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Comparing Effect Estimates in Randomized Trials and Observational Studies From the Same Population : An Application to Percutaneous Coronary Intervention

Matthews, Anthony A. ; Szummer, Karolina ; Dahabreh, Issa J. ; Lindahl, Bertil ; Erlinge, David LU orcid ; Feychting, Maria ; Jernberg, Tomas ; Berglund, Anita and Hernán, Miguel A. (2021) In Journal of the American Heart Association 10(11). p.020357-020357
Abstract

Background To understand when results from observational studies and randomized trials are comparable, we performed an observational emulation of a target trial designed to ask similar questions as the VALIDATE (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy) randomized trial. The VALIDATE trial compared the effect of bivalirudin and heparin during percutaneous coronary intervention on the risk of death, myocardial infarction, and bleeding across Sweden. Methods and Results We specified the protocol of a target trial similar to the VALIDATE trial, then emulated the target trial in the period before the VALIDATE trial took place using data from the... (More)

Background To understand when results from observational studies and randomized trials are comparable, we performed an observational emulation of a target trial designed to ask similar questions as the VALIDATE (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy) randomized trial. The VALIDATE trial compared the effect of bivalirudin and heparin during percutaneous coronary intervention on the risk of death, myocardial infarction, and bleeding across Sweden. Methods and Results We specified the protocol of a target trial similar to the VALIDATE trial, then emulated the target trial in the period before the VALIDATE trial took place using data from the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry-the same registry in which the trial was undertaken. The target trial emulation and the VALIDATE trial both estimated little or no effect of bivalirudin versus heparin on the risk of death or myocardial infarction by 180 days (target trial emulation risk ratio for death, 1.21 [95% CI, 0.88 - 1.54]; VALIDATE trial hazard ratio for death, 1.05 [95% CI, 0.78 - 1.41]). The observational data, however, could not capture less severe cases of bleeding, resulting in an inability to define a bleeding outcome like the trial, and could not accurately estimate the comparative risk of death by 14 days, which may be the result of intractable confounding early in follow-up or the inability to precisely emulate the trial's eligibility criteria. Conclusions Using real-world data to emulate a target trial can deliver accurate effect estimates. Yet, even with rich observational data, it is not always possible to estimate the short-term effect of interventions or the effect on outcomes for which data are not routinely collected.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
methodology, observational studies, randomized controlled trials, registry, SWEDEHEART, target trial emulation
in
Journal of the American Heart Association
volume
10
issue
11
pages
020357 - 020357
publisher
Wiley-Blackwell
external identifiers
  • pmid:33998290
  • scopus:85107390467
ISSN
2047-9980
DOI
10.1161/JAHA.120.020357
language
English
LU publication?
yes
id
2c8e81f6-816d-4d42-8c76-db4093f2c4e5
date added to LUP
2021-06-22 15:41:58
date last changed
2024-09-21 21:50:38
@article{2c8e81f6-816d-4d42-8c76-db4093f2c4e5,
  abstract     = {{<p>Background To understand when results from observational studies and randomized trials are comparable, we performed an observational emulation of a target trial designed to ask similar questions as the VALIDATE (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy) randomized trial. The VALIDATE trial compared the effect of bivalirudin and heparin during percutaneous coronary intervention on the risk of death, myocardial infarction, and bleeding across Sweden. Methods and Results We specified the protocol of a target trial similar to the VALIDATE trial, then emulated the target trial in the period before the VALIDATE trial took place using data from the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry-the same registry in which the trial was undertaken. The target trial emulation and the VALIDATE trial both estimated little or no effect of bivalirudin versus heparin on the risk of death or myocardial infarction by 180 days (target trial emulation risk ratio for death, 1.21 [95% CI, 0.88 - 1.54]; VALIDATE trial hazard ratio for death, 1.05 [95% CI, 0.78 - 1.41]). The observational data, however, could not capture less severe cases of bleeding, resulting in an inability to define a bleeding outcome like the trial, and could not accurately estimate the comparative risk of death by 14 days, which may be the result of intractable confounding early in follow-up or the inability to precisely emulate the trial's eligibility criteria. Conclusions Using real-world data to emulate a target trial can deliver accurate effect estimates. Yet, even with rich observational data, it is not always possible to estimate the short-term effect of interventions or the effect on outcomes for which data are not routinely collected.</p>}},
  author       = {{Matthews, Anthony A. and Szummer, Karolina and Dahabreh, Issa J. and Lindahl, Bertil and Erlinge, David and Feychting, Maria and Jernberg, Tomas and Berglund, Anita and Hernán, Miguel A.}},
  issn         = {{2047-9980}},
  keywords     = {{methodology; observational studies; randomized controlled trials; registry; SWEDEHEART; target trial emulation}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{11}},
  pages        = {{020357--020357}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of the American Heart Association}},
  title        = {{Comparing Effect Estimates in Randomized Trials and Observational Studies From the Same Population : An Application to Percutaneous Coronary Intervention}},
  url          = {{http://dx.doi.org/10.1161/JAHA.120.020357}},
  doi          = {{10.1161/JAHA.120.020357}},
  volume       = {{10}},
  year         = {{2021}},
}