首页 > 最新文献

Clinical Trials最新文献

英文 中文
Challenges in conducting efficacy trials for new COVID-19 vaccines in developed countries. 在发达国家开展新型 COVID-19 疫苗疗效试验所面临的挑战。
IF 2.2 3区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-12-01 Epub Date: 2024-03-29 DOI: 10.1177/17407745241238925
Rafael Dal-Ré, Emmanuel Bottieau, Odile Launay, Frits R Rosendaal, Brigitte Schwarzer-Daum

The protection from COVID-19 vaccination wanes a few months post-administration of the primary vaccination series or booster doses. New COVID-19 vaccine candidates aiming to help control COVID-19 should show long-term efficacy, allowing a possible annual administration. Until correlates of protection are strongly associated with long-term protection, it has been suggested that any new COVID-19 vaccine candidate must demonstrate at least 75% efficacy (although a 40%-60% efficacy would be sufficient) at 12 months in preventing illness in all age groups within a large randomized controlled efficacy trial. This article discusses four of the many scientific, ethical, and operational challenges that these trials will face in developed countries, focusing on a pivotal trial in adults. These challenges are (1) the comparator and trial population; (2) how to enroll sufficient numbers of adult participants of all age groups considering that countries will recommend COVID-19 booster doses to different populations; (3) whether having access to a comparator booster for the trial is actually feasible; and (4) the changing epidemiology of severe acute respiratory syndrome coronavirus 2 across countries involved in the trial. It is desirable that regulatory agencies publish guidance on the requirements that a trial like the one discussed should comply with to be acceptable from a regulatory standpoint. Ideally, this should happen even before there is a vaccine candidate that could fulfill the requirements mentioned above, as it would allow an open discussion among all stakeholders on its appropriateness and feasibility.

接种 COVID-19 疫苗的保护作用会在接种初级系列疫苗或加强剂几个月后减弱。旨在帮助控制 COVID-19 的新 COVID-19 候选疫苗应显示出长期疗效,允许每年接种一次。在保护的相关因素与长期保护密切相关之前,有人建议任何新的 COVID-19 候选疫苗都必须在大型随机对照疗效试验中证明在 12 个月内对所有年龄组的疾病预防至少有 75% 的疗效(尽管 40%-60% 的疗效就足够了)。本文讨论了这些试验在发达国家将面临的众多科学、伦理和操作挑战中的四个挑战,重点是成人关键试验。这些挑战包括:(1) 比较对象和试验人群;(2) 考虑到各国将向不同人群推荐 COVID-19 强化剂量,如何招募足够数量的各年龄组成人参与者;(3) 试验中获得比较对象强化剂是否切实可行;(4) 参与试验的各国严重急性呼吸系统综合征冠状病毒 2 的流行病学变化。监管机构最好能发布指导意见,说明类似上述试验应符合哪些要求才能被监管机构接受。理想情况下,甚至在出现可满足上述要求的候选疫苗之前就应发布指南,因为这将允许所有利益相关者就其适当性和可行性进行公开讨论。
{"title":"Challenges in conducting efficacy trials for new COVID-19 vaccines in developed countries.","authors":"Rafael Dal-Ré, Emmanuel Bottieau, Odile Launay, Frits R Rosendaal, Brigitte Schwarzer-Daum","doi":"10.1177/17407745241238925","DOIUrl":"10.1177/17407745241238925","url":null,"abstract":"<p><p>The protection from COVID-19 vaccination wanes a few months post-administration of the primary vaccination series or booster doses. New COVID-19 vaccine candidates aiming to help control COVID-19 should show long-term efficacy, allowing a possible annual administration. Until correlates of protection are strongly associated with long-term protection, it has been suggested that any new COVID-19 vaccine candidate must demonstrate at least 75% efficacy (although a 40%-60% efficacy would be sufficient) at 12 months in preventing illness in all age groups within a large randomized controlled efficacy trial. This article discusses four of the many scientific, ethical, and operational challenges that these trials will face in developed countries, focusing on a pivotal trial in adults. These challenges are (1) the comparator and trial population; (2) how to enroll sufficient numbers of adult participants of all age groups considering that countries will recommend COVID-19 booster doses to different populations; (3) whether having access to a comparator booster for the trial is actually feasible; and (4) the changing epidemiology of severe acute respiratory syndrome coronavirus 2 across countries involved in the trial. It is desirable that regulatory agencies publish guidance on the requirements that a trial like the one discussed should comply with to be acceptable from a regulatory standpoint. Ideally, this should happen even before there is a vaccine candidate that could fulfill the requirements mentioned above, as it would allow an open discussion among all stakeholders on its appropriateness and feasibility.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"754-758"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Taking clinical decisions seriously in standard-of-care pragmatic clinical trials. 在标准护理实用临床试验中认真对待临床决策。
IF 2.2 3区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-12-01 Epub Date: 2024-08-15 DOI: 10.1177/17407745241266152
Isabel M Astrachan, James Flory, Scott Yh Kim
{"title":"Taking clinical decisions seriously in standard-of-care pragmatic clinical trials.","authors":"Isabel M Astrachan, James Flory, Scott Yh Kim","doi":"10.1177/17407745241266152","DOIUrl":"10.1177/17407745241266152","url":null,"abstract":"","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"669-670"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Ethical considerations for sharing aggregate results from pragmatic clinical trials. 分享实用临床试验综合结果的伦理考虑。
IF 2.2 3区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-25 DOI: 10.1177/17407745241290782
Stephanie R Morain, Abigail Brickler, Joseph Ali, Patricia Pearl O'Rourke, Kayte Spector-Bagdady, Benjamin Wilfond, Vasiliki Rahimzadeh, Caleigh Propes, Kayla Mehl, David Wendler

