By Daniel J. Fox, MPH, Ph.D., founder, Clinical Research Payment Network; cofounder, Land of Lincoln Clinical Research; and CEO, Save Our Sites Conference and Alliance
I was a director of research at a local clinic during the COVID-19 pandemic.
I remember when the world stopped and looked directly at our industry to save it.
Then, the entire world cheered for the pharmaceutical companies, frontline clinical sites, and, importantly, our clinical trial participants when vaccine candidates came to trial. Some of our sponsors released contractual payment withholdings, provided additional support to help us continue trials, and, for the first time to this extent, I witnessed our industry working in unison against a mutual problem.
In retrospect, some lessons were learned, but, to this day, some lessons have not yet been learned. The clinical research industry is not equipped to routinely handle such a burdensome demand. Its specialized systems are not designed to handle global-scale enrollments. Regulations do not readily and rapidly approve and translate technology for patient safety reasons. And, importantly, our clinical research sites do not have the resources they need to battle a worldwide crisis.
Clinical research had to adapt to solve our immediate global challenge. DCT technologies that were poised to deliver clinical trials directly to our patients were rolled out across the community to save the day. Adopting DCTs ensured a place in the future of research, regardless of their exponentially higher costs compared to traditional methods.
Fast forward to 2023 and, sadly, although sound in technology, the embrace of DCTs is waning post-pandemic as Big Pharmacies exit the space and investor shares continue to devalue.
As a result, we as an industry must once again modify our standards not only to better serve our patients but also to prevent the potentially catastrophic costs of future pandemics.
Where do we go now: hybrid models, streamlined systems, real-world data, or something else?
One system synergistically addresses the shortcomings we as a research industry experienced during the pandemic: healthcare.
What if we could leverage our established community healthcare systems to efficiently deliver clinical trial opportunities?
What if our autistic, dementia-suffering, or elderly patient populations who cannot travel to unfamiliar clinical research sites could access trials simply by going to their doctors’ offices?
What if the “research deserts” of the world gained access to lifesaving clinical trials not days of travel away but at their convenient, local community healthcare centers?
What if, in the event of a future global pandemic, we had integrated systems in place to direct patients into clinical trials without having to wait for months on end for the clinical research industry to catch up to global demands? In other words: What if we achieved successful healthcare integration (HI) between healthcare and clinical research industries?
Say Hello To “HI”
HI – to introduce yet another clinical research acronym – is the process of incorporating all or some of a clinical trial’s performance(s) at community healthcare centers for rapid, convenient, and efficient translation of clinical technologies.
HI may be performed through innovative telemedicine, supply logistics, and communications between patients, their physicians, and corresponding clinical trial professionals.
As a result, patients remain within familiar healthcare systems that accommodate their needs, clinical trials access the expanded patient populations needed to rapidly enroll diverse patient populations, clinical sites maintain oversight and expertise throughout their communities, and local physicians do not have to refer patients to unfamiliar organizations or become career investigators to offer trial access to their patients.
You Can’t Do That! Can You?
Yes, we can. The FDA clearly defines HCP office utilization in clinical trials with new guidance and the government is promoting such adoptive practices through government grants to promote DCT utility adoption in private sectors.
Per the FDA’s current draft guidance for DCT utility and adoption (FDA May 2023), scheduled for final publication in December 2023, trial participants may participate in all or some of a clinical trial’s activities at local HCP offices1. The HCP is not required to serve as an investigator on the trial, and the overseeing community site, through the PI and delegated personnel, coordinates trial visits and activities remotely.
Data may be communicated via telemedicine methods or entered directly by HCPs. Additional documentation is recommended via newly established “task logs” to ensure complete and accurate records of trial performance and responsible participants, and, identical to current guidance, the community site serves as the responsible location for monitoring, auditing, and trial housing.
Combined, appropriate site-level SOPS with HI study visits create a comprehensive community research environment that is fully compliant and defensible, rapid in startup and enrollment, and brings strengthened community site and local physician relationships.
HI is not only compliant and defensible but also encouraged, promoted even, through United States government grants as a preventive infrastructural measure against future national crises. A recent BARDA grant announcement, D-COHRe, prioritizes the development of technologies, processes, and systems that enhance DCT utility adoption in private healthcare settings in an effort to rapidly respond to future Public Health Emergencies2 (U.S. Department of Health and Human Services 2023).
Such Power! Why Is The Industry Slow To Adopt HI?
The era of COVID created an outlier of rapid technology adoption through desperation. Historically, clinical research at the site level has always been an industry slow to adopt novel technologies.
For example, the FDA has published guidance for the acceptance of electronic signatures and records for over 20 years3, 7,8 (FDA 2003, 2020, 2023). In 2023, direct site discussions and interviews reveal that over half of our sites continue to document and communicate via paper source and unorganized word processing/spreadsheet systems, with a substantial cohort of sites continuing to collect and process paper-based informed consent forms4 (CRPN 2023).
