Grants and Contracts – Center for Pharmacoepidemiology and Treatment Science

Evaluating the Role of Multimorbidity in Modulating Medication Effects in Older Adults

Project Number: 1R01HL16316301
Principal Investigator: Dr. Chintan Dave
Study Period: 2/2023 – 1/2024
Funding Agency: NHLBI
Total Direct Cost: $3,474,183

This proposal will evaluate the impact of multimorbidity on modulating the safety and effectiveness of cardiometabolic therapies among older adults.

Predictors of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes

Project Number: 3-SRA-2022-1257-S-B
Principal Investigator: Dr. Chintan Dave
Study Period: 8/2022 – 7/2024
Funding Agency: Juvenile Diabetes Research Foundation
Total Direct Cost: $695,404

Completion of this project will generate rigorous and actionable evidence furthering our understanding of both why and which children present in diabetic ketoacidosis at diagnosis of type 1 diabetes.

Advanced Development and Utilization of Assembled Aging Trajectory Files from Multiple Datasets

Project Number: R33 AG068931-01A1
Co-Investigator: Dr. Soko Setoguchi
Study Period: 4/2021 – 3/2026
Funding Agency: NIH/NIA

The goal is to develop sustainable research infrastructure to support projects that address key interdisciplinary aging research questions relevant to care & interventions for people living with chronic illness including ADRD.

Benzodiazepine-related harms in young people: Informing policy, interventions, and prescribing

Project Number: 1K01DA050769-01A1
Principal Investigator: Dr. Greta Bushnell
Study Period: 3/2021 – 2/2026
Funding Agency: NIH/NIDA
Total Direct Cost: $899,782

Benzodiazepines are frequently prescribed to adolescents and young adults, yet we lack key data on misuse, abuse, and overdose risk following benzodiazepine treatment and on what policies reduce benzodiazepine- related harms in young people. The proposed research will examine the risk of overdose and harmful substance use following benzodiazepine treatment and will evaluate whether state prescription drug monitoring program features are associated with a reduction in benzodiazepine-related harms and risky benzodiazepine prescribing.

Neurocognitive Markers of Short-Term Risk for Suicidal Behavior in High-Risk Veterans

Project Number: 5I01CX001826
Co-Investigator: Dr. Chintan Dave
Study Period: 2/2021 – 2/2023
Funding Agency: Health Services and Research (Veterans Health Administration)
Total Direct Cost: $1,432,710

Completion of this project will yield a more accurate clinical risk prediction model for identifying veterans who may be at high near-term risk of attempted suicides.

Live Microbials to Boost Anti-SARS-CoV-2 Immunity Clinical Trial (Live BASIC Trial)

Project Number: N/A
Co-Director, Epidemiology Core: Dr. Daniel Horton
Study Period: 2/2021 – 1/2022
Funding Agency: Danisco USA Inc.

This randomized trial will examine whether persons previously infected by SARS-CoV-2 experience an increase in immune response against SARS-CoV-2 after receiving a special combination of live microbials.

COVID-19 Network of Networks Expanding Clinical and Translational approaches to Predict Severe Illness in Children (CONNECT to Predict SIck Children)

Project Number: 1R61HD105619-01
Co-Principal Investigator: Dr. Daniel Horton
Study Period: 1/2021 – 11/2022
Funding Agency: NIH/NICHD
Total Direct Cost: $1,239,418

Develops models and uses biomarkers to predict risk for severe disease in children and adolescents by systematically integrating social science, epidemiological, genetic, biochemical, immunological, and computational approaches.

Predicative Modeling of the Prevalence of Non-Small Cell Lung Cancer Biomarkers

Contract
Principal Investigator: Dr. Soko Setoguchi
Study Period: 1/2021 – 3/2023
Funding Agency: Daiichi Sankyo Inc.
Total Direct Cost: $525,834

The aims of this project are to develop, internally and externally validate, and pilot test a predictive model to predict HER2 and/or HER3 positive or low status in Non-small cell lung cancer with the application of the models to other large databases in mind.

