Skip to main content Accessibility help
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 1
  • Print publication year: 2004
  • Online publication date: December 2009

17 - Practical considerations in outcomes assessment for clinical trials


While clinical outcomes are often the primary method of evaluation in clinical trials, endpoints requiring patient-reported measures are essential. The scientific literature is full of reports where investigators make logical but unsubstantiated claims of quality-of-life benefits to patients based on the assumption that a change in treatment or a traditional biomedical outcome will improve the patient's quality of life. While in many cases this may be true, surprising results are sometimes obtained when the patient is asked directly. One classic example occurred with a study by Sugarbaker et al. comparing two therapeutic approaches for soft-tissue sarcoma. The first was limb-sparing surgery followed by radiation therapy. The second treatment approach was full amputation of the affected limb. The investigator hypothesized that “Sparing a limb, as opposed to amputating it, offers a quality of life advantage.” Rather than assuming this was true, the investigators tested their hypothesis. Subjects who received the limb-sparing procedures reported limitations in mobility and sexual functioning. These observations were confirmed with physical assessments of mobility and endocrine function. As a result of these studies, the original hypothesis was rejected, radiation therapy was modified, and physical rehabilitation was added to the limb-sparing therapeutic approach.

There is a danger of adding patient-based outcomes to every clinical trial. If the majority of these studies either fail to answer clinically relevant questions or are methodologically weak, eventually a negative perception about patient-centered outcomes will grow in the research community.

Sugarbaker, P. H., Barofsky, I., Rosenberg, S. A., Gianola, F. J. (1986). Quality of life assessment of patients in extremity sarcoma clinical trialsSurgery 91:17–23
Hicks, J. E., Lampert, M. H., Gerber, L. H., Glastein, E., Danoff, J. (1985). Functional outcome update in patients with soft tissue sarcoma undergoing wide local excision and radiation (Abstract). Archives of Physical Medicine and Rehabilitation 66:542–3
Brown, M. L., Lipscomb, J., Snyder, C. (2001). The burden of illness of cancer: economic cost and quality of lifeAnnual Review of Public Health 22:91–113
Revicki, D. A., Rothman, M., Luce, B. (1992). Health-related quality of life assessment and the pharmaceutical industryPharmacoeconomics 1:294–408
Slevin, M. L., Stubbs, L., Plant, H. al. (1990). Attitude to chemotherapy: comparing viewsBritish Medical Journal 300:1458–60
Brinkley, D. (1985). Quality of life in cancer trialsBritish Medical Journal 291:685–6
Moinpour, C., Feigl, P., Metch, al. (1989). Quality of life endpoints in cancer clinical trials: review and recommendationsJournal of the National Cancer Institute 81:485–95
Gotay, C. C., Korn, E. L., McCabe, M. S., Moore, T. D., Cheson, B. D. (1992). Quality of life assessment in cancer treatment protocols: research issues in protocol developmentJournal of the National Cancer Institute 84:575–9
Hillner, B. E., Smith, T. J. (1998). Does a clinical trial warrant an economic analysis? (Editorial)Journal of the National Cancer Institute 90:724–5
O'Brien, this volume, Chapter 25
Hornbrook, this volume, Chapter 24
Bungay, K. M., Boyer, J. G., Steinwald, A. B., Ware, J. E. (1996). Health-related quality of life: an overview. In Principles of Pharmacoeconomics (2nd Edition), ed. J. L. Bootman, R. J. Townsend, W. F. McGhan, pp. 128–48. Cincinnati, OH: Harvey Whitney Books Company
Fairclough, D. L. (2002). Design and Analysis of Quality of Life Studies in Clinical Trials. Boca Raton, FL: Chapman and Hall/CRC
Sprangers, M. A. G., Aaronson, N. K. (1992). The role of health care providers and significant others in evaluating the quality of life of patients with chronic diseases: a reviewJournal of Clinical Epidemiology 45:743–60
Rothman, M. L., Hedrick, S. C., Bulcroft, K. A., Hickam, D. H., Rubinstein, L. Z. (1991). The validity of proxy-generated scores as measures of patient health statusMedical Care 29:115–24
Sneeuw, K. C. A., Aaronson, N. K., Sprangers, M. A. G., Detmar, S. B., Wever, L. D. V., Schornagel, J. H. (1998). Comparison of patient and proxy EORTC QLQ-C30 ratings in assessing the quality of life of cancer patientsJournal of Clinical Epidemiology 51:617–31
Novella, J. L., Jochum, C., Jolly, D., Morrone, I., Ankri, J., Bureau, F., Blanchard, F. (2001). Agreement between patient' and proxies' reports of quality of life in Alzheimer's diseaseQuality of Life Research 10:443–52
Epstein, A. M., Hall, J. A., Togretti, al. (1989). Using proxies to evaluate quality of lifeMedical Care 27(Suppl.): S91–8
