Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012.
Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012.
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DOI：
10.1136/bmjopen-2015-009758
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发表时间：
2015-11-12
期刊：
影响因子：
2.9
通讯作者：
Ross JS
中科院分区：
文献类型：
--
作者：
Miller JE;Korn D;Ross JS
通过以下方式评估新药的临床试验注册、报告和出版率：(1) 法律要求和 (2) 所有人体受试者研究应公开以促进普遍知识的道德标准。对 2012 年批准的药物提交给美国食品和药物管理局 (FDA) 的所有临床试验的横断面分析，这些药物由大型生物制药公司赞助。信息来自 Drugs@FDA、ClinicalTrials.gov、MEDLINE 索引期刊和制药公司通讯。在 ClinicalTrials.gov 中进行临床试验注册和结果报告，在医学文献中发表，并遵守 2007 年 FDA 修正案 (FDAAAA)，在药物层面进行分析。 2012 年，FDA 批准了 10 家大公司赞助的 15 种药物。我们确定了 318 项相关试验，涉及 99 599 名研究参与者。对于每种药物，中位数为 57% (IQR 32–83%) 的试验已注册，20% (IQR 12–28%) 在 ClinicalTrials.gov 上报告了结果，56% (IQR 41–83%) 已发表，65% (IQR 41–83%) 已发表或报告了结果。几乎一半的审查药物至少进行过一项未公开的 II 期或 III 期试验。对于每种药物，支持 FDA 批准的试验中中位数为 17%（IQR 8-20%）需要遵守 FDAAA 强制公开披露的规定；其中，中位数为 67% (IQR 0–100%) 符合 FDAAA 要求。 68% 的研究参与者（99 599 人中的 67 629 人）参加了 FDAAA 受试者试验，51% 的研究参与者（67 629 人中的 33 405 人）参加了不合规试验。不同公司的透明度差异很大。新药的试验披露仍然低于法律和道德标准，药物及其申办者之间的做法存在很大差异。最佳实践不断涌现。我们审查的 10 家公司中有 2 家披露了其 2012 年批准药物的所有试验并遵守了法律披露要求。根据透明度标准对新药进行排名可以提高对法律和道德标准的遵守以及医学知识的质量。
To evaluate clinical trial registration, reporting and publication rates for new drugs by: (1) legal requirements and (2) the ethical standard that all human subjects research should be publicly accessible to contribute to generalisable knowledge. Cross-sectional analysis of all clinical trials submitted to the Food and Drug Administration (FDA) for drugs approved in 2012, sponsored by large biopharmaceutical companies. Information from Drugs@FDA, ClinicalTrials.gov, MEDLINE-indexed journals and drug company communications. Clinical trial registration and results reporting in ClinicalTrials.gov, publication in the medical literature, and compliance with the 2007 FDA Amendments Acts (FDAAA), analysed on the drug level. The FDA approved 15 drugs sponsored by 10 large companies in 2012. We identified 318 relevant trials involving 99 599 research participants. Per drug, a median of 57% (IQR 32–83%) of trials were registered, 20% (IQR 12–28%) reported results in ClinicalTrials.gov, 56% (IQR 41–83%) were published, and 65% (IQR 41–83%) were either published or reported results. Almost half of all reviewed drugs had at least one undisclosed phase II or III trial. Per drug, a median of 17% (IQR 8–20%) of trials supporting FDA approvals were subject to FDAAA mandated public disclosure; of these, a median of 67% (IQR 0–100%) were FDAAA-compliant. 68% of research participants (67 629 of 99 599) participated in FDAAA-subject trials, with 51% (33 405 of 67 629) enrolled in non-compliant trials. Transparency varied widely among companies. Trial disclosures for new drugs remain below legal and ethics standards, with wide variation in practices among drugs and their sponsors. Best practices are emerging. 2 of our 10 reviewed companies disclosed all trials and complied with legal disclosure requirements for their 2012 approved drugs. Ranking new drugs on transparency criteria may improve compliance with legal and ethics standards and the quality of medical knowledge.