A growing literature has explored the ethical obligations and current practices related to sharing aggregate results with research participants. However, no prior work has examined these issues in the context of pragmatic clinical trials. Several characteristics of pragmatic clinical trials may complicate both the ethics and the logistics of sharing aggregate results. Among these characteristics include that pragmatic clinical trials may affect the rights, welfare, and interests of not only patient-subjects but also clinicians, meaning that results may be owed to a broader range of groups than typically considered in other research contexts. In addition, some pragmatic clinical trials are conducted under a waiver of informed consent, meaning sharing results may alert participants that they were enrolled without their consent. This article explores the ethical dimensions that can inform decision-making about sharing aggregate results from pragmatic clinical trials, and provides recommendations for that sharing. A central insight is that healthcare institutions-as key partners for the conduct of pragmatic clinical trials-must also be key partners in decision-making about sharing aggregate pragmatic clinical trial results. We conclude with insights for future research.

越来越多的文献探讨了与研究参与者共享综合结果的相关伦理义务和现行做法。然而,此前还没有研究在实用临床试验的背景下探讨过这些问题。务实临床试验的几个特点可能会使共享总体结果的伦理和后勤问题变得更加复杂。这些特点包括:务实临床试验不仅会影响患者受试者的权利、福利和利益,还会影响临床医生的权利、福利和利益,这意味着与其他研究相比,试验结果可能会涉及更广泛的群体。此外,一些实用临床试验是在放弃知情同意的情况下进行的,这意味着共享结果可能会提醒参与者,他们是在未经同意的情况下参加试验的。本文探讨了伦理方面的问题,这些问题可以为共享实用临床试验的总体结果提供决策依据,并为共享提供建议。其中一个核心观点是,医疗机构作为开展实用临床试验的关键合作伙伴,也必须成为共享实用临床试验总体结果决策的关键合作伙伴。最后,我们提出了对未来研究的见解。
{"title":"Ethical considerations for sharing aggregate results from pragmatic clinical trials.","authors":"Stephanie R Morain, Abigail Brickler, Joseph Ali, Patricia Pearl O'Rourke, Kayte Spector-Bagdady, Benjamin Wilfond, Vasiliki Rahimzadeh, Caleigh Propes, Kayla Mehl, David Wendler","doi":"10.1177/17407745241290782","DOIUrl":"10.1177/17407745241290782","url":null,"abstract":"<p><p>A growing literature has explored the ethical obligations and current practices related to sharing aggregate results with research participants. However, no prior work has examined these issues in the context of pragmatic clinical trials. Several characteristics of pragmatic clinical trials may complicate both the ethics and the logistics of sharing aggregate results. Among these characteristics include that pragmatic clinical trials may affect the rights, welfare, and interests of not only patient-subjects but also clinicians, meaning that results may be owed to a broader range of groups than typically considered in other research contexts. In addition, some pragmatic clinical trials are conducted under a waiver of informed consent, meaning sharing results may alert participants that they were enrolled without their consent. This article explores the ethical dimensions that can inform decision-making about sharing aggregate results from pragmatic clinical trials, and provides recommendations for that sharing. A central insight is that healthcare institutions-as key partners for the conduct of pragmatic clinical trials-must also be key partners in decision-making about sharing aggregate pragmatic clinical trial results. We conclude with insights for future research.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"17407745241290782"},"PeriodicalIF":2.2,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Detecting irregularities in randomized controlled trials using machine learning. 利用机器学习检测随机对照试验中的违规行为。
IF 2.2 3区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-25 DOI: 10.1177/17407745241297947
Walter Nelson, Jeremy Petch, Jonathan Ranisau, Robin Zhao, Kumar Balasubramanian, Shrikant I Bangdiwala

Background: Over the course of a clinical trial, irregularities may arise in the data. Trialists implement human-intensive, expensive central statistical monitoring procedures to identify and correct these irregularities before the results of the trial are analyzed and disseminated. Machine learning algorithms have shown promise for identifying center-level irregularities in multi-center clinical trials with minimal human intervention. We aimed to characterize the form-level data irregularities in several historical clinical trials and evaluate the ability of a machine learning-based outlier detection algorithm to identify them.

Methods: Data irregularities previously identified by humans in historical clinical trials were ascertained by comparing preliminary snapshots of the trial databases to the final, locked databases. We measured the ability of a machine learning based outlier detection algorithm to identify form-level irregularities using concordance (area under the receiver operator characteristic), positive predictive value (precision), and sensitivity (recall).

Results: We examined preliminary snapshots of seven historical clinical trials which randomized a total of 77,001 participants. We extracted a total of 1,267,484 completed entries from 358 case report forms containing irregularities from all snapshots across all trials, containing a total of 24,850 form-wide irregularities (median per-form form-level irregularity rate: 1.81%). Our proposed machine learning algorithm detects form-level irregularities with a median concordance of 0.74 (interquartile range = 0.57-0.89), slightly exceeding the performance of a previously proposed machine learning approach with a median area under the receiver operator characteristic of 0.73 (interquartile range = 0.54-0.88).

