Getz Kenneth A, Stergiopoulos Stella, Short Mary, Surgeon Leon, Krauss Randy, Pretorius Sybrand, Desmond Julian, Dunn Derek
1 Center for the Study of Drug Development, Tufts University, Boston, MA, USA.
2 Eli Lilly & Company, Indianapolis, IN, USA.
Ther Innov Regul Sci. 2016 Jul;50(4):436-441. doi: 10.1177/2168479016632271.
Tufts Center for the Study of Drug Development (Tufts CSDD), in collaboration with 15 pharmaceutical companies and contract research organizations, gathered data on substantial global protocol amendments to better understand how to manage and to reduce the significant unplanned expense and delays associated with major changes to finalized protocol designs.
Data from 836 phase I-IIB/IV protocols were analyzed to understand amendment prevalence. Impact assessments were based on data from 136 randomly selected amendments. Data from 52 protocols were analyzed to derive estimates of the direct cost to implement amendments.
Tufts CSDD found that 57% of protocols had at least one substantial amendment, and nearly half (45%) of these amendments were deemed "avoidable." Phase II and III protocols had a mean number of 2.2 and 2.3 global amendments, respectively. Protocols with one or more global amendments tended to be larger in scope, with longer patient recruitment durations and overall study durations compared with those without a global amendment. Protocols with at least one substantial amendment had fewer actual screened and enrolled patients relative to the original baseline plan than did those protocols without an amendment. The median direct cost to implement a substantial amendment was US$141,000 for a phase II protocol and $535,000 for a phase III protocol.
The study findings provide insights into optimizing development planning, protocol design, and clinical trial management practices.
塔夫茨药物开发研究中心（Tufts CSDD）与15家制药公司及合同研究组织合作，收集了关于全球范围内重大方案修订的数据，以更好地了解如何管理并减少与最终方案设计的重大变更相关的大量意外费用和延误。
分析了来自836项I-IIB/IV期方案的数据，以了解修订的发生率。影响评估基于从136项随机选择的修订中获取的数据。分析了来自52项方案的数据，以得出实施修订的直接成本估算。
塔夫茨CSDD发现，57%的方案至少有一项重大修订，其中近一半（45%）的修订被认为是“可避免的”。II期和III期方案的全球修订平均数量分别为2.2项和2.3项。与没有全球修订的方案相比，有一项或多项全球修订的方案范围往往更大，患者招募持续时间和总体研究持续时间更长。与没有修订的方案相比，至少有一项重大修订的方案实际筛选和入组的患者相对于原始基线计划更少。实施一项重大修订的II期方案的直接成本中位数为14.1万美元，III期方案为53.5万美元。
该研究结果为优化开发计划、方案设计和临床试验管理实践提供了见解。
