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Sites not expected to fade away even as DCTs continue to grow past COVID-19.
By now, the pharmaceutical industry knows decentralized clinical trials (DCTs) are here to stay. DCTs offer many benefits, including helping sponsors reach broader and more diverse patient populations. In an article published last year in Applied Clinical Trials, we noted ZS’s DCT database shows the number of DCTs reported on clinicaltrials.gov increased by 77% between 2019 and 2020—and grew another 34% between 2020 and 2021. We also discussed that multiple studies have demonstrated that DCTs can improve enrollment and retention rates.
While DCT growth accelerated during the pandemic, this trend will outlast COVID-19. ZS’s patient burden collaboration with the Tufts Center for the Study of Drug Development showed that most patients indicated decentralized trial services such as home nurses and home technology will reduce trial burden. And in our March 2021 industry roundtable, most sponsors suggested that decentralized or hybrid clinical trials will become mainstream in three to five years.
As DCT growth continues, clinical trial sites are not expected to fade away. Rather, they will play a critical role in the decentralization process and are evolving through investment in DCT services such as home health and direct-to-patient investigational products, and in supporting technologies such as eConsent, ePRO, telemedicine platforms and wearables.
Though sites are adapting to DCTs, the levels of experience and capabilities they offer can vary significantly. A 2021 Society for Clinical Research Sites (SCRS) survey indicated that only approximately one in four sites offered each type of decentralized service. This means there are few one-stop-shop sites for DCTs, and sponsors will need to rely on a robust site selection process to find sites with the right DCT capabilities and experience to meet their needs. Furthermore, they will need to segment sites by capability and experience to understand which sites would need training, resources and additional sponsor support during activation.
Without the ability to identify sites with the right experience, capabilities and willingness to conduct DCTs, studies could be time-consuming, costly or prone to fail. Additionally, sponsors could miss out on partnering with sites that are a good fit for the trial. For example, in our recent analysis of sites suitable for decentralized Parkinson’s disease trials, we identified two institutes that were similar in the traditional sense, each having more than 20 years of clinical trial experience in the disease area. However, only one had participated in trials in which home health, eCOA, ePRO, eConsent or remote monitoring were offered. In a traditional site selection process, sponsors would have similarly ranked both sites, but with additional insight, it’s clear these sites would perform very differently in a DCT.
Unfortunately, some sponsors are experiencing pitfalls. Some do not have visibility into site readiness for DCTs and are taking the same approach to site selection for DCTs as they would for traditional clinical studies. In one case, we saw a major pharma sponsor plan a fully decentralized study but then err by selecting traditional sites without the proper DCT experience. Not surprisingly, this presented major obstacles during the study. The sponsor likely is not alone, making it imperative that sponsors act now to modernize their site selection processes.
For sponsors to identify and select the right sites for their DCTs, a critical first step is to look holistically at how the strategic planning and site selection processes can be “DCT-compatible.”
First, sponsors must layer a DCT readiness analysis into the existing site selection process and include metrics that assess a site’s willingness, experience and capabilities to conduct DCTs. While traditional site selection metrics look mostly at physician and patient access, therapeutic area experience and site enrollment performance, sponsors will need to augment these metrics with ones specific for DCTs.
Sponsors also should update weighting to account for the importance of the new metrics. For example, if emerging sites are heavily equipped for DCTs but have not had a chance to demonstrate their capabilities in trials, they will not receive a fair chance if too much weight is placed on historic indicators. Thus, any DCT metrics added must include the option to put more or less weight on key metrics so that site scoring is aligned with the objective of the analysis.
While we expect there will be “must-partner” sites with both strong DCT and traditional readiness, sponsors will need to determine how to use less-than-optimal sites to meet specific patient population needs and study goals such as improvement in enrollment rates, patient experience, diversity, equity and inclusion.
DCT readiness assessments should help sponsors select the right sites and help them segment sites based on potential experience and capability gaps. During site activation, sponsors will have the opportunity to provide resources and support such as DCT training and relevant technology. This also will accelerate sites’ adoption of decentralized studies.
Accommodating novel operating models
To further complicate the landscape, sites are partnering with new industry players to adopt novel operating models designed to bridge critical gaps in clinical trial operations. They’re aiming to reach highly qualified patients in a more targeted manner than what is offered by social media and traditional sites. They also want to offer better access to patients in remote areas or underserved populations.