Conclusion: Data irregularities in historical clinical trials were ascertained by comparing preliminary snapshots of the trial database to the final database. These irregularities can be categorized according to their scope. Irregularities can be successfully detected by a machine learning algorithm as early or earlier than a human can, without human intervention. Such an approach may complement existing techniques for central statistical monitoring in large multi-center randomized controlled trials and possibly improve the efficiency of costly data verification processes.

背景:在临床试验过程中,数据可能会出现异常。试验者需要实施人力密集、成本高昂的中央统计监测程序,以便在分析和发布试验结果之前识别并纠正这些违规现象。机器学习算法在识别多中心临床试验中中心层面的违规行为方面大有可为,只需极少的人工干预。我们的目的是描述几项历史临床试验中表格级数据异常的特征,并评估基于机器学习的离群点检测算法识别这些异常的能力:方法:通过比较试验数据库的初步快照和最终锁定的数据库,我们确定了之前由人类在历史临床试验中识别出的数据不规则性。我们使用一致性(接收者运算特征下的面积)、阳性预测值(精确度)和灵敏度(召回率)衡量了基于机器学习的离群点检测算法识别形式级不规范的能力:我们研究了七项历史临床试验的初步快照,这些试验共随机抽取了 77,001 名参与者。我们从所有试验的所有快照中提取了 358 份病例报告表中包含违规行为的 1,267,484 个完整条目,共包含 24,850 个全表违规行为(每表违规率中位数:1.81%)。我们提出的机器学习算法检测表单级不规范性的中位一致性为 0.74(四分位间范围 = 0.57-0.89),略高于之前提出的机器学习方法的性能,后者的接收算子特征下的中位面积为 0.73(四分位间范围 = 0.54-0.88):通过比较试验数据库的初步快照和最终数据库,确定了历史临床试验中的数据不规则性。这些违规数据可根据其范围进行分类。机器学习算法可以在不需要人工干预的情况下,比人类更早或更早地成功检测出违规数据。这种方法可以补充现有的大型多中心随机对照试验中央统计监测技术,并有可能提高成本高昂的数据验证过程的效率。
{"title":"Detecting irregularities in randomized controlled trials using machine learning.","authors":"Walter Nelson, Jeremy Petch, Jonathan Ranisau, Robin Zhao, Kumar Balasubramanian, Shrikant I Bangdiwala","doi":"10.1177/17407745241297947","DOIUrl":"https://doi.org/10.1177/17407745241297947","url":null,"abstract":"<p><strong>Background: </strong>Over the course of a clinical trial, irregularities may arise in the data. Trialists implement human-intensive, expensive central statistical monitoring procedures to identify and correct these irregularities before the results of the trial are analyzed and disseminated. Machine learning algorithms have shown promise for identifying center-level irregularities in multi-center clinical trials with minimal human intervention. We aimed to characterize the form-level data irregularities in several historical clinical trials and evaluate the ability of a machine learning-based outlier detection algorithm to identify them.</p><p><strong>Methods: </strong>Data irregularities previously identified by humans in historical clinical trials were ascertained by comparing preliminary snapshots of the trial databases to the final, locked databases. We measured the ability of a machine learning based outlier detection algorithm to identify form-level irregularities using concordance (area under the receiver operator characteristic), positive predictive value (precision), and sensitivity (recall).</p><p><strong>Results: </strong>We examined preliminary snapshots of seven historical clinical trials which randomized a total of 77,001 participants. We extracted a total of 1,267,484 completed entries from 358 case report forms containing irregularities from all snapshots across all trials, containing a total of 24,850 form-wide irregularities (median per-form form-level irregularity rate: 1.81%). Our proposed machine learning algorithm detects form-level irregularities with a median concordance of 0.74 (interquartile range = 0.57-0.89), slightly exceeding the performance of a previously proposed machine learning approach with a median area under the receiver operator characteristic of 0.73 (interquartile range = 0.54-0.88).</p><p><strong>Conclusion: </strong>Data irregularities in historical clinical trials were ascertained by comparing preliminary snapshots of the trial database to the final database. These irregularities can be categorized according to their scope. Irregularities can be successfully detected by a machine learning algorithm as early or earlier than a human can, without human intervention. Such an approach may complement existing techniques for central statistical monitoring in large multi-center randomized controlled trials and possibly improve the efficiency of costly data verification processes.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"17407745241297947"},"PeriodicalIF":2.2,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
UK paediatric clinical trial protocols: A review of guidance for participant management and care in the event of premature termination. 英国儿科临床试验协议:对提前终止试验时的参与者管理和护理指南的审查。
IF 2.2 3区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-19 DOI: 10.1177/17407745241296864
Helen Pluess-Hall, Paula Smith, Julie Menzies
<p><strong>Background/aims: </strong>Clinical trials provide an opportunity to identify new treatments and can offer patients access to treatments otherwise unavailable. However, approximately 10% of paediatric clinical trials discontinue before the trial has completed. If this premature termination is because the trial treatment(s) being investigated are identified to be ineffective or unsafe, it results in the abrupt discontinuation of the investigational medicinal product for participants. For some participants, there may not be other treatment options to pursue at the trial-end. Trials prematurely terminating can be a distressing experience for all involved and currently there is little published evidence about the guidance provided to healthcare professionals in the event of premature trial termination. The study protocol is the source of guidance for healthcare professionals delivering clinical research, detailing how to conduct all aspects of the trial. The aim was to quantify the proportion of clinical trial protocols that included premature trial termination and subsequently those that provided instructions related to participant management and care. In addition, to analyse the context in which premature termination was included and the detail of any instructions for participant management and care.