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Yale University-Mayo Clinic CERSI

Center of Excellence in Regulatory Science and Innovation

The Yale-Mayo CERSI conducts high-quality, high-impact collaborative research to support several areas of focus in the FDA strategic plan for regulatory science. Research topic areas include: advancing clinical and post-market surveillance of drugs and biologics, advancing clinical and post-market surveillance of medical devices and diagnostic tests, development and application of novel analytics, and fostering patient-centered decision making.

For comments or questions pertaining to our CERSI research projects, contact the Yale-Mayo Clinic CERSI at CERSI@yale.edu.

Current Projects

Modernizing Development, Evaluation, and Post-Market Surveillance of Drugs and Biologics

Characterizing use, safety and efficacy of brand-name and generic drugs used to treat hypothyroidism
Use of instrumental variable approaches to assess the safety and efficacy of brand-name and generic drugs used to treat hypothyroidism

Project Details: To test instrumental variable methods for comparing the effectiveness and safety of brand-name and generic L-thyroxine using large administrative claims data, and to develop toolkits supporting the implementation of these methods in future research.

Project Results: Project complete; no public results

Linking data sources to elucidate non-fatal and fatal opioid-related overdose epidemiology and the role of FDA-regulated products

Project Details: To link Connecticut state-level datasets to assess patterns of FDA-regulated medication receipt and service utilization prior to opioid-related overdoses; to evaluate concordance between prescription records and post-mortem toxicology; and to examine associations between demographics, prescription history, and treatment engagement with subsequent risk of fatal and non-fatal overdose

Project Results:

Merging statewide data in a public/university collaboration to address opioid use disorder and overdose (2021)

Concordance between controlled substance receipt and post-mortem toxicology in opioid-detected overdose deaths: A statewide analysis (2023)

Characterization and analysis of high incidence of potentially unsafe prescribing of some Extended-Release (ER) opioid analgesics using Natural Language Processing (NLP) of Electronic Health Record (EHR) clinical notes

Project Details: To determine the frequency of inappropriately prescribing extended-release opioid analgesics requiring prior opioid tolerance to non-tolerant patients, and to analyze prescribing behaviors by exploring free text fields within the patients’ electronic health records with natural language processing among those identified as being non-opioid tolerant but are receiving a higher dosage opioid prescription.

Project Results:

Assessment of Potentially Inappropriate Prescribing of Opioid Analgesics Requiring Prior Opioid Tolerance (2020)

Understanding the contribution of laboratory data linked to administrative claims: a case study looking at renal function and oral anticoagulant performance in patients with atrial fibrillation
Characterizing safety and efficacy of brand-name and generic drugs used to treat hypothyroidism among patients who switch therapy formulation

Project Details: To examine rates and factors associated with switching between generic levothyroxine products within one year of treatment initiation, and to compare thyrotropin stimulating hormone levels among patients who switch versus those who remain on the same sourced product.

Project Results:

Rates of, and factors associated with, switching among generic levothyroxine preparations in commercially insured American adults (2022)Endocrine 2022 publication

Association Between Generic-to-Generic Levothyroxine Switching and Thyrotropin Levels Among US Adults (2022) JAMA IM 2022 publication

Real-world data to assess variation in opioid prescribing and use for acute pain in diverse populations

Project Details: To assess patients’ pain levels and persistence, functional outcomes, and use of prescribed and over-the-counter pain medications after acute pain episodes; to examine how demographic, clinical, and emotional factors relate to pain and opioid use over time in diverse populations; and to determine how patients handle unused opioids.

Project Results:

Acute pain pathways: protocol for a prospective cohort study (2022)

Quantifying the relationship between inappropriate prescribing of opioid-tolerant-only medications to patients without prior opioid tolerance and opioid-related harms

Project Details: To measure the risk of opioid-related harms associated with inappropriately prescribing opioid-tolerant-only medications to individuals who do not meet the opioid tolerance requirements, using medical billing and mortality data, and to identify factors associated with these harms.

Project Results:

Pending

Trends in opioid use among patients with cancer

Project Details: To assess trends in receipt of new opioid use and new persistent opioid use among patients with cancer by conducting population-level analysis and health system analysis, across distinct cancer stages and treatment scenarios

Project Results:

Trends in new and persistent opioid use in older adults with and without cancer (2024)

Sex differences in immune profiles of PASC before and after vaccination

Project Details: To investigate sex differences in immune responses and symptoms among individuals with Long COVID before and after vaccination, and to compare them to those in individuals with prior COVID-19 but without Long COVID.

Project Results:

Pending

A mixed methods research design to identify factors influencing prescriber decision-making about pain management and opioid prescribing

Project Details: To identify factors influencing prescriber decision-making about opioid pain medication through interviews and focus groups with healthcare providers, and to develop a survey that measures how providers make decisions about prescribing opioid pain medications.

