Will NPRM Changes Affect Your Clinical Trials?

By Ed Miseta, Chief Editor, Clinical Leader

The current regulations on the use of human subjects in clinical trials were put in place in 1981, with the last major revision occurring in 1991. The NIH version of the regulation was written so as to be adopted by any agency and to date the U.S. Department of Health and Human Services (HHS) and 15 other federal departments have adopted it. Obviously, a lot has changed with clinical trials in the last 20 plus years. As a result, a Notice of Proposed Rulemaking (NPRM) is looking to update a few aspects of the regulations.

HHS is now seeking comment on the NPRM, which was published in the Federal Register in September 2015, and its proposals to better protect patients. “For a long time, people believed these regulations were set in stone, because of how difficult it would be to get 16 federal agencies to agree on anything,” says David Forster, Chief Compliance Officer at WIRB-Copernicus Group (WCG). “But then in 2011, there was a proposal (Advanced Notice of Proposed Rulemaking) to make some changes. Some fairly significant changes were suggested, and there were over 1,000 comments submitted. Now, four years later, we have the NPRM. It still has 88 questions available for public comment.”

The overall goal of the proposed rule is to reduce administrative burden where it is not effective in protecting human subjects and to increase that protection in other areas, thereby representing an effort to improve both protection and administrative burden.  

Why Make Changes Now?

Some may wonder why it is necessary to make changes at this point in time. David Borasky, Vice President of Quality Management at Copernicus Group IRB, believes there are several factors in play. The first is that we have a regulatory structure that has been fairly static since the 1980s, while at the same time research has changed quite dramatically. Those two factors are reflected in the NPRM.

“There is a lot of emphasis on things like biospecimens and the importance of privacy in what is now a data-saturated world,” he says. “It has become increasingly obvious to many in the industry that the old regulations did not anticipate things like the Internet, genomics, multi-site research, and the issues that come along with them.”

According to Borasky, the current regulations were written in a world where one institution performed a study in a large academic medical center. At that time, no one foresaw the idea of a large multi-site study, which has now become the norm. This created a need to modernize the regulations.

“From a clinical trials perspective there has also been an attempt to bring a few more things under the umbrella,” states Borasky. “We have always had clinical trials that were FDA regulated and have had that structure over them. There were also clinical trials that were government funded that had the Common Rule structure over them. But that left a gap in the regulations when a study was neither federally funded nor FDA regulated.”

For example, Borasky notes, if clinicians decided they wanted to self-fund a research study that wasn’t under FDA jurisdiction but involved, say, an innovative surgical technique, they sort of fell outside the rules. The new regulations will attempt to capture some of those outliers by having this rule apply to any clinical trial being conducted. The FDA will still have jurisdiction over studies that are FDA regulated.

“The industry needed this update and it has been a long time coming,” adds Borasky. “I think this NPRM addresses as many of the known gaps in the regulation as possible and also tries to be as forward thinking as possible. However, the pace at which science and technology are evolving makes it difficult to predict very far into the future.”

Will Sponsors Be Impacted?

Forster notes a lot of industry-sponsored work is covered by the FDA, so the changes referenced above will likely not have a great impact on them. However, he adds the FDA plans to update its own regulations to be in harmony with these changes once they move to final rule. It’s too early to guess what those changes might be, but it’s likely they will harmonize in areas such as mandating a single IRB, which is already the norm in many industry-sponsored studies. There will also be new rules about consent for biospecimen collection, but a lot of that still has to be determined.

Both Forster and Borasky believe the changes regarding biospecimens will be the trickiest for companies to navigate. The way the rule is written, any biospecimen is considered identifiable. As a result, companies will no longer be able to strip identifiers from the specimen and then do research without consent. The background for this is the belief that a human being can be identified based off of a genetic analysis of their biospecimen.

“This leads to the supposition that they are always identifiable, and we need to treat them as such,” says Borasky. “A lot of bench research could be affected by this as scientists would no longer be able to use specimens without consent. The new rule is stating companies would need to obtain broad consent, meaning patients would have to agree that their samples can be used in future research.”

This ruling means a new administrative structure might have to be put in place to obtain consent from every patient going in for a blood draw or any type of biopsy. Any refusal to consent would also have to be tracked. As a result, diagnostic device manufacturers and others using these samples in bench research and human subject research could be drastically affected.    

IRBs And Patients Are Prepared

IRBs like WCG will have to adopt the new regulations but Forster does not believe there will be any large changes to their framework. SOPs will need to be modified, and there will need to be some changes made to the standards that are applied.  

For patients, the biggest change will be the approach to informed consent. The NPRM discusses getting back to the guiding ethical principles for research. One of those is respect for persons, which is reflected in the consent process.

“The consent documents have gotten out of hand and are now too lengthy and too technical,” says Forster. “Much of this information serves to distract rather than inform research participants. The new rule requires a different approach to informed consent that will impact both subjects and sponsors. Consent regulations are very clear about what elements have to be in a consent document. If approved, consent forms will only be able to contain required elements, plus any additional applicable elements, making for a much more streamlined consent form. Any additional information must appear in an appendix.”

Some industry professionals are concerned the appendix may become a dumping ground for additional information, perhaps even more than what is in current consent forms. That remains to be seen, but Forster believes the end result should still be shorter and clearer consent forms that will help subjects make more informed decisions regarding participation.     

“In the past, the use of leftover biospecimens may have made someone the subject of research without them knowing it,” says Borasky. “This is a way for companies to be transparent with the public about the realities of research. And, for clinical trials that will now be captured by the Common Rule, these consent forms will need to be posted on a public website within 60 days of completion of the enrollment. If the FDA also opts to follow that pathway, sponsors may have some concerns. How this will be done remains to be seen but ClinicalTrials.gov may be a likely landing spot. Either way, this will likely be seen as an enhancement for subjects.”