Korte Eva W H, Welponer Tobias, Kottner Jan, van der Werf Sjoukje, van den Akker Peter C, Horváth Barbara, Kiritsi Dimitra, Laimer Martin, Pasmooij Anna M G, Wally Verena, Bolling Maria C
Department of Dermatology.
Department of Dermatology and Allergology.
Br J Dermatol. 2023 Jul 7;189(1):80-90. doi: 10.1093/bjd/ljad077.
Epidermolysis bullosa (EB) is a rare, genetically and clinically heterogeneous group of skin fragility disorders. No cure is currently available, but many novel and repurposed treatments are upcoming. For adequate evaluation and comparison of clinical studies in EB, well-defined and consistent consensus-endorsed outcomes and outcome measurement instruments are necessary.
To identify previously reported outcomes in EB clinical research, group these outcomes by outcome domains and areas and summarize respective outcome measurement instruments.
A systematic literature search was performed in the databases MEDLINE, Embase, Scopus, Cochrane CENTRAL, CINAHL, PsycINFO and trial registries covering the period between January 1991 and September 2021. Studies were included if they evaluated a treatment in a minimum of three patients with EB. Two reviewers independently performed the study selection and data extraction. All identified outcomes and their respective instruments were mapped onto overarching outcome domains. The outcome domains were stratified according to subgroups of EB type, age group, intervention, decade and phase of clinical trial.
The included studies (n = 207) covered a range of study designs and geographical settings. A total of 1280 outcomes were extracted verbatim and inductively mapped onto 80 outcome domains and 14 outcome areas. We found a steady increase in the number of published clinical trials and outcomes reported over the past 30 years. The included studies mainly focused on recessive dystrophic EB (43%). Wound healing was reported most frequently across all studies and referred to as a primary outcome in 31% of trials. Great heterogeneity of reported outcomes was observed within all stratified subgroups. Moreover, a diverse range of outcome measurement instruments (n = 200) was identified.
We show substantial heterogeneity in reported outcomes and outcome measurement instruments in EB clinical research over the past 30 years. This review is the first step towards harmonization of outcomes in EB, which is necessary to expedite the clinical translation of novel treatments for patients with EB.
大疱性表皮松解症（EB）是一组罕见的、具有遗传和临床异质性的皮肤脆性疾病。目前尚无治愈方法，但许多新的和重新利用的治疗方法即将出现。为了对EB的临床研究进行充分评估和比较，需要明确且一致的、经共识认可的结局指标和结局测量工具。
识别EB临床研究中先前报道的结局指标，按结局领域和方面对这些结局指标进行分组，并总结相应的结局测量工具。
在MEDLINE、Embase、Scopus、Cochrane CENTRAL、CINAHL、PsycINFO数据库以及试验注册库中进行系统文献检索，检索时间范围为1991年1月至2021年9月。纳入的研究需至少评估三名EB患者的治疗情况。两名评审员独立进行研究筛选和数据提取。所有识别出的结局指标及其各自的工具被映射到总体结局领域。结局领域根据EB类型、年龄组、干预措施、年代和临床试验阶段进行分层。
纳入的研究（n = 207）涵盖了一系列研究设计和地理区域。共逐字提取了1280个结局指标，并归纳映射到80个结局领域和14个结局方面。我们发现，在过去30年中，发表的临床试验数量和报道的结局指标数量稳步增加。纳入的研究主要集中于隐性营养不良型EB（43%）。在所有研究中，伤口愈合的报道最为频繁，在31%的试验中被作为主要结局指标。在所有分层亚组中，观察到报道的结局指标存在很大异质性。此外，还识别出了各种各样的结局测量工具（n = 200）。
我们表明，在过去30年的EB临床研究中，报道的结局指标和结局测量工具存在很大异质性。本综述是实现EB结局指标标准化的第一步，这对于加速EB患者新治疗方法的临床转化是必要的。
