Decentralized clinical trials allow researchers to connect with patients across the country and the world. In the case of treatments for rare diseases, decentralized trials can increase participation and create safer, more comfortable experiences for patients.
However, there is still a burden on clinical research organizations (CROs) and sponsors to choose ideal trial sites. The wrong site can corrupt the data and put the entire trial at risk. Here are a few key considerations for early-stage trial site selection.
Clinical research organizations and sponsors use a variety of criteria to evaluate a site. These evaluations contain a set rubric to rate a site for feasibility and risk. The main goal of CROs and sponsors is to decrease risk as much as possible so potential resources don’t go to waste because the data gets thrown out.
Oncology CRO Medelis sets out their top criteria when searching for an early phase clinical trial site, the key features of which include:
Working with a site that has previous experience in phase 1 trials significantly reduces the risk compared to bringing on a new trial provider. The recognizable name might also increase recruitment, decreasing the chances the trial is terminated due to a lack of available patients.
Certainly these rankings aren’t perfect, no matter how CROs hone and improve them.
“Site rankings according to a criteria has limitations,” write Vadim Paluy of Novartis. “For example, site selection based on sorting of predicted enrollment rates does not take into account parameters like cost per patient, site capacity, or ‘soft’ attributes such as experience of [principal investigator], facility quality, etc.”
New sites can also be limited by a lack of historical data, which puts them at a disadvantage over more established locations.
So what else should clinical trial leaders look for in a key early-stage site? Across the board, there are a few key factors that come into play with most trials, regardless of the targeted disease or treatment plan.
A well-developed trial is only as good as the people running it. The staff you work with can have a significant impact on the data and the quality of care offered to patients. “Poorly qualified staff may require more precise monitoring and this, in turn, affects the costs, time, and patient recruitment efficiency,” according to consulting organization Credevo.
You can look at the numbers to see just how much is riding on the staff at your chosen clinical trials sites. As a whole, the cost of site selection is relatively small in the overall budget of clinical trials. Patricio Ledesma, head of clinical operations at Sofpromed, estimates that site selection in the U.S. costs around $8,000. However, a poor site can create long-term issues for CROs and sponsors. Ledesma budgets $188,000 for site management and that can increase if teams aren’t properly trained or can’t supply clean and accurate data.
This is why trial leaders look for organizations with previous experience and past success in their field and in similar clinical trials. The right site selection can reduce the amount of oversight required throughout the process.
A significant aspect of quality staffing is the team’s ability to follow protocol. Deviating from the given processes can corrupt the data and put patients at risk. This is particularly important for decentralized clinical trials, where the trial leaders can’t supervise each patient meeting to make sure protocols are followed.
“Protocol deviations can pose potentially serious threats to the overall success of a Phase 1 clinical trial,” the team at WCCT Global explains. “This being the case, sites should be doing all they can to prevent these risks before they occur. This involves a detailed analysis of the protocol and top-level insight from all who will be involved with the study.”
Also keep in mind the differences between phase 1 trials and trials from other stages. The data set is already small, which means the research team can’t afford to discard significant results.
Clinical sites vying for trials can prove their value by showcasing their patient accessibility. With trial participation overall at already low rates, CROs and sponsors can’t afford to choose a site that won’t be able to drum up enrollment from qualified participants.
This is where some hospitals and research groups are getting creative. For example, transportation is often cited as one of the biggest barriers to clinical trial enrollment, with 42 percent of patients citing travel as a major factor in their enrollment.
In 2019, Dartmouth-Hitchcock Medical Center was awarded a seven-year grant to bring cardiovascular clinical trials to residents in rural Maine and New Hampshire. This grant can prevent trials from termination due to low enrollment while making care more accessible for rural residents. It makes their organization more desirable because they can access more patients for trials.
Trial transportation time and costs aren’t the only obstacles faced by trial participants. Asking patients to travel when they have medical conditions or complications is no easy feat. The farther or more difficult the trip, the greater the potential risk to their health.
“What is often overlooked are the exposures faced by subjects who may need to travel, sometimes between countries, to participate in a study,” says Daniel Brettler, managing director, SVP, and life science practice leader at Conner Strong & Buckelew Insurance. “Increasingly, sponsors are including provisions in their consent documents that obligate them to address injuries or illnesses for subjects and companions/caregivers that might arise during the journey to or from the trial site.”
CROs need to cover more than just travel costs and accommodation during the trial. They also need to ensure the patients will arrive safely or will be cared for if something happens along the way.
Decentralization has exponentially increased the need for digital tools and resources. If a medical center lacks the latest technology, it can slow down the trial or limit the available data.
“Determining a site’s digital readiness is essential, as the pandemic seems to have created the opportunity for access to a broader range of patients, beyond those who live near a site, to include those in rural or in lower income areas, allowing sponsors to meet diversity and geographic targets,” says medical writer Ann Neuer.
Of all the considerations associated with site selection in clinical trials, the patient experience is still one of the most important.
“Patient advocacy groups’ expertise should be solicited, particularly for the more complex therapeutic areas and trials,” writes Erin Stanley at Halloran Consulting. “We know from experience that identifying sites capable of supporting a rare disease population is more nuanced than identifying sites capable of supporting patients with diseases of higher prevalence.”
Patients and caregivers can provide information as to what they value in different experiences to help CROs establish ideal test site locations.
Many patients are willing to share their ideal clinical trial situations. Global healthtech company Xperiome created a knowledge bank for the lived experience of rare disease, called Raremark. They surveyed people with various rare conditions about their views on decentralized clinical trials and found the vast majority of trial participants want to attend a mix of clinical visits, at-home visits, and appointments with their regular doctor or specialist.
Furthermore, 87 percent of patients surveyed had no concerns about decentralized clinical trials. Raremark concludes that it’s in the best interest of CROs to bring the research to the patient instead of requiring them to travel to the trial site.
As more studies become decentralized and more remote tracking options are available, clinical trial participants themselves should be able to set up a study based on their needs and preferences, while still maintaining the data quality the CRO needs.
“A study that is truly ‘patient-centric’ would allow the patient to choose their own adventure,” says Craig Lipset, founder of Clinical Innovation Partners. This means that patients could choose how often they want to visit trial clinics versus their traditional doctors. Patients that could participate at home more would if that made them feel safer and more comfortable.
There is no magic formula for early-stage site selection. CROs constantly evaluate where their trials should be held and why. By focusing on core values, teams can choose the best possible trial sites for patients and for data quality.