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Pharmacoepidemiology and Drug Safety Sep 2017Real-world evidence (RWE) includes data from retrospective or prospective observational studies and observational registries and provides insights beyond those addressed... (Comparative Study)
Comparative Study
Good practices for real-world data studies of treatment and/or comparative effectiveness: Recommendations from the joint ISPOR-ISPE Special Task Force on real-world evidence in health care decision making.
PURPOSE
Real-world evidence (RWE) includes data from retrospective or prospective observational studies and observational registries and provides insights beyond those addressed by randomized controlled trials. RWE studies aim to improve health care decision making.
METHODS
The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the International Society for Pharmacoepidemiology (ISPE) created a task force to make recommendations regarding good procedural practices that would enhance decision makers' confidence in evidence derived from RWD studies. Peer review by ISPOR/ISPE members and task force participants provided a consensus-building iterative process for the topics and framing of recommendations.
RESULTS
The ISPOR/ISPE Task Force recommendations cover seven topics such as study registration, replicability, and stakeholder involvement in RWE studies. These recommendations, in concert with earlier recommendations about study methodology, provide a trustworthy foundation for the expanded use of RWE in health care decision making.
CONCLUSION
The focus of these recommendations is good procedural practices for studies that test a specific hypothesis in a specific population. We recognize that some of the recommendations in this report may not be widely adopted without appropriate incentives from decision makers, journal editors, and other key stakeholders.
Topics: Advisory Committees; Decision Making; Delivery of Health Care; Economics, Pharmaceutical; Humans; Internationality; Pharmacoepidemiology; Pragmatic Clinical Trials as Topic; Prospective Studies; Retrospective Studies; Societies, Scientific; Statistics as Topic; Treatment Outcome
PubMed: 28913966
DOI: 10.1002/pds.4297 -
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 -
BMJ Open Sep 2023Incorrect penicillin allergy records are recognised as an important barrier to the safe treatment of infection and affect an estimated 2.7 million people in England....
Penicillin allergy status and its effect on antibiotic prescribing, patient outcomes and antimicrobial resistance (ALABAMA): protocol for a multicentre, parallel-arm, open-label, randomised pragmatic trial.
INTRODUCTION
Incorrect penicillin allergy records are recognised as an important barrier to the safe treatment of infection and affect an estimated 2.7 million people in England. Penicillin allergy records are associated with worse health outcome and antimicrobial resistance. The ALlergy AntiBiotics And Microbial resistAnce (ALABAMA) trial aims to determine if an intervention package, centred around a penicillin allergy assessment pathway (PAAP) initiated in primary care, is safe and effective in improving patient health outcomes and antibiotic prescribing.
METHODS AND ANALYSIS
The ALABAMA trial is a multicentre, parallel-arm, open-label, randomised pragmatic trial with a nested pilot study. Adults (≥18 years) with a penicillin allergy record and who have received antibiotics in the previous 24 months will be eligible for participation. Between 1592 and 2090 participants will be recruited from participating National Health Service general practices in England. Participants will be randomised to either usual care or intervention to undergo a pre-emptive PAAP using a 1:1 allocation ratio. The primary outcome measure is the percentage of treatment response failures within 28 days of an index prescription. 2090 and 1592 participants are estimated to provide 90% and 80% power, respectively, to detect a clinically important absolute difference of 7.9% in primary outcome at 1 year between groups. The trial includes a mixed-methods process evaluation and cost-effectiveness evaluation.
ETHICS AND DISSEMINATION
This trial has been approved by London Bridge Research Ethics Committee (ref: 19/LO/0176). It will be conducted in compliance with Good Clinical Practice guidelines according to the Declaration of Helsinki. Informed consent will be obtained from all subjects involved in the study. The primary trial results will be submitted for publication to an international, peer-reviewed journal.
TRIAL REGISTRATION
ISRCTN20579216.
Topics: Adult; Humans; Alabama; Anti-Bacterial Agents; Drug Hypersensitivity; Drug Resistance, Bacterial; Hypersensitivity; Multicenter Studies as Topic; Penicillins; Pilot Projects; Randomized Controlled Trials as Topic; State Medicine; Pragmatic Clinical Trials as Topic
PubMed: 37666558
DOI: 10.1136/bmjopen-2023-072253 -
Trials May 2023Central nervous system (CNS) active medications have been consistently linked to falls in older people. However, few randomized trials have evaluated whether CNS-active...
A health-system-embedded deprescribing intervention targeting patients and providers to prevent falls in older adults (STOP-FALLS trial): study protocol for a pragmatic cluster-randomized controlled trial.
BACKGROUND
Central nervous system (CNS) active medications have been consistently linked to falls in older people. However, few randomized trials have evaluated whether CNS-active medication reduction reduces falls and fall-related injuries. The objective of the Reducing CNS-active Medications to Prevent Falls and Injuries in Older Adults (STOP-FALLS) trial is to test the effectiveness of a health-system-embedded deprescribing intervention focused on CNS-active medications on the incidence of medically treated falls among community-dwelling older adults.
