近年来，分子流行病学研究在深入阐述疾病的发生、发展以及其影响因素的规律方面发挥了巨大作用，有效地弥补了传统流行病学无法明确阐明暴露与疾病发生发展具体机制的不足，从而使得疾病的预防和干预手段更具有针对性和有效性。为了加强分子流行病学中观察性研究报告的质量，制定了专门针对涉及生物标志物研究的报告指南，即《分子流行病学观察性研究报告的加强指南》(STROBE-ME)。本文旨在概述STROBE-ME的背景和条目清单。
关键词：加强观察性流行病学研究报告质量; 分子流行病学研究; 观察性研究; 报告规范; STROBE; STROBE-ME
一、STROBE - ME背景
随着分子生物学理论和技术的迅猛发展，越来越多的生物标志物被应用于流行病学研究，这催生了一个新的流行病学分支——分子流行病学(Molecular Epidemiology)。分子流行病学从分子水平探究人群中相关生物标志物的分布以及它们与疾病(或健康)状况之间的关系和影响因素。它将疾病的发生和发展规律描述为各类生物标志物之间的相互作用和分布变迁的过程，有效地弥补了传统流行病学无法明确阐明暴露与疾病之间关系的不足。因此，分子流行病学为疾病的预防和干预手段提供了更具针对性和有效性的基础。
与传统流行病学相比，分子流行病学的观察性研究面临着新的问题和潜在的偏倚来源，如生物标志物测量的准确性和可靠性，生物样本的采集和处理，以及研究伦理等方面。因此，2011年，Gallo等人提出了基于STROBE声明的《加强分子流行病学中观察性研究报告质量指南》(Strengthening the Reporting of Observational Studies in Epidemiology-Molecular Epidemiology，STROBE-ME)，旨在更好地规范涉及生物标志物的观察性研究报告。STROBE-ME在STROBE清单的基础上，结合分子流行病学的特征，扩展了第1、2、3、4、6、8、12、13、19和20个条目，并新增了生物样品采集、生物样品处理、生物样品存储、生物标志物的生化特性、测量的信效度以及内部和外部验证、生物标志物测量值的分布、以及伦理学等7个条目。
二、STROBE - ME声明的条目清单
STROBE - ME声明的条目清单中英文对照
| 内容 | 条目序号 | STROBE条目内容 | STROBE-ME条目内容 |
| Title and abstract 题目与摘要 | 1 | a. Indicate the study's design with a commonly used term in the title or the abstract a. 题目或摘要中要有常用专业术语表述研究设计 | ME-1 State the use of specific biomarker (s) in the title and/or in the abstract if they contribute substantially to the findings ME-1 对结果有重要影响的特定生物标志物需在题目和/或摘要中说明 |
| b. Provide in the abstract an informative and balanced summary of what was done and what was found b. 摘要内容要丰富，并且能准确地表述研究中做了什么、发现了什么 | |||
| Introduction 前言 | |||
| Background rationale 背景与原理 | 2 | Explain the scientific background and rationale for the investigation being reported 对所报告的研究背景和原理进行解释 | ME-2 Explain in the scientific background of the study how/why the specific biomarker (s) have been chosen, potentially among many others (eg., others are studied but reported elsewhere or not studied at all) ME-2在背景部分解释选择特定生物标志物的方法/原因(例如也有其他生物标志物的研究，但在其他地方报告了；或没有研究) |
| Objectives 目标 | 3 | State specific objectives, including any pre-specified hypotheses 阐明研究目标，包括任何预先确定的假设 | ME-3 A priori hypothesis: if one or more biomarkers are used as proxy measures, state the a priori hypothesis on the expected values of the biomarker (s) ME-3先验假设：如果一个或多个生物标志物被用于替代测量，应说明生物标志物预期值的先验假设 |
| Methods 方法 | |||
| Study design 研究设计 | 4 | Present key elements of study design early in the paper 在论文中尽早陈述研究设计的要素 | ME-4 Describe the special study designs for molecular epidemiology (in particular nested case/control and case/cohort) and how they were implemented ME-4描述分子流行病学的特殊研究设计(尤其是巢式病例对照研究和病例队列研究)以及它们是如何实施的 |
| Biological samplecollection 生物样品采集 | ME-4.1 Report on the setting of the biological sample collection; amount of sample; nature of collecting procedures; participant conditions; time between sample collection and relevant clinical or physiological endpoints ME-4.1报告生物样本采集的环境、样本量采集程序的特点、参与者的条件、样品采集与相关临床或生理终点的时间间隔 | ||
| Biologicalsample processing 生物样品处理 | ME-4.2 Describe sample processing (centrifugation, timing, additives, etc) ME-4.2描述样品处理(离心、时间、添加物等) | ||
| Biologicalsample storage 生物样品存储 | ME-4.3 Describe sample storage until biomarker analysis (storage, thawing, manipulatione, etc) ME-4.3描述样品在生物标志物分析前的存储(存储、融解、操作等) | ||
| Biomarkerbiochemical Characteristics 生物标志物的生化特性 | ME-4.4 Report the half-life of the biomarker, and chemical and physical characteristics (e.g., solubility) ME-4.4报告的生物标志物的半衰期，以及化学和物理特性(例如，溶解度) | ||
| Setting 研究现场 | 5 | Describe the setting, locations and relevant dates, including periods of recruitment, exposure, follow-up and data collection 描述研究现场、具体场所和相关时间范围(包括研究对象征集、暴露、随访和数据收集时间) | |
