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PloS One 2024Emulation of the "target trial" (TT), a hypothetical pragmatic randomized controlled trial (RCT), using observational data can be used to mitigate issues commonly...
Designing target trials using electronic health records: A case study of second-line disease-modifying anti-rheumatic drugs and cardiovascular disease outcomes in patients with rheumatoid arthritis.
BACKGROUND
Emulation of the "target trial" (TT), a hypothetical pragmatic randomized controlled trial (RCT), using observational data can be used to mitigate issues commonly encountered in comparative effectiveness research (CER) when randomized trials are not logistically, ethically, or financially feasible. However, cardiovascular (CV) health research has been slow to adopt TT emulation. Here, we demonstrate the design and analysis of a TT emulation using electronic health records to study the comparative effectiveness of the addition of a disease-modifying anti-rheumatic drug (DMARD) to a regimen of methotrexate on CV events among rheumatoid arthritis (RA) patients.
METHODS
We used data from an electronic medical records-based cohort of RA patients from Northwestern Medicine to emulate the TT. Follow-up began 3 months after initial prescription of MTX (2000-2020) and included all available follow-up through June 30, 2020. Weighted pooled logistic regression was used to estimate differences in CVD risk and survival. Cloning was used to handle immortal time bias and weights to improve baseline and time-varying covariate imbalance.
RESULTS
We identified 659 eligible people with RA with average follow-up of 46 months and 31 MACE events. The month 24 adjusted risk difference for MACE comparing initiation vs non-initiation of a DMARD was -1.47% (95% confidence interval [CI]: -4.74, 1.95%), and the marginal hazard ratio (HR) was 0.72 (95% CI: 0.71, 1.23). In analyses subject to immortal time bias, the HR was 0.62 (95% CI: 0.29-1.44).
CONCLUSION
In this sample, we did not observe evidence of differences in risk of MACE, a finding that is compatible with previously published meta-analyses of RCTs. Thoughtful application of the TT framework provides opportunities to conduct CER in observational data. Benchmarking results of observational analyses to previously published RCTs can lend credibility to interpretation.
Topics: Humans; Arthritis, Rheumatoid; Antirheumatic Agents; Electronic Health Records; Cardiovascular Diseases; Female; Male; Middle Aged; Methotrexate; Aged; Treatment Outcome; Randomized Controlled Trials as Topic; Comparative Effectiveness Research; Adult
PubMed: 38875273
DOI: 10.1371/journal.pone.0305467 -
Resuscitation Plus Sep 2024Prospective, trial-based data comparing health-related quality of life (HRQoL) in patients surviving out-of-hospital cardiac arrest (OHCA) through extracorporeal...
BACKGROUND
Prospective, trial-based data comparing health-related quality of life (HRQoL) in patients surviving out-of-hospital cardiac arrest (OHCA) through extracorporeal cardiopulmonary resuscitation (ECPR) or conventional CPR (CCPR) are scarce. We aimed to determine HRQoL during 1-year after refractory OHCA in patients treated with ECPR and CCPR.
METHODS
We present a secondary analysis of the multicenter INCEPTION-trial, which studied the effectiveness of ECPR versus CCPR in patients with refractory OHCA. HRQoL was prospectively assessed using the EQ-5D-5L questionnaire. Poor HRQoL was pragmatically defined as an EQ-5D-5L health utility index (HUI) > 1 SD below the age-adjusted norm. We used mixed linear models to assess the difference in HRQoL over time and univariable analyses to assess factors potentially associated with poor HRQoL.
RESULTS
A total of 134 patients were enrolled, and hospital survival was 20% (27 patients). EQ-5D-5L data were available for 25 patients (5 ECPR and 20 CCPR). One year after OHCA, the estimated mean HUI was 0.73 (0.05) in all patients, 0.84 (0.12) in ECPR survivors, and 0.71 (0.05) in CCPR survivors (p-value 0.31). Eight (32%) survivors had a poor HRQoL. HRQoL was good in 17 (68%) patients, with 100% in ECPR survivors versus 60% in CCPR survivors (p-value 0.14).
