Surveys Point Out Major Motivations and Barriers to Trial Participation

Yedida Y Bogachkov PhD avatar

by Yedida Y Bogachkov PhD |

Share this article:

Share article via email
A bottle half-filled with liquid is labeled

Clinical trials are more attractive to people with ataxias — including those with Friedreich’s ataxia (FA) — when they target specific symptoms, such as walking and balance issues; provide potential benefits to patients and others; and cover costs of travel and accommodation, according to a recent study.

These were among the factors patients considered before joining a clinical trial. On the other hand, fear of side effects was among the major barriers to clinical trial participation in this population.

The findings show that clinical trials for people with ataxias should consider patients’ opinions and attitudes in order to recruit and retain participants.

The study, “The attitude of patients with progressive ataxias towards clinical trials,” was published in the Orphanet Journal of Rare Diseases.

Recommended Reading
rare disease clinical trial participants | Friedreich's Ataxia News | Illustration of woman in cape pushing child in wheelchair

Group Focuses on Rare Disease Clinical Trial Participation

Ataxias are a group of rare disorders in which patients lose muscle control and the ability to coordinate movements, such as walking or picking up objects. FA is the most common form of inherited ataxia.

Clinical trial design in these ataxias is often challenging due to low patient numbers, varied disease presentations, and poorly understood disease progression, which prevent the identification of both specific outcomes measures and patient groups more likely to benefit from treatment.

While more sensitive measures and better biomarker tools are not developed to facilitate short-term trials with fewer patients, the trials overall require a large number of patients to determine a meaningful effect from potential therapies.

“Thus, it is important to understand what drives patients at different stages of the disease to participate in trials,” the researchers wrote.

Researchers at the University College London now sought to define the motivations and barriers to clinical trial participation among people with ataxias, as well as their trial preferences, in an attempt to maximize patient recruitment.

The researchers conducted an online survey of 29 questions relating to patient demographics, personal motivation, and preferences for drug therapy and study design. The survey was sent out to members of two major ataxia charities: Ataxia UK and the Friedreich’s Ataxia Research Alliance (FARA).

Among the 342 responders, the majority (204 patients) had FA. The remaining had inherited cerebellar ataxia or idiopathic cerebellar ataxia. Most of the FA respondents (87.7%) were from the U.S.

When asked about the symptoms they would like addressed in future trials, FA patients most frequently reported problems with walking, balance, and fatigue.

Given the importance of walking and balance to patients, future trials might measure accurate changes in these symptoms, the researchers noted, possibly through the use of wearable devices, which were deemed acceptable by 78.1% of respondents and could also reduce the travel burden in trials.

The investigators also suggest that fatigue may be a useful secondary outcome measure for future trials, given the level of importance patients placed on this symptom.

Potential benefits to self and others were among the respondents’ biggest motivators for clinical trial participation. Financial reimbursement, physician recommendation, and physician availability were other motivations for FA patients.

On the other hand, the major barriers to trial participation among FA patients included costs associated with travel, burden of travel, fear of side effects, and the need to stop their current medication.

Overall, people with FA had the greatest interest in participating in future trials, with 73.9% reporting such interest. The only factor significantly associated with interest in a future trial was having taken part in more than one previously.

While the most popular trials for FA patients were Phase 2 (89.5%), over half of them (57.4%) said they would take part in a Phase 1 trial. Fewer patients were interested in joining when a placebo group was involved, but the option of an open-label extension phase — in which patients who were previously on placebo or treatment are given the option to go on or continue the treatment — swayed respondents.

Overall, about 68.9% of FA patients would be very or extremely willing to participate in a placebo-controlled trial if given an open-label extension, compared with 59.5% if the trial did not have an extension part.

Respondents were also asked what the lowest acceptable level of evidence was that would lead to their participation. Across all patients, 44.6% wanted the therapy to show benefit in those with their condition. A minority were OK with benefit seen in animal (16.5%) or cell (13.7%) models of ataxia, and 11.6% were content with a theoretical benefit.

Further analysis revealed that men, those who used walking aids, and those who had been in multiple trials were all significantly more likely to accept a lower level of evidence.

“Desire for a cure may … explain the striking percentage of patients willing to accept what the scientific community would consider low-level evidence for a trial medication,” the researchers wrote.

Recommended Reading
Main graphic for

I’ll Live With the Pity of Strangers and the Love of Loved Ones

Additionally, 75.2% of FA patients were very or extremely likely to enroll in trials for repurposed medications or those proven safe in unrelated conditions. However, about a third of patients were not prepared to receive their medication through an injection into the spinal canal (intrathecal).

A majority of patients, more than 70%, deemed most trial procedures acceptable. However, some procedures, including fasting, scans longer than one hour, overnight hospital stays, muscle biopsies, and lumbar punctures were deemed acceptable by fewer patients.

Also, most respondents (83.3%) indicated that it was important to have the trial results reported back to them, whether through a meeting with a physician or via a lay summary.

This is “the first study to provide comprehensive practical data from a large sample of ataxia patients, relating to the motivating factors for, and barriers to, clinical trial enrollment,” the researchers wrote. “Such data are essential to inform trial design and conduct by clinicians, researchers, advocacy organisations, regulators, and partners in the pharmaceutical industry.”

“We also hope that this study might encourage others working in rare neurodegenerative diseases to gather the opinions of their patients in order that they too may benefit from their perspective on trial designs,” they added.