</p><p><strong>Methods: </strong>The ClinicalTrials.gov database was searched by a single reviewer for UK interventional drug trials enrolling children with an available study protocol. Protocols were searched to assess if the risk of premature trial termination was identified, the context for premature termination being included, if information was provided to support the management and care of participants should this situation occur and the detail of those instructions. Data were summarised descriptively.</p><p><strong>Results: </strong>Of 245 clinical trial protocols, 235 (95.9%) identified the possibility of premature trial termination, the majority within the context of the sponsor asserting their right to terminate the trial (82.7%, 115/235) and providing reasons why the trial could be stopped (65.5%, 91/235). Forty-two percent (98/235) provided guidance for participant management and care, most commonly to contact/inform the participant (45.9%, 45/98). Directions varied in the quantity and level of detail.</p><p><strong>Conclusions: </strong>This review of UK clinical trial protocol highlights that information surrounding premature termination is lacking, with only 42% providing guidance on the care of trial participants. While this ensures regulatory compliance, it fails to consider the challenge for healthcare professionals in managing participants on-going care or the duty of care owed to participants. Further research is required to understand if additional documents are being used in practice, and if these meet the needs of healthcare professionals in supporting research participants and families during premature trial termination
背景/目的:临床试验为确定新的治疗方法提供了机会,并能为患者提供在其他情况下无法获得的治疗方法。然而,约有 10% 的儿科临床试验在试验结束前就终止了。如果这种提前终止的原因是试验所研究的治疗方法被确认为无效或不安全,那么就会导致试验参与者突然停用试验用医药产品。对于某些参与者来说,试验结束时可能没有其他治疗方案可供选择。试验提前结束可能会给所有参与者带来痛苦,而目前关于在试验提前结束的情况下为医护人员提供指导的公开证据很少。研究方案是医护人员开展临床研究的指导来源,详细说明了如何开展试验的各个方面。研究的目的是量化包含提前终止试验的临床试验方案的比例,以及随后提供与受试者管理和护理相关说明的临床试验方案的比例。此外,还将分析提前终止试验的背景,以及有关参与者管理和护理说明的细节:方法:由一名审稿人在 ClinicalTrials.gov 数据库中搜索英国的介入性药物试验,这些试验均有儿童参与,并提供了研究方案。对试验方案进行检索,以评估是否确定了试验提前终止的风险、提前终止的背景、是否提供了相关信息以支持在出现这种情况时对参与者的管理和护理,以及这些说明的详细内容。对数据进行了描述性总结:在 245 份临床试验方案中,有 235 份(95.9%)确定了提前终止试验的可能性,其中大部分是在申办者主张其有权终止试验的情况下(82.7%,115/235),并提供了可以停止试验的理由(65.5%,91/235)。42%(98/235)的指南提供了参试者管理和护理方面的指导,最常见的是联系/通知参试者(45.9%,45/98)。指导的数量和详细程度各不相同:对英国临床试验方案的审查表明,有关提前终止试验的信息缺乏,只有 42% 的方案提供了有关试验参与者护理的指导。虽然这能确保符合法规要求,但却没有考虑到医护人员在管理参与者的持续护理或对参与者的护理责任方面所面临的挑战。我们需要进一步研究,以了解在实践中是否使用了额外的文件,以及这些文件是否满足了医护人员在试验提前终止期间为研究参与者及其家属提供支持的需求。
{"title":"UK paediatric clinical trial protocols: A review of guidance for participant management and care in the event of premature termination.","authors":"Helen Pluess-Hall, Paula Smith, Julie Menzies","doi":"10.1177/17407745241296864","DOIUrl":"10.1177/17407745241296864","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background/aims: &lt;/strong&gt;Clinical trials provide an opportunity to identify new treatments and can offer patients access to treatments otherwise unavailable. However, approximately 10% of paediatric clinical trials discontinue before the trial has completed. If this premature termination is because the trial treatment(s) being investigated are identified to be ineffective or unsafe, it results in the abrupt discontinuation of the investigational medicinal product for participants. For some participants, there may not be other treatment options to pursue at the trial-end. Trials prematurely terminating can be a distressing experience for all involved and currently there is little published evidence about the guidance provided to healthcare professionals in the event of premature trial termination. The study protocol is the source of guidance for healthcare professionals delivering clinical research, detailing how to conduct all aspects of the trial. The aim was to quantify the proportion of clinical trial protocols that included premature trial termination and subsequently those that provided instructions related to participant management and care. In addition, to analyse the context in which premature termination was included and the detail of any instructions for participant management and care.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The ClinicalTrials.gov database was searched by a single reviewer for UK interventional drug trials enrolling children with an available study protocol. Protocols were searched to assess if the risk of premature trial termination was identified, the context for premature termination being included, if information was provided to support the management and care of participants should this situation occur and the detail of those instructions. Data were summarised descriptively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of 245 clinical trial protocols, 235 (95.9%) identified the possibility of premature trial termination, the majority within the context of the sponsor asserting their right to terminate the trial (82.7%, 115/235) and providing reasons why the trial could be stopped (65.5%, 91/235). Forty-two percent (98/235) provided guidance for participant management and care, most commonly to contact/inform the participant (45.9%, 45/98). Directions varied in the quantity and level of detail.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This review of UK clinical trial protocol highlights that information surrounding premature termination is lacking, with only 42% providing guidance on the care of trial participants. While this ensures regulatory compliance, it fails to consider the challenge for healthcare professionals in managing participants on-going care or the duty of care owed to participants. Further research is required to understand if additional documents are being used in practice, and if these meet the needs of healthcare professionals in supporting research participants and families during premature trial termination","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"17407745241296864"},"PeriodicalIF":2.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Pragmatic monitoring of emerging efficacy data in randomized controlled trials. 对随机对照试验中新出现的疗效数据进行务实监测。
IF 2.2 3区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-09 DOI: 10.1177/17407745241290729
Shrikant I Bangdiwala, Salim Yusuf

