Abstract：
BACKGROUND: Amendments are changes made to a clinical trial after it has received regulatory approval. An amendment can take a significant amount of time and resources to develop, review and implement at participating sites. This can affect the efficient delivery of clinical trials and potentially contribute to research waste. This study aimed to establish what the most common amendments are, why they are submitted, and what, if anything, can be done to avoid them.
METHODS: An explanatory sequential mixed methods design was employed. The first strand involved a content analysis on a sample of amendments, submitted in trials sponsored by a University Hospital NHS Trust between September 2009 and March 2020, to establish the most common changes and reasons for amendments. The second strand involved thematically analysing semi-structured interviews with trial stakeholders to explore their views on the reasons underpinning the submission of amendments, and the potential for efficiencies that could prevent avoidable amendments.
RESULTS: Two hundred forty-two approved amendments were examined from 53 clinical research studies. The \'Addition of sites\' was the most common amendment change, and the most common reason for amendments was \'To achieve the trial\'s recruitment target\'. The root causes for avoidable amendments identified by the 11 interviewees included the following: \'Rushing the initial application knowing an amendment will be needed later\', \'Not involving all the right people to input\' at the start of the trial, and \'Realising it\'s not feasible in practice when delivering the trial\'. Missing regulatory checks following an onerous and error-prone application process were also identified as the cause of some amendments.
CONCLUSIONS: Trials need to be critically reviewed by various stakeholders and have sufficient time allocated to planning and feasibility assessments to avoid some amendments. This may improve clinical trial efficiency, to benefit the trial participants, researchers, funders, sponsors, and regulatory bodies, and potentially bring new treatments to patients faster.
METHODS: An explanatory sequential mixed methods design was employed. The first strand involved a content analysis on a sample of amendments, submitted in trials sponsored by a University Hospital NHS Trust between September 2009 and March 2020, to establish the most common changes and reasons for amendments. The second strand involved thematically analysing semi-structured interviews with trial stakeholders to explore their views on the reasons underpinning the submission of amendments, and the potential for efficiencies that could prevent avoidable amendments.
RESULTS: Two hundred forty-two approved amendments were examined from 53 clinical research studies. The \'Addition of sites\' was the most common amendment change, and the most common reason for amendments was \'To achieve the trial\'s recruitment target\'. The root causes for avoidable amendments identified by the 11 interviewees included the following: \'Rushing the initial application knowing an amendment will be needed later\', \'Not involving all the right people to input\' at the start of the trial, and \'Realising it\'s not feasible in practice when delivering the trial\'. Missing regulatory checks following an onerous and error-prone application process were also identified as the cause of some amendments.
CONCLUSIONS: Trials need to be critically reviewed by various stakeholders and have sufficient time allocated to planning and feasibility assessments to avoid some amendments. This may improve clinical trial efficiency, to benefit the trial participants, researchers, funders, sponsors, and regulatory bodies, and potentially bring new treatments to patients faster.
摘要：
背景：修正案是在临床试验获得监管批准后对其进行的更改。修正案可能需要大量的时间和资源来制定，在参与站点进行审查和实施。这可能会影响临床试验的有效交付，并可能造成研究浪费。这项研究旨在确定最常见的修正案是什么，为什么他们被提交，什么，如果有的话,可以避免它们。
方法：采用解释性序贯混合方法设计。第一条涉及对修正案样本的内容分析，在2009年9月至2020年3月期间由大学医院NHS信托赞助的试验中提交，以确定最常见的更改和修改原因。第二个环节涉及对审判利益相关方的半结构化访谈进行主题分析，以探讨他们对提交修正案的原因的看法，以及可能阻止可避免的修订的潜在效率。
结果：从53项临床研究中检查了242项批准的修正案。“增加网站”是最常见的修正案更改，修改的最常见原因是“为了实现审判的招募目标”。11名受访者确定的可避免的修改的根本原因包括：\“在知道以后需要修改的情况下匆忙提出最初的申请\”，\'在审判开始时不涉及所有合适的人输入\'，和“在交付试验时在实践中实现它是不可行的”。在繁重且容易出错的申请过程中，缺少监管检查也被认为是某些修订的原因。
结论：试验需要各利益相关方进行严格审查，并有足够的时间进行规划和可行性评估，以避免一些修改。这可能会提高临床试验效率，为了使试验参与者受益，研究人员,资助者,赞助商,和监管机构，并有可能更快地为患者带来新的治疗方法。
方法：采用解释性序贯混合方法设计。第一条涉及对修正案样本的内容分析，在2009年9月至2020年3月期间由大学医院NHS信托赞助的试验中提交，以确定最常见的更改和修改原因。第二个环节涉及对审判利益相关方的半结构化访谈进行主题分析，以探讨他们对提交修正案的原因的看法，以及可能阻止可避免的修订的潜在效率。
结果：从53项临床研究中检查了242项批准的修正案。“增加网站”是最常见的修正案更改，修改的最常见原因是“为了实现审判的招募目标”。11名受访者确定的可避免的修改的根本原因包括：\“在知道以后需要修改的情况下匆忙提出最初的申请\”，\'在审判开始时不涉及所有合适的人输入\'，和“在交付试验时在实践中实现它是不可行的”。在繁重且容易出错的申请过程中，缺少监管检查也被认为是某些修订的原因。
结论：试验需要各利益相关方进行严格审查，并有足够的时间进行规划和可行性评估，以避免一些修改。这可能会提高临床试验效率，为了使试验参与者受益，研究人员,资助者,赞助商,和监管机构，并有可能更快地为患者带来新的治疗方法。