One noteworthy model is the integrated research organization (IRO), which involves patients’ regular physicians in all stages of clinical research. This enables more targeted recruitment and retention of patients who are highly qualified for the trial. Furthermore, the IRO model also can lead to better patient diversity by leveraging the relationship between the physician and the patient if the IRO has a strong presence in institutions and community clinics in underserved areas. In our recent article, “How to recruit more diverse clinical trial participants,” more than half of underrepresented patients surveyed indicated they would be more comfortable if the trial principal investigators were the doctor they see regularly.
A decentralized research organization (DRO)—such as Care Access or Emvenio Research (previously Matrix Medical Network)—is another model that can improve recruitment, retention and diversity by bringing trials closer to target patients who were once considered inaccessible. This can be accomplished by using “sites on wheels,” which include mobile investigation teams, on-demand sites and local clinics and pharmacies.
While emerging site operating models are vastly different, one similarity is that most sponsors are not assessing the benefit-to-cost ratios of partnering with these organizations for a trial. This could lead to two scenarios, neither of which are optimal. The first is underusing these new site models, which could possibly cause enrollment, retention and diversity metrics to fall short and bring about less effective patient targeting. The second is overusing trials that do not necessitate these services to meet their recruitment needs, which could lead to unnecessary cost increases.
While we expect most clinical trial sites will continue to be chosen through a site selection process adapted for DCTs and hybrids, we also anticipate a growing percentage of sites will come from partnerships with organizations such as IROs and DROs. Sponsors will need to keep important considerations in mind as they navigate this more complex site landscape.
The first is site strategy. Sponsors must look holistically at their strategic planning processes and site strategy frameworks to ensure they are current and able to assess if novel services should be utilized. It’s critical for sponsors to cover both of the following scenarios as part of their assessment:
For each scenario of the site strategy, sponsors must assess the benefit-to-cost ratio of increasing the percentage of sites chosen through IRO and DRO partnerships for trials. For example, through correlations of how IROs and DROs quantitatively benefit enrollment, retention and diversity, estimate the ratio of quantifiable benefit against any cost premiums.
With DCTs and emerging operating models such as IROs and DROs, the future of clinical trials is here. Now is the time for sponsors to update their site selection strategies to realize the benefits of these new site offerings. For sponsors wondering where to begin and how to ensure success in modernizing site strategies, the following considerations are critical to success.
First, a good starting point is to understand what data is available to provide the insights needed for transformation. For example, does in-house and third-party public data exist to identify trials and sites that have leveraged DCT technologies? What pricing information and correlations between new site operating models and patient recruitment, retention and diversity are available?
Another consideration is how this data will inform budgets and resourcing for DCTs and hybrid trials. It is common for sponsors to assume that both patient facing and non-patient facing hours for sites will decrease with DCTs and hybrid trials, but this is not always the case. According to the 2021 SCRS site survey, sites cited adverse event reporting, screening failures and start-up costs as the top underfunded areas in the trial budget. This data would be critical, for example, to accurately assess the benefit-to-cost ratios of DCTs and hybrid trials, and to inform the trial budget.
It’s also important to understand how can sponsors use that data to improve their site selection decision-making. For example, what analytics and key performance indicators are needed to reveal the best sites for a sponsor’s trials? Is it easy to provide sound justification for partnerships with new research organizations? It’s critical to define study execution expectations and to identify and address potential risks for monitoring and capability gaps, so that sponsors can adequately support the sites with needed technologies and services to execute DCTs and hybrid trials.
Sponsors and sites are driven to improve the patient experience, operational efficiency and patient diversity in clinical trials. For these commitments to materialize, sponsors must enhance their approaches to site selection, engagement and partnerships. Let’s work together to enable a future where clinical trials include the right patients, and let’s meet them where they are.
Fan Gao, PhD, MS, is part of the ZS R&D excellence leadership team. She leads the digital and DCT vertical in clinical development.
Mike Martin leads ZS’s global clinical development practice area.
Arnab Roy is a leader in ZS’s R&D excellence practice area and leads the development and global commercialization of ZS's DCT strategy and analytics solutions.
Ankur Vasudeva is a leader in ZS’s R&D excellence practice area and leads strategy and analytics work in the areas of DCT and clinical feasibility.
William Chaplin and Kevin Peng are consultants for ZS's R&D excellence team and members of the digital and DCT vertical in clinical development.