Monitoring the conduct of phase III randomized controlled trials is driven by ethical reasons to protect the study integrity and the safety of trial participants. We propose a group sequential, pragmatic approach for monitoring the accumulating efficacy information in randomized controlled trials. The "Population Health Research Institute boundary" is simple to implement and sensible, as it considers the reduction in uncertainty with increasing information as the study progresses. It is also pragmatic, since it takes into consideration the typical monitoring behavior of monitoring committees of large multicenter trials and is relatively easily implemented. It not only controls the overall Lan-DeMets type I error probability (alpha) spent, but performs better than other group sequential boundaries for the total nominal study alpha. We illustrate the use of our monitoring approach in the early termination of two past completed trials.

监督 III 期随机对照试验的进行是出于保护研究完整性和试验参与者安全的道德原因。我们提出了一种按组排序的务实方法,用于监测随机对照试验中不断积累的疗效信息。人口健康研究所边界 "既简单易行,又合情合理,因为它考虑到了随着研究的进展,信息的增加会降低不确定性。同时,它也很实用,因为它考虑到了大型多中心试验监测委员会的典型监测行为,而且相对容易实施。它不仅能控制整个 Lan-DeMets I 型误差概率(α)的花费,而且在总名义研究α方面的表现优于其他分组顺序界限。我们在过去完成的两项试验的提前终止中说明了我们的监控方法的使用情况。
{"title":"Pragmatic monitoring of emerging efficacy data in randomized controlled trials.","authors":"Shrikant I Bangdiwala, Salim Yusuf","doi":"10.1177/17407745241290729","DOIUrl":"https://doi.org/10.1177/17407745241290729","url":null,"abstract":"<p><p>Monitoring the conduct of phase III randomized controlled trials is driven by ethical reasons to protect the study integrity and the safety of trial participants. We propose a group sequential, pragmatic approach for monitoring the accumulating efficacy information in randomized controlled trials. The \"Population Health Research Institute boundary\" is simple to implement and sensible, as it considers the reduction in uncertainty with increasing information as the study progresses. It is also pragmatic, since it takes into consideration the typical monitoring behavior of monitoring committees of large multicenter trials and is relatively easily implemented. It not only controls the overall Lan-DeMets type I error probability (alpha) spent, but performs better than other group sequential boundaries for the total nominal study alpha. We illustrate the use of our monitoring approach in the early termination of two past completed trials.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"17407745241290729"},"PeriodicalIF":2.2,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Statistical properties of items and summary scores from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) in a diverse cancer sample. 不同癌症样本中患者报告结果版《不良事件通用术语标准》(PRO-CTCAE®)项目和总分的统计特性。
IF 2.2 3区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-23 DOI: 10.1177/17407745241286065
Carolyn Mead-Harvey, Ethan Basch, Lauren J Rogak, Blake T Langlais, Gita Thanarajasingam, Brenda F Ginos, Minji K Lee, Claire Yee, Sandra A Mitchell, Lori M Minasian, Tito R Mendoza, Antonia V Bennett, Deborah Schrag, Amylou C Dueck, Gina L Mazza

Background/aims: The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) was developed to capture symptomatic adverse events from the patient perspective. We aim to describe statistical properties of PRO-CTCAE items and summary scores and to provide evidence for recommendations regarding PRO-CTCAE administration and reporting.

Methods: Using data from the PRO-CTCAE validation study (NCT02158637), prevalence, means, and standard deviations of PRO-CTCAE items, composite scores, and mean and maximum scores across attributes (frequency, severity, and/or interference) of symptomatic adverse events were calculated. For each adverse event, correlations and agreement between attributes, correlations between attributes and composite scores, and correlations between composite, mean, and maximum scores were estimated.

Results: PRO-CTCAE items were completed by 899 patients with various cancer types. Most patients reported experiencing one or more adverse events, with the most prevalent being fatigue (87.7%), sad/unhappy feelings (66.0%), anxiety (63.6%), pain (63.2%), insomnia (61.8%), and dry mouth (60.0%). Attributes were moderately to strongly correlated within an adverse event (r = 0.53 to 0.77, all p < 0.001) but not fully concordant (κweighted = 0.26 to 0.60, all p < 0.001), with interference demonstrating lowest mean scores and prevalence among attributes of the same adverse event. Attributes were moderately to strongly correlated with composite scores (r = 0.67 to 0.97, all p < 0.001). Composite scores were moderately to strongly correlated with mean and maximum scores for the same adverse event (r = 0.69 to 0.94, all p < 0.001). Correlations between composite scores of different adverse events varied widely (r = 0.04 to 0.68) but were moderate to strong for conceptually related adverse events.

Conclusions: Results provide evidence for PRO-CTCAE administration and reporting recommendations that the full complement of attributes be administered for each adverse event, and that attributes as well as summary scores be reported.

