首页 > 最新文献

Therapeutic innovation & regulatory science最新文献

英文 中文
A Systematic Review of Adaptive Seamless Clinical Trials for Late-Phase Oncology Development. 肿瘤学后期发展的自适应无缝临床试验系统性回顾。
IF 2 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-09-01 Epub Date: 2024-06-11 DOI: 10.1007/s43441-024-00670-1
Kristine Broglio, Freda Cooner, Yujun Wu, Mike Xiao, X Q Xue, Marina Lowen, Izuagie Ikhapoh, Philip He

Introduction: Although oncology has seen large scientific and clinical advances over the last decade, it also has one of the lowest success rates for novel agents across therapeutic areas. Adaptive clinical trial design has been a popular option for increasing clinical trial efficiency and the chances of trial success. Seamless clinical trial design are studies in which two or more clinical trial phases are combined into a single study with a pre-specified transition between stages. This integration of phases may enhance efficiency.

Methods: To understand the precedent for the use of seamless designs, this working group was formed to conduct a comprehensive literature search on seamless clinical trials conducted with confirmatory intent in oncology. Trial design features were extracted into a database and analyzed with descriptive statistics.

Results: A literature search identified 68 clinical trials meeting inclusion and exclusion criteria. The most common design feature was a gate on treatment efficacy, where the trial would only proceed to the second stage if sufficient efficacy was observed in the first. The next most common feature was a selection of a dose or treatment regimen. Inferentially and operationally seamless designs were approximately equally represented.

Discussion: Key statistical considerations for seamless phase II/III designs include optimizing design choices by evaluating and comparing operating characteristics across design alternatives as well as showing control of overall Type I error rates. Executing the transition between phases should be evaluated for issues related to accrual, drug production, and procedures to maintain trial integrity.

Conclusions: While there are unique statistical, regulatory, and operational considerations for seamless designs they are also uniquely suited to many development settings. These include, for example, addressing dose selection under FDA's Project Optimus and addressing the growing use of biomarkers and personalized medicine approaches in cancer treatment.

导言:尽管肿瘤学在过去十年中取得了巨大的科学和临床进步,但它也是所有治疗领域中新型药物成功率最低的领域之一。自适应临床试验设计一直是提高临床试验效率和试验成功几率的热门选择。无缝临床试验设计是指将两个或两个以上的临床试验阶段合并为一项研究,并预先规定阶段之间的过渡。这种阶段整合可提高效率:为了了解使用无缝设计的先例,我们成立了本工作组,对肿瘤学领域以确证为目的的无缝临床试验进行了全面的文献检索。将试验设计特点提取到数据库中,并进行描述性统计分析:文献检索发现了 68 项符合纳入和排除标准的临床试验。最常见的设计特征是疗效关,即只有在第一阶段观察到足够的疗效,试验才会进入第二阶段。其次最常见的特征是选择剂量或治疗方案。推断无缝设计和操作无缝设计的比例大致相当:讨论:II/III 期无缝设计的主要统计考虑因素包括通过评估和比较不同设计方案的操作特征来优化设计选择,以及显示对总体 I 类错误率的控制。应评估与应计制、药物生产和程序有关的问题,以保持试验的完整性:虽然无缝设计在统计、监管和操作方面有其独特的考虑因素,但它们也非常适合许多开发环境。例如,根据 FDA 的 Optimus 项目解决剂量选择问题,以及解决癌症治疗中越来越多地使用生物标记物和个性化医疗方法的问题。
{"title":"A Systematic Review of Adaptive Seamless Clinical Trials for Late-Phase Oncology Development.","authors":"Kristine Broglio, Freda Cooner, Yujun Wu, Mike Xiao, X Q Xue, Marina Lowen, Izuagie Ikhapoh, Philip He","doi":"10.1007/s43441-024-00670-1","DOIUrl":"10.1007/s43441-024-00670-1","url":null,"abstract":"<p><strong>Introduction: </strong>Although oncology has seen large scientific and clinical advances over the last decade, it also has one of the lowest success rates for novel agents across therapeutic areas. Adaptive clinical trial design has been a popular option for increasing clinical trial efficiency and the chances of trial success. Seamless clinical trial design are studies in which two or more clinical trial phases are combined into a single study with a pre-specified transition between stages. This integration of phases may enhance efficiency.</p><p><strong>Methods: </strong>To understand the precedent for the use of seamless designs, this working group was formed to conduct a comprehensive literature search on seamless clinical trials conducted with confirmatory intent in oncology. Trial design features were extracted into a database and analyzed with descriptive statistics.</p><p><strong>Results: </strong>A literature search identified 68 clinical trials meeting inclusion and exclusion criteria. The most common design feature was a gate on treatment efficacy, where the trial would only proceed to the second stage if sufficient efficacy was observed in the first. The next most common feature was a selection of a dose or treatment regimen. Inferentially and operationally seamless designs were approximately equally represented.</p><p><strong>Discussion: </strong>Key statistical considerations for seamless phase II/III designs include optimizing design choices by evaluating and comparing operating characteristics across design alternatives as well as showing control of overall Type I error rates. Executing the transition between phases should be evaluated for issues related to accrual, drug production, and procedures to maintain trial integrity.</p><p><strong>Conclusions: </strong>While there are unique statistical, regulatory, and operational considerations for seamless designs they are also uniquely suited to many development settings. These include, for example, addressing dose selection under FDA's Project Optimus and addressing the growing use of biomarkers and personalized medicine approaches in cancer treatment.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"917-929"},"PeriodicalIF":2.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301616","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
Overdosage Section in US and EU Labeling. 美国和欧盟标签中的超剂量部分。
IF 2 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-09-01 Epub Date: 2024-06-17 DOI: 10.1007/s43441-024-00673-y
Sarah Condon, Thomas G Cantu, Antony Constantinou, Erin C Degnan, Monica Lungu, Marcella G Paglione, Shreya J Parikh, Joanna Szewczyk

