That’s an investigational device? Really?!?

by Andrea Johnson, JD, CIP, Regulatory Specialist in the Research Integrity Office at Oregon Health and Science University 

Personalized medicine is an exciting and growing focus of clinical research. It frequently involves the use of an in vitro diagnostic test (IVD) to identify biological or genetic characteristics about an individual that can predict how a person will respond to different available therapies. This technology may allow providers to determine the best course of treatment for that individual’s disease. IVDs fall within the Food and Drug Administration’s (FDA) definition of medical devices, but the regulatory requirements for their use in the context of a clinical trial are not always immediately apparent. As a result, clinical studies of personalized medicine techniques can create a host of challenging regulatory issues for investigators and institutional review boards (IRBs) alike.

On the final day of the 2012 Advancing Ethical Research Conference, I had the privilege of attending the session titled, In Vitro Diagnostic Devices Used as Integral Parts of Therapeutic Clinical Trials and Companion Devices: IRB Issues and Significant Risk Determinations, presented by Elizabeth Mansfield, PhD, of the FDA and J. Milburn Jessup, MD, of the National Cancer Institute (NCI). This topic has become an important one for me in my current job, and I could write a book discussing my thoughts on this session, but I’ll stick to the highlights here.

First, one of the biggest challenges with IVD studies is simply being able to identify them. Investigators tend not to think of lab tests that determine, for instance, study eligibility as investigational devices. When asked whether the IVDs in the study are approved or cleared by FDA, they might respond with something like, “Well, we use these all the time in clinical practice.” As today’s session made clear, using a test in clinical practice doesn’t mean it is FDA approved. Dr. Mansfield provided the following advice:

  • Search FDA’s online databases to determine whether an IVD is approved or cleared for the proposed use in the study. 
  • Keep in mind that a single IVD consists of all of the components needed to carry out that intended use, including reagents, machines, software, etc. For example, if I’m looking for biomarker XYZ, the IVD includes the entire collection of materials and equipment that I need to test a blood sample for XYZ. 

Second, a key challenge for IRBs in reviewing IVD studies is determining the level of risk (Significant Risk or Nonsignificant Risk) posed by the device. The question is essentially, “What is the risk to the subject if the IVD test result is inaccurate?” In other words, what is the risk that the test may produce inaccurate findings with the result that an investigator provides harmful drugs to subjects. Dr. Jessup’s recommendations for IRBs included:

  • Requesting information on the IVD that details the chances of false negatives or false positives and explains what measures are in place to mitigate that risk. 
  • Including clinical assay developers as IRB members to help inform these determinations. 

Finally, I was very pleased to hear that the FDA is working on new guidance regarding IVDs, which is due out next year!