-
Neuro-Chirurgie Jan 2023To better understand the explanatory-pragmatic distinction in the design and interpretation of randomized controlled trials (RCTs). (Review)
Review
OBJECTIVES
To better understand the explanatory-pragmatic distinction in the design and interpretation of randomized controlled trials (RCTs).
METHODS
We review the explanatory-pragmatic distinction in clinical trial design. We use the PRECIS-2 tool to evaluate the trial design of selected RCTs on percutaneous vertebroplasty for osteoporotic vertebral compression fractures. We discuss difficulties in the selection of criteria and in the construction of PRECIS diagrams. We also examine how inconsistency in the selection of various items of trial design can cause confusion in the interpretation of results.
RESULTS
The selection of criteria and the scoring of multiple PRECIS domains were subjective and thus debatable. The pragmascope patterns of various vertebroplasty trials were heterogeneous. Many trials had both pragmatic and explanatory components. Some placebo-controlled trial goals seem to have been explanatory, but their design actually included enough pragmatic items such that the meaning of negative trial results remains ambiguous.
CONCLUSION
The results of a trial cannot be interpreted without understanding the various design choices made along the explanatory-pragmatic spectrum.
Topics: Humans; Randomized Controlled Trials as Topic; Research Design; Vertebroplasty; Fractures, Compression; Spinal Fractures
PubMed: 36566693
DOI: 10.1016/j.neuchi.2022.101403 -
Journal of the American Geriatrics... Mar 2022Randomized controlled trials are considered the most rigorous research design in efficacy and effectiveness research; however, such trials present numerous challenges...
Randomized controlled trials are considered the most rigorous research design in efficacy and effectiveness research; however, such trials present numerous challenges that limit their applicability in real-world settings. As a consequence, pragmatic trials are increasingly viewed as a research design that overcomes some of these barriers with the potential to produce findings that are more reproducible. Although pragmatic methodology in long-term care is receiving increasing attention as an approach to improve successful dissemination and implementation, pragmatic trials present complexities of their own. To address these complexities and related issues, experts with experience conducting pragmatic trials, developing nursing home policy, participating in advocacy efforts, and providing clinical care in long-term care settings participated in a virtual consensus conference funded by the National Institute on Aging in Spring 2021. Participants identified 4 cross-cutting principles key to dissemination and implementation of pragmatic trial interventions: (1) stakeholder engagement, (2) diversity and inclusion, (3) organizational strain and readiness, and (4) learn from adaptations. Participants emphasized that implementation processes must be grounded in the perspectives of the people who will ultimately be responsible for implementing the intervention once it is proven to be effective. In addition, messaging must speak to long-term care staff and all others who have a stake in its outcomes. Although our understanding of dissemination and implementation strategies remains underdeveloped, this article is designed to guide long-term care researchers and community providers who are increasingly aware of the need for pragmatism in disseminating and implementing evidence-based care interventions.
Topics: Humans; Long-Term Care; Nursing Homes; Pragmatic Clinical Trials as Topic; Stakeholder Participation
PubMed: 35195281
DOI: 10.1111/jgs.17698 -
Journal of Clinical Epidemiology Aug 2017This second article in the series on pragmatic trials describes the challenges in selection of sites for pragmatic clinical trials and the impact on validity, precision,... (Review)
Review
This second article in the series on pragmatic trials describes the challenges in selection of sites for pragmatic clinical trials and the impact on validity, precision, and generalizability of the results. The selection of sites is an important factor for the successful execution of a pragmatic trial and impacts the extent to which the results are applicable to future patients in clinical practice. The first step is to define usual care and understand the heterogeneity of sites, patient demographics, disease prevalence and country choice. Next, specific site characteristics are important to consider such as interest in the objectives of the trial, the level of research experience, availability of resources, and the expected number of eligible patients. It can be advisable to support the sites with implementing the trial-related activities and minimize the additional burden that the research imposes on routine clinical practice. Health care providers should be involved in an early phase of protocol development to generate engagement and ensure an appropriate selection of sites with patients who are representative of the future drug users.
Topics: Clinical Trials as Topic; Data Collection; Epidemiologic Research Design; Humans; Patient Selection; Population Surveillance; Reproducibility of Results; Sample Size
PubMed: 28502811
DOI: 10.1016/j.jclinepi.2017.05.003 -
Malawi Medical Journal : the Journal of... Sep 2022Pragmatic clinical trials generally rely on real world data and have the potential to generate real world evidence. This approach arose from concerns that many trial...
