Patient-Reported Outcomes: The Example of Health-Related Quality of Life—a European Guidance Document for the Improved Integration of Health-Related Quality of Life Assessment in the Drug Regulatory Process

The added value for assessing the health-related quality of life (HRQOL) in chronic conditions is now well documented for evaluation of treatment effectiveness in clinical trials and as a criterion for licensing new medications and in policy decisions. However, European standards still need to be developed for the measurement and reporting of HRQOL in clinical trials. This is one of the objectives of the European Regulatory Issues on Quality of Life Assessment (ERIQA) Working Group. This document reviews the major issues arising from the selection of an HRQOL instrument; the integration of HRQOL assessment into the research protocol (methodological design, practicalities of HRQOL administration and collection, prevention and handling of missing data); the statistical analysis plan; and the presentation and interpretation of the results. Finally, to gain wider acceptance, whether HRQOL is considered as a primary or secondary endpoint, the scientific principles of clinical trial design should apply to HRQOL.

[1]  M. Zimmerman.  Weighted versus unweighted life event scores: is there a difference? , 1983, Journal of human stress.

[2]  B Kirshner,et al.  A methodological framework for assessing health indices. , 1985, Journal of chronic diseases.

[3]  R. Temple,et al.  Food and Drug Administration requirements for approval of new anticancer drugs. , 1985, Cancer treatment reports.

[4]  G H Guyatt,et al.  How should we measure function in patients with chronic heart and lung disease? , 1985, Journal of chronic diseases.

[5]  M. Bergner,et al.  Health status measures: an overview and guide for selection. , 1987, Annual review of public health.

[6]  T. Rector.  Patients' self-assessment of their congestive heart failure : Content, reliability, and validity of a new measure, the Minnesota Living with Heart Failure Questionnaire , 1987 .

[7]  W O Spitzer,et al.  State of science 1986: quality of life and functional status as target variables for research. , 1987, Journal of chronic diseases.

[8]  G. Guyatt,et al.  Measuring change over time: assessing the usefulness of evaluative instruments. , 1987, Journal of chronic diseases.

[9]  H. C. Hutchings,et al.  The cost effectiveness of auranofin: results of a randomized clinical trial. , 1988, The Journal of rheumatology.

[10]  R. Deyo,et al.  Generic and Disease-Specific Measures in Assessing Health Status and Quality of Life , 1989, Medical care.

[11]  Lewis E. Kazis,et al.  Effect Sizes for Interpreting Changes in Health Status , 1989, Medical care.

[12]  P. K. Tandon,et al.  Analysis of quality of life data from a randomized, placebo-controlled heart-failure trial. , 1989, Journal of clinical epidemiology.

[13]  A. Stewart,et al.  Functional status and well-being of patients with chronic conditions. Results from the Medical Outcomes Study. , 1989, JAMA.

[14]  G. Guyatt,et al.  Measurement of health status. Ascertaining the minimal clinically important difference. , 1989, Controlled clinical trials.

[15]  N K Aaronson,et al.  Quality of life assessment in clinical trials: methodologic issues. , 1989, Controlled clinical trials.

[16]  G. Guyatt,et al.  A new measure of health status for clinical trials in inflammatory bowel disease. , 1989, Gastroenterology.

[17]  B. Spilker.  Quality of life assessments in clinical trials , 1990 .

[18]  I. Wiklund,et al.  Factors of importance when evaluating quality of life in clinical trials. , 1990, Controlled clinical trials.

[19]  C. Bulpitt,et al.  The measurement of quality of life in hypertensive patients: a practical approach. , 1990, British journal of clinical pharmacology.

[20]  N. Hollenberg,et al.  Assessment of quality of life by patient and spouse during antihypertensive therapy with atenolol and nifedipine gastrointestinal therapeutic system. , 1991, American journal of hypertension.

[21]  D. V. van Thiel,et al.  Quality of life before and after orthotopic hepatic transplantation. , 1991, Archives of internal medicine.

