Do efficacy results obtained from randomized controlled trials translate to effectiveness data from observational studies for relapsing–remitting multiple sclerosis?

Stefan Verweij*, Wouter Ahmed, Guiling Zhou, Dimitris Mavridis, Stavros Nikolakopoulos, Andre J. Elferink, Katrien Oude Rengerink, Maarten J. Bijlsma, Peter G.M. Mol, Eelko Hak

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Background: Randomized controlled trials are considered the gold standard in regulatory decision making, as observational studies are known to have important methodological limitations. However, real-world evidence may be helpful in specific situations. This review investigates how the effect estimates obtained from randomized controlled trials compare to those obtained from observational studies, using drug therapy for relapsing–remitting multiple sclerosis as an example. Study Design and Setting: A systematic review of randomized controlled trials and observational studies was conducted. The primary outcome was the annualized relapse rate. Using (network) meta-analysis together with posterior predictive distributions, the drug-specific rate ratios from the network of randomized controlled trials were compared with those from the network of observational studies. Results: Effect estimates from 26 observational studies showed greater magnitudes and were less precise compared to estimates obtained from 21 randomized controlled trials. Twenty of the 28 treatment comparisons between designs had similar rate ratios. Seven inconsistencies in observed rate ratios could be attributed to two specific disease-modifying therapies. Conclusion: In this case study, estimates from observational studies predominantly agreed with estimates from randomized controlled trials given their posterior predictive distributions. Multiple observational studies together may therefore supplement additional pivotal randomized controlled trials in relapsing–remitting multiple sclerosis, for instance facilitating the extrapolation of trial results to the broader patient population.

Original languageEnglish
Article numbere5810
JournalPharmacoepidemiology and Drug Safety
Volume33
Issue number5
DOIs
Publication statusPublished - May 2024

Keywords

  • network meta-analysis
  • posterior predictive distributions
  • randomized controlled trials
  • real-world evidence
  • relapsing–remitting multiple sclerosis

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