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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 -
Future Oncology (London, England) Oct 2021Oncology trials are the cornerstone of effective and safe therapeutic discoveries. However, there is increasing demand for pragmatism and patient engagement in the... (Review)
Review
Oncology trials are the cornerstone of effective and safe therapeutic discoveries. However, there is increasing demand for pragmatism and patient engagement in the design, implementation and dissemination of oncology trials. Many researchers are uncertain about making trials more practical and even less knowledgeable about how to meaningfully engage patients without compromising scientific rigor to meet regulatory requirements. The present work provides practical guidance for addressing both pragmaticism and meaningful patient engagement. Applying evidence-based approaches like PRECIS-2-tool and the 10-Step Engagement Framework offer practical guidance to make future trials in oncology truly pragmatic and patient-centered. Consequently, such patient-centered trials have improved participation, faster recruitment and greater retention, and uptake of innovative technologies in community-based care.
Topics: Humans; Neoplasms; Patient Advocacy; Patient Participation; Patient-Centered Care; Pragmatic Clinical Trials as Topic; Precision Medicine; Quality of Life; Research Design
PubMed: 34337970
DOI: 10.2217/fon-2021-0556 -
Journal of Evaluation in Clinical... Oct 2019
Topics: Bias; Clinical Trials as Topic; Comparative Effectiveness Research; Evidence-Based Practice; Humans; Treatment Outcome
PubMed: 31063238
DOI: 10.1111/jep.13155 -
Advances in Therapy Mar 2020Traditional efficacy double-blind randomised controlled trials (DBRCTs) measure the benefit a treatment produces under near-ideal test conditions in highly selected... (Review)
Review
Traditional efficacy double-blind randomised controlled trials (DBRCTs) measure the benefit a treatment produces under near-ideal test conditions in highly selected patient populations; however, the behaviour of patients and investigators in such trials is highly controlled, highly compliant and adherent, and non-representative of routine clinical practice. Pragmatic effectiveness trials measure the benefit a treatment produces in patients in everyday "real-world" practice. Ideally, effectiveness trials should recruit patients as similar as possible to those who will ultimately be prescribed the medicine, and create freedom within the study design to allow normal behaviours of patients and healthcare professionals (HCPs) to be expressed. The Salford Lung Study (SLS) was a world-first, prospective, phase III, pragmatic randomised controlled trial (RCT) programme in patients with chronic obstructive pulmonary disease and asthma to evaluate the effectiveness of a pre-licensed medication (fluticasone furoate/vilanterol) in real-world practice using electronic health records and through collaboratively engaging general practitioners and community pharmacists in clinical research. The real-world aspect of SLS was unique, requiring careful planning and attention to the goals of maximising the external validity of the trials while maintaining scientific rigour and securing suitable electronic processes for proper interpretation of safety data. Key learnings from SLS that may inform the design of future pragmatic effectiveness RCTs include: (1) ensuring the trial setting and operational infrastructure are aligned with routine clinical care; (2) recruiting a broad patient population with characteristics as close as possible to patients in routine clinical practice, to maximise the generalisability and applicability of trial results; (3) ensuring that patients and HCPs are suitably engaged in the trial, to maximise the chances of successful trial delivery; and (4) careful study design, incorporating outcomes of value to patients, HCPs, policymakers and payers, and using pre-planned analyses to address scientifically valid research hypotheses to ensure robustness of the trial data.
Topics: Androstadienes; Benzyl Alcohols; Bronchodilator Agents; Chlorobenzenes; Clinical Trials, Phase III as Topic; Double-Blind Method; Drug Therapy, Combination; Electronic Health Records; Health Behavior; Humans; Patient Selection; Product Surveillance, Postmarketing; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Reproducibility of Results
PubMed: 31927698
DOI: 10.1007/s12325-019-01192-1 -
The British Journal of Dermatology Sep 2019
Topics: Pragmatic Clinical Trials as Topic; Research Design
PubMed: 31475345
DOI: 10.1111/bjd.17889 -
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 -
American Journal of Kidney Diseases :... Jun 2021Hyperphosphatemia is a risk factor for poor clinical outcomes in patients with kidney failure receiving maintenance dialysis. Opinion-based clinical practice guidelines...
RATIONALE & OBJECTIVE
Hyperphosphatemia is a risk factor for poor clinical outcomes in patients with kidney failure receiving maintenance dialysis. Opinion-based clinical practice guidelines recommend the use of phosphate binders and dietary phosphate restriction to lower serum phosphate levels toward the normal range in patients receiving maintenance dialysis, but the benefits of these approaches and the optimal serum phosphate target have not been tested in randomized trials. It is also unknown if aggressive treatment that achieves unnecessarily low serum phosphate levels worsens outcomes.
STUDY DESIGN
Multicenter, pragmatic, cluster-randomized clinical trial.
SETTING & PARTICIPANTS
HiLo will randomize 80-120 dialysis facilities operated by DaVita Inc and the University of Utah to enroll 4,400 patients undergoing 3-times-weekly, in-center hemodialysis.
