Ethics Review of Pediatric Multi-Center Drug Trials

Abstract

The assessment of safety and efficacy of therapeutics for children and adolescents requires the use of multi-centered designs. However, the need to obtain ethical approval from multiple independent research ethics boards (REBs) presents as a challenge to investigators and sponsors who must consider local requirements while ensuring that the protection of human subjects is consistent across sites. In pediatrics, this requirement is complicated by pediatric-specific ethical concerns such as the acquisition of assent and consent and the need for pediatric expertise to assess the scholarly merit of the proposed research. Efforts to tackle these challenges have focused on the process of ethics review, which will improve efficiency. In addition to improving process, we suggest further research to fill gaps in the evidence base for recommendations and decisions made by REBs, specifically their effectiveness to protect human subjects. Evidence gathered will contribute to the successful development, adoption and implementation of harmonized guidance to apply ethics principles in order to protect children through research rather than from research.

Should the Decisions of Institutional Review Boards Be Consistent?

“…As a result of two recent federal policies, most federally funded multisite research in the United States is now required to undergo review by a single IRB . Australia has taken similar measures: investigators involved in multisite research are required to submit a national application form recognized across the country . Several jurisdictions in Canada are moving toward centralized ethics committee review as well, although not all have done so …”

Challenges of designing multicenter trials in pediatric heart failure

“…Human subject review boards are becoming more familiar with intervention studies in children that carry more than minimal risk, however studies of acute decompensated heart failure in children still pose challenges because the risk of an adverse event is particularly high [43,45]. This raises the level of scrutiny of the study protocol and may prolong the approval process.…”

Streamlining review of research involving humans: Canadian models: Table 1

“…Each jurisdiction housing the participating research sites comes equipped with its own regulatory mechanisms, procedures and bureaucracies. This can pose a number of practical and interpretive challenges6 7 to ensuring an equally high standard of participant protections across all research sites, not the least of which can include reconciling data privacy and security statutes, ensuring specific protections for research with vulnerable populations and navigating issues of broad consent in using biobanked samples. Where policies regulating health research are not federalised, multi-jurisdictional ethics review can complicate abilities to collaborate and, ultimately, limit clinical translation possibilities.…”