PCORnet® Study Publications

PCORnet® Study	Research Question(s)	Citation(s)
Advancing Public Health Use of Electronic Health Record Data Therapeutic Area: Infectious Disease	Research Question(s): How can we use nationally distributed healthcare data infrastructure to (1) improve the capacity of data and information systems to conduct monitoring and surveillance and (2) increase the capability to use data to inform public health decision-making and support evidence-based practices and policies?	Zhang, Y., Romieu-Hernandez, A., Boehmer, T.K. et al. Association between SARS-CoV-2 infection and select symptoms and conditions 31 to 150 days after testing among children and adults. BMC Infect Dis 24, 181 (2024). https://doi.org/10.1186/s12879-024-09076-8 Jackson SL, Lekiachvili A, Block JP, et al. Preventive Service Usage and New Chronic Disease Diagnoses: Using PCORnet Data to Identify Emerging Trends, United States, 2018-2022. Prev Chronic Dis. 2024 Jul 3;21:E49. doi: 10.5888/pcd21.230415 Ghildayal N, Nagavedu K, Wiltz JL, et al. Public Health Surveillance in Electronic Health Records: Lessons From PCORnet. Prev Chronic Dis. 2024 Jul 11;21:E51. doi: 10.5888/pcd21.230417
Comparative Effectiveness of Prophylactic ICD versus Non-ICD Therapy in Contemporary Heart Failure Patients with a Low Risk for Arrhythmic Death (CONTEMP-ICD) Therapeutic Area: Cardiovascular	Research Question(s): Is implantable cardioverter-defibrillator beneficial in eligible heart failure patients with low arrhythmia risk?	Goldenberg I, Zareba W, Ezekowitz JA, et al. Rationale and design of the comparative effectiveness of ICD vs non-ICD therapy in contemporary heart failure patients at a low risk for arrhythmic death (CONTEMP-ICD) trial. Am Heart J. 2026;291:162-174. doi:10.1016/j.ahj.2025.08.020 Goldenberg I, Ezekowitz J, Albert C, et al. Reassessing the need for primary prevention implantable cardioverter defibrillators in contemporary patients with heart failure. Heart Rhythm. 2025;22(4):1040-1051. doi:10.1016/j.hrthm.2024.10.078
Behavioral Economic and Staffing Strategies to Increase Adoption of the ABCDEF Bundle in the ICU (BEST-ICU) Therapeutic Area: Healthcare Delivery	Research Question(s): What is the best way to encourage ICU clinicians to consistently and completely implement the ABCDEF Bundle in their care of mechanically ventilated patients?	Conte M, Schlaeger J, Marsolo K, et al. Computable phenotypes for research using real-world data: experiences from the NIH Pragmatic Trials Collaboratory. J Am Med Inform Assoc. In review.
Measuring Co-creation During the Engagement Process in Research: A Pathway Forward Therapeutic Area: Engagement Methods	Research Question(s): How can we measure the process of co-creation in a way that is pragmatic, valid, reliable, and associated with meaningful engagement outcomes?	Jolles MP, Willging C, Tufte J, et al. Development and validation of a pragmatic measure of cocreation in research engagement: a study protocol. BMJ Open. 2024;14(12):e091966. doi: 10.1136/bmjopen-2024-091966
HERO Registry & Trial: Healthcare Worker Exposure Response and Outcomes Therapeutic Area: Infectious Disease	Research Question(s): Can a research registry of people working in healthcare help to answer important questions about the COVID-19 pandemic on medications, vaccines and healthcare worker well-being?	Friedland A, Hernandez AF, Anstrom KJ, et al. Design of healthcare worker exposure response and outcomes (HERO) research platform. Contemp Clin Trials, 2021; 109:106525. doi.org/10.1016/j.cct.2021.106525 Naggie S, Milstone A, Castro M, et al. Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial (HERO-HCQ). Medrxiv, 2021. doi.org/10.1101/2021.08.19.21262275
PANDA – MSD: Predictive Analytics via Networked Distributed Algorithms for Multi – System Diseases Therapeutic Area: Rare Diseases	Research Question(s): Can the use of EHR data develop predictive tools to assist healthcare providers in reaching earlier diagnoses and interventions, and improve the diagnostic journey and clinical outcomes of patients with rare diseases?	Jian X, Zhang D, Yu Z, et al. Leveraging undecided cases in chart-reviewed phenotypes to enhance EHR-based association studies. J Biomed Inform. 2025;166:104839. doi:10.1016/j.jbi.2025.104839 Tong J, Li L, Reps JM, et al. Advancing Interpretable Regression Analysis for Binary Data: A Novel Distributed Algorithm Approach. Stat Med. 2024;43(29):5573-5582. doi:10.1002/sim.10250 Wu Q, Tong J, Zhang B, et al. Real-World Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents. Ann Intern Med. 2024;177(2):165-176. doi:10.7326/M23-1754
Understanding How Antibiotic Use Affects Childhood Obesity and Growth Therapeutic Area: Metabolic Disorders	Research Question(s): How does antibiotic use before age two affect weight and growth in children?	Block JP, Bailey LC, Gillman M, et al. Early Antibiotic Exposure and Weight Outcomes in Young Children. Pediatrics, 2018; 142(6), p.e20180290. doi:10.1542/peds.2018-0290 Heerman WJ, Daley MF, Boone-Heinonen J, et al. Maternal antibiotic use during pregnancy and childhood obesity at age 5 years. Int J Obes (Lond). 2019;43(6):1202-1209. doi:10.1038/s41366-018-0316-6
