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: adoption/de-adoption of FDA-approved medical products, postmarket surveillance, development and application of novel analytics, and patient-centered regulatory decision-making.
For comments or questions pertaining to our CERSI research projects, contact the Yale-Mayo Clinic CERSI at CERSI@yale.edu.
Generic drugs are approved based on bioequivalence to the brand-name agents. However, there are sometimes concerns among patients and clinicians that generic and brand-name drugs are not equivalent and have differing effects. Building on our ongoing research, we will test different methods to compare the effectiveness and safety of generic and brand-name drugs using a large administrative claims data source that includes information on privately insured and Medicare Advantage enrollees of all ages. Further, we will create packages that will ease the implementation of these methods for future research. Collaborators from the University of Washington are involved in this project.
A novel sync-for-science mobile application has been developed that unobtrusively enables patients to provide their own outcomes (through short questionnaires and through synchronizing data from mobile health trackers) to the FDA after they have received a procedure that utilizes medical devices. In addition, with user permission, this application draws data from the electronic medical record to complement patient-reported data. In this project, we will conduct a pilot study testing this mobile health application to enable the FDA to conduct post-market surveillance of two procedures that use medical devices: the multiple devices (including sutures and stapler) used to perform bariatric surgeries (either sleeve gastrectomy or gastric bypass) in patients seeking weight loss and an ablation catheter when used in patients with atrial fibrillation seeking a return to sinus rhythm. Patients will be enrolled before receiving each of the devices and then will be asked to report specific symptoms related to their need for the procedure and those that may be expected at baseline (enrollment, which is pre-procedure), and 1, 4, and 8 weeks post-procedure. Additionally, patients will be asked 2-3 short questions every 3-4 days for the first 30 days post-procedure related to post-procedure symptoms. We will also test if these patients’ electronic health record data from multiple health systems where they receive care can be synchronized into a research-ready database. Patients will also be provided with syncable devices to provide additional insights into their health and health outcomes. Finally, we will test the feasibility of obtaining medication data from pharmacies or the current needs to create a functional system that can integrate pharmacy data into the mobile application. Integration of these multiple data sources (patient-reported outcomes, wearable/mobile device data, electronic health record data, and pharmacy data) have the potential to ultimately enable a more robust and thorough post-marketing surveillance strategy by leveraging the potential of digital health technologies. Non-Federal entities involved in this project include Me2Health (the developers of the Hugo mHealth application), Johnson & Johnson (collaborator- provides input on project and funds to Me2Health for development of Hugo mHealth application) and AliveCor (donated Kardia Mobile devices for this project).
ClinicalTrials.gov Identifier: NCT03436082
Non-Federal Entity Collaborators: Karla Childers, MSJ, Paul Coplan, ScD, MBA, and Stephen Johnston, MSc (Johnson and Johnson)
This project seeks to understand how linking laboratory data to insurance claims can help examine a drug’s performance after approval. We will conduct a case study looking at renal function and the performance of oral anticoagulant drugs in patients with atrial fibrillation (AF). The 30 million patients with AF are at nearly a five-fold risk of stroke. Lifelong oral anticoagulation is recommended in most patients with AF to prevent stroke. However, treatment decisions can be complicated by the presence of chronic kidney disease (CKD), as poor renal function increases the risks of both stroke and bleeding ( a major complication of oral anticoagulation treatment), and may change the risk-benefit ratio of different treatment options. This project proposes to answer three important questions pertaining to the impact of renal function on oral anticoagulation treatment in patients with AF. First, in patients with severe-to-no renal impairment, we will assess the comparative effectiveness and safety of different oral anticoagulant drugs across the range of renal function. Second, in patients on dialysis who have substantial risks of both stroke and bleeding, we will compare different potential treatment options, including warfarin, non-vitamin K antagonist oral anticoagulants (NOACs), and no treatment. Third, we will use novel analytic methods to identify patient characteristics that contribute to the heterogeneity in treatment effects.
