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Evaluating treatment efficacy: potential biases behind randomized controlled trials.

Osteoarthritis affects millions of Americans, creating significant loss in quality of life and much disability. Individuals with this disease and their caregivers alike would no doubt wish for expanded options for therapies that are effective and safe. Simplicity of administration and low cost would make a treatment even more desirable. With this in mind, readers of this issue of the Journal of Clinical Rheumatology may find the article by McKay et alof substantial interest. McKay et al evaluated the efficacy of a new herbal cream named Arthritis Relief Plus in a small, randomized, double-blind clinical trial. Recruited from a community-based arthritis clinic, 11 patients were randomized to the active treatment, and 8 patients received a specially formulated placebo cream that contained identical amounts of capsaicin and menthol as the active product, molasses, arrowroot powder, and neem powder but none of the other herbal constituents. Patients met the diagnostic criteria of osteoarthritis and had involvement of various joints. Only the most affected joint was treated, which was not matched between the 2 groups. The treatment and placebo creams were applied daily, and patients performed self-evaluation of pain and stiffness each day and were evaluated in an arthritis clinic biweekly for a total treatment duration of 28 days. Pain and stiffness, scored on a 100-point visual analog scale (VAS) by patients, were the outcome measures. McKay et al found significantly decreased pain and stiffness levels in the actively treated group compared with placebo at weeks 2, 3, and 4. By week 4, pain was reduced by 77% in the active treatment group (16% reduction in placebo group) and stiffness was reduced by 86% (18% placebo). No adverse effects were reported. The authors conclude that Arthritis Relief Plus can provide an alternative or adjunctive treatment in osteoarthritis and may reduce dependency on non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics. The reported efficacy of this herbal cream in this trial is impressive, if not somewhat incredible. As the authors themselves note, efficacy of NSAIDS as found in clinical trials is only on the order of 30%. Can a simple topical ointment be exceedingly more efficacious than long-standing oral treatments for osteoarthritis such as NSAIDs? The study by McKay et al was reportedly a randomized, double-blind trial, and such studies are relied upon as the most reliable evidence of a treatment’s efficacy. However, randomized controlled trials (RCTs) do have potential biases and these should be considered before the results of any RCT are subscribed to. First of all, in the McKay et al article, the number of patients studied was small, which was acknowledged by the authors, but the limitation of the small sample size was incorrectly disregarded as being “offset somewhat by the large treatment effect obtained.” Because a positive result was found, the problem of the small number of patients is not one of power but rather that small samples have a greater chance of imbalance of confounders 137 Journal of CLINICAL RHEUMATOLOGY