Comparing the Benefits and Harms of Three Types of Weight Loss Surgery — The PCORnet® Bariatric Study Therapeutic Area: Metabolic Disorders	Research Question(s): We don’t know much about the long-term effectiveness of bariatric interventions. Can we use PCORnet to compare compare weight loss and safety among three popular bariatric procedures?	Inge TH, Coley RY., Bazzano LA,. et al. Comparative effectiveness of bariatric procedures among adolescents: the PCORnet bariatric study. SOARD, 2018, 14(9):1374-1386. doi.org/10.1016/j.soard.2018.04.002 McTigue KM, Wellman R, Nauman E, et al. PCORnet Bariatric Study Collaborative. Comparing the 5-Year Diabetes Outcomes of Sleeve Gastrectomy and Gastric Bypass: The National Patient-Centered Clinical Research Network (PCORNet) Bariatric Study. JAMA Surg. 2020;155(5):e200087. doi:10.1001/jamasurg.2020.0087
Cardiovascular Multicenter Observational Investigation of Lipid Care in the United States-2 (cvMOBIUS2) Therapeutic Area: Cardiovascular	Research Question(s):Can we reduce the number of people who die from atherosclerotic cardiovascular disease (ASCVD) related deaths by using PCSK9 medicines to lower their cholesterol?	Navar AM, Shah NP, Shrader P, et al. Achievement of LDL-C <55 mg/dL among US adults: Findings from the cvMOBIUS2 registry. Am Heart J. 2025;279:107-117. doi:10.1016/j.ahj.2024.06.012 Shoji S, Shah NP, Shrader P, et al. Achievement of guideline-based lipid goals among very-high-risk patients with atherosclerotic cardiovascular disease and type 2 diabetes: results in 213,380 individuals from the cvMOBIUS2 registry. Am J Prev Cardiol. 2024;21:100921. Published 2024 Dec 21. doi:10.1016/j.ajpc.2024.100921
The RECOVER Post-Acute Sequelae of SARS-CoV-2 (PASC) Electronic Health Record (EHR) Cohort Study Therapeutic Area: Infectious Disease	Research Question(s): What are the long term health effects of COVID-19 after a person has recovered from infection? How can we better detect, predict, treat these health effects and prevent future infection?	Forrest CB, Burrows EK, Mejias A, et al. Severity of Acute COVID-19 in Children <18 Years Old March 2020 to December 2021. Pediatrics. 2022 Apr 1;149(4):e2021055765. doi:10.1542/peds.2021-055765 Rao S, Lee GM, Razzaghi H, et al. Clinical Features and Burden of Postacute Sequelae of SARS-CoV-2 Infection in Children and Adolescents. JAMA Pediatr. 2022;176(10):1000. doi:10.1001/jamapediatrics.2022.2800 Bose-Brill S, Hirabayashi K, Schwimmer E, et al; Researching COVID to Enhance Recovery consortium. Pediatric nirmatrelvir/ritonavir prescribing patterns during the COVID-19 pandemic. Hosp Pediatr. 2024;14(8):e341-e348. doi:10.1542/hpeds.2023-007132
Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term (ADAPTABLE) Therapeutic Area: Cardiovascular	Research Question: Which dose of daily aspirin offers the right balance of effectiveness and minimal risk of bleeding? Can PCORnet be used to find the answer using a clinical trial model wherein patients are drivers of engagement?	Marquis-Gravel G, Roe MT, Robertson HR, et al. Rationale and design of the apsirin dosing- a patient-centric trial assessing benefits and long-term effectiveness (ADAPTABLE) Trial. JAMA Cardiol, 2020; 5(5): 598-607. doi:10.1001/jamacardio.2020.0116 Jones WS, Mulder H, Wruck LM, et al. Comparative effectiveness of aspirin dosing in cardiovascular disease. N Engl J Med, 2021; 384(21); 1981-1990. doi:10.1056/NEJMoa2102137
Characterization of Patients with Heart Failure and Patients with Atrial Fibrillation and Atrial Flutter in PCORnet Data Therapeutic Area: Cardiovascular	Research Question(s): What is the occurrence of vascular, bleeding, or other events in Atrial Fibrillation or Atrial Flutter Patients patients?	Rao VN, Cyr D, Wruck L, et al. Electronic health record characterization and outcomes of heart failure with preserved ejection fraction. American Heart Journal. 2023. Vol263, Pg 1-14, ISSN 0002-8703. doi.org/10.1016/j.ahj.2023.04.013
Using PCORnet to Compare Blood Pressure Control Strategies Therapeutic Area: Cardiovascular	Research Question(s): How well are clinics and patients controlling blood pressure, and would new programs or technologies help improve blood pressure control?	Cooper-DeHoff RM, Fontil V, Carton T, et al. Tracking blood pressure control performance and process metrics in 25 US health systems: The PCORnet Blood Pressure Control Laboratory. J Am Heart Assoc, 2021; 10(21): e022224. doi:10.1161/JAHA.121.022224
PCORnet® Study of Post-Acute Sequelae of SARS-CoV-2 Infection in Adults (PCORnetPASC) Therapeutic Area: Infectious Disease	Research Question(s): What are the long term health effects of COVID-19 after a person has recovered from infection? How can we better detect, predict, and treat these health effects and prevent future infection?	Hernandez-Romieu AC, Carton TW, Saydah S, et al. Prevalence of select new symptoms and conditions among person aged younger than 20 years and 20 years or older at 31 to 150 days after testing positive or negative for SARS-CoV-2. JAMA Netw Open. 2022;5(2):e2147053. doi.org/10.1001/jamanetworkopen.2021.47053
Comparative Effectiveness of Palliative Surgery vs Additional Anti-Seizure Medications for Lennox-Gastaut Syndrome Therapeutic Area: Neurology	Research Question(s): Which treatment options are most likely to improve important clinical outcomes in my child (or patient) with LGS? My child has hundreds of seizures a week, and multiple different drugs have failed to get her seizures under control. What is the best possible next step?	Lam S, Rosenman M, Dixon-Salazar D, et al. Comparative effectiveness of epilepsy surgery versus additional anti-seizure medications for Lennox-Gastaut syndrome: study protocol for a multicenter, mixed-methods study. Front Neurol 2025;16:1569551. doi: 10.3389/fneur.2025.1569551 Bliss ND, Patel AD, Dixon-Salazar T, et al. Patient family engagement and partnership: Pilot survey results in assessing behavior, communication, and quality of life in children with Lennox-Gastaut syndrome and other drug-resistant epilepsy. Epilepsy Behav 2023;148:109451. doi: 10.1016/j.yebeh.2023.109451 Votoupal M, Muller R, Patel AD, et al. Navigating the diagnosis: A survey on caregivers’ journeys to Lennox-Gastaut syndrome. Epilepsy Behav 2025;171:110600. doi: 10.1016/j.yebeh.2025.110600
