首页 > 最新文献

Therapeutic innovation & regulatory science最新文献

英文 中文
Real-World Evidence to Support the Registration of a New Osteoporosis Medicinal Product in Europe. 支持骨质疏松症新药在欧洲注册的现实世界证据。
IF 1.5 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-05-01 Epub Date: 2024-02-10 DOI: 10.1007/s43441-024-00616-7
Colleen Davenport, Patricia Gravel, Yamei Wang, Setareh A Williams, Alethea Wieland, Bruce Mitlak

Real-World Evidence (RWE), which has historically been used to support post-approval safety studies, has recently gained acceptance for new drug applications as supportive evidence or as new clinical evidence for medicinal products with orphan designation and/or in disease areas with high unmet need. Here, we present a case study for the use of RWE in the approval of abaloparatide in the European Union (EU) under the tradename Eladynos. In addition to data from the pivotal Phase 3 study, the marketing authorization application (MAA) included clinical data from additional interventional and observational studies, as well as post-marketing data obtained from the United States (US) market since approval of abaloparatide by the Food and Drug Administration (FDA) in 2017. The new interventional studies were not designed to assess fracture efficacy and cardiovascular safety which were topics of concern raised by the Committee for Medicinal Products for Human Use (CHMP) during their review of the initial MAA submitted in 2015. However, these studies taken together with the RWE formed the basis for a new MAA. Prior to the planned resubmission in the EU, national Scientific Advice (SA) was sought on the proposed clinical program, specifically on the relevance of Real-World Data (RWD) derived from an observational study to support and complement the efficacy and safety data already available from prospective randomized clinical trials. This case study demonstrates successful use of RWE to address a previously identified gap raised by the CHMP during the review of an earlier MAA, which led to the approval of Eladynos for the treatment of osteoporosis in the EU.

真实世界证据(RWE)在历史上一直被用于支持批准后的安全性研究,最近在新药申请中作为支持性证据或作为孤儿药和/或需求未得到满足的疾病领域的新临床证据得到了认可。在此,我们将介绍一个案例,说明在欧盟(EU)批准阿巴帕肽(商品名为 Eladynos)时使用 RWE 的情况。除了来自关键性 3 期研究的数据外,上市许可申请(MAA)还包括来自其他介入性和观察性研究的临床数据,以及自 2017 年食品药品管理局(FDA)批准阿巴拉帕肽以来从美国市场获得的上市后数据。新的介入性研究并非旨在评估骨折疗效和心血管安全性,而这正是人用医药产品委员会(CHMP)在审查2015年提交的初始MAA时提出的关注主题。然而,这些研究与 RWE 一起构成了新 MAA 的基础。在计划向欧盟重新提交之前,就拟议的临床计划征求了国家科学建议(SA),特别是关于从观察性研究中获得的真实世界数据(RWD)的相关性,以支持和补充前瞻性随机临床试验中已有的疗效和安全性数据。本案例研究表明,RWE 的成功应用解决了 CHMP 在审查早期 MAA 时提出的差距问题,从而使 Eladynos 在欧盟获批用于治疗骨质疏松症。
{"title":"Real-World Evidence to Support the Registration of a New Osteoporosis Medicinal Product in Europe.","authors":"Colleen Davenport, Patricia Gravel, Yamei Wang, Setareh A Williams, Alethea Wieland, Bruce Mitlak","doi":"10.1007/s43441-024-00616-7","DOIUrl":"10.1007/s43441-024-00616-7","url":null,"abstract":"<p><p>Real-World Evidence (RWE), which has historically been used to support post-approval safety studies, has recently gained acceptance for new drug applications as supportive evidence or as new clinical evidence for medicinal products with orphan designation and/or in disease areas with high unmet need. Here, we present a case study for the use of RWE in the approval of abaloparatide in the European Union (EU) under the tradename Eladynos. In addition to data from the pivotal Phase 3 study, the marketing authorization application (MAA) included clinical data from additional interventional and observational studies, as well as post-marketing data obtained from the United States (US) market since approval of abaloparatide by the Food and Drug Administration (FDA) in 2017. The new interventional studies were not designed to assess fracture efficacy and cardiovascular safety which were topics of concern raised by the Committee for Medicinal Products for Human Use (CHMP) during their review of the initial MAA submitted in 2015. However, these studies taken together with the RWE formed the basis for a new MAA. Prior to the planned resubmission in the EU, national Scientific Advice (SA) was sought on the proposed clinical program, specifically on the relevance of Real-World Data (RWD) derived from an observational study to support and complement the efficacy and safety data already available from prospective randomized clinical trials. This case study demonstrates successful use of RWE to address a previously identified gap raised by the CHMP during the review of an earlier MAA, which led to the approval of Eladynos for the treatment of osteoporosis in the EU.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"505-518"},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11043175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Practical Guidelines for Standardised Resolution of Important Protocol Deviations in Clinical Trials Conducted in Sub-Saharan Africa. 在撒哈拉以南非洲进行的临床试验中标准化解决重要协议偏差的实用指南》。
IF 1.5 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-05-01 Epub Date: 2024-01-29 DOI: 10.1007/s43441-023-00604-3
Armel Zemsi, Lorraine Jinette Guedem Nekame, Nuredin Mohammed, Elizabeth Stanley Batchilly, Edgard Dabira, Sheikh Omar Sillah, Gibbi Sey, Daisy H Williams, Bai-Lamin Dondeh, Carla Cerami, Ed Clarke, Umberto D'Alessandro

A clinical trial is any research on human subjects that involves an investigational medicinal product or device. Investigational medicinal products include unlicensed drugs or drugs used outside the product license (e.g. for a new indication) (ICH-GCP). As per the internationally accepted ICH-GCP guidelines, clinical trials should be conducted strictly per the approved protocol. However, during the lifecycle of a trial, protocol deviations may occur. Under ICH efficacy guidelines, protocol deviations are divided into non-important (minor) or important (major), and the latter can jeopardise the participant's rights, safety or the quality of data generated by the study. Existing guidelines on protocol deviation management do not detail or standardise actions to be taken for participants, investigational products, data or samples as part of a holistic management of important protocol deviations. Herein, we propose guidelines to address the current literature gap and promote the standardisation of actions to address important protocol deviations in clinical trials. The advised actions should complement the existing local institutional review board and national regulatory authority requirements.