The Prescribing Information (PI) in the United States (US) and the Summary of Product Characteristics (SmPC) in the European Union (EU) are approved by the US Food & Drug Administration (FDA), and the European Medicines Agency (EMA), respectively. The inclusion of overdosage information in these documents is a regulatory requirement in both regions. This research evaluates the content of the overdosage section of US and EU labeling. The overdosage sections of labels for drugs approved in the US in three time periods were analyzed: 2000-2001, 2010-2011, and 2020-2021. EU labels for these same products were also reviewed if registered through the Centralized Procedure. Data collection and analyses were performed using a predefined questionnaire, focusing on adherence to regulatory requirements and identifying areas where additional regulatory guidance may be beneficial. The findings indicate that the content of the overdosage sections largely comply with the regulatory requirements of their respective regions. Fewer than half of the labels included information on supratherapeutic doses observed from clinical studies, risk factors for overdose or population specific data associated with overdose. Inconsistencies were noted concerning the incorporation of animal data when human data were available, in addition to the referencing of Poison Centers. The overall utility of non-specific treatment recommendations, in addition to gastric lavage is discussed. While the content of the overdosage section generally aligns with regulatory expectations, additional regulatory guidance could enhance consistency in how this section of labeling is presented and clarify expectations to improve its usefulness for health care professionals (HCPs).

美国的处方信息 (PI) 和欧盟的产品特征概要 (SmPC) 分别由美国食品药品管理局 (FDA) 和欧洲药品管理局 (EMA) 批准。在这些文件中纳入过量用药信息是这两个地区的监管要求。本研究对美国和欧盟标签中的超剂量部分的内容进行了评估。研究分析了 2000-2001、2010-2011 和 2020-2021 这三个时期美国批准的药品标签中的用药过量部分。如果通过集中程序注册,还对这些相同产品的欧盟标签进行了审查。数据收集和分析采用预定义的调查问卷进行,重点关注监管要求的遵守情况,并找出可能有利于提供更多监管指导的领域。调查结果表明,超剂量部分的内容基本符合各自地区的监管要求。只有不到一半的标签包含了临床研究观察到的超治疗剂量、用药过量的风险因素或与用药过量相关的特定人群数据等信息。除了参考毒物中心的资料外,还注意到在有人类数据的情况下纳入动物数据的不一致之处。除洗胃外,还讨论了非特异性治疗建议的总体效用。虽然过量用药部分的内容总体上符合监管要求,但额外的监管指导可加强标签中这部分内容表述的一致性,并明确要求,以提高其对医护专业人员 (HCP) 的实用性。
{"title":"Overdosage Section in US and EU Labeling.","authors":"Sarah Condon, Thomas G Cantu, Antony Constantinou, Erin C Degnan, Monica Lungu, Marcella G Paglione, Shreya J Parikh, Joanna Szewczyk","doi":"10.1007/s43441-024-00673-y","DOIUrl":"10.1007/s43441-024-00673-y","url":null,"abstract":"<p><p>The Prescribing Information (PI) in the United States (US) and the Summary of Product Characteristics (SmPC) in the European Union (EU) are approved by the US Food & Drug Administration (FDA), and the European Medicines Agency (EMA), respectively. The inclusion of overdosage information in these documents is a regulatory requirement in both regions. This research evaluates the content of the overdosage section of US and EU labeling. The overdosage sections of labels for drugs approved in the US in three time periods were analyzed: 2000-2001, 2010-2011, and 2020-2021. EU labels for these same products were also reviewed if registered through the Centralized Procedure. Data collection and analyses were performed using a predefined questionnaire, focusing on adherence to regulatory requirements and identifying areas where additional regulatory guidance may be beneficial. The findings indicate that the content of the overdosage sections largely comply with the regulatory requirements of their respective regions. Fewer than half of the labels included information on supratherapeutic doses observed from clinical studies, risk factors for overdose or population specific data associated with overdose. Inconsistencies were noted concerning the incorporation of animal data when human data were available, in addition to the referencing of Poison Centers. The overall utility of non-specific treatment recommendations, in addition to gastric lavage is discussed. While the content of the overdosage section generally aligns with regulatory expectations, additional regulatory guidance could enhance consistency in how this section of labeling is presented and clarify expectations to improve its usefulness for health care professionals (HCPs).</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"946-952"},"PeriodicalIF":2.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421104","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
Patient and Public Perceptions in Canada About Decentralized and Hybrid Clinical Trials: "It's About Time we Bring Trials to People". 加拿大患者和公众对分散和混合临床试验的看法:"是时候把试验带到人们身边了"。
IF 2 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-09-01 Epub Date: 2024-06-21 DOI: 10.1007/s43441-024-00665-y
Dawn P Richards, John Queenan, Linnea Aasen-Johnston, Heather Douglas, Terry Hawrysh, Michael Lapenna, Donna Lillie, Emily I McIntosh, Jenna Shea, Maureen Smith, Susan Marlin

Background: Little is known about patient and the public perspectives on decentralized and hybrid clinical trials in Canada.

Methods: We conducted an online survey (English and French) promoted on social media to understand perspectives of people in Canada about decentralized and hybrid clinical trials. The survey had two sections. We co-produced this project entirely with patient, caregiver, and family partners.

Results: The survey had 284 (14 French) individuals who started or completed Section 1, and 180 (16 French) individuals who started or completed Section 2. People prefer to have options to participate in clinical trials where aspects are decentralized or hybridized. 79% of respondents preferred to have options related to study visits. There were concerns about handling adverse events or potential complications in decentralized trials, however, communication options such as a dedicated contact person for participants was deemed helpful. Most respondents were amenable to informed consent being done at a satellite site closer to home or via technology and were split on privacy concerns about this. Most preferred travel to a site within an hour, depending on what the trial was for or its impact on quality of life. Due to the response rate, we were unable to explore associations with gender, age, health status, geography, ethnicity, and prior clinical trial participation.

Conclusion: Our findings indicate an openness in Canada to participating in trials that decentralize or hybridize some aspects. These trials are perceived to provide benefits to participants and ways to increase equity and accessibility for participants.