[22]  I. Wiklund,et al.  The relationship between exercise tolerance and quality of life in angina pectoris , 1991, Clinical cardiology.

[23]  R A Deyo,et al.  Reproducibility and responsiveness of health status measures. Statistics and strategies for evaluation. , 1991, Controlled clinical trials.

[24]  D. Hickam,et al.  The Validity of Proxy-Generated Scores as Measures of Patient Health Status , 1991, Medical care.

[25]  A. Laupacis,et al.  The use of generic and specific quality-of-life measures in hemodialysis patients treated with erythropoietin. The Canadian Erythropoietin Study Group. , 1991, Controlled clinical trials.

[26]  B. Spilker.  Guide to clinical trials , 1991 .

[27]  G H Guyatt,et al.  Measuring health status: what are the necessary measurement properties? , 1992, Journal of clinical epidemiology.

[28]  D. Spiegelhalter,et al.  Quality of life measures in health care. I: Applications and issues in assessment. , 1992, BMJ.

[29]  D. Spiegelhalter,et al.  Quality of life measures in health care. II: Design, analysis, and interpretation. , 1992, BMJ.

[30]  N. Aaronson,et al.  The role of health care providers and significant others in evaluating the quality of life of patients with chronic disease: A review , 1992 .

[31]  Gordon Guyatt,et al.  Measuring Health-Related Quality of Life , 1993, Annals of Internal Medicine.

[32]  C. Moinpour,et al.  Pitfalls in quality-of-life assessment: lessons from a Southwest Oncology Group breast cancer clinical trial. , 1993, Oncology Nursing Forum.

[33]  Quality of Life Studies from the Perspective of an FDA Reviewing Statistician* , 1993 .

[34]  G. Guyatt,et al.  Measuring quality of life in asthma. , 1993, The American review of respiratory disease.

[35]  C. Bombardier,et al.  Cross-cultural adaptation of health-related quality of life measures: literature review and proposed guidelines. , 1993, Journal of clinical epidemiology.

[36]  Myfanwy Morgan,et al.  Health Status and Health Policy: Allocating Resources to Health Care , 1994 .

[37]  G H Guyatt,et al.  Determining a minimal important change in a disease-specific Quality of Life Questionnaire. , 1994, Journal of clinical epidemiology.

[38]  A. Laupacis,et al.  Low-dose cyclosporine for the treatment of Crohn's disease. The Canadian Crohn's Relapse Prevention Trial Investigators. , 1994, The New England journal of medicine.

[39]  G. Guyatt,et al.  Randomised controlled trial of respiratory rehabilitation , 1994, The Lancet.

[40]  M. Testa,et al.  Methods for quality-of-life studies. , 1994, Annual review of public health.

[41]  T M Gill,et al.  A critical appraisal of the quality of quality-of-life measurements. , 1994, JAMA.

[42]  I. Wiklund.  Aspects of quality of life in gastrointestinal disease: some methodological issues. , 1995, Scandinavian journal of gastroenterology. Supplement.

[43]  D G Altman,et al.  Statistics notes: Absence of evidence is not evidence of absence , 1995 .

[44]  A. Fletcher.  Quality-of-life measurements in the evaluation of treatment: proposed guidelines. , 1995, British journal of clinical pharmacology.

[45]  R. Gelber,et al.  Quality-of-life assessment in clinical trials. , 1995, Cancer treatment and research.

[46]  The quality of quality-of-life measurements. , 1995, JAMA.

[47]  J. Williams,et al.  Gastrointestinal Quality of Life Index: Development, validation and application of a new instrument , 1995, The British journal of surgery.

[48]  D. Sackett,et al.  The number needed to treat: a clinically useful measure of treatment effect , 1995, BMJ.

[49]  S. Sabesin,et al.  Clinical effectiveness and quality of life with ranitidine vs placebo in gastroesophageal reflux disease patients: a clinical experience network (CEN) study. , 1995, The Journal of family practice.