临床试验是指任何涉及研究用医药产品或器械的人体研究。研究用医药产品包括未经许可的药物或在产品许可证之外使用的药物(如用于新适应症)(ICH-GCP)。根据国际公认的 ICH-GCP 指南,临床试验应严格按照批准的方案进行。然而,在试验的生命周期内,可能会出现方案偏离的情况。根据 ICH 疗效指南,方案偏差分为非重要(次要)和重要(主要)两种,后者可能会危及参与者的权利、安全或研究产生的数据质量。现有的方案偏差管理指南并没有详细说明或规范对参与者、研究产品、数据或样本所采取的行动,作为重要方案偏差整体管理的一部分。在此,我们提出指导方针,以解决目前的文献空白,并促进处理临床试验中重要方案偏差的行动标准化。建议的行动应与当地机构审查委员会和国家监管机构的现有要求相辅相成。
{"title":"Practical Guidelines for Standardised Resolution of Important Protocol Deviations in Clinical Trials Conducted in Sub-Saharan Africa.","authors":"Armel Zemsi, Lorraine Jinette Guedem Nekame, Nuredin Mohammed, Elizabeth Stanley Batchilly, Edgard Dabira, Sheikh Omar Sillah, Gibbi Sey, Daisy H Williams, Bai-Lamin Dondeh, Carla Cerami, Ed Clarke, Umberto D'Alessandro","doi":"10.1007/s43441-023-00604-3","DOIUrl":"10.1007/s43441-023-00604-3","url":null,"abstract":"<p><p>A clinical trial is any research on human subjects that involves an investigational medicinal product or device. Investigational medicinal products include unlicensed drugs or drugs used outside the product license (e.g. for a new indication) (ICH-GCP). As per the internationally accepted ICH-GCP guidelines, clinical trials should be conducted strictly per the approved protocol. However, during the lifecycle of a trial, protocol deviations may occur. Under ICH efficacy guidelines, protocol deviations are divided into non-important (minor) or important (major), and the latter can jeopardise the participant's rights, safety or the quality of data generated by the study. Existing guidelines on protocol deviation management do not detail or standardise actions to be taken for participants, investigational products, data or samples as part of a holistic management of important protocol deviations. Herein, we propose guidelines to address the current literature gap and promote the standardisation of actions to address important protocol deviations in clinical trials. The advised actions should complement the existing local institutional review board and national regulatory authority requirements.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"395-403"},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11043146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139571508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Modified Delphi Study to Establish Essential Clinical Pharmacology Competencies. 修改后的德尔菲研究,以确定临床药理学的基本能力。
IF 1.5 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-05-01 Epub Date: 2024-02-06 DOI: 10.1007/s43441-023-00609-y
Bernadette Johnson-Williams, Kellie Reynolds, Joga Gobburu, Albert Rundio

Introduction: Competency-based education has been commonly used to enhance the healthcare workforce for some time. A translational discipline that is integral to drug development and impactful on healthcare and public health is clinical pharmacology. With such contribution, it is essential that the clinical pharmacology workforce is adequately equipped to address the demands of emerging trends of drug development.

Objectives: The primary objective of this study was to determine the most significant competencies needed for a clinical pharmacologist in the regulatory environment.

Methods: A two round modified Delphi technique was administered to 29 clinical pharmacologists within the Office of Clinical Pharmacology (OCP) between November 2021-January 2022. A questionnaire consisting of core and technical competencies was administered electronically using SurveyMonkey ® to gain consensus about essential clinical pharmacology competencies. Participants used a Likert scale to rank importance of competencies from strongly agree (1), agree (2), neutral (3), disagree (4), strongly disagree (5). Participants also suggested topics to be included in the next round. Consensus was set at 60%. The competencies receiving the most consensus at 60% in round one and the new topics proceeded to the second round. In the second and final round, participants ranked the suggested competencies. Descriptive statistics and a McNemar change test were utilized to analyze data. Only data from the participants who completed both rounds was used in the study.

Results: In round one participants ranked all fifty-six core and technical competencies as essential with consensus of at least 60%. In round two, participants ranked sixty-two competencies as essential with consensus of at least 60%. A McNemar change test demonstrated stability of ranking between rounds.

Conclusion: Essential core and technical competencies can build education programs to sustain the emerging clinical pharmacology workforce in the Office of Clinical Pharmacology. The Delphi technique is a suitable approach to determine essential competencies because it cultivates consensus and gains insight from experts in the forefront of drug development.