背景/目的:患者报告结果版不良事件通用术语标准(PRO-CTCAE®)旨在从患者角度捕捉症状性不良事件。我们旨在描述 PRO-CTCAE 项目和总分的统计特性,并为有关 PRO-CTCAE 管理和报告的建议提供证据:利用 PRO-CTCAE 验证研究(NCT02158637)的数据,计算了 PRO-CTCAE 项目、综合评分以及症状性不良事件不同属性(频率、严重程度和/或干扰)的平均分和最高分的流行率、平均值和标准偏差。对每种不良事件的属性之间的相关性和一致性、属性与综合评分之间的相关性以及综合评分、平均分和最高分之间的相关性进行了估算:899名不同癌症类型的患者完成了PRO-CTCAE项目。大多数患者报告经历了一种或多种不良事件,其中最普遍的不良事件是疲劳(87.7%)、悲伤/不开心(66.0%)、焦虑(63.6%)、疼痛(63.2%)、失眠(61.8%)和口干(60.0%)。在一个不良事件中,属性的相关性为中度到高度相关(r = 0.53 到 0.77,所有 p 加权 = 0.26 到 0.60,所有 p r = 0.67 到 0.97,所有 p r = 0.69 到 0.94,所有 p r = 0.04 到 0.68),但在概念相关的不良事件中,属性的相关性为中度到高度相关:结论:研究结果为 PRO-CTCAE 的管理和报告建议提供了证据,建议对每种不良事件进行全套属性管理,并报告属性和总分。
{"title":"Statistical properties of items and summary scores from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE<sup>®</sup>) in a diverse cancer sample.","authors":"Carolyn Mead-Harvey, Ethan Basch, Lauren J Rogak, Blake T Langlais, Gita Thanarajasingam, Brenda F Ginos, Minji K Lee, Claire Yee, Sandra A Mitchell, Lori M Minasian, Tito R Mendoza, Antonia V Bennett, Deborah Schrag, Amylou C Dueck, Gina L Mazza","doi":"10.1177/17407745241286065","DOIUrl":"10.1177/17407745241286065","url":null,"abstract":"<p><strong>Background/aims: </strong>The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE<sup>®</sup>) was developed to capture symptomatic adverse events from the patient perspective. We aim to describe statistical properties of PRO-CTCAE items and summary scores and to provide evidence for recommendations regarding PRO-CTCAE administration and reporting.</p><p><strong>Methods: </strong>Using data from the PRO-CTCAE validation study (NCT02158637), prevalence, means, and standard deviations of PRO-CTCAE items, composite scores, and mean and maximum scores across attributes (frequency, severity, and/or interference) of symptomatic adverse events were calculated. For each adverse event, correlations and agreement between attributes, correlations between attributes and composite scores, and correlations between composite, mean, and maximum scores were estimated.</p><p><strong>Results: </strong>PRO-CTCAE items were completed by 899 patients with various cancer types. Most patients reported experiencing one or more adverse events, with the most prevalent being fatigue (87.7%), sad/unhappy feelings (66.0%), anxiety (63.6%), pain (63.2%), insomnia (61.8%), and dry mouth (60.0%). Attributes were moderately to strongly correlated within an adverse event (<i>r</i> = 0.53 to 0.77, all <i>p</i> < 0.001) but not fully concordant (κ<sub>weighted</sub> = 0.26 to 0.60, all <i>p</i> < 0.001), with interference demonstrating lowest mean scores and prevalence among attributes of the same adverse event. Attributes were moderately to strongly correlated with composite scores (<i>r</i> = 0.67 to 0.97, all <i>p</i> < 0.001). Composite scores were moderately to strongly correlated with mean and maximum scores for the same adverse event (<i>r</i> = 0.69 to 0.94, all <i>p</i> < 0.001). Correlations between composite scores of different adverse events varied widely (<i>r</i> = 0.04 to 0.68) but were moderate to strong for conceptually related adverse events.</p><p><strong>Conclusions: </strong>Results provide evidence for PRO-CTCAE administration and reporting recommendations that the full complement of attributes be administered for each adverse event, and that attributes as well as summary scores be reported.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"17407745241286065"},"PeriodicalIF":2.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 state of individual participant data sharing for the highest-revenue medicines. 收入最高的药品的个人参与者数据共享情况。
IF 2.2 3区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-15 DOI: 10.1177/17407745241286147
Natansh D Modi, Lee X Li, Jessica M Logan, Michael D Wiese, Ahmad Y Abuhelwa, Ross A McKinnon, Andrew Rowland, Michael J Sorich, Ashley M Hopkins

Background: Amid growing emphasis from pharmaceutical companies, advocacy groups, and regulatory bodies for sharing of individual participant data, recent audits reveal limited sharing, particularly for high-revenue medicines. Therefore, this study aimed to assess the individual participant data-sharing eligibility of clinical trials supporting the Food and Drug Administration approval of the top 30 highest-revenue medicines for 2021.

Methods: A cross-sectional analysis was conducted on 316 clinical trials supporting approval of the top 30 revenue-generating medicines of 2021. The study assessed whether these trials were eligible for individual participant data sharing, defined as being publicly listed on a data-sharing platform or confirmed by the trial sponsors as in scope for independent researcher individual participant data investigations. Information was gathered from various sources including ClinicalTrials.gov, the European Union Clinical Trials Register, and PubMed. Key factors such as the trial phase, completion dates, and the nature of the data-sharing process were also examined.