背景:人们对加拿大患者和公众对分散和混合临床试验的看法知之甚少:我们在社交媒体上开展了一项在线调查(英语和法语),以了解加拿大人对分散和混合临床试验的看法。调查分为两个部分。我们与患者、护理人员和家庭合作伙伴共同完成了这一项目:调查中有 284 人(14 名法国人)开始或完成了第一部分,180 人(16 名法国人)开始或完成了第二部分。人们更愿意选择参与分散或混合的临床试验。79%的受访者倾向于拥有与研究考察相关的选择权。有人担心在分散试验中如何处理不良事件或潜在的并发症,不过,他们认为专门的参试者联系人等沟通方式很有帮助。大多数受访者同意在离家较近的卫星试验点或通过技术手段进行知情同意,但在隐私问题上存在分歧。根据试验的目的或对生活质量的影响,大多数人倾向于在一小时内前往试验地点。由于回复率的原因,我们无法探讨与性别、年龄、健康状况、地理位置、种族和之前参与临床试验的关系:我们的研究结果表明,加拿大对参与分散或混合某些方面的试验持开放态度。这些试验被认为能为参与者带来益处,并能提高参与者的公平性和可及性。
{"title":"Patient and Public Perceptions in Canada About Decentralized and Hybrid Clinical Trials: \"It's About Time we Bring Trials to People\".","authors":"Dawn P Richards, John Queenan, Linnea Aasen-Johnston, Heather Douglas, Terry Hawrysh, Michael Lapenna, Donna Lillie, Emily I McIntosh, Jenna Shea, Maureen Smith, Susan Marlin","doi":"10.1007/s43441-024-00665-y","DOIUrl":"10.1007/s43441-024-00665-y","url":null,"abstract":"<p><strong>Background: </strong>Little is known about patient and the public perspectives on decentralized and hybrid clinical trials in Canada.</p><p><strong>Methods: </strong>We conducted an online survey (English and French) promoted on social media to understand perspectives of people in Canada about decentralized and hybrid clinical trials. The survey had two sections. We co-produced this project entirely with patient, caregiver, and family partners.</p><p><strong>Results: </strong>The survey had 284 (14 French) individuals who started or completed Section 1, and 180 (16 French) individuals who started or completed Section 2. People prefer to have options to participate in clinical trials where aspects are decentralized or hybridized. 79% of respondents preferred to have options related to study visits. There were concerns about handling adverse events or potential complications in decentralized trials, however, communication options such as a dedicated contact person for participants was deemed helpful. Most respondents were amenable to informed consent being done at a satellite site closer to home or via technology and were split on privacy concerns about this. Most preferred travel to a site within an hour, depending on what the trial was for or its impact on quality of life. Due to the response rate, we were unable to explore associations with gender, age, health status, geography, ethnicity, and prior clinical trial participation.</p><p><strong>Conclusion: </strong>Our findings indicate an openness in Canada to participating in trials that decentralize or hybridize some aspects. These trials are perceived to provide benefits to participants and ways to increase equity and accessibility for participants.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"965-977"},"PeriodicalIF":2.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432832","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
Use of Seamless Study Designs in Oncology Clinical Development- A Survey Conducted by IDSWG Oncology Sub-team. 肿瘤学临床开发中无缝研究设计的使用--IDSWG 肿瘤学分小组开展的一项调查。
IF 2 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-09-01 Epub Date: 2024-06-22 DOI: 10.1007/s43441-024-00676-9
Yingwen Dong, Gautier Paux, Kristine Broglio, Freda Cooner, Guozhi Gao, Wei He, Lei Gao, Xiaoqiang Xue, Philip He

Seamless study designs have the potential to accelerate clinical development. The use of innovative seamless designs has been increasing in the oncology area; however, while the concept of seamless designs becomes more popular and accepted, many challenges remain in both the design and conduct of these trials. This may be especially true when seamless designs are used in late phase development supporting regulatory decision-making. The Innovative Design Scientific Working Group (IDSWG) Oncology team conducted a survey to understand the current use of seamless study designs for registration purposes in oncology clinical development. The survey was designed to provide insights into the benefits and to identify the roadblocks. A total of 16 questions were included in the survey that was distributed using the ASA Biopharmaceutical Section and IDSWG email listings from August to September 2022. A total of 51 responses were received, with 39 (76%) respondents indicating that their organizations had seamless oncology studies in planning or implementation for registration purposes. Detailed survey results are presented in the manuscript. Overall, while seamless designs offer advantages in terms of timeline reduction and cost saving, they also present challenges related to additional complexity and the need for efficient surrogate clinical endpoints in oncology drug development.

无缝研究设计具有加速临床开发的潜力。在肿瘤学领域,创新性无缝设计的使用越来越多;然而,尽管无缝设计的概念越来越受欢迎和被接受,但在这些试验的设计和实施过程中仍然存在许多挑战。当无缝设计用于支持监管决策的晚期研发时,情况可能尤其如此。创新设计科学工作组(IDSWG)肿瘤学团队进行了一项调查,以了解目前在肿瘤学临床开发中为注册目的使用无缝研究设计的情况。该调查旨在深入了解无缝研究设计的益处,并找出存在的障碍。调查共包括 16 个问题,于 2022 年 8 月至 9 月期间通过 ASA 生物制药分会和 IDSWG 电子邮件列表分发。共收到 51 份回复,其中 39 位(76%)受访者表示其所在机构正在规划或实施以注册为目的的无缝肿瘤研究。详细调查结果见手稿。总之,虽然无缝设计在缩短时间和节约成本方面具有优势,但它们也带来了挑战,即增加了肿瘤药物开发的复杂性和对高效替代临床终点的需求。
{"title":"Use of Seamless Study Designs in Oncology Clinical Development- A Survey Conducted by IDSWG Oncology Sub-team.","authors":"Yingwen Dong, Gautier Paux, Kristine Broglio, Freda Cooner, Guozhi Gao, Wei He, Lei Gao, Xiaoqiang Xue, Philip He","doi":"10.1007/s43441-024-00676-9","DOIUrl":"10.1007/s43441-024-00676-9","url":null,"abstract":"<p><p>Seamless study designs have the potential to accelerate clinical development. The use of innovative seamless designs has been increasing in the oncology area; however, while the concept of seamless designs becomes more popular and accepted, many challenges remain in both the design and conduct of these trials. This may be especially true when seamless designs are used in late phase development supporting regulatory decision-making. The Innovative Design Scientific Working Group (IDSWG) Oncology team conducted a survey to understand the current use of seamless study designs for registration purposes in oncology clinical development. The survey was designed to provide insights into the benefits and to identify the roadblocks. A total of 16 questions were included in the survey that was distributed using the ASA Biopharmaceutical Section and IDSWG email listings from August to September 2022. A total of 51 responses were received, with 39 (76%) respondents indicating that their organizations had seamless oncology studies in planning or implementation for registration purposes. Detailed survey results are presented in the manuscript. Overall, while seamless designs offer advantages in terms of timeline reduction and cost saving, they also present challenges related to additional complexity and the need for efficient surrogate clinical endpoints in oncology drug development.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"978-986"},"PeriodicalIF":2.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440917","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
Standalone Regulatory Agreements for Product-Development Collaborations in the Medical Products Industry. 医疗产品行业产品开发合作的独立监管协议。
IF 2 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-09-01 Epub Date: 2024-05-31 DOI: 10.1007/s43441-024-00646-1
Mary E Wilhelm, Nancy Pire-Smerkanich, Frances J Richmond