Nelson, L. M., Longstreth, W. T., Koepsel, T. D., Belle, G. (1990). Proxy respondents in epidemiologic researchEpidemiology Reviews 12:71–89
Farrow, D. C., Samet, J. M. (1990). Comparability of information provided by elderly cancer patients regarding health and functional status, social network and life eventsEpidemiology 1:370–6
Groenvold, M., Klee, M. C., Sprangers, M. A. G., Aaronson, N. K. (1997). Validation of the EORTC QLQ-C30 quality of life questionnaire through combined qualitative and quantitative assessment of patient-observer agreementJournal of Clinical Epidemiology 50:441–50
Fitzsimmons, D., George, S., Payne, S., Johnson, C. D. (1990). Differences in perceptions of quality of life issues between health professionals and patient with pancreatic cancerPsycho-Oncology 8:135–43
Gabriel, S. E., Kneeland, T. S., Melton, L. J., Moncur, M. M., Ettiger, B., Tosteson, A. N. A. (1999). Health-related quality of life in economic evaluations for osteoporosis: whose values should we use?Medical Decision Making 19:141–8
Llewellyn-Thomas, H., Sutherland, H. J., Tibshirani, al. (1984). Describing health states. Methodologic issues in obtaining values for health statesMedical Care 22:543–52
Patrick, D. L., Sittampalam, Y., Somerville, S. al. (1985). A cross-cultural comparison of health status valuesAmerican Journal of Public Health 75:1402–7
Balaban, D. J., Sagi, P. C., Goldfarb, N. I., Mettler, S. (1986). Weights for scoring the quality of well-being instrument among rheumatoid arthritics. A comparison to general population weightsMedical Care 24:973–80
Sackett, D. L., Torrance, G. (1978). The utility of different health states as perceived by the general publicJournal of Chronic Disease 31:697–704
Schipper, H. (1990). Guidelines and caveats for quality of life measurement in clinical practice and researchOncology 4:51–7
Wiklund, I., Dimenas, E., Wahl, M. (1990). Factors of importance when evaluating quality of life in clinical trialsControlled Clinical Trials 11:169–79
TeVelde, A., Sprangers, M. A., Aaronson, N. K. (1996). Feasibility, psychometric performance and stability across modes of administration of the CARES-SFAnnals of Oncology 7:381–90
Kissinger, P., Rice, J., Farley, al. (1999). Application of computer-assisted interviews to sexual behavior researchAmerican Journal of Epidemiology 149:950–4
Turner, C. F., Ku, L., Rogers, S. al. (1998). Adolescent sexual behavior, drug use, and violence: increased reporting with computer survey technologyScience 280:867–73
Skinner, H. A., Allen, B. A. (1983). Does the computer make a difference? Computerized versus face-to-face versus self-report assessment of alcohol, drug and tobacco useJournal of Consulting Clinical Psychology 51:267–75
Weinberger, M., Oddone, E. Z., Samsa, G. al. (1996). Are HRQOL measures affected by the mode of administration?Journal of Clinical Epidemiology 49:135–40
Cella, D. F. (1995). Methods and problems in measuring QOL. Support Care in Cancer 3:11–22
McHorney, D. A., Kosinski, M., Ware, J. E. (1994). Comparison of the cost and quality of norms for the SF-36 health survey collected by mail versus telephone interview: results from a national surveyMedical Care 32:551–67
Leidy, N. K., Elixhauser, A., Rentz, A. al. (1999) Telephone validation of the QOL in epilepsy inventory-89 (QOLIE-89)Epilepsia 40:97–106
Gasquet, I., Falissard, B., Ravaud, P. (2001). Impact of reminders and methods of questionnaire distribution on patient response to mail-back satisfaction surveyJournal of Clinical Epidemiology 54:1174–80
Velikova, G., Wright, E. P., Smith, A. al. (1999). Automated collection of quality of life data: a comparison of paper and computer-touchscreen questionnairesJournal of Clinical Oncology 17:998–1000
Kleinman, L., Leidy, N. K., Crawley, J., Bonomi, A., Schoenfeld, P. (2001). A comparative trial of paper-and-pencil versus computer administration of the QOL in Reflux and Dyspepsia (QOLRAD) questionnaireMedical Care 39:181–9
Buxton, J., White, M., Osoba, D. (1998). Patients' experiences using a computerized program with a touch-sensitive video monitor for the assessment of health-related quality of lifeQuality of Life Research 7:513–19
Yarnold, P. R., Stewart, M. J., Stille, F. al. (1996). Assessing functional status of elderly adults via microcomputerPerception and Motor Skills 82:689–90
Crawley, J. A., Bleinman, L., Dominitz, J. (2000). User preferences for computer administration of quality of life instrumentsDrug Information Journal 34:137–44
Burke, K. C., Baker, J. H., Hillis, A. (1995). Test-retest reliability in psychiatric patients of the SF-36 health surveyInternational Journal of Methods in Psychological Research 5:189–94
Drummond, H. E., Gosh, S., Ferguson, al. (1995). Electronic quality of life questionnaires: a comparison of pen-based electronic questionnaires with conventional paper in a gastrointestinal studyQuality of Life Research 4:21–6
