A New Study Explains Level of US FDA Impact on Drug Study Design

Investigators examining the level of interaction among the US Food and Drug Administration and pharmaceutical organizations identified that no meetings to talk about study design had taken place in 20% of latest new drug approvals.

The research, presented in JAMA, also reports that when meetings did take place, a quarter of the suggestions made by the US FDA, for the enhancement of research design or major outcomes, were not heeded.

Federal regulations promote meetings among the FDA and pharmaceutical organizations to be able to enhance research that aim to examine the effectiveness and safety of new medicines.

These meetings can frequently lead to FDA suggestions for enhancing the clinical trials. However, not only are such of meetings not compulsory, but also pharmaceutical organizations are not bound to adhere to any suggestions that might be made.

The study was performed by Dr. Steven Voloshin and co-workers. The team performed an evaluation of about 200 FDA records relevant to 35 new drugs, accepted between 1st February 2011 to 29th February 2012.

The records involved filing checklists, medical assessments, memos, minutes from meetings, statistical assessments and summary evaluations.

All responses from the FDA in the documents were examined, together with suggestions made about the pattern of drug studies – controls, dosage and study time periods, for instance – and their major outcomes. How these suggestions would impact the quality of the research was also characterized and documented.

40 out of 53 FDA suggestions were complied with

Pharmaceutical organizations met with the FDA to talk about the research for 28 of the 35 recently approved medicines. A overall of 53 suggestions were produced by the FDA concerning study design or major outcome for 21 of the drug approvals.

The investigators considered that 51 of these suggestions would raise the quality of the drug research, through measures like as adding controls or extending the study’s timeframe. The other two recommendations were considered to have an unclear effect.

Of the 53 suggestions designed by the FDA, pharmaceutical organizations were identified to comply with only 40 (75%). Examples of non-compliance involved selecting progression-free ahead of entire survival as a major study outcome, and performing uncontrolled research when randomized studies of the drugs brentuximab and crizotinib were requested.

Pharmaceutical organizations also have the possibility to ask for that the FDA evaluate key trial protocols. The FDA agrees to not object to any study design problems when examining medicines for approval if they have formerly endorsed trial protocols.

In the research, the scientists identified that protocol reviews were requested in 21 of the 35 new drug approval cases. In these 21 reviews, the FDA only recommended protocol in 12 cases.

The authors understand that their research was restricted by only examining drugs that had been provided acceptance by the US FDA. However, they take into consideration that refused drugs may have reduced compliance with suggestions and fewer special protocol evaluation endorsements.

To be able to enhance the quality of drug approval research, the authors recommend improving the abilities of the FDA as a potential approach:

“One method for improving quality of drug approval research would be to institute mandatory FDA evaluation of pivotal trial protocols with the power to issue binding suggestions, which may be even more essential with progressively flexible acceptance pathways.”

An earlier report requested by the FDA recommended that stronger early FDA participation could enhance the approval process, via boosting up the acceptance of effective drugs and determining more clearly inadequate or harmful ones, states the authors.