导言:一段时间以来,能力本位教育已普遍用于提高医疗保健人员的能力。临床药理学是一门转化学科,与药物开发密不可分,并对医疗保健和公共卫生产生影响。临床药理学的贡献如此之大,因此临床药理学人员必须具备足够的能力,以应对药物开发新趋势的需求:本研究的主要目的是确定临床药理学家在监管环境中所需的最重要能力:在 2021 年 11 月至 2022 年 1 月期间,对临床药理学办公室 (OCP) 的 29 名临床药理学家进行了两轮改良德尔菲技术调查。使用 SurveyMonkey ® 以电子方式发放了一份由核心能力和技术能力组成的调查问卷,以就基本临床药理学能力达成共识。参与者使用李克特量表对能力的重要性进行了排序:非常同意 (1)、同意 (2)、中立 (3)、不同意 (4)、非常不同意 (5)。与会者还提出了下一轮的议题。共识率设定为 60%。在第一轮中获得最多共识(60%)的能力和新议题进入第二轮。在第二轮也是最后一轮中,参与者对建议的能力进行排名。数据分析采用了描述性统计和 McNemar 变化检验。研究仅使用了完成两轮的参与者的数据:在第一轮中,参与者将所有 56 项核心能力和技术能力都列为必备能力,共识度至少达到 60%。在第二轮中,参与者将六十二项能力列为必备能力,共识度至少为 60%。McNemar 变化测试表明,各轮之间的排序具有稳定性:结论:基本核心能力和技术能力可以建立教育计划,以维持临床药理办公室新兴的临床药理人才队伍。德尔菲技术是确定基本能力的合适方法,因为它能达成共识,并从药物开发前沿的专家那里获得真知灼见。
{"title":"A Modified Delphi Study to Establish Essential Clinical Pharmacology Competencies.","authors":"Bernadette Johnson-Williams, Kellie Reynolds, Joga Gobburu, Albert Rundio","doi":"10.1007/s43441-023-00609-y","DOIUrl":"10.1007/s43441-023-00609-y","url":null,"abstract":"<p><strong>Introduction: </strong>Competency-based education has been commonly used to enhance the healthcare workforce for some time. A translational discipline that is integral to drug development and impactful on healthcare and public health is clinical pharmacology. With such contribution, it is essential that the clinical pharmacology workforce is adequately equipped to address the demands of emerging trends of drug development.</p><p><strong>Objectives: </strong>The primary objective of this study was to determine the most significant competencies needed for a clinical pharmacologist in the regulatory environment.</p><p><strong>Methods: </strong>A two round modified Delphi technique was administered to 29 clinical pharmacologists within the Office of Clinical Pharmacology (OCP) between November 2021-January 2022. A questionnaire consisting of core and technical competencies was administered electronically using SurveyMonkey ® to gain consensus about essential clinical pharmacology competencies. Participants used a Likert scale to rank importance of competencies from strongly agree (1), agree (2), neutral (3), disagree (4), strongly disagree (5). Participants also suggested topics to be included in the next round. Consensus was set at 60%. The competencies receiving the most consensus at 60% in round one and the new topics proceeded to the second round. In the second and final round, participants ranked the suggested competencies. Descriptive statistics and a McNemar change test were utilized to analyze data. Only data from the participants who completed both rounds was used in the study.</p><p><strong>Results: </strong>In round one participants ranked all fifty-six core and technical competencies as essential with consensus of at least 60%. In round two, participants ranked sixty-two competencies as essential with consensus of at least 60%. A McNemar change test demonstrated stability of ranking between rounds.</p><p><strong>Conclusion: </strong>Essential core and technical competencies can build education programs to sustain the emerging clinical pharmacology workforce in the Office of Clinical Pharmacology. The Delphi technique is a suitable approach to determine essential competencies because it cultivates consensus and gains insight from experts in the forefront of drug development.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"473-482"},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11043191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Incorporating Prior Data in Quantitative Benefit-Risk Assessments: Case Study of a Bayesian Method. 将先验数据纳入量化效益-风险评估:贝叶斯方法案例研究。
IF 1.5 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-05-01 Epub Date: 2024-01-24 DOI: 10.1007/s43441-023-00611-4
Sai Dharmarajan, Zhong Yuan, Yeh-Fong Chen, Leila Lackey, Saurabh Mukhopadhyay, Pritibha Singh, Ram Tiwari

Background: Multiple criteria decision analysis (MCDA) and stochastic multi-criteria acceptability analysis (SMAA) in their current implementation cannot incorporate prior or external information on benefits and risks. We demonstrate how to incorporate prior data using a Bayesian mixture model approach while conducting quantitative benefit-risk assessments (qBRA) for medical products.

Methods: We implemented MCDA and SMAA in a Bayesian framework. To incorporate information from a prior study, we use mixture priors on each benefit and risk attribute that mixes information from a previous study with a vague prior distribution. The degree of borrowing is varied using a mixing proportion parameter.

Results: A demonstration case study for qBRA using the supplementary New Drug Application (sNDA) filing for Rivaroxaban for the indication of reduction in the risk of major thrombotic vascular events in patients with peripheral artery disease (PAD) was used to illustrate the method. Net utility scores, obtained from the randomized controlled trial data to support the sNDA, from the MCDA for Rivaraxoban and comparator were 0.48 and 0.56, respectively, with Rivaroxaban being the preferred alternative only 33% of the time. We show that with only 30% borrowing from a previous RCT, the MCDA and SMAA results are favorable for Rivaroxaban, accounting for the seemingly aberrant results on all-cause death in the trial data used to support the sNDA.

Conclusion: Our method to formally incorporate prior data in MCDA and SMAA is easy to use and interpret. Software in the form of an RShiny App is available here: https://sai-dharmarajan.shinyapps.io/BayesianMCDA_SMAA/ .

