• A Role for Observational Epidemiology?
  • August 12, 2010 | Author: David A. Oliver
  • Law Firm: Vorys, Sater, Seymour and Pease LLP - Houston Office
  • The Institute of Medicine's "Ethical Issues in Studying the Safety of Approved Drugs: A Letter Report (2010)" is a slog punctuated by the occasional eye-roller. Perhaps because of the presence of undefined ethical issues, technical discussions of drug trials are interrupted with fawning nods to stakeholders "who have kinds of knowledge different from those of technical experts" and a promise to incorporate their different ways of knowing. Sheesh. Anyway, the report does suggest something profoundly important and that is a shift away from the randomized controlled trial (the so-called gold standard) to observational epidemiological studies when making decisions about whether an approved drug ought to be pulled from the market.

    Observational epidemiology has been on life support for years. It worked very well on the big risks but when it was turned loose on smaller risks, or worse yet, simply unleashed upon mounds of raw data without any a priori hypothesis to be tested, it failed altogether and often as not wound up falsely indicting random aspects of daily life as wanton spree killers. The failures of course were due neither to the math nor the principles but rather to the misuses to which it was put - especially by expert witnesses who knew better. Nevertheless, finding a role for epidemiology in a world of small risks has been a topic of much debate. Online, and free, you can find the debate in full at "The Triumph of the Null Hypothesis: Epidemiology in an Age of Change" and Jan P Vandenbroucke's commentary, "Seen from Another Angle".

    For the Institute of Medicine (IOM), at least given qualms about the ethics of randomized controlled trials particularly after questions have been raised about a drug, Vandenbroucke's view has apparently prevailed. The IOM concluded that "under specific circumstances, observational studies may be adequate to ... identify the presence of an important safety issue ..."; and further that such studies "could provide useful and valid estimates of the risk associated with a safety signal." And, when a drug trial is ongoing, e.g. TIDE, "if new evidence from any source, including the trial itself, is determined to be sufficiently compelling to ground a policy decision without waiting for additional new information, allowing the trial to continue would be unethical."

    So, if observational epidemiology prompted by a potential signal of a serious risk were to suggest a small risk, the drug could be pulled from the market and the only test capable of answering the question of whether or not it actually posed a risk would be stopped and prohibited from being run? It sounds like it. If that's the case observational epidemiology has come roaring back to attain a position of power and prestige not held in many years.