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The role of systematic reviews in pharmacovigilance planning and Clinical Trials Authorisation application: example

Carrol Gamble1, Andrew Wolf, Ian Sinha

  • 1Clinical Trials Research Centre, University of Liverpool, Liverpool, Merseyside, United Kingdom. c.gamble@liv.ac.uk

Plos One
|April 5, 2013
PubMed

Insights

This systematic review assessed the safety of midazolam and clonidine for pediatric sedation. No new adverse reactions were found beyond existing drug information, supporting their use in clinical trials.

Area of Science:

  • Pediatric Intensive Care
  • Pharmacology
  • Clinical Trials

Background:

  • Sedation is vital for children on mechanical ventilation in Pediatric Intensive Care Units (PICUs).
  • Limited evidence exists from randomized controlled trials (RCTs) for sedatives like midazolam and clonidine.
  • A trial comparing midazolam and clonidine necessitated a safety profile review for regulatory approval.

Purpose of the Study:

  • To systematically review the safety profiles of midazolam and clonidine for pediatric sedation.
  • To inform the pharmacovigilance plan for a planned clinical trial comparing these sedatives.
  • To support the application for Clinical Trials Authorisation.

Main Methods:

  • Searched Medline for RCTs, controlled trials, observational studies, case reports, and series.
  • Obtained Summary of Product Characteristics (SmPC) for both sedatives.
  • Requested adverse drug reaction reports from the MHRA.

Main Results:

  • Identified 80 full texts for midazolam and 6 for clonidine from initial abstracts.
  • 33 studies provided data for midazolam, and 2 for clonidine.
  • MHRA reported 10 and 3 suspected adverse drug reactions for midazolam and clonidine, respectively.

Conclusions:

  • No novel adverse reactions were identified beyond those listed in the SmPC.
  • The established safety profiles and widespread use supported restricting the pharmacovigilance plan to adverse reactions.
  • Clinical Trials Authorisation was granted based on SmPC data and the defined pharmacovigilance plan.
Abstract

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