| Participants 研究对象 | 6 | a. Cohort study—give the eligibility criteria, and the sources and methods of selection of participants. Describe methods of follow-up Case-control study—give the eligibility criteria, and the sources and methods of case ascertainment and control selection. Give the rationale for the choice of cases and controls Cross-sectional study—give the eligibility criteria and the sources and methods of selection of participants a. 队列研究—描述选择研究对象的合格标准、人群来源和选择方法；描述随访方法 病例对照研究—描述选择确诊病例和对照的合格标准、人群来源和选择方法；描述选择病例和对照的原理 横断面研究—描述选择研究对象的合格标准、人群来源和选择方法 | ME-6 Report any habit, clinical conditions, physiological factor, or working or living condition that might affect the characteristics or concentrations of the biomarker ME-6报告任何可能影响生物标志物特性或浓度的因素，包括研究对象的习惯，临床条件，生理因素，工作或生活条件等 |
| b. Cohort study—for matched studies, give matching criteria and number of exposed and unexposed Case control study—for matched studies, give matching criteria and the number of controls per case b. 队列研究—配对研究描述配对标准和暴露与非暴露数目 病例对照研究—配对研究描述配对标准和每个病例对应的对照数目 | |||
| Variables 研究变量 | 7 | Clearly define all outcomes, exposures, predictors, potential confounders and effect modifiers. Give diagnostic criteria, if applicable 明确定义结局、暴露、预测因子、潜在的混杂因子和效应修饰因子。如果可能，给出诊断标准 | |
| Data sources/ measurement 数据来源/测量 | 8 | For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe comparability of assessment methods, if there is more than one group 对每个变量，描述其数据来源和详细的判定(测量)方法。如果有多组，还应描述各组之间判定方法的可比性 | ME-8 Laboratory methods: report type of assayused, detection limit, quantity of biological sample used, outliers, timing in the assay procedures (when applicable) and calibration procedures or any standard used ME-8实验方法：报告使用的检测类型，检出限，使用的生物样品的数量，异常值，检测程序的时间(适用时)和校准程序或使用标准 |
| Bias 偏倚 | 9 | Describe any efforts to address potential sources of bias 描述减少潜在偏倚的过程 | |
| Study size 样本大小 | 10 | Explain how the study size was arrived at 解释样本大小的确定方法 | |
| QuantitativeVariables 定量变量 | 11 | Explain how quantitative variables were handled in the analyses. If applicable, describe which groupings were chosen and why 解释分析中如何处理定量变量。如果可能，描述怎样选择分组及分组原因 | |
| Statistical methods 统计学方法 | 12 | a. Describe all statistical methods, including those used to control for confounding a. 描述所有统计方法，包括控制混杂的方法 | ME-12 Describe how biomarkers were introduced into statistical models ME-12描述生物标志物是如何引入统计模型的 |
| b. Describe any methods used to examine subgroups and interactions b. 描述亚组和交互作用检查方法 | |||
| c. Explain how missing data were addressed c. 描述缺失值的处理方法 | |||
| d. Cohort study—if applicable, explain how loss to follow-up was addressed Case-control study—if applicable, explain how matching of cases and controls was addressed Cross-sectional study—if applicable, describe analytical methods taking account of sampling strategy d. 队列研究—如果可能，解释失访的处理方法 病例对照研究—如果可能，解释病例和对照的匹配方法 横断面研究—如果可能，描述根据抽样策略确定的统计方法 | |||
| e. Describe any sensitivity analyses e. 描述敏感性分析 | |||
| Validity/reliability of measurement and internal/external validation 测量的信效度和内、外部检验 | ME-12.1 Report on the validity and reliability of measurement of the biomarker (s) coming from the literature and any internal or external validation used in the study ME-12.1报告文献中生物标志物测量的效度和信度，以及研究中使用的任何内部或外部检验 | ||
| Results 结果 | |||
| Participants 研究对象 | 13 | a. Report the numbers of individuals at each stage of the study-e.g., numbers potentially eligible, examined for eligiblity, confirmed eligible, included in the study, completing follow-up and analysed a. 报告研究的各个阶段研究对象的数量，如可能合格的数量、被检验是否合格的数量、证实合格的数量、纳入研究的数量、完成随访的数量和分析的数量 | ME-13 Give reason for loss of biological samples at each stage ME-13给出每阶段生物样品缺失的原因 |
