Dominic Chiarelli

by Dominic Chiarelli

2016: Clinical Research Legal and Regulatory Year in Review

Happy New Year!

This past year brimmed with significant events. Most people, however, are probably not including clinical research in their reflections on the year that was and what it may mean moving forward.

But those of us within the clinical research space know that 2016 ushered in major legal, regulatory, and policy changes that will serve to reshape the research landscape in 2017 and beyond. The following is a brief examination of some of the highlights from 2016.


Accelerating the Discovery, Development, and Delivery of New Treatments

The 21st Century Cures Act (Cures), which became law on December 13, 2016, represents a comprehensive commitment to and reform of clinical research. Cures provides significant funding for innovation projects intended to push medical research in several key areas and requires the Federal Food and Drug Administration (FDA) to take significant action to modernize trial design principles, increase access to investigational products, and remove administrative barriers for research. Cures will also result in significant revisions at the National Institutes of Health (NIH). This includes firmly establishing the NIH’s authority to compel data sharing for the research it funds as well as strengthening the legal standing and prevalence of a NIH Certificate of Confidentiality for sensitive research.


Establishing Greater Efficiencies in the Performance of Multi-Site Research

The Final NIH Policy for the Use of a Single Institutional Review Board for Multi-Site Research is intended to enhance and streamline the IRB review process so that research can proceed as expeditiously as possible without compromise to the ethical principles and protections for human subjects. This new policy, which is consistent with the Common Rule’s Cooperative Research provision, requires that all domestic sites of NIH-funded multi-site trials rely on a single Institutional Review Board (sIRB) to satisfy the ethical review requirements of 45 CFR Part 46.

NIH grant applicants will soon need to include a plan for utilizing a single Institution Review Board (sIRB), including rationale for the selection, and a statement confirming that all sites can and will adhere to the sIRB policy. All participating sites will need to be comfortable with executing a reliance agreement with the sIRB and will remain responsible for meeting all other regulatory obligations, including obtaining informed consent, monitoring the research, and reporting unanticipated problems and study progress.

The NIH will be issuing multiple guidance documents in the coming year—covering how sIRB costs can be charged, considerations in selecting a sIRB, and model communication plans—to help ease the research community into this new paradigm for ethics review.


Retiring Heightened Oversight for Gene Transfer Research

The Final Action Under the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) is intended to maximize the benefits of the NIH Recombinant DNA Advisory Committee (RAC) by limiting gene transfer protocol reviews to exceptional cases only. This revision to the NIH Guidelines largely removes the requirement for RAC review for gene transfer protocols involving human subjects. This change was motivated by a report requested from the Institute of Medicine that found “the major concerns about recombinant DNA from 40 years ago do not raise the same level of concern today, as hundreds of gene therapy clinical trials have evaluated the technique’s safety and effectiveness.”

The NIH Guidelines now include criteria and a process for referring protocols for RAC review, which generally involves an oversight body determining a protocol would significantly benefit from RAC review and that at least one of three criteria, all based on the amount of unknown risk, are met. The registration process, which still generally applies to all gene transfer research, was also concordantly revised to account for the new referral process and to reduce the submission requirements.


Improving Availability and Quality of Clinical Trial Information

The U.S Department of Health and Human Services (HHS) Final Rule for Clinical Trials Registration and Results Information Submission and NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information are intended to improve public access to information about clinical trials. This new regulation and policy are intended to work together to strengthen by clarifying and expanding its requirements. The hope being that these changes, which are many, will help it to fulfill its intended purpose—providing the public with meaningful information to a wide range of clinical trials.

One example of an important and wide sweeping change is the handling of summary results information. will now include summary results information for any listed clinical trial within one year of its completion. This includes trials involving investigational products that are not commercially available and NIH funded trials that do not involve the study of FDA regulated products.

The summary results information required has also been significantly expanded to include the full protocol, statistical analysis plan, and a more comprehensive report of any adverse events. Another example of an important change is that expanded access information must be included whenever a sponsor of a registered clinical trial is also the manufacturer of the investigational drug product. This will provide patients with greater visibility to the possible availability of an investigational drug product outside the context of a clinical trial.


Maintaining the Status Quo

Despite all this significant change, 2016 may be most notable for what did not happen.

The regulated community hotly anticipated finalization of the widely unpopular Notice of Proposed Rulemaking for the Federal Policy for the Protection of Human Subjects. These revisions would have significantly altered the Common Rule and ushered in new concepts like broad consent, excluded activities, self-identified exempt status, IRB liability for compliance with the Common Rule, and single IRB review for all cooperative research and not just research funded by NIH. The question now is whether the proposed rule, which was more than four years in the making, will ever be made final.

The laboratory and precision medicine community also hotly anticipated that the FDA would finalize its draft Framework for Regulatory Oversight of Laboratory Developed Tests (LDT) sometime in 2016. This Framework would formally move the FDA to a more risk-based approach to regulating LDTs, which do in fact meet the definition of a medical device, and would have resulted in significantly more oversight regarding the analytical and clinical validity of LDTs that are used as diagnostic tests. The FDA, however, has recently indicated that it will delay finalizing this guidance and the belief is that it may never be finalized.


What’s in Store for 2017?

2017 is going to be a busy and likely turbulent year for all those that work in clinical research. The FDA and NIH will be dutifully scrutinizing their regulatory framework with an eye toward improvements while also churning out much needed guidance in support of the changes promulgated in 2016 as well as to meet their own strategic agendas.

Sponsors, investigators, and IRBs will be tackling significant revisions to the conduct, oversight, and reporting of multi-site clinical research and the seemingly ever changing regulatory approach to the study or integration of newer technologies, like mobile health, regenerative products, precision medicine, and electronic consent.


Kinetiq is ready discuss the year that was 2016

Have questions about the changing regulatory landscape in 2017 and beyond? We're here to discuss any of the draft or finalized FDA guidance, or the year to come.

Contact Us

Tags: , , , , , , , , ,