Importance of patient engagement in the conduct of pragmatic multicenter randomized controlled trials: The ADAPTABLE experience.

BACKGROUND/AIMS: Actively engaging patient partners in the conduct of trials is crucial to ensure the studies answer genuine, patient-centered, unmet clinical needs, and to facilitate participant recruitment and retention. The aim of this article is to demonstrate the feasibility of patient engagement within a large pragmatic multicenter randomized controlled trial, specifically for the purposes of dissemination of study information/updates and to favorize recruitment and retention. METHODS: In the patient-centric, pragmatic ADAPTABLE randomized trial, transparent and timely dissemination of information on the study updates to the trial participants was undertaken to create meaningful engagement and to facilitate retention. A national panel of patient partners, the Adaptors, were directly involved in this information dissemination strategy, and study participants were engaged both nationally and locally to design recruitment methods iteratively during the conduct of the trial. All Adaptors had a lived experience with cardiovascular disease. RESULTS: Adaptors attended bi-weekly meetings facilitated by the director of the study's patient-powered research network. They drafted and/or edited newsletters and ad hoc educational information written in a lay-friendly manner for study participants, which were regularly distributed to the ADAPTABLE community, in addition to online forums where participants could share their experience of their involvement in ADAPTABLE. To spur recruitment, a patient-driven initiative was to draft letters sharing their story, which were distributed by the local study teams. Patient partners thought that using patients' voice to provide their perspectives on why they believed this project was important would be more engaging for prospective participants than traditional approaches. CONCLUSIONS: ADAPTABLE's experience has demonstrated the feasibility of engaging patients as partners in the conduct of a large-scale, multi-center, pragmatic randomized controlled trial. Future trials should embrace and iteratively improve this model by engaging patient partners as early as study protocol development and funding applications, and quantify its impact on the effectiveness and value of the trial.

Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and COVID-19-related outcomes: A patient-level analysis of the PCORnet blood pressure control lab.

SARS-CoV-2 accesses host cells via angiotensin-converting enzyme-2, which is also affected by commonly used angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), raising concerns that ACEI or ARB exposure may portend differential COVID-19 outcomes. In parallel cohort studies of outpatient and inpatient COVID-19-diagnosed adults with hypertension, we assessed associations between antihypertensive exposure (ACEI/ARB vs. non-ACEI/ARB antihypertensives, as well as between ACEI- vs. ARB) at the time of COVID-19 diagnosis, using electronic health record data from PCORnet health systems. The primary outcomes were all-cause hospitalization or death (outpatient cohort) or all-cause death (inpatient), analyzed via Cox regression weighted by inverse probability of treatment weights. From February 2020 through December 9, 2020, 11,246 patients (3477 person-years) and 2200 patients (777 person-years) were included from 17 health systems in outpatient and inpatient cohorts, respectively. There were 1015 all-cause hospitalization or deaths in the outpatient cohort (incidence, 29.2 events per 100 person-years), with no significant difference by ACEI/ARB use (adjusted HR 1.01; 95% CI 0.88, 1.15). In the inpatient cohort, there were 218 all-cause deaths (incidence, 28.1 per 100 person-years) and ACEI/ARB exposure was associated with reduced death (adjusted HR, 0.76; 95% CI, 0.57, 0.99). ACEI, versus ARB exposure, was associated with higher risk of hospitalization in the outpatient cohort, but no difference in all-cause death in either cohort. There was no evidence of effect modification across pre-specified baseline characteristics. Our results suggest ACEI and ARB exposure have no detrimental effect on hospitalizations and may reduce death among hypertensive patients diagnosed with COVID-19.

An online intervention for increasing physical activity in individuals with mood disorders at risk for cardiovascular disease: Design considerations.

BACKGROUND: Physical activity can mitigate the risk of cardiovascular diseases, but the presence of mood disorders makes it challenging to follow or develop a regular exercise habit. We conducted an online comparative effectiveness study (Healthy Hearts Healthy Minds) to evaluate whether an online psychosocial intervention adjunctive to an activity monitor (Fitbit) can improve adherence to physical activity among individuals with mood disorders who have or are at-risk for cardiovascular disease (CVD). METHODS: In this paper, we explore design considerations (including both procedural challenges and achievements) of relevance to our study. RESULTS: Challenges of this study included navigating a complex IRB review process, integrating two study platforms, automating study procedures, and optimizing participant engagement. Achievements of this study included building trust with collaborators, leveraging existing online communities, generating daily data reports, and conducting patient-centered research. LIMITATIONS: These design considerations are based on a single online comparative effectiveness study, and other online intervention studies may be presented with other unique challenges that are specific to their study format or aims. Consistent with some of the generalizability challenges facing other online studies, participants in this study were overall highly educated (most had at least a college degree). CONCLUSIONS: We successfully conducted a large-scale virtual online intervention to increase physical activity of participants with comorbid mood and cardiovascular disorders by overcoming substantial operational and technical challenges. We hope that this exploration of design considerations in the context of our online study can inform upcoming online intervention studies.

