Differences Between Trial Populations and Approved Label Populations of New Drugs in the United States and Europe (2012 to 2023) : A Cross-Sectional Study.

IF 19.6 1区医学 Q1 MEDICINE, GENERAL & INTERNAL

Annals of Internal Medicine Pub Date : 2025-07-08 DOI:10.7326/ANNALS-24-03242

Kerstin N Vokinger, Miquel Serra-Burriel, Camille E G Glaus, Lara Welti, Joseph S Ross, Aaron S Kesselheim

{"title":"Differences Between Trial Populations and Approved Label Populations of New Drugs in the United States and Europe (2012 to 2023) : A Cross-Sectional Study.","authors":"Kerstin N Vokinger, Miquel Serra-Burriel, Camille E G Glaus, Lara Welti, Joseph S Ross, Aaron S Kesselheim","doi":"10.7326/ANNALS-24-03242","DOIUrl":null,"url":null,"abstract":"Background: Drugs are approved when their benefits outweigh their risks based on the results of clinical trials. It remains unclear how often regulatory agencies extrapolate or restrict the approval compared with the trial.Objective: To analyze the differences in the characteristics of enrolled patients between trial populations and approved label populations in the United States, European Union (EU), and Switzerland for new drugs.Design: Cross-sectional study.Setting: Inclusion of all new drugs that were approved by all 3 agencies from 2012 to 2023 and comparison of trial populations with the approved label populations.Patients: Aggregated and anonymized patient data included in trial data and approved label information were analyzed.Measurements: The eligibility criteria of the trial population with the approved label population in the United States, EU, and Switzerland were compared for 5 categories: age, disease subtype, disease severity, patient fitness, and prior therapy. Linear regression models were performed, and the proportions of more extensive and more restrictive evaluations were determined.Results: 263 drugs (278 indications) were included in the study cohort. Overall, approved label populations were broader than trial populations and more pronounced in the United States compared with the EU and Switzerland. Patient fitness was the most often at variance with 276 approved indications (99.3% [95% CI, 99.2% to 99.4%]) in the United States and EU, and 275 (98.9% [CI, 98.8% to 99%]) in Switzerland, followed by disease severity with 143 approved indications (51% [CI, 49% to 54%]) in the United States, 119 (43%, [CI, 40% to 46%]) in the EU, and 111 (40% [CI, 37% to 43%]) in Switzerland.Limitation: Reporting of trial eligibility criteria lacked uniformity.Conclusion: Postapproval trials and surveillance are indicated for drugs for which broadening has occurred to ensure safety and efficacy for patient subpopulations that were not included in the trials.Primary funding source: Kaiser Permanente Institute of Health Policy; Swiss National Science Foundation (SNSF).","PeriodicalId":7932,"journal":{"name":"Annals of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":19.6000,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Internal Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7326/ANNALS-24-03242","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Drugs are approved when their benefits outweigh their risks based on the results of clinical trials. It remains unclear how often regulatory agencies extrapolate or restrict the approval compared with the trial.

Objective: To analyze the differences in the characteristics of enrolled patients between trial populations and approved label populations in the United States, European Union (EU), and Switzerland for new drugs.

Design: Cross-sectional study.

Setting: Inclusion of all new drugs that were approved by all 3 agencies from 2012 to 2023 and comparison of trial populations with the approved label populations.

Patients: Aggregated and anonymized patient data included in trial data and approved label information were analyzed.

Measurements: The eligibility criteria of the trial population with the approved label population in the United States, EU, and Switzerland were compared for 5 categories: age, disease subtype, disease severity, patient fitness, and prior therapy. Linear regression models were performed, and the proportions of more extensive and more restrictive evaluations were determined.

Results: 263 drugs (278 indications) were included in the study cohort. Overall, approved label populations were broader than trial populations and more pronounced in the United States compared with the EU and Switzerland. Patient fitness was the most often at variance with 276 approved indications (99.3% [95% CI, 99.2% to 99.4%]) in the United States and EU, and 275 (98.9% [CI, 98.8% to 99%]) in Switzerland, followed by disease severity with 143 approved indications (51% [CI, 49% to 54%]) in the United States, 119 (43%, [CI, 40% to 46%]) in the EU, and 111 (40% [CI, 37% to 43%]) in Switzerland.

Limitation: Reporting of trial eligibility criteria lacked uniformity.

Conclusion: Postapproval trials and surveillance are indicated for drugs for which broadening has occurred to ensure safety and efficacy for patient subpopulations that were not included in the trials.

Primary funding source: Kaiser Permanente Institute of Health Policy; Swiss National Science Foundation (SNSF).

查看原文本刊更多论文

美国和欧洲新药试验人群和批准标签人群的差异（2012 - 2023）：一项横断面研究。

背景：基于临床试验的结果，当药物的益处大于风险时，药物就会被批准。目前尚不清楚，与试验相比，监管机构多久会推断或限制批准。目的：分析美国、欧盟（EU）和瑞士新药批准标签人群与试验人群入组患者特征的差异。设计：横断面研究。设定：纳入2012年至2023年所有3家机构批准的所有新药，并将试验人群与已批准的标签人群进行比较。患者：汇总和匿名的患者数据包括在试验数据和批准的标签信息进行分析。测量：试验人群的资格标准与美国、欧盟和瑞士批准的标签人群进行了5个类别的比较：年龄、疾病亚型、疾病严重程度、患者健康和既往治疗。进行了线性回归模型，并确定了更广泛和更严格的评价比例。结果：263种药物（278种适应症）被纳入研究队列。总的来说，批准的标签人群比试验人群更广泛，与欧盟和瑞士相比，美国的标签人群更明显。患者适应度差异最大，美国和欧盟有276个批准适应症（99.3% [95% CI， 99.2%至99.4%]），瑞士有275个（98.9% [CI， 98.8%至99%]），其次是疾病严重程度，美国有143个批准适应症（51% [CI， 49%至54%]），欧盟有119个（43% [CI， 40%至46%]），瑞士有111个（40% [CI， 37%至43%]）。局限性：试验资格标准报告缺乏一致性。结论：批准后的试验和监测适用于已经扩大的药物，以确保未包括在试验中的患者亚群的安全性和有效性。主要资金来源：Kaiser Permanente卫生政策研究所；瑞士国家科学基金会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Annals of Internal Medicine 医学-医学：内科

CiteScore

23.90

自引率

1.80%

发文量

1136

审稿时长

3-8 weeks

期刊介绍： Established in 1927 by the American College of Physicians (ACP), Annals of Internal Medicine is the premier internal medicine journal. Annals of Internal Medicine’s mission is to promote excellence in medicine, enable physicians and other health care professionals to be well informed members of the medical community and society, advance standards in the conduct and reporting of medical research, and contribute to improving the health of people worldwide. To achieve this mission, the journal publishes a wide variety of original research, review articles, practice guidelines, and commentary relevant to clinical practice, health care delivery, public health, health care policy, medical education, ethics, and research methodology. In addition, the journal publishes personal narratives that convey the feeling and the art of medicine.