Matthias Egger

The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies

Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a studys generalizability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover 3 main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors, to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Eighteen items are common to all 3 study designs and 4 are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available at http://www.annals.org and on the Web sites of PLoS Medicine and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.

CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials

Overwhelming evidence shows the quality of reporting of randomised controlled trials (RCTs) is not optimal. Without transparent reporting, readers cannot judge the reliability and validity of trial findings nor extract information for systematic reviews. Recent methodological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which are considered the gold standard for evaluating interventions because of their ability to minimise or avoid bias. A group of scientists and editors developed the CONSORT (Consolidated Standards of Reporting Trials) statement to improve the quality of reporting of RCTs. It was first published in 1996 and updated in 2001. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have endorsed the CONSORT statement. The statement facilitates critical appraisal and interpretation of RCTs. During the 2001 CONSORT revision, it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports. A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement. After an expert meeting in January 2007, the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement. This update improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition, such as selective outcome reporting bias. This explanatory and elaboration document-intended to enhance the use, understanding, and dissemination of the CONSORT statement-has also been extensively revised. It presents the meaning and rationale for each new and updated checklist item providing examples of good reporting and, where possible, references to relevant empirical studies. Several examples of flow diagrams are included. The CONSORT 2010 Statement, this revised explanatory and elaboration document, and the associated website (www.consort-statement.org) should be helpful resources to improve reporting of randomised trials.

Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies.

BACKGROUND Excess bodyweight, expressed as increased body-mass index (BMI), is associated with the risk of some common adult cancers. We did a systematic review and meta-analysis to assess the strength of associations between BMI and different sites of cancer and to investigate differences in these associations between sex and ethnic groups. METHODS We did electronic searches on Medline and Embase (1966 to November 2007), and searched reports to identify prospective studies of incident cases of 20 cancer types. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with a 5 kg/m2 increase in BMI. FINDINGS We analysed 221 datasets (141 articles), including 282,137 incident cases. In men, a 5 kg/m2 increase in BMI was strongly associated with oesophageal adenocarcinoma (RR 1.52, p<0.0001) and with thyroid (1.33, p=0.02), colon (1.24, p<0.0001), and renal (1.24, p <0.0001) cancers. In women, we recorded strong associations between a 5 kg/m2 increase in BMI and endometrial (1.59, p<0.0001), gallbladder (1.59, p=0.04), oesophageal adenocarcinoma (1.51, p<0.0001), and renal (1.34, p<0.0001) cancers. We noted weaker positive associations (RR <1.20) between increased BMI and rectal cancer and malignant melanoma in men; postmenopausal breast, pancreatic, thyroid, and colon cancers in women; and leukaemia, multiple myeloma, and non-Hodgkin lymphoma in both sexes. Associations were stronger in men than in women for colon (p<0.0001) cancer. Associations were generally similar in studies from North America, Europe and Australia, and the Asia-Pacific region, but we recorded stronger associations in Asia-Pacific populations between increased BMI and premenopausal (p=0.009) and postmenopausal (p=0.06) breast cancers. INTERPRETATION Increased BMI is associated with increased risk of common and less common malignancies. For some cancer types, associations differ between sexes and populations of different ethnic origins. These epidemiological observations should inform the exploration of biological mechanisms that link obesity with cancer.

Systematic reviews in health care: Assessing the quality of controlled clinical trials.

This is the first in a series of four articles The quality of controlled trials is of obvious relevance to systematic reviews. If the “raw material” is flawed then the conclusions of systematic reviews cannot be trusted. Many reviewers formally assess the quality of primary trials by following the recommendations of the Cochrane Collaboration and other experts. 1 2 However, the methodology for both the assessment of quality and its incorporation into systematic reviews and meta-analysis are a matter of ongoing debate.3-5 In this article we discuss the concept of study quality and the methods used to assess quality. #### Components of internal and external validity of controlled clinical trials Internal validity —extent to which systematic error (bias) is minimised in clinical trials Quality is a multidimensional concept, which could relate to the design, conduct, and analysis of a trial, its clinical relevance, or quality of reporting.6 The validity of the findings generated by a study clearly is an important dimension of quality. In the 1950s the social scientist Campbell proposed a useful distinction between internal and external validity (see box below). 7 8 Internal validity implies that the differences observed between groups of patients allocated to different …

Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration.