Project Results:

Pendiing

Prescription Stimulants for Attention-Deficit/Hyperactivity Disorder (ADHD): Prescribing Patterns and Associated Consequences in the Veterans Health Administration[JR1] [JR1]**NEW please add

Project Details: To characterize stimulant prescribing patterns among adults with ADHD, identify associated patient- and facility-level factors, validate structured data to identify ADHD and stimulant use disorder, and assess its related risks.

Project Results:

PendingTBD

Modernizing Development, Evaluation, and Post-Market Surveillance of Medical Devices and Diagnostic Tests

Post-market surveillance with a novel mHealth platform

Project Details: To explore whether a new mobile health technology that integrates patient-reported outcomes, wearable device data, electronic health records, and pharmacy data can support FDA post-market surveillance of medical devices

Project Results:

Aggregating multiple real-world data sources using a patient-centered health-data-sharing platform (2020)

Real world short- and intermediate-term safety outcomes following atrial fibrillation ablation

Project Details: To use real-world claims data to characterize short- and intermediate-term complication rates of atrial fibrillation ablation, with an emphasis on atrioesophageal fistula

Project Results:

Catheter-related complications and mortality of atrial fibrillation ablation following introduction of contact force-sensing technology (2020)

Implementation of a stakeholder survey to facilitate enhanced pediatric medical device innovation

Project Details: To implement a stakeholder survey to assess how the current regulatory environment influences business decision-making, particularly for medical devices for pediatric and special populations, and to identify strategies that incentivize innovation and foster a supportive marketplace for technologies that improve their care.

Project Results:

Pending

Identification of FDA-approved devices using Unique Device Identifiers (UDIs) from routinely collected electronic medical record data[MB1] [MB1]**New, please add

Project Details: To characterize Class I medical device recalls and to evaluate whether recall notices include complete Unique Device Identifiers to support effective identification and management of recalled devices.

Project Results:

Availability of Unique Device Identifiers for Class I Medical Device Recalls From 2018 to 2022 (2023)

Characterization of US Food and Drug Administration Class I Recalls from 2018 to 2022 for Moderate- and High-Risk Medical Devices: A Cross-Sectional Study (2023)

Evaluating mobile health tool use for capturing patient-centered outcome measures in heart failure patients

Project Details: To evaluate the feasibility of using mobile health platforms, including smartphones and wearable devices, to capture functionality, symptoms, continuous activity levels, and quality of life measures in patients with heart failure.

Project Results:

Pending

Standardizing multi-model data for the diagnosis and prognosis of coccidioidomycosis as a model for establishing harmonized core data for additional infectious diseases

Project Details: To measure how closely a prototype rapid antibody test can approximate the traditional methods used to measure titers of antibodies against Coccidioides and identify the most informative combinations of clinical data for diagnosing, monitoring, and treating coccidioidomycosis

Project Results:

Pending

Redefining the paradigm for Lyme disease diagnosis and therapeutics

Project Details: To develop and publicly release a LymeX data schema for Lyme disease diagnostics to support clinical trials and documentation of the broad manifestations of all stages of Lyme disease

Project Results:

Pending

Development and Application of Novel Analytics

Utilization and adverse events associated with mechanical circulatory support devices among patients with acute myocardial infarction and cardiogenic shock undergoing PCI
Understanding the use of existing real-world data for medical product evaluation

Project Details: To better understand the potential advantages and limitations of applying observational research methods to real-world clinical data to emulate the populations and results of ongoing clinical trials used for FDA regulatory evaluations.

Project Results:

Real-world Cardiovascular Outcomes Associated With Degarelix vs Leuprolide for Prostate Cancer Treatment (2021)

Emulating the GRADE trial using real world data: retrospective comparative effectiveness study (2022)

Assessing the use of observational methods and real-world data to emulate ongoing randomized controlled trials (2023)

Bayesian adaptive basket trial designs for neoantigen based immunotherapy with borrowing strength across subpopulations within the trial and from external controls

Project Details: To develop and evaluate the validity of Bayesian basket trial designs borrowing information across subpopulations within neoantigen-based immunotherapy trials and from external controls.

Project Results:

Pending

Informatics driven real world analysis of SARS-CoV-2 serologic response and in vitro diagnostic accuracy

Project Details: To implement real-time identification of specimens for clinical serologic test validation and to characterize the antibody response to SARS-CoV-2 infection and the performance of serologic assays over time.

Project complete; no public results

Evaluate application of artificial intelligence to adaptive enrichment clinical trials

Project Details: To evaluate the applicability of AI-identified treatment outcomes during trial progression to predict treatment effect heterogeneity at trial completion, and to assess the use of AI-based adaptive strategies for mid-course trial enrichment and modification of enrollment criteria.

Project Results:

Pending

Identifying, selecting, and utilizing quantitative bias analysis methods

Project Details: To identify, compare, and evaluate quantitative bias analysis methods for observational studies, develop a user-friendly decision tree to guide method selection, and assess its feasibility using published research.

