Clinical Researcher—April 2021 (Volume 35, Issue 3)

SITES & SPONSORS

Mark Clements, MD, PhD, CPI, FAAP; Komathi Stem, MS

 

COVID-19’s effect on clinical trials is a tale of two outcomes.

Near-term, the pandemic has been devastatingly disruptive. About 80% of non-COVID-19 trials were either stopped or interrupted.{1} As of January 2021, COVID-19 had stopped more than 2,000 clinical trials.{2}

But, like a wildfire that cracks open the cones of sequoia trees to release their seeds, COVID-19 has germinated widespread adoption of underutilized trial models, tactics, and tools such as virtual/decentralized clinical trials (DCTs), telehealth visits, remote patient monitoring (RPM), and the use of real-world data (RWD). These new practices have taken root and will have a lasting impact on how clinical trials are designed and conducted.

DCTs: The Cat’s Out of the Bag

In 2015, the Clinical Trial Transformation Initiative (CTTI) recommended that trial sponsors consider fully or partially decentralized DCTs, defined as trials executed through telemedicine and mobile/local healthcare providers.{3} Although a shift toward virtual trials has been gradually building, many sponsors have been hesitant to adopt this model due to concerns about whether their trials would be accepted by the U.S. Food and Drug Administration (FDA).

Thanks to COVID-19, these worries have dissipated. With a nationwide lockdown issued in March 2020, the FDA recognized the safety risks of in-person clinical trials and issued guidance encouraging researchers to consider alternatives for patient assessments and data collection, including virtual visits, remote data collection, and RPM.{4}

Almost immediately, the popularity of DCTs skyrocketed. Before the March lockdown, one company that supports virtual clinical trials had about a dozen calls a week from potential clients. By June, it was receiving hundreds of weekly inquiries.{5}

For years, patient advocates have been pushing for more virtual trials to make participation easier. At the same time, trial sponsors, contract research organizations, and study site investigators have recognized that DCTs can:

• Remove obstacles to patient enrollment and participation, the top cause of trial delays or terminations.
• Reduce high rates of participant drop-outs, which rose from 15% in 2012 to 19% in late-stage studies globally.{6}
• Increase diversity in patient populations.
• Provide participants with greater control, convenience, and comfort.

Although elements of the DCT model (full or hybrid) can be integrated into any clinical trial, this approach is especially suitable for studies that collect physiological data from devices in the patients’ home (e.g., blood pressure cuffs, glucose, and insulin dosing data).

Having proven their mettle in the cauldron of COVID-19, DCTs are here to stay. As Esther Krofah, executive director of the Washington, D.C. think tank FasterCures, notes, “We’re going to see virtual trials as a new, normal part of clinical research. The cat is out of the bag.”{5}

Digitization Improves Patient Access and Participation

The FDA’s embrace of DCTs has accelerated the digitization of all aspects of clinical trials, from design and patient recruitment to data collection and analysis. For example, by taking advantage of robust patient databases and sophisticated social media tools, sponsors can not only increase awareness for their recruitment campaigns but also more precisely target the right patient populations. Researchers from Harvard and MIT report that digitized DCTs may help increase trial access and diversity, especially for women and participants from rural areas and racial groups traditionally underrepresented in clinical research.{7}

Perhaps most importantly, telehealth visits and the use of remote monitoring tools can remove barriers that prohibit patients’ full participation for the duration of in-person trials. By minimizing or eliminating problems with transportation and infrequent communications, clinical trials can become part of participants’ everyday lives. This will allow investigators to more easily, effectively, and precisely track how each patient is responding to treatments and intervene as needed in real-time. In addition, the trial data will provide more meaningful insights about patients’ real-world experiences with the drug or medical device under investigation.

RWD Comes of Age

For more than a decade, clinical trials have been collecting and using RWD, whether self-reported by the patient or from mobile devices, wearables, or other biosensors. In the past year, however, as COVID-19 made remote trials the new normal, RWD have become an integral element of trial protocols.