Empagliflozin Diabetic Kidney Disease (Empa DKD) Therapeutic Area: Nephrology	Research Question(s): Can we better understand why patients with type-2 diabetes may not receive guideline-recommended screening for diabetic kidney disease? Which medications may be most effective at improving kidney and heart outcomes in patients with and without type-2 diabetes?	Edmonston, D, Mulder, H, Lydon, E. et al. Kidney and Cardiovascular Effectiveness of SGLT2 Inhibitors vs GLP-1 Receptor Agonists in Type 2 Diabetes. JACC. 2024 Aug, 84 (8) 696–708. doi.org/10.1016/j.jacc.2024.06.016 Edmonston D, Mulder H, Lydon E, et al. Kidney and Cardiovascular Effectiveness of Empagliflozin Compared With Dipeptidyl Peptidase-4 Inhibitors in Patients With Type 2 Diabetes. Am J Cardiol. 2024;221:52-63. doi:10.1016/j.amjcard.2024.04.011
Semantic Data Quality Standards for Multi-Center Clinical Research Studies and Networks Therapeutic Area: Data Science	Research Question(s): Can we find ways to more accurately describe how suitable data are to answer a specific research question? What are the tools that can be used across studies to consistently describe whether the data are high quality?	Razzaghi H, Dickinson K, Wieand K, et al. A multifaceted approach to advancing data quality and fitness standards in multi-institutional networks. J Am Med Inform Assoc. 2025;ocaf181. doi:10.1093/jamia/ocaf181
Comparing patient-reported impact of COVID-19 shelter-in-place policies and access to containment and mitigation strategies, overall and in vulnerable populations Therapeutic Area: Infectious Disease	Research Question(s): What is the comparative impact of different shelter-in-place/reopening policies, overall and in vulnerable populations, on patient-reported financial insecurity, mental health, and other subjective outcomes important to patients? What is the comparative effectiveness of county-level containment and mitigation strategies at achieving timely access to testing, healthcare, information, and contact tracing, overall and in vulnerable populations? What is the comparative accuracy of different algorithms designed to predict risk of infection and severe COVID-19 among patients with symptoms, overall and in vulnerable populations?	Beatty AL, Peyser ND, Butcher XE, et al. The COVID-19 citizen science study: protocol for a longitudinal digital health cohort. JMIR Res Protoc, 2021; 10(8):e28169. doi:10.2196/28169
Neuroendocrine Tumors – Patient Reported Outcomes (NET-PRO) Therapeutic Area: Oncology	Research Question(s): Which care options work, for whom, and under which circumstances in order to improve symptom management, treatment outcomes and quality of life among NET patients? Common treatment combinations and their relation to disease symptoms and quality of life Identification of the best ordering of treatments and relation to patient outcomes and survival The impact of patient traits and tumor characteristics on treatment choice(s) and survival	Hourcade JP, O’Rorke M, Chrischilles E, et al. Personal Health Record Software for Neuroendocrine Tumors: Patient Centered Design Approach. JMIR Hum Factors. 2025;12:e68788. Published 2025 Jun 3. doi:10.2196/68788
Outcomes Database to Prospectively Assess Changing Therapy Landscape in Renal Cell Carcinoma (ODYSSEY RCC) Therapeutic Area: Oncology	Research Question(s): Can a research registry of patients with metastatic renal cell carcinoma (mRCC) patients help us better understand cancer management and health-related quality of life while receiving mRCC specific treatment? In combination with patient and physician surveys, PCORnet will be used to help us answer these questions.	Bhavsar NA, Harrison MR, Scales CD, et al. Design and Rationale of the Outcomes Database to Prospectively Assess the Changing Therapy Landscape in Renal Cell Carcinoma Registry: A Multi-institutional, Prospective Study of Patients with Metastatic Renal Cell Carcinoma. Eur Urol Open Sci. 2024;66:75-81. Published 2024 Jul 3. doi:10.1016/j.euros.2024.06.007
A Patient-Centered PaTH to Addressing Diabetes Therapeutic Area: Metabolic Disorders	Research Question(s): How often is intensive behavioral therapy (IBT) being utilized in primary care and how has it impacted weight and diabetes outcomes for patients with and at-risk of type 2 diabetes? What is the impact of telemedicine utilization during the COVID-19 pandemic for patients with and at-risk of type 2 diabetes? What are demographic and clinical characteristics associated with severe COVID-19 outcomes across multiple phases of the COVID pandemic for patients with or at-risk of type 2 diabetes?	Kraschnewski JL, Kong L, Francis E, et al. A Patient-Centered PaTH to Address Diabetes: Protocol for a Study on the Impact of Obesity Counseling. JMIR Res Protoc. 2019 Apr 4;8(4):e12054. doi.org/10.2196/12054 Soleymani T, Lehman EB, Kong L, et al. Bariatric surgery and COVID-19 outcomes: results from the PaTH to Health: Diabetes study. Surg Obes Relat Dis. 2024;20(11):1039-1045. doi:10.1016/j.soard.2024.05.016