BACKGROUND
Pragmatic clinical trials generally rely on real world data and have the potential to generate real world evidence. This approach arose from concerns that many trial results did not adequately inform real world practice. However, maintaining the real world setting during the conduct of a trial and ensuring adequate protection for research participants can be challenging. Best practices in research oversight for pragmatic clinical trials are nascent and underdeveloped, especially in developing countries.
METHODS
We use the PRECIS-2 tool to present a case study from Lilongwe in Malawi to describe ethical and regulatory challenges encountered during the conduct of a pragmatic trial and suggest possible solutions.
RESULTS
In this article, we highlight the following six issues: (1) one public facility hosting several pragmatic trials within the same period; (2) research participants refusing financial incentives; (3) inadequate infrastructure and high workload to conduct research; (4) silos among partner organisations involved in delivery of health care; (5) individuals influencing the implementation of revised national guidelines; (6) difficulties with access to electronic medical records.
CONCLUSION
Multiple stakeholder engagement is critical to the conduct of pragmatic trials, and even with careful stakeholder engagement, continuous monitoring by gatekeepers is essential. In the Malawian context, active engagement of the district research committees can complement the work of the research ethics committees (RECs).
Topics: Humans; Delivery of Health Care; Malawi; Pragmatic Clinical Trials as Topic; Organizational Case Studies
PubMed: 36406092
DOI: 10.4314/mmj.v34i3.12 -
Journal of Orthopaedic Trauma Mar 2021The insights that real-world data (RWD) can provide, beyond what can be learned within the traditional clinical trial setting, have gained enormous traction in recent...
The insights that real-world data (RWD) can provide, beyond what can be learned within the traditional clinical trial setting, have gained enormous traction in recent years. RWD, which are increasingly available and accessible, can further our understanding of disease, disease progression, and safety and effectiveness of treatments with the speed and accuracy required by the health care environment and patients today. Over the decades since RWD were first recognized, innovation has evolved to take real-world research beyond finding ways to identify, store, and analyze large volumes of data. The research community has developed strong methods to address challenges of using RWD and as a result has increased the acceptance of RWD in research, practice, and policy. Historic concerns about RWD relate to data quality, privacy, and transparency; however, new tools, methods, and approaches mitigate these challenges and expand the utility of RWD to new applications. Specific guidelines for RWD use have been developed and published by numerous groups, including regulatory authorities. These and other efforts have shown that the more RWD are used and understood and the more the tools for handling it are refined, the more useful it will be.
Topics: Big Data; Delivery of Health Care; Humans; Pragmatic Clinical Trials as Topic
PubMed: 33587539
DOI: 10.1097/BOT.0000000000002037 -
American Journal of Kidney Diseases :... Nov 2019A pragmatic cluster-randomized trial (CRT) is a research design that may be used to efficiently test promising interventions that directly inform dialysis care. While... (Review)
Review
A pragmatic cluster-randomized trial (CRT) is a research design that may be used to efficiently test promising interventions that directly inform dialysis care. While the Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials provides general ethical guidance for CRTs, the dialysis setting raises additional considerations. In this article, we outline ethical issues raised by pragmatic CRTs in dialysis facilities. These issues may be divided into 7 key domains: justifying the use of cluster randomization, adopting randomly allocated individual-level interventions as a facility standard of care, conducting benefit-harm analyses, gatekeepers and their responsibilities, obtaining informed consent from research participants, patient notification, and including vulnerable participants. We describe existing guidelines relevant to each domain, illustrate how they were considered in the Time to Reduce Mortality in End-Stage Renal Disease (TiME) trial (a prototypical pragmatic hemodialysis CRT), and highlight remaining areas of uncertainty. The following is the first step in an interdisciplinary mixed-methods research project to guide the design and conduct of pragmatic CRTs in dialysis facilities. Subsequent work will expand on these concepts and when possible, argue for a preferred solution.
Topics: Ethics, Medical; Humans; Kidney Failure, Chronic; Personal Autonomy; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Renal Dialysis
PubMed: 31227227
DOI: 10.1053/j.ajkd.2019.04.019 -
Journal of the American Society of... Oct 2016Randomized controlled trials in CKD lag in number behind those of other chronic diseases, despite the high morbidity and mortality experienced by patients with kidney... (Review)
Review
Randomized controlled trials in CKD lag in number behind those of other chronic diseases, despite the high morbidity and mortality experienced by patients with kidney disease and the exorbitant costs of their health care. Observational studies of CKD frequently yield seemingly paradoxic associations of traditional risk factors with outcomes, making it difficult to extrapolate the results of trials conducted in people with normal kidney function to patients with CKD. However, many completed trials in CKD have been limited by intermediate outcomes of unclear clinical significance or narrow eligibility criteria that limit external validity, and implementation of proven therapies remains a challenge. It is therefore imperative that the nephrology community capitalize on recent interest in novel approaches to trial design, such as pragmatic clinical trials. These trials are meant to promote research within real world settings to yield clinically relevant results with greater applicability than those of traditional trials, while maintaining many advantages, such as controlling for potential sources of bias. We provide a description of pragmatic clinical trials and a discussion of advantages, disadvantages, and practical challenges inherent to this study design, in the context of specific scientific questions relevant to patients with CKD.
