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The 21st Century Cures Act, passed in December, contains provisions that many have questioned and criticized. This review of those provisions shows that progress in this sector is being made.
A review of Cures Act provisions that modernize and streamline processes we should have revised long ago.
Despite vast bipartisan support, when the 21st Century Cures Act was passed in early December, it was met with immediate criticism. The Cures Act provides more than $6 billion in research dollars, including funds for opioid addiction research, precision medicine and the Cancer Moonshot program, and represents the largest piece of healthcare legislation since the Affordable Care Act. Several provisions, however, amend the review and approval processes of the FDA and other regulatory bodies-controversial changes that will shake up drug and medical device markets in unprecedented ways.
Not surprisingly, these changes have been met with a considerable degree of angst.
When there is talk of streamlined regulatory reviews and expedited approvals, it is natural to question which steps will be cut out of the process and if we can afford to lose them. Frequently, we see validation in passing multiple checkpoints, especially ones that have been in place for a long time.
But we must ask ourselves: In the face of a growing gap between supply and demand for life-saving treatments, is it ethical if we never stop to question whether we can confidently stand by the measures by which we define risk and benefit?
Among others, I believe the following provisions of the Cures Act will successfully preserve conscionable safeguards of safety and efficacy, eliminate undue development hurdles, and increase patient access to breakthrough treatments.
Central IRBs for Medical Device Studies [Section 3056]
Today, sponsors of a multisite device research protocol are faced with an exponentially higher administrative burden than those conducting single-site non-device investigations because of a local review requirements specific to research with devices. Thus, a 15-site study involving an investigational device could involve 15 local institutional review boards (IRBs), each with its own requirements. This means that each IRB can (and often does) request changes to protocols as well as consent forms, resulting in significant delays and complications as revisions are made to satisfy the disparate requests.
Section 3056 of the Cures Act comes on the heels of an NIH policy, effective September 2017, which establishes the expectation that a single IRB of record will be used for NIH-funded multisite studies. The Cures Act provision strikes the statutory requirements that medical device clinical investigations be overseen by a “local IRB,” permitting both investigational drug and device research to have a single IRB of record in multi-site studies.
Moving forward, with research protocols being reviewed once on behalf of all sites and the sponsor responding to only one IRB’s feedback, study timelines can be planned more accurately, and sponsors and sites can focus more on overall study management and safety. In addition, the IRB can work with the sponsor to develop a unified informed consent for use by all sites, so subjects receive consistent information over the course of the study regardless of where they may be enrolled.
Along with the recent final revisions to the Common Rule, the Cures Act provision has driven home the federal government’s message that where multisite research is concerned, a single IRB is now the preferred course.
Through centralized oversight of multicenter medical device studies by a single IRB, we can minimize administrative burdens, costs and delays while accelerating a scientifically sound review and approval process.
Harmonization of Informed Consent [Sections 3023-4]
Harmonizing government regulations has been a significant ask by the national community, evidenced by the existence of the HHS Secretary’s Advisory Committee on Human Research Protections Subcommittee on Harmonization, which is tasked specifically with providing guidance on regulatory issues that would benefit from harmonization.
Section 3023 of the Cures Act addresses this demand by requiring harmonization of the differences between the HHS Common Rule and FDA regulations. Specifically, the provision calls for the Secretary of HHS to synchronize the two sets of regulations “to the extent practicable and consistent with other statutory provisions” within three years of the Cures Act’s enactment. The goal? To minimize regulatory duplication and undue delays, to facilitate multisite research and to incorporate local considerations and protections of vulnerable populations.
The disparity of informed consent regulations between HHS and FDA has been a longtime complication for clinical researchers. It is not an uncommon scenario for a human subject’s informed consent to be waived under HHS but not under FDA regulations. This is particularly difficult with respect to research involving the collection of specimens.
Furthering this provision’s harmonization efforts, section 3024 goes on to amend the Federal Food, Drug and Cosmetic Act to grant FDA the ability to allow waiver or alteration of informed consent for investigational drug and device studies when research activities post no more than minimal risk and include appropriate protections for the subjects’ rights, safety and welfare. Finally, FDA and HHS will be consistent in this regard.
Prioritization of Breakthrough and Humanitarian Use Devices [Sections 3051-2]Patient demand for access to investigational new drugs has grown in recent years, as seen through increased social media activity and the right-to-try laws on the books in many states. The Cures Act may help to close the gap between supply and demand for breakthrough and humanitarian use devices that would benefit patients suffering with difficult-to-treat conditions.
Section 3051 of the Cures Act builds upon the Expedited Access Pathway, a voluntary program designed to prioritize the review of certain devices for life-threatening or irreversibly debilitating diseases. Finalized in guidance published in April 2015, the EAP is a program in which the FDA works with sponsors to minimize medical device development costs and timelines while maintaining the same standards for safety and effectiveness. Per the Cures Act legislation, this Pathway would now be open to additional device types, increasing the number of breakthrough devices receiving priority review.
In addition, as a counterpart to the orphan drug designation, for which the FDA has seen a dramatic rise in requests in recent years, the humanitarian device exemption (HDE) is expanded in section 3052 of the Cures Act. Currently, the exemption can only be applied to devices that treat diseases and conditions that affect up to 4,000 individuals annually in the United States. The new legislation raises this cap to 8,000. This will allow sponsors to obtain approval based on safety data and probable benefit and increase patient access to devices for a greater variety of rare conditions.
While some of the changes may be viewed as concessions, they also rise to the level of rational and necessary improvements in our current regulatory landscape. The provisions outlined above will remove unnecessary hurdles within the drug and device development pipeline and may allow many more patients suffering from rare conditions to take advantage of the potential breakthrough treatments they’ve been waiting for.
Our road does not end here, however. Regardless of how much progress is made in the years ahead, in both research and regulation, we must continue to monitor and refine our methods – study after study, bill after bill – with the well-being of patients and participants always at heart.
Michele Russell-Einhorn, JD, is Vice President of Human Research Protection Services and Institutional Official at Schulman IRB.