-
Osteoarthritis and Cartilage Mar 2021
Topics: Cognitive Behavioral Therapy; Humans; Low Back Pain; Mediation Analysis; Patient Satisfaction; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33429055
DOI: 10.1016/j.joca.2020.12.011 -
PloS One 2023Postoperative pulmonary complications (PPCs) are a major cause of morbidity and mortality after open abdominal surgery. Optimized perioperative lung expansion may...
BACKGROUND
Postoperative pulmonary complications (PPCs) are a major cause of morbidity and mortality after open abdominal surgery. Optimized perioperative lung expansion may minimize the synergistic factors responsible for the multiple-hit perioperative pulmonary dysfunction. This ongoing study will assess whether an anesthesia-centered bundle focused on perioperative lung expansion results in decreased incidence and severity of PPCs after open abdominal surgery.
METHODS
Prospective multicenter randomized controlled pragmatic trial in 750 adult patients with at least moderate risk for PPCs undergoing prolonged (≥2 hour) open abdominal surgery. Participants are randomized to receive either a bundle intervention focused on perioperative lung expansion or usual care. The bundle intervention includes preoperative patient education, intraoperative protective ventilation with individualized positive end-expiratory pressure to maximize respiratory system compliance, optimized neuromuscular blockade and reversal management, and postoperative incentive spirometry and early mobilization. Primary outcome is the distribution of the highest PPC severity by postoperative day 7. Secondary outcomes include the proportion of participants with: PPC grades 1-2 through POD 7; PPC grades 3-4 through POD 7, 30 and 90; intraoperative hypoxemia, rescue recruitment maneuvers, or cardiovascular events; and any major extrapulmonary postoperative complications. Additional secondary and exploratory outcomes include individual PPCs by POD 7, length of postoperative oxygen therapy or other respiratory support, hospital resource use parameters, Patient-Reported Outcomes Measurements (PROMIS®) questionnaires for dyspnea and fatigue collected before and at days 7, 30 and 90 after surgery, and plasma concentrations of lung injury biomarkers (IL6, IL-8, RAGE, CC16, Ang-2) analyzed from samples obtained before, end of, and 24 hours after surgery.
DISCUSSION
Participant recruitment for this study started January 2020; results are expected in 2024. At the conclusion of this trial, we will determine if this anesthesia-centered strategy focused on perioperative lung expansion reduces lung morbidity and healthcare utilization after open abdominal surgery.
TRIAL REGISTRATION
ClinicalTrial.gov NCT04108130.
Topics: Adult; Humans; Anesthesia; Lung; Lung Diseases; Multicenter Studies as Topic; Positive-Pressure Respiration; Postoperative Complications; Prospective Studies; Randomized Controlled Trials as Topic; Pragmatic Clinical Trials as Topic
PubMed: 37023031
DOI: 10.1371/journal.pone.0283748 -
Academic Emergency Medicine : Official... Oct 2022Pragmatic clinical trials (PCTs) focus on correlation between treatment and outcomes in real-world clinical practice, yet a guide highlighting key study considerations...
Pragmatic clinical trials (PCTs) focus on correlation between treatment and outcomes in real-world clinical practice, yet a guide highlighting key study considerations and design types for emergency medicine investigators pursuing this important study type is not available. Investigators conducting emergency department (ED)-based PCTs face multiple decisions within the planning phase to ensure robust and meaningful study findings. The PRagmatic Explanatory Continuum Indicator Summary 2 (PRECIS-2) tool allows trialists to consider both pragmatic and explanatory components across nine domains, shaping the trial design to the purpose intended by the investigators. Aside from the PRECIS-2 tool domains, ED-based investigators conducting PCTs should also consider randomization techniques, human subjects concerns, and integration of trial components within the electronic health record. The authors additionally highlight the advantages, disadvantages, and rationale for the use of four common randomized study design types to be considered in PCTs: parallel, crossover, factorial, and stepped-wedge. With increasing emphasis on the conduct of PCTs, emergency medicine investigators will benefit from a rigorous approach to clinical trial design.
Topics: Emergency Medicine; Humans; Pragmatic Clinical Trials as Topic; Research Design
PubMed: 35475533
DOI: 10.1111/acem.14513 -
Clinical Trials (London, England) Dec 2021Pragmatic clinical trials are increasingly used to generate knowledge about real-world clinical interventions. However, they involve some distinctive ethical and...
Pragmatic clinical trials are increasingly used to generate knowledge about real-world clinical interventions. However, they involve some distinctive ethical and regulatory challenges. In this article, we examine a set of issues related to incentives and other payments to patients in pragmatic clinical trials. Although many of the ethical concerns related to incentives and payments in explanatory trials pertain to pragmatic clinical trials, the pragmatic features may introduce additional challenges. These include those related to the risk of incentives and payments undermining the scientific validity and social value of pragmatic clinical trials, the sources of data used in pragmatic clinical trials, and when the pragmatic clinical trials are conducted under waivers of consent. Based on our examination of these matters, we offer some preliminary recommendations regarding incentives and payments in pragmatic clinical trials, recognizing that additional data and experiences are needed to refine them.
