随机对照试验(randomized controlled trial，RCT)常作为评价干预效果的最佳研究设计，但现有研究中报告关于不良事件(adverse event)或危害(harm)相关数据的报告质量有待提高，准确、规范、全面地报告RCT研究中的不良事件、副作用或危害，有利于读者对结果进行批判性评价和理解。本文主要概述随机对照试验中的不良事件的CONSORT扩展版(Consolidated Standards of Reporting Trials-Harms, CONSORT-Harms)。
关键词：CONSORT; 随机对照试验报告规范; 不良事件; 危害; 随机对照试验中的不良事件; CONSORT - Harms
一、CONSORT - Harms背景介绍
随机对照试验(randomized controlled trial，RCT)主要研究某种干预措施或治疗方案的效果，也是发现药物危害的重要途径之一，但是其危害、副作用或不良事件易被有偏或粗略报告。因此，提高RCT试验中关于危害相关数据的报告质量是高质量的RCT报告的重要组成部分，也更利于读者或决策者更加全面的了解某种干预措施或治疗方案的临床效应。
CONSORT学组鼓励作者使用“危害”代替“安全性”，因为安全性(safety)是个褒义性术语，可能会掩盖药品或者干预措施引起的重大的危害或潜在危害。2003年5月，CONSORT学组在CONSORT声明标准版的基础上新提出了报告“危害”的10条推荐意见，并附上了说明及实例，CONSORT-Harms于2004年正式发表。
二、CONSORT – Harms条目清单
表1 CONSORT - Harms条目清单中英文对照
| 内容 | 条目 序号 | 标准清单内容 | HARM扩展版内容 |
| Title and abstract 标题与摘要 | 1 | How participants were allocated to interventions (e.g.,"random allocation" "randomized", or "randomly assigned" ) 如何把患者分配到不同的干预组(如“随机分配”“随机化”) | If the study collected data on harms and benefits, the title or abstract should so state 如果研究收集了危害和疔效的数据，题目或者摘要中应该进行说明 |
| Introduction 引言 | |||
| Background 背景 | 2 | Scientific background and explanation of rationale 论述研究背景和解释相关原理 | If the trial addresses both harms and benefits, the introduction should so state 如果试验研究了危害和疗效，引言中应该进行描述 |
| Methods 方法 | |||
| Participants 研究对象 | 3 | Eligibility criteria for participants, settings and locations where the data were collected 报告纳入标准和数据收集的环境和地点 | |
| Interventions 干预 | 4 | Precise details of the interventions intended for each group and how and when they were actually administered 准确描述每组的干预，以及实施干预的过程和时间 | |
| Objectives 目的 | 5 | Specific objectives and hypotheses 明确说明目标和假设 | |
| Outcomes 结局 | 6 | Clearly defined primary and secondary outcome measures and, when applicable, any methods used to enhance the quality of measurements (e.g., multiple observations, training of assessors) 清楚定义主要结局和次要结局，如果可以的话，还应报告提高结局测量质量的方法(如多次测量，测量者培训) | List addressed adverse events with definitions for each (with attention, when relevant, to grading, expected vs. unexpected events, reference to standardized and validated definitions, and description of new definitions) Clarify how harms-related information was collected (mode of data collection, timing, attribution methods, intensity of ascertainment, and harms-related monitoring and stopping rules, if pertinent) 列举所研究的每个不良事件的定义(应特别注意，什么时候相关、分级、预期或非预期的事件、标准的定义、可验证方式及新定义) 明确危害相关信息的收集(数据采集模式、观察时间、归因方法、确定强度；如果相关的话，还包括危害相关监测和停止的原则) |
| Sample size 样本量 | 7 | How sample size was determined and, when applicable, explanation of any interim analyses and stopping rules 报告如何确定样本量，可以的话还应该 报告中期分析结果和终止试验的规则 | |
| Randomization sequence generation 随机分配序列的产生 | 8 | Method used to generate the random allocation sequence, including details of any restriction (e.g., blocking, stratification) 报告产生随机分配序列的方法，包括任何限制性随机化的细节(如区组、分层) | |
| Allocation concealment 分配隐匿 | 9 | Method used to implement the random allocation sequence (e.g., numbered containers or central telephone), clarifying whether the sequence was concealed until interventions were assigned 报告实施随机的方法(如编码的容器或 中心电话)，明确在实施干预之前是否 进行分配隐藏 | |
| Implementation 随机化实施 | 10 | Who generated the allocation sequence, who enrolled participants, and who assigned participants to their groups 说明由谁生成随机分配序列，谁招募研究对象，谁对研究对象进行分组 | |
| Blinding 盲法 | 11 | Whether or not participants, those administering the interventions, and those assessing the outcomes were blinded to group assignment. If done, how the success of blinding was evaluated 报告研究对象、干预实施者、结局评佔 者是否不知道分组情况，如何评价盲法 是否成功 | |
