Required adaptations to clinical trial design and execution, implemented during the COVID-19 pandemic, have put a new focus on the development of patient-focused, decentralized clinical trials (DCTs). Now a new call-to-action details practical steps for the oncology research and clinical care communities to expand access to clinical trials and enable patients to participate closer to their homes.

The Call to Action was published on January 9, 2024 in Cancer, an international interdisciplinary journal published by the American Cancer Society (ACS). [1]

The paper, authored by members of an American Society of Clinical Oncology (ASCO) Task Force, highlights the importance of enabling patients to receive clinical trial related testing and care near their homes, rather than requiring patients to travel to major research institutions hours from where they live.

“There are patients who travel 3-4 hours for routine labs and imaging at research centers even though it’s testing that is readily available in their communities,” noted ASCO Chief Medical Officer Julie Gralow, MD, FACP, FASCO.

“Enacting these strategies makes participation in clinical trials a possibility for far more patients, especially those who are often underrepresented,” Garlow added.

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Roadblocks
Unnecessary roadblocks perpetuate the underrepresentation in cancer treatment trials. While 15% to 19% of the U.S. population live in rural areas, over half (66%) of rural counties do not have an oncologist. Forcing patients in rural areas to travel further than necessary to receive routine care to participate in clinical trials is not a sustainable model, nor does it allow all patients access to novel treatment options.

These concepts are not new to the research community. During the COVID-19 pandemic, the Food and Drug Administration (FDA) and the National Cancer Institute (NCI) made several accommodations, moving cancer research towards a decentralized model, which allowed research to continue and kept patients safe.

While the pandemic-era accommodations and strategies to make clinical trials more convenient showed the feasibility and benefits of decentralizing elements of clinical trials, the Task Force identified current instances of sponsors and institutions reverting back to traditional research models as the stressors of the pandemic decreased.

Hence, following concerns in the clinical research community that after COVID-19 restrictions would be lifted, participation in remote and local clinical trials would decrease, the FDA, in May 2023, issued a draft guidance for sponsors, investigators, and other stakeholders for implementing decentralized clinical trials (DCTs), noting the potential for DCTs to expand access to diverse patient populations and aid trial efficiencies.

FDA Guidance
However, while the Food and Drug Administration’s draft guidance include recommendations for clinical trials outside the traditional clinical trial sites, including a patient’s home or a local healthcare facility and the use of digital health technologies, the Food and Drug Administration warns that data collected in a decentralized clinical trial, may differ from data obtain in a traditional clinical trial setting. This is, according to the agency, due to the variability of precision assessments performed in regional or local healthcare centers. In turn, this could, potentially, affect the validity of findings of non-inferiority [2], which is an important measurement to demonstrated that the effect of a new treatment is not worse than that of an active control or the current standard of care by more than a specified margin.

The Task Force main concern is that the draft guidance does, unfortunately, not adequately address the obstacles to DCTs for patient’s diagnosed with cancer.  This is, in part, due to the fact that clinical research in oncology and hematology is complex, but also because of the variety of health care, treatment and research settings in which these patients are seen.[3] Furthermore, while DCT are expected to become a common approach to clinical research, and available tools and strategies can indeed ensure a patient’s safety and secure research integrity and, at the same time, reduce unnecessary burdens for patients as well costs associated with trial participation in a traditional trial setting, the FDA and other regulators worldwide pay little attention to the distinct ethical challenges DCTs may pose.

A recent report published in the Lancet Digital Health, discusses the need for increased ethical vigilance,  patient’s safety and rights, scientific validity, and ethics oversight. [4] The article concluded that despite the promise of DCTs to address many of the deficits seen in traditional clinical trial settings, not all trials are suitable for a decentralized approach, requiring careful consideration in trial design, planning and execution.[4] They authors argue that to ensure that the inclusion of DCT results in robust scientific evidence, while protecting the rights and wellbeing of research participants, adherence to clear ethical standards is essential.[4]

Tangible opportunities
ASCO’s Calls-to-action and tangible opportunities for change identified in the paper include:

  • Clarifying the requirements of the FDA Statement of Investigator (Form 1572) [5]
  • Routinely accepting testing from local laboratories and imaging centers
  • Creating and nurturing partnerships to increase patient and clinician local access to clinical trials

“Inequities in cancer care begin with the underrepresentation of certain populations in cancer research, which is why it’s so important that the research community removes barriers to trials,” noted  R. Donald Harvey, PharmD, BCOP, FCCP, FHOPA, FASCO, co-author of the paper, and Director of Phase I Clinical Trials Program at Winship Cancer Institute of Emory University.