Validity of Claims-Based Definitions for Interstitial Lung Disease in Japan

Project Number: A548VA01
Principal Investigator: Dr. Soko Setoguchi
Study Period: 1/2021 – 03/2023
Funding Agency: Pfizer Japan Inc.
Total Direct Cost: $136,915

The major goals of this project are 1) identifying, approaching, and recruiting potential Japanese academic collaborators for the ILD validation study; 2) drafting and finalizing study protocol and other study materials for the validation of interstitial lung disease (ILD) with input from Pfizer investigators, Japanese academic collaborators, and site investigators; 3) overseeing the conduct of the feasibility assessment, pilot study, and main study by closely working with CRO; 4) analyzing the de-identified site data from EP-CRSU Co., Ltd.; and drafting the study report to support the writing of the manuscripts for ILD.

PCORI Associate Editor

Contract subcontract
Subaward Principal Investigator: Dr. Soko Setoguchi
Study Period: 1/2021 – 12/2022
Funding Agency: PICORI contract with OHSU
Total Direct Cost: $46,038

Dr. Soko Setoguchi will serve as an Associate Editor in the review process for PCORI Primary Research Projects, per OHSU’s agreement with PCORI.

Validity of Claims-Based Definitions for Thromboembolic Events in Japan

Project Number: A3921333
Principal Investigator: Dr. Soko Setoguchi
Study Period: 11/2020 – 10/2021
Funding Agency: Pfizer Japan Inc.
Total Direct Cost: $63,574

The major goals of this project are 1) identifying, approaching, and recruiting potential Japanese academic collaborators for the pulmonary embolism and deep vein thrombosis and (PE-DVT) validation study; 2) drafting and finalizing study protocol and other study materials for the validation of PE-DVT (which will likely be revised during the pilot study) with input from Pfizer investigators, Japanese academic collaborators, and site investigators; 3) overseeing the conduct of the feasibility assessment, pilot study, and main study by closely working with the local CRO, EP-CRSU Co., Ltd. (see Table 1 below for more details); and 4) analyzing the de-identified site data from EP-CRSU Co., Ltd.; and drafting the study report to support the writing of the manuscripts for PE-DVT.

Clinical and Translational Science Award (COMBAT COVID)

Project Number: 3UL1TR001445-05S2
Subaward Principal Investigator: Dr. Soko Setoguchi
Study Period: 9/2020 – 3/2022
Funding Agency: NIH/NCATS
Total Direct Cost: $53,418

The purpose of the collaborative is to accumulate a set of row level data on patients with COVID- 19 testing or persons under investigation (PUI). This will be an exercise in data ingestion, extract, transfer, and loading, which will perform data cleaning, data normalization and data integration across much of the eastern seaboard. This data will feed into National COVID Cohort Collaborative and make the process of data ingestion more seamless.

Supplement, New Jersey Alliance for Clinical and Translational Science: NJ ACTS

Project Number: UL1TR003017-02S1
Co-Director, Epidemiology Core: Dr. Daniel Horton
Study Period: 7/2020 – 2/2021
Funding Agency: NIH/NCATS

Our CTSA Hub focuses on two overarching themes: the heterogeneity of disease pathogenesis and response to treatment, and the value of linking large clinical databases with interventional clinical investigations to identify cause-and-effect and predict therapeutic responses. NJ ACTS will provide an alliance that will catalyze clinical research and training across New Jersey to improve population health and contribute to the CTSA Consortium.

An Integrated Clinical Research Database for CF Patients and Families

Project Number: SETOGU20AB0
Principal Investigator: Dr. Soko Setoguchi
Study Period: 6/2020 – 5/2021
Funding Agency: Cystic Fibrosis Foundation
Total Direct Cost: $114,991

In this pilot study, using data from Cystic Fibrosis Foundation Patient Registry (CFFPR) and Medicaid (2015-2016), we will establish a linkage between these two databases and assess the utility of this linked data set for clinical research in CF patients by conducting descriptive analyses for the linked patients. We will also apply previously established methods to link CF infants to their family members in Medicaid data, in order to assess the feasibility of research examining the impact of prenatal events in children with CF.