背景:多标准决策分析(MCDA)和随机多标准可接受性分析(SMAA)在目前的实施中无法纳入有关效益和风险的先验或外部信息。我们展示了如何使用贝叶斯混合模型方法在对医疗产品进行量化效益-风险评估(qBRA)时纳入先验数据:我们在贝叶斯框架内实施了 MCDA 和 SMAA。为了纳入先前研究的信息,我们在每个效益和风险属性上使用了混合先验,将先前研究的信息与模糊先验分布混合在一起。借用程度可通过混合比例参数来改变:结果:我们利用利伐沙班的补充新药申请(sNDA)来进行 qBRA 的示范案例研究,该新药申请的适应症是降低外周动脉疾病(PAD)患者发生重大血栓性血管事件的风险。从支持 sNDA 的随机对照试验数据中获得的利伐沙班和对比药的 MCDA 净效用分数分别为 0.48 和 0.56,其中只有 33% 的情况下利伐沙班是首选。我们的研究表明,只有30%的时间借鉴了先前的一项RCT,MCDA和SMAA结果对利伐沙班有利,从而解释了用于支持sNDA的试验数据在全因死亡方面看似反常的结果:我们将先前数据正式纳入 MCDA 和 SMAA 的方法易于使用和解释。RShiny应用程序形式的软件可在此处获取:https://sai-dharmarajan.shinyapps.io/BayesianMCDA_SMAA/ 。
{"title":"Incorporating Prior Data in Quantitative Benefit-Risk Assessments: Case Study of a Bayesian Method.","authors":"Sai Dharmarajan, Zhong Yuan, Yeh-Fong Chen, Leila Lackey, Saurabh Mukhopadhyay, Pritibha Singh, Ram Tiwari","doi":"10.1007/s43441-023-00611-4","DOIUrl":"10.1007/s43441-023-00611-4","url":null,"abstract":"<p><strong>Background: </strong>Multiple criteria decision analysis (MCDA) and stochastic multi-criteria acceptability analysis (SMAA) in their current implementation cannot incorporate prior or external information on benefits and risks. We demonstrate how to incorporate prior data using a Bayesian mixture model approach while conducting quantitative benefit-risk assessments (qBRA) for medical products.</p><p><strong>Methods: </strong>We implemented MCDA and SMAA in a Bayesian framework. To incorporate information from a prior study, we use mixture priors on each benefit and risk attribute that mixes information from a previous study with a vague prior distribution. The degree of borrowing is varied using a mixing proportion parameter.</p><p><strong>Results: </strong>A demonstration case study for qBRA using the supplementary New Drug Application (sNDA) filing for Rivaroxaban for the indication of reduction in the risk of major thrombotic vascular events in patients with peripheral artery disease (PAD) was used to illustrate the method. Net utility scores, obtained from the randomized controlled trial data to support the sNDA, from the MCDA for Rivaraxoban and comparator were 0.48 and 0.56, respectively, with Rivaroxaban being the preferred alternative only 33% of the time. We show that with only 30% borrowing from a previous RCT, the MCDA and SMAA results are favorable for Rivaroxaban, accounting for the seemingly aberrant results on all-cause death in the trial data used to support the sNDA.</p><p><strong>Conclusion: </strong>Our method to formally incorporate prior data in MCDA and SMAA is easy to use and interpret. Software in the form of an RShiny App is available here: https://sai-dharmarajan.shinyapps.io/BayesianMCDA_SMAA/ .</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"415-422"},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139543108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Evolving Regulatory Paradigm of AI in MedTech: A Review of Perspectives and Where We Are Today. 医疗技术领域人工智能监管范式的演变:观点回顾与现状。
IF 1.5 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-05-01 Epub Date: 2024-03-25 DOI: 10.1007/s43441-024-00628-3
Karen Zhou, Ginny Gattinger

Artificial intelligence (AI)-enabled technologies in the MedTech sector hold the promise to transform healthcare delivery by improving access, quality, and outcomes. As the regulatory contours of these technologies are being defined, there is a notable lack of literature on the key stakeholders such as the organizations and interest groups that have a significant input in shaping the regulatory framework. This article explores the perspectives and contributions of these stakeholders in shaping the regulatory paradigm of AI-enabled medical technologies. The formation of an AI regulatory framework requires the convergence of ethical, regulatory, technical, societal, and practical considerations. These multiple perspectives contribute to the various dimensions of an evolving regulatory paradigm. From the global governance guidelines set by the World Health Organization (WHO) to national regulations, the article sheds light not just on these multiple perspectives but also on their interconnectedness in shaping the regulatory landscape of AI.

医疗技术领域的人工智能(AI)技术有望通过改善医疗服务的可及性、质量和效果来改变医疗服务。在确定这些技术的监管轮廓时,明显缺乏有关主要利益相关者的文献,例如对监管框架的形成有重要影响的组织和利益集团。本文探讨了这些利益相关者在塑造人工智能医疗技术监管模式方面的观点和贡献。人工智能监管框架的形成需要汇集伦理、监管、技术、社会和实践方面的考虑。这些多重视角有助于形成不断发展的监管范式的各个层面。从世界卫生组织(WHO)制定的全球治理准则到国家法规,文章不仅揭示了这些多重视角,还揭示了它们在塑造人工智能监管格局方面的相互联系。
{"title":"The Evolving Regulatory Paradigm of AI in MedTech: A Review of Perspectives and Where We Are Today.","authors":"Karen Zhou, Ginny Gattinger","doi":"10.1007/s43441-024-00628-3","DOIUrl":"10.1007/s43441-024-00628-3","url":null,"abstract":"<p><p>Artificial intelligence (AI)-enabled technologies in the MedTech sector hold the promise to transform healthcare delivery by improving access, quality, and outcomes. As the regulatory contours of these technologies are being defined, there is a notable lack of literature on the key stakeholders such as the organizations and interest groups that have a significant input in shaping the regulatory framework. This article explores the perspectives and contributions of these stakeholders in shaping the regulatory paradigm of AI-enabled medical technologies. The formation of an AI regulatory framework requires the convergence of ethical, regulatory, technical, societal, and practical considerations. These multiple perspectives contribute to the various dimensions of an evolving regulatory paradigm. From the global governance guidelines set by the World Health Organization (WHO) to national regulations, the article sheds light not just on these multiple perspectives but also on their interconnectedness in shaping the regulatory landscape of AI.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"456-464"},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11043174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Building a Competency Framework to Integrate Inter-disciplinary Precision Medicine Capabilities into the Medical Technology and Pharmaceutical Industry. 建立能力框架,将跨学科精准医学能力融入医疗技术和制药行业。
IF 1.5 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-05-01 Epub Date: 2024-03-15 DOI: 10.1007/s43441-024-00626-5
Nicholette Conway, Orin Chisholm

Introduction: Integration of precision medicine (PM) competencies across the Medical Technology and Pharmaceutical industry is critical to enable industry professionals to understand and develop the skills needed to navigate the opportunities arising from rapid scientific and technological innovation in PM. Our objective was to identify the key competency domains required by industry professionals to enable them to upskill themselves in PM-related aspects of their roles.

Methods: A desktop research review of current literature, curriculum, and healthcare trends identified a core set of domains and subdomains related to PM competencies that were consistent across multiple disciplines and competency frameworks. A survey was used to confirm the applicability of these domains to the cross-functional and multi-disciplinary work practices of industry professionals. Companies were requested to trial the domains to determine their relevance in practice and feedback was obtained.

