50 Chapter 3 Methods Systematic review search strategy and study selection A systematic review was conducted. Briefly, the search included studies describing determinants in primary care in developed countries through 9 September 2021. The protocol developed to conduct this study was registered in PROSPERO (online supplemental file 1). PubMed, Embase, Web of Science and the Cochrane Library databases were searched. The full electronic search strategy can be found in online supplemental file 2. We additionally searched grey literature (i.e., abstracts of conferences, symposia and meetings) and relevant references found in initially identified studies found in Embase, Web of Science and the Cochrane Library. There were no language restrictions in the search. The reporting of our systematic review was based on the protocol specified by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (online supplemental file 3) (19). Studies were, regardless of their design, selected for reviewing if they provided a definition of inappropriate antibiotic prescription according to the guidelines used in that study. Only studies performed in developed countries, as defined by the United Nations (UN), in which the GP plays a ‘gatekeeper’ role in the healthcare system, were included (Supplemental files 4, 5) (20,21). This gatekeeper role is defined by the UN as a compulsory GP referral to access most types of specialist care, except in case of emergency (21). Studies had to report determinants that influence the inappropriate prescribing of antibiotics as an outcome. Studies on specific subgroups of patients (e.g., those with specific comorbidities) or specific diseases (such as asthma or chronic obstructive pulmonary disease) were excluded as reasons for appropriate or inappropriate antibiotic prescriptions for these groups differ, while our aim was to develop a framework for the whole population. Two reviewers (MS and FLB) independently reviewed the titles, index terms and abstracts of the identified references and rated each abstract according to the inclusion and exclusion criteria. Full texts of potentially relevant abstracts were assessed for eligibility by two reviewers (MS and FLB). Discrepancies were resolved by consensus. If consensus could not be reached, a third reviewer (MGJdB or MEN) was consulted. Data extraction and quality assessment The determinants of inappropriate prescription of antibiotics were extracted from the included studies, along with the study design, geographical location, disease group, definition of inappropriate prescribing, study population and research period. ORs describing associations between determinants and inadequate prescription were
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