Institute for Safe Medication Practices, Alexandria, Virginia.
Department of Epidemiology and Biostatistics, Milken Institute of Public Health, George Washington University, Washington, DC.
JAMA Intern Med. 2018 Nov 1;178(11):1451-1457. doi: 10.1001/jamainternmed.2018.3931.
A critical question in health care is the extent of scientific evidence that should be required to establish that a new therapeutic agent has benefits that outweigh its risks. Estimating the costs of this evidence of efficacy provides an important perspective.
To estimate costs and assess scientific characteristics of pivotal efficacy trials that supported the approval of new therapeutic agents by the US Food and Drug Administration (FDA) from 2015 to 2016.
This study identified 59 novel therapeutic drugs using the annual summary reports from the FDA Center for Drug Evaluation and Research. ClinicalTrials.gov, FDA reviews, and peer-reviewed publications that were publicly available in 2017 were used to identify 52 characteristics of each efficacy trial. Costs were calculated with a global clinical trial cost assessment tool available to contract research organizations and pharmaceutical sponsors.
Estimated mean cost and 95% CIs based on industry benchmark data from 60 countries. Measures of trials' scientific characteristics included trial design (no control group, placebo, and active drug), end point (surrogate outcome, clinical scale, and clinical outcome), patient enrollment, and treatment duration.
A total of 138 pivotal clinical trials provided the basis for approval of 59 new therapeutic agents by the FDA from 2015 to 2016, with a median estimated cost of $19.0 million (interquartile range, $12.2 million-$33.1 million). Estimated costs ranged from less than $5 million for trials without a control group for 3 orphan drugs with fewer than 15 patients each to $346.8 million (95% CI, $252.0 million-$441.5 million) for a noninferiority trial with end points assessing clinical benefit. Twenty-six of 138 trials (18.8%) were uncontrolled, with a mean estimated cost of $13.5 million (95% CI, $10.1 million-$16.9 million). Trials designed with placebo or active drug comparators had an estimated mean cost of $35.1 million (95% CI, $25.4 million-$44.8 million). Costs also varied by trial end point, treatment duration, patient enrollment, and therapeutic area.
The highest-cost trials were those in which the new agent had to be proved to be noninferior with clinical benefit end points compared with an agent already available or those that required larger patient populations to achieve statistical power to document smaller treatment effects or accrue infrequently occurring end points.
医疗保健中的一个关键问题是，为了确定新的治疗药物的益处超过其风险，需要多少科学证据。评估这种疗效证据的成本提供了一个重要的视角。
估计 2015 年至 2016 年美国食品和药物管理局（FDA）批准的新型治疗药物的成本，并评估其疗效的关键试验的科学特征。
本研究使用 FDA 药物评价和研究中心的年度总结报告确定了 59 种新型治疗药物。临床Trials.gov、FDA 审查和 2017 年公开的同行评议出版物用于确定每个疗效试验的 52 个特征。成本使用全球临床试验成本评估工具计算，该工具可用于合同研究组织和制药赞助商。
根据来自 60 个国家的行业基准数据计算的估计平均成本和 95%置信区间。试验科学特征的衡量标准包括试验设计（无对照组、安慰剂和活性药物）、终点（替代终点、临床量表和临床终点）、患者入组和治疗持续时间。
2015 年至 2016 年，138 项关键临床试验为 59 种新治疗药物的 FDA 批准提供了依据，中位估计成本为 1900 万美元（四分位距，1220 万美元至 3310 万美元）。估计成本从每个患者少于 15 人的 3 种孤儿药物的无对照组试验的不到 500 万美元到评估临床获益的终点的非劣效性试验的 34.68 亿美元（95%CI，25.20 亿美元至 44.15 亿美元）不等。138 项试验中有 26 项（18.8%）为非对照试验，估计平均成本为 1350 万美元（95%CI，1010 万美元至 1690 万美元）。使用安慰剂或活性药物对照设计的试验估计平均成本为 3510 万美元（95%CI，2540 万美元至 4480 万美元）。成本还因试验终点、治疗持续时间、患者入组和治疗领域而异。
成本最高的试验是那些需要证明新药物在具有临床获益终点的情况下不劣于已有药物或需要更大的患者群体才能获得证明较小治疗效果或累积罕见终点的统计学效力的试验。
