ProjectFlow: a configurable workflow management application for point of care research.

OBJECTIVE: To best meet our point-of-care research (POC-R) needs, we developed ProjectFlow, a configurable, clinical research workflow management application. In this article, we describe ProjectFlow and how it is used to manage study processes for the Diuretic Comparison Project (DCP) and the Research Precision Oncology Program (RePOP). MATERIALS AND METHODS: The Veterans Health Administration (VHA) is the largest integrated health care system in the United States. ProjectFlow is a flexible web-based workflow management tool specifically created to facilitate conduct of our clinical research initiatives within the VHA. The application was developed using the Grails web framework and allows researchers to create custom workflows using Business Process Model and Notation. RESULTS: As of January 2021, ProjectFlow has facilitated management of study recruitment, enrollment, randomization, and drug orders for over 10 000 patients for the DCP clinical trial. It has also helped us evaluate over 3800 patients for recruitment and enroll over 370 of them into RePOP for use in data sharing partnerships and predictive analytics aimed at optimizing cancer treatment in the VHA. DISCUSSION: The POC-R study design embeds research processes within day-to-day clinical care and leverages longitudinal electronic health record (EHR) data for study recruitment, monitoring, and outcome reporting. Software that allows flexibility in study workflow creation and integrates with enterprise EHR systems is critical to the success of POC-R. CONCLUSIONS: We developed a flexible web-based informatics solution called ProjectFlow that supports custom research workflow configuration and has ability to integrate data from existing VHA EHR systems.

Effect of Pharmacogenetic Testing for Statin Myopathy Risk vs Usual Care on Blood Cholesterol: A Randomized Clinical Trial.

Importance: Nonadherence to statin guidelines is common. The solute carrier organic anion transporter family member 1B1 (SLCO1B1) genotype is associated with simvastatin myopathy risk and is proposed for clinical implementation. The unintended harms of using pharmacogenetic information to guide pharmacotherapy remain a concern for some stakeholders. Objective: To determine the impact of delivering SLCO1B1 pharmacogenetic results to physicians on the effectiveness of atherosclerotic cardiovascular disease (ASCVD) prevention (measured by low-density lipoprotein cholesterol [LDL-C] levels) and concordance with prescribing guidelines for statin safety and effectiveness. Design, Setting, and Participants: This randomized clinical trial was performed from December 2015 to July 2019 at 8 primary care practices in the Veterans Affairs Boston Healthcare System. Participants included statin-naive patients with elevated ASCVD risk. Data analysis was performed from October 2019 to September 2020. Interventions: SLCO1B1 genotyping and results reporting to primary care physicians at baseline (intervention group) vs after 1 year (control group). Main Outcomes and Measures: The primary outcome was the 1-year change in LDL-C level. The secondary outcomes were 1-year concordance with American College of Cardiology-American Heart Association and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for statin therapy and statin-associated muscle symptoms (SAMS). Results: Among 408 patients (mean [SD] age, 64.1 [7.8] years; 25 women [6.1%]), 193 were randomized to the intervention group and 215 were randomized to the control group. Overall, 120 participants (29%) had a SLCO1B1 genotype indicating increased simvastatin myopathy risk. Physicians offered statin therapy to 65 participants (33.7%) in the intervention group and 69 participants (32.1%) in the control group. Compared with patients whose physicians did not know their SLCO1B1 results at baseline, patients whose physicians received the results had noninferior reductions in LDL-C at 12 months (mean [SE] change in LDL-C, -1.1 [1.2] mg/dL in the intervention group and -2.2 [1.3] mg/dL in the control group; difference, -1.1 mg/dL; 90% CI, -4.1 to 1.8 mg/dL; P < .001 for noninferiority margin of 10 mg/dL). The proportion of patients with American College of Cardiology-American Heart Association guideline-concordant statin prescriptions in the intervention group was noninferior to that in the control group (12 patients [6.2%] vs 14 patients [6.5%]; difference, -0.003; 90% CI, -0.038 to 0.032; P < .001 for noninferiority margin of 15%). All patients in both groups were concordant with CPIC guidelines for safe statin prescribing. Physicians documented 2 and 3 cases of SAMS in the intervention and control groups, respectively, none of which was associated with a CPIC guideline-discordant prescription. Among patients with a decreased or poor SLCO1B1 transporter function genotype, simvastatin was prescribed to 1 patient in the control group but none in the intervention group. Conclusions and Relevance: Clinical testing and reporting of SLCO1B1 results for statin myopathy risk did not result in poorer ASCVD prevention in a routine primary care setting and may have been associated with physicians avoiding simvastatin prescriptions for patients at genetic risk for SAMS. Such an absence of harm should reassure stakeholders contemplating the clinical use of available pharmacogenetic results. Trial Registration: ClinicalTrials.gov Identifier: NCT02871934.

Pragmatic Trials in Genomic Medicine: The Integrating Pharmacogenetics In Clinical Care (I-PICC) Study.

