Researchers Share Strategies to Improve Clinical Trial Recruitment

Publicity in national news outlets and an online self-screening questionnaire helped improve recruitment for a clinical trial in secondary progressive multiple sclerosis (SPMS), a new study highlights.

“We have described our experience of recruiting participants with SPMS into two large RCTs [randomized clinical trials] in order to identify areas where the efficiency of recruitment could be improved,” researchers wrote.

The study, “Optimising recruitment in clinical trials for progressive multiple sclerosis: observational analysis from the MS-SMART and MS-STAT2 randomised controlled trials,” was published in Trials.

Clinical trials are the gold standard for determining whether a potential treatment works or not. To conduct robust trials, researchers need to recruit participants who match trial criteria and are willing and able to participate. This process is often slow, which contributes to trial delays.

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A team led by scientists at University College London (UCL) shared lessons learned from recruiting SPMS patients into two clinical trials sponsored by UCL. The data were restricted only to participants recruited at UCL, about one-third of the total patients in both trials.

One trial, a Phase 2b study called MS-SMART (NCT01910259), recruited SPMS patients between February 2015 and May 2016. The trial was testing three potential treatments, but results failed to show benefits for any of the treatments.

The other study, the MS-STAT2 Phase 3 trial (NCT03387670), opened in May 2018 and finished recruitment of nearly 1,000 SPMS patients in September 2021. The ongoing study is testing whether a cholesterol-lowering medication called simvastatin can slow disability progression in SPMS; results are expected in 2025.

Recruitment processes were generally similar in both trials — potential participants would express their interest, then undergo a screen for eligibility. In both studies, the majority of patients expressing their interest were referred through an online portal.

“An online portal therefore appears to be an important aspect for recruitment in multi-centre trials in progressive MS,” the researchers wrote.

In MS-SMART, the resulting referrals were screened mainly via phone calls from researchers. Based on this initial experience, the researchers introduced a self-screening questionnaire into the online portal in the latter MS-STAT2 study, in addition to the phone-based screening.

Refining recruitment tools

This questionnaire “facilitated the early identification of many potential participants who were unlikely to be eligible for the trial,” the team wrote. Out of 4,605 entries in the online portal, 3,080 (67%) of the patients were automatically informed that they were not eligible for the study — mainly due to age or travel restrictions.

“Contacting 3000 ineligible patients would have been an enormous use of precious resource,” the researchers wrote. “Empowering candidates to quickly determine their own eligibility also importantly avoids the inevitable dissatisfaction of ineligible patients waiting many weeks to be contacted by a member of the trial team.”

Despite the use of this self-screening, only 40% of potential participants in MS-STAT2 were deemed eligible for the study after a screening call with a researcher. A similar proportion (39%) of eligible participants was reported in MS-SMART.

“With each pre-screening discussion typically taking up to 30 [minutes], across the two trials, we estimate over 500 [hours] of specialist clinician time was spend discussing the studies with ultimately ineligible candidates,” the researchers wrote.

As a possible explanation for similar rates of eligibility, the team noted that only 51% of patients in MS-STAT2 were referred through the online portal, so the other 49% did not complete the self-screen.

Based on these findings, the scientists recommended that “all potential participants, regardless of their referral source, should be directed to a mandatory trial online portal, including a self-screening questionnaire.”

The team also noted that for patients ultimately deemed ineligible, the most common reasons were related to logistics and travel. They highlighted the importance of including details about travel requirements in the self-screen questionnaire.

“The number of appointments requiring face to face attendance should be detailed. … Potential participants should then be asked to indicate, as part of self-screening, whether they feel able to meet the burden of visits required by the trial, and whether they have considered the logistics of regular travel to the trial sites,” the team wrote.

In MS-SMART and MS-STAT2, the final stage before enrollment was an in-person assessment. The percentage of patients who attended these meetings was 75% in MS-SMART, and 94% in MS-STAT2. This difference was mainly attributed to reminder texts before the meeting being incorporated in the latter trial.

While the MS-STAT2 trial was recruiting, a number of local and national events were put on to publicize the study. Analyses of online portal entry completions showed marked spikes when the trial was publicized nationally (on BBC) and some smaller spikes when it appeared in newspaper stories, whereas local events showed no clear effect.

“This suggests that for large trials, publicity efforts should be focussed on achieving coverage in national media outlets,” the researchers concluded.