[50]  Quality of life and regulatory issues. , 1996, Scandinavian journal of gastroenterology. Supplement.

[51]  D. Simonson,et al.  Assessment of quality-of-life outcomes. , 1996, The New England journal of medicine.

[52]  B. Spilker,et al.  Quality of life and pharmacoeconomics in clinical trials , 1996 .

[53]  D G Altman,et al.  Absence of evidence is not evidence of absence. , 1996, Australian veterinary journal.

[54]  D. Osoba,et al.  Rationale for the timing of health-related quality-of-life (HQL) assessments in oncological palliative therapy. , 1996, Cancer treatment reviews.

[55]  K N Lohr,et al.  Evaluating quality-of-life and health status instruments: development of scientific review criteria. , 1996, Clinical therapeutics.

[56]  M. Limburg,et al.  Assessing quality of life after stroke. The value and limitations of proxy ratings. , 1997, Stroke.

[57]  J. Galmiche,et al.  Treating the symptoms of gastro‐oesophageal reflux disease: a double‐blind comparison of omeprazole and cisapride , 1997, Alimentary pharmacology & therapeutics.

[58]  D. Osoba,et al.  The use of significant others as proxy raters of the quality of life of patients with brain cancer. , 1997, Medical care.

[59]  D A Revicki,et al.  Health-related quality-of-life assessment and planning for the pharmaceutical industry. , 1997, Clinical therapeutics.

[60]  S. Kong,et al.  Methodologic Assessments of Quality of Life Measures in Clinical Trials , 1997, The Annals of pharmacotherapy.

[61]  N. Aaronson,et al.  Value of caregiver ratings in evaluating the quality of life of patients with cancer. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[62]  D. Feeny,et al.  Use of the Health Utilities Index with stroke patients and their caregivers. , 1997, Stroke.

[63]  P. Fayers,et al.  Quality of life assessment in clinical trials—guidelines and a checklist for protocol writers: the U.K. Medical Research Council experience , 1997 .

[64]  P. Lehert,et al.  The Effects of Naftidrofuryl on Quality of Life , 1997 .

[65]  D G Altman,et al.  Confidence intervals for the number needed to treat , 1998, BMJ.

[66]  M Sullivan,et al.  Translating health status questionnaires and evaluating their quality: the IQOLA Project approach. International Quality of Life Assessment. , 1998, Journal of clinical epidemiology.

[67]  I. Wiklund,et al.  Quality of Life in Reflux and Dyspepsia patients. Psychometric documentation of a new disease-specific questionnaire (QOLRAD). , 1998, The European journal of surgery. Supplement. : = Acta chirurgica. Supplement.

[68]  Compliance with QOL assessment in multi-centre German breast cancer trials. , 1998, Statistics in medicine.

[69]  D. Machin,et al.  Suggestions for the presentation of quality of life data from clinical trials. , 1998, Statistics in medicine.

[70]  R. Kay.  Statistical Principles for Clinical Trials , 1998, The Journal of international medical research.

[71]  D. Osoba,et al.  Missing quality of life data in cancer clinical trials: serious problems and challenges. , 1998, Statistics in medicine.

[72]  M Sullivan,et al.  Tests of data quality, scaling assumptions, and reliability of the SF-36 in eleven countries: results from the IQOLA Project. International Quality of Life Assessment. , 1998, Journal of clinical epidemiology.

[73]  A. Troxel,et al.  Statistical analysis of quality of life with missing data in cancer clinical trials. , 1998, Statistics in medicine.

[74]  J. Donovan,et al.  Reporting on quality of life in randomised controlled trials: bibliographic study , 1998, BMJ.

[75]  D. Cella,et al.  Comparison of several model-based methods for analysing incomplete quality of life data in cancer clinical trials. , 1998, Statistics in medicine.

