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Randomized controlled trials are considered the gold standard in assessing treatment efficacy and safety. However, their results can have limited external validity when applied to day\u2010to\u2010day patients. Pharmacoepidemiological studies aim to assess the effect\/s of treatments in actual practice conditions, but they are limited by the quality, completeness, and inherent bias due to confounding. Sources of information include prospectively collected (primary) as well as readily available routinely collected (secondary) (eg, electronic medical records, administrative\/claims databases) data. Although the former enable the collection of ad hoc measurements, the latter provide a unique opportunity for the study of large representative populations and for the assessment of rare events at relatively low cost. Observational cohort and case\u2010control studies, the most commonly implemented study designs in pharmacoepidemiology, each have their strengths and limitations. However, the choice of the study design depends on the research question that needs to be answered. Despite the many advantages of observational studies, they also have limitations. First, missing data is a common issue in routine data, frequently dealt with using multiple imputation. Second, confounding by indication arises because of the lack of randomization; multivariable regression and more specific techniques such as propensity scores (adjustment, matching, stratification, trimming, or weighting) are used to minimize such biases. In addition, immortal time bias (time period during which a subject is artefactually event\u2010free by study design) and time\u2010varying confounding (patient characteristics changing over time) are other types of biases usually accounted for using time\u2010dependent modeling. Finally, residual \u201cuncontrolled\u201d confounding is difficult to assess, and hence to account for it, sensitivity analyses and specific methods (eg, instrumental variables) should be considered. \u00a9 2018 The Authors<jats:italic>JBMR Plus<\/jats:italic>published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jbm4.10051","type":"journal-article","created":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T14:31:53Z","timestamp":1522679513000},"page":"187-194","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Challenges and Opportunities of Pharmacoepidemiology in Bone Diseases"],"prefix":"10.1093","volume":"2","author":[{"given":"Dunia","family":"Alarkawi","sequence":"first","affiliation":[{"name":"Bone Biology Division Garvan Institute of Medical Research School of Medicine University of New South Wales Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Sanni","family":"Ali","sequence":"additional","affiliation":[{"name":"Centre for Statistics in Medicine and Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences (NDORMS) University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Bliuc","sequence":"additional","affiliation":[{"name":"Bone Biology Division Garvan Institute of Medical Research School of Medicine University of New South Wales Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline R","family":"Center","sequence":"additional","affiliation":[{"name":"Bone Biology Division Garvan Institute of Medical Research School of Medicine University of New South Wales Sydney Australia"},{"name":"Clinical School St Vincent's Hospital Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Prieto\u2010Alhambra","sequence":"additional","affiliation":[{"name":"Centre for Statistics in Medicine and Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences (NDORMS) University of Oxford Oxford UK"},{"name":"MRC Lifecourse Epidemiology Unit Southampton UK"},{"name":"GREMPAL Research Group (Idiap Jordi Gol Primary Care Research Institute) and CIBERFes Universitat Autonoma de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,4,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1471"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","unstructured":"StromBL.What is pharmacoepidemiology? 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