This trend began to gain momentum following the 2016 passage of the 21st Century Cures Act and the FDA’s launch of a program focused on using RWD and real-world evidence (RWE) to support regulatory decision making, including approval of new indications for approved drugs and biologics. The FDA also encouraged researchers to consider situations where RWE trials could generate useful information.{8} Today, medical product developers are using RWD and RWE to support clinical trial designs (e.g., large simple trials, pragmatic clinical trials) and observational studies to generate innovative treatment approaches.{9}

Clinical Research Platforms: Connectivity is the Key to Success

The shift to DCTs coupled with the proliferation of digitized health data has elevated the importance of clinical research platforms, which must help administrators and investigators:

• Collect, manage, analyze, and disseminate voluminous patient-reported and physiological data generated by computers, mobile devices, wearables, and other biosensors.
• Establish seamless connections between trial managers, patients, devices, trial data, and information systems.

To accomplish this, a modern research platform ideally should:

• Enable data collection from whatever devices a patient wants to use or allowed by their medical insurance.
• Offer patient-friendly collection tools that allow participants to easily upload and share their data remotely or in the clinic.
• Integrate multiple flows of data and enable investigators to view all patient information through a single portal.
• Provide rich sets of RWD, which can be invaluable for researching a wide range of interventions, variables, and specific patient populations.
• Monitor and measure safety signals (e.g., low blood sugar in diabetes studies) to enable prophylactic or real-time interventions.
• Enhance personalized and continuous patient engagement to improve adherence and data quality.
• Include sophisticated analytical capabilities to provide insights into patient behaviors.

By creating robust research platforms, companies will be able to track, analyze, and share much larger and more diverse datasets from more complex studies.

Conclusion

In an industry that often seems resistant to change, the pandemic has triggered widespread adoption of novel remote monitoring technologies and decentralized approaches. Although still in its early stages, this modernization of clinical trials will continue to be fueled post-COVID-19 by exponential growth in digital health adoption and capabilities. Future clinical trials promise to be increasingly efficient, diverse, and patient-centric while providing researchers with richer, more timely, and more meaningful information.

References

1. Dorn, AV. 2020. COVID-19 and readjusting clinical trials. The Lancet 396(10250):523–4. https://doi.org/10.1016/S0140-6736(20)31787-6
2. Carlisle BG. 2021. Clinical Trials Stopped by COVID-19. The Grey Literature. https://covid19.bgcarlisle.com/
3. Clinical Trials Transformation Initiative. Decentralized Clinical Trials. Published September 2018. https://www.ctti-clinicaltrials.org/projects/decentralized-clinical-trials
4. Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency: Guidance for Industry, Investigators, and Institutional Review Boards. U.S. Food and Drug Administration. Published March 2020 (Updated January 2021).
5. Ledford H. 2020. The coronavirus outbreak could make it quicker and easier to trial drugs. Nature 582(172). https://doi.org/10.1038/d41586-020-01524-0
6. Tufts Center for the Study of Drug Development. 2020. Tufts CSDD Impact Report. https://static1.squarespace.com/static/5a9eb0c8e2ccd1158288d8dc/t/5e303c3dd4520c015cb8a4b1/1580219453985/JanFeb2020_CropSummary.JPG
7. Plana D, Arfe A, Sinha MS. 2020. Re-envisioning clinical trials during the COVID-19 pandemic. Health Affairs. https://www.healthaffairs.org/do/10.1377/hblog20200702.963588/full/
8. Klonoff DC. 2020. The New FDA Real-World Evidence Program to Support Development of Drugs and Biologics. Journal of Diabetes Science and Technology.
9. U.S. Food and Drug Administration. 2020. Real-world data (RWD) and real-world evidence (RWE) are playing an increasing role in health care decisions.

Mark Clements, MD, PhD, CPI, FAAP, is Chief Medical Officer at Glooko Inc., a Professor of Pediatrics at the University of Missouri-Kansas City School of Medicine, and a pediatric endocrinologist at Children’s Mercy Kansas City. A clinical researcher of new diabetes treatments and technologies, he has served as a principal investigator or co-investigator in more than 30 clinical studies and patient registries. He currently serves as data science co-lead for the Type 1 Diabetes Exchange Quality Improvement Collaborative.

Komathi Stem, MS, is Chief Operating Officer at Glooko Inc. A biomedical engineer, clinical researcher, and entrepreneur who is passionate about leveraging digital technologies to accelerate clinical research and transform healthcare, she has more than 25 years of experience as a drug development/health information technology executive across multiple therapeutic areas and phases for biologic and small molecule drugs.