CONCLUSION
One year after refractory OHCA, 68% of the survivors had a good HRQoL. We found no statistically significant difference in HRQoL one year after OHCA in patients treated with ECPR compared to CCPR. However, numerical differences may be clinically relevant in favor of ECPR.
PubMed: 38873275
DOI: 10.1016/j.resplu.2024.100669 -
BMJ Open Jun 2024Clinical assessment in emergency departments (EDs) for possible acute myocardial infarction (AMI) requires at least one cardiac troponin (cTn) blood test. The...
Protocol for Improving Care by FAster risk-STratification through use of high sensitivity point-of-care troponin in patients presenting with possible acute coronary syndrome in the EmeRgency department (ICare-FASTER): a stepped-wedge cluster randomised quality improvement initiative.
INTRODUCTION
Clinical assessment in emergency departments (EDs) for possible acute myocardial infarction (AMI) requires at least one cardiac troponin (cTn) blood test. The turn-around time from blood draw to posting results in the clinical portal for central laboratory analysers is ~1-2 hours. New generation, high-sensitivity, point-of-care cardiac troponin I (POC-cTnI) assays use whole blood on a bedside (or near bedside) analyser that provides a rapid (8 min) result. This may expedite clinical decision-making and reduce length of stay. Our purpose is to determine if utilisation of a POC-cTnI testing reduces ED length of stay. We also aim to establish an optimised implementation process for the amended clinical pathway.
METHODS AND ANALYSIS
This quality improvement initiative has a pragmatic multihospital stepped-wedge cross-sectional cluster randomised design. Consecutive patients presenting to the ED with symptoms suggestive of possible AMI and having a cTn test will be included. Clusters (comprising one or two hospitals each) will change from their usual-care pathway to an amended pathway using POC-cTnI-the 'intervention'. The dates of change will be randomised. Changes occur at 1 month intervals, with a minimum 2 month 'run-in' period. The intervention pathway will use a POC-cTnI measurement as an alternate to the laboratory-based cTn measurement. Clinical decision-making steps and logic will otherwise remain unchanged. The POC-cTnI is the Siemens (Erlangen Germany) Atellica VTLi high-sensitivity cTnI assay. The primary outcome is ED length of stay. The safety outcome is cardiac death or AMI within 30 days for patients discharged directly from the ED.
ETHICS AND DISSEMINATION
Ethics approval has been granted by the New Zealand Southern Health and Disability Ethics Committee, reference 21/STH/9. Results will be published in a peer-reviewed journal. Lay and academic presentations will be made. Māori-specific results will be disseminated to Māori stakeholders.
TRIAL REGISTRATION NUMBER
ACTRN12619001189112.
Topics: Humans; Emergency Service, Hospital; Quality Improvement; Acute Coronary Syndrome; Point-of-Care Systems; Cross-Sectional Studies; Risk Assessment; Troponin I; Myocardial Infarction; Length of Stay; Point-of-Care Testing; Biomarkers; Clinical Decision-Making
PubMed: 38871661
DOI: 10.1136/bmjopen-2023-083752 -
JMIR Formative Research Jun 2024Chronic kidney disease (CKD) is a major public health concern. Adequate self-management skills are vital to reduce CKD burden, optimize patient health outcomes, and...
BACKGROUND
Chronic kidney disease (CKD) is a major public health concern. Adequate self-management skills are vital to reduce CKD burden, optimize patient health outcomes, and control health care expenditures. Using eHealth to support CKD self-management has the potential to promote healthy behaviors and improve health outcomes of patients with CKD. However, knowledge of the implementation of such interventions in general, and in China specifically, is still limited.
OBJECTIVE
This study aims to develop a tailored eHealth self-management intervention for patients with CKD in China based on the Dutch Medical Dashboard (MD) eHealth self-management intervention.