ACTIV-6: COVID-19 Study of Repurposed Medications Therapeutic Area: Infectious Disease	Research Question(s): Can repurposed medications reduce symptoms of non-hospitalized participants with mild to moderate COVID-19?	Naggie S, Boulware DR, Lindsell CJ, et al. Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2022;328(16):1595–1603. doi:10.1001/jama.2022.18590 McCarthy MW, Naggie S, Boulware DR, et al. Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2023;329(4):296–305. doi:10.1001/jama.2022.24100 Naggie S, Boulware DR, Lindsell CJ, et al. Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19: A Randomized Clinical Trial. JAMA. 2023;329(11):888–897. doi:10.1001/jama.2023.1650
Biologic Abatement and Capturing Kids’ Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA) Therapeutic Area: Autoimmune (Allergy and Immunology)	Research Question(s): This trial will compare how patients with inactive spondyloarthritis on tumor necrosis factor inhibitor (TNFi) treatment respond to three treatment options that doctors currently use: Continue standard TNFi medication, Space out the time between usual TNFi medication doses, or Stop the TNFi medication. If we can safely prolong the time between doses or completely take away TNFi therapy in this population, we may remove unnecessary medication exposure, improve patient quality of life, and lower medication costs.	Weiss PF, Sears CE, Brandon TG, et al. Biologic Abatement and Capturing Kids’ Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA): study protocol for a randomized pragmatic trial. Trials. 2023;24(1):100. Published 2023 Feb 8. doi:10.1186/s13063-022-07038-6
Pediatric KIDney Stone (PKIDS) Care Improvement Network Therapeutic Area: Nephrology	Research Question(s): What are the differences in stone clearance and the lived experiences of youth, age 8-21 years, following ureteroscopy (URS), shock wave lithotripsy (SWL), and percutaneous nephrolithotomy (PCNL) for the removal of kidney and ureteral stones?	Ellison JS, Lorenzo M, Beck H on behalf of the Pediatric KIDney Stone Care Improvement Network, et al. Comparative effectiveness of paediatric kidney stone surgery (the PKIDS trial): study protocol for a patient-centred pragmatic clinical trial. BMJ Open 2022;12:e056789. doi:10.1136/bmjopen-2021-056789
Evaluating the Comparative Effectiveness of Telemedicine in Primary Care: Learning from the COVID-19 Pandemic Therapeutic Area: Healthcare Delivery	Research Question(s): What are the features of primary care telemedicine programs that have been newly implemented or expanded in response to the COVID-19 pandemic, and how do different populations experience these programs?	Lin, J.J., Horowitz, C.R., Ancker, J.S. An Urgent Need for Guidelines for Telemedicine Use. J Gen Intern Med 38, 1061–1062 (2023). doi:10.1007/s11606-022-07905-7 Yu J, Andreadis K, Schpero WL, et al. Patient experiences with and preferences for telemedicine relative to in-person care during the COVID-19 pandemic. Telemedicine and e-Health. Published online 2023. doi:10.1089/tmj.2022.0311 Muellers KA, Andreadis K, Ancker JS, et al. Provider and patient experiences of delays in primary care during the early COVID-19 pandemic. Journal for Healthcare Quality. 2023;45(3):169-176. doi:10.1097/jhq.0000000000000380
Cognitive Behavioral Therapy and Real-Time Pain Management Intervention for Sickle Cell via Mobile Applications (CaRISMA) Therapeutic Area: Mental and Behavioral Health	Research Question(s): Does mobile phone-delivered computerized cognitive behavioral therapy provide a greater benefit for daily pain and depression in adult patients with sickle cell disease than digital education?	Badawy SM, Abebe KZ, Reichman CA, et al. Comparing the effectiveness of education versus digital cognitive behavioral therapy for adults with sickle cell disease: protocol for the cognitive behavioral therapy and real-time pain management intervention for sickle cell via mobile applications (CaRISMA) study. JMIR Res Protoc, 2021; 10(5):e29014. doi:10.2196/29014
Medications and Weight Gain in PCORnet: The MedWeight Study Therapeutic Area: Metabolic Disorders	Research Question(s): How do six classes of commonly prescribed medications influence weight, risk for diabetes, and cholesterol over time?	Sun JW, Young JG, Sarvet AL, et al. Comparison of rates of Type 2 Diabetes in adults and children treated with anticonvulsant mood stabilizers. JAMA Netw Open. 2022;5(4). doi:10.1001/jamanetworkopen.2022.6484 Petimar J, Young JG, Yu H, et al. Medication-Induced Weight Change Across Common Antidepressant Treatments : A Target Trial Emulation Study. Ann Intern Med. 2024;177(8):993-1003. doi:10.7326/M23-2742 Lin PD, Rifas-Shiman S, Merriman J, et al. Trends of Antihypertensive Prescription Among US Adults From 2010 to 2019 and Changes Following Treatment Guidelines: Analysis of Multicenter Electronic Health Records. J Am Heart Assoc. 2024;13(9):e032197. doi:10.1161/JAHA.123.032197
Pragmatic Evaluation of Events and Benefits of Lipid-lowering in Older Adults (PREVENTABLE) Therapeutic Area: Cardiovascular	Research Question(s): Can a statin help prevent dementia and disability in adults aged 75 or older, as well as heart attacks and other cardiovascular-related deaths, while not increasing risks of adverse health outcomes?	Sachs BC, Rapp SR, Kistler CE, et al. The pragmatic evaluation of events and benefits of lipid-lowering in older adults (PREVENTABLE) trial: study design and procedures for cognitive assessment and adjudication. Alzherimers. Dement., 2021; 17(Supp.9). doi.org/10.1002/alz.054022