Background: Medical-product companies often outsource research and manufacturing needs to contracting or partnering organizations but then must manage a challenging patchwork of regulatory activities. A standalone regulatory agreement could clarify the relationships and responsibilities between companies working jointly on a single regulated product. This study explored the need for and current use of standalone regulatory agreements.

Methods: A survey instrument was developed using an implementation framework and disseminated to mid- to senior-level employees and consultants for sponsor and vendor companies in the medical products sector.

Results: Of 294 respondents, about half, primarily from companies with more than 200 employees, were familiar with standalone regulatory agreements, and half of this subgroup had moved forward to implement them. Such agreements were considered beneficial to clarify regulatory roles and responsibilities, standardize regulatory expectations between the companies, and stimulate earlier discussion about joint regulatory strategies. However, the development of regulatory agreements appears challenged by the fact that such agreements are not required by regulatory agencies overseeing medical products and have no standardized templates, agency or industry guidance. Respondents whose organizations do not now use regulatory agreements either had not considered or did not see a need for a standalone agreement.

Conclusions: Standalone regulatory agreements are becoming more common but are not yet implemented fully by most companies. Their usefulness and content appeared to depend upon the type of partner, the complexity of the relationship and the availability of internal expertise and support.

背景:医疗产品公司经常将研究和生产需求外包给承包或合作组织,但随后必须管理具有挑战性的拼凑监管活动。一份独立的监管协议可以明确共同开发单一监管产品的公司之间的关系和责任。本研究探讨了对独立监管协议的需求和目前的使用情况:方法:利用实施框架开发了一种调查工具,并分发给医疗产品行业赞助商和供应商公司的中高层员工和顾问:在 294 名受访者中,约半数(主要来自员工人数超过 200 人的公司)熟悉独立监管协议,其中半数已着手实施。这些协议被认为有利于明确监管角色和责任,统一公司之间的监管预期,并促进更早地讨论联合监管战略。不过,监管协议的制定似乎面临挑战,因为监管医疗产品的监管机构并不要求签订此类协议,也没有标准化模板、机构或行业指导。目前没有使用监管协议的受访机构要么没有考虑过,要么认为没有必要签订独立协议:独立监管协议正变得越来越普遍,但大多数公司尚未全面实施。独立监管协议的有用性和内容似乎取决于合作伙伴的类型、关系的复杂程度以及是否具备内部专业知识和支持。
{"title":"Standalone Regulatory Agreements for Product-Development Collaborations in the Medical Products Industry.","authors":"Mary E Wilhelm, Nancy Pire-Smerkanich, Frances J Richmond","doi":"10.1007/s43441-024-00646-1","DOIUrl":"10.1007/s43441-024-00646-1","url":null,"abstract":"<p><strong>Background: </strong>Medical-product companies often outsource research and manufacturing needs to contracting or partnering organizations but then must manage a challenging patchwork of regulatory activities. A standalone regulatory agreement could clarify the relationships and responsibilities between companies working jointly on a single regulated product. This study explored the need for and current use of standalone regulatory agreements.</p><p><strong>Methods: </strong>A survey instrument was developed using an implementation framework and disseminated to mid- to senior-level employees and consultants for sponsor and vendor companies in the medical products sector.</p><p><strong>Results: </strong>Of 294 respondents, about half, primarily from companies with more than 200 employees, were familiar with standalone regulatory agreements, and half of this subgroup had moved forward to implement them. Such agreements were considered beneficial to clarify regulatory roles and responsibilities, standardize regulatory expectations between the companies, and stimulate earlier discussion about joint regulatory strategies. However, the development of regulatory agreements appears challenged by the fact that such agreements are not required by regulatory agencies overseeing medical products and have no standardized templates, agency or industry guidance. Respondents whose organizations do not now use regulatory agreements either had not considered or did not see a need for a standalone agreement.</p><p><strong>Conclusions: </strong>Standalone regulatory agreements are becoming more common but are not yet implemented fully by most companies. Their usefulness and content appeared to depend upon the type of partner, the complexity of the relationship and the availability of internal expertise and support.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"897-909"},"PeriodicalIF":2.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184639","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
Regulatory Framework for Drug-Device Combination Products in the United States, Europe, and Korea. 美国、欧洲和韩国的药物-器械组合产品监管框架。
IF 2 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-09-01 Epub Date: 2024-05-08 DOI: 10.1007/s43441-024-00661-2
Joo Hee Kim, Sera Kwon, Ju Eun Seol, Mi Hye Kim, Su Dong Kim