Topics: Humans; Pragmatic Clinical Trials as Topic; Renal Insufficiency, Chronic
PubMed: 27283497
DOI: 10.1681/ASN.2015111264 -
Current Heart Failure Reports Apr 2017Randomized controlled trials (RCTs) in heart failure (HF) are becoming increasingly complex and expensive to conduct and if positive deliver expensive therapy tested... (Review)
Review
PURPOSE OF REVIEW
Randomized controlled trials (RCTs) in heart failure (HF) are becoming increasingly complex and expensive to conduct and if positive deliver expensive therapy tested only in selected populations.
RECENT FINDINGS
Electronic health records and clinical cardiovascular quality registries are providing opportunities for pragmatic and registry-based prospective randomized clinical trials (RRCTs). Simplified regulatory, ethics, and consent procedures; recruitment integrated into real-world care; and simplified or automated baseline and outcome collection allow assessment of study power and feasibility, fast and efficient recruitment, delivery of generalizable findings at low cost, and potentially evidence-based and novel use of generic drugs with low costs to society. There have been no RRCTs in HF to date. Major challenges include generating funding, international collaboration, and the monitoring of safety and adherence for chronic HF treatments. Here, we use the Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction (SPIRRIT-HFpEF), to be conducted in the Swedish Heart Failure Registry, to exemplify the advantages and challenges of HF RRCTs.
Topics: Chronic Disease; Feasibility Studies; Heart Failure; Humans; Patient Selection; Pragmatic Clinical Trials as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Registries
PubMed: 28247180
DOI: 10.1007/s11897-017-0325-0 -
Journal of the American College of... Oct 2016Large randomized clinical trials in cardiovascular disease have proliferated over the past 3 decades, with results that have influenced every aspect of cardiology... (Review)
Review
Large randomized clinical trials in cardiovascular disease have proliferated over the past 3 decades, with results that have influenced every aspect of cardiology practice. Despite these advances, there remains a substantial need for more high-quality evidence to inform cardiovascular clinical practice, given the increasing prevalence of cardiovascular disease around the world. Traditional clinical trials are increasingly challenging due to rising costs, increasing complexity and length, and burdensome institutional and regulatory requirements. This review will examine the current landscape of cardiovascular clinical trials in the United States, highlight recently conducted registry-based clinical trials, and discuss the potential attributes of the recently launched pragmatic clinical trial by the Patient-Centered Outcomes Research Institute's National Patient-Centered Clinical Research Network, called the ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing the Benefits and Long-term Effectiveness) trial.
Topics: Cardiovascular Diseases; Humans; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Registries; United States
PubMed: 27765193
DOI: 10.1016/j.jacc.2016.07.781 -
Mayo Clinic Proceedings Nov 2023Pragmatic randomized clinical trials (pRCTs) have a unique set of considerations for data and safety monitoring. Because of their unconventional trial designs coupled... (Review)
Review
Pragmatic randomized clinical trials (pRCTs) have a unique set of considerations for data and safety monitoring. Because of their unconventional trial designs coupled with collection of multilevel data and implementation outcomes in real-world settings, thoughtful consideration is needed on the presentation of the trial design and accruing data to facilitate review and decision-making by the trial's data and safety monitoring board (DSMB). To our knowledge, there is limited information available in practical guidelines for generalists and medical general practitioners on what to monitor and to report to the DSMB during the conduct of pRCTs and what the DSMB should focus on in its review of reports. This article discusses these matters in the context of 3 case studies focusing on a set of critical data and safety monitoring questions that would be of interest to the generalist conducting pRCTs. In considering these questions, we provide tabular and graphical illustrations of how data can be presented to the DSMB while drawing attention to those areas that the DSMB should focus on in its review of the trial. The strategies and viewpoints discussed herein provide practical guidelines and can serve as a resource for the generalist conducting pRCTs.
Topics: Humans; Randomized Controlled Trials as Topic; Clinical Trials Data Monitoring Committees
PubMed: 37923529
DOI: 10.1016/j.mayocp.2023.02.019