The PCORnet Blood Pressure Control Laboratory: A Platform for Surveillance and Efficient Trials.

BACKGROUND: Uncontrolled blood pressure (BP) is a leading preventable cause of death that remains common in the US population despite the availability of effective medications. New technology and program innovation has high potential to improve BP but may be expensive and burdensome for patients, clinicians, health systems, and payers and may not produce desired results or reduce existing disparities in BP control. METHODS AND RESULTS: The PCORnet Blood Pressure Control Laboratory is a platform designed to enable national surveillance and facilitate quality improvement and comparative effectiveness research. The platform uses PCORnet, the National Patient-Centered Clinical Research Network, for engagement of health systems and collection of electronic health record data, and the Eureka Research Platform for eConsent and collection of patient-reported outcomes and mHealth data from wearable devices and smartphones. Three demonstration projects are underway: BP track will conduct national surveillance of BP control and related clinical processes by measuring theory-derived pragmatic BP control metrics using electronic health record data, with a focus on tracking disparities over time; BP MAP will conduct a cluster-randomized trial comparing effectiveness of 2 versions of a BP control quality improvement program; BP Home will conduct an individual patient-level randomized trial comparing effectiveness of smartphone-linked versus standard home BP monitoring. Thus far, BP Track has collected electronic health record data from over 826 000 eligible patients with hypertension who completed ≈3.1 million ambulatory visits. Preliminary results demonstrate substantial room for improvement in BP control (<140/90 mm Hg), which was 58% overall, and in the clinical processes relevant for BP control. For example, only 12% of patients with hypertension with a high BP measurement during an ambulatory visit received an order for a new antihypertensive medication. CONCLUSIONS: The PCORnet Blood Pressure Control Laboratory is designed to be a reusable platform for efficient surveillance and comparative effectiveness research; results from demonstration projects are forthcoming.

Rationale and Design of the Aspirin Dosing-A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE) Trial.

Importance: Determining the right dosage of aspirin for the secondary prevention treatment of atherosclerotic cardiovascular disease (ASCVD) remains an unanswered and critical question. Objective: To report the rationale and design for a randomized clinical trial to determine the optimal dosage of aspirin to be used for secondary prevention of ASCVD, using an innovative research method. Design, Setting, and Participants: This pragmatic, open-label, patient-centered, randomized clinical trial is being conducted in 15 000 patients within the National Patient-Centered Clinical Research Network (PCORnet), a distributed research network of partners including clinical research networks, health plan research networks, and patient-powered research networks across the United States. Patients with established ASCVD treated in routine clinical practice within the network are eligible. Patient recruitment began in April 2016. Enrollment was completed in June 2019. Final follow-up is expected to be completed by June 2020. Interventions: Participants are randomized on a web platform in a 1:1 fashion to either 81 mg or 325 mg of aspirin daily. Main Outcomes and Measures: The primary efficacy end point is the composite of all-cause mortality, hospitalization for nonfatal myocardial infarction, or hospitalization for a nonfatal stroke. The primary safety end point is hospitalization for major bleeding associated with a blood-product transfusion. End points are captured through regular queries of the health systems' common data model within the structure of PCORnet's distributed data environment. Conclusions and Relevance: As a pragmatic study and the first interventional trial conducted within the PCORnet electronic data infrastructure, this trial is testing several unique and innovative operational approaches that have the potential to disrupt and transform the conduct of future patient-centered randomized clinical trials by evaluating treatments integrated in clinical practice while at the same time determining the optimal dosage of aspirin for secondary prevention of ASCVD. Trial Registration: ClinicalTrials.gov Identifier: NCT02697916.

Patient-reported triggers of paroxysmal atrial fibrillation.

BACKGROUND: Triggers for discrete atrial fibrillation (AF) events remain poorly studied and incompletely characterized. OBJECTIVE: The purpose of this study was to describe common triggers for AF and their relationships with patient characteristics. METHODS: We invited symptomatic, paroxysmal AF patients enrolled in the Health eHeart Study and through the patient-centered advocacy organization StopAfib.org to complete a questionnaire regarding their AF triggers and cardiovascular risk factors. RESULTS: Of 1295 participants with symptomatic AF, 957 (74%) reported triggers for episodes of AF. In comparison to participants without triggers and after multivariate adjustment, those reporting triggers had a 71% lower odds of congestive heart failure (odds ratio [OR] 0.29; 95% confidence interval [CI] 0.14-0.60; P = .001) and a >2-fold greater odds of a family history of AF (OR 2.04; 95% CI 1.21-3.47; P = .008). The most commonly reported triggers were alcohol (35%), caffeine (28%), exercise (23%), and lack of sleep (21%). Multivariable models revealed that younger patients, women, and those with an AF family history more commonly experienced various triggers. Patients reported a median of 2 different triggers (interquartile range 1-3). Female sex, Hispanic ethnicity, obstructive sleep apnea, and a family history of AF were each associated with a greater number of AF triggers. Vagally mediated triggers tended to cluster together within individuals. CONCLUSION: The majority of patient-reported triggers are modifiable, potentially identifying accessible means to prevent and reduce AF episodes. Exploring the interactions between AF patient type, including underlying genetic differences, and common exposures may be fruitful areas of investigation.

