Assessing the Impact of US Food and Drug Administration Breakthrough Therapy Designation Timing on Trial Characteristics and Development Speed
Assessing the Impact of US Food and Drug Administration Breakthrough Therapy Designation Timing on Trial Characteristics and Development Speed
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DOI：
10.1002/cpt.2318
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发表时间：
2021-07-01
影响因子：
6.7
通讯作者：
Darrow, Jonathan J.
中科院分区：
文献类型：
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作者：
Pregelj, Lisette;Hine, Damian C.;Darrow, Jonathan J.
美国国会于2012年创建了突破性疗法称号，通过有效的临床试验设计和与美国食品和药物管理局（FDA）审查员的密切互动，加快药物开发和审查。然而，在2013-2018年批准的116项支持突破性指定药物的关键试验中，96项（83%）在指定被授予时已经进行或完成，限制了指定影响试验设计的潜力。我们发现这些试验与20项（17%）在批准时尚未开始的试验（受指定影响的可能性更大）在阶段、规模、干预模式（单臂与多臂）或加速批准（AA）途径下替代终点的使用方面没有差异。这一发现表明，与以前的研究相反，观察到的试验特征不太可能归因于该名称，而是其他因素，如疾病类别（如肿瘤）可能同时驱动试验设计和突破性命名。然而，在我们的样本中，在获得指定后开始的20项试验比未指定药物的试验缩短了8个多月。这表明，在临床开发早期授予的指定可以通过影响临床项目的其他方面而不是设计特征（如FDA反应的时间）来缩短试验时间。另外，某些药物可能更有可能获得早期的指定，并有较短的试验持续时间，例如，因为治疗类别或大的效应量。
The US Congress created the Breakthrough Therapy designation in 2012 to expedite drug development and review through efficient clinical trial design and intensive interaction with US Food and Drug Administration (FDA) reviewers. Yet, of the 116 pivotal trials supporting Breakthrough-designated drugs approved 2013-2018, 96 (83%) were already underway or completed when the designation was granted, limiting the potential of the designation to influence trial design. We found no difference between these trials and the 20 (17%) that had not yet begun when the designation was granted (which had greater potential to be impacted by the designation) with respect to phase, size, intervention model (single-arm vs. multi-arm), or use of surrogate end points under the Accelerated Approval (AA) pathway. This finding suggests that, in contrast to previous studies, observed trial characteristics were not likely attributable to the designation, and instead other factors such as disease category (e.g., oncology) may be driving both trial design and Breakthrough designation. The 20 trials in our sample that began after designation was granted were, however, over 8 months shorter than trials of nondesignated drugs. This suggests that designations granted early in clinical development may reduce trial time by influencing aspects of clinical programs other than design characteristics, such as timelines for FDA responses. Alternately, certain drugs may be more likely to both receive an early designation and have a shorter trial duration, for example, because of therapeutic category or large effect size.