Advancing Public Health Use of Electronic Health Record Data

Therapeutic Area: Infectious Disease

Research Question(s):
How can we use nationally distributed healthcare data infrastructure to (1) improve the capacity of data and information systems to conduct monitoring and surveillance and (2) increase the capability to use data to inform public health decision-making and support evidence-based practices and policies?

Zhang, Y., Romieu-Hernandez, A., Boehmer, T.K. et al. Association between SARS-CoV-2 infection and select symptoms and conditions 31 to 150 days after testing among children and adults. BMC Infect Dis 24, 181 (2024). https://doi.org/10.1186/s12879-024-09076-8

Jackson SL, Lekiachvili A, Block JP, et al. Preventive Service Usage and New Chronic Disease Diagnoses: Using PCORnet Data to Identify Emerging Trends, United States, 2018-2022. Prev Chronic Dis. 2024 Jul 3;21:E49. doi: 10.5888/pcd21.230415

Ghildayal N, Nagavedu K, Wiltz JL, et al. Public Health Surveillance in Electronic Health Records: Lessons From PCORnet. Prev Chronic Dis. 2024 Jul 11;21:E51. doi: 10.5888/pcd21.230417

Comparative Effectiveness of Prophylactic ICD versus Non-ICD Therapy in Contemporary Heart Failure Patients with a Low Risk for Arrhythmic Death (CONTEMP-ICD)

Therapeutic Area: Cardiovascular

Research Question(s):
Is implantable cardioverter-defibrillator beneficial in eligible heart failure patients with low arrhythmia risk?

Goldenberg I, Zareba W, Ezekowitz JA, et al. Rationale and design of the comparative effectiveness of ICD vs non-ICD therapy in contemporary heart failure patients at a low risk for arrhythmic death (CONTEMP-ICD) trial. Am Heart J. 2026;291:162-174. doi:10.1016/j.ahj.2025.08.020

Goldenberg I, Ezekowitz J, Albert C, et al. Reassessing the need for primary prevention implantable cardioverter defibrillators in contemporary patients with heart failure. Heart Rhythm. 2025;22(4):1040-1051. doi:10.1016/j.hrthm.2024.10.078

Behavioral Economic and Staffing Strategies to Increase Adoption of the ABCDEF Bundle in the ICU (BEST-ICU)

Therapeutic Area: Healthcare Delivery

Research Question(s):
What is the best way to encourage ICU clinicians to consistently and completely implement the ABCDEF Bundle in their care of mechanically ventilated patients?

Conte M, Schlaeger J, Marsolo K, et al. Computable phenotypes for research using real-world data: experiences from the NIH Pragmatic Trials Collaboratory. J Am Med Inform Assoc. In review.

Measuring Co-creation During the Engagement Process in Research: A Pathway Forward

Therapeutic Area: Engagement Methods

Research Question(s):
How can we measure the process of co-creation in a way that is pragmatic, valid, reliable, and associated with meaningful engagement outcomes?

Jolles MP, Willging C, Tufte J, et al. Development and validation of a pragmatic measure of cocreation in research engagement: a study protocol. BMJ Open. 2024;14(12):e091966. doi: 10.1136/bmjopen-2024-091966

HERO Registry & Trial: Healthcare Worker Exposure Response and Outcomes

Therapeutic Area: Infectious Disease

Research Question(s):
Can a research registry of people working in healthcare help to answer important questions about the COVID-19 pandemic on medications, vaccines and healthcare worker well-being?

Friedland A, Hernandez AF, Anstrom KJ, et al. Design of healthcare worker exposure response and outcomes (HERO) research platform. Contemp Clin Trials, 2021; 109:106525. doi.org/10.1016/j.cct.2021.106525

Naggie S, Milstone A, Castro M, et al. Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial (HERO-HCQ). Medrxiv, 2021. doi.org/10.1101/2021.08.19.21262275

PANDA – MSD: Predictive Analytics via Networked Distributed Algorithms for Multi – System Diseases

Therapeutic Area: Rare Diseases

Research Question(s):
Can the use of EHR data develop predictive tools to assist healthcare providers in reaching earlier diagnoses and interventions, and improve the diagnostic journey and clinical outcomes of patients with rare diseases?

Jian X, Zhang D, Yu Z, et al. Leveraging undecided cases in chart-reviewed phenotypes to enhance EHR-based association studies. J Biomed Inform. 2025;166:104839. doi:10.1016/j.jbi.2025.104839

Tong J, Li L, Reps JM, et al. Advancing Interpretable Regression Analysis for Binary Data: A Novel Distributed Algorithm Approach. Stat Med. 2024;43(29):5573-5582. doi:10.1002/sim.10250

Wu Q, Tong J, Zhang B, et al. Real-World Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents. Ann Intern Med. 2024;177(2):165-176. doi:10.7326/M23-1754

Understanding How Antibiotic Use Affects Childhood Obesity and Growth

Therapeutic Area: Metabolic Disorders

Research Question(s):
How does antibiotic use before age two affect weight and growth in children?

Block JP, Bailey LC, Gillman M, et al. Early Antibiotic Exposure and Weight Outcomes in Young Children. Pediatrics, 2018; 142(6), p.e20180290. doi:10.1542/peds.2018-0290

Heerman WJ, Daley MF, Boone-Heinonen J, et al. Maternal antibiotic use during pregnancy and childhood obesity at age 5 years. Int J Obes (Lond). 2019;43(6):1202-1209. doi:10.1038/s41366-018-0316-6

Comparing the Benefits and Harms of Three Types of Weight Loss Surgery — The PCORnet® Bariatric Study

Therapeutic Area: Metabolic Disorders

Research Question(s):
We don’t know much about the long-term effectiveness of bariatric interventions. Can we use PCORnet to compare compare weight loss and safety among three popular bariatric procedures?

