Compared to randomized studies, observational studies may overestimate the effectiveness of DOACs: a metaepidemiological approach.
Anticoagulants
/ therapeutic use
Biomedical Research
/ standards
Data Collection
/ standards
Female
Guidelines as Topic
Humans
Male
Middle Aged
Observational Studies as Topic
/ standards
Proportional Hazards Models
Prospective Studies
Randomized Controlled Trials as Topic
/ standards
Research Design
Retrospective Studies
Treatment Outcome
Venous Thromboembolism
/ drug therapy
Direct oral anticoagulants
Metaepidemiological study
Observational studies
Overestimation
Randomized controlled trial
Ratio of hazard ratio
Residual confounding
Journal
Journal of clinical epidemiology
ISSN: 1878-5921
Titre abrégé: J Clin Epidemiol
Pays: United States
ID NLM: 8801383
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
20
05
2020
revised:
01
10
2020
accepted:
15
10
2020
pubmed:
21
10
2020
medline:
15
9
2021
entrez:
20
10
2020
Statut:
ppublish
Résumé
Randomized controlled trials (RCTs) are criticized for including patients who are overselected. Health authorities consequently encourage "real-world" postmarketing cohort studies. Our objective was to determine the differences between RCTs and observational studies as regards their populations and efficacy/safety results. A systematic review was conducted to identify RCTs and observational studies including patients with venous thromboembolism receiving direct oral anticoagulants or conventional treatment. Ratios of hazard ratio (RHR) comparing epidemiological studies (prospective and retrospective cohort studies and studies using living databases) with RCTs were computed. Six RCTs (27,121 patients) and twenty observational studies (248,971 patients) were identified and analyzed. Prospective cohort studies seemed to recruit patients who were no less selected than those of RCTs whereas other types of observational studies may reflect the population treated in real life. Among observational studies, prospective cohort studies yielded the most favorable estimates of treatment effect compared with RCTs. These studies were associated with a nonsignificant 33% increase in efficacy estimate (RHR 0.67, [95% CI, 0.39-1.18]) but no effect on safety estimate. Studies using living databases were associated with nonsignificant trends toward a greater effect on efficacy (RHR 0.82, [0.66-1.01]) and a smaller effect on safety (RHR 1.33, [0.96-1.84]). Overall, in this clinical setting, an exaggeration of the treatment efficacy estimate was seen with observational studies compared with RCTs. As the presence of residual confounding cannot be excluded, these results should be interpreted cautiously.
Sections du résumé
BACKGROUND AND OBJECTIVES
Randomized controlled trials (RCTs) are criticized for including patients who are overselected. Health authorities consequently encourage "real-world" postmarketing cohort studies. Our objective was to determine the differences between RCTs and observational studies as regards their populations and efficacy/safety results.
METHODS
A systematic review was conducted to identify RCTs and observational studies including patients with venous thromboembolism receiving direct oral anticoagulants or conventional treatment. Ratios of hazard ratio (RHR) comparing epidemiological studies (prospective and retrospective cohort studies and studies using living databases) with RCTs were computed.
RESULTS
Six RCTs (27,121 patients) and twenty observational studies (248,971 patients) were identified and analyzed. Prospective cohort studies seemed to recruit patients who were no less selected than those of RCTs whereas other types of observational studies may reflect the population treated in real life. Among observational studies, prospective cohort studies yielded the most favorable estimates of treatment effect compared with RCTs. These studies were associated with a nonsignificant 33% increase in efficacy estimate (RHR 0.67, [95% CI, 0.39-1.18]) but no effect on safety estimate. Studies using living databases were associated with nonsignificant trends toward a greater effect on efficacy (RHR 0.82, [0.66-1.01]) and a smaller effect on safety (RHR 1.33, [0.96-1.84]).
DISCUSSION
Overall, in this clinical setting, an exaggeration of the treatment efficacy estimate was seen with observational studies compared with RCTs.
CONCLUSIONS
As the presence of residual confounding cannot be excluded, these results should be interpreted cautiously.
Identifiants
pubmed: 33080342
pii: S0895-4356(20)31152-5
doi: 10.1016/j.jclinepi.2020.10.013
pii:
doi:
Substances chimiques
Anticoagulants
0
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
49-58Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.