Safety of multicomponent meningococcal group B vaccine (4CMenB) in routine infant immunisation in the UK: a prospective surveillance study.

Background: Safety data for the multicomponent meningococcal group B vaccine (4CMenB) has so far been limited to experience from clinical trials and isolated local outbreaks. Since the UK is the first country to implement a nationwide routine immunisation programme with 4CMenB (at age 8 weeks, 16 weeks, and then 1 year), we aimed to assess the safety of 4CMenB in this setting.

Methods: In this prospective surveillance study, we assessed suspected adverse reactions of 4CMenB in children up to age 18 months reported in the UK Yellow Card Scheme and primary care records extracted from the Clinical Practice Research Datalink (CPRD).

Good Signal Detection Practices: Evidence from IMI PROTECT.

Over a period of 5 years, the Innovative Medicines Initiative PROTECT (Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium) project has addressed key research questions relevant to the science of safety signal detection. The results of studies conducted into quantitative signal detection in spontaneous reporting, clinical trial and electronic health records databases are summarised and 39 recommendations have been formulated, many based on comparative analyses across a range of databases (e.g.

Performance of Stratified and Subgrouped Disproportionality Analyses in Spontaneous Databases.

Introduction: Disproportionality analyses are used in many organisations to identify adverse drug reactions (ADRs) from spontaneous report data. Reporting patterns vary over time, with patient demographics, and between different geographical regions, and therefore subgroup analyses or adjustment by stratification may be beneficial.

Objective: The objective of this study was to evaluate the performance of subgroup and stratified disproportionality analyses for a number of key covariates within spontaneous report databases of differing sizes and characteristics.

Comparison of statistical signal detection methods within and across spontaneous reporting databases.

Background: Most pharmacovigilance departments maintain a system to identify adverse drug reactions (ADRs) through analysis of spontaneous reports. The signal detection algorithms (SDAs) and the nature of the reporting databases vary between operators and it is unclear whether any algorithm can be expected to provide good performance in a wide range of environments.

Objective: The objective of this study was to compare the performance of commonly used algorithms across spontaneous reporting databases operated by pharmaceutical companies and national and international pharmacovigilance organisations.

Bivalent human papillomavirus vaccine and the risk of fatigue syndromes in girls in the UK.

Introduction: Over 70% of cervical cancers are related to human papillomavirus types 16 and 18. In 2008, the vaccine Cervarix, protecting against these two strains, was introduced into the routine UK immunisation programme for girls aged 12-13 years, with a catch-up in girls aged up to 18 years. As part of the risk management planning for this new campaign, the Medicines and Healthcare products Regulatory Agency (MHRA) anticipated a range of conditions, including chronic fatigue syndrome, which might be reported as adverse events in temporal association with the vaccine.

Development of a novel regulatory pharmacovigilance prioritisation system: an evaluation of its performance at the UK Medicines and Healthcare products Regulatory Agency.

Background: The prioritisation of drug safety issues for further evaluation or regulatory action is critical to ensure that acceptable timelines and appropriate resource allocation are defined to meet public health and regulatory obligations.

Objective: Our objective was to develop, pilot and implement a novel tool for prioritising pharmacovigilance issues within the Medicines and Healthcare products Regulatory Agency (MHRA).

Methods: An initial system was developed empirically and then piloted over a 10-month period in the pharmacovigilance signal management meeting at the MHRA that discusses potential pharmacovigilance issues, and determines, through consensus, their priority and a timescale for action.

Risk of death and cardiovascular outcomes with thiazolidinediones: a study with the general practice research database and secondary care data.

Objective: To describe the likely extent of confounding in evaluating the risks of cardiovascular (CV) events and mortality in patients using diabetes medication.

Methods: The General Practice Research Database was used to identify inception cohorts of insulin and different oral antidiabetics. An analysis of bias and incidence of mortality, acute coronary syndrome, stroke and heart failure were analysed in GPRD, Hospital Episode Statistics and death certificates.

Risk of convulsions in children after monovalent H1N1 (2009) and trivalent influenza vaccines: a database study.

The monovalent H1N1 (2009) pandemic influenza vaccine used predominantly in the UK in 2009/10 was a split virion vaccine with a novel oil-in-water adjuvant (ASO3). While this was highly immunogenic it was also reactogenic especially for fever in children. There is a paucity of comparative data on reactogenicity of trivalent influenza vaccine (TIV).