Decentralized clinical trials (DCTs) have been defined as patient-centric studies executed through telemedicine and mobile/local healthcare providers using processes and technologies differing from the traditional clinical trial model.⁴ DCTs were designed to augment or replace traditional in-clinic approaches with direct-to-patient (DTP) and data-driven alternatives, with an emphasis on in-home care that offered access to larger patient populations and reduced trial costs. They offer a strategy for technology-enhanced clinical trials that are more accessible to patients by moving clinical trial activities to a wider variety of settings, including telehealth and remote patient monitoring options.

The COVID-19 pandemic accelerated the use of DCTs when travel restrictions and clinical trial site closures were prevalent. The European Commission issued “Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) Pandemic”¹ and the U.S. Food and Drug Administration (FDA) Commissioner Scott Gottlieb, M.D., issued a statement on new strategies to modernize clinical trials.² Although these guidance documents were temporary measures meant to improve disrupted clinical trial operations, updates like these paved the way for introducing innovative ways, such as the use of DCTs, to conduct clinical trials.³

What Do the Regulations Require?

The regulatory landscape continues to evolve, and researchers must align their trials with the latest guidance keeping in mind that DCTs are still in their infancy and without defined criteria in place.

Researchers must consider that each regulatory agency will have specific regulations on a decentralized clinical trial. They may include requirements for safety reporting, data collection and use of technology.

In addition, these agencies may also have guidance documents available for sponsors and investigators on conducting DCTs. For example, the FDA issued guidance for researchers on conducting clinical trials during the COVID-19 health emergency and all DCTs should be compliant with the ICH E6 Good Clinical Practice (GCP) Guideline ensuring human subject protection and high-quality data.^5,6

Before researchers can decide whether a DCT model fits their study design, they must ensure that all regulations, guidance documents and guidelines are reviewed for all states and/or countries that the study will be conducted in.

Full or Hybrid DCT: Determine the Best Fit

The goal of a DCT is to expand clinical trial access to patients and providers, and researchers should determine clinical trial needs prior to the start of the study to determine the ideal and plausible approach. This means assessing the study hypothesis and determining if there are critical procedures or lab work that need to be completed at a trial site instead of utilizing telemedicine or in-home visits.

A hybrid approach combines digital technology with occasional trial site visits and is best for studies that require radiological procedures or complicated blood draws that cannot be accomplished outside of a medical site.

A full DCT approach incorporates smartphones and wearables and provides access to tele-visits in conjunction with home healthcare providers, nurses, mobile phlebotomists and other local healthcare providers.

Whether using a full DCT or hybrid DCT method, the details should be clearly outlined in the study protocol and explained to participants during the informed consent process to ensure all participants make a knowledgeable decision about their participation in the study.

Determining Feasibility of a DCT

The adoption of a DCT to answer clinical research questions is dependent on several factors. First, study protocols must be patient-centric and designed to allow for less complicated trial procedures and remote patient visits.⁷ Secondly, technology solutions and infrastructure need to be in place to capture data remotely yet be aggregated and analyzed centrally.

Proper training of digital tools and platforms must be conducted at the patient, site and sponsor level. Lastly, each step and process in the study conduct phase must be evaluated as to whether decentralization will improve patient compliance and engagement, accelerate timelines and decrease site burden.⁸

Making a DCT Successful

Life science companies will need to employ three strategies to make a DCT or hybrid DCT successful:

Incorporating Technology. Technology is key to delivering a DCT, starting with artificial intelligence (AI) and natural language processing (NLP) tools to identify a diverse set of eligible trial participants and incorporating smartphones, wearables, telemedicine and home healthcare providers.

Smartphones and wearables are considered digital health technology (DHT) tools. Researchers should ensure their proposed DHT tools are qualified according to the FDA’s Medical Device Development Tool (MDDT) Qualification Program to collect data or generate evidence within a clinical trial context.