Combination products (CPs) combine two or more product types such as drugs, devices, and/or biological products for increased safety and clinical effectiveness. The emergence of innovative CPs poses new challenges for regulatory agencies in assigning jurisdiction for premarket review and oversight. In US, the 1990 Safe Medical Devices Act defines and provides classification criteria for CPs, and the US government has developed a regulatory process through multiple acts, including the 21st Century Cures Act of 2016. Meanwhile, regulators in the European Union (EU) and the Republic of Korea have recently recognized the importance of premarket pathways for CPs. The European Medicines Agency (EMA) has issued guidelines and explanations on compliance issues related to drug-device CPs under MDR. EMA doesn't have the definitions of CPs, but uses the term drug-device combination products (drug-device CPs). CPs are categorized as drugs or medical devices, which follow their relevant regulatory framework. The Ministry of Food and Drug Safety (MFDS) in Korea has legal definitions of CPs under the Notice of the MFDS. CPs are designated as drugs or medical devices according to their primary mode of actions (PMOA) and follow regulatory processes through the framework of drugs or medical devices. This study aims to comprehensively summarize the regulatory oversight of CPs by analyzing the regulatory policies and legal frameworks in the US, the EU, and Korea. The regulatory challenges encountered when developing CPs are also discussed. With specific emphasis on the combination of drugs and devices, this study provides in-depth insights into the regulatory landscape, shedding light on the unique challenges associated with the development of CPs for this particular intersection of drugs and devices.

组合产品(CPs)结合了两种或两种以上的产品类型,如药物、器械和/或生物制品,以提高安全性和临床有效性。创新型 CP 的出现给监管机构分配上市前审查和监督的管辖权带来了新的挑战。在美国,1990 年的《安全医疗器械法案》定义并提供了 CP 的分类标准,美国政府通过多项法案制定了监管流程,包括 2016 年的《21 世纪治愈法案》。与此同时,欧盟(EU)和大韩民国的监管机构最近也认识到了CP上市前途径的重要性。欧洲药品管理局(EMA)就 MDR 下与药物-器械 CP 相关的合规问题发布了指南和解释。EMA 没有 CP 的定义,但使用了药物-器械组合产品(药物-器械 CP)这一术语。CPs 被归类为药物或医疗器械,并遵循其相关的监管框架。韩国食品和药品安全部(MFDS)在其《通知》中对 CP 有法律定义。氯化石蜡根据其主要作用模式(PMOA)被指定为药品或医疗器械,并按照药品或医疗器械的框架进行监管。本研究旨在通过分析美国、欧盟和韩国的监管政策和法律框架,全面总结 CPs 的监管情况。本研究还讨论了在开发 CP 时遇到的监管挑战。本研究特别强调了药物和器械的组合,深入剖析了监管环境,揭示了针对药物和器械这一特殊交叉领域开发 CPs 所面临的独特挑战。
{"title":"Regulatory Framework for Drug-Device Combination Products in the United States, Europe, and Korea.","authors":"Joo Hee Kim, Sera Kwon, Ju Eun Seol, Mi Hye Kim, Su Dong Kim","doi":"10.1007/s43441-024-00661-2","DOIUrl":"10.1007/s43441-024-00661-2","url":null,"abstract":"<p><p>Combination products (CPs) combine two or more product types such as drugs, devices, and/or biological products for increased safety and clinical effectiveness. The emergence of innovative CPs poses new challenges for regulatory agencies in assigning jurisdiction for premarket review and oversight. In US, the 1990 Safe Medical Devices Act defines and provides classification criteria for CPs, and the US government has developed a regulatory process through multiple acts, including the 21st Century Cures Act of 2016. Meanwhile, regulators in the European Union (EU) and the Republic of Korea have recently recognized the importance of premarket pathways for CPs. The European Medicines Agency (EMA) has issued guidelines and explanations on compliance issues related to drug-device CPs under MDR. EMA doesn't have the definitions of CPs, but uses the term drug-device combination products (drug-device CPs). CPs are categorized as drugs or medical devices, which follow their relevant regulatory framework. The Ministry of Food and Drug Safety (MFDS) in Korea has legal definitions of CPs under the Notice of the MFDS. CPs are designated as drugs or medical devices according to their primary mode of actions (PMOA) and follow regulatory processes through the framework of drugs or medical devices. This study aims to comprehensively summarize the regulatory oversight of CPs by analyzing the regulatory policies and legal frameworks in the US, the EU, and Korea. The regulatory challenges encountered when developing CPs are also discussed. With specific emphasis on the combination of drugs and devices, this study provides in-depth insights into the regulatory landscape, shedding light on the unique challenges associated with the development of CPs for this particular intersection of drugs and devices.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"796-806"},"PeriodicalIF":2.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140877429","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
Good Statistical Monitoring: A Flexible Open-Source Tool to Detect Risks in Clinical Trials. 良好的统计监测:检测临床试验风险的灵活开源工具。
IF 2 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-09-01 Epub Date: 2024-05-09 DOI: 10.1007/s43441-024-00651-4
George Wu, Spencer Childress, Zhongkai Wang, Matt Roumaya, Colleen McLaughlin Stern, Chelsea Dickens, Jeremy Wildfire

Background: Risk-based quality management is a regulatory-recommended approach to manage risk in a clinical trial. A key element of this strategy is to conduct risk-based monitoring to detect potential risks to critical data and processes earlier. However, there are limited publicly available tools to perform the analytics required for this purpose. Good Statistical Monitoring is a new open-source solution developed to help address this need.

Methods: A team of statisticians, data scientists, clinicians, data managers, clinical operations, regulatory, and quality compliance staff collaborated to design Good Statistical Monitoring, an R package, to flexibly and efficiently implement end-to-end analyses of key risks. The package currently supports the mapping of clinical trial data from a variety of formats, evaluation of 12 key risk indicators, interactive visualization of analysis results, and creation of standardized reports.

Results: The Good Statistical Monitoring package is freely available on GitHub and empowers clinical study teams to proactively monitor key risks. It employs a modular workflow to perform risk assessments that can be customized by replacing any workflow component with a study-specific alternative. Results can be exported to other clinical systems or can be viewed as an interactive report to facilitate follow-up risk mitigation. Rigorous testing and qualification are performed as part of each release to ensure package quality.

