Clinical Research in Vulnerable Populations: Variability and Focus of Institutional Review Boards' Responses.
BACKGROUND
Children 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.


OBJECTIVE
To evaluate the review process of IRBs for two different "miscellaneous" multicenter clinical research protocols involving vulnerable subjects (children and adult stroke patients).


METHODS
Descriptive 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.


RESULTS
Protocol 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.


CONCLUSIONS
Both 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.
Coordination Center for Clinical Trials (KKS), University Hospital Heidelberg, Heidelberg, Germany.
Bärbel
B
Kästner
Coordination Center for Clinical Trials (KKS), University Hospital Heidelberg, Heidelberg, Germany.
Simone
S
Behre
Pediatric Neurology and Metabolic Medicine, Center for Rare Disease, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.
Nadine
N
Lutz
Pediatric Neurology and Metabolic Medicine, Center for Rare Disease, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.
Friederike
F
Bürger
Coordination Center for Clinical Trials (KKS), University Hospital Heidelberg, Heidelberg, Germany.
Steffen
S
Luntz
Institute for Human Genetics, University Hospital Heidelberg, Heidelberg, Germany.
Katrin
K
Hinderhofer
Neuroradiology, Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany.
Martin
M
Bendszus
Pediatric Neurology and Metabolic Medicine, Center for Rare Disease, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.
Georg F
GF
Hoffmann
Pediatric Neurology and Metabolic Medicine, Center for Rare Disease, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.
Markus
M
Ries
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D028744:Ethics Committees, Research; D005062:European Union; D000795:Fabry Disease / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015607:Stents