Draft ICH E6(R3) Guideline for GCP Presents Opportunity for Input from Stakeholders in DCTs

Dr. Pamela Tenaerts, Chief Science Officer, Medable

The latest regulatory guidance addressing elements of decentralized clinical trials (DCTs) is the draft ICH E6(R3) Good Clinical Practice (GCP) guideline from the International Council for Harmonization (ICH). Much like recent guidances proposed by the U.S. Food and Drug Administration (FDA) and regulatory authorities in other nations, the ICH document outlines regulators’ expectations on how DCTs should be conducted, and with its addition to the list, stakeholders in digital, hybrid, and fully decentralized trials may feel a growing urgency to harmonize global regulations to prevent any roadblocks to adopting the beneficial technologies they associate with improving speed, patient access/diversity, and data quality in their trials.

The ICH represents a collaboration of FDA, the European Medicines Agency (EMA), and Japan’s health regulatory authority designed, in part, to streamline medical research across their regional and multinational activities. With ICH guidelines on clinical trials and other matters tied to pharmaceutical and medical device development also being unofficially followed by many other nations, one thought leader in the clinical research enterprise says that now is the time for interested parties to make their voices heard by visiting here and commenting on the draft guidance by the deadline of September 5.

The fact that there are many guidances in development concerning DCTs is positive, noted Dr. Pamela Tenaerts, Chief Science Officer for Medable, in information shared with ACRP. However, she pointed out, the sheer number of different documents means that they do not always align or harmonize globally, and sponsors run trials in many regulatory jurisdictions requiring compliance with a “whole quilt” of applicable regulations and laws.

Tenaerts said that these regulations can be related to DCTs more generally or can be more specific to a particular element, such as an informed consent guidance about specific types of technology applications, and that managing them can become very complex. This is why Medable “is petitioning [industry stakeholders] to join the conversation and make their voices heard by commenting on the new draft guidance,” she added.

“We applaud regulators who are taking significant steps toward creating a flexible, forward-looking framework to allow for adaptation as science and technology advances,” Tenaerts said. “But more work is needed—another action we can all take is to collect prospective data [to answer questions about] how various decentralized elements are impacting clinical trials. [For example, are] participants more diverse? Are enrollment timelines decreased? Are trial data of the quality we need? Having this knowledge in the public domain would increase confidence and get us into a trusted and verified space.”

Tenaerts graciously took time to answer some follow-up questions posed by ACRP about current draft guidances on DCTs.

Q: When final guidances are eventually settled upon in the U.S. and by ICH, do you think is it possible that DCTs will be regulated significantly differently in these settings?

A: We do not expect significant differences in how DCTs will be regulated once E6(R3) is finalized and adopted. However, we anticipate some remaining harmonization issues between the FDA’s DCT draft guidance and the European Union/EMA recommendations paper (although maybe less so with the EMA). Highlighting these issues during the comment period and requesting clarification is one way to decrease inconsistencies.

Q: What are the foreseeable biggest impacts on study sites, and what can be done now to alleviate the potential inconveniences of managing DCTs in multinational trial circumstances under different rules?

A: The FDA draft guidance’s introduction of the “task log,” as well as its concepts surrounding the management of activities performed by local healthcare providers who are not study/site staff, may lead to confusion on how to operationalize [DCT plans]. Another potential issue is the lack of clarity around the principal investigator’s responsibility for study activities conducted by healthcare practitioners. To reduce clinical operational complexity, a more harmonized approach should be taken in E6(R3) that considers the additional burdens the new task logs would place on sites. With both the FDA DCT draft guidance and the ICH E6(R3) guidance requesting comments, the hope is that they come closer together on these issues.

Tenaerts added that stakeholders should submit their comments directly to their respective national competent authorities if they are soliciting feedback. Commentary from the U.S. on the ICH draft guidance is being managed by the FDA in the form of the public docket, which closes on September 5, 2023. Stakeholders from ICH Member countries/regions are encouraged to submit their comments to their respective regulatory authorities, noting the deadline for comments indicated beneath each draft guideline.

Edited by Gary Cramer