METHODS
We used an intervention mapping approach. In phase 1, a systematic review and 2 qualitative studies were conducted to examine the needs, beliefs, and perceptions of patients with CKD and health care professionals regarding CKD self-management and eHealth interventions. Afterward, key factors gathered from the aforementioned studies were categorized following the 5 domains of the Consolidated Framework for Implementation Research (CFIR). In phase 2, we specified program outcomes, performance objectives, determinants, theory-based methods, and practical strategies. Knowledge obtained from previous results was combined to complement core components of the MD self-management intervention and adapt them for Chinese patients with CKD. Additionally, the CFIR-Expert Recommendations for Implementing Change Matching Tool was pragmatically used to generate a list of potential implementation strategies to address the key factors influencing the implementation of eHealth CKD self-management interventions, and implementation strategies were discussed and finalized with the intervention monitoring group.
RESULTS
An overview of the CFIR domains showed the essential factors influencing the implementation of eHealth CKD self-management interventions in Chinese settings, including "knowledge and beliefs" in the domain "individual characteristics," "quality and advantage of eHealth intervention" in the domain "intervention characteristics," "compatibility" in the domain "inner setting," and "cultural context" in the domain "outer setting." To ensure the effectiveness of the Dutch MD-based self-management intervention, we did not change the core self-management intervention components of MD that underlie its effectiveness, such as self-monitoring. We identified surface-level cultural adaptations involving customizing intervention content, messages, and approaches to the observable cultural characteristics of the local population to enhance the intervention's appeal, receptivity, and feasibility, such as providing video or voice call options to support interactions with health care professionals. Furthermore, the adapted modules such as Knowledge Center and My Self-Monitoring were developed in a mobile health app.
CONCLUSIONS
Our study resulted in the delivery of a culturally tailored, standardized eHealth self-management intervention for patients with CKD in China that has the potential to optimize patients' self-management skills and improve health status and quality of life. Moreover, our study's research approach and results can inform future research on the tailoring and translation of evidence-based, eHealth self-management interventions to various contexts.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04212923; https://classic.clinicaltrials.gov/ct2/show/NCT04212923.
PubMed: 38869943
DOI: 10.2196/48605 -
BMJ (Clinical Research Ed.) Jun 2024
PubMed: 38866412
DOI: 10.1136/bmj.q1261 -
JMIR Research Protocols Jun 2024Clinical trials examining lifestyle interventions for weight loss in cancer survivors have been demonstrated to be safe, feasible, and effective. However, scalable...
BACKGROUND
Clinical trials examining lifestyle interventions for weight loss in cancer survivors have been demonstrated to be safe, feasible, and effective. However, scalable weight loss programs are needed to support their widespread implementation. The ASPIRE trial was designed to evaluate real-world, lifestyle-based, weight loss programs for cancer survivors throughout Maryland.
OBJECTIVE
The objectives of this protocol paper are to describe the design of a nonrandomized pragmatic trial, study recruitment, and baseline characteristics of participants.
METHODS
Participants were aged ≥18 years, residing in Maryland, with a BMI ≥25 kg/m, who reported a diagnosis of a malignant solid tumor, completed curative treatment, and had no ongoing or planned cancer treatment. Enrollment criteria were minimized to increase generalizability. The primary recruitment source was the Johns Hopkins Health System electronic health records (EHRs). Participants selected 1 of 3 remotely delivered weight loss programs: self-directed, app-supported, or coach-supported program.