Results: Four PM-relevant domains were identified from the literature review: medical science and technology; translational and clinical application; governance and regulation and professional practice. Survey results refined these domains, and case studies within companies confirmed the potential for this framework to be used as an adjunct to current role specific competency frameworks to provide a specific focus on needed PM capabilities.

Conclusion: The framework was well accepted by local industry as a supplement to role specific competency frameworks to provide a structure on how to integrate new and evolving technologies into their current workforce development planning and build a continuous learning and cross-disciplinary mindset.

导言:整合整个医疗技术和制药行业的精准医疗(PM)能力对于让行业专业人士了解和发展所需的技能至关重要,以把握精准医疗领域快速的科技创新所带来的机遇。我们的目标是确定行业专业人员所需的关键能力领域,使他们能够在与 PM 相关的方面提升自己的能力:方法:通过对当前文献、课程和医疗保健趋势的桌面研究回顾,确定了一套与项目管理能力相关的核心领域和子领域,这些领域在多个学科和能力框架中是一致的。通过调查确认了这些领域对行业专业人员跨职能和多学科工作实践的适用性。要求各公司试用这些领域,以确定它们在实践中的相关性,并获得了反馈意见:结果:从文献综述中确定了四个与项目管理相关的领域:医学科学与技术、转化与临床应用、治理与监管以及专业实践。调查结果完善了这些领域,公司内部的案例研究证实,该框架有可能作为当前特定角色能力框架的辅助工具,为所需的项目管理能力提供具体重点:该框架作为特定角色能力框架的补充,为如何将新技术和不断发展的技术融入当前劳动力发展规划以及建立持续学习和跨学科思维提供了一个架构,得到了本地行业的广泛认可。
{"title":"Building a Competency Framework to Integrate Inter-disciplinary Precision Medicine Capabilities into the Medical Technology and Pharmaceutical Industry.","authors":"Nicholette Conway, Orin Chisholm","doi":"10.1007/s43441-024-00626-5","DOIUrl":"10.1007/s43441-024-00626-5","url":null,"abstract":"<p><strong>Introduction: </strong>Integration of precision medicine (PM) competencies across the Medical Technology and Pharmaceutical industry is critical to enable industry professionals to understand and develop the skills needed to navigate the opportunities arising from rapid scientific and technological innovation in PM. Our objective was to identify the key competency domains required by industry professionals to enable them to upskill themselves in PM-related aspects of their roles.</p><p><strong>Methods: </strong>A desktop research review of current literature, curriculum, and healthcare trends identified a core set of domains and subdomains related to PM competencies that were consistent across multiple disciplines and competency frameworks. A survey was used to confirm the applicability of these domains to the cross-functional and multi-disciplinary work practices of industry professionals. Companies were requested to trial the domains to determine their relevance in practice and feedback was obtained.</p><p><strong>Results: </strong>Four PM-relevant domains were identified from the literature review: medical science and technology; translational and clinical application; governance and regulation and professional practice. Survey results refined these domains, and case studies within companies confirmed the potential for this framework to be used as an adjunct to current role specific competency frameworks to provide a specific focus on needed PM capabilities.</p><p><strong>Conclusion: </strong>The framework was well accepted by local industry as a supplement to role specific competency frameworks to provide a structure on how to integrate new and evolving technologies into their current workforce development planning and build a continuous learning and cross-disciplinary mindset.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"567-577"},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11043185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140140779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Approaches to Design an Efficient, Predictable Global Post-approval Change Management System that Facilitates Continual Improvement and Drug Product Availability. 设计高效、可预测的全球批准后变更管理系统以促进持续改进和药品供应的方法。
IF 1.5 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-05-01 Epub Date: 2024-02-18 DOI: 10.1007/s43441-024-00614-9
Anders Vinther, Emma Ramnarine, Thierry Gastineau, Laura O'Brien, Oliver Brehm, David Fryrear

The complexity and inter-connectedness of operating in a global world for drug product supply has become an undeniable reality, further underscored by the COVID-19 pandemic. For Post-Approval Changes (PACs) that are an inevitable part of a product's commercial life, the impact of the growing global regulatory complexity and related drug shortages has brought the Global PAC Management System to an inflection point in particular for companies that have their products marketed in many countries.This paper illustrates through data analyzed for the first time from 145,000 + PACs for 156 countries, collected by 18 global pharma companies over a 3-year period (2019-2021), how severe the problem of global regulatory complexity is. Only PACs requiring national regulatory agency (NRA) approval prior to implementation were included in the data set. 1 of the 156 country NRAs approved all submitted PACs within a period of 6 months. The 6-month timeline was chosen because it is the recommended review timeline for major changes in the WHO guidance for vaccines and biotherapeutic products. 10 out of the 156 (6%) countries had no more than 10% of the PACs reviewed and approved in > 6 months. In 33 (22%) countries more than half of the PACs took > 6 months for approval. It is rare that the same PAC is approved globally within 6 months as individual NRAs take from a few months to years (in some cases > 5 years) for their review.The global PAC management complexity has steadily grown over the past 20 years. Attempts thus far to solve this problem have not made any meaningful difference. Senior leaders and decision-makers across the interdependent components of the complex Global PAC Management System (industry and regulators) must come together and collaboratively manage the problem holistically with the objective of ensuring global drug product availability instead of continuing with distinct stakeholder or country-focused solutions, which can tend to worsen the problem.In this paper, the Chief Quality Officers (CQOs) from 18 of the largest innovator pharma companies (see Acknowledgements) are speaking with One-Voice-of-Quality for PACs (1VQ for PACs Initiative). They are recommending a set of 8 approaches to activate a holistic transformation of the Global PAC Management System. This article presents their view on the problem of global regulatory complexity for managing PACs, it's impact on continual improvement and the risk to drug product supply, as well as approaches that can help alleviate the problem.