Conclusions: Good Statistical Monitoring is an open-source solution designed to enable clinical study teams to implement statistical monitoring of critical risks, as part of a comprehensive risk-based quality management strategy.

背景:基于风险的质量管理是监管机构推荐的一种管理临床试验风险的方法。该策略的一个关键要素是进行基于风险的监控,以尽早发现关键数据和流程的潜在风险。然而,目前可用于执行这一目的所需分析的公开工具非常有限。Good Statistical Monitoring 是一种新的开源解决方案,旨在帮助满足这一需求:一个由统计学家、数据科学家、临床医生、数据管理人员、临床运营、监管和质量合规人员组成的团队合作设计了一个 R 软件包 Good Statistical Monitoring,以灵活高效地实施关键风险的端到端分析。该软件包目前支持多种格式的临床试验数据映射、12 个关键风险指标的评估、分析结果的交互式可视化以及标准化报告的创建:Good Statistical Monitoring 软件包可在 GitHub 上免费下载,使临床研究团队能够主动监控关键风险。它采用模块化工作流程来执行风险评估,可以通过用特定研究的替代方案替换任何工作流程组件来进行定制。评估结果可导出到其他临床系统,也可作为交互式报告查看,以方便后续风险缓解工作。每次发布都会进行严格的测试和鉴定,以确保软件包的质量:作为基于风险的全面质量管理策略的一部分,Good Statistical Monitoring 是一个开源解决方案,旨在帮助临床研究团队实施关键风险的统计监测。
{"title":"Good Statistical Monitoring: A Flexible Open-Source Tool to Detect Risks in Clinical Trials.","authors":"George Wu, Spencer Childress, Zhongkai Wang, Matt Roumaya, Colleen McLaughlin Stern, Chelsea Dickens, Jeremy Wildfire","doi":"10.1007/s43441-024-00651-4","DOIUrl":"10.1007/s43441-024-00651-4","url":null,"abstract":"<p><strong>Background: </strong>Risk-based quality management is a regulatory-recommended approach to manage risk in a clinical trial. A key element of this strategy is to conduct risk-based monitoring to detect potential risks to critical data and processes earlier. However, there are limited publicly available tools to perform the analytics required for this purpose. Good Statistical Monitoring is a new open-source solution developed to help address this need.</p><p><strong>Methods: </strong>A team of statisticians, data scientists, clinicians, data managers, clinical operations, regulatory, and quality compliance staff collaborated to design Good Statistical Monitoring, an R package, to flexibly and efficiently implement end-to-end analyses of key risks. The package currently supports the mapping of clinical trial data from a variety of formats, evaluation of 12 key risk indicators, interactive visualization of analysis results, and creation of standardized reports.</p><p><strong>Results: </strong>The Good Statistical Monitoring package is freely available on GitHub and empowers clinical study teams to proactively monitor key risks. It employs a modular workflow to perform risk assessments that can be customized by replacing any workflow component with a study-specific alternative. Results can be exported to other clinical systems or can be viewed as an interactive report to facilitate follow-up risk mitigation. Rigorous testing and qualification are performed as part of each release to ensure package quality.</p><p><strong>Conclusions: </strong>Good Statistical Monitoring is an open-source solution designed to enable clinical study teams to implement statistical monitoring of critical risks, as part of a comprehensive risk-based quality management strategy.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"838-844"},"PeriodicalIF":2.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899593","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
New Estimates on the Cost of a Delay Day in Drug Development. 关于药物开发延迟一天的成本的新估算。
IF 2 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-09-01 Epub Date: 2024-05-21 DOI: 10.1007/s43441-024-00667-w
Zachary P Smith, Joseph A DiMasi, Kenneth A Getz

Two frequently cited figures by clinical research insiders and observers - the cost of missing a day to generate prescription drug sales and the cost of a day to conduct a clinical trial - are outdated and based on anecdotal evidence. In late 2023, the Tufts Center for the Study of Drug Development conducted empirical research to gather more accurate and granular estimates and to test whether average sales per day have changed over time. 645 drugs launched since 2000, and 409 clinical trial budgets were drawn from commercially available and proprietary data sets and analyzed. The results indicate that a single day equals approximately $500,000 in lost prescription drug or biologic sales, with daily prescription sales for infectious, hematologic, cardiovascular, and gastrointestinal diseases among the highest. The results also show that each year, the average sales per day of prescription drugs and biologics has decreased by approximately $80,000-$100,000. The estimated direct daily cost to conduct a clinical trial is approximately $40,000 per day for phase II and III clinical trials, with those in respiratory, rheumatology, and dermatology having the highest relative daily direct costs.

临床研究业内人士和观察家经常引用的两个数字--错过一天产生处方药销售额的成本和错过一天进行临床试验的成本--已经过时,而且是基于传闻证据。2023 年底,塔夫茨药物开发研究中心开展了实证研究,以收集更准确、更细化的估算数据,并检验日平均销售额是否随时间推移而发生变化。研究人员从商业可用数据集和专有数据集中提取并分析了自 2000 年以来上市的 645 种药物和 409 项临床试验预算。结果表明,一天的处方药或生物制剂销售损失约等于 50 万美元,其中传染病、血液病、心血管病和胃肠道疾病的处方药日销售额最高。结果还显示,处方药和生物制剂的日均销售额每年都会减少约 8 万至 10 万美元。在 II 期和 III 期临床试验中,估计每天进行临床试验的直接成本约为 40,000 美元,其中呼吸系统、风湿病和皮肤病领域每天的相对直接成本最高。
{"title":"New Estimates on the Cost of a Delay Day in Drug Development.","authors":"Zachary P Smith, Joseph A DiMasi, Kenneth A Getz","doi":"10.1007/s43441-024-00667-w","DOIUrl":"10.1007/s43441-024-00667-w","url":null,"abstract":"<p><p>Two frequently cited figures by clinical research insiders and observers - the cost of missing a day to generate prescription drug sales and the cost of a day to conduct a clinical trial - are outdated and based on anecdotal evidence. In late 2023, the Tufts Center for the Study of Drug Development conducted empirical research to gather more accurate and granular estimates and to test whether average sales per day have changed over time. 645 drugs launched since 2000, and 409 clinical trial budgets were drawn from commercially available and proprietary data sets and analyzed. The results indicate that a single day equals approximately $500,000 in lost prescription drug or biologic sales, with daily prescription sales for infectious, hematologic, cardiovascular, and gastrointestinal diseases among the highest. The results also show that each year, the average sales per day of prescription drugs and biologics has decreased by approximately $80,000-$100,000. The estimated direct daily cost to conduct a clinical trial is approximately $40,000 per day for phase II and III clinical trials, with those in respiratory, rheumatology, and dermatology having the highest relative daily direct costs.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"855-862"},"PeriodicalIF":2.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076749","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
EU's Medical Device Expert Panels: Analysis of Membership and Published Clinical Evaluation Consultation Procedure (CECP) Results. 欧盟医疗器械专家组:对成员资格和已公布的临床评估咨询程序 (CECP) 结果的分析。
IF 2 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-09-01 Epub Date: 2024-06-10 DOI: 10.1007/s43441-024-00632-7
Colleen Watson, Frances J Richmond

