By: Ivor Clarke - Co-founder - SubjectWell
Pfizer conducted the first randomized virtual clinical trial under an investigational new drug application in 2011.1 Introducing inventive protocol modifications, the Pfizer trial shipped all study drugs to the patients’ homes, required no in-person visits, and data was collected via cell phone and web-based technology. A breakthrough for the healthcare industry, this first step into decentralized clinical trials (DCTs) explored how lowering the patient burden could impact clinical research participation and substantiate the virtual trial model. Pfizer later commented that their first DCT pilot proved to be a learning experience, validating new technology, the utilization of centralized investigators, and gauging patients’ substantial interest in DCTs, but ultimately fell short of recruiting 600 patients from 10 US states.
The outcome of the first virtual trial highlights the persistent challenge faced by clinical research to find patients. And decentralized trials often exacerbate this problem. DCTs minimize the role of sites and remove access to their established patients, an integral and traditional piece of the clinical trial puzzle. With fewer to no sites involved in hybrid and decentralized trials, trial managers and contract research organizations (CROs) will need to replace local patient lists as the primary source for locating trial participants and supplement the high-touch approach needed to shepherd patients through the enrollment process, also previously provided by sites.
This situation leads us to consider two questions:
With the industry already challenged to recruit patients, where will trial participants come from when the site recruiting model is minimized by decentralized and hybrid trials?
Are the DCT benefits to patients and sponsors compelling enough to overcome this lack of access to local patients?
The Existing Challenge: Patient Recruitment is an Ongoing Struggle for Clinical Research
Finding and keeping patients in clinical trials is difficult, and recruitment is not becoming any easier with the trend toward increasingly complex trials. The specificity for inclusion-exclusion criteria in protocols has narrowed, and with this comes an increased regulatory and patient screening burden on the sites.
In other trends impacting recruiting, fewer individuals rely on general practitioners or family practice physicians for their healthcare. This usage shift is driven by millennials, America’s largest generation, 45% of whom do not have a regular primary care doctor and opt for the convenience of urgent care instead.2 Surveys exploring healthcare providers (HCPs) visit frequency, found that US patients with more frequent HCP visits were more likely to participate in a clinical trial.3 And while the number of patient referrals from primary care to clinical trials is modest, fewer patient relationships with family doctors and fewer visits to HCPs in general make this referral pathway less likely.
In terms of medical coverage, despite 92% of the American population having some health insurance, a recent patient survey found that only 55% of individuals from the US ranked their trust in the healthcare system as high.4 Building up a patient’s low trust to convince them to go the extra mile to partake in clinical research will be a challenge.
Additionally, recruitment of diverse communities continues to be an issue. The 2019 census survey data showed the US population to be 13% Black and 19% Hispanic.5 In contrast, the FDA’s Drug Trials Snapshots Report from 2020 reported Black patients underrepresented in clinical trials at only 8% and Hispanic patients at 11%.6 And only recently has the clinical trial industry began to acknowledge and address representation. In 2020 the FDA offered guidance to improve diversity in trials. This issue of lack of diverse representation in trials was laid bare recently, throughout the fast-tracked COVID-19 research. Recent data showed the Black population accounted for 21% of deaths from COVID-19, yet only 3% of Black individuals participated in clinical trials related to COVID-19 vaccines.7
The Shake Up: DCTs Turn Traditional Recruitment Upside Down
With the challenge of patient recruitment as a backdrop, decentralized trials shuffle patient access and ultimately redefine successful recruiting. Traditional recruitment leverages the research site’s existing patient population, adding local and sponsor-driven advertising to augment a geographically focused patient search – usually created on a study-by-study basis.
In contrast, hybrid and decentralized trials reduce site involvement – removing the primary source and geographic focus for patient recruiting. To compensate, DCTs leverage optimized and centralized digital campaigns with an expanded recruiting radius, untethered from site location. To process large patient volumes and prevent delays, centralized referral intake and web-based technologies are needed. Similarly, centralized patient screening and enrollment responsibilities can be supported virtually by trained medical professionals.
DCTs also shake up the management of patient relationships when fewer principal investigators and site coordinators are involved. Ensuring study compliance and attendance at screening appointments and follow-up visits will require new methods. Plus, consideration must be given on how to substitute the consistency and personal touch provided by site coordinators to support patients from screening through consent.
The Upside: DCTs Have Big Patient Appeal and Sponsor Benefits
Less than 10 years after the Pfizer virtual pilot, COVID-19 pulled DCTs to the forefront as in-person restrictions created significant obstacles and challenges for researchers. And it turns out, patients tried and liked the new convenient and patient-centric accommodations, including sending medications directly to homes, engaging with research professionals through telehealth services, receiving care from visiting nurses, collecting lab samples at home, and use of mobile applications.8 For patients, the more flexible the clinical trial, the better.
Through the lens of recruitment, the patient accommodations are a major advantage when presenting a decentralized clinical trial as a care option, if not the ultimate deciding factor. For instance:
- Limiting the number of required site visits lowers travel time, as more than 70% of the American population lives more than two hours away from a research site.9
- By limiting travel time and the number of site visits, patients with inflexible work schedules can now participate.
Like patients, sponsors will also benefit from decentralization. DCTs reduce recruitment hurdles for sponsors looking to reliably enroll patients, increase compliance and reduce drop-out rates. Leveraging mobile applications for data collection lowers the patient burden, with the sponsor upside of increasing compliance, collecting real-time data, and the opportunity to build a higher quality data set. With the removal of the geographic boundary imposed by site locations, decentralized trials expand access to a larger and more diverse patient population, who were not previously candidates for clinical research solely due to their location.
