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The British Journal of General Practice... Feb 2022
Topics: General Practice; Humans; Pragmatic Clinical Trials as Topic
PubMed: 35091399
DOI: 10.3399/bjgp22X718289 -
The New England Journal of Medicine Aug 2016
Topics: Follow-Up Studies; Humans; Patient Selection; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 27518663
DOI: 10.1056/NEJMra1510059 -
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 -
The New England Journal of Medicine Oct 2017
Topics: Clinical Protocols; Data Interpretation, Statistical; Humans; Intention to Treat Analysis; Patient Compliance; Pragmatic Clinical Trials as Topic; Research Design
PubMed: 28976864
DOI: 10.1056/NEJMsm1605385 -
Journal of Clinical Epidemiology Sep 2021We established a large database of trials to serve as a resource for future methodological and ethical analyses. Here, we use meta-data to describe the broad landscape... (Review)
Review
OBJECTIVE
We established a large database of trials to serve as a resource for future methodological and ethical analyses. Here, we use meta-data to describe the broad landscape of pragmatic trials including research areas, identification as pragmatic, quality of trial registry data and enrolment.
STUDY DESIGN AND SETTING
Trials were identified by a validated search filter and included if a primary report of a health-related randomized trial published January 2014-April 2019. Data were collated from MEDLINE, Web of Science, ClinicalTrials.gov, and full text.
RESULTS
4337 eligible trials were identified from 13,065 records, of which 1988 were registered in ClinicalTrials.gov. Research areas were diverse, with the most common being general and internal medicine; public, environmental and occupational health; and health care sciences and services. The term "pragmatic" was seldom used in titles or abstracts. Several domains in ClinicalTrials.gov had questionable data quality. We estimated that one-fifth of trials under-accrued by at least 15%.
CONCLUSION
There is a need to improve reporting of pragmatic trials and quality of trial registry data. Under accrual remains a challenge in pragmatic RCTs despite calls for more streamlined recruitment approaches. The diversity of pragmatic trials should be reflected in future ethical analyses.
Topics: Abstracting and Indexing; Humans; Pragmatic Clinical Trials as Topic; Registries; Research Design
PubMed: 33789151
DOI: 10.1016/j.jclinepi.2021.03.021 -
Journal of Evaluation in Clinical... Dec 2019For over 50 years, clinical research methodology has wrestled with the problem of the lack of correspondence between tests of treatments and applications of treatments....
For over 50 years, clinical research methodology has wrestled with the problem of the lack of correspondence between tests of treatments and applications of treatments. The former comprise of trials featuring scrupulous control of patient eligibility, treatment compliance, clinician expertise, follow-up intensity, and so on. In applying a validated treatment, the practitioner has to confront considerable real-world variation in potential patients and in implementation regimes. The remedy, going by the name of "pragmatic trials," is to conduct clinical trials in conditions corresponding more closely to everyday practice. This solution has proved easier to utter than to execute, and the paper reviews the extensive literature on pragmatic trials, seeking to assess whether it has terminated in clarity or contestation.
Topics: Biomedical Research; Comparative Effectiveness Research; Critical Pathways; Data Accuracy; Humans; Patient Compliance; Practice Patterns, Physicians'; Pragmatic Clinical Trials as Topic; Professional Practice
PubMed: 31313412
DOI: 10.1111/jep.13216 -
Current Osteoporosis Reports Dec 2019In this review, we present the application of pragmatic clinical trials for evaluating interventions in osteoporosis, and we discuss methodological considerations for... (Review)
Review
PURPOSE OF REVIEW
In this review, we present the application of pragmatic clinical trials for evaluating interventions in osteoporosis, and we discuss methodological considerations for designing and conducting a pragmatic clinical trial compared with a classical randomized clinical trial.
RECENT FINDINGS
Pragmatic clinical trials are a popular study design testing effectiveness of health interventions and are intended to address the limitations associated with traditional explanatory randomized clinical trials testing efficacy of interventions. To date, only few pragmatic clinical trials have been conducted in osteoporosis. Pragmatic clinical trials are conducted under routine clinical practice setting and are intended to inform policy makers and clinical decisions. Osteoporosis is a chronic disease well-suited to this particular study design given the existence of a clear and specific natural endpoint, namely fracture occurrence, and the availability of several treatments to prevent fractures.