Additional complexities, such as lack of awareness of clinical research as a generalized option, lagging interest from and education of healthcare professionals, the prolonged regulatory uncertainties of industry sponsors, financial incompatibility, and the limited infrastructure, and therefore inability of our clinical research sites to afford and accept new technologies, continue to limit scaled HI adoption.
Beyond logistical hurdles, a financial barrier to fully adopt HI remains. Clinical research and healthcare do not speak the same financial language. While our doctors expect to discuss business in payor combinations and Medicare rates, clinical research communicates resource allocation in fixed contracts and finite rates. As the smaller of the two industries, clinical research must adapt its financial models into a compatible resource language to fully integrate into healthcare systems.
Adoption and acceptance are possible with enhanced education, awareness, financial alignment, and infrastructural development. Successful HI adoption, however, will likely require substantial time and resources to incorporate its concept into everyday community practices.
How Will HI Change The Clinical Research Ecosystem?
HI provides a revolutionary new logistic to allow for diverse and rapid enrollment in aggressive timelines for streamlined, efficient, cost-saving new expectations. Its adoption throughout the industry is not only promoted by regulators and the government for rapid crisis response but also through the necessity to adapt to increased costs and regulations.
The U.S. Congress passed FDORA5 (FDA 2022), which will require sponsors to present diversity plans with every submission. Without an approved waiver, FDORA requires diverse patient population trial enrollments for improved diversity, equity, and inclusion in clinical research. Scientifically, increased diversity may also increase the chances of different biological responses in clinical trials, which will reduce statistically significant power and therefore require increased n values to demonstrate clinical effect.
The increased n values resulting from new diversity requirements will demand additional trial enrollments in diverse populations that are not currently accessible to required levels in the industry’s current infrastructure.
Combine regulatory requirements for increasingly diverse trial enrollments with the skyrocketing costs of the industry’s current trial performances6 (Miseta 2022), and we find the industry’s current processes will not survive regulatory scrutiny or consequential financial requirements.
Thus, HI is not only an efficient response to public health emergencies. It is also the solution our industry needs to meet enhanced FDA DEI requirements and deflating efficiency measures needed to battle the exponentially increasing costs we experience in the current clinical trial economy.
What’s Next For HI?
The FDA publishes its official DCT utility guidance at the end of 2023. Once published, the guidance will provide sponsors the clarity and defensibility needed to build DCT-capable trial visits, and therefore potential HI, into their protocols. DCT-compatible study visits reviewed and approved by IRBs may therefore trigger interest in DCT capabilities among clinical research sites.
New clinical trial DEI requirements combined with DCT-capable protocols will likely make sites that have established DCT protocols, community relationships with healthcare centers, and a reputation for successful DCT visit performance first-choice sites during feasibility and site selection.
As a site, receiving trial awards without having DCT capabilities may be possible in the next five years. However, just as eCOA and electronic medical records continue to increase healthcare and study infrastructural expectations, the ability to attract continued business without adapting to ongoing changes in the industry may be a challenge for sites.
Imagine a world where participating in a clinical trial is just as common and convenient as going to the dentist or a routine doctor’s visit. Healthcare and research records flow seamlessly and synergistically improve technology for everyone. Doctors and administrators won’t know the difference between clinical and research income and their healthcare income. And, through streamlined industry systems, the cost to perform clinical trials reduces along with the costs of new and lifesaving therapies.
It’s not utopian science fiction. It’s now, and healthcare integration processes offer a beginning to realizing this future. We need only create the required community infrastructure and support the concept of HI as a society to once and for all put the “clinical” into “clinical research.”
- 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.
- 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.
- Food and Drug Administration (FDA). 2023. Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations Questions and Answers – Guidance for Industry – DRAFT GUIDANCE. Revision 1. U.S. Department of Health and Human Services. March 2023.
- Clinical Research Payment Network (CRPN). 2023. Confidential Site Profile Questionnaires.
- Food and Drug Administration (FDA). 2022. Food and Drug Omnibus Reform Act of 2022.
- Miseta, Ed. 2022. Site Prices Are Skyrocketing – Here’s Why & What You Can Do About It. Clinical Leader. July 13, 2022.
- Food and Drug Administration (FDA). 2020. Enhancing the Diversity of Clinical Trial Populations – Eligibility Criteria, Enrollment Practices, and Trial Designs – Guidance for Industry. U.S. Department of Health and Human Services. November 2020.
- Food and Drug Administration (FDA). 2003. Part 11, Electronic Records; Electronic Signatures – Scope and Application.
About the Author:
Daniel Fox, MPH, Ph.D., is the founder and executive of the Clinical Research Payment Network, Land of Lincoln Clinical Research, and Save Our Sites Conference and Alliance. He has worked in the translational sciences, from bacteria and animals to pharmaceutical manufacturing, quality control, and clinical site administration, for over 15 years and strives 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. Dr. Fox specializes in legal 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.