Editors Note: In order to encourage dissemination of the STROBE Statement, this article is being published simultaneously in Annals of Internal Medicine, Epidemiology, and PLoS Medicine. It is freely accessible on the Annals of Internal Medicine Web site ( www.annals.org ) and will also be published on the Web sites of Epidemiology and PLoS Medicine. The authors jointly hold the copyright of this article. For details on further use, see the STROBE Web site (www.strobe-statement.org). Rational health care practices require knowledge about the etiology and pathogenesis, diagnosis, prognosis, and treatment of diseases. Randomized trials provide valuable evidence about treatments and other interventions. However, much of clinical or public health knowledge comes from observational research (1). About 9 of 10 research papers published in clinical specialty journals describe observational research (2, 3). The STROBE Statement Reporting of observational research is often not detailed and clear enough to assess the strengths and weaknesses of the investigation (4, 5). To improve the reporting of observational research, we developed a checklist of items that should be addressed: the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement (Appendix Table). Items relate to the title, abstract, introduction, methods, results, and discussion sections of articles. The STROBE Statement has recently been published in several journals (6). Our aim is to ensure clear presentation of what was planned, done, and found in an observational study. We stress that the recommendations are not prescriptions for setting up or conducting studies, nor do they dictate methodology or mandate a uniform presentation. Appendix Table. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Checklist of Items That Should Be Addressed in Reports of Observational Studies STROBE provides general reporting recommendations for descriptive observational studies and studies that investigate associations between exposures and health outcomes. STROBE addresses the 3 main types of observational studies: cohort, casecontrol, and cross-sectional studies. Authors use diverse terminology to describe these study designs. For instance, follow-up study and longitudinal study are used as synonyms for cohort study, and prevalence study as a synonym for cross-sectional study. We chose the present terminology because it is in common use. Unfortunately, terminology is often used incorrectly (7) or imprecisely (8). In Box 1, we describe the hallmarks of the 3 study designs. Box 1. Main Study Designs Covered by STROBE The Scope of Observational Research Observational studies serve a wide range of purposes, from reporting a first hint of a potential cause of a disease to verifying the magnitude of previously reported associations. Ideas for studies may arise from clinical observations or from biological insight. Ideas may also arise from informal looks at data that lead to further explorations. Like a clinician who has seen thousands of patients and notes 1 that strikes her attention, the researcher may note something special in the data. Adjusting for multiple looks at the data may not be possible or desirable (9), but further studies to confirm or refute initial observations are often needed (10). Existing data may be used to examine new ideas about potential causal factors, and may be sufficient for rejection or confirmation. In other instances, studies follow that are specifically designed to overcome potential problems with previous reports. The latter studies will gather new data and will be planned for that purpose, in contrast to analyses of existing data. This leads to diverse viewpoints, for example, on the merits of looking at subgroups or the importance of a predetermined sample size. STROBE tries to accommodate these diverse uses of observational researchfrom discovery to refutation or confirmation. Where necessary, we will indicate in what circumstances specific recommendations apply. How to Use this Paper This paper is linked to the shorter STROBE paper that introduced the items of the checklist in several journals (6), and forms an integral part of the STROBE Statement. Our intention is to explain how to report research well, not how research should be done. We offer a detailed explanation for each checklist item. Each explanation is preceded by an example of what we consider transparent reporting. This does not mean that the study from which the example was taken was uniformly well reported or well done; nor does it mean that its findings were reliable, in the sense that they were later confirmed by others: It only means that this particular item was well reported in that study. In addition to explanations and examples, we included boxes with supplementary information. These are intended for readers who want to refresh their memories about some theoretical points or be quickly informed about technical background details. A full understanding of these points may require studying the textbooks or methodological papers that are cited. STROBE recommendations do not specifically address topics, such as genetic linkage studies, infectious disease modeling, or case reports and case series (11, 12). As many of the key elements in STROBE apply to these designs, authors who report such studies may nevertheless find our recommendations useful. For authors of observational studies that specifically address diagnostic tests, tumor markers, and genetic associations, STARD (13), REMARK (14), and STREGA (15) recommendations may be particularly useful. The Items in the STROBE Checklist We now discuss and explain the 22 items in the STROBE checklist (Appendix Table) and give published examples for each item. Some examples have been edited by removing citations or spelling out abbreviations. Eighteen items apply to all 3 study designs, whereas 4 are design-specific. Starred items (for example, item 8) indicate that the information should be given separately for cases and controls in casecontrol studies, or exposed and unexposed groups in cohort and cross-sectional studies. We advise authors to address all items somewhere in their paper, but we do not prescribe a precise location or order. For instance, we discuss the reporting of results under a number of separate items, while recognizing that authors might address several items within a single section of text or in a table. Title and Abstract 1(a) Indicate the studys design with a commonly used term in the title or the abstract. Example Leukaemia incidence among workers in the shoe and boot manufacturing industry: a casecontrol study (18). Explanation Readers should be able to easily identify the design that was used from the title or abstract. An explicit, commonly used term for the study design also helps ensure correct indexing of articles in electronic databases (19, 20). 1(b) Provide in the abstract an informative and balanced summary of what was done and what was found. Example Background: The expected survival of HIV-infected patients is of major public health interest. Objective: To estimate survival time and age-specific mortality rates of an HIV-infected population compared with that of the general population. Design: Population-based cohort study. Setting: All HIV-infected persons receiving care in Denmark from 1995 to 2005. Patients: Each member of the nationwide Danish HIV Cohort Study was matched with as many as 99 persons from the general population according to sex, date of birth, and municipality of residence. Measurements: The authors computed KaplanMeier life tables with age as the time scale to estimate survival from age 25 years. Patients with HIV infection and corresponding persons from the general population were observed from the date of the patients HIV diagnosis until death, emigration, or 1 May 2005. Results: 3990 HIV-infected patients and 379 872 persons from the general population were included in the study, yielding 22 744 (median, 5.8 y/person) and 2 689 287 (median, 8.4 y/person) person-years of observation. Three percent of participants were lost to follow-up. From age 25 years, the median survival was 19.9 years (95% CI, 18.5 to 21.3) among patients with HIV infection and 51.1 years (CI, 50.9 to 51.5) among the general population. For HIV-infected patients, survival increased to 32.5 years (CI, 29.4 to 34.7) during the 2000 to 2005 period. In the subgroup that excluded persons with known hepatitis C coinfection (16%), median survival was 38.9 years (CI, 35.4 to 40.1) during this same period. The relative mortality rates for patients with HIV infection compared with those for the general population decreased with increasing age, whereas the excess mortality rate increased with increasing age. Limitations: The observed mortality rates are assumed to apply beyond the current maximum observation time of 10 years. Conclusions: The estimated median survival is more than 35 years for a young person diagnosed with HIV infection in the late highly active antiretroviral therapy era. However, an ongoing effort is still needed to further reduce mortality rates for these persons compared with the general population (21). Explanation The abstract provides key information that enables readers to understand a study and decide whether to read the article. Typical components include a statement of the research question, a short description of methods and results, and a conclusion (22). Abstracts should summarize key details of studies and should only present information that is provided in the article. We advise presenting key results in a numerical form that includes numbers of participants, estimates of associations, and appropriate measures of variability and uncertainty (for example, odds ratios with confidence intervals). We regard it insufficient to state only that an exposure is or is not significantly associated with an outcom

