Nate Hughes, MPH, MPP, M. Phil.
Johns Hopkins Bloomberg School of Public Health Alumnus
A recent survey from Applied Clinical Trials noted that 76% of 252 sponsor respondents recognized that COVID-19 accelerated their adoption of decentralized clinical trials (or “DCT”) including wearable devices, protocol redesign, and investigator-facing technologies.
In May 2023, the FDA issued clairvoyant guidance on decentralized clinical trials, a nonbinding recommendation to sponsors in the DCT field to, among several other considerations, strive for diversity and inclusiveness in trial populations. According to STAT News: “In one Food and Drug Administration analysis of clinical trials conducted between 2015 and 2018 showed that 78% of participants were non-Hispanic white people. More than 97% of participants in a Phase 2 trial of the Alzheimer’s drug crenezumab were white and just 2.8% where Hispanic even though Hispanic people are 1.2 times more likely to develop Alzheimer’s” (In a “A Drive to Increase Diversity in Clinical Trials”).
Some examples of DCT companies that are changing the landscape of clinical trials are the following: Science 37, THREAD, UNLEARN AI, Curebase, Reify Health, and CLIMB to name a few.
The DCT movement, born out of the COVID pandemic, reconfigures the notion that clinical trials monitoring must be done onsite, ultimately determining that a fully remote or adopt a hybrid approach where some physical-site attendance is required. Aside from the ability to increase patient enrollment and retention by casting a wider recruitment net, and thereby reducing the costs associated with onsite trials, perhaps the most exciting benefit of DCT is increasing the diversity of underrepresented groups, contingent on inclusion/exclusion criteria in protocols. According to “Online Patient Recruitment in Clinical Trials: Systematic Review and Meta Analysis” from J Med Internet Res. 2020 Nov; 22(11): e22179:
“Recruitment for clinical trials continues to be a challenge, as patient recruitment is the single biggest cause of trial delays. Around 80% of trials fail to meet the initial enrollment target and timeline, and these delays can result in lost revenue of as much as US $8 million per day for drug developing companies.”
Let’s look at the potential benefits and drawbacks to DCT:
- Greater enrollment flexibility with increase in generalizability of trial inclusion by mitigating the need for onsite visits and promoting hybrid site monitoring with first SIV.
- Potentially significant cost savings for sponsors.
- Increased patient retention and lower dop out rates
- Improving rates of follow-up
- More interaction with patients can translate to a better “continuous” patient experience and better outcomes in case of side effects/emergency.
- Potentially higher data quality/data capture.
- With the emerging increase in DCT technologies, there will invariably be an increase in patient awareness over time. For example, by the end of 2023 13 new cell or gene therapies could be approved in the US, Europe, or both, however the need for patients to become aware of these approved therapies has never been greater. The advent of more approved personalized medicine, with the increasing complexity of telehealth visits and/or self-administration in outpatient settings, especially in local communities, should lead to a positive affect on clinical trial awareness, and thus, a positive net effect on enrollment and retention.
- Ability for real-time “continuous monitoring” of patients.
- Potential increase in diversity of underrepresented groups with new next generation platforms which increase “patientricity.”
Now let’s examine some potential disadvantages of DCT:
- Lowering the frequency of onsite visits can also, with it, bring potentially less adherence to patient safety, if patients are self-administering at home.
- Greater reliance on technology training both for DCT trial participants and for the staff administering these technologies.
- Data security and privacy concerns around data breeches and patient confidentiality. This includes potentially compromising both the quality and reliability of data collection.
- Regulatory concerns
- Technological barriers since this assumes access to technological platforms is a given.
- Therapy and disease limitations – DCT does not capture every condition or illness due to technical requirements.
- Hidden costs associated with new technological platforms, also known as pass though or third-party vendor costs.
- Some clients prefer brick and mortar sites depending on the inclusion/exclusion criteria, and thus a particular study might be a better “fit” for onsite analysis, data collection, and monitoring.
One such example of a DCT is Curebase’s collaboration with Blue Note Therapeutics in 2022 on a prescription digital therapeutics (PDT) oncology trial with a goal of maximizing recruitment efforts by screening, consenting, and navigating patients through the reporting and activities required for the study with a total of 353 patients for a fully remote trial.
This discussion has focused on both the positive and negative net effects of DCT. While there is ample room for both arguments as part of a general polemical discussion in clinical trial optimization, one thing cannot be ignored: DCT is here to stay. To quote Luca Issi, from Genetic Medicine Leads a Surge of Innovation in Biotech, “We believe the ultimate ‘winner’ in this field may not necessarily be the companies with the most attention-grabbing technology, but those that can successfully target the right indications and cleverly design clinical trials.” Or to take it one step further and paraphrase Charles Darwin, who could have replaced the epochal tone about evolution with redesigning clinical trials, “It is not the strongest of the species that survives, nor the most intelligent. It is the one that is most adaptable to change.”