Measurement of Patient-Reported Outcomes of Health Services

  • Joseph C. CappelleriEmail author
  • Andrew G. Bushmakin
Reference work entry
Part of the Health Services Research book series (HEALTHSR)


A patient-reported outcome (PRO) is any report on the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else. The measurement of PROs should address key protocol elements that include the rationale for the specific aspect of PRO being measured, explicit research objectives and endpoints, strategies for minimizing the exclusion of subjects from the study, rationale for timing of assessments and off-study rules, rationale for instruction selection, details for administration of PRO assessments to minimize bias and missing data, sample size estimation, and analytic plan. Another key element involves the measurement properties of a PRO. These protocol elements are central to this chapter as they relate to the design and measurement of PROs. These elements are discussed and framed within the five characteristics that tend to be associated with PROs: missing and incomplete data, psychometric validation, interpretation, multiple testing, and longitudinal analysis. Special consideration is given for developing a PRO measurement strategy in a regulatory context where the intent is to have a labeling claim on a PRO.


  1. Alcion L, Petersen JL, Temple S, Arndt S. Probabilistic index: an intuitive non-parametric approach to measuring the size of treatment effects. Stat Med. 2006;25:591–602.CrossRefGoogle Scholar
  2. Brooks MM, Jenkins LS, Schron EB, Steinberg JS, Cross JA, Paeth DS. Quality of life at baseline: is assessment after randomization valid? Med Care. 1998;26:1515–9.CrossRefGoogle Scholar
  3. Brown TA. Confirmatory factor analysis for applied research. New York: The Guilford Press; 2006.Google Scholar
  4. Cappelleri JC, Gerber RA. Exploratory factor analysis. In: Chow S-C, editor. Encyclopedia of biopharmaceutical statistics.3rd ed., revised and expanded. New York: Informa Healthcare; 2010. p. 480–5.CrossRefGoogle Scholar
  5. Cella D, Li JZ, Cappelleri JC, Bushmakin A, Charbonneau C, Kim ST, Chen I, Michaelson MD, Motzer RJ. Quality of life in patients with metastatic renal cell carcinoma treated with sunitinib versus interferon-alfa: Results from a phase III randomized trial. J Clin Oncol. 2008;26:3763–9.PubMedCrossRefGoogle Scholar
  6. Fairclough DL. Patient reported outcomes as endpoints in medical research. Stat Methods Med Res. 2004;13:115–38.PubMedCrossRefGoogle Scholar
  7. Fairclough DL. Analysing longitudinal studies of QoL. In: Fayers P, Hayes R, editors. Assessing quality of life in clinical trials. Oxford: Oxford University Press; 2005. p. 149–65.Google Scholar
  8. Fairclough DL. Design and analysis of quality of life studies in clinical trials. 2nd ed. Boca Raton: Chapman & Hall/CRC; 2010.Google Scholar
  9. Fayers FM, Machin D. Quality of life: the assessment, analysis and interpretation of patient-reported outcomes. 2nd ed. Chichester: Wiley; 2007.CrossRefGoogle Scholar
  10. Fayers PM, Aaronson NK, Bjordal K, Groenvold M, Curran D, Bottomley A. On behalf of the EORTC quality of life group. In: EORTC QLQ-C30 scoring manual. 3rd ed. Brussels: EORTC; 2001.Google Scholar
  11. Fetting JJ, Gray R, Fairclough DL, Smith TJ, Margolin KA, Citron ML, Grove-Conrad M, Cella D, Pandya K, Robert N, Henderson C, Osborne K, Abeloff MD. A 16-week multidrug regimen versus cyclophosphamide, doxorubicin and 5-flurouracil as adjuvant therapy for node-positive, receptor negative breast cancer: an intergroup study. J Clin Oncol. 1998;16:2382–91.PubMedCrossRefGoogle Scholar
  12. Fitzmaurice GH, Laird NM, Ware JH. Applied longitudinal analysis. 2nd ed. Hoboken: Wiley; 2011.CrossRefGoogle Scholar
  13. Food and Drug Administration. Guidance for industry on patient-reported outcome measures: Use in medical product development to support labeling claims. Fed Regist. 2009;74(235):65132–3.Google Scholar
  14. Gotay CC, Korn EL, McCabe MS, Moore TD, Cheson BD. Building quality of life assessment into cancer treatment studies. Oncology. 1992;6:25–8.PubMedGoogle Scholar
  15. Johnson JR, Temple R. Food and drug administration requirements for approval of new anticancer drugs. Cancer Treat Rep. 1985;69:1155–9.PubMedGoogle Scholar
  16. Luo X, Cappelleri JC. A practical guide on interpreting and evaluating patient-reported outcomes in clinical trials. Clin Res Regul Aff. 2008;25:197–211.CrossRefGoogle Scholar
  17. Mallinckrodt CH, Lane PW, Schnell D, Peng Y, Mancuso JP. Recommendations for the primary analysis of continuous endpoints in longitudinal clinical trials. Drug Inf J. 2008;42:303–19.CrossRefGoogle Scholar
  18. National Research Council. The prevention and treatment of missing data in clinical trials. Washington, DC: The National Academies Press; 2010.Google Scholar
  19. Patrick DL, Burke LB, Powers JH, Scott JA, Rock EP, Dawisha S, O’Neill R, Kennedy DL. Patient-reported outcomes to support medical product labeling claims: FDA perspective. Value Health. 2007;10:S125–37.PubMedCrossRefGoogle Scholar
  20. Revicki D, Hays RD, Cella D, Sloan J. Recommended methods for determining responsiveness and minimally important differences for patient-reported outcomes. J Clin Epidemiol. 2008;61:102–9.PubMedCrossRefGoogle Scholar
  21. Rothman ML, Beltran P, Cappelleri JC, Lipscomb J, Teschendorf B, Mayo/FDA Patient-Reported Outcomes Consensus Meeting Group. Patient-reported outcomes: conceptual issues. Value Health. 2007;10:S66–75.PubMedCrossRefGoogle Scholar
  22. Russell IJ, Crofford LJ, Leon T, Cappelleri JC, Bushmakin AG, Whalen E, Barrett JA, Sadosky A. The effects of pregabalin on sleep disturbance symptoms among individuals with fibromyalgia syndrome. Sleep Med. 2009;10:604–10.PubMedCrossRefGoogle Scholar
  23. Snyder CF, Watson ME, Jackson JD, Cella D, Halyard MY, Mayo/FDA Patient-Reported Outcomes Consensus Meeting Group. Patient-reported outcomes instruction selection: designing a measurement strategy. Value Health. 2007;10:S76–85.PubMedCrossRefGoogle Scholar
  24. Streiner DL, Norman GR. Health measurement scales: a practical guide to their development and use. 4th ed. New York: Oxford University Press; 2008.CrossRefGoogle Scholar
  25. Wang XS, Fairclough DL, Liao Z, Komaki R, Chang JY, Mobley GM, Cleeland CS. Longitudinal study of the relationship between chemoradiation therapy for non-small-cell lung cancer and patient symptoms. J Clin Oncol. 2006;24:4485–91.PubMedCrossRefGoogle Scholar
  26. Wiklund I. Assessment of patient-reported outcomes in clinical trials: the example of health-related quality of life. Fundam Clin Pharmacol. 2004;18:351–63.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Global Product DevelopmentPfizer IncGrotonUSA

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