O'Connor, K. P., Hallam, R. S., Hinchliffe, R. (1989). Evaluation of a computer interview system for use with neuro-otology patientsClinical Otolaryngology 14:3–9
American Psychological Association (1986). Guidelines of Computer Based Tests and Interpretation (p. 18). American Psychological Association
Hopwood, P., Harvey, A., Davies, J., Stephens, R. al. (1997). Survey of the Administration of Quality of Life Questionnaires in three multicentre randomised trials in cancerEuropean Journal of Cancer 90:49–57
Fairclough, D. L., Cella, D. F. (1996). A Cooperative Group report on quality of life research: lessons learned. Eastern Cooperative Oncology Group (ECOG)Journal of the National Cancer Institute 40:73–5
Young, T., Maher, J. (1999). Collecting quality of life data in EORTC clinical trials — what happens in practice?Psycho-Oncology 8, 260–3
Cella, D. F., Skeel, R. T., Bonomi, A. E. (1993). Policies and Procedures Manual. Eastern Cooperative Oncology Group Quality of Life Subcommittee, Boston MA. (Unpublished)
Brooks, M. M., Jenkins, L. S., Schron, E. B., Steinberg, J. S., Cross, J. A., Paeth, D. S. (1998). Quality of life at baseline: is assessment after randomization valid?Medical Care 36:1515–19
Fairclough, D. L. (1996). Quality of life in cancer clinical trials: now that we have the data, what do we do?Journal of Applied Statistical Science 4:253–69
Curren, D., Fayers, P., Molenbergerghs, G., Machin, D. (1998). Analysis of incomplete quality of life data in clinical trials. In Quality of Life Assessment in Clinical Trials: Methods and Practice, ed. M. Staquet, R. Hays, P. Fayers, pp. 249–80. Oxford: Oxford University Press
Korn, E. L., O'Fallon, J. (1990). Statistical considerations. Statistics Working Group. In Quality of Life Assessment in Cancer Clinical Trials, Report on Workshop on Quality of Life Research in Cancer Clinical Trials, Division of Cancer Prevention and Control. Bethesda, MD: National Cancer Institute
Heyting, A., Tolboom, J. T. B. M., Essers, J. G. A. (1992). Statistical handling of dropouts in longitudinal clinical trialsStatistics in Medicine 11:2043–61
Gould, A. L. (1980). A new approach to the analysis of clinical drug trials with withdrawalsBiometrics 36:721–27
Jennrich, R. I., Schluchter, M. D. (1986). Unbalanced repeated-measures models with structured covariance matricesBiometrics 42:805–20
Laird, N. M. (1988). Missing data in longitudinal studiesStatistics in Medicine 7:305–15
Little, R. J. A. (1995). Modeling the dropout mechanism in repeated-measures studiesJournal of the American Statistical Association 90:1112–21
Zwinderman, A. H. (1992). Statistical analysis of longitudinal quality of life data with missing measurementsQuality of Life Research 1:219–24
Wu, M. C., Bailey, K. R. (1988). Analyzing changes in the presence of informative right censoring caused by death and withdrawalStatistics in Medicine 7:337–46
Wu, M. C., Carroll, R. J. (1988). Estimation and comparison of changes in the presence of informative right censoring by modeling the censoring processBiometrics 44:175–88
Mori, M., Woodworth, G. G., Woolson, R. F. (1992). Application of empirical Bayes inference to estimation of rate of change in the presence of informative right censoringStatistics in Medicine 11:621–31
Diggle, P. J., Kenward, M. G. (1994). Informative dropout in longitudinal data analysis (with discussion)Applied Statistics 43:49–93
Schluchter, M. D. (1992). Methods for the analysis of informatively censored longitudinal dataStatistics in Medicine 11:1861–70
DeGruttola, V., Tu, X. M. (1994). Modeling progression of CD4-lymphocyte count and its relationship to survival timeBiometrics 50:1003–14
Rubin, D. B. (1987). Multiple Imputation for Nonresponse in Surveys. New York: John Wiley
Rubin, D. B., Schenker, N. (1991). Multiple imputation in health-care data bases: an overview and some applicationsStatistics in Medicine 10:585–98
Schafer, J. L. (1998). Analysis of Incomplete Multivariate Data. London: Chapman and Hall
Crawford, S. L., Tennstedt, S. L., McKinlay, J. B. (1995). A comparison of analytic methods for non-random missingness of outcome dataJournal of Clinical Epidemiology 48:209–19
Lavori, P. W., Dawson, R., Shera, D. (1995). A multiple imputation strategy for clinical trials with truncation of patient dataStatistics in Medicine 14:1913–25
Fairclough, D. L. (2002). Multiple imputation for non-random missing data in longitudinal studies of health-related quality of life. In Statistical Methods for Quality of Life Studies: Design, Measurement and Analysis, ed. M. Mesbah, B. F. Cole, M.-L. T. Lee. Boston: Kluwer Academic Publishers, pp. 323–37
Fairclough, D. L., Peterson, H., Cella, D., Bonomi, P. (1998). Comparison of model based methods dependent on the missing data mechanism in two clinical trials of cancer therapyStatistics in Medicine 17:781–96