Acceptable risks and burdens for children in research without direct benefit: a systematic analysis of the decisions
Anna E Westra1, Rám N Sukhai, Jan M Wit
1Department of Paediatrics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. a.e.westra@lumc.nl
Insights
The minimal risk and burden requirement for pediatric research occasionally rejects vital studies. Revising regulations could allow exceptions for crucial early-phase drug trials, improving pediatric care.
Area of Science:
- Pediatric Research Ethics
- Clinical Trial Regulation
- Medical Research Governance
Background:
- The "minimal risk and burden" standard for pediatric research without direct benefit aims to protect subjects.
- This standard may hinder the acquisition of data crucial for advancing pediatric care.
- European Union recommendations suggest allowing higher risk levels in certain pediatric research.
Purpose of the Study:
- To assess if the "minimal risk and burden" requirement compromises data collection for pediatric care improvement.
- To analyze the impact of this requirement on research approval rates.
- To offer evidence-based insights into the EU's recommendation for higher risk tolerance.
Main Methods:
- Systematic analysis of research approval and rejection decisions by the Dutch Central Committee on Research involving Human Subjects (CCMO).
- Reviewed 165 pediatric research proposals without direct benefit (2000-2007).
- Conducted an in-depth analysis of 27 drug studies (18 early-phase, 9 other) without direct benefit.
Main Results:
- 11 out of 165 studies were rejected due to non-minimal risk/burden.
- The "minimal risk and burden" criterion was the sole rejection reason in 3 cases, including 2 early-phase drug studies.
- Four early-phase drug studies with non-minimal risk/burden were approved, indicating potential flexibility or inconsistency.
Conclusions:
- The "minimal risk and burden" rule can lead to the rejection of important pediatric research protocols.
- Early-phase drug studies frequently exceed the minimal risk threshold.
- Current practices of approving non-compliant studies lack transparency; regulatory revision is needed to legitimize exceptions.
Objectives:
To evaluate whether the requirement of "minimal risk and burden" for paediatric research without direct benefit to the subjects compromises the ability to obtain data necessary for improving paediatric care. To provide evidence-based reflections on the EU recommendation that allows for a higher level of risk.
Design And Setting:
Systematic analysis of the approval/rejection decisions made by the Dutch Central Committee on Research involving Human Subjects (CCMO).
Review Methods:
The analysis included 165 proposals for paediatric research without direct benefit that were reviewed by the CCMO between January, 2000, and July, 2007. A separate, in-depth analysis of all drug studies included 18 early phase drug studies and nine other drug studies without direct benefit.
Results:
11 out of 165 studies were definitively rejected because the CCMO did not regard the risk and/or burden to be minimal. In three of these 11 cases (including two early phase drug studies) the requirement of minimal risk and burden was cited as the only reason for rejection. Four other early phase drug studies also involved risks and/or burdens that were not regarded to be minimal but were nevertheless approved.
Conclusions:
The requirement of minimal risk and burden, aiming to protect research subjects, occasionally leads to rejection of protocols. Early phase drug studies relatively often do not comply with the requirement. Committees may find ways to approve important studies that formally should be rejected, but that is not a desirable solution. The regulatory framework should be revised to make such occasional exceptions to the requirement legitimate and transparent.
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