Are randomized control trial outcomes influenced by the inclusion of a placebo group? A systematic review of nonsteroidal antiinflammatory drug trials for arthritis treatment

Placebo groups are often included in randomized control trials evaluating d rug therapy, yet we know Little about the placebo effect. The purpose of ou r study was to evaluate how the presence of a placebo group in a randomized control trial (RCT) influences the patients' ratings of the efficacy of an active drug therapy and their reporting of its adverse effects. We identif ied studies published between 1966 and 1994 using MEDLINE. Randomized contr ol trials evaluating acetylsalicylic acid, diclofenac, or indomethacin for the treatment of osteo or rheumatoid arthritis were included in our sample. Two investigators independently extracted data. Fifty-eight treatment arms met our inclusion criteria and were available for analysis. Twenty-five tr eatment arms evaluated a nonsteroidal antiinflammatory drug (NSAID) in plac ebo control trials and 33 in comparative trials. Using a logistic regressio n model to adjust for the differences between the evaluated drugs and betwe en the types of arthritis, we found that patients receiving an NSAID in a p lacebo control trial were more likely to withdraw due to inefficacy (OR = 1 .3; 95% CI, 1.0 to 1.6; P = 0.04). Using a similar model, withdrawals due t o adverse effects were found to be more common when the NSAID was given in trials that did not include a placebo group (OR = 1.5; 95% CI, 1.1 to 1.9; P = 0.002) as were reports of cutaneous (OR = 4.2; 95% CI, 1.7 to 9.9), gas trointestinal (OR = 1.6; 95% CI, 1.3 to 2.0), and other types (OR = 5.3; 95 % CI, 3.8 to 7.4) of adverse effects. Although reports of central nervous s ystem adverse effects were more frequent in the comparative trials, this di fference was not significant. Including a placebo group in a RCT changes ho w patients rate the efficacy and adverse effects of their therapy. Our resu lts highlight the need to consider the placebo effect in the design and ana lyses of clinical trials. J CLIN EPIDEMIOL 52;2:113-122, 1999. (C) 1999 Els evier Science Inc.