Topics: Humans; Osteoporosis; Osteoporotic Fractures; Pragmatic Clinical Trials as Topic
PubMed: 31773402
DOI: 10.1007/s11914-019-00551-9 -
Journal of Clinical Epidemiology Dec 2022To review the pragmatism of published randomized trials of remdesivir and favipiravir based on the Pragmatic-Explanatory Continuum Indicator Summary (PRECIS-2) framework. (Review)
Review
How pragmatic are randomized trials of remdesivir and favipiravir for in-hospital treatment of COVID-19: a descriptive methodological review of trial design using the PRECIS-2 framework.
OBJECTIVES
To review the pragmatism of published randomized trials of remdesivir and favipiravir based on the Pragmatic-Explanatory Continuum Indicator Summary (PRECIS-2) framework.
STUDY DESIGN AND SETTING
Ten eligible trials were identified from an existing comprehensive living review and were evaluated across the nine PRECIS-2 domains by two independent reviewers.
RESULTS
All 10 trials had mostly pragmatic design characteristics. Four of the domains (i.e., recruitment, setting, organization, and primary analysis) were found to be pragmatic with most trials scoring four or five across the two interventions. In comparison scores for four other design domains (i.e., eligibility, follow-up, flexibility of delivery, and primary outcome) varied across the trials with some design choices being more explanatory.
CONCLUSION
In our descriptive review of randomized controlled trails for two drugs for patients infected with COVID-19 early in the pandemic, we found that most trials had more pragmatic than explanatory characteristics. Some design choices for some of the trials, however, were not consistent with the urgent goal of informing clinical decision making in an epidemic. PRECIS-2 should be used as a guide by trialists, to help them match their trial design choices to the intended purpose of their trial.
Topics: Humans; COVID-19 Drug Treatment; Hospitals; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Research Design
PubMed: 36265553
DOI: 10.1016/j.jclinepi.2022.10.013 -
Expert Review of Pharmacoeconomics &... Feb 2010The debate concerning the adoption of a pragmatic or explanatory attitude to clinical trials as well as the exact points of distinction between the two attitudes, has... (Review)
Review
The debate concerning the adoption of a pragmatic or explanatory attitude to clinical trials as well as the exact points of distinction between the two attitudes, has lasted for more than 40 years. Recently, new methodological proposals have been given as a pragmatic-explanatory continuum indicator summary tool and mechanistic-practical framework to distinguish the two attitudes. In this review, we provide a guide to the literature concerning the debate regarding the choice between explanatory and pragmatic attitudes in trial-based economic evaluations, focusing on the therapies for burns.
Topics: Burns; Clinical Trials as Topic; Humans; Models, Economic; Research Design; Treatment Outcome
PubMed: 20121563
DOI: 10.1586/erp.09.75 -
Polskie Archiwum Medycyny Wewnetrznej 2011Most clinical trials assessing the role of a specific intervention attempt to answer an explanatory question: under ideal circumstances of risk and responsiveness, can... (Review)
Review
Most clinical trials assessing the role of a specific intervention attempt to answer an explanatory question: under ideal circumstances of risk and responsiveness, can the expert care of individual with a particular condition reduce their risks of a relevant but restricted set of outcomes? Such explanatory trials (also called efficacy trials) are of direct relevance to expert clinicians and their highly compliant patients. Another question, potentially of broader clinical or health care policy relevance is: Does this treatment improve patient-important outcomes when applied by typical clinicians to typical patients? Answering this latter question is the goal of pragmatic trial, also labeled by some as "management" or "effectiveness" trial. The methodological and organizational differences between explanatory and pragmatic trials include, among others, patients eligibility (restricted to highly responsive and compliant patients in explanatory trials vs. everyone with condition of interest in pragmatic trials), experimental and comparator intervention (blinded and inflexible with strict instructions vs. flexible with cross-over permitted and no blinding), types of practitioners (only those with documented high expertise vs. all who usually provide given mode of care), and outcome measurement (often limited to biologic effects vs. broad overall health effects sometimes based on administrative data bases on mortality and utilization). Those aspects of study design and conduct and their role in determining a place of an intervention in clinical practice are reviewed in this paper.
Topics: Anti-Asthmatic Agents; Asthma; Clinical Trials as Topic; Humans; Patient Selection; Practice Guidelines as Topic; Precision Medicine; Research Design; Severity of Illness Index; Treatment Outcome
PubMed: 21878863
DOI: No ID Found