Protocols and planning key to avoiding warning letters; FDA

In 2010, 95 per cent of US Food and Drug Administration (FDA) warning letters were related to the protocol. By designing a good protocol, identifying the goal of the trial, the risks involved, and sticking to the plan throughout the study, many common problems can be avoided.

Many clinical trial failures occur because people fail to see the big picture and primary objective of the study, David Lepay, senior advisor for clinical science, office of the commissioner, FDA, told an audience at DIA 2011.

It is impossible for a single clinical trial to answer every question so “prospective prioritisation​” should be performed to identify the primary objective well before the study runs into problems.

Lepay listed 11 other categories, in addition to prioritisation, that must be considered to ensure a clinical trial will be effective. For example, Lepay emphasised the importance of documentation. “If it isn’t documented it didn’t happen​”, Lepay said.

The organisation of documents and the site in general are also important. A well organised site and documentation system gives an FDA inspector a good first impression and starts the visit in a positive way.

Thoughtful automation​

The rise of eClinical systems should, in theory, simplify some record keeping processes, but it also creates its own problems. It is important sites consider what controls are needed and that their processes meet requirements for the maintenance of accurate records.

Providing sites adopt a policy of “thoughtful automation​” though there is the potential for technology to improve trial quality. “The FDA very much encourages automation in clinical trials​”, said Lepay.

In the presentation Lepay listed 12 aspects to avoiding warning letters. These are: prioritisation; standardisation; protection; education; supervision; communication; organisation; documentation; thoughtful automation; correction and prevention; randomisation; and globalisation.