Semantics Matter: DCTs And An Industry Decentralized

By Daniel J. Fox, MPH, Ph.D., clinical site advocate; founder/cofounder and executive leader, Clinical Research Payment Network; Land of Lincoln Clinical Research; DiversiTrials; and Save Our Sites Conference and Alliance (former)

Amidst one of the greatest global health crises in over 100 years, national decentralized clinical trials (DCTs) organizations hit the industry like a storm. Investor-backed giants injected resources into what they thought would be once-in-a-lifetime returns on investments during the desperate times and high demands of the COVID-19 pandemic. They promised all the patients without those pesky local sites getting in the way. They claimed the quadrupled RFP will be worth it in the end when you eliminate the waste of inefficient trials at the local level. And because it was COVID and our world was in a state of crisis, the industry listened. Yet, many of our local community sites interpreted their introduction as an attempt to cut them out of the process or to replace their frontline efforts altogether (Costello and Larrabee 2021).

We remember those social media posts: “DCT is the future! If you don’t adopt it, you will go extinct.” The local community site was not only under attack but also under greater scrutiny as national corporations and pharmacies swooped in to take control of frontline local community activities, physicians’ decisions, and patients.

Fast forward several years. The pandemic has gradually left the world’s priorities, and the allure of “convenience” of national DCT efforts has subsided as hefty price tags (and equally impressive revenue anticipated by investors) are no longer justified. Sponsors instead are falling back into their pre-COVID budgets, standards, and site expectations. One by one, the same organizations promising a site-free future are closing their doors as they realize the finances of clinical trials are nowhere near what they projected during pandemic times.

The federal government and the FDA, however, are hard at work creating policies to be better prepared in the event of another public health emergency. The FDA’s DCT guidance, poised to be final any month, spells out clearly how the industry may implement decentralized methods for compliant trial performance. And yet, even as the FDA forges the path for streamlined and efficient trial delivery to our communities, the industry as a whole remains stagnant.

Why are we as an industry resisting the adoption and acceptance of solutions that were designed to save the world (Dulko et al. 2023)?

Why are programs such as BARDA’s D-COHRe, ARPA-H’s Advancing Clinical Trial Readiness (ACTR) (ARPA-H 2023), and Healthcare Integration (Fox 2023) initiatives exploring ways to encourage the adoption of decentralized programs across research deserts, in local healthcare organizations, and for every American within a 30-minute drive?

Why, after our industry literally saved the world from a global crisis, are we falling back into our old and obsolete ways?

Frankly, for me and others, after navigating a global crisis as a community research site and struggling to survive, all while national DCT organizations were poised to make local sites obsolete, the term DCT leaves a sour taste in our collective mouths.

Still, the concepts and principles of these innovative decentralized strategies hold promise to enhance clinical trials and set a new standard for quality and efficiency. To salvage some of the innovation we gained during the pandemic, we must spark awareness, acceptance, and adoption of the value of decentralized elements (not entire trials) throughout our industry’s site communities.

If the term “DCT” cannot accomplish this objective, perhaps it is time for an industrywide rebranding.

If Not “DCT,” Then What?

Similar to “patients” or “subjects” terminologies being seen as obsolete and, at times, inappropriate to today’s modern world, and therefore GCP standards formally adopting “participant” (Bhatt 2023), “DCT” is plagued with a stigma that prevents its methods from being adopted among local and community clinical research sites. Quite simply, it’s an outdated term with destructive correlations that deters many community sites from considering innovative ways to serve our society.

To spur innovation and adoption at an industrywide scale, what then should we call these decentralized units of innovation?

Sufficient reasoning for using terms such as decentralized activities, components, and elements may also lead us to refer to decentralized methods and processes and thereby decentralized visits and ultimately trials. Each term could be validated and justified across the industry. However, we need to consider the perspectives of the same stakeholders we are targeting for adoption: the sites. From a community site’s perspective, decentralized clinical visits (DCVs) as a term aligns substantially at regulatory, legal, and operational levels.

Perhaps rebranding as “DCVs” has a better chance of industrywide adoption. Let’s explore why.

Regulations Cite “Visits,” Not “Trials”

Although the title is to the contrary, the FDA’s Draft DCT Guidance clarifies the regulations around decentralized activities specifically to “remote clinical trial visits” (emphasis my own) in a trial protocol’s schedule of assessments. Specifically, lines 118-121 state investigators can consider telehealth visits and that protocols (approved by the IRB) should specify when telehealth visits are appropriate (FDA 2023). Every visit is under review with an understanding of whether it needs to be at the clinical research site because of its complexity or decentralized at another location, such as a doctor’s office or the trial participant's home, at the discretion of the PI (lines 91; 243-245).

In the guidance, the FDA even indicates an alignment between decentralized activities and visits, whether in-person or by telemedicine, overseen and performed by investigators, site personnel, and community healthcare providers.