在全球范围内运作药品供应的复杂性和相互关联性已成为不可否认的现实,COVID-19 大流行病进一步凸显了这一点。对于产品商业生命周期中不可避免的批准后变更(PAC)而言,全球监管复杂性的不断增加以及相关药品短缺的影响,已使全球 PAC 管理系统面临拐点,尤其是对于产品在多个国家上市的公司而言。本文通过首次分析 18 家全球制药公司在 3 年内(2019-2021 年)从 156 个国家收集的 145,000 + PAC 中获得的数据,说明了全球监管复杂性问题的严重性。数据集仅包括在实施前需要国家监管机构(NRA)批准的 PAC。156 个国家的国家监管机构中有 1 个在 6 个月内批准了所有提交的 PAC。之所以选择 6 个月的时限,是因为这是世卫组织疫苗和生物治疗产品指南中重大变更的建议审查时限。在 156 个国家中,有 10 个国家(6%)在 6 个月内审查和批准的 PAC 不超过 10%。在 33 个国家(22%)中,一半以上的 PAC 需要 6 个月以上的时间才能获得批准。在过去 20 年中,全球 PAC 管理的复杂性不断增加。过去 20 年来,全球 PAC 管理的复杂性不断增加。复杂的全球 PAC 管理系统中相互依存的各个组成部分(行业和监管机构)的高层领导和决策者必须走到一起,以确保全球药品供应为目标,共同合作管理这一问题,而不是继续采用以利益相关者或国家为重点的不同解决方案,因为这些解决方案往往会使问题更加恶化。在本文中,来自 18 家最大的创新制药公司(见致谢)的首席质量官 (CQO) 就 PAC 的 "一个质量声音"(1VQ for PACs Initiative)发表了看法。他们推荐了一套 8 种方法,以启动全球 PAC 管理系统的整体转型。本文介绍了他们对管理 PAC 的全球监管复杂性问题、其对持续改进的影响和对药品供应的风险的看法,以及有助于缓解这一问题的方法。
{"title":"Approaches to Design an Efficient, Predictable Global Post-approval Change Management System that Facilitates Continual Improvement and Drug Product Availability.","authors":"Anders Vinther, Emma Ramnarine, Thierry Gastineau, Laura O'Brien, Oliver Brehm, David Fryrear","doi":"10.1007/s43441-024-00614-9","DOIUrl":"10.1007/s43441-024-00614-9","url":null,"abstract":"<p><p>The complexity and inter-connectedness of operating in a global world for drug product supply has become an undeniable reality, further underscored by the COVID-19 pandemic. For Post-Approval Changes (PACs) that are an inevitable part of a product's commercial life, the impact of the growing global regulatory complexity and related drug shortages has brought the Global PAC Management System to an inflection point in particular for companies that have their products marketed in many countries.This paper illustrates through data analyzed for the first time from 145,000 + PACs for 156 countries, collected by 18 global pharma companies over a 3-year period (2019-2021), how severe the problem of global regulatory complexity is. Only PACs requiring national regulatory agency (NRA) approval prior to implementation were included in the data set. 1 of the 156 country NRAs approved all submitted PACs within a period of 6 months. The 6-month timeline was chosen because it is the recommended review timeline for major changes in the WHO guidance for vaccines and biotherapeutic products. 10 out of the 156 (6%) countries had no more than 10% of the PACs reviewed and approved in > 6 months. In 33 (22%) countries more than half of the PACs took > 6 months for approval. It is rare that the same PAC is approved globally within 6 months as individual NRAs take from a few months to years (in some cases > 5 years) for their review.The global PAC management complexity has steadily grown over the past 20 years. Attempts thus far to solve this problem have not made any meaningful difference. Senior leaders and decision-makers across the interdependent components of the complex Global PAC Management System (industry and regulators) must come together and collaboratively manage the problem holistically with the objective of ensuring global drug product availability instead of continuing with distinct stakeholder or country-focused solutions, which can tend to worsen the problem.In this paper, the Chief Quality Officers (CQOs) from 18 of the largest innovator pharma companies (see Acknowledgements) are speaking with One-Voice-of-Quality for PACs (1VQ for PACs Initiative). They are recommending a set of 8 approaches to activate a holistic transformation of the Global PAC Management System. This article presents their view on the problem of global regulatory complexity for managing PACs, it's impact on continual improvement and the risk to drug product supply, as well as approaches that can help alleviate the problem.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"433-442"},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11043098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139900431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Access to Innovative Medicines: Regulation Change and Factors Associated with Drug Approval Lag in Malaysia. 获取创新药物:马来西亚的法规变化和药物审批滞后的相关因素。
IF 1.5 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-05-01 Epub Date: 2024-02-20 DOI: 10.1007/s43441-024-00620-x
Wan Lee Chow, Nur Afiqah Mohd Salleh, Tse Siang Kang

Background: Drug approval lag is the time difference for new medicine to obtain marketing authorization approval in the study country compared to the first global approval. Drug approval lag delays the availability of innovative medicine to patients. This may lead to delay in treatment and severe public health implications. The study aimed to determine drug approval lag in Malaysia, the factors associated with drug approval lag (drug characteristics, regulatory factors and applicant type) and the association of the submission lag and review time with the regulation change.

Methods: All new pharmaceutical products approved between January 2015 and March 2021 were examined (n = 136) using publicly available information. Factors associated with drug approval lag were determined using multiple linear regression.

Results: The median drug approval lag was 855 days. Drug approval lag was associated with drug characteristics and regulatory factors. Median submission lag and median review time for products which fulfilled the requirement for the new regulations (Conditional Registration/ Facilitated Registration Pathway) were shorter compared to products which did not fulfil the requirement.

Conclusion: Drug approval lag may delay the access of innovative medicine to patients, and this may lead to an increase in morbidity, mortality and healthcare costs. Good Regulatory Practices ensure efficient and transparent regulatory system which support the public health policy objectives in the most efficient way. The new regulations in Malaysia reduced the median submission lag and review time. The findings may be useful for regulators to consider for future policy development for medication access.

