Long-term nonsteroidal anti-inflammatory drug (NSAID) use was protective against Alzheimer disease. Findings were clearest for ibuprofen. A beta (1-42)-suppressing NSAIDs did not differ from others.

ABSTRACT

Objective. Investigators in trials of glucosamine report a range of estimates for efficacy, making conclusions difficult. We undertook this study to identify factors that explain heterogeneity in trials of glucosamine.Methods. We searched for reports of trial results in Ovid Medline, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and proceedings of scientific conferences. We selected reports of randomized, double-blind, placebocontrolled trials of glucosamine for pain from osteoarthritis of the knee or hip. We extracted data regarding features of design, subjects, and markers of industry involvement, including industry funding, whether a drug was supplied by industry, industry participation, and industry-affiliated authorship. We examined which factors best accounted for differences in the effect sizes of studies grouped by these characteristics, and we examined changes in I 2 , a measure of heterogeneity. Results. Fifteen trials met our inclusion criteria. The summary effect size was 0.35 (95% confidence interval 0.14, 0.56). I 2 was 0.80. Except for allocation concealment, no feature of study design explained this substantial heterogeneity. Summary effect sizes ranged from 0.05 to 0.16 in trials without industry involvement, but the range was 0.47-0.55 in trials with industry involvement. The effect size was 0.06 for trials using glucosamine hydrochloride and 0.44 for trials using glucosamine sulfate. Trials using Rottapharm products had an effect size of 0.55, compared with 0.11 for the rest.Conclusion. Heterogeneity among trials of glucosamine is larger than would be expected by chance. Glucosamine hydrochloride is not effective. Among trials with industry involvement, effect sizes were consistently higher. Potential explanations include different glucosamine preparations, inadequate allocation concealment, and industry bias.Osteoarthritis (OA) is one of the most common chronic diseases affecting Americans and is a major source of disability in elderly persons (1). Pharmacologic therapy for pain relief is widely perceived to be the backbone of effective management. Unfortunately, many of the most effective pain relievers, especially nonsteroidal antiinflammatory drugs, have well-known side effects that limit their use.Glucosamine, which is classified as a "dietary supplement" in the US and is available over the counter, appears to be safe and is widely marketed for pain relief in OA. However, its efficacy is uncertain. While several trials have suggested that glucosamine has a marginal, if any, effect compared with placebo, others report robust efficacy.In a series of trials using similar methods and subjects, we would expect random variation in the estimate of the true effect of an intervention. If the observed variation in outcomes from trial to trial is consistent with chance variation, then the trials are said to be homogeneous (i.e., the trials are all evaluating the same effect and their conclusions are similar). If the observed variation in outcomes is...