McWilliams Rita, Hoover-Fong Julie, Hamosh Ada, Beck Suzanne, Beaty Terri, Cutting Garry
Bloomberg School of Public Health, Johns Hopkins Medical Institutions, Baltimore, Md, USA.
JAMA. 2003 Jul 16;290(3):360-6. doi: 10.1001/jama.290.3.360.
Sequencing of the human genome provides an immense resource for studies correlating DNA variation and epidemiology. However, appropriately powered genetic epidemiology studies often require recruitment from multiple sites.
To document the burden imposed by review of multicenter studies and to determine the variability among local institutional review boards (IRBs) in the approval of a multicenter genetic epidemiology study.
A PubMed search was performed to determine the frequency of citations of multicenter studies by 5-year intervals from 1974 through 2002. A 7-question survey was sent to all participating study centers to obtain information on frequency of IRB meetings, dates for submission and approval, use/nonuse of a specific consent form, type of review performed, types of consent forms required, preparation time, and number of changes requested by the IRB at each center. Centers also provided a copy of all consent forms they generated and IRB correspondence regarding the study.
Thirty-one of 42 cystic fibrosis care centers in this single US multicenter genetic epidemiology study of cystic fibrosis replied, yielding a 74% response rate.
Frequency of published research studies and consistency among IRBs.
The number of all published single-center studies has increased 1.3-fold since 1985, while the number of published epidemiology and genetic epidemiology multicenter studies increased by 8- and 9-fold, respectively, during this same period. Evaluation of the risk of the same genetic epidemiology study by 31 IRBs ranged from minimal to high, resulting in 7 expedited reviews (23%) and 24 full reviews (77%). The number of consents required by the IRBs ranged from 1 to 4; 15 IRBs (48%) required 2 or more consents, while 10 (32%) did not require assent for children. The most common concern (52%) of IRBs pertained to the genetic aspects of the study.
Review of a protocol for a multicenter genetic epidemiology study by local IRBs was highly variable. Lack of uniformity in the review process creates uneven human subjects protection and incurs considerable inefficiency. The need for reform, such as the proposed centralized review, is underscored by the ever increasing rate of genetic discoveries facilitated by the Human Genome Project and the unprecedented opportunity to assess the relevance of genetic variation to public health.
人类基因组测序为研究DNA变异与流行病学之间的关系提供了丰富的资源。然而，具备足够效力的遗传流行病学研究通常需要从多个地点招募参与者。
记录多中心研究审查所带来的负担，并确定当地机构审查委员会（IRB）在批准一项多中心遗传流行病学研究时的差异。
通过PubMed检索，确定1974年至2002年期间以5年为间隔的多中心研究被引用的频率。向所有参与研究的中心发送了一份包含7个问题的调查问卷，以获取有关IRB会议频率、提交和批准日期、是否使用特定同意书、进行的审查类型、所需同意书类型、准备时间以及每个中心IRB要求的修改数量等信息。各中心还提供了他们生成的所有同意书副本以及与该研究相关的IRB通信。
在这项美国关于囊性纤维化的单一多中心遗传流行病学研究中，42个囊性纤维化护理中心中有31个回复，回复率为74%。
已发表研究的频率以及IRB之间的一致性。
自1985年以来，所有已发表的单中心研究数量增加了1.3倍，而在此期间，已发表的流行病学和遗传流行病学多中心研究数量分别增加了8倍和9倍。31个IRB对同一遗传流行病学研究的风险评估范围从最低到最高，结果有7次快速审查（23%）和24次全面审查（77%）。IRB要求的同意书数量从1份到4份不等；15个IRB（48%）要求2份或更多同意书，而10个（32%）对儿童不要求同意。IRB最常见的担忧（52%）与研究的遗传方面有关。
当地IRB对多中心遗传流行病学研究方案的审查差异很大。审查过程缺乏一致性导致对人类受试者的保护不均衡，并造成相当大的低效率。人类基因组计划推动的遗传发现速度不断加快，以及评估遗传变异与公共卫生相关性的前所未有的机会，凸显了进行改革（如提议的集中审查）的必要性。