The MDDT Qualification Program can help indicate if a DHT would be generally suitable for use in clinical development programs, but participation in the program is voluntary and is only meant to give sponsors and investigators confidence that the use of a DHT tool is acceptable to the FDA.⁹

Collecting Data. Life science companies will need to ensure accurate collection of data whether directly from patients through wearables, in-home and in-clinic visits or extracted from electronic medical records (EMRs). This data will need to be aggregated and translated into study reports and prepared for regulatory review. Managing this data, whether from multiple trial sites or through digital technologies, will require intuitive, fit-for-purpose technologies, regulatory requirement expertise or a partnership with a data science company.¹⁰

Easing the Burden on Patients. Life science companies will need to work with sponsors or partners on protocol design to incorporate patient centeredness and decentralized components to help ease the burden on patients. ⁹ The use of technology will allow patients to participate from the comfort of their homes and still receive medication reminders and study-specific educational information.

All clinical trials are dependent on establishing the right research question, study protocol and best use of technology. Whether to use a full DCT or hybrid DCT approach can be determined by the investigators and sponsors when seeking to answer the research questions and determining the best fit for trial participants.

As an industry, if we want DCTs to become a permanent part of the clinical research landscape, then it will require everyone embracing a more open, information-sharing ecosystem involving public and private data resources, a data governance framework, partnership opportunities and a willingness to continue utilizing technology-enhanced solutions.

References:

1. European Medicines Agency, Guidance on the management of Clinical Trials During the COVID-19 (Coronavirus) Pandemic, Version 5, October 2, 2022, available at https://ec.europa.eu/health/sites/default/files/files/eudralex/vol-10/guidanceclinicaltrials_covid19_en.pdf
2. Statement by FDA Commissioner Scott Gottlieb, M.D., on new strategies to modernize clinical trials to advance precision medicine, patient protections and more efficient product development, U.S. Food & Drug Admin., available at https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-new-strategies-modernize-clinical-trials-advance (last updated Mar. 14, 2019).
3. Van Norman G. A. (2021). Decentralized Clinical Trials: The Future of Medical Product Development? Basic to translational science, 6(4), 384–387. https://doi.org/10.1016/j.jacbts.2021.01.011
4. Clinical Trial Transformation Initiative, CTTI Recommendations: Decentralized Clinical Trials2 (2018), available at https://ctti-clinicaltrials.org/wp-content/uploads/2021/06/CTTI_DCT_Recs.pdf
5. S. Food & Drug Admin., Guidance for Industry, Investigators, and Institutional Review Boards: Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency 26 (2020), available at https://www.fda.gov/media/136238/download
6. International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Explanatory Note available at https://database.ich.org/sites/default/files/ICH_E6-R3_GCP-Principles_Draft_2021_0419.pdf
7. No place like home? Stepping up the decentralization of clinical trials, available at https://www.mckinsey.com/industries/life-sciences/our-insights/no-place-like-home-stepping-up-the-decentralization-of-clinical-trials
8. Why Decentralisation Is The Future Of Clinical trials, October6, 2022, available at https://mdgroup.com/blog/why-decentralisation-is-the-future-of-clinical-trials/
9. S. Food & Drug Admin., Medical Device Development Tools (MDDT), available at https://www.fda.gov/medical-devices/science-and-research-medical-devices/medical-device-development-tools-mddt?elq=c35f8b9a94034655a63b0ff2a847c15c&elqCampaignId=2595&elqTrackId=33C31492255977A002E994D6B25854D7&elqaid=3421&elqat=1#:~:text=The%20FDA%27s%20Medical%20Device%20Development%20Tools%20%28MDDT%29%20program,in%20the%20development%20and%20evaluation%20of%20medical%20devices.
10. RWE focus is shifting to R&D, early investments begin to pay off. Retrieved March 2021 available at https://www2.deloitte.com/us/en/insights/industry/health-care/real-world-evidence-study.html
11. Overcoming Study-Patient Burdens in Medical Research, available at https://sanguinebio.com/overcoming-study-patient-burdens-in-medical-research/