Pragmatic clinical trials (PCTs) have an established presence in clinical research and yet have only recently garnered attention within the landscape of genomic medicine. Using the PRagmatic-Explanatory Continuum Indicator Summary 2 (PRECIS-2) as a framework, this paper illustrates the application of PCT principles to The Integrating Pharmacogenetics In Clinical Care (I-PICC) Study, a trial of pharmacogenetic testing prior to statin initiation for cardiovascular disease prevention in primary care. The trial achieved high engagement with providers (85% enrolled of those approached) and enrolled a representative sample of participants for which statin therapy would be recommended. The I-PICC Study has a high level of pragmatism, which should enhance the generalizability of its findings. The PRECIS-2 may be useful in the design and evaluation of PCTs of genomic medicine interventions, contributing to the generation of evidence that can bridge the gap between genomics innovation and clinical adoption.

The Integrating Pharmacogenetics in Clinical Care (I-PICC) Study: Protocol for a point-of-care randomized controlled trial of statin pharmacogenetics in primary care.

BACKGROUND: The association between the SLCO1B1 rs4149056 variant and statin-associated muscle symptoms (SAMS) is well validated, but the clinical utility of its implementation in patient care is unknown. DESIGN: The Integrating Pharmacogenetics in Clinical Care (I-PICC) Study is a pseudo-cluster randomized controlled trial of SLCO1B1 genotyping among statin-naïve primary care and women's health patients across the Veteran Affairs Boston Healthcare System. Eligible patients of enrolled primary care providers are aged 40-75 and have elevated risk of cardiovascular disease by American College of Cardiology/American Heart Association (ACC/AHA) guidelines. Patients give consent by telephone in advance of an upcoming appointment, but they are enrolled only if and when their provider co-signs an order for SLCO1B1 testing, performed on a blood sample already collected in clinical care. Enrolled patients are randomly allocated to have their providers receive results through the electronic health record at baseline (PGx + arm) versus after 12 months (PGx- arm). The primary outcome is the change in low-density lipoprotein cholesterol (LDL-C) after one year. Secondary outcomes are concordance with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for simvastatin prescribing, concordance with ACC/AHA guidelines for statin use, and incidence of SAMS. With 408 patients, the study has >80% power to exclude a between-group LDL-C difference of 10 mg/dL (non-inferiority design) and to detect between-group differences of 15% in CPIC guideline concordance (superiority design). CONCLUSION: The outcomes of the I-PICC Study will inform the clinical utility of preemptive SLCO1B1 testing in the routine practice of medicine, including its proposed benefits and unforeseen risks.

Comparison of Outcomes in DeBakey Type AI Versus AII Aortic Dissection.

The DeBakey classification divides type A acute aortic dissection (AAD) into type I and type II; the latter limited to the ascending aorta. We endeavored to examine differences in DeBakey groups in a contemporary registry. We divided 1,872 patients with noniatrogenic AAD from the International Registry of Acute Aortic Dissection into type I (n = 1691, 90.3%) and type II (n = 181, 9.7%). Patients with type II AAD were older. On presentation, patients with type I AAD reported more back and abdominal pain and were more likely to have pulse deficit. Intramural hematoma was more frequent in type II AAD. Most patients with both types were treated surgically. Lower rates of renal failure, coma, mesenteric and limb ischemia were noted in those with type II AAD. In-hospital death was less frequent (16.6% vs 22.5%) after type II AAD, a trend that did not reach significance. There was no difference in the incidence of new dissection, rapid aortic growth, late aortic intervention or survival at 5 years. In conclusion, AAD limited to the ascending aorta (DeBakey type II) appears to be associated with improved clinical outcomes compared with dissection that extend to the aortic arch or beyond. Although fewer dissection-related complications were noted in patients presenting with type II AAD, as was a trend toward reduced in-hospital mortality, 5-year survival and descending aortic sequelae are not reduced in this contemporary report from International Registry of Acute Aortic Dissection.

Aortic stiffness and cardiovascular risk in type 2 diabetes.

OBJECTIVE: Damage to large arteries is a major contributor to high cardiovascular morbi-mortality in type 2 diabetic patients. Pulse wave velocity (PWV), depending on both structural and functional characteristics of the arterial wall, has poorly been ascertained in its ability to be a marker of cardiovascular risk in diabetic patients. In order to determine the factors influencing aortic stiffness, and the potential predictor role of this measurement, a cross-sectional study on a cohort of 618 type 2 diabetic patients with or without cardiovascular events was conducted. METHODS: Aortic PWV (estimated by carotid-femoral PWV measurement) was determined using an automatic device and cardiovascular risk was determined, using Framingham equation (10-year absolute cardiovascular disease risk), in individuals without previous cardiovascular events. Multilinear regression analysis was performed to assess relationships between aortic PWV, population characteristics and the presence of cardiovascular disease. Multivariate models (with and without PWV) were compared to determine whether aortic PWV improves explicative model of presence of cardiovascular disease. RESULTS: Increased aortic PWV was strongly associated with presence of coronary, cerebral and peripheral vascular diseases. Increased aortic PWV was independently associated with previous cardiovascular events and improved the explicative model of presence of cardiovascular disease above the known cardiovascular risk factors. CONCLUSION: This study provides evidence that aortic PWV is a forceful independent marker of cardiovascular disease in diabetic patients, as it has already been demonstrated in hypertensive individuals. Prospective trials are needed to assess the improvement in cardiovascular risk prediction for widespread use of aortic PWV in diabetic patients.