We will answer these questions by leveraging the power of a large observational database, OptumLabs Data Warehouse, which contains over 160 million privately insured and Medicare Advantage enrollees of all ages, races, and from 50 states and the USRDS data. The proposed work could provide important new evidence on the safety and effectiveness of oral anticoagulants in relation to renal function and will help physicians and patients make a choice among different treatment options.
Non-Federal Entity Collaborators: Brahmajee Nallamothu, MD, MPH, and Rajiv Saran, MD, MS, MBBS - Co-Investigators (University of Michigan)
Non-Federal Entity Collaborators: James Hummel, MD- Co-Investigator (University of Wisconsin School of Medicine)
This project proposes to advance our understanding of cardiogenic shock with the ultimate aim of enabling patients and providers to estimate risk and develop optimal, individualized treatment plans. Specifically, we will use the NCDR CathPCI and ACTION-GWTG registries, two national registries of patients with acute myocardial infarction (ACTION-GWTG) and patients undergoing stent procedures (CathPCI). Given the substantial morbidity and mortality associated with cardiogenic shock, the proposed work will enable us to advance our understanding of this condition, develop better treatment approaches, and will enhance regulatory science by improving the safety and effectiveness of mechanical circulatory support devices through helping target them to patients who will benefit. Collaborators from Texas A&M University are involved in this project.
Non-Federal Entity Collaborators: Jeptha Curtis, MD, Frederick Masoudi, MD, MSPH, and John Messenger, MD- Co-Investigators (American College of Cardiology)
The goal of this project is to survey members of industry to better inform the growth of a marketplace that supports the development of devices for pediatric populations that are approved or cleared and labeled for use in pediatrics. Previous initiatives led by the FDA have identified some of the key challenges and barriers to market; however, a streamlined and targeted approach to address these challenges has not been outlined. This project seeks to prioritize the barriers to market that will inform regulatory decision-making and promote innovation.
Non-Federal Entity Collaborators: Andrew Lo, PhD- Co-Investigator (Massachusetts Institute of Technology)
Recently, new mobile health technologies have emerged as clinical tools and offer an opportunity to overcome the challenges in measuring functional capacity and recording symptoms. These technologies capture and integrate data from disparate sources reflecting patients’ functional status and symptomatology and have the potential of serving as surrogate endpoints for new HF therapy approvals. BodyGuardian Heart (FDA 510(k) cleared) is a mobile health technology capable of connecting to wireless scales and blood pressure monitors and Wavelet is a wrist-based wearable sensor that captures heart rate, respiration rate, and accelerometer data. A novel mobile health platform, Sentinel-HF (built and developed by Biofourmis) using an advanced analytics engine (BiovitalsTM), is capable of monitoring a patient’s physiology through its connection with wearable biosensors, functional capacity, and assessment of QoL through validated PROMs.
The goal of this project is to test the feasibility of obtaining quantifiable and reliable measures of functional capacity and QoL using these novel mobile platforms in HF patients. This study will not only advance the science but also inform the FDA how these measures can be used as alternative trial endpoints. Acute Decompensated Heart Failure (ADHF) patients will be recruited post-discharge from National Heart Centre and National University Hospital in Singapore. Patients will be monitored at home using Bluetooth connected wearable biosensors for a period of 60 days. Patients will also use the smartphone application to 1) perform a weekly 6MWT, and 2) report their symptoms and quality of life using QoL questionnaires.
Non-Federal Entity Collaborators: Kuldeep Singh Rajput, Maulik Majmudar, MD, and Carolyn Lam, MBBS, PhD, MS (Biofourmis)
This work will seek to understand from a qualitative perspective differences in patient scores between those who identify as male and female. This study will further validate the usage of KCCQ as a clinical endpoint and provide an example to industrial sponsors of how to account for gender differences in a patient-reported outcome. An improved understanding of the KCCQ to address both male and female patients will advance clinical study design and analyses of heart failure trials. Furthermore, this work will also address improved health communication by initiating the work to make KCCQ clear and applicable to female patients, improving both patient care and regulatory decisions.