The attitude of patients with progressive ataxias towards clinical trials

Abstract

Background The development of new therapies may rely on the conduct of human experimentation as well as later clinical trials of therapeutic interventions. Ethical considerations seek to protect the patient from risk but few have sought to ascertain the attitude to such risk of patients with progressive debilitating or terminal conditions, for which no mitigating or curative therapies exist. Such understanding is also important if recruitment is to be maximized. We therefore sought to define the motivations for and barriers to trial participation amongst patients with progressive ataxias, as well as their condition-specific trial preferences. Methods We conducted an online survey consisting of 29 questions covering four key domains (demographics, personal motivation, drug therapy and study design) relating to the design of clinical trials. Two major ataxia charities, Ataxia UK and the Friedreich’s Ataxia Research Alliance (FARA) sent the survey to their members. Responses were analysed by disease and by ambulatory status. Results Of 342 respondents, 204 reported a diagnosis of Friedreich’s ataxia (FRDA), 55 inherited cerebellar ataxia (CA) and 70 idiopathic CA. The most important symptoms to be addressed by a trial were considered to be balance problems and ambulation, although these were superseded by speech problems in wheelchair users. Common motivations for participation were potential benefits to self and others. Reasons for non-participation included concerns about side effects, and the burden and cost of travel. Financial reimbursement for expenses was reported to be likely to increase trial engagement, Phase two trials were the most popular to participate in, and the use of a placebo arm was seen as a disincentive. Across all disease subgroups, drug repurposing trials proved popular and just under 70% of participants would be prepared to undergo intrathecal drug administration. Conclusions Knowledge of motivations for and barriers to trial participation as well as the acceptability of investigations, time commitments and routes of drug administration should inform better, more patient focused trial design. This in turn may improve recruitment and retention of participants to future trials.

Preferences for genetic interventions for SCA and Huntington’s disease: results of a discrete choice experiment among patients.

“…Two previous studies used a survey to get insight into SCA and HD patients' preferences regarding genetic interventions in the hypothetical context of a clinical trial (19,20). These qualitative studies showed that patients are willing to undergo genetic interventions, and the potential bene t is a common motivation to participate in a trial with genetic interventions (20). However, the likelihood of patients with HD to enroll in a trial lowered in scenarios with more invasive surgical interventions (19), while respondents in the current study preferred a single operation over repeated lumbar punctures.…”

“…Since the search led to only two relevant results, the search was extended by also including studies of other neurodegenerative disorders. In total, four papers were eligible and data regarding different characteristics of genetic interventions were extracted in an Excel spreadsheet (19)(20)(21)(22). Second, a list of possible relevant attributes was made by the rst author, based on the results of the literature review.…”

Impact of ataxia aetiology on self-reported mental health, fatigue, cognition and ataxia symptom severity

“…Considering this is a brief tool which could be administered online, it has potential for remote monitoring of ataxia symptomology for patients and supporting online recruitment for research. This is particularly advantageous considering the difficulties with recruiting patients with ataxia into trials and may mitigate some of the barriers such as the burden and costs of travel to clinics [27]. Due to the significant differences between participants with ataxia and healthy controls on the PROM-Ataxia-SF, it may also have a role in informing diagnosis.…”

Quantitative speech assessment in ataxia- Consensus recommendations by the Ataxia Global Initiative Working Group on Digital-motor Biomarkers

“…This may be due to the relatively limited in uence of speech on overall scores in commonly used disease severity scales (i.e., SARA, ICARS, mFARS) (21). On the other hand, speech is considered key feature for measurement in patients [https://www.ataxia.org/ataxiapfdd/], becoming the most important quality of life when individuals become non-ambulant (22,23). When it is examined, published cohort studies are often small and restricted to specialized centres which are informative, but their generalizability is limited.…”