcitabine, given the side effects of the treatment.” EMA refusal of the marketing authorisation for TARCEVA erlotinib - EMA/284207/2006 HRQL “The study did not show any improvement in the quality of life of the patients treated. EMA major concerns for refusal of the marketing authorisation to TARCEVA in pancreatic cancer ?

27 A clinical endpoint is an aspect of a patient’s clinical or health status that is measured to assess the benefit or harm of a treatment. A clinical endpoint describes a valid measure of clinical benefit due to treatment: the impact of treatment on how a patient feels, functions and survives. Final EunetHTA guideline, Feburary 2013 European Network HTA Joint Action WP5 - Methodology guidelines ”Clinical endpoints” HTA : Health Technology Assessment For reimbursement purpose

28 Future: ePRO & eHealth


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