Creating a well-designed registry takes significant forethought and planning. A number of factors combine to create a well-balanced registry design, such as having appropriate data governance (e.g. data ownership, access and sharing), objectives, evidence assessment, data minimization, regulatory compliance, funding and more. For more information, see the Clinical Trials Transformation Initiative (CTTI) document entitled, CTTI RECOMMENDATIONS: REGISTRY TRIALS, and the AdvaMed Registry Principles. CTTI is a public-private consortium co-founded by FDA and Duke University.
Leveraged properly, registry data can create efficiencies in the product development and approval processes, as well as postmarket compliance.
Section VI of the Real-Word Evidence (RWE) guidance gives generalized illustrations of how real-world evidence, which is derived from real-world data (RWD), has actually been used to support regulatory decision making. FDA provides examples of how registries are used in each of the following:
A. Expanded indications for use
B. Postmarket surveillance studies (Section 522)
C. Post-Approval device surveillance as a condition of approval
D. Control group
E. Supplementary data
F. Objective performance criteria and performance goals (no specific registry examples here).
Manufacturers that start planning early enough can create registries that will not only help speed regulatory decisions but could save the manufacturer time and money in gathering data needed for FDA requirements. See this example from Section VI.C:
For example, a new breakthrough Class III medical device was approved based on prospective, randomized, and controlled clinical trial data. Early in the PMA review process, the manufacturer began to consider postmarket commitments, and began discussions with FDA and other stakeholders. A registry was launched that generated RWD that could meet FDA’s data requirements, as well as others. Because the new registry was constructed early enough to collect information about all patients receiving this device upon approval, FDA could provide an earlier device approval conditioned on further robust RWD collection and reporting in the postmarket setting. This registry has since been used to a) collect surveillance data on subsequent devices with similar designs and indications, b) collect and retrospectively analyze RWD on all uses of the devices to support new expanded indications for use, and c) support embedded prospective clinical investigations under IDE for new devices and new generations of approved devices. No IDE is necessary for the general data collection activities of the registry, as it collects RWD on all uses of otherwise approved medical devices and it does not influence the treatment decisions and/or follow-up care that patients receive. The retrospective analysis of RWD for uses that are outside the approved indications for use did not require an IDE because treatment decisions were not influenced by the expectation of conducting the future analysis, but was still reviewed by an IRB for human subject protection issues.
Section V discusses data relevance and reliability, both of which are essential to using RWD as RWE. For example, Section VB(2) refers to a number of published recommendations concerning quality control for registries.
The RWE Guidance also discusses when an IDE may be necessary with regard to the creation or use of the registry. Regardless of whether an IDE is necessary, the RWE Guidance makes clear that IRB review, informed consent and financial disclosure, as well as other laws on human subject protection, may apply to RWE generation activities.
In the IRB ICF Guidance, FDA announces its intention not to object to an IRB’s waiver or alteration of informed consent requirements for FDA-regulated minimal risk studies that have adequate human subject protections. The IRB must find and document that:
The IRB ICF Guidance goes on to explain that FDA does not intend to object to a sponsor initiating, or an investigator conducting, a minimal risk investigation under these circumstances.
The IRB ICF Guidance takes effect immediately (it will be withdrawn after FDA promulgates regulations on the topic) and aligns FDA’s policy on waiving informed consent with the Common Rule, which has permitted waiver since 1991.
The IRB ICF Guidance is expected to facilitate drug, device and biologic manufacturers in collecting RWD and RWE from low-risk research activities, such as observational studies or registries, and using those results to support FDA submissions.
This contents of this alert should not be construed as legal advice or a legal opinion on any specific facts or circumstances. This content is not intended to and does not, by its receipt, create an attorney-client relationship. The contents are intended for general informational purposes only. We urge you to consult your attorney about the specific situation and any legal questions you may have. Attorney advertising in some jurisdictions. © 2023 Leibowitz Law. All rights reserved. “Leibowitz Law” is a trade name of Leibowitz LLC.
To be notified when we post new Insights, please sign up for our email list. As industry thought leaders, Leibowitz Law Insights address developing issues at the intersection of law, regulation, technology and life sciences…