[76]  G. Molenberghs,et al.  Analysis of incomplete quality-of-life data in clinical trials , 1998 .

[77]  E. Juniper,et al.  Quality of life questionnaires: does statistically significant = clinically important? , 1998, The Journal of allergy and clinical immunology.

[78]  G. Guyatt,et al.  Interpreting treatment effects in randomised trials , 1998, BMJ.

[79]  V. Gebski,et al.  Practical approaches to minimize problems with missing quality of life data. , 1998, Statistics in medicine.

[80]  Ron D. Hays,et al.  Quality of life assessment in clinical trials : methods and practice , 1998 .

[81]  D. Osoba,et al.  Interpreting the significance of changes in health-related quality-of-life scores. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[82]  L. Okamoto,et al.  The effect of fluticasone propionate on functional status and sleep in children with asthma and on the quality of life of their parents. , 1998, The Journal of allergy and clinical immunology.

[83]  L4: CROSS-CULTURAL ADAPTATION OF THE PEDIATRIC ASTHMA CAREGIVER QUALITY OF LIFE QUESTIONNAIRE (PACQLQ) IN 19 COUNTRIES , 1999 .

[84]  D A Revicki,et al.  Recommendations for evaluating the validity of quality of life claims for labeling and promotion. , 1999, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[85]  O. Chassany,et al.  Treatment of gastro-oesophageal reflux disease in adults , 1999, BMJ.

[86]  H. Faller,et al.  Coping, distress, and survival among patients with lung cancer. , 1999, Archives of general psychiatry.

[87]  Reporting on quality of life in RCTs. Authors are creating database of quality of life questionnaires. , 1999, BMJ.

[88]  Strategies and pitfalls in quality of life research. , 1999, Hepatology.

[89]  O. Chassany,et al.  Validation of a specific quality of life questionnaire for functional digestive disorders , 1999, Gut.

[90]  O. Chassany,et al.  Ethics and clinical trials 1 , 1999, Fundamental & clinical pharmacology.

[91]  Progress in obesity research: 8 , 1999 .

[92]  W M Tierney,et al.  Linking clinical relevance and statistical significance in evaluating intra-individual changes in health-related quality of life. , 1999, Medical care.

[93]  J. Weinman,et al.  Physical and Psychological Correlates of Functioning in Patients with Chronic Obstructive Pulmonary Disease , 2000, The Journal of asthma : official journal of the Association for the Care of Asthma.

[94]  N. Aaronson,et al.  Quality of life evaluation in oncological clinical trials - the EORTC model. The EORTC Quality of Life Study Group. , 2000, European journal of cancer.

[95]  [Does dehydroepiandrosterone improve well-being?]. , 2000, Presse medicale.

[96]  S. Silver,et al.  Heart Failure , 1937, The New England journal of medicine.

[97]  J. Ware.  SF-36 health survey: Manual and interpretation guide , 2003 .

[98]  J. Ware,et al.  A questionnaire to assess the generic and disease-specific health outcomes of patients with chronic hepatitis C , 2004, Quality of Life Research.

[99]  L. Offerhaus.  Measurement of the quality of life in clinical trials: in pursuit of the unapproachable? , 2004, European Journal of Clinical Pharmacology.

[100]  D. Machin,et al.  Randomized trials with quality of life endpoints: Are doctors' ratings of patients' physical symptoms interchangeable with patients' self-ratings? , 1997, Quality of Life Research.

[101]  Psychometric properties of a specific quality of life questionnaire in angina pectoris patients , 1995, Quality of Life Research.

[102]  D. Osoba,et al.  Guidelines for reporting results of quality of life assessments in clinical trials , 1996, Quality of Life Research.

[103]  D. Cella,et al.  Developing and evaluating cross-cultural instruments from minimum requirements to optimal models , 1993, Quality of Life Research.

[104]  R. Epstein,et al.  Interpretation of quality of life changes , 1993, Quality of Life Research.