Systematic reviews of adverse effects: framework for a structured approach

Abstract

Background: As every healthcare intervention carries some risk of harm, clinical decision making needs to be supported by a systematic assessment of the balance of benefit to harm. A systematic review that considers only the favourable outcomes of an intervention, without also assessing the adverse effects, can mislead by introducing a bias favouring the intervention.Much of the current guidance on systematic reviews is directed towards the evaluation of effectiveness; but this differs in important ways from the methods used in assessing the safety and tolerability of an intervention. A detailed discussion of why, how and when to include adverse effects in a systematic review, is required.Methods: This discussion paper, which presupposes a basic knowledge of systematic review methodology, was developed by consensus among experienced reviewers, members of the Adverse Effects Subgroup of The Cochrane Collaboration, and supplemented by a consultation of content experts in reviews methodology, as well as those working in drug safety. Results:A logical framework for making decisions in reviews that incorporate adverse effects is provided. We explore situations where a comprehensive investigation of adverse effects is warranted and suggest strategies to identify practicable and clinically useful outcomes. The advantages and disadvantages of including observational and experimental study designs are reviewed. The consequences of including separate studies for intended and unintended effects are explained. Detailed advice is given on designing electronic searches for studies with adverse effects data. Reviewers of adverse effects are given general guidance on the assessment of study bias, data collection, analysis, presentation and the interpretation of harms in a systematic review. Conclusion:Readers need to be able to recognize how strategic choices made in the review process determine what harms are found, and how the findings may affect clinical decisions. Researchers undertaking a systematic review that incorporates adverse effect data should understand the rationale for the suggested methods and be able to implement them in their review.

Renal and Bone Adverse Effects of a Tenofovir-Based Regimen in the Treatment of HIV-Infected Children: A Systematic Review

“…The following databases were searched by Rose I Okonkwo (RIO) from 1 May, 2014 to 18 [20]. Once all databases searches had been conducted, duplicate citations were identified and excluded using reference management software (RefWorks 2.0 [http://www.refworks.com/]).…”

Clinical Features, Testing, and Management of Patients with Suspected Prosthetic Hip-Associated Cobalt Toxicity: a Systematic Review of Cases

“…In order to maximize identification of relevant literature, we utilized a combination of index terms and freetext terms as has been previously recommended by the Cochrane Adverse Effects Methods Group [14]. MEDLINE search terms (medical subject headings and free-text) included "cobalt toxicity," "cobalt," "intoxication," "poisoning," "arthroprosthetic cobaltism," "hip prosthesis," "joint replacement," and "arthroplasty" while filtering by "case reports," "clinical trial," "comparative study," "controlled clinical trial," or "randomized controlled trial."…”

“…Further, because no comparative data between symptomatic and asymptomatic patients with Co-HP exist, we relied on review of case reports, the least robust form of evidence. We attempted to minimize these limitations by adhering to guidance for systematic review methodology published in the general and toxicology literature [14,52,53].…”

Open Issues in Intelligent Personal Health Record – An Updated Status Report for 2012

“…Like the case with adverse effect [50,89], there are many different ways of expressing the meaning of contraindication, some of which are tricky [131]. Initially, it is difficult to manually construct a comprehensive list of contraindication-related phrases.…”

“…For each listed side effect, its incidence statistics reflecting the likelihood of developing it could be displayed. To compile side effects of SCAs, we can adopt a method similar to those used for compiling drug side/adverse effects from various resources, such as electronic health knowledge resources [27,68,89], historical data in electronic health records [148], and medical message board posts [15]. To obtain incidence statistics of side effects of SCAs, we can adopt a method similar to those used for estimating incidence statistics of drug adverse effects from various resources [36,50,68].…”