Project leader: Perren Cobb, MD
Initial contract value: $4,911,531
Contract modifications: $1,493,019 (see Updates below)
Project dates: September 2014 - September 2019
In emergency situations, rapid response is critical. This includes public health emergencies, like influenza or infectious disease outbreaks, when FDA works with other agencies to help get safe and effective medical countermeasures (MCMs) to people who need them.
To ensure that these products are safe and effective, FDA may require further study of drugs after they are approved. For example, when it would not be ethical or feasible to test effectiveness in humans—such as countermeasures for potential bioterror threat agents—products may be approved under the Animal Rule.
Studies done after approval are called Phase 4 trials, and patients who receive the product are monitored for side effects. People who oversee the trials collect data and report their findings about how the product worked. Like all clinical trials, these studies must be approved by an Institutional Review Board (IRB) before they begin, but that process can take months.
These extra studies and other requirements—in place to protect patients—can make evaluating the effectiveness of new treatments during emergency situations especially challenging.
In collaboration with the Biomedical Advanced Research and Development Authority (BARDA), FDA has awarded Discovery, the Critical Care Research Network, University of Southern California2 a four-year contract3 to help speed access to and evaluation of medical countermeasures during public health emergencies.
Discovery will work to pre-position Phase 4 studies in advance of a public health emergency. This includes obtaining full IRB approval before an event happens, to allow for the collection of data during an emergency.
As part of this project, critical care physicians nationwide will work with government agencies to address challenges with collecting clinical data in emergency situations. They will also work toward agreements for a central IRB, such as the NIH-administered Public Health Emergency Research Review Board, to review trial protocols for many institutions simultaneously.
Discovery will also develop a treatment protocol for intravenous (IV) zanamivir, an investigational antiviral influenza treatment. The IV formulation of zanamivir is currently available only by enrollment in a clinical trial, or under an emergency Investigational New Drug (eIND) request to the manufacturer. This project will allow the use of IV zanamivir in hospitalized adult and pediatric patients with severe influenza during the 2015-2016 flu season and allow FDA to collect valuable standardized information on the clinical use of this investigational drug, with data consistently collected across multiple sites.
In addition to helping doctors more easily obtain this treatment for their patients, this project will test the data collection and reporting system during peak times, to help streamline electronic case report forms (eCRFs) for future seasons.
The objective of this project is to develop methods for obtaining safety and limited efficacy data from patients who receive a medical countermeasure during a public health emergency. The Discovery Program for Emergency Preparedness (Discovery-PREP) will:
Develop and pre-position a simple influenza treatment protocol (using IV zanamivir) in 20 hospitals throughout the United States (starting with 10 hospitals during the 2015-2016 flu season)
Create an agreement between Discovery-PREP hospitals to use a central IRB for the expedited review of clinical protocols in emergency situations
Develop an eCRF that collects data and converts it to Study Data Tabulation Model (SDTM) format for use with the IV zanamivir clinical protocol (goal: the eCRF will automatically populate from the electronic health record)
Create a data dissemination plan to share key findings from the treatment of critically ill patients in emergency situations with FDA and other stakeholders
Working with physicians and Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) partner agencies, this project will support streamlined data collection during public health emergencies and facilitate rapid, efficient data dissemination. FDA and federal partners will, in turn, use this information to facilitate timely decision-making about these important medical countermeasures to protect public health.
FDA exercised three annual options (from 2015 to 2017, at $150,000 each) to update the study’s clinical protocol and obtain Institutional Review Board (IRB) approvals, as well as a fourth option in 2018 for $696,995, to sustain operational data collection tools for medical countermeasures. In addition, FDA issued a special contract modification in FY 2017 for $346,014.
This modification enables Discovery to develop a single treatment protocol to study three Phase 4 anthrax therapeutics, and develop a randomized, controlled trial treatment protocol to study antiviral therapeutic agent(s)4 for antigenically distinct or emerging influenza strains (e.g., H7N9). These potential influenza countermeasures may be novel antivirals or monoclonal antibodies. The protocol may include more than one (investigational or approved) anti-influenza MCM, be adaptive in nature to allow rapid addition of new MCMs, and may ultimately be used as a template or framework protocol for other emerging infectious diseases.
This project was funded through the MCMi Regulatory Science Extramural Research program
1 Formerly the United States Critical Illness and Injury Trials Group
2 Discovery is funded by the National Institute of General Medical Sciences, part of the National Institutes of Health, to create a clinical research framework that reduces the barriers to investigation.
3 The contract has a four-year base period. Separate options may be funded in years 2 through 5 to sustain data collection established during the base period.
4 Therapeutic agents to be studied will be identified by FDA and/or BARDA.