非劣效性与等效性随机对照试验(non-inferiority/equivalence randomized trial)是阳性对照/标准对照研究中的核心设计类型，其数量不断增长。非劣效性与等效性随机对照试验CONSORT扩展版是CONSORT声明扩展的重要内容。本文概述非劣效性与等效性随机对照试验CONSORT扩展版相关内容。
关键词：非劣效性研究; 等效性研究; 随机对照试验; 报告规范; 临床试验报告的统一标准; CONSORT扩展版
一、非劣效性与等效性随机对照试验报告规范背景
非劣效性与等效性随机对照试验的产生，一方面是因为某种疾病已经有了疗效确切的药物或方法，仍使用安慰剂作为对照组进行试验，会产生伦理学问题，此时须使用标准药物或疗法作为对照；另一方面随着有效药物的大量出现，研发有突破性疗效的药物越来越难，临床试验的目的也开始转变，在标准药物或方法作为对照组的试验中，更多的是探索新药与标准药物或方法相比，疗效是否相当或不差于后者，而并非必须优于标准药物或方法。由此，提出了非劣效性与等效性试验(non-inferiority/equivalence trial)的概念。非劣效性试验(non-inferiority trial)是指确定一种新的药物或疗法在非劣效性界值(Δ)内是否不劣于标准药物或疗法，等效性试验(equivalence trial)是指确定一种新的药物或疗法在临床可接受的差异(等效性界值：-Δ~Δ)内与标准药物或疗法相当。
鉴于非劣效性与等效性试验数量的不断增长及相关报道中暴露出的问题。2004年10月，CONSORT小组制定了《非劣效性和等效性随机试验的报告：CONSORT声明扩展版》，于2006年3月正式发表。2010年，CONSORT小组又在CONSORT清单的基础上进行了相应的修改和扩展，于2012年底发表了《非劣效性和等效性试验的CONSORT扩展声明》，这是目前公认的非劣效性和等效性试验的报告规范。该扩展版一共包括6个部分，25大条目，根据非劣效性和等效性试验的特点对CONSORT声明的第1、2、4、5、6、7、12、17、22共9个条目进行了修订扩展，余相同。
二、非劣效性与等效性试验的CONSORT扩展版条目清单
(一) 非劣效性与等效性试验的CONSORT扩展版条目清单
表1 非劣效性与等效性试验CONSORT扩展版的条目清单中英文对照
| 内容 | 条目序号 | 标准清单内容 | 非劣效性和等效性设计的扩展内容 |
| Title and abstract 标题与摘要 | 1a | Identification as a randomized trial in the title 在题目中体现随机化试验 | ldentification as a non-inferiority/equivalence randomized trial in the title 题目中明确说明为非劣效性或等效性随机试验 |
| 1b | Structured summary of trial design, methods, results, and conclusions (for specific guidance see CONSORT for abstracts) 结构化摘要，包括试验设计、方法、结果和结论(详见CONSORT摘要) | See Table 2 见表2 | |
| Introduction 引言 | |||
| Background and objectives 背景和目的 | 2a | Scientific background and explanation of rationale 研究的科学背景和试验的理由 | Rationale for using a non-inferiority/equivalence design 使用非劣效性或等效性设计的理论基础 |
| 2b | Specific objectives or hypotheses 研究目的或假设 | Hypotheses concerning non-inferiority/equivalence, specifying the non-inferiority/equivalence margin with the rationale for its choice 非劣效性或等效性的假设，指明选定非劣效性或等效性界值的理论基础 | |
| Methods 方法 | |||
| Trial design 试验设计 | 3a | Description of trial design (such as parallel, factorial), including allocation ratio 描述试验设计(如平行、析因设计)，包括分配比例 | |
| 3b | Important changes to methods after trial commencement (such as eligibility criteria), with reasons 试验开始后方法上的重要改变(如纳入排除标准)及原因 | ||
| Participants 研究对象 | 4a | Eligibility criteria for participants 研究对象的纳入排除标准 | Whether participants in the non-inferiority/equivalence trial are similar to those in any trial(s) that established efficacy of the reference treatment 详细说明非劣效性或等效性试验的受试者是否与用于确定对照组干预措施有效性试验的受试者相似 |
| 4b | Settings and locations where the data were collected 数据收集的机构和地点 | ||
| Interventions 干预 | 5 | The interventions for each group with sufficient details to allow replication, including how and when they were actually administered 各组干预的详细内容，包括何时、如何实际开展，以便能够重复 | Whether the reference treatment in the non-inferiority/equivalence trial is identical (or very similar) to that in any trial(s) that established efficacy 详细说明非劣效性或等效性试验中用到的对照干预是否与以前确定有效性的试验中用到的处理相同(或非常相似) |
| Outcomes 结局 | 6a | Completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed 完整明确地定义预先规定的主要和次要结局指标，包括何时、如何评价 | Specify the non-inferiority/equivalence outcome(s) and whether hypotheses for main and secondary outcome(s) are non-inferiority or superiority. Whether the outcomes in the non-inferiority/equivalence trial are identical (or very similar) to those in any trial(s) that established efficacy of the reference treatment 清楚定义非劣效性或等效性试验的结局，并明确主要和次要结局的假设是否为非劣效性或优效性检验。同时详细说明非劣效性或等效性试验中用到的结局是否与以前确立对照治疗有效性试验中用到的结局相同(或非常相似) |
| 6b | Any changes to trial outcomes after the trial commenced, with reasons 试验开始后结局的改变及原因 | ||