Results: Of the 316 trials, 201 (64%) were confirmed eligible for sharing, meaning they were either publicly listed on a data-sharing platform or confirmed by the trial sponsors as in scope for independent researcher individual participant data investigations. A total of 102 (32%) were confirmed ineligible, and for 13 (4%), the sponsor indicated that a full research proposal would be required to determine eligibility. The analysis also revealed a higher rate of individual participant data sharing among companies that utilized independent platforms, such as Vivli, for managing their individual participant data-sharing process. Trials not marked as completed had significantly lower eligibility for individual participant data sharing.

Conclusion: This study highlights that a substantial portion of trials for top revenue-generating medicines are eligible for individual participant data sharing. However, challenges persist, particularly for trials that are marked as ongoing and for trials where the sharing processes are managed internally by pharmaceutical companies. Data-sharing rates could be improved by adopting open-access individual participant data-sharing models or using independent platforms. Standardizing policies to facilitate immediate individual participant data availability for approved medicines is necessary.

背景:在制药公司、倡导团体和监管机构日益强调共享受试者个人数据的同时,最近的审计显示共享数据有限,尤其是高收入药物。因此,本研究旨在评估支持美国食品和药物管理局批准 2021 年收入最高的前 30 种药品的临床试验的个体参与者数据共享资格:对支持 2021 年收入最高的 30 种药品审批的 316 项临床试验进行了横向分析。研究评估了这些试验是否符合个体参与者数据共享的条件,即在数据共享平台上公开列出或经试验申办者确认属于独立研究人员个体参与者数据调查范围。研究人员从各种渠道收集信息,包括 ClinicalTrials.gov、欧盟临床试验注册中心和 PubMed。此外,还对试验阶段、完成日期和数据共享过程的性质等关键因素进行了研究:在316项试验中,有201项(64%)被确认符合共享条件,这意味着这些试验要么在数据共享平台上公开列出,要么经试验发起人确认属于独立研究人员对个体参与者数据进行调查的范围。共有 102 个项目(32%)被确认为不符合条件,13 个项目(4%)的发起人表示需要一份完整的研究计划书才能确定是否符合条件。分析还显示,在利用 Vivli 等独立平台管理个人参与者数据共享流程的公司中,个人参与者数据共享率较高。未标注为已完成的试验的个人参与者数据共享资格明显较低:本研究强调,大部分创收最高的药品试验都符合个体参与者数据共享的条件。然而,挑战依然存在,尤其是那些被标注为正在进行的试验和由制药公司内部管理共享流程的试验。通过采用开放式个人参与者数据共享模式或使用独立平台,可以提高数据共享率。有必要对政策进行标准化,以促进已批准药物的个人参与者数据的即时可用性。
{"title":"The state of individual participant data sharing for the highest-revenue medicines.","authors":"Natansh D Modi, Lee X Li, Jessica M Logan, Michael D Wiese, Ahmad Y Abuhelwa, Ross A McKinnon, Andrew Rowland, Michael J Sorich, Ashley M Hopkins","doi":"10.1177/17407745241286147","DOIUrl":"https://doi.org/10.1177/17407745241286147","url":null,"abstract":"<p><strong>Background: </strong>Amid growing emphasis from pharmaceutical companies, advocacy groups, and regulatory bodies for sharing of individual participant data, recent audits reveal limited sharing, particularly for high-revenue medicines. Therefore, this study aimed to assess the individual participant data-sharing eligibility of clinical trials supporting the Food and Drug Administration approval of the top 30 highest-revenue medicines for 2021.</p><p><strong>Methods: </strong>A cross-sectional analysis was conducted on 316 clinical trials supporting approval of the top 30 revenue-generating medicines of 2021. The study assessed whether these trials were eligible for individual participant data sharing, defined as being publicly listed on a data-sharing platform or confirmed by the trial sponsors as in scope for independent researcher individual participant data investigations. Information was gathered from various sources including ClinicalTrials.gov, the European Union Clinical Trials Register, and PubMed. Key factors such as the trial phase, completion dates, and the nature of the data-sharing process were also examined.</p><p><strong>Results: </strong>Of the 316 trials, 201 (64%) were confirmed eligible for sharing, meaning they were either publicly listed on a data-sharing platform or confirmed by the trial sponsors as in scope for independent researcher individual participant data investigations. A total of 102 (32%) were confirmed ineligible, and for 13 (4%), the sponsor indicated that a full research proposal would be required to determine eligibility. The analysis also revealed a higher rate of individual participant data sharing among companies that utilized independent platforms, such as Vivli, for managing their individual participant data-sharing process. Trials not marked as completed had significantly lower eligibility for individual participant data sharing.</p><p><strong>Conclusion: </strong>This study highlights that a substantial portion of trials for top revenue-generating medicines are eligible for individual participant data sharing. However, challenges persist, particularly for trials that are marked as ongoing and for trials where the sharing processes are managed internally by pharmaceutical companies. Data-sharing rates could be improved by adopting open-access individual participant data-sharing models or using independent platforms. Standardizing policies to facilitate immediate individual participant data availability for approved medicines is necessary.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"17407745241286147"},"PeriodicalIF":2.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Using non-inferiority test of proportions in design of randomized non-inferiority trials with time-to-event endpoint with a focus on low-event-rate setting. 在设计以时间为终点的随机非劣效性试验时使用比例非劣效性检验,重点关注低事件率环境。
IF 2.2 3区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-12 DOI: 10.1177/17407745241284786
Lingyun Ji, Todd A Alonzo

Background/aims: For cancers with low incidence, low event rates, and a time-to-event endpoint, a randomized non-inferiority trial designed based on the logrank test can require a large sample size with significantly prolonged enrollment duration, making such a non-inferiority trial not feasible. This article evaluates a design based on a non-inferiority test of proportions, compares its required sample size to the non-inferiority logrank test, assesses whether there are scenarios for which a non-inferiority test of proportions can be more efficient, and provides guidelines in usage of a non-inferiority test of proportions.