Cohort study of SARS-CoV-2 incidence, risk factors, and disease severity in healthcare workers

Project Number: U01AI122285
Co-Director, Epidemiology Core: Dr. Daniel Horton
Study Period: 5/2020 – 4/2021
Funding Agency: NIH/NIAID

Our CTSA Hub focuses on two overarching themes: the heterogeneity of disease pathogenesis and response to treatment, We will establish a prospective cohort of healthcare workers in a large university-based health system in north and central New Jersey to assess the prevalence and incidence of SARS-CoV- 2 infection. We will determine risk factors for infection and for severe illness, and risks for transmission to and from these healthcare workers.

A Novel Approach to Examine Within-Class Therapeutic Exchangability of Medications

Project Number: 5R01AG063937-02
Principal Investigator: Dr. Tobias Gerhard
Study Period: 4/2020 – 3/2025
Funding Agency: NIH/NIA
Total Direct Cost: $1,934,699

Despite the absence of supporting evidence, treatment guidelines and prescription drug insurance formularies typically assume that individual drugs within medication classes are equally effective and equally safe. Yet, when incorrect, these assumptions expose patients to suboptimal treatments and clinical harms, particularly older adults, who are disproportionately affected by chronic conditions and take more prescription medications than any other population. Taking advantage of natural experiments created by the design of the Medicare prescription drug benefit, the proposed study will use existing data on more than 22 million Medicare beneficiaries to answer key questions about the comparative benefits and harms among drugs within each of four therapeutic classes widely-used among older adults.

Real-World Safety of Tofacitinib in Patients with RA in Japan – A Feasibility Assessment and Protocol Development

Project Number: N/A
Principal Investigator: Dr. Soko Setoguchi
Study Period: 1/2020 – 3/2020
Funding Agency: Pfizer Japan Inc.
Total Direct Cost: $53,846

The major goals of this project are 1) drafting and finalizing study protocol for the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) application; 2) identifying, approaching, and recruiting potential Japanese academic collaborators and working with the collaborators on the NDB application; and 3) identifying different paths to access NDB data, and recommending the best option for the study.

Feasibility Assessment for Validating Thromboembolic Events in Japan

Project Number: N/A
Principal Investigator: Dr. Soko Setoguchi
Study Period: 1/2020 – 3/2020
Funding Agency: Pfizer Japan Inc.
Total Direct Cost: $61,539

The major goals of this project are 1) identifying, approaching, and recruiting potential Japanese hospital or academic collaborators and sites for the PE/DVT validation study; 2) drafting literature searches on PE/DVT in Japan, Japanese validation studies, and exploration of potential approaches to conduct validation studies in Japan; 3) drafting study concept and feasibility assessment report for the PE/DVT validation study; and 4) drafting study protocol for the PE/DVT validation study.

Data Analysis for Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) Study

Project Number: 75N95019C00057
Subaward Principal Investigator: Dr. Tobias Gerhard
Study Period: 9/2019 – 9/2021
Funding Agency: NIH/NIA
Total Direct Cost: $278,563

There is an urgent need to discover effective treatments for Alzheimer’s Disease (AD) which currently affects more than five million Americans. Original research performed in the Unit of Clinical and Translational Neuroscience, NIA Intramural Research Program (IRP) has identified several commonly used medications that may protect against AD. The purpose of the project is to perform data analysis to confirm whether these drugs protect against AD.

Optimizing and Personalizing Interventions for Schizophrenia Across the Lifespan (OPAL): Identifying age-related antecedents to suicide in schizophrenia

Project Number: 3P50MH115843-02S2
Subaward Principal Investigator: Dr. Tobias Gerhard
Study Period: 8/2019 – 12/2020
Funding Agency: NIH/NIMH
Total Direct Cost: $139,803

The suicide supplement, part of “Optimizing and Personalizing Interventions for Schizophrenia Across the Lifespan” (OPAL) center, will serve as the basis for a competitive application to NIMH for age-specific research on where, when, and how to identify suicide risk and to intervene to prevent suicide in schizophrenia.

