ARTHRITIS & RHEUMATISM Vol. 44, No. 5, May 2001, pp 1105–1113 © 2001, American College of Rheumatology Published by Wiley-Liss, Inc. Problems in the Development and Validation of Questionnaire-Based Screening Instruments for Ascertaining Cases With Symptomatic Knee Osteoarthritis The Framingham Study Michael LaValley, Timothy E. McAlindon, Stephen Evans, Christine E. Chaisson, and David T. Felson Objective. To determine if screening for symptom- atic knee osteoarthritis (OA) for clinical trials and epidemiologic studies could be satisfactorily done with- out performing knee radiographs and to develop effi- cient screening instruments for symptomatic knee OA based on self-reported symptoms and functional limita- tions. Methods. We administered a mailed question- naire containing many different questions on knee symptoms and functional limitations to 1,921 partici- pants of the Framingham Study who had previously been screened for symptomatic OA with a history and knee radiographs. Recursive partitioning methods (us- ing the Classification and Regression Trees [CART] program) were used to create a set of screening instru- ments for symptomatic knee OA, which was defined as knee symptoms on most days and radiographic evidence of OA. Three screening instruments were developed to maximize the sensitivity, specificity, and efficiency. Results. The sensitive instrument had 84% sensi- tivity and 73% specificity. The specific instrument had 46% sensitivity and 94% specificity. The efficient instru- ment had 56% sensitivity and 85% specificity. Sensitiv- ity was lower and specificity was higher when these instruments were used to screen for radiographic OA. All instruments had higher sensitivity but lower speci- ficity when used for older subjects (age >60) with greater disease prevalence. However, using any of these instruments as a single-step screening mechanism re- sulted in considerable misclassification. Conclusion. We conclude that none of these in- struments has adequate diagnostic test performance to serve as a single-step evaluation of the presence or absence of symptomatic knee OA. Osteoarthritis (OA) of the knee is a major cause of pain, disability, and cost in the general population, particularly among the elderly (1–3). Currently, there are few effective preventive strategies or medical thera- pies for this disorder (4,5). Further research is therefore needed to study risk factors for knee OA and to develop and test medical treatments. However, issues surrounding case ascertainment hamper OA studies (6). Strategies employing radiogra- phy as the only step in case detection are costly and expose many individuals without OA to radiation. If a set of questions could adequately identify those with OA, the cost of disease assessment would drop dramat- ically and many large-scale surveys and epidemiologic studies could begin to provide valid and highly useful data on OA. Further, large-scale inexpensive trials of treatments aimed at symptoms could be performed, facilitating the development of greatly needed new therapies. Some recent studies have characterized those who self-report arthritis as having either arthritis or OA (7), but the validity of this approach has not been critically evaluated. Last, federal and state health agen- Supported by NIH Arthritis Center grants AR-20613 and AG-09300 and by NIH/National Heart, Lung, and Blood Institute contract N01-HC-38038 to the Framingham Heart Study. Michael LaValley, PhD, Timothy E. McAlindon, MD, MPH, Stephen Evans, MPH, Christine E. Chaisson, MPH, David T. Felson, MD, MPH: Boston University, Boston, Massachusetts. Address correspondence and reprint requests to Michael LaValley, PhD, Boston University Arthritis Center, 715 Albany Street, A203, Boston, MA 02118. Submitted for publication July 25, 2000; accepted in revised form December 19, 2000. 1105