Burt Consultancy, LLC., Durham, North Carolina, USA.
Department of Psychology, University of Bath, UK.
Clin Transl Sci. 2017 Nov;10(6):470-479. doi: 10.1111/cts.12478. Epub 2017 Jul 4.
The "false-negatives" of clinical development are the effective treatments wrongly determined ineffective. Statistical errors leading to "false-negatives" are larger than those leading to "false-positives," especially in typically underpowered early-phase trials. In addition, "false-negatives" are usually eliminated from further testing, thereby limiting the information available on them. We simulated the impact of early-phase power on economic productivity in three developmental scenarios. Scenario 1, representing the current status quo, assumed 50% statistical power at phase II and 90% at phase III. Scenario 2 assumed increased power (80%), and Scenario 3, increased stringency of alpha (1%) at phase II. Scenario 2 led, on average, to a 60.4% increase in productivity and 52.4% increase in profit. Scenario 3 had no meaningful advantages. Our results suggest that additional costs incurred by increasing the power of phase II studies are offset by the increase in productivity. We discuss the implications of our results and propose corrective measures.
临床试验中的“假阴性”是指被错误判定为无效的有效治疗方法。导致“假阴性”的统计误差比导致“假阳性”的误差更大，尤其是在通常样本量不足的早期试验中。此外，“假阴性”通常会被排除在进一步的测试之外，从而限制了可用的相关信息。我们在三种开发情景下模拟了早期阶段的效力对经济生产力的影响。情景 1 代表当前的现状，假设在第 II 阶段有 50%的统计效力，在第 III 阶段有 90%的统计效力。情景 2 假设增加了效力（80%），情景 3 假设在第 II 阶段增加了α的严格性（1%）。平均而言，情景 2 导致生产力提高 60.4%，利润提高 52.4%。情景 3 没有明显的优势。我们的结果表明，通过提高第 II 阶段研究的效力而产生的额外成本，被生产力的提高所抵消。我们讨论了我们的结果的影响，并提出了纠正措施。
