Laska and co-workers1 have mustered impressive new evidence for the efficacy of caffeine as an analgesic adjuvant while simultaneously providing an example of how results from a number of controlled clinical trials, the majority of which do not individually meet the usually accepted levels of statistical significance for verifying a drug effect, may be combined to provide substantial evidence of drug efficacy. Caffeine has long been a constituent of both over-the-counter (OTC) and prescription analgesic combinations in conjunction with aspirin, acetaminophen, phenacetin, and salicylamide. However, critiques have repeatedly noted that the then-available evidence for caffeine's contribution to the efficacy of such combinations was tenuous at best.2-5
The major problem in demonstrating caffeine's contribution is the limited assay sensitivity of controlled clinical trials used to evaluate mild analgesics and their combinations.3 Because of the multiplicity of known and unknown variables that affect the course of a patient's pain
Beaver WT. Caffeine Revisited. JAMA. 1984;251(13):1732–1733. doi:10.1001/jama.1984.03340370064033
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