An overview of methodological flaws of real-world studies investigating drug safety in the post-marketing setting

ABSTRACT

Introduction

The evaluation of the post-marketing safety profile of drugs is a continuous monitoring process for approved and marketed medicines and it is crucial for detecting new adverse drug reactions. As such, real-world studies are essential to complement pre-marketing evidence with information concerning drug risk-benefit profile and use in wider patient populations and they have a great potential to support post-marketing drug safety evaluations.

Areas covered

A detailed description of the main limitations of real-world data sources (i.e. claims databases, electronic healthcare records, drug/disease registers and spontaneous reporting system databases) and of the main methodological challenges of real-world studies in generating real-world evidence is provided.

Expert opinion

Real-world evidence biases can be ascribed to both the methodological approach and the specific limitations of the different real-world data sources used to carry out the study. As such, it is crucial to characterize the quality of real-world data, by establishing guidelines and best practices for the assessment of data fitness for purpose. On the other hand, it is important that real-world studies are conducted using a rigorous methodology, aimed at minimizing the risk of bias.

KEYWORDS:

• pharmacoepidemiology
• pharmacovigilance
• real-world data
• real-world evidence
• real-world studies

Article highlights

• Real-world studies are essential to complement pre-marketing evidence with information concerning drug risk-benefit profile and use in wider patient populations. As such, they are becoming increasingly accepted by regulators to support decision-making for new drug approvals or extensions of marketing authorizations.

• To generate reliable real-world evidence, it is important to be aware of the strengths and limitations of real-world data sources (i.e. claims databases, electronic healthcare records, drug and disease registers and spontaneous reporting system databases) and to assess data fitness for purpose to answer specific clinical questions before using them for research purposes.

• The reliability of real-world evidence also depends on the choice of study design. Based on the scientific question and the study population, using a rigorous methodology is essential to minimize the risk of bias.

• The complexity of real-world studies requires a multidisciplinary approach, including the expertise of professional pharmacoepidemiologists for the choice of study design and analytical approaches, as well as the interpretation of real-world data. For these reasons, it is important that pharmacoepidemiologists are included in research teams exploring real-world evidence using different types of real-world data sources.

Declaration of interest

G Trifirò has served in the last 3 years on advisory boards/seminars funded by Sanofi, Eli Lilly, AstraZeneca, AbbVie, Novo Nordisk, Gilead, and Amgen; he is also a scientific coordinator of the academic spin-off ‘INSPIRE srl,’ which has received funding for conducting observational studies from several pharmaceutical companies. None of these listed activities is related to the topic of the article. 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 apart from those disclosed.

Reviewer disclosures

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

Author contribution statement

G Trifirò conceived the study. S Crisafulli and Z Khan wrote the draft of the paper. Y Karatas and M Tuccori critically revised the manuscript. All authors have read and approved the final version of the manuscript.

Additional information

Funding

This paper was not funded.