OpportunityTitle: Rapid Influenza testing and Multicenter Antiviral Feasability  Studies in Season 4
AdditionalInformationOnEligibility: Eligibility Category(s):  Johns Hopkins University is the only eligible applicant that could implement the described project within the next 3 months and continue to support ASPR and BARDA influenza therapeutic goal
Description: The Biomedical Advanced Research and Development Authority (BARDA), within the Office of the Assistant Secretary for Preparedness and Response (ASPR) in the U.S. Department of Health and Human Services (HHS), supports advanced development and availability of countermeasures for CBRN threats, pandemic influenza, and emerging infectious diseases through advanced product development, stockpile acquisition/building, manufacturing infrastructure building, and product innovation. BARDA establishes and maintains business collaborations by means of grants, cooperative agreements, and contracts with the public and private sectors, domestically and internationally. The current cooperative agreement between ASPR/BARDA and Johns Hopkins University (JHU) integrates rapid influenza molecular testing into Emergency Department (ED) clinical practice with assessment of clinical course following antiviral treatment and adoption of electronic communications that can assist clinicians and public health practice with local management of influenza infections. JHU along with three other EDs enrolled 1,997 high risk adult patients during the 2013-14 influenza season. Using a Clinician Decision Guide instituted at initial ED triage based on standardized symptom criteria and an electronic scoring system nearly 6,000 patients were tested by the rapid molecular test, and over 1,000 of these patients were positive for influenza virus during the 2014-15 season. These data highlighted the important role of the ED with diagnosing and treating influenza in the community, and the opportunity to improve patient care with clinician guidelines for whom (and when) to test for influenza virus, and in accordance with CDC recommendations, instituting therapy as early as possible. A PHEMCE goal is to improve enrollment of high risk individuals, such as those presenting to the JHU ED, in clinical trials of candidate medical countermeasures, including influenza therapeutics, as well as therapeutics for other emerging infectious diseases. Patients, both hospitalized and those discharged from the ED, can be treated early and also provide a target population that can be more effectively monitored for clinical response to therapeutics. In this regard, the diagnostic triage standard operating procedure (SOP) approach already developed and instituted at JHU to expedite treatment at the initial point of care by electronically prompting clinicians with influenza test positive results, provides an excellent opportunity to improve future therapeutic utilization and development. Using this triage SOP facilitates capturing endpoints clinically relevant to high risk patients, and also enables initiating early antiviral therapy, either oral or intravenous during the ED visit. This preparedness strategy also extends to emerging infectious diseases which like influenza are unpredictable and may have no evidence-based treatment options. Historically, influenza therapeutic studies have been difficult, lengthy, and expensive yet only demonstrating borderline benefit in subjects with uncomplicated influenza illness despite enrollments of approximately 400 to over 700 influenza-infected subjects at many clinical research sites (enrollments averaging one subject per clinical site, with as many as 90 and up to 200 engaged clinical sites), in many countries both in the northern and southern hemispheres. These studies are fraught with problems related to management logistics, compliance monitoring and statistical variability given the small number of subjects per site. During the 2015-16 influenza season, the JHU ED piloted an open label, randomized study with two neuraminidase inhibitors (one administered by IV and the other orally) for enrolling and treating high risk subjects presenting to the ED for clinical care, with follow-up of both discharged and hospitalized subjects. In spite of the late and less severe 2015-16 influenza season, JHU enrolled over 50 subjects with over 20 hospitalized. Influenza virus resistance to neuraminidase inhibitors remains a substantial public health vulnerability given that these are the only treatments commonly prescribed and FDA-licensed for influenza treatment. These preliminary and prior data from JHU collaborations highlight the opportunity to enable more expeditious safety and efficacy studies with non-neuraminidase therapeutic candidates in the pipeline. The JHU-developed methodology, if adopted by pharmaceutical companies, could drastically and beneficially change the landscape for future influenza therapeutic studies. Importantly, this same model is likely to be extremely useful in a response to serious emerging disease threats to the U.S. and globally. Applying the experience and demonstrated capability with implementing these clinical studies in multiple settings can lead to the advanced development of new medical countermeasures for influenza and could serve as a model for other emerging infectious diseases. Larger numbers of enrolled high risk subjects could be achieved by expanding the single investigator study to additional investigational sites and engaging a Contract Research Organization to perform sponsor-related duties and functions. To fund, design, and implement such a pilot study in less than 6 months would also be an important demonstration of the capability to rapidly respond to influenza, and other infectious disease threats. Finally, the continued testing of large numbers of patients for influenza in a third influenza season and collection of study data in near real-time can assist in responding to influenza outbreaks and also provide an operational venue for rapid administration of therapeutics guided by validated diagnostic practice to efficiently triage and manage individuals presenting to the ED.
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CloseDateExplanation: The deadline for the submission of applications under this FOA is 08/08/2016 at 11:59 pm EST.  Applications must be submitted electronically via Grants.gov by 11:59 p.m. Eastern Time on 08/08/2016 Applications that are submitted after the deadlines w