| Sample size 样本量 | 7a | How sample size was determined 样本量如何确定 | Whether the sample size was calculated using a non-inferiority/equivalence criterion and, if so, what the non-inferiority/equivalence margin was 详细说明样本量的计算是否按照非劣效性或等效性标准，并说明选定非劣效性或等效性界值的理论基础 |
| 7b | When applicable, explanation of any interim analyses and stopping guidelines 对期中分析和中止试验的条件、时间进行解释(如适用) | To which outcome(s) they apply and whether related to a non-inferiority/equivalence hypothesis 详细说明对哪些结局指标进行了期中分析或中止试验，并说明是否与非劣效性或等效性假设相关 | |
| Randomization 随机化 | |||
| Sequence generation 序列生成 | 8a | Method used to generate the random allocation sequence 产生随机分配序列的方法 | |
| 8b | Type of randomization; details of any restriction(such as blocking and block size) 随机化类型；任何限定情况的详细信息(如区组和区组大小) | ||
| Allocation concealment mechanism 分配隐藏机制 | 9 | Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned 实施随机序列的方法(如连续编码的容器)，阐明隐藏分配序列的措施 | |
| Implementation 实施 | 10 | Who generated the random allocation sequence who enrolled participants，and who assigned participants to interventions 产生分配序列、纳入研究对象、分配研究对象的人员 | |
| Blinding 盲法 | 11a | If done, who was blinded after assignment to interventions ( for example, participants.care providers，those assessing outcomes ) and how 如果实施了盲法，应说明对谁设盲(如研究对象、干预提供者、结局评价者)，如何实施的 | |
| 11b | If relevant, description of the similarity of interventions 组间干预的相似性 | ||
| Statistical methods 统计方法 | 12a | Statistical methods used to compare groups for primary and secondary outcomes 组间比较，主要结局与次要结局的统计方法 | Whether a 1- or 2-sided confidence interval approach was used 指明采用的是单侧还是双侧置信区间评估 |
| 12b | Methods for additional analyses, such as subgroup analyses and adjusted 其他分析方法，如亚组分析和校正分析 | ||
| Results 结果 | |||
| Participant flow (a diagram is strongly recommended 研究对象纳入流程(强烈推荐流程图) | 13a | For each group, the numbers of participants who were randomly assigned, received intended treatment,and were analyzed for the primary outcome 各组接受随机分配、接受干预和进入主要结局分析的研究对象数量 | |
| 13b | For each group, losses and exclusions after randomization, together with reasons 各组随机化之后发生的脱落或失访、排除，以及原因 | ||
| Recruitment 研究对象的招募 | 14a | Dates defining the periods of recruitment and follow-up 招募研究对象和随访的日期范围 | |
| 14b | Why the trial ended or was stopped 研究结束或停止的原因 | ||
| Baseline data 基线数据 | 15 | A table showing baseline demographic and clinical characteristics for each group 反映各组基线人口学特征和临床特征的表格 | |
| Number analyzed 分析数量 | 16 | For each group, number of participants (denominator) included in each analysis and whether the analysis was by original assigned groups 各组纳入分析的研究对象数量(分母)，是否按照最初分组进行分析 | |
| Outcomes and estimation 结局和效应估计 | 17a | For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval) 对每个主要和次要结局，报告各组结果、效应估计和精确度(如95%置信区间) | For the outcome(s) for which non-inferiority/equivalence was hypothesized, a figure showing confidence intervals and the non-interiority/equivalence margin may be useful 对于非劣效性或等效性假设的结局，可利用图形表示置信区间和非劣效性/等效性界值 |
| 17b | For binary outcomes presentation of both absolute and relative effect sizes is recommended 对二分类结局，报告绝对效应和相对效应 | ||
| Ancillary analyses 其他分析 | 18 | Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing prespecified from exploratory 报告其他分析(包括亚组分析和校正分析)结果，区分预先设定的分析和探索性分析 | |
| Harms 损害 | 19 | All important harms or unintended effects in each group 所有重要损害或未预期到的效应 | |
| Discussion 讨论 | |||
| Limitations 局限性 | 20 | Trial limitations; addressing sources of potential bias; imprecision; and, if relevant, multiplicity of analyses 试验局限性；关注偏倚的来源；不精确程度；多重比较问题 | |
| Generalizability 外推性 | 21 | Generalizability (external validity, applicability) of the trial findings 试验结果的外推性(外部有效性、适用性) | |