Antibiotics, Juvenile Idiopathic Arthritis, and Antirheumatic Treatment Response

Project Number: 1R01AR074436-01A1
Principal Investigator: Dr. Daniel Horton
Study Period: 8/2019 – 6/2023
Funding Agency: NIH/NIAMS
Total Direct Cost: $1,535,371

The proposed study will investigate whether antibiotics could contribute to the development of juvenile idiopathic arthritis and impair the ability of children with juvenile idiopathic arthritis to respond to standard treatments, such as methotrexate. This research could support novel efforts to curb antibiotic overuse in children and to alter gut bacteria (for example, through diet or probiotics) as a way to prevent juvenile idiopathic arthritis and promote the use of effective, tailored, and appropriate medicines.

Health outcomes for patients dually diagnosed with diabetes and cardiovascular diseases

Project Number: 5KL2TR003018
Principal Investigator: Dr. Chintan Dave
Study Period: 7/2019 – 6/2021
Funding Agency: NIH/NCATS
Total Direct Cost: 80% Effort

The overarching aim of this proposal is to examine the clinical issues that arise in patients who are dually diagnosed with diabetes and cardiovascular diseases. One such issue is the effects of glucose altering non-diabetic medications (e.g. antihypertensives) and incidence of severe hypoglycemic and hyperglycemic events. This KL2 will leverage robust observational data to address these uncertainties.

Strengthening the Evidence-Base for Drug-Disease Interactions in Older Adults

Project Number: 5R01AG061092-02
Principal Investigator: Dr. Tobias Gerhard
Study Period: 7/2019 – 2/2024
Funding Agency: NIH/NIA
Total Direct Cost: $1,821,212

Drug-disease interactions affect a large and growing number of older adults and have been associated with severe adverse outcomes including increased mortality. Warnings and contraindications are in place for many thousands of drug-disease combinations but, despite their substantial public health impact, virtually none of these warnings are based on evidence from well-designed studies. The proposed study will use four carefully selected examples of hypothesized drug-disease interactions of widely used drugs to begin a line of work that leverages extremely large data resources together with innovative methods from multiple fields to generate definitive quantitative data on the effects of patient-specific comorbidities on the safety and effectiveness of their therapeutic regimens.

Optimizing and Personalizing Interventions for Schizophrenia Across the Lifespan (OPAL): Understanding the Co-occurrence of Schizophrenia and Alzheimer’s Disease and Related Dementias

Project Number: 3P50MH115843-02S1
Principal Investigator: Dr. Tobias Gerhard
Study Period: 7/2019 – 7/2020
Funding Agency: NIH/NIMH
Total Direct Cost: $165,660

The proposed study examines the incidence of Alzheimer’s disease and its related dementias (ADRD) diagnoses among older persons diagnosed with schizophrenia and investigate how this co-occurrence affects health service use, pharmacologic treatment, and outcomes in this population. This project is part of “Optimizing and Personalizing Interventions for Schizophrenia Across the Lifespan” (OPAL) center that aims to accelerate the adaptation, development and implementation of effective, personalized treatments in real‐world settings for people diagnosed with schizophrenia.

Disease Recapture after Drug Discontinuation and Flare in JIA

Project Number: N/A
Co-Investigator: Dr. Daniel Horton
Study Period: 7/2019 – 6/2021
Funding Agency: Rheumatology Research Foundation

This study will measure how often JIA flares after tapering or stopping medicine can be well-controlled again within 6 months and will identify children whose flare may be more or less likely to be well-controlled quickly.

Clinical Outcomes of Multimorbid Older Adults Co-Diagnosed with Diabetes and Cardiovascular Diseases

Project Number: 1KL2 TR003018
Principal Investigator: Dr. Chintan Dave
Study Period: 7/2019 – 6/2021
Funding Agency: NJ ACTS / NCATS
Total Direct Cost: $358,480

The overarching aim of this proposal is to examine the clinical issues that arise in older adults dually diagnosed with diabetes and cardiovascular diseases.

