title: Safety reporting in developing country vaccine clinical trials-a systematic review.
abstract: With more vaccines becoming available worldwide, vaccine research is on the rise in developing countries. To gain a better understanding of safety reporting from vaccine clinical research in developing countries, we conducted a systematic review in Medline and Embase (1989-2011) of published randomized clinical trials (RCTs) reporting safety outcomes with ≥50% developing country participation (PROSPERO systematic review registration number: CRD42012002025). Developing country vaccine RCTs were analyzed with respect to the number of participants, age groups studied, inclusion of safety information, number of reported adverse events following immunization (AEFI), type and duration of safety follow-up, use of standardized AEFI case definitions, grading of AEFI severity, and the reporting of levels of diagnostic certainty for AEFI. The systematic search yielded a total number of 50 randomized vaccine clinical trials investigating 12 different vaccines, most commonly rotavirus and malaria vaccines. In these trials, 94,459 AEFI were reported from 446,908 participants receiving 735,920 vaccine doses. All 50 RCTs mentioned safety outcomes with 70% using definitions for at least one AEFI. The most commonly defined AEFI was fever (27), followed by local (16) and systemic reactions (14). Logistic regression analysis revealed a positive correlation between the implementation of a fever case definition and the reporting rate for fever as an AEFI (p=0.027). Overall, 16 different definitions for fever and 7 different definitions for erythema were applied. Predefined AEFI case definitions by the Brighton Collaboration were used in only two out of 50 RCTs. The search was limited to RCTs published in English or German and may be missing studies published locally. The reported systematic review suggests room for improvement with respect to the harmonization of safety reporting from developing country vaccine clinical trials and the implementation of standardized case definitions.
authors.affiliation: Department of Pediatrics, Division of Pneumonology-Immunology, Charité University Medical Center, Berlin, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Muehlhans
authors.forename: Georgina
authors.initials: G
authors.lastname: Richard
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ali
authors.forename: Gabriela
authors.initials: G
authors.lastname: Codarini
authors.forename: Chris
authors.initials: C
authors.lastname: Elemuwa
authors.forename: Ali
authors.initials: A
authors.lastname: Khamesipour
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maurer
authors.forename: Edison
authors.initials: E
authors.lastname: Mworozi
authors.forename: Sonali
authors.initials: S
authors.lastname: Kochhar
authors.forename: Gabriella
authors.initials: G
authors.lastname: Rundblad
authors.forename: Dominique
authors.initials: D
authors.lastname: Vuitton
authors.forename: Barbara
authors.initials: B
authors.lastname: Rath
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000458:organization & administration*; D003906:Developing Countries; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D014612:Vaccines / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D014612:Vaccines