Company-funded studies of approved drugs may not catch safety issues

(Reuters Health) - Studies drug companies fund after medicines go on sale may be too small to detect rare side effects, a recent German study suggests.

Even if these so-called post-marketing studies do uncover previously undetected adverse events, physicians conducting the trials are often required to keep results confidential, limiting the potential for regulators or patients to learn about safety issues, according to the study in The BMJ.

When drugs are approved based on tests in only a few thousand patients, very little is known about long-term safety or the potential for rare side effects to occur when tens of thousands of people take the medicines, said lead study author Dr. Angela Spelsberg, medical director of the Comprehensive Cancer Center in Aachen, Germany.

“The fact that many physicians are obliged by contracts to handle adverse drug reactions as confidential business information rather than reporting them is very disturbing,” Spelsberg added by email. “In light of the indispensable role of general practitioners and clinicians in detecting, diagnosing and publicly reporting adverse drug reactions, this means a very big threat to public safety.”

For the study, Spelsberg and colleagues made freedom of information requests to three regulatory authorities responsible for registering post-marketing studies in Germany and obtained data on 558 studies.

On average, these studies had about 2,300 patients and 270 physicians. Trials that include so many doctors and so few patients can have lower data quality because it’s cumbersome to effectively train and monitor so many physicians, Spelsberg said.

Doctors were paid 441 euros per patient on average to participate in the studies, and 19,424 euros on average per trial. In some trials, doctors earned in excess of 2 million euros.

The studies analyzed included a wide variety of drugs and non-pharmaceutical products, and only one third examined recently approved medicines. About 12 percent of the studies assessed non-prescription drugs, while about 15 percent looked at biotech medicines and 11 percent evaluated cancer treatments.

Not one adverse event report could be identified from any of the 558 post-marketing studies.

Less than 1 percent of the studies could be verified as published in scientific journals.

One limitation of the current study is that it looked at data from notifications to regulators but not real trial data, the authors note.

Researchers also may have overestimated the number of participating physicians because doctors often work on multiple post-marketing studies, the authors also point out. In addition, they lacked data on any post-marketing trial results published after 2015.

Still, the study offers fresh insight into several potential shortcomings of post-marketing drug studies, said Dr. Barbara Mintzes of the University of Sydney in Australia.

“When a drug first comes to market it has been tested on average in 2,000 to 3,000 people, too few people to uncover most rare serious harmful drug effects,” Mintzes, who wasn’t involved in the study, said by email. “Often, patients at greatest risk of harm like the frail elderly or people with several serious health conditions are excluded from the trials, so post-marketing safety studies are very important.”

When post-marketing studies aren’t done, aren’t publicized, or are too small to uncover rare side effects, patients can be exposed to unsafe or ineffective medicines, said Stacie Dusetzina, a researcher at the University of North Carolina at Chapel Hill who wasn’t involved in the study.

“Before the drug is approved there is very strict oversight and management by sponsors; after the drug is approved the follow-through on reporting is more mixed,” Dusetzina added by email. “Finding the right balance is important for ensuring that patients have timely access to drugs and that we know the risks and benefits for most patients.”

SOURCE: The BMJ, online February 7, 2017.