The removal of a geographic boundary also changes the type of advertising and outreach needed to reach patients. DCTs enable the redirection of recruiting efforts from traditional, local advertising to partnering with specific online patient advocacy groups to find qualified candidates. This approach strengthens relationships with care-groups, which had not been a priority previously.
The Outcome: What We Can Expect for DCTs in the Future
The future of DCTs comes with a slew of unknowns, including post-COVID adoption rates. Drug-based interventional DCTs grew at an annual rate of 7% between 2014 and 2019.10 After the onset of COVID-19, between the second halves of 2019 and 2020, the growth rate for DCTs jumped to 77%, according to data from more than 1,000 trials.10 A 2020 global survey reported North America as the decentralized trial epicenter with the most reported DCTs and one of the regions with the fastest increase in DCT adoption, with 76% of survey respondents reporting that at least some of their trials have already been decentralized.11 The same year, the FDA responded to the trend, announcing the new Digital Health Center of Excellence to advance the use of digital health technology, including mobile health devices and wearables in the study of medical products. Patient demand, industry adoption and FDA support all point to decentralization as a permanent addition to clinical research, despite the challenges to traditional, site-based recruitment and engagement.
In response, a number of successful DCT startups and large CROs with DCT focused business units launched technical platforms and services to support decentralization and address the widening recruitment gap created by decentralization. The multitude of possible solutions will likely have overlaps and adjacencies, with new products, vendors, and technologies driving both innovation and confusion simultaneously. It will become exceedingly important during these times to stay focused on the needs and desires of patients and implement as many practices as possible to help not only find but keep these patients.
Monitoring the success of the varying DCT strategies and platforms will be crucial. In addition to staying patient-centric, DCTs will need to address existing recruiting and retention issues, expand access to a broader array of patients (including diverse communities) and reduce the amount of time to last patient in without adding substantially to trial cost. However, it will also be important to consider which enrollment interactions should take place in person and which would benefit from the move to a decentralized process.
We are at the beginning of the rise of decentralization, but as the clinical trial industry has demonstrated year after year, technologies and tactics will evolve to meet the ever more complex and growing demand for clinical research. Particularly concerning patient recruitment, DCTs could be the foundation needed to finally include a greater portion of the population in clinical trials.
References
- Pfizer conducts first “virtual” clinical trial allowing patients to participate regardless of geography. Press release. Pfizer; June 7, 2011. Accessed July 8, 2021. https://www.pfizer.com/news/press-release/press-release-detail/pfizer_conducts_first_virtual_clinical_trial_allowing_patients_to_participate_regardless_of_geography
- Boodman S. Spurred by convenience, millennials often spurn the ‘family doctor’ model. KHN. Posted October 9, 2018. Accessed July 8, 2021. https://khn.org/news/spurred-by-convenience-millennials-often-spurn-the-family-doctor-model/
- Clarke I. Higher frequency of HCP visits in the US correlates to greater likelihood of clinical trial participation. SubjectWell. July 6, 2021. Accessed July 8, 2021. https://www.subjectwell.com/news/higher-frequency-of-hcp-visits-in-the-us-correlates-to-greater-likelihood-of-clinical-trial-participation/
- Keisler-Starkey S, Bunch L. Health insurance coverage in the United States: 2019. United States Census Bureau. P60-271. Published September 15, 2020. Accessed July 8, 2021. https://www.census.gov/library/publications/2020/demo/p60-271.html
- United States Census Bureau. 2019 US Census. Accessed July 8, 2021. https://www.census.gov/quickfacts/fact/table/US/PST045219
- U.S. Food & Drug Administration. 2020 Drug Trials Snapshots Summary Report. Accessed July 8, 2021.
- Warren R, Forrow L, Hodge Sr DA, Truog RD, Trustworthiness before trust – Covid-19 vaccine trials and the black community. The New England Journal of Medicine. 2020. Accessed July 8, 2021. https://www.nejm.org/doi/full/10.1056/NEJMp2030033
- Clarke I. SubjectWell and Reify Health survey clinical trial sites, examined patient concerns and site safety protocols in the face of COVID-19. Press release. SubjectWell; October 7, 2020. Accessed July 8, 2021. https://www.subjectwell.com/news/subjectwell-and-reify-health-surveyed-clinical-trial-sites-examined-patient-concerns-and-site-safety-protocols-in-the-face-of-covid-19/
- Tenaerts P. Can decentralized clinical trials improve patient diversity? The Association of Clinical Research Professionals blog. Posted April 16, 2021. Accessed July 8, 2021. https:// acrpnet.org/2021/04/16/can-decentralized-clinical-trials-improve-patient-diversity/
- Gao,F. Why Decentralized Clinical Trials Are the Way of the Future. Applied Clinical Trials. Posted April 5, 2021. Accessed July 8, 2021. https://www.appliedclinicaltrialsonline.com/ view/why-decentralized-clinical-trials-are-the-way-of-the-future
- Chancellor C. Decentralized and hybrid trials 2020. Pharma Intelligence Informa. July 21, 2020. Accessed July 8, 2021. https://pharmaintelligence.informa.com/resources/product-content/sitecore/shell/~/media/informa-shop-window/pharma/2020/covid-24-campaign/slides/decentralized-clinical-trials-in-2020.pdf
Ivor Clarke is CEO and co-founder of SubjectWell, the risk-free clinical trials marketplace for patient recruitment. Since 2012, SubjectWell has been raising awareness about the benefits of clinical research and engaging the 96% of Americans who have never participated in a clinical trial. Ivor has over 12 years of C-suite experience in online marketing and specializes in the creation/ operation of enterprise SaaS solutions. Before SubjectWell, Ivor served as President of Brightfire, a digital marketing startup.
Subscribe to our e-Newsletters
Stay up to date with the latest news, articles, and events. Plus, get special offers
from Pharmaceutical Outsourcing – all delivered right to your inbox! Sign up now!