Inge TH, Coley RY., Bazzano LA,. et al. Comparative effectiveness of bariatric procedures among adolescents: the PCORnet bariatric study. SOARD, 2018, 14(9):1374-1386. doi.org/10.1016/j.soard.2018.04.002

McTigue KM, Wellman R, Nauman E, et al. PCORnet Bariatric Study Collaborative. Comparing the 5-Year Diabetes Outcomes of Sleeve Gastrectomy and Gastric Bypass: The National Patient-Centered Clinical Research Network (PCORNet) Bariatric Study. JAMA Surg. 2020;155(5):e200087. doi:10.1001/jamasurg.2020.0087

Cardiovascular Multicenter Observational Investigation of Lipid Care in the United States-2 (cvMOBIUS2)

Therapeutic Area: Cardiovascular

Research Question(s):Can we reduce the number of people who die from atherosclerotic cardiovascular disease (ASCVD) related deaths by using PCSK9 medicines to lower their cholesterol?

Navar AM, Shah NP, Shrader P, et al. Achievement of LDL-C <55 mg/dL among US adults: Findings from the cvMOBIUS2 registry. Am Heart J. 2025;279:107-117. doi:10.1016/j.ahj.2024.06.012

Shoji S, Shah NP, Shrader P, et al. Achievement of guideline-based lipid goals among very-high-risk patients with atherosclerotic cardiovascular disease and type 2 diabetes: results in 213,380 individuals from the cvMOBIUS2 registry. Am J Prev Cardiol. 2024;21:100921. Published 2024 Dec 21. doi:10.1016/j.ajpc.2024.100921

The RECOVER Post-Acute Sequelae of SARS-CoV-2 (PASC) Electronic Health Record (EHR) Cohort Study

Therapeutic Area: Infectious Disease

Research Question(s):

What are the long term health effects of COVID-19 after a person has recovered from infection?
How can we better detect, predict, treat these health effects and prevent future infection?

Forrest CB, Burrows EK, Mejias A, et al. Severity of Acute COVID-19 in Children <18 Years Old March 2020 to December 2021. Pediatrics. 2022 Apr 1;149(4):e2021055765. doi:10.1542/peds.2021-055765

Rao S, Lee GM, Razzaghi H, et al. Clinical Features and Burden of Postacute Sequelae of SARS-CoV-2 Infection in Children and Adolescents. JAMA Pediatr. 2022;176(10):1000. doi:10.1001/jamapediatrics.2022.2800

Bose-Brill S, Hirabayashi K, Schwimmer E, et al; Researching COVID to Enhance Recovery consortium. Pediatric nirmatrelvir/ritonavir prescribing patterns during the COVID-19 pandemic. Hosp Pediatr. 2024;14(8):e341-e348. doi:10.1542/hpeds.2023-007132

Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term (ADAPTABLE)

Therapeutic Area: Cardiovascular

Research Question: Which dose of daily aspirin offers the right balance of effectiveness and minimal risk of bleeding? Can PCORnet be used to find the answer using a clinical trial model wherein patients are drivers of engagement?

Marquis-Gravel G, Roe MT, Robertson HR, et al. Rationale and design of the apsirin dosing- a patient-centric trial assessing benefits and long-term effectiveness (ADAPTABLE) Trial. JAMA Cardiol, 2020; 5(5): 598-607. doi:10.1001/jamacardio.2020.0116

Jones WS, Mulder H, Wruck LM, et al. Comparative effectiveness of aspirin dosing in cardiovascular disease. N Engl J Med, 2021; 384(21); 1981-1990. doi:10.1056/NEJMoa2102137

Characterization of Patients with Heart Failure and Patients with Atrial Fibrillation and Atrial Flutter in PCORnet Data

Therapeutic Area: Cardiovascular

Research Question(s):
What is the occurrence of vascular, bleeding, or other events in Atrial Fibrillation or Atrial Flutter Patients patients?

Rao VN, Cyr D, Wruck L, et al. Electronic health record characterization and outcomes of heart failure with preserved ejection fraction. American Heart Journal. 2023. Vol263, Pg 1-14, ISSN 0002-8703. doi.org/10.1016/j.ahj.2023.04.013

Using PCORnet to Compare Blood Pressure Control Strategies

Therapeutic Area: Cardiovascular

Research Question(s):
How well are clinics and patients controlling blood pressure, and would new programs or technologies help improve blood pressure control?

Cooper-DeHoff RM, Fontil V, Carton T, et al. Tracking blood pressure control performance and process metrics in 25 US health systems: The PCORnet Blood Pressure Control Laboratory. J Am Heart Assoc, 2021; 10(21): e022224. doi:10.1161/JAHA.121.022224

PCORnet® Study of Post-Acute Sequelae of SARS-CoV-2 Infection in Adults (PCORnetPASC)

Therapeutic Area: Infectious Disease

Research Question(s):

What are the long term health effects of COVID-19 after a person has recovered from infection?
How can we better detect, predict, and treat these health effects and prevent future infection?

Hernandez-Romieu AC, Carton TW, Saydah S, et al. Prevalence of select new symptoms and conditions among person aged younger than 20 years and 20 years or older at 31 to 150 days after testing positive or negative for SARS-CoV-2. JAMA Netw Open. 2022;5(2):e2147053. doi.org/10.1001/jamanetworkopen.2021.47053

Comparative Effectiveness of Palliative Surgery vs Additional Anti-Seizure Medications for Lennox-Gastaut Syndrome

Therapeutic Area: Neurology

Research Question(s):

Which treatment options are most likely to improve important clinical outcomes in my child (or patient) with LGS?
My child has hundreds of seizures a week, and multiple different drugs have failed to get her seizures under control. What is the best possible next step?

