Abstract

PURPOSE:

This study explores the ethical issues contained in warning letters issued to clinical researchers by the Food and Drug Administration (FDA) in the USA.

METHODS:

The online FDA Warning Letter Index was reviewed for letters issued to drug and device researchers in the USA and Canada under the violation subject "Clinical Investigator" for the period February 2002 through February 2004. The resultant letters were evaluated for the presence of 7 research ethics themes: deviation from investigational plan; informed consent; adverse event reporting; study reporting; study supervision; institutional review-board approval; and misconduct.

RESULTS:

Thirty-six FDA warning letters addressing violations of 58 protocols were issued to researchers during the 25 months studied. Researchers performing pulmonary medicine studies received the most warning letters (12), followed by oncology (10) and cardiology (9) researchers. The most common regulatory violations were deviation from the research plan, a flawed or nonexistent consent process, and failure to report or late reporting of adverse events. Three warning letters (8%) mentioned study misconduct, including data fabrication.

CONCLUSIONS:

Warning letters are informative about good practice, ethics and participant protection in research. As distressing as the content in an FDA warning letter may be to investigators receiving it, that information can become an educational tool for all members of the research team. These letters are also informative as to what the FDA is looking for when they audit clinical trials.