Breaking Boundaries by Shifting to Decentralized Clinical Trials

During the early months of the COVID-19 pandemic, clinical trial enrolments were largely paused unless the trial was directly related to vaccine development or COVID-19 care. While the majority of clinical trials initiated before the pandemic were relatively spared, the initiation of non-COVID-19 studies significantly decreased.

The successful continuation or initiation of clinical trials during the first two years of the pandemic was made possible by Health Canada and the Food and Drug Administration (FDA), which allowed trial sponsors, investigators and research ethics boards the flexibility to modify the study of protocol-specific procedures and processes while “assuring the safety of trial participants, maintaining compliance with good clinical practice (GCP), and minimizing risks to trial integrity for the duration of the COVID-19 public health emergency”^[1].  

Adopting flexibility in protocol procedures resulted in the decentralization of certain processes. These included using virtual methods (telephone, videoconferencing) for informed consent discussions and monitoring study participants; using local mobile healthcare providers for participant monitoring and administering the investigational drug and delivering the drug to the participant’s home. This decentralized approach helped to overcome the challenges caused by the implementation of various public health measures such as physical distancing, travel limitations, stay-at-home orders, deployment of researchers to supplement hospital staff as well as from closures of investigational sites.

CLINICAL TRIAL DESIGN

Centralized Clinical Trials: A centralized clinical trial is a trial conducted at one investigational site. Both the administration of the investigational drug and ongoing patient outcome assessments are conducted face to face under the direction and oversight of one research team. This provides researchers a high level of control over the study.

Centralized trials often struggle with participant recruitment and retention as participants may not want to travel or cannot travel the long distances to a research facility. According to the findings of the Patient Voice Survey 2021, 90% of patients are not willing to travel more than one hour to participate in a trial^[2]. This limits the pool of available participants, resulting in the underrepresentation of diverse populations.

Decentralized Clinical Trials: There is no one definition of decentralized clinical trials. The definition that captures the spectrum of this approach is that provided by the Clinical Trials Transformation Initiative (CTTI):

“CTTI defines decentralized clinical trials (DCTs) as those in which some or all study assessments or visits are conducted at locations other than the investigator site via any or all of the following DCT elements: tele-visits; mobile or local healthcare providers, including local labs and imaging centres; and home delivery of investigational products.”^[3]

The inconvenience along with cost of travel, scheduled clinic appointments and loss of income can be significant barriers to participation in a centralized trial. The leveraging of digital and virtual technology in the decentralized clinical trial model reduces the burden of patient participation and adds flexibility to the conduct of the trial.

“In a fully decentralized clinical trial, subject recruitment, delivery and administration of study medication, and acquisition of trial outcomes data all proceed without involving in-person contact between the study team and the patient/subject.”^[4]

The adoption of decentralized trials does not come without challenges. These include participant access to reliable internet services and technology, the need to provide training to participants on the proper use of computer applications and possibly on wearable devices, troubleshooting technology issues, the logistics of drug distribution and management when shipping to local communities and possible participants’ homes and protecting participant privacy.

DECENTRALIZED CLINICAL TRIALS – PART OF A STRATEGY TO ENHANCE PARTICIPANT DIVERSITY

According to the Deloitte Report “2022 Global Life Sciences Outlook Digitalization at scale: Delivering on the promise of science”^[5] amongst other recent articles, the continued use of digital technology is expected to continue, enabling decentralization of trials and more diversity in clinical trial participants. 

The lack of diversity in trial participants has been recognized as having “negatively impact[ed] the scientific evidence base of medical product safety and efficacy”^[6]. Women, racial and ethnic minorities are often underrepresented in clinical trials. This reduces the trial’s ability to generate sufficient data about the risks and benefits of an investigational drug product when generalized to all populations once approved.

Decentralized trials have the potential for recruiting more diverse populations by bringing the trial to participants’ homes. One researcher suggests that recruitment should not simply focus on the number of participants but rather the number of participants who represent the population in the country where the trial is held^[7]. A multi-faceted approach is required to address the various challenges that impact participant recruitment, diversity and retention.

Understanding the barriers to diversity and overcoming them is important. These resources outline how to better increase diversity for clinical trials:

• Advancing the Landscape: Increasing Diversity in Clinical Trials
• Paving the way for diversity and inclusion in clinical trials: establishing a platform for improvement
• Five Key Strategies for Enhancing Diversity in Clinical Trials

RESOURCES FOR ADOPTING DECENTRALIZED CLINICAL TRIALS

The article Legal, Regulatory, and Practical Issues to Consider When Adopting Decentralized Clinical Trials: Recommendations From the Clinical Trials Transformation Initiative summarizes key issues to consider and address when adopting a decentralized clinical trial strategy. Although the findings of the expert group are specific to the U.S., many issues are similar to those encountered in Canada and Europe, and applicable recommendations can be adapted to those countries. 

The guide What Research Sites Need to Know About Decentralized Clinical Trials provides insight on  the benefits and challenges of adopting a decentralized trial strategy.  

BOTTOM LINE

Sponsors and clinical researchers planning to adopt a decentralized approach to enhance participant recruitment and diversity should consider the pros and cons of this approach and understand the barriers to engaging underrepresented racial and ethnic populations.

CNA CANADA INSURANCE SOLUTIONS

The main exposure with clinical trials is bodily injury to the participants of the trial. Whether you’re an organization that specializes in clinical research and development or that manufactures medical devices or pharmaceuticals, you need an insurance carrier that understands your unique risks.  CNA Canada offers a wide range of insurance solutions for life sciences organizations.

In Canada, products and/or services described are provided by Continental Casualty Company, a CNA property/casualty insurance company. The information is intended to present a general overview for illustrative purposes only. Read CNA’s General Disclaimer.

[1] Food and Drug Administration (FDA). (March 2020, Updated August 2021.) Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency: Guidance for Industry, Investigators, and Institutional Review Boards. Retrieved at: https://www.fda.gov/media/136238/download.

[2] ICON. (2021.) Biopharma perspective: the promise of decentralized models and diversity in clinical trials. Retrieved at: https://www.iconplc.com/insights/transforming-trials/decentralised-and-hybrid-clinical-trials/biopharma-perspective-panel-discussion/.

[3] Clinical Trials Transformation Initiative (CTTI). (2022.) Digital Health Trials - Recommendations to Sponsors for Planning Decentralized Trials. Retrieved from https://ctti-clinicaltrials.org/wp-content/uploads/2022/04/CTTI-Digital-Health-Trials-Planning-Decentralized-Trials-Recs.pdf

[4] Van Norman, Gail. (2021.) Decentralized Clinical Trials The Future of Medical Product Development? Retrieved at: https://www.sciencedirect.com/science/article/pii/S2452302X2100053X?via%3Dihub.

[5] Deloitte. (2022.) 2022 Global Life Sciences Outlook Digitalization at scale: Delivering on the promise of science. Retrieved from: https://www2.deloitte.com/content/dam/Deloitte/global/Documents/Life-Sciences-Health-Care/gx-lshc-dei-global-life-sciences-outlook-report.pdf

[6] Clinical Trials Transformation Initiative. (2021.) Advancing the Landscape: Increasing Diversity in Clinical Trials. Retrieved from: https://ctti-clinicaltrials.org/topics/quality/diversity/advancing-the-landscape-increasing-diversity-in-clinical-trials/

[7] Op. cit. ICON.