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The idea for the registration of observational epidemiologic studies (with their protocols, hypotheses, and analysis plans) is modeled on the registration of randomized clinical trials (RCTs). The movement that led to the registration of RCTs was fed by distrust that important findings would be with

This thesis investigates the validity and usefulness of physician's preference-based instrumental variable analysis in clinical epidemiological studies. Chapter 2 describes a survey amongst general practitioners, showing substantial variation in prescribing preference and showing prescribing patterns which suggest the stochastic monotonicity assumption may be plausible for physician's preference as an instrumental variable. Chapter 3 describes an application of physician's preference-based instrumental variable analysis in a moderate-sized study, showing uninformatively wide confidence intervals which limit the usefulness of instrumental variable analysis in this setting. Chapter 4 focuses on the bias-variance trade-off of instrumental variable analysis in comparison to conventional analyses, using simulations and theoretical derivations. Chapter 5 compares instrumental variable and conventional estimates of the effect of third versus second generation oral contraceptives on occurrence of venous thromboembolism. The similarity of these estimates under different sets of assumptions suggests major confounding is unlikely. Chapter 6 contains a suggestion for an additional step for reporting of instrumental variable analyses. The focus shifts to Mendelian randomisation in the second part of the thesis. Chapter 7 reviews the methodological approaches used in Mendelian randomisation studies and the quality of reporting. Chapter 8 shows that collider-stratification bias may exist in Mendelian randomisation studies in elderly populations.

Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalisability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results and discussion sections of articles. Eighteen items are common to cohort studies, case-control studies and cross-sectional studies and four are specific to each of the three study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors and readers. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, one or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated Web site (http://www.strobe-statement.org/) should be helpful resources to improve reporting of observational research., In this explanatory and elaboration document Mattias Egger and colleagues provide the meaning and rationale of each checklist item on the STROBE Statement.