“The strategies in this paper are tangible, actionable ways to do that and we are optimistic and eager to help ensure they are adopted,” Harvey concluded.

Without a doubt, ASCO’s Calls-to-action is designed to ensure that all patients diagnosed with cancer have proper access to clinical trials and are, in addition, routinely able to participate in research closer to their home. The Task Force believes that the key to realize this is to help regional and local clinicians in community oncology programs and practices,  to facilitate clinical trial participation.

The Task Forces concludes that meeting the many changes in developing DCTs in oncology and hematology is critical to transforming clinical trials to help ensure that all patients with cancer have timely access to novel therapies, minimal participant burden, and continuity of care throughout their treatment.[1].

The emerging possibilities towards implementing DCTs may be instrumental in eliminating known impediments to clinical trial participation and retention, improving patient access and meeting their specific needs. This greater flexibility in how clinical trials are being conducted may be especially beneficial for cancer patient in underserved settings, where time, financial, and logistical burdens related to participating in a traditional clinical trial setting to receive study-related treatment and/or testing may be hindered. [1][6]

But despite changing in how clinical trials may be conducted and benefit patients, one of the most important observations is that results from decentralized oncology and hematology studies, conducted during the COVID-19 pandemic, showed minimal to no impact on overall data integrity. [1][6]

Reference
[1] Harvey RD, Miller TM, Hurley PA, Thota R, Black LJ, Bruinooge SS, Boehmer LM, Fleury ME, Kamboj J, Rizvi MA, Symington BE, Tap WD, Waterhouse DM, Levit LA, Merrill JK, Prindiville SA, Pollastro T, Brewer JR, Byatt LP, Hamroun L, Kim ES, Holland N, Nowakowski GS. A call to action to advance patient-focused and decentralized clinical trials. First published: 09 January 2024 DOI 10.1002/cncr.35145
[2] US Food and Drug Administration. Non-Inferiority Clinical Trials to Establish Effectiveness; Guidance for Industry; U.S. Department of Health and Human Services Food and Drug Administratio. Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER). November 2016. Online. Last accessed on January 9, 2024.
[3] US Food and Drug Administration (FDA). Decentralized clinical trials for drugs, biological products, and devices. FDA; 2023Online. Last accesses on January 9, 2024
[4] Vayena E, Blasimme A, Sugarman J. Decentralised clinical trials: ethical opportunities and challenges. Lancet Digit Health. 2023 Jun;5(6):e390-e394. doi: 10.1016/S2589-7500(23)00052-3. Epub 2023 Apr 25. PMID: 37105800; PMCID: PMC10129131.
[5] US Food and drug Administration. Information Sheet Guidance for Sponsors, Clinical Investigators, and IRBs; Frequently Asked Questions – Statement of Investigator (Form FDA 1572). U.S. Department of Health and Human Services; Food and Drug Administration; Office of Good Clinical Practice. Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER). May 2010. Online. Last accesses January 9, 2024. [Download]
[6] Unger JM, Stires H, Levit LA, Stewart M, McKelvey BA, Canin B, Dressler E, Flaherty K, Fredette P, Jones L, McCann P, Miller T, Onitilo AA, Palmieri F, Patel T, Paul R, Smith GL, Bruinooge SS, Garrett-Mayer E, Lei XJ, Alva A, Schenkel C. Sponsor Perspectives on the Impact of the COVID-19 Pandemic on Interventional Cancer Clinical Trial Protocols and Data Quality. JCO Oncol Pract. 2023 Oct;19(10):907-916. doi: 10.1200/OP.23.00185. Epub 2023 Aug 29. PMID: 37643386; PMCID: PMC10615547.

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This article was first published in ADC Review | Journal of Antibody-drug Conjugates.

 

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