RESULTS
Participants were recruited across all 5 geographic regions of Maryland. Targeted invitations using EHRs accounted for 287 (84.4%) of the 340 participants enrolled. Of the 5644 patients invited through EHR, 5.1% (287/5644) enrolled. Participants had a mean age of 60.7 (SD 10.8) years, 74.7% (254/340) were female, 55.9% (190/340) identified as non-Hispanic Black, 58.5% (199/340) had a bachelor's degree, and the average BMI was 34.1 kg/m (SD 5.9 kg/m). The most common types of cancers were breast (168/340, 49.4%), prostate (72/340, 21.2%), and thyroid (39/340, 8.5%). The self-directed weight loss program (n=91) included 25 participants who agreed to provide weights through a study scale; the app-supported program (n=142) included 108 individuals who agreed to provide their weight measurements; and the coach-supported weight loss program included 107 participants. We anticipate final analysis will take place in the fall of 2024.
CONCLUSIONS
Using EHR-based recruitment efforts, this study took a pragmatic approach to reach and enroll cancer survivors into remotely delivered weight loss programs.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04534309; https://clinicaltrials.gov/study/NCT04534309.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/54126.
Topics: Humans; Female; Cancer Survivors; Male; Maryland; Middle Aged; Weight Reduction Programs; Adult; Aged; Weight Loss; Neoplasms
PubMed: 38865181
DOI: 10.2196/54126 -
Journal of Primary Care & Community... 2024Recruiting organizations (i.e., health plans, health systems, or clinical practices) is important for implementation science, yet limited research explores effective...
INTRODUCTION
Recruiting organizations (i.e., health plans, health systems, or clinical practices) is important for implementation science, yet limited research explores effective strategies for engaging organizations in pragmatic studies. We explore the effort required to meet recruitment targets for a pragmatic implementation trial, characteristics of engaged and non-engaged clinical practices, and reasons health plans and rural clinical practices chose to participate.
METHODS
We explored recruitment activities and factors associated with organizational enrollment in SMARTER CRC, a randomized pragmatic trial to increase rates of CRC screening in rural populations. We sought to recruit 30 rural primary care practices within participating Medicaid health plans. We tracked recruitment outreach contacts, meeting content, and outcomes using tracking logs. Informed by the Consolidated Framework for Implementation Research, we analyzed interviews, surveys, and publicly available clinical practice data to identify facilitators of participation.
RESULTS
Overall recruitment activities spanned January 2020 to April 2021. Five of the 9 health plans approached agreed to participate (55%). Three of the health plans chose to operate centrally as 1 site based on network structure, resulting in 3 recruited health plan sites. Of the 101 identified practices, 76 met study eligibility criteria; 51% (n = 39) enrolled. Between recruitment and randomization, 1 practice was excluded, 5 withdrew, and 7 practices were collapsed into 3 sites for randomization purposes based on clinical practice structure, leaving 29 randomized sites. Successful recruitment required iterative outreach across time, with a range of 2 to 17 encounters per clinical practice. Facilitators to recruitment included multi-modal outreach, prior relationships, effective messaging, flexibility, and good timing.
CONCLUSION
Recruiting health plans and rural clinical practices was complex and iterative. Leveraging existing relationships and allocating time and resources to engage clinical practices in pragmatic implementation research may facilitate more diverse representation in future trials and generalizability of research findings.
Topics: Humans; Early Detection of Cancer; Primary Health Care; United States; Rural Health Services; Patient Selection; Rural Population; Colorectal Neoplasms; Medicaid; Community-Institutional Relations
PubMed: 38864248
DOI: 10.1177/21501319241259915 -
Registry-based randomised controlled trials: conduct, advantages and challenges-a systematic review.Trials Jun 2024Registry-based randomised controlled trials (rRCTs) have been described as pragmatic studies utilising patient data embedded in large-scale registries to facilitate key...
BACKGROUND
Registry-based randomised controlled trials (rRCTs) have been described as pragmatic studies utilising patient data embedded in large-scale registries to facilitate key clinical trial procedures including recruitment, randomisation and the collection of outcome data. Whilst the practice of utilising registries to support the conduct of randomised trials is increasing, the use of the registries within rRCTs is inconsistent. The purpose of this systematic review is to explore the conduct of rRCTs using a patient registry to facilitate trial recruitment and the collection of outcome data, and to discuss the advantages and challenges of rRCTs.
