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Headache Jul 2019
Topics: Epidemiologic Studies; Humans; Migraine Disorders; Observational Studies as Topic; Research Design
PubMed: 31297809
DOI: 10.1111/head.13572 -
Pharmacoepidemiology and Drug Safety Oct 2020There is a need to develop hybrid trial methodology combining the best parts of traditional randomized controlled trials (RCTs) and observational study designs to... (Review)
Review
PURPOSE
There is a need to develop hybrid trial methodology combining the best parts of traditional randomized controlled trials (RCTs) and observational study designs to produce real-world evidence (RWE) that provides adequate scientific evidence for regulatory decision-making.
METHODS
This review explores how hybrid study designs that include features of RCTs and studies with real-world data (RWD) can combine the advantages of both to generate RWE that is fit for regulatory purposes.
RESULTS
Some hybrid designs include randomization and use pragmatic outcomes; other designs use single-arm trial data supplemented with external comparators derived from RWD or leverage novel data collection approaches to capture long-term outcomes in a real-world setting. Some of these approaches have already been successfully used in regulatory decisions, raising the possibility that studies using RWD could increasingly be used to augment or replace traditional RCTs for the demonstration of drug effectiveness in certain contexts. These changes come against a background of long reliance on RCTs for regulatory decision-making, which are labor-intensive, costly, and produce data that can have limited applicability in real-world clinical practice.
CONCLUSIONS
While RWE from observational studies is well accepted for satisfying postapproval safety monitoring requirements, it has not commonly been used to demonstrate drug effectiveness for regulatory purposes. However, this position is changing as regulatory opinions, guidance frameworks, and RWD methodologies are evolving, with growing recognition of the value of using RWE that is acceptable for regulatory decision-making.
Topics: Decision Making; Drug Approval; Humans; Observational Studies as Topic; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Research Design
PubMed: 31823482
DOI: 10.1002/pds.4932 -
Journal of the American Society of... Aug 2023Target trial emulation has drastically improved the quality of observational studies investigating the effects of interventions. Its ability to prevent avoidable biases... (Review)
Review
Target trial emulation has drastically improved the quality of observational studies investigating the effects of interventions. Its ability to prevent avoidable biases that have plagued many observational analyses has contributed to its recent popularity. This review explains what target trial emulation is, why it should be the standard approach for causal observational studies that investigate interventions, and how to do a target trial emulation analysis. We discuss the merits of target trial emulation compared with often used, but biased analyses, as well as potential caveats, and provide clinicians and researchers with the tools to better interpret results from observational studies investigating the effects of interventions.
Topics: Causality; Observational Studies as Topic
PubMed: 37131279
DOI: 10.1681/ASN.0000000000000152 -
The New England Journal of Medicine Dec 2016
Topics: Clinical Trials as Topic; Evidence-Based Practice; Government Regulation; Humans; Observational Studies as Topic; Prescription Fees; Research Design; United States; United States Food and Drug Administration
PubMed: 27959688
DOI: 10.1056/NEJMsb1609216 -
European Journal of Endocrinology Dec 2020The name of the study should properly reflect the actual conduct and analysis of the study. This short paper provides guidance on how to properly name the study design....
The name of the study should properly reflect the actual conduct and analysis of the study. This short paper provides guidance on how to properly name the study design. The first distinction is between a trial (intervention given to patients to study its effect) and an observational study. For observational studies, it should further be decided whether it is cross-sectional or whether follow-up time is taken into account (cohort or case-control study). The distinction prospective-retrospective has two disadvantages: prospective is often seen as marker of higher quality, which is not necessarily true; there is no unifying definition that makes a proper distinction between retrospective and prospective possible.