Lam S, Rosenman M, Dixon-Salazar D, et al. Comparative effectiveness of epilepsy surgery versus additional anti-seizure medications for Lennox-Gastaut syndrome: study protocol for a multicenter, mixed-methods study. Front Neurol 2025;16:1569551. doi: 10.3389/fneur.2025.1569551

Bliss ND, Patel AD, Dixon-Salazar T, et al. Patient family engagement and partnership: Pilot survey results in assessing behavior, communication, and quality of life in children with Lennox-Gastaut syndrome and other drug-resistant epilepsy. Epilepsy Behav 2023;148:109451. doi: 10.1016/j.yebeh.2023.109451

Votoupal M, Muller R, Patel AD, et al. Navigating the diagnosis: A survey on caregivers’ journeys to Lennox-Gastaut syndrome. Epilepsy Behav 2025;171:110600. doi: 10.1016/j.yebeh.2025.110600

Empagliflozin Diabetic Kidney Disease (Empa DKD)

Therapeutic Area: Nephrology

Research Question(s):

Can we better understand why patients with type-2 diabetes may not receive guideline-recommended screening for diabetic kidney disease?
Which medications may be most effective at improving kidney and heart outcomes in patients with and without type-2 diabetes?

Edmonston, D, Mulder, H, Lydon, E. et al. Kidney and Cardiovascular Effectiveness of SGLT2 Inhibitors vs GLP-1 Receptor Agonists in Type 2 Diabetes. JACC. 2024 Aug, 84 (8) 696–708. doi.org/10.1016/j.jacc.2024.06.016

Edmonston D, Mulder H, Lydon E, et al. Kidney and Cardiovascular Effectiveness of Empagliflozin Compared With Dipeptidyl Peptidase-4 Inhibitors in Patients With Type 2 Diabetes. Am J Cardiol. 2024;221:52-63. doi:10.1016/j.amjcard.2024.04.011

Semantic Data Quality Standards for Multi-Center Clinical Research Studies and Networks

Therapeutic Area: Data Science

Research Question(s):

Can we find ways to more accurately describe how suitable data are to answer a specific research question?
What are the tools that can be used across studies to consistently describe whether the data are high quality?

Razzaghi H, Dickinson K, Wieand K, et al. A multifaceted approach to advancing data quality and fitness standards in multi-institutional networks. J Am Med Inform Assoc. 2025;ocaf181. doi:10.1093/jamia/ocaf181

Comparing patient-reported impact of COVID-19 shelter-in-place policies and access to containment and mitigation strategies, overall and in vulnerable populations

Therapeutic Area: Infectious Disease

Research Question(s):

What is the comparative impact of different shelter-in-place/reopening policies, overall and in vulnerable populations, on patient-reported financial insecurity, mental health, and other subjective outcomes important to patients?
What is the comparative effectiveness of county-level containment and mitigation strategies at achieving timely access to testing, healthcare, information, and contact tracing, overall and in vulnerable populations?
What is the comparative accuracy of different algorithms designed to predict risk of infection and severe COVID-19 among patients with symptoms, overall and in vulnerable populations?

Beatty AL, Peyser ND, Butcher XE, et al. The COVID-19 citizen science study: protocol for a longitudinal digital health cohort. JMIR Res Protoc, 2021; 10(8):e28169. doi:10.2196/28169

Neuroendocrine Tumors – Patient Reported Outcomes (NET-PRO)

Therapeutic Area: Oncology

Research Question(s):

Which care options work, for whom, and under which circumstances in order to improve symptom management, treatment outcomes and quality of life among NET patients?

Common treatment combinations and their relation to disease symptoms and quality of life
Identification of the best ordering of treatments and relation to patient outcomes and survival
The impact of patient traits and tumor characteristics on treatment choice(s) and survival

Hourcade JP, O’Rorke M, Chrischilles E, et al. Personal Health Record Software for Neuroendocrine Tumors: Patient Centered Design Approach. JMIR Hum Factors. 2025;12:e68788. Published 2025 Jun 3. doi:10.2196/68788

Outcomes Database to Prospectively Assess Changing Therapy Landscape in Renal Cell Carcinoma (ODYSSEY RCC)

Therapeutic Area: Oncology

Research Question(s):

Can a research registry of patients with metastatic renal cell carcinoma (mRCC) patients help us better understand cancer management and health-related quality of life while receiving mRCC specific treatment? In combination with patient and physician surveys, PCORnet will be used to help us answer these questions.

Bhavsar NA, Harrison MR, Scales CD, et al. Design and Rationale of the Outcomes Database to Prospectively Assess the Changing Therapy Landscape in Renal Cell Carcinoma Registry: A Multi-institutional, Prospective Study of Patients with Metastatic Renal Cell Carcinoma. Eur Urol Open Sci. 2024;66:75-81. Published 2024 Jul 3. doi:10.1016/j.euros.2024.06.007

A Patient-Centered PaTH to Addressing Diabetes

Therapeutic Area: Metabolic Disorders

Research Question(s):

How often is intensive behavioral therapy (IBT) being utilized in primary care and how has it impacted weight and diabetes outcomes for patients with and at-risk of type 2 diabetes?
What is the impact of telemedicine utilization during the COVID-19 pandemic for patients with and at-risk of type 2 diabetes?
What are demographic and clinical characteristics associated with severe COVID-19 outcomes across multiple phases of the COVID pandemic for patients with or at-risk of type 2 diabetes?

Kraschnewski JL, Kong L, Francis E, et al. A Patient-Centered PaTH to Address Diabetes: Protocol for a Study on the Impact of Obesity Counseling. JMIR Res Protoc. 2019 Apr 4;8(4):e12054. doi.org/10.2196/12054

Soleymani T, Lehman EB, Kong L, et al. Bariatric surgery and COVID-19 outcomes: results from the PaTH to Health: Diabetes study. Surg Obes Relat Dis. 2024;20(11):1039-1045. doi:10.1016/j.soard.2024.05.016

ACTIV-6: COVID-19 Study of Repurposed Medications

Therapeutic Area: Infectious Disease

Research Question(s):
Can repurposed medications reduce symptoms of non-hospitalized participants with mild to moderate COVID-19?