INTERVENTION
Phosphate binder prescriptions and dietary recommendations to achieve the "Hi" serum phosphate target (≥6.5 mg/dL) or the "Lo" serum phosphate target (<5.5 mg/dL).
OUTCOMES
Primary outcome: Hierarchical composite outcome of all-cause mortality and all-cause hospitalization. Main secondary outcomes: Individual components of the primary outcome.
RESULTS
The trial is currently enrolling.
LIMITATIONS
HiLo will not adjudicate causes of hospitalizations or mortality and does not protocolize use of specific phosphate binder classes.
CONCLUSIONS
HiLo aims to address an important clinical question while more generally advancing methods for pragmatic clinical trials in nephrology by introducing multiple innovative features including stakeholder engagement in the study design, liberal eligibility criteria, use of electronic informed consent, engagement of dietitians to implement the interventions in real-world practice, leveraging electronic health records to eliminate dedicated study visits, remote monitoring of serum phosphate separation between trial arms, and use of a novel hierarchical composite outcome.
TRIAL REGISTRATION
Registered at ClinicalTrials.gov with study number NCT04095039.
Topics: Humans; Hyperphosphatemia; Kidney Failure, Chronic; Multicenter Studies as Topic; Phosphates; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Renal Dialysis
PubMed: 33279558
DOI: 10.1053/j.ajkd.2020.10.008 -
American Heart Journal May 2021The MITIGATE study aims to evaluate the real-world clinical effectiveness of pre-treatment with icosapent ethyl (IPE), compared with usual care, on laboratory-confirmed...
OBJECTIVE
The MITIGATE study aims to evaluate the real-world clinical effectiveness of pre-treatment with icosapent ethyl (IPE), compared with usual care, on laboratory-confirmed viral upper respiratory infection (URI)-related morbidity and mortality in adults with established atherosclerotic cardiovascular disease (ASCVD).
BACKGROUND
IPE is a highly purified and stable omega-3 fatty acid prescription medication that is approved for cardiovascular risk reduction in high-risk adults on statin therapy with elevated triglycerides. Preclinical data and clinical observations suggest that IPE may have pleiotropic effects including antiviral and anti-inflammatory properties that may prevent or reduce the downstream sequelae and cardiopulmonary consequences of viral URIs.
METHODS
MITIGATE is a virtual, electronic health record-based, open-label, randomized, pragmatic clinical trial enrolling ∼16,500 participants within Kaiser Permanente Northern California - a fully integrated and learning health care delivery system with 21 hospitals and >255 ambulatory clinics serving ∼4.5 million members. Adults ≥50 years with established ASCVD and no prior history of coronavirus disease 2019 (COVID-19) will be prospectively identified and pre-randomized in a 1:10 allocation ratio (∼ 1,500 IPE: ∼15,000 usual care) stratified by age and previous respiratory health status to the intervention (IPE 2 grams by mouth twice daily with meals) vs the control group (usual care) for a minimum follow-up duration of 6 months. The co-primary endpoints are moderate-to-severe laboratory-confirmed viral URI and worst clinical status due to a viral URI at any point in time.
CONCLUSION
The MITIGATE study will inform clinical practice by providing evidence on the real-world clinical effectiveness of pretreatment with IPE to prevent and/or reduce the sequelae of laboratory-confirmed viral URIs in a high-risk cohort of patients with established ASCVD.
Topics: Aged; Female; Humans; Male; Middle Aged; Atherosclerosis; Cardiovascular Diseases; COVID-19; Eicosapentaenoic Acid; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intention to Treat Analysis; Platelet Aggregation Inhibitors; Prospective Studies; Respiratory Tract Infections; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Pragmatic Clinical Trials as Topic
PubMed: 33516752
DOI: 10.1016/j.ahj.2021.01.018 -
European Urology Focus Jan 2024While prehabilitation is on the verge of being a standard of care, ENHANCE is a pragmatic trial to further improve treatment of urologic cancers with an indication for...
While prehabilitation is on the verge of being a standard of care, ENHANCE is a pragmatic trial to further improve treatment of urologic cancers with an indication for surgery. The PRIMER trial and a Belgian randomized study will focus on the feasibility of at-home prehabilitation.
Topics: Humans; Postoperative Complications; Preoperative Care; Preoperative Exercise; Urology; Clinical Trials as Topic
PubMed: 37884402
DOI: 10.1016/j.euf.2023.10.011 -
Geriatric Nursing (New York, N.Y.) 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 data 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 recommended 4 cross-cutting principles key to dissemination and implementation of pragmatic trial interventions: (1) engage stakeholders, (2) ensure diversity and inclusion, (3) assess organizational strain and readiness, and (4) learn from adaptations. Specifically related to implementation, participants provided 2 recommendations: (1) integrate interventions into existing workflows and (2) maintain agility and responsiveness. Finally, participants had 3 recommendations specific to dissemination: (1) package the message for the audience, (2) engage diverse audiences, and (3) apply dissemination and diffusion tools. 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
PubMed: 35219533
DOI: 10.1016/j.gerinurse.2022.02.006