背景:药品审批滞后是指新药品在研究国家获得上市许可批准与首次获得全球批准之间的时间差。药物审批滞后会延误患者获得创新药物的时间。这可能会导致治疗延误,并对公共卫生造成严重影响。本研究旨在确定马来西亚的药品审批滞后情况、与药品审批滞后相关的因素(药品特征、监管因素和申请人类型)以及提交滞后和审查时间与监管变化的关联:利用公开信息,对 2015 年 1 月至 2021 年 3 月期间批准的所有新药产品(n = 136)进行了研究。采用多元线性回归法确定了与药品审批滞后相关的因素:结果:药品审批滞后期的中位数为 855 天。药物审批滞后与药物特性和监管因素有关。与不符合要求的产品相比,符合新法规要求(有条件注册/简化注册途径)的产品的中位提交滞后期和中位审查时间较短:结论:药物审批滞后可能会延迟患者获得创新药物的时间,从而导致发病率、死亡率和医疗成本的增加。良好监管规范确保监管系统高效透明,以最有效的方式支持公共卫生政策目标。马来西亚的新法规缩短了提交滞后和审查时间的中位数。这些研究结果可供监管机构在今后制定药品使用政策时参考。
{"title":"Access to Innovative Medicines: Regulation Change and Factors Associated with Drug Approval Lag in Malaysia.","authors":"Wan Lee Chow, Nur Afiqah Mohd Salleh, Tse Siang Kang","doi":"10.1007/s43441-024-00620-x","DOIUrl":"10.1007/s43441-024-00620-x","url":null,"abstract":"<p><strong>Background: </strong>Drug approval lag is the time difference for new medicine to obtain marketing authorization approval in the study country compared to the first global approval. Drug approval lag delays the availability of innovative medicine to patients. This may lead to delay in treatment and severe public health implications. The study aimed to determine drug approval lag in Malaysia, the factors associated with drug approval lag (drug characteristics, regulatory factors and applicant type) and the association of the submission lag and review time with the regulation change.</p><p><strong>Methods: </strong>All new pharmaceutical products approved between January 2015 and March 2021 were examined (n = 136) using publicly available information. Factors associated with drug approval lag were determined using multiple linear regression.</p><p><strong>Results: </strong>The median drug approval lag was 855 days. Drug approval lag was associated with drug characteristics and regulatory factors. Median submission lag and median review time for products which fulfilled the requirement for the new regulations (Conditional Registration/ Facilitated Registration Pathway) were shorter compared to products which did not fulfil the requirement.</p><p><strong>Conclusion: </strong>Drug approval lag may delay the access of innovative medicine to patients, and this may lead to an increase in morbidity, mortality and healthcare costs. Good Regulatory Practices ensure efficient and transparent regulatory system which support the public health policy objectives in the most efficient way. The new regulations in Malaysia reduced the median submission lag and review time. The findings may be useful for regulators to consider for future policy development for medication access.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"528-538"},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Decentralized Clinical Trials: Scientific Considerations Through the Lens of the Estimand Framework. 分散临床试验:从 Estimand 框架的角度考虑科学问题。
IF 1.5 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-05-01 Epub Date: 2024-02-05 DOI: 10.1007/s43441-024-00615-8
Rima Izem, Emmanuel Zuber, Nadia Daizadeh, Frank Bretz, Oleksandr Sverdlov, Pascal Edrich, Janice Branson, Evgeny Degtyarev, Nikolaos Sfikas, Robert Hemmings

While industry and regulators' interest in decentralized clinical trials (DCTs) is long-standing, the Covid-19 pandemic accelerated and broadened the adoption and experience with these trials. The key idea in decentralization is bringing the clinical trial design, typically on-site, closer to the patient's experience (on-site or off-site). Thus, potential benefits of DCTs include reducing the burden of participation in trials, broadening access to a more diverse population, or using innovative endpoints collected off-site. This paper helps researchers to carefully evaluate the added value and the implications of DCTs beyond the operational aspects of their implementation. The proposed approach is to use the ICH E9(R1) estimand framework to guide the strategic decisions around each decentralization component. Furthermore, the framework can guide the process for clinical trialists to systematically consider the implications of decentralization, in turn, for each attribute of the estimand. We illustrate the use of this approach with a fully DCT case study and show that the proposed systematic process can uncover the scientific opportunities, assumptions, and potential risks associated with a possible use of decentralization components in the design of a trial. This process can also highlight the benefits of specifying estimand attributes in a granular way. Thus, we demonstrate that bringing a decentralization component into the design will not only impact estimators and estimation but can also correspond to addressing more granular questions, thereby uncovering new target estimands.

