The Validity of Disease-Specific Quality of Life Attributions Among Adults with Multiple Chronic Conditions


  • John E. Ware Jr. John Ware Research Group, Watertown, MA, USA
  • Barbara Gandek University of Massachusetts Medical School, Worcester, MA, USA
  • Jeroan Allison University of Massachusetts Medical School, Worcester, MA, USA



Patient-reported outcomes, Health-related quality of life, Disease-specific measures, Multiple chronic conditions, Validity, Multitrait-multimethod analysis.


Background: A crucial assumption underlying all disease-specific quality of life (QOL) measures, that patients can validly differentiate a specific disease in the presence of multiple chronic conditions, has not been tested using multiple methods. Our objective was to evaluate the convergent and discriminant validity of QOL attributions to specific diseases among adults with multiple chronic conditions (MCC).

Methods: Adults age 18 and older (N=4,480) sampled from eight pre-identified condition groups (asthma, COPD, angina/MI with angina, congestive heart failure, diabetes, chronic kidney disease, osteoarthritis, rheumatoid arthritis) completed an Internet survey. Comorbid conditions were determined using a 35-condition checklist. Product-moment correlations were analyzed separately by pre-identified condition group using the multitrait-multimethod of construct validation, where traits were defined by 9-26 conditions and each condition was measured by two methods: disease severity rating and Disease-specific Quality of Life Impact Scale (QDIS) global rating. A third method (symptom or clinical marker) was available for the eight pre-identified conditions. Convergent validity was supported when correlations among different methods of measuring the same condition (trait) were substantial (r≥ 0.40). Discriminant validity was supported when correlations between the same and different methods of measuring different conditions were significantly lower than corresponding convergent correlations.

Results: In support of convergent validity, 22 of 24 convergent correlations were substantial (r=0.38-0.84, median=0.53). In support of discriminant validity, 833 of 924 tests (90.2%) yielded significantly higher convergent than discriminant correlations across the eight pre-identified conditions. Exceptions to this pattern of results were most often observed for comorbid conditions within the same clinical area.

Conclusions: Collectively, convergent and discriminant test results support the construct validity of disease-specific QOL impact attributions across MCC within the eight pre-identified conditions. Noteworthy exceptions should be considered when interpreting some specific QOL impact attributions and warrant further study. Pursuit of a summary disease-specific QOL impact score standardized across MCC is recommended.


National Quality Forum. Multiple chronic conditions measurement framework. Washington, DC: National Quality Forum 2012.

Gijsen R, Hoeymans N, Schellevis FG, Ruwaard D, Satariano WA, van den Bos GA. Causes and consequences of comorbidity: a review. J Clin Epidemiol 2001; 54: 661-74. DOI:

Marengoni A, Angleman S, Melis R, Mangialasche F, Karp A, Garmen A, et al. Aging with multimorbidity: a systematic review of the literature. Ageing Res Rev 2011; 10: 430-9. DOI:

Salive ME. Multimorbidity in older adults. Epidemiol Rev 2013; 35: 75-83. DOI:

Safford MM, Allison JJ, Kiefe CI. Patient complexity: more than comorbidity. The vector model of complexity. J Gen Intern Med 2007; 22 Suppl 3: 382-90. DOI:

Boyd CM, Darer J, Boult C, Fried LP, Boult L, Wu AW. Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases: implications for pay for performance. JAMA 2005; 294: 716-24. DOI:

Tinetti ME, Studenski SA. Comparative effectiveness research and patients with multiple chronic conditions. N Engl J Med 2011; 364: 2478-81. DOI:

de Groot V, Beckerman H, Lankhorst GJ, Bouter LM. How to measure comorbidity. A critical review of available methods. J Clin Epidemiol 2003; 56: 221-9. DOI:

Fortin M, Lapointe L, Hudon C, Vanasse A, Ntetu AL, Maltais D. Multimorbidity and quality of life in primary care: a systematic review. Health Qual Life Outcomes 2004; 2: 51. DOI:

Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40: 373-83. DOI:

Diederichs C, Berger K, Bartels DB. The measurement of multiple chronic diseases--a systematic review on existing multimorbidity indices. J Gerontol A Biol Sci Med Sci 2011; 66: 301-11. DOI:

Working Group on Health Outcomes for Older Persons with Multiple Chronic Conditions. Universal health outcome measures for older persons with multiple chronic conditions. J Am Geriatr Soc 2012; 60: 2333-41. DOI:

U.S. Department of Health and Human Services, Food and Drug Administration. Guidance for industry - Patient-reported outcome measures: Use in medical product development to support labeling claims. Rockville, MD: Food and Drug Administration, 2009.

Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 1988; 15: 1833-40.

Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire. Am Rev Respir Dis 1992; 145: 1321-7. DOI:

Wilson IB, Cleary PD. Linking clinical variables with health-related quality of life. A conceptual model of patient outcomes. JAMA 1995; 273: 59-65. DOI:

Nathan RA, Sorkness CA, Kosinski M, Schatz M, Li JT, Marcus P, et al. Development of the Asthma Control Test: a survey for assessing asthma control. J Allergy Clin Immunol 2004; 113: 59-65. DOI:

Rector TS, Kubo SH, Cohn JN. Patients' self-assessment of their congestive heart failure: Content, reliability, and validity of a new measure, the Minnesota Living with Heart Failure questionnaire. Heart Failure 1987; 3: 198-209.

Hays RD, Kallich JD, Mapes DL, Coons SJ, Carter WB. Development of the Kidney Disease Quality of Life (KDQOL) instrument. Qual Life Res 1994; 3: 329-38. DOI:

Ware JE Jr. Standards for validating health measures: Definition and content. J Chronic Dis 1987; 40: 473-80. DOI:

Ware JE Jr., Gandek B, Guyer R, Deng N. Standardizing disease-specific quality of life measures across multiple chronic conditions: Development and initial evaluation of the QOL Disease Impact Scale (QDIS®). In review

EuroQol Group. EuroQol--a new facility for the measurement of health-related quality of life. Health Policy 1990; 16: 199-208. DOI:

Cella D, Riley W, Stone A, Rothrock N, Reeve B, Yount S, et al. The Patient-reported Outcomes Measurement Information System (PROMIS) developed and tested its first wave of adult self-reported health outcome item banks: 2005-2008. J Clin Epidemiol 2010; 63: 1179-94. DOI:

Ware JE Jr., Sherbourne CD. The MOS 36-item Short-Form Health Survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30: 473-83. DOI:

Wiebe S, Guyatt G, Weaver B, Matijevic S, Sidwell C. Comparative responsiveness of generic and specific quality-of-life instruments. J Clin Epidemiol 2003; 56: 52-60. DOI:

Ware JE Jr., Guyer R, Harrington M, Boulanger R. Evaluation of a more comprehensive survey item bank for standardizing disease-specific impact comparisons across chronic conditions. Qual Life Res 2012; 21: 27-8.

Ware JE Jr., Harrington M, Guyer R, Boulanger R. A system for integrating generic and disease-specific patient-reported outcome (PRO) measures. Mapi Research Institute Patient Reported Outcomes Newsletter 2012: 1-4.

Brown TA. Confirmatory Factor Analysis for Applied Research. 2nd ed. New York: Guilford Press, 2015.

Deng N, Anatchkova MD, Waring ME, Han KT, Ware JE,Jr. Testing item response theory invariance of the standardized Quality-of-life Disease Impact Scale (QDIS®) in acute coronary syndrome patients: Differential functioning of items and test. Qual Life Res 2015; 24: 1809-22. DOI:

GfK United States. KnowledgePanel Design Summary. http://www gfk com/Documents/GfK-KnowledgePanel-Design-Summary.pdf; Accessed November 3, 2014.

AAPOR Standards Committee Task Force. Research Synthesis: AAPOR Report on Online Panels. Public Opinion Quarterly 2010; 74: 711-81. DOI:

Campbell DT, Fiske DW. Convergent and discriminant validation by the multitrait-multimethod matrix. Psychol Bull 1959; 56: 81-105. DOI:

Lin P, Ware JE Jr, Meyer K, Richardson M, Bjorner JB. Methods for psychometric and clinical evaluations of CAT-based measures of disease impact in chronic kidney disease (CKD). Value Health 2010; 13: A244. DOI:

Deng N, Allison JJ, Fang HJ, Ash AS, Ware JE Jr. Using the bootstrap to establish statistical significance for relative validity comparisons among patient-reported outcome measures. Health Qual Life Outcomes 2013; 11: 89. DOI:

Frei A, Muggensturm P, Putcha N, Siebeling L, Zoller M, Boyd CM et al. Five comorbidities reflected the health status in patients with chronic obstructive pulmonary disease: the newly developed COMCOLD index. J Clin Epidemiol 2014; 67: 904-11. DOI:

Ware JE Jr., Gandek B, Kulasekaran A, Guyer R. Evaluation of smoking-specific and generic quality of life measures in current and former smokers in Germany and the United States. Health Qual Life Outcomes 2015; 13: 128. DOI:

Bayliss EA, Ellis JL, Steiner JF. Subjective assessments of comorbidity correlate with quality of life health outcomes: initial validation of a comorbidity assessment instrument. Health Qual Life Outcomes 2005; 3: 51. DOI:

Spertus JA, Winder JA, Dewhurst TA, Deyo RA, Prodzinski J, McDonell M, et al. Development and evaluation of the Seattle Angina Questionnaire: a new functional status measure for coronary artery disease. J Am Coll Cardiol 1995; 25: 333-41. DOI:




How to Cite

Ware Jr., J. E., Gandek, B., & Allison, J. (2016). The Validity of Disease-Specific Quality of Life Attributions Among Adults with Multiple Chronic Conditions. International Journal of Statistics in Medical Research, 5(1), 17–40.



Special Issue - Methods for Estimating Treatment Effects of Persons with Multiple Chronic Conditions