Program on Regulation, Therapeutics, and Law (PORTAL), Brigham and Women's Hospital, Boston, Massachusetts.
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
JAMA Intern Med. 2018 Nov 1;178(11):1458-1466. doi: 10.1001/jamainternmed.2018.3933.
Pharmaceutical manufacturers can receive 6 additional months of market exclusivity for performing pediatric clinical trials of brand-name drugs widely used in adults. Congress created this incentive in 1997 because these drugs were being used off-label in children without such trials.
To review updates to drug labeling and the cost to consumers of extending market exclusivity related to the pediatric exclusivity program.
From government records, we identified 54 drugs that earned the pediatric exclusivity incentive between 2007 and 2012. We evaluated labeling changes from the pediatric studies. We then extracted trial details from clinical review documents and used industry estimates of trial costs on a per-patient basis to estimate cost of investment for trials (with a 10% cost of capital). To calculate the net return and cost to consumers during the 6-month exclusivity period, we estimated additional revenue for the 48 drugs with available information.
For each drug, we evaluated labeling changes and costs associated with pediatric trials under the Best Pharmaceuticals for Children Act and the cost to consumers of 6-month market exclusivity extensions.
The 141 trials in our sample enrolled 20 240 children (interquartile range [IQR], 2-3 trials and 127-556 patients per drug). These trials led to 29 extended indications and 3 new indications, as well as new safety information for 16 drugs. Median cost of investment for trials was $36.4 million (IQR, $16.6 to $100.6 million). Among 48 drugs with available financial information, median net return was $176.0 million (IQR, $47.0 million to $404.1 million), with a median ratio of net return to cost of investment of 680% (IQR, 80% to 1270%).
Clinical trials conducted under the US Food and Drug Administration's pediatric exclusivity program have provided important information about the effectiveness and safety of drugs used in children. The costs to consumers have been high, exceeding the estimated costs of investment for conducting the trials. As an alternative, policymakers should consider direct funding of such studies.
药品制造商可为广泛用于成年患者的品牌药物进行儿科临床试验，从而获得额外 6 个月的市场独占权。国会于 1997 年制定了这一激励措施，因为这些药物在儿童中未经许可使用，没有进行临床试验。
审查与儿科独占性计划相关的药物标签更新和消费者为延长市场独占性所支付的费用。
我们从政府记录中确定了在 2007 年至 2012 年期间获得儿科独占性激励的 54 种药物。我们评估了从儿科研究中获得的标签变化。然后，我们从临床审查文件中提取了试验细节，并使用行业估计的每位患者试验成本来估计试验投资成本（资本成本为 10%）。为了计算 6 个月独占期内的净回报和消费者成本，我们根据可用信息估计了 48 种药物的额外收入。
对于每种药物，我们评估了最佳儿科药物法案下儿科试验的标签变化和相关成本，以及 6 个月市场独占性扩展对消费者的成本。
我们样本中的 141 项试验共纳入 20240 名儿童（四分位距 [IQR]，2-3 项试验和每药 127-556 名患者）。这些试验导致 29 项扩展适应症和 3 项新适应症，以及 16 种药物的新安全性信息。试验投资的中位数成本为 3640 万美元（IQR，1660 万至 1.006 亿美元）。在有可用财务信息的 48 种药物中，中位数净回报为 1.760 亿美元（IQR，4700 万美元至 4.104 亿美元），净回报与投资成本的中位数比率为 680%（IQR，80%至 1270%）。
在美国食品和药物管理局的儿科独占性计划下进行的临床试验提供了有关儿童用药有效性和安全性的重要信息。消费者的成本很高，超过了进行试验的估计投资成本。作为替代方案，政策制定者应考虑直接为此类研究提供资金。