Topics: Case-Control Studies; Clinical Trials as Topic; Cohort Studies; Cross-Sectional Studies; Humans; Observational Studies as Topic; Prospective Studies; Research Design; Retrospective Studies; Terminology as Topic
PubMed: 33055302
DOI: 10.1530/EJE-20-0873 -
JAMA Surgery Aug 2021
Topics: Biomedical Research; Checklist; Guidelines as Topic; Humans; Meta-Analysis as Topic; Observational Studies as Topic; Research Design
PubMed: 33825847
DOI: 10.1001/jamasurg.2021.0522 -
British Journal of Hospital Medicine... May 2020The numbers of clinical trials have increased exponentially over the last decade, amplifying the pressure to select an appropriate study design to obtain reliable and... (Review)
Review
The numbers of clinical trials have increased exponentially over the last decade, amplifying the pressure to select an appropriate study design to obtain reliable and valid evidence. The ability to find, critically appraise and use evidence to develop new interventions is fundamental to evidence-based medicine. Different study designs have their own advantages and disadvantages, and provide different evidentiary value. This article provides an overview of clinical trials, illustrating that, ultimately, the study design chosen needs to meet experimental and funding limitations, while minimising error.
Topics: Clinical Trials as Topic; Humans; Observational Studies as Topic; Research Design; Systematic Reviews as Topic
PubMed: 32468947
DOI: 10.12968/hmed.2020.0127 -
European Journal of Epidemiology Jan 2023A detailed examination of the 1930 Lanarkshire Milk Experiment (LME) by the famous statistician William Sealy Gossett ("Student"), which appeared in Biometrika in 1931,... (Review)
Review
A detailed examination of the 1930 Lanarkshire Milk Experiment (LME) by the famous statistician William Sealy Gossett ("Student"), which appeared in Biometrika in 1931, is re-examined from a more modern perspective. The LME had a complicated design whereby 67 schools in Lanarkshire were allocated to receive either raw or pasteurised milk but pupils within the schools were allocated to either receive milk or to act as controls. Student's criticisms are considered in detail and examined in terms of subsequent developments on the design and analysis of experiments, in particular as regards appropriate estimation of standard errors of treatment estimates when an incomplete blocks structure has been used. An analogy with a more modern trial in osteoarthritis is made. Suggestions are made as to how analysis might proceed if the original data were available. Some lessons for observational studies in epidemiology are drawn and it is speculated that hidden clustering structures might be an explanation as to why results may vary from observational study to observational study by more than conventionally calculated standard errors might suggest.
Topics: Humans; Animals; Milk; Schools; Observational Studies as Topic
PubMed: 36477576
DOI: 10.1007/s10654-022-00941-x -
International Heart Journal Apr 2017The FMDJ study, a multicenter prospective observational study conducted in Japan, demonstrated the acceptable reliability of measurement of flow-mediated vasodilatation... (Review)
Review
The FMDJ study, a multicenter prospective observational study conducted in Japan, demonstrated the acceptable reliability of measurement of flow-mediated vasodilatation (FMD) using a semi-automatic device in individual institutions. However, in about 10% of Japanese subjects, adequate scans to determine the brachial arterial diameter failed to be obtained. The prevalence of inadequate scans was higher in women than in men, while obesity had no influence on the inadequate scan rate. The FMDJ study also proposed that attending periodic refresher courses on the measurement of FMD is needed for maintaining competency. Finally, the FMDJ study proposed reference values for FMD. Thus, FMD measurement may be categorized as a clinically applicable tool on the basis of class IIb (exploratory cohort study with good reference standards) evidence.
Topics: Diagnostic Techniques, Cardiovascular; Humans; Multicenter Studies as Topic; Observational Studies as Topic; Reference Values; Vasodilation
PubMed: 28367852
DOI: 10.1536/ihj.17-013 -
The New England Journal of Medicine Oct 2021
Topics: Causality; Confounding Factors, Epidemiologic; Data Interpretation, Statistical; Epidemiologic Research Design; Humans; Observational Studies as Topic; Public Health
PubMed: 34596980
DOI: 10.1056/NEJMp2113319