Stimulated Reporting   (July 13, 2007)

A friend forwarded to me a recent newspaper article titled "Diabetes Drug Side Effect Reports Triple" and was extremely worried. Sure sounds scary, doesn't it? Fortunately, things are not as bad as it sounds from this headline. It's a phenomenon called "stimulated reporting," namely that media attention stimulates physicians and patients to report side events.

The point of the story was that since the recent publicity about Avandia, the number of reports to the FDA of Avandia's side effects (adverse events in medical lingo) tripled. That does not mean that the number of side effects tripled due to media attention. In fact, the number of side effects almost inevitably went down during the past month or two, as physicians heard about the cardiac issue and withdrew some of their patients from the drug - and they would be most likely to withdraw the highest-risk patients (that is, the ones who were at most risk of cardiac events).

A more appropriate analysis of the increased number of reports would have included information about the date when the event occurred. Based on my own experience when I worked as a pharmacovigilance physician for Rezulin, every time there's publicity about a drug's problems, there's a spike in reports - but the reports are about events that happened long before the publicity.

A hypothetical example: an obese middle-aged patient with diabetes, hypertension, high cholesterol, severe heart disease, and who's still a smoker, and who also has a strong family history of heart disease, takes a diabetes drug for months or years, then has a heart attack. At the time of the heart attack, no one suspects that the drug had anything to do with the heart attack, as there are tons of risk factors. But then, suppose that several years after the heart attack, there's publicity that the diabetes drug might cause an increased risk of heart attacks, and the patient or family calls the prescribing physician and demands that the physician report the case. Bingo, another example of stimulated reporting.

So, whereas there's legitimate concern about Avandia's safety profile, and legitimate worry about the adverse event reporting systems, headlines don't always tell the whole story. And detailed analysis of reported adverse events is needed to understand the true safety profile of any medication.