Topics: Ethics, Research; Humans; Motivation; Policy; Pragmatic Clinical Trials as Topic; Research Design
PubMed: 34766524
DOI: 10.1177/17407745211048178 -
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 -
Health Expectations : An International... Jun 2022Better transparency of research results and participant engagement may help address poor participant accrual in paediatric clinical research. We conducted formative... (Review)
Review
INTRODUCTION
Better transparency of research results and participant engagement may help address poor participant accrual in paediatric clinical research. We conducted formative research to assess the acceptability of lay summaries and thank you notes, as well as to refine and expand guidance on participant and family engagement in Pediatric Trials Network's (PTN) pragmatic paediatric clinical research.
METHODS
Informed by draft PTN guidance, we conducted in-depth qualitative interviews with adolescent clinical trial participants and caregivers of paediatric participants in four trials conducted by PTN across eight sites. Participants were shown multiple versions of mock lay summaries and thank you notes and asked questions on their preferences for content and layout, and on trial communications. We used applied thematic analysis to analyse the data.
RESULTS
We interviewed 27 individuals engaged in PTN research: 24 caregivers and 3 adolescents. During a trial, participants want regular updates on study progress, reminders of the study purpose and reassurances of data confidentiality. After the trial, participants want to learn the aggregated results, particularly medication effectiveness. Participants reported that lay summaries should include a review of the study's purpose, methods and length, and that they expect to learn individual-level results. Participants stated that thank you notes must be of sufficient length to be meaningful.
CONCLUSIONS
This is the first study to describe stakeholder preferences for thank you note content and layout. Using these findings, we finalized PTN's trial communication guidance for use in future PTN trials. Research is needed to determine the effect of lay summaries and thank you notes on improving public transparency regarding clinical trials and paediatric trial recruitment and completion.
PATIENT OR PUBLIC CONTRIBUTION
By design, stakeholders (adolescent trial participants and caregivers of pediatric trial participants) contributed to PTN's guidance on the content and layout of lay summaries and thank you notes through their participation in the in-depth interviews.
Topics: Adolescent; Caregivers; Communication; Humans; Pragmatic Clinical Trials as Topic
PubMed: 35246906
DOI: 10.1111/hex.13448 -
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 -
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 -
Journal of Clinical Epidemiology Oct 2021Feasibility studies are increasingly being used to support the development of, and investigate uncertainties around, future large-scale trials. The future trial can be...
BACKGROUND AND OBJECTIVE
Feasibility studies are increasingly being used to support the development of, and investigate uncertainties around, future large-scale trials. The future trial can be designed with either a pragmatic or explanatory mindset. Whereas pragmatic trials aim to inform the choice between different care options and thus, are designed to resemble conditions outside of a clinical trial environment, explanatory trials examine the benefit of a treatment under more controlled conditions. There is existing guidance for designing feasibility studies, but none that explicitly considers the goals of pragmatic designs. We aimed to identify unique areas of uncertainty that are relevant to planning a pragmatic trial.
RESULTS
We identified ten relevant domains, partly based on the pragmatic-explanatory continuum indicator summary-2 (PRECIS-2) framework, and describe potential questions of uncertainty within each: intervention development, research ethics, participant identification and eligibility, recruitment of individuals, setting, organization, flexibility of delivery, flexibility of adherence, follow-up, and importance of primary outcome to patients and decision-makers. We present examples to illustrate how uncertainty in these domains might be addressed within a feasibility study.
CONCLUSION
Researchers planning a feasibility study in advance of a pragmatic trial should consider feasibility objectives specifically relevant to areas of uncertainty for pragmatic trials.
Topics: Biomedical Research; Feasibility Studies; Guidelines as Topic; Humans; Pilot Projects; Pragmatic Clinical Trials as Topic; Research Design; Uncertainty
PubMed: 34229091
DOI: 10.1016/j.jclinepi.2021.06.029 -
Current Oncology Reports Apr 2020Real-world data (RWD) applications in healthcare that support learning health systems and pragmatic clinical trials are gaining momentum, largely due to legislation... (Review)
Review
PURPOSE OF REVIEW
Real-world data (RWD) applications in healthcare that support learning health systems and pragmatic clinical trials are gaining momentum, largely due to legislation supporting real-world evidence (RWE) for drug approvals. Clinical notes are thought to be the cornerstone of RWD applications, particularly for conditions with limited effective treatments, extrapolation of treatments from other conditions, or heterogenous disease biology and clinical phenotypes.
RECENT FINDINGS
Here, we discuss current issues in applying RWD captured at the point-of-care and provide a framework for clinicians to engage in RWD collection. To achieve clinically meaningful results, RWD must be reliably captured using consistent terminology in the description of our patients. RWD complements traditional clinical trials and research by informing the generalizability of results, generating new hypotheses, and creating a large data network for scientific discovery. Effective clinician engagement in the development of RWD applications is necessary for continued progress in the field.
Topics: Clinical Trials as Topic; Datasets as Topic; Drug Approval; Electronic Health Records; Humans; Molecular Biology; Point-of-Care Systems
PubMed: 32297007
DOI: 10.1007/s11912-020-00904-z