Meta-analysis: principles and procedures.

Meta-analysis is a statistical procedure that integrates the results of several independent studies considered to be “combinable.”1 Well conducted meta-analyses allow a more objective appraisal of the evidence than traditional narrative reviews, provide a more precise estimate of a treatment effect, and may explain heterogeneity between the results of individual studies.2 Ill conducted meta-analyses, on the other hand, may be biased owing to exclusion of relevant studies or inclusion of inadequate studies.3 Misleading analyses can generally be avoided if a few basic principles are observed. In this article we discuss these principles, along with the practical steps in performing meta-analysis. Meta-analysis should be viewed as an observational study of the evidence. The steps involved are similar to any other research undertaking: formulation of the problem to be addressed, collection and analysis of the data, and reporting of the results. Researchers should write in advance a detailed research protocol that clearly states the objectives, the hypotheses to be tested, the subgroups of interest, and the proposed methods and criteria for identifying and selecting relevant studies and extracting and analysing information. As with criteria for including and excluding patients in clinical studies, eligibility criteria have to be defined for the data to be included. Criteria relate to the quality of trials and to the combinability of treatments, patients, outcomes, and lengths of follow up. Quality and design features of a study can influence the results.4 5 Ideally, researchers should consider including only controlled trials with proper randomisation of patients that report on all initially included patients according to the intention to treat principle and with an objective, preferably blinded, outcome assessment.6 Assessing the quality of a study …

Original ArticleThe Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies

Much of biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a studys generalizability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Eighteen items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the web sites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.

Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study

Objective To examine whether the association of inadequate or unclear allocation concealment and lack of blinding with biased estimates of intervention effects varies with the nature of the intervention or outcome. Design Combined analysis of data from three meta-epidemiological studies based on collections of meta-analyses. Data sources 146 meta-analyses including 1346 trials examining a wide range of interventions and outcomes. Main outcome measures Ratios of odds ratios quantifying the degree of bias associated with inadequate or unclear allocation concealment, and lack of blinding, for trials with different types of intervention and outcome. A ratio of odds ratios <1 implies that inadequately concealed or non-blinded trials exaggerate intervention effect estimates. Results In trials with subjective outcomes effect estimates were exaggerated when there was inadequate or unclear allocation concealment (ratio of odds ratios 0.69 (95% CI 0.59 to 0.82)) or lack of blinding (0.75 (0.61 to 0.93)). In contrast, there was little evidence of bias in trials with objective outcomes: ratios of odds ratios 0.91 (0.80 to 1.03) for inadequate or unclear allocation concealment and 1.01 (0.92 to 1.10) for lack of blinding. There was little evidence for a difference between trials of drug and non-drug interventions. Except for trials with all cause mortality as the outcome, the magnitude of bias varied between meta-analyses. Conclusions The average bias associated with defects in the conduct of randomised trials varies with the type of outcome. Systematic reviewers should routinely assess the risk of bias in the results of trials, and should report meta-analyses restricted to trials at low risk of bias either as the primary analysis or in conjunction with less restrictive analyses.

[The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting of observational studies].

Much of biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a studys generalizability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Eighteen items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the web sites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.

Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies

Poor reporting of research hampers assessment and makes it less useful. An international group of methodologists, researchers, and journal editors sets out guidelines to improve reports of observational studies