Archive for April 27th, 2009

Human subjects protections and research ethics: Where the rubber hits the road for science-based medicine

Arguably the most difficult aspect of science-based medicine is where the rubber hits the road, so to speak. That’s where scientists and physicians take the results of preclinical studies performed in vitro in biochemical assays and cell culture models and in vivo in animal models to humans. There are numerous reasons for this, not the least of which that preclinical models, contrary to what animal rights activists would like you to believe, do not predict human responses to new therapeutic agents as much as we would like. However, the single biggest reason that we cannot answer questions in human studies as easily as we can in cell culture and animal studies is ethics. Of course, answering questions using cell culture and animal studies is not “easy,” either, but performing studies using human beings as subjects is an order of magnitude (at least) more difficult because the potential to cause harm exists, and if harm is caused by the experimental treatment under study, that harm will be done to human beings, rather than cells in a dish or mice bred for research.

The “gold standard” type of study that we do to test the efficacy of a new drug is known as the randomized, placebo-controlled, double-blinded study, often abbreviated RCT. Indeed, this remains the gold standard and is accorded the highest level of “power” in the framework of evidence-based medicine. Of course, as we have argued time and time again, using the RCT to test therapies that are incredibly implausible on a strictly scientific basis (homeopathy or reiki, for instance) inevitably leads to numerous “false positives” in which the therapy appears to produce results statistically significantly better than the control. John Ioannidis has done numerous clever analyses that demonstrate how easily clinical research is led astray if it is not grounded in scientific plausibility. Indeed, the probability of false positive studies increases, the more improbable the modality. It is for these very reasons that we have proposed the concept of science-based medicine, which takes into account estimates of prior probability based on preclinical studies and basic scientific principles, rather than evidence-based medicine, which does not. Indeed, Wally Sampson has even proposed a “plausibility scale” for rating RCTs, and Steve Novella has pointed out how difficult it can be to interpret the medical literature.

Posted in: Clinical Trials, Medical Ethics, Politics and Regulation, Surgical Procedures, Vaccines

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