The Future of Clinical Trials is Virtual
The COVID-19 pandemic has caused significant disruption to global clinical research. By some accounts, enrollment into clinical studies was down nearly 70% in the early months of the pandemic. [1] The post COVID-19 world presents a very different set of operational considerations for sponsors, including a renewed focus on ways to make clinical trials more patient-centric, reducing overall risks to patients and research staff, while reducing persistent inefficiencies within the clinical research process. In our view, a virtual trial framework addresses all of these important considerations. A virtual clinical trial is one where patient assessments and data collection do not occur in traditional settings, but instead are facilitated via remote interactions.
Inefficiencies are already considerable within clinical research, with 85% of money spent on recruitment wasted according to a 2009 estimate. [2] The reasons for this are many, but trial design and methodology limitations, in addition to poor recruitment and retention contribute significantly. [2-4] In our view, virtual trials can help to significantly address these problems. Virtual trials take full advantage of technology to assist with the conduct of each stage of the clinical trial including recruitment, informed consent, preliminary participant screening through to measurement of clinical endpoints and monitoring for potential adverse events.
Responding to COVID-19, the Food & Drug Administration (FDA) has developed guidance to protect both participants and research staff by advocating for remote data collection. [5] Before the pandemic, the virtual evolution of clinical trials was already well underway. Over 1,170 studies starting in 2017 and registered on clinicaltrials.gov incorporated connected digital products to facilitate remote data collection. [6] While in many cases necessitated by COVID-19, incorporating virtual design elements within a clinical trial can provide important ancillary benefits. Dr. Stephen Hahn, the FDA commissioner, recently supported retaining aspects of virtual trials post-COVID-19: “It could really help us expedite and maybe we get that cycle time even shorter if we use some of these processes moving forward.” [7]
Better Participant Recruitment and Retention
Empirical reviews identifying barriers to traditional clinical trials highlight that one factor in poor recruitment and retention rates are the burdens placed on participants through in-person visits or procedures. [8,9] In-person visits may place financial, physical, and time pressures on individuals, leading to reduced participation and greater loss from follow up. [8,9] Early feasibility studies using remote participant visits demonstrated high satisfaction with participation, and increased willingness and ability to participate in trials with remote data collection. [10]
Virtual trials also confer additional benefits by facilitating more efficient recruitment while positioning the primary research team at one central location. This can decrease associated administrative burdens and lead to faster initiation of the trial. With technology, we can engage patients from a broader geographical span, ensuring more diverse and representative enrollment and help manage trials with greater ease and accuracy, and in turn rely more directly on data from validated digital sources. Taken together, these benefits expedite the conduct of clinical trials and keep the costs lower than traditional research approaches.
Longer-term retention challenges can also be addressed through the implementation of virtual trials. Overall adherence and engagement can be increased and retention may be higher because of the ease of an in-home, digital experience versus having to regularly travel to sites and manually document changes in baseline health.
Collection of Novel Outcomes & Biomarkers
The decentralisation of trial design widens the scope for collecting novel outcomes and biomarkers. These measures can be defined according to where (healthcare setting vs at home) and how (in-person vs. fully virtual) the data is collected. [11] Moving into the community and reducing researcher input can facilitate near-continuous data collection complementing endpoints traditionally captured through on-site visits.
The virtual trial framework is particularly well-suited for the development of digital therapeutics. Digital therapeutics by their nature must be studied and validated in a real- world setting to provide representative data. Interestingly, the digital therapeutic itself can serve as both an intervention to be studied and a research tool by generating novel continuous participant data.
Overcoming the Challenges of Virtually Collected Data
Remote data collection has limitations however and can generate its own problems. Arguably the most important aspect of trial design is hypothesis generation and sponsors need to ensure that their methodology is hypothesis-driven, rather than by the availability of technology. For some clinical questions, remote data collection may not be appropriate. Furthermore, while it may be acceptable to collect certain endpoints remotely, an appropriately validated instrument may not exist.
Finally, because study data is often coming from several different sources (eCOA, central labs, in-app), it is imperative that the sponsor and CRO have systems in place that can accurately integrate and process the information, yielding reliable study data for the patient, provider, payers as well as regulatory bodies. This challenge of remotely captured data-integration is often underestimated and requires a focused collaborative approach amongst the various partners to deliver a seamlessly integrated solution.
Embracing the Future of Clinical Research
The current disruption to clinical research presents a clear inflection point, introducing an opportunity to adopt novel technologies and methodological approaches to improve clinical trials. The benefits of virtual trials extend to patient recruitment, engagement, retention, and data collection with a favorable overall impact on trial duration and associated costs. It is imperative that we embrace these opportunities for innovation as we transition to the new normal of the post-COVID world.
Footnotes:
(1) E. Cahan, Science Magazine, Clinical trials rebound after COVID-19 crash, but can enrollment gains continue? https://www.sciencemag.org/news/2020/07/clinical-trials-rebound-after-covid-19-crash-can-enrollment-gains-continue
(2) Chalmers I, Glasziou P. Avoidable waste in the production and reporting of research evidence. The Lancet. 2009; 374 (9683): 86-89
(3) Fogel DB. Factors associated with clinical trials that fail and opportunities for improving the likelihood of success: a review. Contemporary clinical trials communications. 2018; 11 156-164.
(4) Heneghan C, Goldacre B, Mahtani KR. Why clinical trial outcomes fail to translate into benefits for patients. Trials. 2017; 18 (1): 122.
(5) de Paula BH, Araújo I, Bandeira L, Barreto NM, Doherty GJ. Recommendations from national regulatory agencies for ongoing cancer trials during the COVID-19 pandemic. The Lancet Oncology. 2020; 21 (5): 624-627.
(6) Marra C, Chen JL, Coravos A, Stern AD. Quantifying the use of connected digital products in clinical research. NPJ Digital Medicine. 2020; 3 (1): 1-5
(7) Baumann J. Clinical Trial Tweaks Forced by Virus Should Stay, Hahn Says. Available from: https://news.bloomberglaw.com/pharma-and-life-sciences/clinical-trial-tweaks-forced-by-virus-should-stay-hahn-says.
(8) Ross S, Grant A, Counsell C, Gillespie W, Russell I, Prescott R. Barriers to participation in randomised controlled trials: a systematic review. Journal of clinical epidemiology. 1999; 52 (12): 1143-1156.
(9) Naidoo N, Ravaud P, Young B, Amiel P, Schanté D, Clarke M, et al. The research burden of randomized controlled trial participation: a systematic thematic synthesis of qualitative evidence. BMC medicine. 2020; 18 (1): 6.
(10) Dorsey E, Wagner JD, Bull MT, Rizzieri A, Grischkan J, Achey MA, et al. Feasibility of virtual research visits in fox trial finder. Journal of Parkinson’s disease. 2015; 5 (3): 505-515.
(11) Coravos A, Goldsack JC, Karlin DR, Nebeker C, Perakslis E, Zimmerman N, et al. Digital medicine: a primer on measurement. Digital Biomarkers. 2019; 3 (2): 31-71.
(12) Adams JL, Dinesh K, Xiong M, Tarolli CG, Sharma S, Sheth N, et al. Multiple wearable sensors in Parkinson and Huntington disease individuals: a pilot study in clinic and at home. Digital Biomarkers. 2017; 1 (1): 52-63