| Statistical methods 统计方法 | 12 | Statistical methods used to compare groups or primary outcome(s); Methods for additional analyses, such as subgroup analyses and adjusted analyses 说明比较主要结局指标的统计方法；其他分析方法，如亚组分析和调整分析 | Describe plans for presenting and analyzing information on harms (including coding, handling of recurrent events, specification of timing issues, handling of continuous measures, and any statistical analyses) 详细描述分析危害信息的计划(包括编码、复发事件处理、观察时间点的分类、连续变量处理和统计分析) |
| Results 结果 | |||
| Participant flow 研究对象纳入流程 | 13 | Flow of participants through each stage ( a diagram is strongly recommended ). Specifically, for each group report the numbers of participants randomly assigned, receiving intended treatment, completing the study protocol, and analyzed for the primary outcome. Describe protocol deviations from study as planned, together with reasons 报告每一阶段参与试验的研究对象人数(强烈建议使用流程图)——即每个组的随机分配的人数、接受治疗的人数、完成治疗方案的人数、用于主要结局分析的人数等。对于违背研究计划的地方，还要对其原因加以解释 | Describe for each arm the participant withdrawals that are due to harms and their experiences with the allocated treatment 描述每组研究对象因为接受分配治疗后的不良事件而退出的情况 |
| Recruitment 招募 | 14 | Dates defining the periods of recruitment and follow-up 说明招募和随访的日期 | |
| Baseline data 基线数据 | 15 | Baseline demographic and clinical characteristics of each group 描述基线时每组的人口统计学资料和临床特征 | |
| Number analyzed 分析数量 | 16 | Number of participants (denominator) in each group included in each analysis and whether the analysis was by "intention-to-treat". State the results in absolute numbers when feasible (e.g., 10/20, not 50%) 每项分析中都需要报告每组分析的研究对象人数(分母)，注明是否采用了意向性分析；如果可能，应该采用绝对数报告结果(例如10/20，而非50%) | Provide the denominators for analyses on harms 提供分析危害事件的分母 |
| Outcomes and estimation 结局和效应估计 | 17 | For each primary and secondary outcome, a summary of results for each group, and he estimated effect size and its precision (e.g., 95% confidence interval) 对于每一项主要结局和次要结局，需报告每组的结果、效应值及其精确度(如95%置信区间) | Present the absolute risk per arm and per adverse event type, grade, and seriousness, and present appropriate metrics for recurrent events, continuous variables, and scale variables, whenever pertinent 确定因果关联后，需要报告每个治疗组每种不良事件的绝对危险度，分级和严重程度，并且提出适合的评价复发事件、连续变量和等级变量的指标 |
| Ancillary analyses 其他分析 | 18 | Address multiplicity by reporting any other analyses performed, including subgroup analyses and adjusted analyses, including which are prespecified and which are exploratory 若处理多因素，应报告其他分析，包括亚组分析和调整分析，并指出哪些是事先设定的，哪些是探素性的 | Describe any subgroup analyses and exploratory analyses for harms 描述涉及危害的任何亚组分析和探索性分析 |
| Adverse events 不良事件 | 19 | All important adverse events or side effects in each intervention group 报告每个组发生的所有重要的不良事件或副作用 | |
| Discussion 讨论 | |||
| Interpretation 解释 | 20 | Interpretation of the results, taking into account study hypotheses, sources of potential bias or imprecision, and the dangers associated with multiplicity of analyses and outcomes 解释结果时要考虑研究假设、潜在的偏倚或不精确的原因，以及多重比较和多种结局的问题 | Provide a balanced discussion of benefits and harms with emphasis on study limitations, generalizability, and other sources of information on harms 提供疗效和危害的权衡讨论，强调研究的局限性和外推性，以及危害信息的其他来源 |
| Generalizability 外推性 | 21 | Generalizability (external validity) of the trial findings 解释试验结果的外推性(外部真实性) | |
| Overall evidence 整体证据 | 22 | General interpretation of the results in the context of current evidence 基于当前证据对结果进行概括性解释 | |
三、CONSORT - Harms使用注意事项
作者可以参考CONSORT - Harms扩展版来撰写RCT报告中涉及危害、副作用及不良事件内容，以提高规范性及完整性；审稿专家和编辑可参考CONSORT - Harms扩展版来审阅RCT报告；读者可通过CONSORT - Harms扩展版了解RCT报告中危害相关信息的关注内容。值得注意的是，CONSORT - Harms并不是评估RCT研究质量的工具，不宜使用该清单构建总体质量得分。
注：本文内容是参考相关文献后对CONSORT - Harms原文的概述，仅代表本网站观点。关于CONSORT - Harms的更多内容详见官方网站(http://www.consort-statement.org)或论文Better reporting of harms in randomized trials: an extension of the CONSORT statement (https://pubmed.ncbi.nlm.nih.gov/15545678/)、更好地报告随机试验中的危害(http://www.cjebm.com/article/zgxzyxzz/2006/9/682)：CONSORT声明扩展版。
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