FDA-regulated clinical trials rarely report violations

1. This study, which identified clinical trials that the FDA deemed to have committed significant violations, determined that fewer than 5% of the publications that resulted from these trials actually mentioned committing violations, even though three-fourths of them received the results of the inspection before the publication date.

2. The most common types of violations included failure to follow the investigational plan, inadequate recordkeeping, issues with patient safety, rights, and welfare.

Evidence Rating Level: 3 (Fair)          

Study Rundown: The Food and Drug Administration is involved in regularly inspecting clinical trials to ensure that the investigators followed good clinical practices throughout their research. However, in cases where significant violations are identified, the FDA and the investigational group often does not make that readily available to the larger scientific community. This study, which identified clinical trials that the FDA deemed to have committed significant violations, was carried out to determine the nature of those violations and whether they were acknowledged. Of the articles that arose from trials that had significant violations, fewer than 5% actually mentioned committing those violations, even though three-fourths of them received the results of the inspection before the publication date. The most common types of violations included failure to follow the investigational plan, inadequate recordkeeping, issues with patient safety, rights, and welfare.

The strength of the study was that the investigators highlighted the types of violations committed by the trials, and that they focused only on the most severe types of violations. The weakness of the study include the fact that not all of trials were likely included since the FDA database is not up to date, and the fact that only trials from one point in time were included. This study does, however, encourage future investigations into this important topic.

Click to read the study, published today in JAMA Internal Medicine

Relevant Reading: Analysis of warning letters issued by the US Food and Drug Administration to clinical investigators, institutional review boards and sponsors: a retrospective study

In-Depth [cross-sectional study]: Clinical trials that were deemed by the FDA to have significant violations (entitiled “official action indicated”, or OAI) were searched in the FDA database in July 2012. This search was supplemented by Google searches of the FDA.gov domain. Additionally, all warning letters issued to a clinical investigator were reviewed as well. A total of 421 OAI-rated inspections were found using these methods. These documents were reviewed, and when a clinical trial was identified, the literature was searched for any resultant publications.

In the final analysis, 57 trials, resulting in 78 published articles in peer-reviewed journals, were included. Of these articles, only 3 (4%) mentioned the violations determined by the FDA, even though 59 of the 78 articles (76%) received the results of the inspection at least six months before the publication date. The types of violations most commonly noted were falsification of information (39%), problems with adverse events reporting (25%), failure to follow the investigational plan (74%), inadequate recordkeeping (61%), failure to protect patient safety, rights, and welfare (53%), and other violations (20%).

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