Conducting and Reporting Systematic Reviews of Adverse Events

• Author / Creator

  Zorzela, Liliane Medianeira

• Introduction Systematic reviews (SRs) synthesize published and sometimes unpublished data and are often based on randomized controlled trials (RCTs). However, RCTs are known to be poor at identifying and reporting harms. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) Statement was published in 2009 to offer guidance on the minimum reporting standards when publishing a SR. Thus far, PRISMA has mainly focused on efficacy, but there is a need for evidence on both efficacy and harms of interventions. Propofol is an anesthetic intervention used for pediatric sedation, but there have been several case reports of ‘propofol infusion syndrome’ (PRIS), a poorly understood syndrome often leading to death. In several countries, regulatory agencies have contraindicated the use of propofol infusion in pediatric intensive care units. However, propofol is still used despite the liability concerns. The overall goals of this thesis were to improve methods of conducting and reporting systematic reviews of adverse events. More specifically, (i) to develop an extension for the PRISMA Statement, for SRs addressing adverse events (AEs): the PRISMA Harms; (ii) to identify if propofol is associated with serious AEs in children and measure if the inclusion of non-randomized studies in a SR of AEs provides further information than data from RCTs alone. Methods There were 2 distinct methods used in this doctoral thesis. The first was to develop the PRISMA Harms guideline. We followed the recommended steps for guideline development: 1) to document if there is need for the development of a guideline; 2) to employ a Delphi process to identify relevant items to be included in the reporting guideline; 3) to have an in-person consensus building meeting; and 4) to write the guideline. The second was to identify if propofol infusion is associated with serious AEs in pediatric patients and to measure if the inclusion of non-randomized studies provides more relevant data than clinical trials alone, we conducted a SR of propofol infusion in pediatric patients including both clinical trials and observational studies. Results For the PRISMA Harms development, the first step identified 309 reviews of AEs and documented weaknesses in reporting and the need for a guideline. The second step conducted three Delphi rounds sent to 352 participants, 166 responses were received. The in-person meeting had 25 participants and the final PRISMA Harms manuscript was developed after multiple revisions containing 4 mandatory items and 14 recommended items for reviews addressing harms. The propofol SR identified 91 serious AEs (PRIS or cardiac arrest) associated with propofol infusion, 21 identified in a single unpublished RCT and all the other serious AEs emerged from non-randomized studies. In the included studies, a total of 5633 children received propofol for more than 60 minutes and did not have any serious events (i.e., PRIS or cardiac arrest) associated with it. Conclusion Through this work we developed PRISMA Harms, an international reporting guideline to improve harms reporting in SRs. Further, we documented serious AEs associated with propofol infusion in children and the relevance of including non-randomized and unpublished studies in SRs of AEs, providing both clinical and methodological significant information.

• Subjects / Keywords

  • PRISMA Harms
  • Systematic reviews
  • Pediatrics
  • Propofol
  • Adverse events

• Graduation date

  Spring 2015

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R34B2XD1B

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.