Seems simple, yes? And so a group of Duke University researchers developed a hypothetical model to estimate the expected incremental number of adverse drug events that could be avoided once a drug is widely available. The upshot: "Requiring larger preapproval databases could be a cost-effective means of reducing adverse events in post-approval populations," they write inHealth Affairs.
As you may recall, most industry-sponsored clinical trials of new drugs are designed to determine efficacy in order to gain regulatory approval. But the researchers note that detecting adverse drug events is "rarely considered when sample-size calculations are undertaken for clinical trials." Thus, the statistical power to find side effects is "inherently a by-product" of establishing efficacy.
Their hypothetical study with 4,000 patients in each patient group improved the odds of detecting a side effect that affected slightly more than 1 percent of patients. The statistical power was 76 percent in the safety database with 2,000 patients and 96 percent in the database with 4,000 patients. They developed their scenario by reviewing literature on Vioxx and Celebrex, and suggest heart problems may have been detected sooner with larger clinical trial populations.
"Assuming that detection of a statistically significant increase in the risk of side effects would prevent regulatory approval, about 57,000 adverse events on average would be avoided in the target population with the smaller database, and approximately 72,000 would be avoided with the larger database," they write. "Thus, in the base-case analysis, an additional 15,000 adverse events would be avoided, on average, if larger databases were required to evaluate safety concerns."
In an accompanying editorial, Alan Garber, a staff physician at the VA Palo Alto HealthCare System and a Stanford University health policy professor, writes: "For most drugs, a requirement for more preapproval data will inevitably slow the approval process. Entry delays may impose only minor costs if alternative therapies of nearly equal effectiveness are available, but the consequences are much more costly if the drug in question is a unique treatment for a life-threatening condition. In retrospect, critics will claim that the delay was harmful if the drug is later found to be safe and highly effective, while the delay will be viewed as prudent policy if the drug in question is found to be harmful."