Act Now to Ensure Clear and Harmonized Regulations for Modern Clinical Trials

By Leanne Madre, Kevin Potgieter, and Dr. Pamela Tenaerts

When technology enters a regulated environment, early adopters often cite regulatory uncertainty as a hurdle. In fact, a 2021 Clinical Trials Transformation Initiative (CTTI) survey showed that regulatory uncertainty and lack of harmonization were the top reasons that hindered adoption of elements of decentralized clinical trials (DCTs). 

During the COVID-19 pandemic, the increased adoption of decentralized methodologies was guided by temporary guidances put out by many regulators such as FDA’s March 2020 “Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency” and the corresponding EMA guidance, which explicitly mentioned it would expire at the end of the designated Public Health Emergency. 

Where are we now, two years later?

Many regulators have released documents clarifying their expectations for the responsible adoption of trials with decentralized elements. The EMA issued a recommendations paper in December 2022 that clarified their stance on many aspects of decentralization and the FDA released a similar guidance in May 2023. Further, many other global regulators – Denmark, Switzerland, Taiwan, China, and numerous others – have released their draft guidances. 

The latest regulatory guidance that addresses DCT elements is the draft ICH E6(R3) Guideline for Good Clinical Practice. It too outlines regulators’ expectations on how DCT elements should be conducted and was prepared under the auspices of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. 

Slide from Decentralized Clinical Trials Update Expert Meeting Aug 2023

In short – there are many ‘guidances’ around DCTs, which is positive. However, the sheer number of different documents means that they do not always align or harmonize globally. We know that sponsors run trials in many regulatory jurisdictions requiring compliance with the whole quilt of applicable regulations and laws. These regulations can be related to DCTs more generally or be more specific to a particular element, such as a consent guidance about specific types of technology applications. Managing that can become very complex.

So what is an adopter of trials with decentralized elements to do?

Join the conversation and make your voice heard

Regulatory agencies often offer a feedback period during which every stakeholder has an opportunity to comment on and offer suggestions on draft guidances. For ICH E6(R3) in the United States, that time is now and ends on September 5, 2023 (other regulators may have different timelines). There were a total of 82 comments on the recently closed docket for the FDA DCT draft guidance, most of which were submitted in the last two weeks before the end of the comment period. The ICH E6(R3) FDA docket has only garnered eight comments (as of August 16, 2023), but we are still three weeks from the deadline.  

We applaud the ICH for its thoughtful update to GCP, and in particular, highlight the value of aligning and cross-referencing with other ICH guidelines. The ICH recognizes the value of modern approaches to clinical research, including the use of technology to improve efficiency, patient focus, and data quality. Regulators are taking significant steps towards creating a flexible, forward-looking framework to allow for adaptation as science and technology advances. Another action we can all take is to collect prospective data on how various decentralized elements are impacting clinical trials: Are participants more diverse? Are enrollment timelines decreased? Is 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. 

Clinical trials with decentralized elements are here to stay – in fact, eventually we are not going to make this distinction…all trials will have some elements of decentralization and digitization. They will simply be called “clinical trials.” Elements of decentralization, as discussed in the ICH’s new draft guidance, may warrant some clarification and offer an opportunity for harmonization. For example, discussion on PI oversight and data management are two important areas that need further clarity. All stakeholders should pay attention now, and take an active role in the discussion by commenting on these and other guidances. 

For all of our talk about clinical trial transformation, now is the time to walk the walk. Every stakeholder must be an active part of the solution, so contribute, comment, act. The time is now – be part of the revolution, let your voices be heard, or accept the consequences. Together, we can ensure scalable, responsible DCT adoption industrywide.

Medable is adding our comments to the ICH E6(R3) draft guidance now…we hope you’ll join us.