METHODS
A systematic search of the literature was conducted using five databases from inception to June 2020: PubMed, Embase (through Ovid), CINAHL, Scopus and the Cochrane Controlled Register of Trials (CENTRAL). The search strategy comprised of MESH terms and key words related to rRCTs. Study selection was performed independently by two reviewers. A risk of bias for each study was completed. A narrative synthesis was conducted.
RESULTS
A total 47,862 titles were screened and 24 rRCTs were included. Eleven rRCTs (45.8%) used more than one registry to facilitate trial conduct. Six rRCTs (25%) randomised participants via a specific randomisation module embedded within a registry. Recruitment ranged between 209 to 106,000 participants. Advantages of rRCTs are recruitment efficiency, shorter trial times, cost effectiveness, outcome data completeness, smaller carbon footprint, lower participant burden and the ability to conduct multiple trials from the same registry. Challenges are data collection/management, quality assurance issues and the timing of informed consent.
CONCLUSIONS
Optimising the design of rRCTs is dependent on the capabilities of the registry. New registries should be designed and existing registries reviewed to enable the conduct of rRCTs. At all times, data management and quality assurance of all registry data should be given key consideration. We suggest the inclusion of the term 'registry-based' in the title of all rRCT manuscripts and a clear simple breakdown of the registry-based conduct of the trial in the abstract to facilitate indexing in the major databases.
Topics: Humans; Patient Selection; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Registries; Research Design
PubMed: 38863017
DOI: 10.1186/s13063-024-08209-3 -
Clinical and Translational Science Jun 2024Specific selective serotonin reuptake inhibitors (SSRIs) metabolism is strongly influenced by two pharmacogenes, CYP2D6 and CYP2C19. However, the effectiveness of... (Randomized Controlled Trial)
Randomized Controlled Trial
Specific selective serotonin reuptake inhibitors (SSRIs) metabolism is strongly influenced by two pharmacogenes, CYP2D6 and CYP2C19. However, the effectiveness of prospectively using pharmacogenetic variants to select or dose SSRIs for depression is uncertain in routine clinical practice. The objective of this prospective, multicenter, pragmatic randomized controlled trial is to determine the effectiveness of genotype-guided selection and dosing of antidepressants on control of depression in participants who are 8 years or older with ≥3 months of depressive symptoms who require new or revised therapy. Those randomized to the intervention arm undergo pharmacogenetic testing at baseline and receive a pharmacy consult and/or automated clinical decision support intervention based on an actionable phenotype, while those randomized to the control arm have pharmacogenetic testing at the end of 6-months. In both groups, depression and drug tolerability outcomes are assessed at baseline, 1 month, 3 months (primary), and 6 months. The primary end point is defined by change in Patient-Reported Outcomes Measurement Information System (PROMIS) Depression score assessed at 3 months versus baseline. Secondary end points include change inpatient health questionnaire (PHQ-8) measure of depression severity, remission rates defined by PROMIS score < 16, medication adherence, and medication side effects. The primary analysis will compare the PROMIS score difference between trial arms among those with an actionable CYP2D6 or CYP2C19 genetic result or a CYP2D6 drug-drug interaction. The trial has completed accrual of 1461 participants, of which 562 were found to have an actionable phenotype to date, and follow-up will be complete in April of 2024.
Topics: Humans; Cytochrome P-450 CYP2D6; Selective Serotonin Reuptake Inhibitors; Pharmacogenomic Testing; Cytochrome P-450 CYP2C19; Depression; Prospective Studies; Female; Male; Pharmacogenomic Variants; Adult; Pragmatic Clinical Trials as Topic; Antidepressive Agents
PubMed: 38860639
DOI: 10.1111/cts.13822 -
Journal of Asthma and Allergy 2024
PubMed: 38860029
DOI: 10.2147/JAA.S451689