METHODS
We will conduct a pragmatic, cluster-randomized, parallel-group, controlled clinical trial within Kaiser Permanente Washington to test the effectiveness of a 12-month deprescribing intervention consisting of (1) an educational brochure and self-care handouts mailed to older adults prescribed one or more CNS-active medications (aged 60 + : opioids, benzodiazepines and Z-drugs; aged 65 + : skeletal muscle relaxants, tricyclic antidepressants, and antihistamines) and (2) decision support for their primary health care providers. Outcomes are examined over 18-26 months post-intervention. The primary outcome is first incident (post-baseline) medically treated fall as determined from health plan data. Our sample size calculations ensure at least 80% power to detect a 20% reduction in the rate of medically treated falls for participants receiving care within the intervention (n = 9) versus usual care clinics (n = 9) assuming 18 months of follow-up. Secondary outcomes include medication discontinuation or dose reduction of any target medications. Safety outcomes include serious adverse drug withdrawal events, unintentional overdose, and death. We will also examine medication signetur fields for attempts to decrease medications. We will report factors affecting implementation of the intervention.
DISCUSSION
The STOP-FALLS trial will provide new information about whether a health-system-embedded deprescribing intervention that targets older participants and their primary care providers reduces medically treated falls and CNS-active medication use. Insights into factors affecting implementation will inform future research and healthcare organizations that may be interested in replicating the intervention.
TRIAL REGISTRATION
ClinicalTrial.gov NCT05689554. Registered on 18 January 2023, retrospectively registered.
Topics: Aged; Humans; Analgesics, Opioid; Benzodiazepines; Deprescriptions; Pragmatic Clinical Trials as Topic
PubMed: 37170329
DOI: 10.1186/s13063-023-07336-7 -
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 -
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 -
Clinical Trials (London, England) Feb 2018With increasing emphasis on pragmatic trials, new randomized clinical trial designs are being proposed to enhance the "real world" nature of the data generated. We...
BACKGROUND
With increasing emphasis on pragmatic trials, new randomized clinical trial designs are being proposed to enhance the "real world" nature of the data generated. We describe one such design, appropriate for unmasked pragmatic clinical trials in which the control arm receives usual care, called "Trials within Cohorts" that is increasingly used in various countries because of its efficiency in recruitment, advantages in reducing subject burden, and ability to better mimic real-world consent processes.
METHODS
Descriptive, ethical, and US regulatory analysis of the Trials within Cohorts design.
RESULTS
Trials within Cohorts design involves, after recruitment into a cohort, randomization of eligible subjects, followed by an asymmetric treatment of the two arms: those selected for the experimental arm provide informed consent for the intervention trial, while the data from the control arm are used based on prior broad permission. Thus, unlike the traditional Zelen post-randomization consent design, the cohort participants are informed about future research within the cohort; however, the extent of this disclosure currently varies among studies. Thus, ethical analysis is provided for two types of situations: when the pre-randomization disclosure and consent regarding the embedded trials are fairly explicit and detailed versus when they consist of only general statements about future data use. These differing ethical situations could have implications for how ethics review committees apply US research rules regarding waivers and alterations of informed consent.
CONCLUSION
Trials within Cohorts is a promising new pragmatic randomized controlled trial design that is being increasingly used in various countries. Although the asymmetric consent procedures for the experimental versus control arm subjects can initially raise ethical concerns, it is ethically superior to previous post-randomization consent designs and can have important advantages over traditional trial designs.
Topics: Cohort Studies; Disclosure; Humans; Informed Consent; Random Allocation; Randomized Controlled Trials as Topic; Research Design; United States
PubMed: 29224380
DOI: 10.1177/1740774517746620 -
Contemporary Clinical Trials Aug 2022Home-based testing for COVID-19 has potential to reduce existing health care disparities among underserved populations in the United States. However, implementation of...
BACKGROUND
Home-based testing for COVID-19 has potential to reduce existing health care disparities among underserved populations in the United States. However, implementation of home-based tests in these communities may face significant barriers. This study evaluates the acceptability, feasibility, and success of home-based testing and the potential added benefit of active support from trusted community health workers for Native Americans and Hispanic/Latino adults living in rural Montana and Washington states.
METHODS/DESIGN
The academic-community research team designed the trial to be responsive to community needs for understanding barriers and supports to home-based COVID-19 testing. The "Protecting Our Community" study is a two-arm pragmatic randomized controlled trial in which a total of 400 participants are randomized to active or passive arms. Participants of both study arms receive a commercially available home collection COVID-19 test kit, which is completed by mailing a self-collected nasal swab to a central laboratory. The primary study outcome is return of the kit to the central lab within 14 days. The cultural, social, behavioral, and economic barriers to home-based COVID-19 testing are also assessed by qualitative research methods. A survey and semi-structured interviews are conducted after the trial to evaluate perceptions and experience of home-based testing.
DISCUSSION
Implementing home-based testing in underserved populations, including among Native American and Hispanic/Latino communities, may require additional support to be successful. The Protecting Our Community trial examines the effect of trusted community health workers on use of home-based testing, which may be adaptable for community-driven models of home-based testing in other underserved populations.
Topics: COVID-19; COVID-19 Testing; Hispanic or Latino; Humans; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; SARS-CoV-2; United States; American Indian or Alaska Native
PubMed: 35691487
DOI: 10.1016/j.cct.2022.106820 -
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 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