van den Bor Rutger M, Oosterman Bas J, Oostendorp Martinus B, Grobbee Diederick E, Roes Kit C B
1 Julius Clinical Ltd, Zeist, the Netherlands.
2 Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands.
Ther Innov Regul Sci. 2016 Jan;50(1):82-90. doi: 10.1177/2168479015602042.
One approach to increase the efficiency of clinical trial monitoring is to replace 100% source data verification (SDV) by verification of samples of source data. An intuitive strategy for determining appropriate sampling plans (ie, sample sizes and the maximum tolerable number of transcription errors in the samples) is to use acceptance sampling methodology. Expanding upon earlier work in which the use of acceptance sampling strategies for sampling-based SDV was proposed, we describe an alternative acceptance sampling strategy that, instead of relying on sampling standards, evaluates all possible sampling plans algorithmically, thereby ensuring that selected sampling plans conform to prespecified criteria.
Empirical trial data guided the design of the proposed strategy. In addition, extensive simulations, also based on the empirical data, were performed to assess the performance in terms of workload reductions and the post-SDV error proportion of applying the proposed strategy.
13 different scenarios were simulated, but results of the default scenario show that the average pre-SDV error proportion per trial of .056 was reduced to .023 by inspecting only 40.5% of the case report form entries. Of the inspected data entries, almost half (18.0/40.5) was, on average, SDV-ed as part of the sampling process; remaining entries were inspected during full inspections after too many errors were observed in the samples.
Our results suggest that major reductions in workload can be achieved, while maintaining acceptable data quality levels. However, the results also indicate that the proposed strategy is conservative and further improvement is possible.
提高临床试验监查效率的一种方法是用源数据样本核查取代100%的源数据验证（SDV）。确定适当抽样计划（即样本量和样本中转录错误的最大可容忍数量）的一种直观策略是使用验收抽样方法。在早期工作提出将验收抽样策略用于基于抽样的SDV的基础上，我们描述了一种替代验收抽样策略，该策略不是依赖抽样标准，而是通过算法评估所有可能的抽样计划，从而确保所选抽样计划符合预先设定的标准。
实证试验数据指导了所提出策略的设计。此外，还基于实证数据进行了广泛的模拟，以评估在减少工作量以及应用所提出策略后的SDV后错误比例方面的性能。
模拟了13种不同的情况，但默认情况的结果表明，通过仅检查40.5%的病例报告表条目，每个试验的平均SDV前错误比例从0.056降至0.023。在检查的数据条目中，平均几乎一半（18.0/40.5）在抽样过程中作为抽样的一部分进行了SDV；在样本中观察到太多错误后，其余条目在全面检查期间进行检查。
我们的结果表明，在保持可接受的数据质量水平的同时，可以大幅减少工作量。然而，结果也表明所提出的策略较为保守，还有进一步改进的可能。