Naggie S, Boulware DR, Lindsell CJ, et al. Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2022;328(16):1595–1603. doi:10.1001/jama.2022.18590

McCarthy MW, Naggie S, Boulware DR, et al. Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2023;329(4):296–305. doi:10.1001/jama.2022.24100

Naggie S, Boulware DR, Lindsell CJ, et al. Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19: A Randomized Clinical Trial. JAMA. 2023;329(11):888–897. doi:10.1001/jama.2023.1650

Biologic Abatement and Capturing Kids’ Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA)

Therapeutic Area: Autoimmune (Allergy and Immunology)

Research Question(s):

This trial will compare how patients with inactive spondyloarthritis on tumor necrosis factor inhibitor (TNFi) treatment respond to three treatment options that doctors currently use:

Continue standard TNFi medication,
Space out the time between usual TNFi medication doses, or
Stop the TNFi medication. If we can safely prolong the time between doses or completely take away TNFi therapy in this population, we may remove unnecessary medication exposure, improve patient quality of life, and lower medication costs.

Weiss PF, Sears CE, Brandon TG, et al. Biologic Abatement and Capturing Kids’ Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA): study protocol for a randomized pragmatic trial. Trials. 2023;24(1):100. Published 2023 Feb 8. doi:10.1186/s13063-022-07038-6

Pediatric KIDney Stone (PKIDS) Care Improvement Network

Therapeutic Area: Nephrology

Research Question(s):
What are the differences in stone clearance and the lived experiences of youth, age 8-21 years, following ureteroscopy (URS), shock wave lithotripsy (SWL), and percutaneous nephrolithotomy (PCNL) for the removal of kidney and ureteral stones?

Ellison JS, Lorenzo M, Beck H on behalf of the Pediatric KIDney Stone Care Improvement Network, et al. Comparative effectiveness of paediatric kidney stone surgery (the PKIDS trial): study protocol for a patient-centred pragmatic clinical trial. BMJ Open 2022;12:e056789. doi:10.1136/bmjopen-2021-056789

Evaluating the Comparative Effectiveness of Telemedicine in Primary Care: Learning from the COVID-19 Pandemic

Therapeutic Area: Healthcare Delivery

Research Question(s):
What are the features of primary care telemedicine programs that have been newly implemented or expanded in response to the COVID-19 pandemic, and how do different populations experience these programs?

Lin, J.J., Horowitz, C.R., Ancker, J.S. An Urgent Need for Guidelines for Telemedicine Use. J Gen Intern Med 38, 1061–1062 (2023). doi:10.1007/s11606-022-07905-7

Yu J, Andreadis K, Schpero WL, et al. Patient experiences with and preferences for telemedicine relative to in-person care during the COVID-19 pandemic. Telemedicine and e-Health. Published online 2023. doi:10.1089/tmj.2022.0311

Muellers KA, Andreadis K, Ancker JS, et al. Provider and patient experiences of delays in primary care during the early COVID-19 pandemic. Journal for Healthcare Quality. 2023;45(3):169-176. doi:10.1097/jhq.0000000000000380

Cognitive Behavioral Therapy and Real-Time Pain Management Intervention for Sickle Cell via Mobile Applications (CaRISMA)

Therapeutic Area: Mental and Behavioral Health

Research Question(s):
Does mobile phone-delivered computerized cognitive behavioral therapy provide a greater benefit for daily pain and depression in adult patients with sickle cell disease than digital education?

Badawy SM, Abebe KZ, Reichman CA, et al. Comparing the effectiveness of education versus digital cognitive behavioral therapy for adults with sickle cell disease: protocol for the cognitive behavioral therapy and real-time pain management intervention for sickle cell via mobile applications (CaRISMA) study. JMIR Res Protoc, 2021; 10(5):e29014. doi:10.2196/29014

Medications and Weight Gain in PCORnet: The MedWeight Study

Therapeutic Area: Metabolic Disorders

Research Question(s):
How do six classes of commonly prescribed medications influence weight, risk for diabetes, and cholesterol over time?

Sun JW, Young JG, Sarvet AL, et al. Comparison of rates of Type 2 Diabetes in adults and children treated with anticonvulsant mood stabilizers. JAMA Netw Open. 2022;5(4). doi:10.1001/jamanetworkopen.2022.6484

Petimar J, Young JG, Yu H, et al. Medication-Induced Weight Change Across Common Antidepressant Treatments : A Target Trial Emulation Study. Ann Intern Med. 2024;177(8):993-1003. doi:10.7326/M23-2742

Lin PD, Rifas-Shiman S, Merriman J, et al. Trends of Antihypertensive Prescription Among US Adults From 2010 to 2019 and Changes Following Treatment Guidelines: Analysis of Multicenter Electronic Health Records. J Am Heart Assoc. 2024;13(9):e032197. doi:10.1161/JAHA.123.032197

Pragmatic Evaluation of Events and Benefits of Lipid-lowering in Older Adults (PREVENTABLE)

Therapeutic Area: Cardiovascular

Research Question(s):
Can a statin help prevent dementia and disability in adults aged 75 or older, as well as heart attacks and other cardiovascular-related deaths, while not increasing risks of adverse health outcomes?

Sachs BC, Rapp SR, Kistler CE, et al. The pragmatic evaluation of events and benefits of lipid-lowering in older adults (PREVENTABLE) trial: study design and procedures for cognitive assessment and adjudication. Alzherimers. Dement., 2021; 17(Supp.9). doi.org/10.1002/alz.054022

PCORnet® Study Publications

PCORnet®: Accelerating Patient-Centered Comparative Clinical Effectiveness Research

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