The revision may make the research process less daunting, according to Nancy Stark.
FDA is revisiting a decade-old regulation that allows emergency clinical research when it is impossible to obtain informed consent from a patient. It also recently issued a draft guidance to further clarify the criteria for performing emergency clinical research. The action comes after 10 years of manufacturers' struggling to balance ethics and patient safety with obtaining valid data.
Nancy Stark, president of Clinical Device Group Inc. (Chicago) has worked with a couple of companies that have attempted emergency research. She says she has found the process to be daunting. “It's extremely difficult, because many institutional review boards [IRBs] simply won't consider it. I'm glad they're revisiting the regulation, because it is ineffective.”
There's also no doubt that the regulation—21 CFR 50.24—is controversial. “I totally agree with those who say there's a serious ethical question in using an investigational product on somebody who has no say in it,” says Jonathan Kahan, partner at Hogan & Hartson LLP (Washington, DC). “On the other hand, how can you possibly develop a device and get it onto the market when the only way to use it is on someone who may not be able to give consent, and you need a waiver? You can't give an advance waiver, because people do not know whether they are going to be put in that situation.” The testing of emergency treatments usually occurs in life-threatening conditions.
One of the biggest differences between the emergency clinical research rule and other clinical research regulations is a public disclosure requirement. The emergency research rule calls for community notification before starting a study, along with reporting research results at its conclusion. “Speaking in public about clinical research that hasn't yet occurred is something industry doesn't often do,” says Barry Sall, principal consultant at Parexel Consulting (Waltham, MA).
FDA needs to provide more direction to help sponsors, IRBs, and clinical investigators comply with the complex regulation. The draft guidance, titled “Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors; Exception from Informed Consent Requirements for Emergency Research,” aims to accomplish the following:
• Provide more explanation on the roles and responsibilities of IRBs, clinical investigators, and sponsors.
• Expand community consultation and public disclosure discussion.
• Clarify terms in the regulation that are difficult to interpret.
Although FDA has heard the concerns from many sides of the issue, the agency has had no methodical way to address them in the past. The agency will take the comments on the guidance and feedback provided at a public hearing held in October to evaluate the current structure of the regulation and determine whether changes are needed. Written and electronic comments are due by November 27.
Barry Sall hopes FDA's guidance will have a clearer process for all parties.
“This whole emergency-use regulation is complicated, and any assistance by the agency to help parties understand it is a plus,” says Sall. “Hopefully, with a clearer process and better definition, it will be easier for sponsors, IRBs, and investigators to fulfill their responsibilities.”
Those parties also need to have a practical system in place to carry out their duties in the field reliably. This includes determining who would attempt to inform next of kin and how it would be documented, says Sall. People in the emergency medical system that are not normally involved in clinical research also need to be aware of their obligations. These factors are just part of the process of ensuring that trial data are credible and ethical without compromising the rights of study subjects.
Some companies have found it so hard to do the research in the United States that they have gone to other countries in efforts to gather data on unapproved devices. Stark says that manufacturers are conducting research in Asia, India, Eastern Europe, and South America, and she endorses the practice. “Go do your clinical study wherever you can get it done,” she advises. “Do your top-notch best to follow ISO 14155 [Clinical Investigation of Medical Devices for Human Subjects], and comply with the host country's regulations.”
Stark advises that after a study is completed, a firm should approach FDA with scientifically valid data. The strategy is that either an IRB will be willing to work with the company at that point, or that FDA will grant the company 510(k) clearance or premarket approval (PMA) on the condition that postmarket studies are performed. This method still is not easy, and Stark says such an approach is attempted more with products outside the realm of emergency clinical research.
Kahan says that FDA might have to change the regulation a bit. By taking another look at the regulation, he thinks the agency is on the right track. The reevaluation of the rule is part of the agency's Human Subject Protection and Bioresearch Monitoring Program. The program seeks to bolster the protection of patients in clinical trials and the resulting data. The initiative was announced in June.
FDA's draft guidance is available at www.fda.gov/ohrms/dockets/98fr/06d-0331-gdl0001.pdf.