| Interpretation 结果解释 | 22 | Interpretation consistent with results, balancing benefits and harms, and considering other relevant evidence 权衡收益和损害，并考虑其他相关证据，对结果进行解释 | Interpret results in relation to the non-inferiority/equivalence hypothesis. lf a superiority conclusion is drawn for outcome(s) for which non-inferiority/equivalence was hypothesized, provide justification for switching 解读结果需考虑非劣效性或等效性假设；若在非劣效性或等效性试验中得出优效的结论，需提供转为优效性结论的理由 |
| Other information 其他信息 | |||
| Registration 注册 | 23 | Registration number and name of trial registry 注册机构与注册号 | |
| Protocol 研究方案 | 24 | Where the full trial protocol can be accessed, if available 可以获得完整研究方案的地方 (如适用) | |
| Funding 资助 | 25 | Sources of funding and other support(such as supply of drugs), role of funders 资助来源和其他支持，资助者的作用 | |
(二) 非劣效性与等效性试验CONSORT扩展版摘要条目清单
表2 非劣效性与等效性试验CONSORT扩展版摘要条目清单的中英文对照
| 内容条目 | 标准清单内容 | 非劣效性或等效性设计的扩展内容 |
| Title 题目 | Identification of study as randomised 可通过标题判断为随机试验 | Identification of study as a non-inferiority/equivalence trial 可通过标题判断为非劣效性或等效性试验 |
| Trial design 试验设计 | Description of the trial design (for example, parallel, cluster, non-inferiority) 试验设计描述(如平行对照、整设计、非劣效性研究) | |
| Methods 方法 | ||
| Participants 研究对象 | Eligibility criteria for participants and the settings where the data were collected 研究对象的纳入排除标准和资料的收集 | |
| Interventions 干预 | Interventions intended for each group 针对每组的干预措施 | |
| Objective 目的 | Specific objective or hypothesis 具体目的或假设 | Specific hypothesis concerning non-inferiority/equivalence, including noninferiority margin 有关非劣效性/等效性的具体假设，包括非劣效性/等效性界值 |
| Outcome 结局指标 | Clearly defined primary outcome for this report 明确定义研究的主要结局指标 | Clarify for all reported outcomes whether non-inferiority/equivalence or superiority 明确所有报告的结局是否为非劣效性/优效性 |
| Randomisation 随机化 | How participants were allocated to interventions 如何对研究对象分配干预措施 | |
| Blinding (masking) 盲法 | Whether or not participants, care givers, and those assessing the outcomes were blinded to group assignment 研究对象、护理人员和结局评估者是否对分组不知情 | |
| Results 结果 | ||
| Numbers randomised 数量随机化 | Number of participants randomised to each group 随机分配到每组的受试者数量 | |
| Recruitment 招募 | Trial status 研究状态 | |
| Numbers analysed 数据分析 | Number of participants analysed in each group 每组分析的受试者数量 | |
| Outcome 结果 | For the primary outcome, a result for each group and the estimated effect size and its precision 各组每一项主要结局和次要结局指标的结果，效应估计值及其精确性 | For the primary non-inferiority/equivalence outcome, results in relation to noninferiority margin 主要非劣效性/优效性结局，结果及非劣效性/优效性界值 |
| Harms 不良反应 | Important adverse events or side effects 重大不良事件或副作用 | |
| Conclusions 结论 | General interpretation of the results 对结果的总体解释 | Interpretation taking into account the non-inferiority/equivalence hypotheses and any superiority hypotheses 根据非劣效性/优效性假设进行解读 |
| Trial registration 研究注册 | Registration number and name of trial register 临床试验注册号和注册机构名称 | |
| Funding 资助 | Source of funding 资金来源 | |
三、非劣效性与等效性试验CONSORT扩展版使用注意事项
非劣效性与等效性试验在设计时，为了更好地了解此类试验设计、实施和分析中的注意事项，建议参考非劣效性与等效性随机对照试验CONSORT扩展版；投稿时，根据需要或要求可将非劣效性与等效性随机对照试验CONSORT扩展版清单(checklist)作为投稿材料之一递交，并引用已发表的相关报告规范文献。审稿人也可根据编辑部要求参照非劣效性与等效性随机对照试验CONSORT扩展版标准和作者提供的清单来审稿。一般CONSORT声明的注意事项和局限性同样适用于本扩展版声明。
注: 本文内容是参考相关文献后对PRCT CONSORT扩展版报告规范原文的概述，仅代表本网站观点。关于非劣效性与等效性试验CONSORT扩展版的更多内容详见官方网站(http://www.consort-statement.org)或论文Reporting of Noninferiority and Equivalence Randomized Trials Extension of the CONSORT 2010 Statement (https://pubmed.ncbi.nlm.nih.gov/23268518/)。
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