The reporting of observational studies of drug effectiveness and safety: recommendations to extend existing guidelines

ABSTRACT

Introduction

The use of observational data to assess drug effectiveness and safety can provide relevant information, much of which may not be feasible to obtain through randomized clinical trials. Because observational studies provide critical drug safety and effectiveness information that influences drug policy and prescribing practices, transparent, consistent, and accurate reporting of these studies is critical.

Areas Covered

We provide recommendations to extend existing reporting guidelines, covering the main components of primary research studies (methods, results, discussion).

Expert Opinion

Our recommendations include extending drug safety and effectiveness guidelines to include explicit checklist items on: study registration, causal diagrams, rationale for measures of effect, comprehensive assessment of bias, comprehensive data cleaning steps, drug equivalents, subject-level drug data visualization, sex and gender-based analyses and results, patient-oriented outcomes, and patient involvement in research.

KEYWORDS:

• Drug effectiveness
• drug safety
• reporting guidelines
• reporting items
• reporting checklist

Article highlights

• Reporting guidelines aim to promote transparent, consistent, and accurate reporting of empirical research findings.

• Several issues specific to observational studies of drug safety and effectiveness are not well reflected within existing reporting guidelines; this article provides recommendations to extend existing guidelines.

• Recommendations for extending reporting guidelines methodology sections include the following items: study registration, causal diagrams, rationale for measures of effect, comprehensive data cleaning steps, drug equivalents, sex and gender-based analyses, patient-oriented outcomes, and patient/public involvement.

• Recommendations for extending reporting guidelines results sections include the following items: sex and gender-based results, and subject-level drug data visualization.

• Recommendations for extending reporting guidelines discussion sections include the following item: comprehensive assessment of bias.

This box summarizes key points contained in the article.

Author contributions

JC was responsible for the review concept, chaired the panel, and drafted the manuscript. HT was responsible for the review concept and drafted the manuscript. LA, GC, MDV, ME, FL, AG, GG, MH, CJ, RK, TK, LL, MM, MS, BT, and FW were members of the expert panel and critically revised the manuscript.

Declaration of interest

H Tremlett is the Canada Research Chair for Neuroepidemiology and Multiple Sclerosis. Current research support received from the National Multiple Sclerosis Society, the Canadian Institutes of Health Research, the Multiple Sclerosis Society of Canada and the Multiple Sclerosis Scientific Research Foundation. In addition, in the last 5 years, has received research support from the UK MS Trust; travel expenses to present at CME conferences from the Consortium of MS Centres (2018), the National MS Society (2016, 2018), ECTRIMS/ACTRIMS (2015, 2016, 2017, 2018, 2019, 2020), American Academy of Neurology (2015, 2016, 2019). Speaker honoraria are either declined or donated to an MS charity or to an unrestricted grant for use by H Tremlett’s research group. M Harrison is supported by a Michael Smith Foundation for Health Research Scholar Award 2017 (#16,813). M Harrison holds the UBC Professorship in Sustainable Health Care, which between 2014 and 2017 was funded by Amgen Canada, AstraZeneca Canada, Eli Lilly Canada, GlaxoSmithKline, Merck Canada, Novartis Pharmaceuticals Canada, Pfizer Canada, Boehringer Ingelheim (Canada), Hoffman-La Roche, LifeScan Canada, and Lundbeck Canada. M De Vera holds a Tier 2 Canada Research Chair and is a recipient of a Scholar Award from the Michael Smith Foundation for Health Research. M Etminan is a consultant in the Invokana and Risperdal litigations for work unrelated to this manuscript. L Azoulay served as a consultant for Janssen and Pfizer for work unrelated to this manuscript. T Kendzerska receives salary support from the PSI Foundation. M Sadatsafavi is receiving salary support from The Canadian Institutes of Health Research and Michael Smith Foundation for Health Research. He has received honoraria from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, and Teva. He has received research funds directly into his research account within The University of British Columbia from Boehringer Ingelheim and AstraZeneca. None of the above-mentioned activities were directly related to this work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary Material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the Craig H. Neilsen Foundation (Grant no. 650576). Dr. Cragg holds a Tier 2 Canada Research Chair (CRC).