Randomized Controlled Trials and Adverse Effects

Most health care scholars–whether they are scientists, doctors or economists–believe that randomized controlled trials (RCTs) are the best means by which one can test whether or not a drug is efficacious. Despite its high cost, RCTs are able to abstract from confounding factors by randomly assigning similar patients to both a treatment and a placebo-controlled group.

Dr. James Gaulte of the Retired Doc’s Thoughts blog, however, notes that RCT are not ideal when trying to capture what will be a drug’s side effects (a.k.a. adverse effects).

RCTs are typically short lived and even the larger ones often are too small to have adequate power to detect low frequency AEs. Further,RCTs are designed to demonstrate efficacy-or in some cases the much weaker standard of proof- non-inferiority. The patients in the trial often are less diverse and complicated that a typical subset of patients from real clinical life that will likely be taking the medication.

…It falls on the shoulders of case reports and observational data and meta-analyses to fill in the gaps regarding those less common AEs and those that only develop after the patient has been on the medication for a longer period of time.

A recent meta-analysis study by Dr. Steven Nissen in the NEJM found that patients who took the diabetes drug Avandia had a 43 percent increased risk of heart attack and a 64 percent higher risk of any heart-related death (also see Scientific AmericanEarly Critic…“). The weight of this finding should not be underestimated; this report lead to Avandia-maker GlaxoSmithKline to lose £9.8 billion worth of market value according to the UK’s Independent (“GSK…“).

In the future, more post-FDA approval studies such as Dr. Nissen’s are needed in order to continue to accumulate knowledge regarding each pharmaceutical’s possible adverse effects.