Exploring Meaningful Patient Engagement in ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-term Effectiveness).

BACKGROUND: Genuine patient engagement can improve research relevance, impact and is required for studies using the National Patient-Centered Clinical Research Network including major multicenter research projects. It is unclear, however, how best to integrate patients into governance of such projects. METHODS: ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-term Effectiveness) is the first major multicenter research project to be conducted in National Patient-Centered Clinical Research Network. Here, we provide a description of how we implemented patient engagement in ADAPTABLE thus far, including a description of committee structures and composition, first-hand patient testimonials, specific contributions, and lessons learned during the planning and early implementation of ADAPTABLE. RESULTS: We recruited 1 patient leader from 6 of the 7 enrolling networks to serve on a Patient Review Board for ADAPTABLE, supported the Board with an experienced patient engagement team including an "investigator-advocate" not otherwise involved in the trial, and facilitated bidirectional communication between the Board and ADAPTABLE Coordinating Center. The Board has reviewed and provided substantial input on the informed consent procedure, recruitment materials, patient portal design, and study policy including compensation of participants. Although it was "too late" for some suggested modifications, most modifications suggested by the patient leaders have been implemented, and they are enthusiastic about the study and their role. The patient leaders also attend Steering and Executive Committee calls; these experiences have been somewhat less productive. CONCLUSIONS: With adequate support, a cadre of committed patient leaders can provide substantial value to design and implementation of a major multicenter clinical trial.

Impact of patients' psychiatric hospitalization on caregivers: a systematic review.

OBJECTIVE: A systematic literature review was conducted to assess the impact of patients' psychiatric hospitalizations on caregivers. METHODS: A systematic search of the Web of Knowledge, PsycINFO, and MEDLINE (PubMed) was conducted for peer-reviewed articles published in English before August 31, 2013. Qualitative, quantitative, and mixed-methods studies were included if they focused on the outcomes of caregivers of either adult or youth patients and presented data collected directly from caregivers of patients who had been psychiatrically hospitalized. RESULTS: Twenty-nine articles met the inclusion criteria. The review found that caregivers are heterogeneous in their reaction to patients' psychiatric hospitalization; however, many report distress. Many caregivers have reported experiencing stigma, disruptions in daily life, worse general medical health, economic strain, and changes in relationships after hospitalization. Negative reactions to the hospitalization may decrease over time, but distress can remain elevated compared with the general population. Nonetheless, many caregivers have also reported experiencing positive changes as a result of the hospitalization. The reaction of caregivers may be influenced by the severity of the patient's psychiatric problems as well as the caregiver's demographic characteristics and style of coping. CONCLUSIONS: Caregivers experience a range of reactions to psychiatric hospitalizations. Providing caregivers with psychoeducation about their possible reaction to hospitalization and teaching them coping techniques may improve clinical outcomes for patients. Future research is needed to understand the heterogeneity in caregivers' reactions to patients' psychiatric hospitalization.

Suicide attempts in a longitudinal sample of adolescents followed through adulthood: Evidence of escalation.

OBJECTIVES: This study was designed to examine escalation in repeat suicide attempts from adolescence through adulthood, as predicted by sensitization models (and reflected in increasing intent and lethality with repeat attempts, decreasing amount of time between attempts, and decreasing stress to trigger attempts). METHOD: In a prospective study of 180 adolescents followed through adulthood after a psychiatric hospitalization, suicide attempts, and antecedent life events were repeatedly assessed (M = 12.6 assessments, SD = 5.1) over an average of 13 years 6 months (SD = 4 years 5 months). Multivariate logistic, multiple linear, and negative binomial regression models were used to examine patterns over time. RESULTS: After age 17-18, the majority of suicide attempts were repeat attempts (i.e., made by individuals with prior suicidal behavior). Intent increased both with increasing age, and with number of prior attempts. Medical lethality increased as a function of age but not recurrent attempts. The time between successive suicide attempts decreased as a function of number of attempts. The amount of precipitating life stress was not related to attempts. CONCLUSIONS: Adolescents and young adults show evidence of escalation of recurrent suicidal behavior, with increasing suicidal intent and decreasing time between successive attempts. However, evidence that sensitization processes account for this escalation was inconclusive. Effective prevention programs that reduce the likelihood of individuals attempting suicide for the first time (and entering this cycle of escalation), and relapse prevention interventions that interrupt the cycle of escalating suicidal behavior among individuals who already have made attempts are critically needed. (PsycINFO Database Record