Background: The new EU Medical Device Regulation (MDR) places greater importance on the role of clinical evidence to establish safety and performance. Article 54 of the MDR calls for expert committees to independently review the scientific, technical, and clinical evidence supporting the market authorization of certain novel devices independently from the established process of Notified Body reviews. These experts provide a review and opinion that ultimately is taken into consideration alongside the information reviewed by the Notified Body during the review process. Four expert committees (General and Plastic Surgery and Dentistry; Orthopaedics, Traumatology, Rehabilitation, Rheumatology; Circulatory System; and Neurology) have published at least one Scientific Opinion (SO) under the Clinical Evaluation Consultation Procedure (CECP) in 2021-2022.

Methods: The four expert committees with published CECP opinions were reviewed to assess the academic backgrounds and professional expertise of each member with respect to clinical, technical, and biological domains on a 0-2 scale for each domain. A content review was conducted on the 10 CECP opinions published by these committees to assess their consistency with the goals and outcome expectations set by the MDR. The extent of content related to each of the clinical, technical, and biological domains was also assessed on a 0-2 scale.

Results: All committees were composed primarily by members with strong clinical expertise, but only a few had strong technical and biological expertise. Across committees, the average scores of members related to academic background and professional expertise both ranged from 1.64 to 2.00 in the clinical domain, but only 0-0.15 and 0.15-0.69, respectively, in the biological domain, and 0.12-0.55 and 0.23-0.73, respectively, in the technical domain. A content review for the 10 SOs showed that all opinions focused exclusively or primarily on the clinical evidence. Three contained a modest amount of additional text directed at technical/engineering issues and five at biological issues.

Conclusion: Expert committees are composed predominantly of expert clinical reviewers but have many fewer members with significant technical or biological expertise. This may limit the ability of the committees to evaluate the significant technical and biological risks that are often best understood by preclinical testing. Broadening the expertise across the committees may improve the depth of their benefit/risk critiques.

背景:新的欧盟医疗器械法规 (MDR) 更加重视临床证据在确定安全性和性能方面的作用。MDR 第 54 条要求专家委员会独立审查支持某些新型器械上市许可的科学、技术和临床证据,而不局限于指定机构审查的既定程序。这些专家提供的审查意见和观点最终会与指定机构在审查过程中审查的信息一并考虑。2021-2022 年,四个专家委员会(普通外科、整形外科和牙科;矫形外科、创伤科、康复科、风湿科;循环系统;神经内科)根据临床评估咨询程序 (CECP) 至少发表了一份科学意见 (SO):对已发表 CECP 意见的四个专家委员会进行审查,以评估每位成员在临床、技术和生物领域的学术背景和专业知识,每个领域的评分标准为 0-2 分。对这些委员会发表的 10 份 CECP 意见进行了内容审查,以评估这些意见是否符合《医疗诊断程序》设定的目标和预期结果。与临床、技术和生物领域相关内容的程度也按 0-2 分制进行了评估:结果:所有委员会的主要成员都具有很强的临床专业知识,但只有少数成员具有很强的技术和生物专业知识。各委员会成员在学术背景和专业知识方面的平均得分在临床领域从 1.64 到 2.00 不等,但在生物领域分别仅为 0-0.15 和 0.15-0.69,在技术领域分别为 0.12-0.55 和 0.23-0.73。对 10 份战略目标的内容审查显示,所有意见都只关注或主要关注临床证据。三份意见书包含少量针对技术/工程问题的附加文字,五份针对生物问题:专家委员会主要由临床专家评审员组成,但具有丰富技术或生物专业知识的成员较少。这可能会限制委员会评估重大技术和生物风险的能力,而临床前试验往往最能了解这些风险。拓宽各委员会的专业知识,可提高其效益/风险点评的深度。
{"title":"EU's Medical Device Expert Panels: Analysis of Membership and Published Clinical Evaluation Consultation Procedure (CECP) Results.","authors":"Colleen Watson, Frances J Richmond","doi":"10.1007/s43441-024-00632-7","DOIUrl":"10.1007/s43441-024-00632-7","url":null,"abstract":"<p><strong>Background: </strong>The new EU Medical Device Regulation (MDR) places greater importance on the role of clinical evidence to establish safety and performance. Article 54 of the MDR calls for expert committees to independently review the scientific, technical, and clinical evidence supporting the market authorization of certain novel devices independently from the established process of Notified Body reviews. These experts provide a review and opinion that ultimately is taken into consideration alongside the information reviewed by the Notified Body during the review process. Four expert committees (General and Plastic Surgery and Dentistry; Orthopaedics, Traumatology, Rehabilitation, Rheumatology; Circulatory System; and Neurology) have published at least one Scientific Opinion (SO) under the Clinical Evaluation Consultation Procedure (CECP) in 2021-2022.</p><p><strong>Methods: </strong>The four expert committees with published CECP opinions were reviewed to assess the academic backgrounds and professional expertise of each member with respect to clinical, technical, and biological domains on a 0-2 scale for each domain. A content review was conducted on the 10 CECP opinions published by these committees to assess their consistency with the goals and outcome expectations set by the MDR. The extent of content related to each of the clinical, technical, and biological domains was also assessed on a 0-2 scale.</p><p><strong>Results: </strong>All committees were composed primarily by members with strong clinical expertise, but only a few had strong technical and biological expertise. Across committees, the average scores of members related to academic background and professional expertise both ranged from 1.64 to 2.00 in the clinical domain, but only 0-0.15 and 0.15-0.69, respectively, in the biological domain, and 0.12-0.55 and 0.23-0.73, respectively, in the technical domain. A content review for the 10 SOs showed that all opinions focused exclusively or primarily on the clinical evidence. Three contained a modest amount of additional text directed at technical/engineering issues and five at biological issues.</p><p><strong>Conclusion: </strong>Expert committees are composed predominantly of expert clinical reviewers but have many fewer members with significant technical or biological expertise. This may limit the ability of the committees to evaluate the significant technical and biological risks that are often best understood by preclinical testing. Broadening the expertise across the committees may improve the depth of their benefit/risk critiques.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"910-916"},"PeriodicalIF":2.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296741","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
New Benchmarks on Protocol Amendment Experience in Oncology Clinical Trials. 肿瘤临床试验协议修订经验的新基准。
IF 1.5 4区 医学 Q4 MEDICAL INFORMATICS Pub Date : 2024-07-01 Epub Date: 2024-03-26 DOI: 10.1007/s43441-024-00629-2
Emily Botto, Zachary Smith, Kenneth Getz

