The patient\u2019s view on rare disease trial design \u2013 a qualitative study

C M W Gaasterland,M C Jansen – Van Der Weide,O Timmis,M Donk,M J Du Prie – Olthof,K Leeson-Beevers,C Lavery,M M Kaatee,R Kaczmarek,E Vroom,J H Van Der Lee,V Van Nederveen,N O’Neill

doi:10.1186/s13023-019-1002-z

Abstract

BackgroundClinical trials in rare diseases are more challenging than trials in frequent diseases. Small numbers of eligible trial participants, often complicated by heterogeneity among rare disease patients, hamper the design and conduct of a ‘classical’ Randomized Controlled Trial. Therefore, novel designs are developed by statisticians. However, it is important to be aware of possible design aspects that may jeopardize the feasibility of trial conduct. If the burden of participation is considered out of proportion by patients or parents, recruitment may fail or participants may drop out before trial completion. In order to maximize the chance of success of trials in small populations, it is important to know which aspects of trial design are considered important by patients.ResultsWe have interviewed all ten members of the Patient Think Tank (PTT) of the ASTERIX project, a European research consortium on methodology for clinical trials in small populations. The PTT members are rare disease patient representatives who have completed extensive training in clinical trial methodology. We have analyzed the interviews qualitatively according to Grounded Theory using a thematic analysis, and we structured the topics in four chronologically ordered themes: 1. Involvement in trial design; 2. Opinions on trial design; 3. Trial participation; 4. Phase after the trial. Our main findings are that the PTT-members recommend that patients are involved in trial design from an early stage on, and have influence on the outcomes and measurement instruments that are chosen in the trial, the length of the study, the choice of participants, and the information that is sent to potential participants. Also, according to the PTT-members, patient groups should consider setting up disease registries, placebo groups should be minimized, and more education on clinical trials is advised.ConclusionsRare disease patient representatives who have been educated about clinical trial methodology think it is important to involve patient representatives in research at an early stage. They can be of advice in trial design in such a way that the ratio of potential benefit and burden of trial participation as well as the chosen outcome measures and in- and exclusion criteria are optimized.

Highlights

ResultsWe have interviewed all ten members of the Patient Think Tank (PTT) of the ASTERIX project, a European research consortium on methodology for clinical trials in small populations
A disease is defined as rare when the prevalence is lower than one in 2000 individuals in the European Union [1]
Data collection The Patient Think Tank (PTT)-members were approached by the patient contact person of ASTERIX and were asked if they would be interested in participating in an interview about their experience with rare disease research, and what aspects of trial design they would perceive as important

Summary

Results

We present the themes that arose from the interviews according to the chronology of the design development and conduct of a clinical trial; the first theme is Involvement in trial design, the second theme is Opinions on trial design, the third theme is Trial participation, and the last theme is Phase after the trial. One of the members stated that, apart from fundamental issues such as randomization and comparison with placebo or a different comparator, the specific statistical design of the trial, e.g. the use of co-primary outcomes or the number of interim analyses, is not very relevant for patient groups to be involved in, honesty about this to patients who are participating in a trial is very important. I mean healthy patients, because nobody knows on what day, or what time of any day that they could be struck by with a very serious acute illness, like I was..’ Another PTT-member mentioned that it is important that in prospective trials participants are informed clearly about the consequences if they choose to participate a trial. Further down the line, so once the trial closes, I don’t think that there’s a huge amount of information provided to patients.’

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