Disease Outcomes in Older adults under extreme Heat, AiR pollution and Medication use (DO-NO-HARM)

Project Number: 1R01AG060232-01A1
Principal Investigator: Dr. Soko Setoguchi
Study Period: 6/2019 – 4/2024
Funding Agency: NIH/NIA
Total Direct Cost: $2,174,188

The major goals of this project are to assess the effects of extreme heat among users and non-users of commonly-used medications in high-risk older adults, to assess the synergistic effects of air pollution, i.e., particulate matter (PM) and ozone, among users and non-users of medications known to cause cardiovascular (CV), thromboembolic, and bleeding events in high-risk older adults, and to assess the synergistic effects of extreme heat and air pollution among users and non-users of the aforementioned medications.

New Jersey Alliance for Clinical and Translational Science: NJ ACTS

Project Number: UL1TR003017-01
BERD – Large Linked Data Sets Co-Lead: Dr. Tobias Gerhard
Study Period: 3/2019 – 2/2024
Funding Agency: NIH/NCATS

To advance clinical and translational science across the continuum by training the next generation of researchers and by understanding the heterogeneity of disease and of response to interventions in diverse individuals, communities and populations. Building on a solid foundation, we seek to leverage our strengths with those of the CTSA Consortium to propel discovery, development and dissemination in translational research across New Jersey.

New Jersey Alliance for Clinical and Translational Science: NJ ACTS

Project Number: 3UL1TR003017-02S2
Co-Investigator: Dr. Daniel Horton
Study Period: 3/2019 – 2/2024
Funding Agency: NIH/NCATS

Through ongoing follow-up of identified under-represented minority members in existing healthcare worker cohorts, we will advance COVID-19 testing in their communities by providing access to testing for their households and extended families. We will compare this outreach approach with other more conventional means of stimulating testing. In light of the continuing COVID-19 pandemic, this research will help us to find better ways to reach members of vulnerable under-represented minority communities to lessen the impact of COVID-19.

Opioid Overdoses among Medicaid Beneficiaries: Predictors, Outcomes, and State Policy Effects

Project Number: 1R01DA047347-01
Principal Investigator: Dr. Daniel Horton
Study Period: 3/2019 – 1/2023
Funding Agency: NIH/NIDA

This study will identify the interacting roles of patient, treatment and policy factors in overdose risk, and actionable points for intervention using Medicaid data linked with the National Death Index.

Characterizing the Acute Heart Failure Patient Population in Japan

Project Number: N/A
Principal Investigator: Dr. Soko Setoguchi
Study Period: 3/2019 – 3/2020
Funding Agency: Bristol Meyer Squibb
Total Direct Cost: $53,231

The major goals of this project are 1) to describe demographic, clinical, and hospital characteristics among acute heart failure with reduced ejection fraction (HFrEF) patients, 2) to describe incidence of mortality, readmission, and prolonged length of stay (LOS) among acute HFrEF patients, and 3) to determine the predictors of HF-related mortality, readmission, and prolonged LOS among acute HFrEF patients.

Modifying the Risk and Outcome of Heart Failure in Patients with Rheumatoid Arthritis

Project Number: WI236029
Principal Investigator: Dr. Soko Setoguchi
Study Period: 10/2018 – 3/2023
Funding Agency: Pfizer Inc.
Total Direct Cost: $611,373

The major goals of this project are to assess the burden and outcome of heart failure (HF) hospitalizations in large rheumatoid arthritis population versus general population, to compare tofacitinib with other biologic Disease-modifying antirheumatic drugs (DMARDs), and to assess the feasibility of estimating the effectiveness of biologic DMARDs separately on HF with reduced ejection fraction and HF with preserved ejection fraction.

Drugs, Germs, and Joints: Antibiotics, Gut Microbiota, and Juvenile Idiopathic Arthritis

Project Number: K23-AR070286-01
Principal Investigator: Dr. Daniel Horton
Study Period: 9/2016 – 8/2021
Funding Agency: NIH/NIAMS
Total Direct Cost: $879,100

This project will examine the complex relationship between antibiotics, infections, and the microbiome in relation to the development and activity of juvenile idiopathic arthritis. New insights into the mechanisms underlying juvenile idiopathic arthritis and the role of antibiotics may ultimately lead to new, less toxic ways of treating, preventing, or even curing these chronic childhood diseases.