尽管业界和监管机构对分散临床试验(DCT)的兴趣由来已久,但 Covid-19 大流行加速并扩大了这些试验的应用和经验。分散临床试验的关键理念是使临床试验设计(通常是现场设计)更贴近患者的体验(现场或非现场)。因此,分散临床试验的潜在益处包括减轻参与试验的负担、扩大更多不同人群的参与范围或使用场外收集的创新终点。本文将帮助研究人员仔细评估 DCT 的附加值及其实施操作之外的影响。建议采用的方法是使用 ICH E9(R1) 估计指标框架来指导围绕每个权力下放组成部分的战略决策。此外,该框架还能指导临床试验人员依次系统地考虑权力下放对估算指标每个属性的影响。我们通过一个完全 DCT 的案例研究来说明这种方法的使用,并表明所建议的系统流程可以发现与试验设计中可能使用的分散化组件相关的科学机遇、假设和潜在风险。这一过程还能突出以细粒度的方式指定估计值属性的好处。因此,我们证明,在设计中引入分散成分不仅会影响估算者和估算,还能解决更细化的问题,从而发现新的目标估算值。
{"title":"Decentralized Clinical Trials: Scientific Considerations Through the Lens of the Estimand Framework.","authors":"Rima Izem, Emmanuel Zuber, Nadia Daizadeh, Frank Bretz, Oleksandr Sverdlov, Pascal Edrich, Janice Branson, Evgeny Degtyarev, Nikolaos Sfikas, Robert Hemmings","doi":"10.1007/s43441-024-00615-8","DOIUrl":"10.1007/s43441-024-00615-8","url":null,"abstract":"<p><p>While industry and regulators' interest in decentralized clinical trials (DCTs) is long-standing, the Covid-19 pandemic accelerated and broadened the adoption and experience with these trials. The key idea in decentralization is bringing the clinical trial design, typically on-site, closer to the patient's experience (on-site or off-site). Thus, potential benefits of DCTs include reducing the burden of participation in trials, broadening access to a more diverse population, or using innovative endpoints collected off-site. This paper helps researchers to carefully evaluate the added value and the implications of DCTs beyond the operational aspects of their implementation. The proposed approach is to use the ICH E9(R1) estimand framework to guide the strategic decisions around each decentralization component. Furthermore, the framework can guide the process for clinical trialists to systematically consider the implications of decentralization, in turn, for each attribute of the estimand. We illustrate the use of this approach with a fully DCT case study and show that the proposed systematic process can uncover the scientific opportunities, assumptions, and potential risks associated with a possible use of decentralization components in the design of a trial. This process can also highlight the benefits of specifying estimand attributes in a granular way. Thus, we demonstrate that bringing a decentralization component into the design will not only impact estimators and estimation but can also correspond to addressing more granular questions, thereby uncovering new target estimands.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"495-504"},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
New Benchmarks on Protocol Amendment Practices, Trends and their Impact on Clinical Trial Performance. 协议修订实践、趋势及其对临床试验绩效影响的新基准。
IF 1.5 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-05-01 Epub Date: 2024-03-04 DOI: 10.1007/s43441-024-00622-9
Kenneth Getz, Zachary Smith, Emily Botto, Elisabeth Murphy, Arnaud Dauchy

The Tufts Center for the Study of Drug Development (Tufts CSDD) conducted a follow-up study in 2022 to assess trends in protocol amendment experiences and the impact amendments have had on clinical trial performance, particularly during the COVID-19 pandemic. Sixteen pharmaceutical companies and contract research organizations provided data on 950 protocols and 2188 amendments. The results show that, since 2015, the prevalence of protocols with at least one amendment in phases I-IV has increased substantially (from 57 to 76%) and the mean number of amendments per protocol has increased 60% to 3.3, up from 2.1. Phase I and III protocols saw the highest increases in the mean number of amendments implemented per protocol. A much higher percentage of amendments-77%-were deemed unavoidable with regulatory agency requests and changes to the study strategy as the top reasons cited for amending a protocol. The total average duration to implement an amendment has nearly tripled during the past decade. The time from identifying the need-to-amend to last oversight approval now takes an average of 260 days and the mean duration during which investigative sites operate with different versions of the clinical trial protocol spans 215 days. Protocols that implemented at least one amendment were more effective at increasing patient screening volume and reducing the actual number of patients enrolled relative to plan. Lastly, the prevalence of protocols with at least one amendment and mean number of amendments was significantly higher for protocols conducted during the pandemic.

塔夫茨药物开发研究中心(Tufts CSDD)于 2022 年开展了一项后续研究,以评估方案修订经验的趋势以及修订对临床试验绩效的影响,尤其是在 COVID-19 大流行期间。16 家制药公司和合同研究组织提供了 950 个方案和 2188 次修订的数据。结果显示,自 2015 年以来,I-IV 期至少有一次修订的方案比例大幅增加(从 57% 增加到 76%),每个方案的平均修订次数从 2.1 次增加到 3.3 次,增幅达 60%。第 I 和第 III 阶段规程的平均修正次数增幅最大。更高的修订比例(77%)被认为是不可避免的,监管机构的要求和研究策略的改变是修订方案的首要原因。在过去十年中,实施修订的总平均时间几乎增加了两倍。现在,从确定需要修订到最后获得监管机构批准平均需要 260 天,研究机构使用不同版本临床试验方案的平均时间为 215 天。至少实施过一次修订的方案在增加患者筛选量和减少实际入组患者数量方面比计划更为有效。最后,在大流行期间实施的方案中,至少进行过一次修订的方案比例和平均修订次数明显更高。
{"title":"New Benchmarks on Protocol Amendment Practices, Trends and their Impact on Clinical Trial Performance.","authors":"Kenneth Getz, Zachary Smith, Emily Botto, Elisabeth Murphy, Arnaud Dauchy","doi":"10.1007/s43441-024-00622-9","DOIUrl":"10.1007/s43441-024-00622-9","url":null,"abstract":"<p><p>The Tufts Center for the Study of Drug Development (Tufts CSDD) conducted a follow-up study in 2022 to assess trends in protocol amendment experiences and the impact amendments have had on clinical trial performance, particularly during the COVID-19 pandemic. Sixteen pharmaceutical companies and contract research organizations provided data on 950 protocols and 2188 amendments. The results show that, since 2015, the prevalence of protocols with at least one amendment in phases I-IV has increased substantially (from 57 to 76%) and the mean number of amendments per protocol has increased 60% to 3.3, up from 2.1. Phase I and III protocols saw the highest increases in the mean number of amendments implemented per protocol. A much higher percentage of amendments-77%-were deemed unavoidable with regulatory agency requests and changes to the study strategy as the top reasons cited for amending a protocol. The total average duration to implement an amendment has nearly tripled during the past decade. The time from identifying the need-to-amend to last oversight approval now takes an average of 260 days and the mean duration during which investigative sites operate with different versions of the clinical trial protocol spans 215 days. Protocols that implemented at least one amendment were more effective at increasing patient screening volume and reducing the actual number of patients enrolled relative to plan. Lastly, the prevalence of protocols with at least one amendment and mean number of amendments was significantly higher for protocols conducted during the pandemic.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"539-548"},"PeriodicalIF":1.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Therapeutic innovation & regulatory science
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1