Introduction There have been public health concerns about a potential association between human papillomavirus (HPV) vaccines and premature ovarian failure (POF) in young women. Objective To identify a potential safety signal of POF after HPV vaccination using the United States (US) Vaccine Adverse Event Reporting System (VAERS) database. Methods We manually selected relevant MedDRA preferred terms related to POF and identified in VAERS all POF reports in women less than 40 years of age between 2 July 1990 and 14 May 2018, followed by a review of narratives to confirm the cases. We conducted descriptive analyses on age, POF type, HPV vaccine type (HPV2, HPV4, HPV9), time to onset of POF, and dose rank. We described trends in reporting over time and assessed a potential safety signal using the proportional reporting ratio (PRR). Results Of the 228,341 eligible POF reports, 281 (0.1%) were suspected to be associated with HPV vaccines. Median patient age was 15 years (range 11-39 years). POF events consisted mainly of amenorrhea (80.4%) and premature menopause (15.3%). Mean number of reported POF events significantly increased after the first HPV vaccine launch in 2006 with 22.2 POF cases/year up from 1.4 POF cases/year before the launch. PRR was 46.1 (95% confidence interval: 31.7-67.2) and sensitivity analyses yielded similar estimates. Conclusion Our study suggests the presence of a potential safety signal of POF associated with HPV vaccination, which may only be partly attributed to notoriety bias. Due to the well-known limitations of spontaneous reporting data, further investigations are warranted.

Background: Drug utilization studies (DUSs) are increasingly being conducted in Latin America, especially in countries with a universal healthcare coverage, to inform policies and decision making. The need for an ethical framework specific to DUSs in Latin America has been recognized. Objectives: To describe the ethical and/or legal requirements applicable to DUSs in Latin American countries with universal healthcare coverage. Methods: We conducted a nonsystematic scoping review on DUSs in this region, covering the period from January 1, 2012, to July 1, 2017, and reviewed legislations and data protection requirements in each country. We also surveyed 45 ethics committees and 22 key informants to determine specific ethical requirements for various types of DUSs differing in data collection methods, study populations, and settings. Results: Local legislations on DUSs are highly heterogeneous across Latin America. In Chile and Guatemala, authorization from the national health authority must be obtained for accessing clinical records, whereas in Argentina, no authorization is required for the secondary use of existing data. In Argentina, Brazil, Costa Rica, Guatemala, and Peru, a national ethics committee approval is required in addition to a site-specific approval. Requirements for patient informed consent also vary across countries and depend on the type of DUS and study population. Conclusions: The lack of consensus in the legislative and ethical frameworks applicable to DUSs across Latin America leads to operational challenges for the implementation of multinational studies. In many countries, absence of a framework leads to precautionary stringent requirements, which restricts the feasibility of DUSs.