Project Results:

Quantitative bias analysis methods for summary-level epidemiologic data in the peer-reviewed literature: a systematic review (2024)

Community-level emerging substance misuse simulation

Project Details: To analyze polydrug use prior to concurrent use of specific non-opioid drug classes as influences on timing and likelihood of use transitions and outcomes, and to simulate naloxone use patterns and harm reduction strategies across varying naloxone products, distribution strategies, opioid types, populations, and bystander involvements.

Project Results:

Pending

Evaluate the application of machine learning algorithms to the management of postpartum hemorrhage

Project Details: To determine the sources of variation in postpartum hemorrhage management across different populations of women using machine learning algorithms; to evaluate their associations with patients’ clinical and sociodemographic factors; and to assess links between management patterns and severe maternal outcomes.

Project Results:

Pending

Real-world outcomes of novel PET imaging tracers for prostate cancer

Project Details: To evaluate how PSMA-PET imaging influences short-term clinical decisions related to prostate cancer staging, monitoring, and treatment, and to model its long-term effects on treatment duration, side effects, quality of life, and survival outcomes.

Project Results:

Long-Term Outcomes of Prostate-Specific Membrane Antigen-PET Imaging of Recurrent Prostate Cancer (2024)

Development of optical and digital microscopy hardware, software, and statistical methods to enable computational pathology in low resources

Project Details: To develop and integrate low-cost optical and digital microscopy tools, software, and statistical methods to enable remote and AI-supported computational pathology in low-resource environments, and to generate reference data for evaluating immune cell density scoring tools.

Project Results:

Initial interactions with the FDA on developing a validation dataset as a medical device development tool (2023)

A machine-learning model to identify women with anti-nuclear antibody related connective tissue diseases

Project Details: To develop and validate a machine learning model using real-world electronic health record data to identify individuals with anti-nuclear antibody related connective tissue diseases among those who test positive on ANA screening.

Project Results:

Pending

Fostering Patient-Centered Decision Making

Qualitative analysis of gender differences in heart failure PROs

Project Details: To conduct qualitative analysis to understand gender-based differences in interpretation and response to the Kansas City Cardiomyopathy Questionnaire among patients with heart failure and to improve its validity and clarity for female patients.

Project Results:

Investigating gender-based differential item functioning on the Kansas City Cardiomyopathy Questionnaire (KCCQ) using qualitative content analysis (2023)

Methods to capture post-market patient preference information

Project Details: To design and compare between three methods- a direct from encounter method and two immediately post-encounter methods- for identifying patient preferences that influence real-time decisions about using marketed medical products

Project Results:

Comparing Methods for Identifying Post-Market Patient Preferences at the Point of Decision-Making: Insights from Patients with Chronic Pain Considering a Spinal Cord Stimulator Device (2024)

Integrating 4 methods to evaluate physical function in patients with cancer (In4M): protocol for a prospective cohort study

Project Details: To evaluate and compare clinician-reported, patient-reported, and wearable device-based methods for measuring physical function in patients with cancer undergoing chemotherapy, including associated challenges, burden, and usability, and to examine how longitudinal changes in physical function relate to the likelihood and severity of chemotherapy side effects.

Project Results:

Integrating 4 methods to evaluate physical function in patients with cancer (In4M): protocol for a prospective cohort study (2024)

Patient and provider informed labeling of AI/ML-based software to enable transparency and trust

Project Details: To develop and pilot-test a dynamic, patient-centered digital labeling approach for AI/ML-based medical devices to assess patient acceptance, usability, and comprehension.

Project Results:

Trustworthy and ethical AI-enabled cardiovascular care: a rapid review (2024)

Improving the diagnosis and treatment of women with myocardial ischemia and no obstructive coronary artery disease

Project Details: To develop and validate a patient-reported outcome measure to assess the overall health status in women with myocardial ischemia and no obstructive coronary arteries (INOCA), and to evaluate its validity across specific INOCA subtypes.

Project Results:

Pending

Qualitative techniques to define meaningful within-patient change in symptoms of advanced cancer patients

Project Details: To define meaningful within-patient change in symptoms and side effects among advanced cancer patients using qualitative methods, and to evaluate a patient-centered approach for interpreting changes in selected patient-reported outcome measures.

Project Results:

Pending

A positive deviance approach for representing women, older adults and patients identifying as racial and ethnic minorities in oncology research

Project Details: To identify and qualitatively assess shared strategies used by trial sponsors to perform exceptionally in enrolling diverse and representative participants in cancer research, using a positive deviance approach

Project Results:

Pending

Longitudinal analysis & visualization of patient-reported physical function & symptom data

Project Details: To analyze and visualize patient survey data on physical function and side effects from rare cancer clinical trials, and to obtain initial feedback from patient advocates, clinicians/clinical investigators, and FDA decision makers on these visualizations.

Project Results:

Pending