Background: The drug development industry's focus on cancer-related treatments continues to rise, with narrow patient populations and complex procedures increasing the complexity of oncology protocols at an accelerated rate compared to non-oncology drugs. Tufts Center for the Study of Drug Development utilized data from a study investigating the impact of protocol amendments to compare how oncology clinical trials differ from non-oncology and identify opportunities to optimize performance in oncology clinical trials.

Methods: Sixteen drug development industry companies contributed data from 950 protocols and 2,188 amendments to a study conducted in 2022 investigating protocol amendments. Analysis compared differences in amendment impact and causes between 249 oncology and 701 non-oncology protocols.

Results: Compared to non-oncology, oncology protocols had a significantly higher prevalence (72.1% and 91.1%, respectively) and number (3.0 and 4.0, respectively) of protocol amendments. Oncology protocols with amendments had significantly lower participant completion rates compared to oncology protocols without amendments, while no significant differences were found among non-oncology. During the COVID-19 pandemic, the study found an increased number of substantial amendments, lower completion rates, and higher dropout rates among oncology protocols compared to before the pandemic.

Conclusions: Efforts to prevent avoidable protocol amendments in the industry have not been effective in oncology, where increasingly complex designs are reflected in difficult to predict cycle times, barriers to recruitment and retention and an increase in protocol amendments.

背景:药物开发行业对癌症相关治疗的关注度持续上升,与非肿瘤药物相比,狭窄的患者群体和复杂的程序加速了肿瘤方案的复杂性。塔夫茨药物开发研究中心利用一项调查方案修订影响的研究数据,比较了肿瘤临床试验与非肿瘤临床试验的不同之处,并确定了优化肿瘤临床试验绩效的机会:16 家药物开发行业公司为 2022 年开展的一项调查方案修订的研究提供了 950 项方案和 2188 项修订的数据。分析比较了 249 个肿瘤学方案和 701 个非肿瘤学方案在修订影响和原因方面的差异:与非肿瘤学方案相比,肿瘤学方案的修订率(分别为 72.1% 和 91.1%)和修订数量(分别为 3.0 和 4.0)都明显更高。与未进行修订的肿瘤学方案相比,进行了修订的肿瘤学方案的参与者完成率明显较低,而在非肿瘤学方案中未发现明显差异。在 COVID-19 大流行期间,研究发现与大流行之前相比,肿瘤学方案的实质性修订数量增加、完成率降低、退出率升高:结论:业界为防止可避免的方案修订所做的努力在肿瘤学领域并不奏效,肿瘤学领域日益复杂的设计反映在难以预测的周期时间、招募和留用的障碍以及方案修订的增加上。
{"title":"New Benchmarks on Protocol Amendment Experience in Oncology Clinical Trials.","authors":"Emily Botto, Zachary Smith, Kenneth Getz","doi":"10.1007/s43441-024-00629-2","DOIUrl":"10.1007/s43441-024-00629-2","url":null,"abstract":"<p><strong>Background: </strong>The drug development industry's focus on cancer-related treatments continues to rise, with narrow patient populations and complex procedures increasing the complexity of oncology protocols at an accelerated rate compared to non-oncology drugs. Tufts Center for the Study of Drug Development utilized data from a study investigating the impact of protocol amendments to compare how oncology clinical trials differ from non-oncology and identify opportunities to optimize performance in oncology clinical trials.</p><p><strong>Methods: </strong>Sixteen drug development industry companies contributed data from 950 protocols and 2,188 amendments to a study conducted in 2022 investigating protocol amendments. Analysis compared differences in amendment impact and causes between 249 oncology and 701 non-oncology protocols.</p><p><strong>Results: </strong>Compared to non-oncology, oncology protocols had a significantly higher prevalence (72.1% and 91.1%, respectively) and number (3.0 and 4.0, respectively) of protocol amendments. Oncology protocols with amendments had significantly lower participant completion rates compared to oncology protocols without amendments, while no significant differences were found among non-oncology. During the COVID-19 pandemic, the study found an increased number of substantial amendments, lower completion rates, and higher dropout rates among oncology protocols compared to before the pandemic.</p><p><strong>Conclusions: </strong>Efforts to prevent avoidable protocol amendments in the industry have not been effective in oncology, where increasingly complex designs are reflected in difficult to predict cycle times, barriers to recruitment and retention and an increase in protocol amendments.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"645-654"},"PeriodicalIF":1.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140294600","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