WITHDRAWN - How is drug safety monitored in UK primary care? Can we be sure that new drugs are safe to prescribe?

Problem

It has long been recognised that it is not possible to know all potential hazards of a drug before it is marketed. This led to the introduction of the Yellow Card system in 1964, in which doctors report suspected adverse drug reactions (ADRs) to the Medicines and Healthcare products Regulatory Agency (MHRA). While this Yellow Card system was a good start, it is a passive system that relies on prescribers suspecting that an ADR has occurred. A system to monitor all adverse events, not just ADRs, was needed.

Approach

The Drug Safety Research Unit (DSRU), established in 1981, proactively monitors the safety of drugs once they are prescribed in the real world. The DSRU uses an observational method called Modified Prescription-Event Monitoring (MPEM) to monitor the safety of new medicines prescribed by GPs in England. It relies on GPs completing and returning forms sent to them by the DSRU.

Findings

A topical example of the DSRU’s monitoring of medicines prescribed in primary care is the MPEM study of rivaroxaban, a new oral anticoagulant. This study is ongoing, so here results of a planned interim analysis are presented. The interim evaluable cohort of 8372 patients was identified from rivaroxaban prescriptions dispensed between December 2011 and July 2015. MPEM questionnaires requesting drug utilisation information were sent to prescribing GPs at ≥3 months and ≥12 months after the first rivaroxaban prescription issued for each patient. One study objective was to evaluate prescribing in real-life clinical practice in primary care in England. Of all indications reported (n=8925), the most frequent were non-valvular atrial fibrillation (AF) (4932, 60.2%) and indications associated with venous thromboembolism (VTE) (3064, 37.4%). Where information was received, rivaroxaban was initiated more frequently in secondary care than primary care (4467, 55.3% vs 3530, 43.7%) and the most frequent reason for a GP prescribing rivaroxaban was recommendation by a specialist (4509, 56.3%). The study also aimed to characterise baseline risk of bleeding in patients with AF. Of the 4764 (56.9%) of patients who had AF, 4193 (88.0%) were aged >65 years, 662 (13.9%) had stroke history, 114 (2.4%) had bleeding history and 85 (1.8%) had excessive alcohol intake.

Consequences

The interim analysis reveals that rivaroxaban is largely prescribed within the licensed indications of AF and VTE and that history of stroke is very common amongst patients prescribed rivaroxaban, in line with the approved indications. Final results of the rivaroxaban MPEM study are anticipated in 2017, after which incidence of adverse events in the first 12 months of rivaroxaban treatment will be reported.

Over 120 PEM/MPEM studies have been completed by the DSRU since 1981. The DSRU is grateful to the thousands of GPs who have completed MPEM questionnaires and contributed to protecting public health.