Strategies for secondary use of real-world clinical and administrative data for outcome ascertainment in pragmatic clinical trials.

BACKGROUND: Pragmatic trials are gaining popularity as a cost-effective way to examine treatment effectiveness and generate timely comparative evidence. Incorporating supplementary real-world data is recommended for robust outcome monitoring. However, detailed operational guidelines are needed to inform effective use and integration of heterogeneous databases. OBJECTIVE: Lessons learned from the Veterans Affairs (VA) Diuretic Comparison Project (DCP) are reviewed, providing adaptable recommendations to capture clinical outcomes from real-world data. METHODS: Non-cancer deaths and major cardiovascular (CV) outcomes were determined using VA, Medicare, and National Death Index (NDI) data. Multiple ascertainment strategies were applied, including claims-based algorithms, natural language processing, and systematic chart review. RESULTS: During a mean follow-up of 2.4 (SD = 1.4) years, 907 CV events were identified within the VA healthcare system. Slight delays (∼1 year) were expected in obtaining Medicare data. An additional 298 patients were found having a CV event outside of the VA in 2016 - 2021, increasing the CV event rate from 3.5 % to 5.7 % (770 of 13,523 randomized). NDI data required âˆ¼2 years waiting period. Such inclusion did not increase the number of deaths identified (all 894 deaths were captured by VA data) but enhanced the accuracy in determining cause of death. CONCLUSION: Our experience supports the recommendation of integrating multiple data sources to improve clinical outcome ascertainment. While this approach is promising, hierarchical data aggregation is required when facing different acquisition timelines, information availability/completeness, coding practice, and system configurations. It may not be feasible to implement comparable applications and solutions to studies conducted under different constraints and practice. The recommendations provide guidance and possible action plans for researchers who are interested in applying cross-source data to ascertain all study outcomes.

A Centralized EHR-Based Model for the Recruitment of Rural and Lower Socioeconomic Participants in Pragmatic Trials: A Secondary Analysis of the Diuretic Comparison Project.

Importance: Participant diversity is important for reducing study bias and increasing generalizability of comparative effectiveness research. Objective: Demonstrate the operational efficiency of a centralized electronic health record (EHR)-based model for recruiting difficult-to-reach participants in a pragmatic trial. Design, Setting, and Participants: This comparative effectiveness study was a secondary analysis of Diuretic Comparison Project, a randomized clinical trial conducted between 2016 and 2022 (mean [SD] follow-up, 2.4 [1.4] years) comparing 2 commonly prescribed antihypertensives, which used an EHR-based recruitment model. Electronic study workflows, in tandem with routine clinical practice, were adapted by 72 Veteran Affairs (VA) primary care networks. Data were analyzed from August to December 2022. Main Outcomes and Measures: Measures reflecting recruitment capacity (monthly rate), operational efficiency (median time for completion of electronic procedures), and geographic reach (percentage of patients recruited from rural areas) were examined. Results: A total of 13 523 patients with hypertension (mean [SD] age, 72 [5.4] years; 13 092 male [96.8%]) were recruited from 537 outpatient clinics. Approximately 205 patients were randomized per month and a median of 35 days (Q1-Q3, 23-80 days) was needed to complete electronic recruitment. The annual income was below the national median for 69% of the cohort. Patients from all 50 states, Puerto Rico, and the District of Columbia were included and 45% resided in rural areas. Conclusions and Relevance: In this secondary analysis of a multicenter pragmatic trial, a centralized EHR-based recruitment model was associated with improved participation from underrepresented groups. These participants often are difficult to reach, with their exclusion potentially biasing trial results; eliminating in-person study visits and local site involvement can minimize barriers for the recruitment of patients from rural and lower socioeconomic areas. Trial Registration: The Diuretic Comparison Project (DCP) was registered on ClinicalTrials.gov Identifier: NCT02185417.

Veterans Healthcare Administration providers' attitudes and perceptions regarding pragmatic trials embedded at the point of care.