| b. Give reasons for non-participation at each stage b. 描述各个阶段研究对象退出的原因 | |||
| c. Consider use of a flow diagram c. 考虑使用流程图 | |||
| Descriptive data 描述性资料 | 14 | a. Give characteristics of study participants (e.g., demographic, clinical, social) and information on exposures and potential confounders a. 描述研究对象的特征(如人口学、临床和社会特征)以及关于暴露和潜在混杂因子的信息 | |
| b. Indicate the number of participants with missing data for each variable of interest b. 指出每个变量存在缺失值的研究对象数目 | |||
| c. Cohort study—summarize follow-up time, e.g. average and total amount c. 队列研究—总结随访时间(如平均时间、总和时间) | |||
| Distribution ofbiomarker measurement 生物标志物测量值的分布 | ME-14.1 Give the distribution of the biomarker measurement (including mean, median, range, and variance) ME-14.1给出生物标志物测量值的分布(包括均值、中位数、范围和方差) | ||
| Outcome data 结局资料 | 15 | Cohort study—report numbers of outcome events or summary measures over time 队列研究—报告发生结局事件的数量或人时综合指标 | |
| Case-control study—report numbers in each exposure category or summary measures of exposure 病例对照研究—报告各个暴露类别的数量或暴露综合指标 | |||
| Cross-sectional study—report numbers of outcome events or summary measures 横断面研究——报告结局事件的数量或相关综合指标 | |||
| Main results 主要结果 | 16 | a. Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (e.g., 95% confidence intervals). Make clear which confounders were adjusted for and why they were included a. 给出未校正的和校正混杂因子的关联强度估计值、精确度(如95% CI)。闸明根据哪些混杂因子进行调整以及选择这些因子的原因 | |
| b. Report category boundaries when continuous variables were categorized b. 当对连续性变量分组时报告分组界值 | |||
| c. If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period c. 如果有关联，可将有意义时期内的相对危险度转换成绝对危险度 | |||
| Other analyses 其他分析 | 17 | Report other analyses performed--e.g., analyses of subgroups and interactions and sensitivity analyses 报告进行的其他分析，如亚组和交互作用分析、敏感性分析 | |
| Discussion 讨论 | |||
| Key results 重要结果 | 18 | Summarize key results with reference to study objectives 概括与研究假设有关的重要结果 | |
| Limitations 局限性 | 19 | Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss both direction and magnitude of any potential bias 结合潜在偏倚和不精确的来源，讨论研究的局限性。讨论潜在偏倚的方向和大小 | ME-19 Describe main limitations in laboratory procedures ME-19描述实验程序的主要局限性 |
| Interpretation 解释 | 20 | Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies and other relevant evidence 结合研究目的、局限性、多重比较、类似研究的结果和其他相关证据，谨慎给出一个总体的结果解释 | ME-20 Give an interpretation of results in termsof a priori biological plausibility ME-20根据先验的生物学合理性对结果作出解释 |
| Generalizability 可推广性 | 21 | Discuss the generalizability (external validity) of the study results 讨论研究结果的可推广性(外部真实性) | |
| Other information 其他信息 | |||
| Funding 资助 | 22 | Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based 给出当前研究的资助来源和资助者。如果可能，给出原始研究的资助情况 | |
| Ethics 伦理学 | ME-22.1 Describe informed consent and approval from ethical committee (s). Specify whether samples were anonymous, anonymised or identifiable ME-22.1描述知情同意和伦理委员会的批准，尤其是样品匿名还是可识别 | ||
三、STROBE - ME声明使用注意事项
STROBE-ME主要适用于除遗传关联性研究(STREGA声明)和传染性疾病(STROME-ID声明)以外的分子流行病学研究。STROBE-ME是一份规范性文件，旨在指导使用生物标志物(包括暴露、内剂量标志物、早期生物变化标志物、易感性标志物等)作为解释变量的分子流行病学研究报告。然而，它并不包含涉及信度、效度测量和转化研究的生物标志物的研究设计。STROBE-ME不能用于评估研究质量，注意不要误用或滥用该指南。
此外，考虑到研究的多样性和文章篇幅的限制，一篇文章不可能详尽地报告所有的规范条目。研究人员应根据研究的特点，侧重描述与该研究最为重要的条目，并清楚地说明其所侧重的内容。
注：本文内容是参考相关文献后对STROBE-ME声明原文的概述，仅代表本网站观点。关于STROBE-ME声明的更多内容详见官方网站(http：//www.strobe-statement.org)或Valentina·Gallo等发表的论文“Strengthening the Reporting of Observational studies in Epidemiology – Molecular Epidemiology (STROBE-ME): An Extension of the STROBE Statement (https://pubmed.ncbi.nlm.nih.gov/22039356/)”。
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