Studies To Approve Pediatric Use of Adult Drugs Often Have Serious Problems: Report

The findings of a new study warns that clinical trials designed to test whether drugs are safe and effective for children are not as stringent as they should be. 

In a report published in the medical journal The BMJ (formerly the British Medical Journal) on September 23, researchers indicate that there is a significant drop in the quality of clinical trials done to gain expanded FDA approval when compared to studies originally done to put the medications on the market, and the problem is particularly evident when it comes to pediatric uses.

The FDA requires that any drug uses, whether new or an expansion of approved uses for an existing medication, must have clinical trial data backing up the indication. While it is common for doctors to prescribe medications “off-label” for specific purposes that may not be approved by the FDA, drug companies are prohibited from promoting such indications until they have established that it is safe and effective.

Researchers with Brigham and Women’s Hospital in Boston looked at publicly accessible data on what are known as supplemental indications, which are when a drug company seeks to expand the approved uses of an existing drug. For approvals issued by the FDA between 2005 and 2014, researchers found 295 such supplemental indications.

According to the findings, only 30% of supplemental approvals for totally new drug uses were supported by efficacy trials with active comparators. That compares to 51% for modified use approvals and only 11% in cases where the company sought to expand the population, such as approval for use by children.

“Supplements that expanded a drugs approved patient population were supported by the fewest active comparator trials and studies using clinical outcome endpoints,” the researchers noted. “Almost all of the supplements expanding a drug’s approved patient population were for pediatric patients, and nearly half of these supplemental indication approvals were supported by uncontrolled studies or no additional clinical studies, with approval based on extrapolation from adult studies alone.”

Researchers say they did not go far enough to conclude that any of the indications for pediatric use of adult drugs were mistaken, but noted that children have “unique physiologies and pharmacokinetic characteristics” that require drug companies do additional trials that are separate from tests done on adults.

Part of the problem may be that drug companies that get pediatric approval for existing drugs receive an additional six months of market exclusivity on that drug, meaning that they can hold the patent for an additional half year before generic versions are allowed to enter the market.

21st Century Cures Bill May Make Situation Worse

The study also warns that recent legislation known as the 21st Century Cures, which was recently passed by the House of Representatives and promises to make drug approval testing even less stringent, could result in even less rigorous testing of pediatric uses.

Consumer advocates have previously raised concerns that the FDA is not adequately protecting patients from dangerous drugs and medical devices, often failing to require stringent premarket studies to identify dangerous side effects or defects before the wide use of new treatments. Despite questions about the latitude already provided to manufacturers, the bill would further loosen the approval process by allowing the agency to approve drugs and medical devices that have not had clinical trials, critics warn.

The bill comes amid a push for drug companies to release clinical trial data following incidents of ghost-writing and study-tampering that has involved powerful drugs that were later approved by the FDA. Independent researchers warn that in some cases it appears the agency was outright lied to about adverse events and effectiveness of drugs in company-sponsored clinical trials.

In February, a study found that the FDA was finding evidence of clinical trial fraud, but not reporting it in most cases.

Supporters of the bill say more flexibility in the FDA approval requirements is necessary to speed up the process of getting vital drugs to patients in a timely manner.