If we’re going to keep putting millions of American children on ADHD drugs, we really need to study the meds longer and better to pick up rare and late-onset side effects.
That’s my takeaway from a study just out from Boston Children’s Hospital. It found that in many cases, ADHD drugs had not been studied for long enough — really, can a clinical trial of a few weeks be long enough for a drug that’s typically taken for many years? — or in enough people. And drug company promises to keep studying the drugs’ effects even after the FDA approves them have often fallen by the wayside.
From the press release:
Over the last 60 years, the U.S. Food and Drug Administration (FDA) approved 20 medications for attention deficit/hyperactivity disorder (ADHD) based on clinical trials that were not designed to study their long-term efficacy and safety or to detect rare adverse events, researchers at Boston Children’s Hospital report today in PLOS ONE. The study highlights gaps in how the long-term safety of drugs intended for chronic use in children is assessed as part of the FDA approval process.
“This study doesn’t address whether ADHD drugs are safe, though their safety has since been established through years of clinical experience,” says study senior author Kenneth Mandl, MD, MPH, Boston Children’s chair in biomedical informatics and population health and director of the Intelligent Health Laboratory in Boston Children’s Informatics Program. “Instead, we point to the need for an agenda emphasizing improved assessment of rare adverse events and long-term safety through post-marketing trials, comparative effectiveness trials and more active FDA enforcement.”
The team identified 32 clinical trials on the 20 drugs. Only five trials were focused specifically on drug safety. The team calculated that each drug was tested in a median of 75 patients prior to FDA approval, with a median trial duration of four weeks. Eleven of the 20 drugs were approved after having been tested in fewer than 100 patients, and 14 in fewer than 300. Seven drugs that the FDA had previously approved for other conditions (e.g., obesity) were approved for ADHD without any condition-specific trials or trials in children.
For context, the authors note that the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)—a forum for best practices in drug development—recommends that drugs intended for chronic use in non-life-threatening conditions (such as ADHD) should be tested in a minimum of 300 to 600 patients for at least six months, in a minimum of 100 patients for at least one year, and in about 1,500 patients total before regulatory approval.
The paper ends with what, for academia, amounts to a clarion call to arms: “An ambitious agenda to assess long-term outcomes in the millions of patients on these medications is warranted.” And study co-author Dr. Ken Mandl told the Boston Globe: “This is a wake up call for what’s lacking in the drug approval process and what we want to see in the future.”