Contracts Pay By “Visits,” Not “Trials”

As we look at the industry’s business cycles, we recognize that sites are awarded trials, negotiate contracts and budgets, perform trial services, and, unless otherwise specified in cases such as unscheduled visits or partial screen fail activity, are paid according to the clinical trial agreement by visits. In fact, many of the larger sponsors in the industry are eliminating visit itemization in their budgeted schedules of assessment and instead are condensing financial clarity not by services performed, but rather by clinical trial visits completed.  

Sponsors and CROs may operate under business parameters by trial; however, the same terminology they developed for site adoption is likely incompatible with frontline business models, policies, and processes. Therefore, to align with the business and financial relationships of understanding at the site level for increased awareness, adoption, and acceptance, the appropriate segmentation of service may be defined by visit just as it is in site contracts and budgets.

Sites Perform “Trials” Through “Visits” In Operations

“Visits” are the core of site operations. They are how CRAs inquire about trial performance, how CRCs organize their calendars, and how we as an industry organize our data management, collections, and compliance.

From source (144-145) and scheduling (213-214) to informed consents (353) and safety monitoring (453-454), to speak in “visits” is to speak the language not only of the FDA’s guidance (FDA 2023) but also of the professionals at clinical research sites who are performing trial services.

Thus, utilizing this terminology is fully compatible as a universal business increment at site regulatory, financial, and operational levels.

If We Want Widespread Adoption, Words And Roles Matter

“DCT” served its purpose in our industry by signifying during a crisis the innovative potential we as an industry may accomplish to save the world. In the end, however, the term became tainted across the frontlines as an intent to replace our patient-facing professionals. We know simply by the name that sites were not the consulting majority behind the “DCT” movement. Sites hear the term and are reminded of contentious times when organizations intended to eliminate them from the clinical trial equation. The need for fast and efficient trials to save the world may have ended for now, but bad memories linger.

If we want clinical research to advance by adopting new methods to perform trials, then the sites must be the ones to develop, take ownership of, and operate them. Sites can advance DCVs going forward if we simply give them the chance, especially given their federal obligation to own and operate.

References:

1. ARPA-H. 2023. Biden-Harris Administration’s ARPA-H initiative invests to improve clinical trials and drive better health outcomes. Accessed Online: https://arpa-h.gov/news-and-events/arpa-h-advances-initiative-improve-clinical trials
2. Bhatt, A. 2023. The revamped Good Clinical Practice E6(R3) guideline: Profound changes in principles and practice! Perspect Clin Res. 2023 Oct-Dec; 14(4): 167-171.
3. Costello, M. and Larrabee, P. 2021. Sites Still Necessary for Decentralized Trials. Applied Clinical Trials. Vol. 30. Issue 10. 13 October 2021.
4. Dulko, D. et al. 2023. From a decentralized clinical trial to a decentralized and clinical trial-in-a-box platform: Towards patient-centric and equitable trials. Journal of Clinical and Translational Science. Vol 7, Issue 1 09 October 2023.
5. Food and Drug Administration (FDA). 2023. Decentralized Clinical Trials for Drugs, Biological Products, and Devices: Guidance for Industry, Investigators, and Other Stakeholders – DRAFT GUIDANCE. U.S. Department of Health and Human Services. May 2023.
6. Fox, D. 2023. Healthcare Integration: How Do We Put The “Clinical” Into “Clinical Research”? Clinical Leader. November 17, 2023. Accessed Online: https://www.clinicalleader.com/doc/healthcare-integration-how-do-we-put-the-clinical-into-clinical-research-0001
7. Petrini, C. et al. 2022. Decentralized clinical trials (DCTs): A few ethical considerations. Frontiers in Public Health. Vol. 10. 14 December 2022.
8. Sacks, L. 2023. The Evolving Role of Decentralized Clinical Trials and Digital Health Technologies. CDER Conversations. 02 May 2023. Accessed Online: https://www.fda.gov/drugs/cder-conversations/evolving-role-decentralized-clinical trials-and-digital-health-technologies
9. United States Department of Health and Human Services. 2023. Strategic Partnership Solicitation for Decentralized Clinical Operations for Healthcare and Research (D-COHRe). June 20, 2023.

About the Author:

Daniel J. Fox, MPH, Ph.D., is the founder/cofounder and executive of the Clinical Research Payment Network, Land of Lincoln Clinical Research, DiversiTrials, and formerly the Save Our Sites Conference and Alliance. His experience in the translational sciences, from bacteria and animals to pharmaceutical manufacturing, quality control, and clinical site administration, for over 15 years and personal family loss drives him to be a servant community leader to ensure open access to clinical trials for everyone regardless of where they live, what they look like, or how much money they have.

Fox specializes in legal, regulatory, and financial translational sciences with a focus on ensuring our clinical research stakeholders (our sponsors, PIs, site staff, and, importantly, patients) have everything they need, from payments and SOPs to protocols, equipment, and networks, to perform successful quality research and advance healthcare technology as quickly, efficiently, and safely as possible.