Background The Veterans Healthcare Administration (VA) is implementing an adaptation of a pragmatic trial program, Point of Care Research (POC-R). The goal of POC-R is to embed research into clinical practice, contributing to a Learning Healthcare System. Provider acceptance and participation in POC-R is essential to its successful implementation. The purpose of this study is to evaluate provider's perceptions and beliefs regarding the POC-R program. Methods Provider focus groups and interviews were conducted at seven VA medical facilities involving 62 providers. A semi-structured script was used that included descriptions of four use cases and targeted questions regarding perceptions, concerns, and attitudes about the POC-R program. Sessions were audio-taped, de-identified, transcribed, and analyzed using systematic qualitative techniques to create response categories and overarching themes. Results The emergent themes were as follows: (1) POC-R is a valuable component of evidence-based practice, providing an opportunity to base clinical practice on more generalizable evidence as well as providing tools to improve local practice; (2) POC-R highlights the tension between the need for autonomy of practice and compliance with protocols; (3) POC-R may create increased time and burden resulting from added research responsibilities; (4) concern about the scientific validity and reliability of results; (5) potential for a negative impact on the provider-patient relationship; and (6) uncertainty regarding what constitutes equipoise, given differences in provider knowledge and preferences. Despite substantive concerns, barriers were generally felt to be solvable. Implementation should include provider education, careful attention to workflow for all arms of the study, inclusion of the entire team, and adequate oversight. Limitations The study design is qualitative with limited implications for causal inference. Participants are from the VA and may not be representative of other clinicians. Conclusion VA providers are supportive of the importance and value of pragmatic trials in general and of POC-R in particular. However, providers have significant concerns regarding the burden, ethics, and evidence regarding equipoise. Results are discussed in terms of implementation recommendations.

Noninvasive monitoring of left ventricular end-diastolic pressure reduces rehospitalization rates in patients hospitalized for heart failure: a randomized controlled trial.

BACKGROUND: In patients admitted for heart failure (HF), unrecognized elevation of left ventricular end-diastolic pressure (LVEDP) at the time of discharge may have a role in the high rehospitalization rate for HF on follow-up. METHODS AND RESULTS: In a small, prospective study (n = 50), patients admitted for HF were randomized to management guided by daily noninvasive estimated LVEDP monitoring (Group I, open) to a target LVEDP of <20 mm Hg or management based on clinical assessment alone without knowledge of the estimated LVEDP (Group II, blinded). Noninvasive estimated LVEDP was measured by the VeriCor monitor, which uses the Valsalva maneuver to derive the LVEDP. The primary endpoints were the reduction of estimated LVEDP at discharge and the HF rehospitalization rate on follow-up. Estimated LVEDP was significantly reduced at discharge in the open group compared with the blinded group (mean estimated LVEDP 19.7 ± 1.3 mm Hg vs 25.6 ± 1.5 mm Hg, respectively, P = 0.01). The rehospitalization rates for HF on follow-up were significantly improved in the open group compared with the blinded group (at 1 month: 0% vs 25%, respectively [P = .05]; at 3 months: 0% vs 32% [P = .01]; at 6 months: 4% vs 36% [P = .01]; at 1 year: 16% vs 48% [P = .03]). CONCLUSIONS: When HF is managed by clinical assessment only, estimated LVEDPs remain high at discharge, resulting in early and frequent rehospitalization for HF. Therapy guided by estimated LVEDP monitoring optimizes filling pressures and reduces HF rehospitalization rates.

Evaluation of a noninvasive system for determining left ventricular filling pressure.

BACKGROUND: Measurement of left ventricular filling pressure (LVFP) provides an accurate assessment of left ventricular failure. Clinical and radiographic methods of estimating LVFP are unreliable. The noninvasive method of analyzing the decline in the arterial pressure during the strain phase of the Valsalva maneuver may be used to directly measure LVFP. OBJECTIVE: To examine the relationship and the level of accuracy of a noninvasive system (VeriCor) in directly determining left ventricular end diastolic pressure (LVEDP) using simultaneously recorded VeriCor and LVEDP measurements obtained during left heart catheterization. METHODS: During elective right and left heart catheterization, LVFP was assessed by measuring pulmonary capillary wedge pressure (PCWP) and LVEDP in 57 patients followed immediately by a Valsalva maneuver using the VeriCor assembly to estimate these pressures noninvasively. RESULTS: VeriCor measurements had a significant correlation with the catheter-measured LVEDP (r = 0.86), comparable to the correlation of the catheter-measured PCWP with LVEDP (r = 0.81). The predictive accuracy of VeriCor for LVEDP, however, appeared to be superior to that of catheter-measured PCWP for LVEDP: 84% of VeriCor measurements compared with only 41% of PCWP measurements were within 4 mm Hg of catheter-measured LVEDP, and 93% of VeriCor measurements compared with only 67% of PCWP measurements were within 6 mm Hg of catheter-measured LVEDP. CONCLUSION: VeriCor is a reliable noninvasive tool for measuring LVFP.