Pediatric clinical Research Office, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.
Department of Cognitive Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Orphanet J Rare Dis. 2019 Feb 7;14(1):31. doi: 10.1186/s13023-019-1002-z.
Clinical 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.
We 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.
Rare 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.
罕见病临床试验比常见病临床试验更具挑战性。合格的试验参与者人数较少，而且罕见病患者之间常常存在异质性，这给“经典”随机对照试验的设计和实施带来了困难。因此，统计学家开发了新的设计。然而，了解可能危及试验实施可行性的设计方面非常重要。如果患者或其父母认为参与的负担不成比例，那么招募可能会失败，或者参与者可能会在试验完成前退出。为了最大限度地提高小人群试验成功的机会，了解患者认为哪些试验设计方面重要非常重要。
我们采访了 ASTERIX 项目患者智囊团（PTT）的所有十名成员，ASTERIX 是一个关于小人群临床试验方法的欧洲研究联盟。PTT 成员是完成了临床试验方法广泛培训的罕见病患者代表。我们按照扎根理论使用主题分析对访谈进行了定性分析，并将主题分为四个按时间顺序排列的主题：1. 参与试验设计；2. 对试验设计的意见；3. 试验参与；4. 试验后阶段。我们的主要发现是，PTT 成员建议从早期开始让患者参与试验设计，并对试验中选择的结果和测量工具、研究的长度、参与者的选择以及发送给潜在参与者的信息产生影响。此外，根据 PTT 成员的意见，患者团体应考虑建立疾病登记处，尽量减少安慰剂组，并建议开展更多关于临床试验的教育。
接受过临床试验方法教育的罕见病患者代表认为，让患者代表在早期参与研究非常重要。他们可以在试验设计方面提供建议，以优化潜在获益与参与试验的负担之比，以及所选的结果测量指标和纳入排除标准。