Methods: This article describes the sample size calculation for a randomized non-inferiority trial based on a non-inferiority logrank test or a non-inferiority test of proportions. The sample size required by the two design methods are compared for a wide range of scenarios, varying the underlying Weibull survival functions, the non-inferiority margin, and loss to follow-up rate.

Results: Our results showed that there are scenarios for which the non-inferiority test of proportions can have significantly reduced sample size. Specifically, the non-inferiority test of proportions can be considered for cancers with more than 80% long-term survival rate. We provide guidance in choice of this design approach based on parameters of the Weibull survival functions, the non-inferiority margin, and loss to follow-up rate.

Conclusion: For cancers with low incidence and low event rates, a non-inferiority trial based on the logrank test is not feasible due to its large required sample size and prolonged enrollment duration. The use of a non-inferiority test of proportions can make a randomized non-inferiority Phase III trial feasible.

背景/目的:对于发病率低、事件发生率低且以时间为终点的癌症,基于logrank检验设计的随机非劣效性试验可能需要较大的样本量,且入组时间明显延长,因此这种非劣效性试验并不可行。本文评估了基于非劣效性比例检验的设计,比较了其与非劣效性 logrank 检验所需的样本量,评估了是否存在非劣效性比例检验更有效的情况,并提供了使用非劣效性比例检验的指南:本文介绍了基于非劣效 logrank 检验或非劣效比例检验的随机非劣效试验的样本量计算。文章比较了两种设计方法在不同情况下所需的样本量,包括基础 Weibull 生存函数、非劣效边际和随访损失率:结果:我们的研究结果表明,在某些情况下,比例非劣效性检验可以显著减少样本量。具体来说,对于长期生存率超过 80% 的癌症,可以考虑采用比例非劣效性检验。我们根据 Weibull 生存函数的参数、非劣效边际和随访损失率,为选择这种设计方法提供指导:结论:对于低发病率和低事件发生率的癌症,基于对数秩检验的非劣效性试验是不可行的,因为它所需的样本量大,入组时间长。使用比例非劣效性检验可以使随机非劣效性 III 期试验变得可行。
{"title":"Using non-inferiority test of proportions in design of randomized non-inferiority trials with time-to-event endpoint with a focus on low-event-rate setting.","authors":"Lingyun Ji, Todd A Alonzo","doi":"10.1177/17407745241284786","DOIUrl":"10.1177/17407745241284786","url":null,"abstract":"<p><strong>Background/aims: </strong>For cancers with low incidence, low event rates, and a time-to-event endpoint, a randomized non-inferiority trial designed based on the logrank test can require a large sample size with significantly prolonged enrollment duration, making such a non-inferiority trial not feasible. This article evaluates a design based on a non-inferiority test of proportions, compares its required sample size to the non-inferiority logrank test, assesses whether there are scenarios for which a non-inferiority test of proportions can be more efficient, and provides guidelines in usage of a non-inferiority test of proportions.</p><p><strong>Methods: </strong>This article describes the sample size calculation for a randomized non-inferiority trial based on a non-inferiority logrank test or a non-inferiority test of proportions. The sample size required by the two design methods are compared for a wide range of scenarios, varying the underlying Weibull survival functions, the non-inferiority margin, and loss to follow-up rate.</p><p><strong>Results: </strong>Our results showed that there are scenarios for which the non-inferiority test of proportions can have significantly reduced sample size. Specifically, the non-inferiority test of proportions can be considered for cancers with more than 80% long-term survival rate. We provide guidance in choice of this design approach based on parameters of the Weibull survival functions, the non-inferiority margin, and loss to follow-up rate.</p><p><strong>Conclusion: </strong>For cancers with low incidence and low event rates, a non-inferiority trial based on the logrank test is not feasible due to its large required sample size and prolonged enrollment duration. The use of a non-inferiority test of proportions can make a randomized non-inferiority Phase III trial feasible.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"17407745241284786"},"PeriodicalIF":2.2,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
15th Annual University of Pennsylvania conference on statistical issues in clinical trial/advances in time-to-event analyses in clinical trials (afternoon panel discussion). 宾夕法尼亚大学第 15 届年会,主题为临床试验中的统计问题/临床试验中时间到事件分析的进展(下午小组讨论)。
IF 2.2 3区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-01 Epub Date: 2024-10-08 DOI: 10.1177/17407745241271939
Ionut Bebu, Rebecca A Betensky, Michael P Fay
{"title":"15th Annual University of Pennsylvania conference on statistical issues in clinical trial/advances in time-to-event analyses in clinical trials (afternoon panel discussion).","authors":"Ionut Bebu, Rebecca A Betensky, Michael P Fay","doi":"10.1177/17407745241271939","DOIUrl":"10.1177/17407745241271939","url":null,"abstract":"","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":" ","pages":"612-622"},"PeriodicalIF":2.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Clinical Trials
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