Clinical Research in Vulnerable Populations: Variability and Focus of Institutional Review Boards’ Responses

Abstract

BackgroundChildren and patients with cognitive deficits may find it difficult to understand the implication of research. In the European Union (EU), clinical studies outside the EU directives concerning medicinal products or medical devices, i.e., “miscellaneous clinical studies”, have no legally mandated timelines for institutional review boards’ (IRB) decisions.GoalTo evaluate the review process of IRBs for two different “miscellaneous” multicenter clinical research protocols involving vulnerable subjects (children and adult stroke patients).MethodsDescriptive and comparative statistics. Protocol 1 is a prospective, multicenter, cross-sectional screening study of a symptomatic pediatric population at risk for Fabry disease involving genetic testing (NCT02152189). Protocol 2 is a prospective, multicenter, randomized, controlled, open-label, blinded endpoint post-market study to evaluate the effectiveness of stent retrievers (NCT02135926). After having obtained positive initial IRB votes at the main study site, both protocols were subsequently submitted to the remaining IRBs.ResultsProtocol 1 was submitted to 19 IRBs. No IRB objected to the study. Median time-to-final vote was 34 (IQR 10–65; range 0 to 130) days. Two IRBs accepted the coordinating center’s IRB votes without re-evaluation. Changes to the informed consent documents were asked by 7/19 IRBs, amendments to the protocol by 2. Protocol 2 was submitted to 16 IRBs. Fifteen decisions were made. No IRB objected to the study. Median time-to final vote was 59 (IQR 10 to 65; range 0 to 128) days, which was not statistically significantly different compared with protocol 1 (Wilcoxon test). Two IRBs accepted a previous IRB decision and did not conduct an independent review. Eight/16 IRBs required changes to the informed consent documents; two IRBs recommended an amendment of the protocol.ConclusionBoth clinical research protocols involving vulnerable populations were well accepted. IRB workflows and decision times varied substantially. Some IRBs accepted a previous IRB decision without the necessity of another reevaluation process. Requested changes were focused on the informed consent documents. A more standardized approach across jurisdictions is desirable.

Ultra‐orphan lysosomal storage diseases: A cross‐sectional quantitative analysis of the natural history of alpha‐mannosidosis

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A cross-sectional quantitative analysis of the natural history of Farber disease: an ultra-orphan condition with rheumatologic and neurological cardinal disease features

“…22 Besides raising disease awareness, screening specific populations at risk within patient groups with commonly encountered conditions that may phenotypically overlap with Farber disease-e.g., rheumatologic disorders, developmental delay, organomegaly, and bone disease-may be another method of reducing time to diagnosis in this rare condition. 23 Patients whose data were published after 2000 lived longer compared with patients with data published earlier, but this phenomenon was probably biased by the fact that a substantially higher proportion of data for less severely affected patients (i.e., those with residual AC activity above 5.1%) was published after 2000. An effect of improved standard of care is therefore less likely, but not impossible.…”

Conducting an investigator-initiated randomized double-blinded intervention trial in acute decompensation of inborn errors of metabolism: Lessons from the N-Carbamylglutamate Consortium

“…Median time from initial IRB application until final IRB approval (68 days; Table 1) was in fact longer than prior published mean times in interventional trials (38-42 days [22–24]). Although in some cases, this length of time was increased due to personnel turnover, it may also highlight the difficulties that Institutional Review Boards have with understanding rare genetic disorders which they may not have previously encountered.…”