HHS STTR PA-15-076

Despite advances in the treatment of chronic viral hepatitis B and C, the persistence of these and the emergence of other hepatitis viruses continue to remain a public health challenge in the United States. Currently, it is estimated that 3.5 to 5.3 million persons in the United States are afflicted by viral hepatitis. The consequences of acute and chronic viral hepatitis vary, but can be severe and lead to acute liver failure, cirrhosis of the liver, and predispose afflicted persons to hepatocellular carcinoma. Once liver failure ensues from either acute or chronic viral hepatitis or if liver cancer emerges predisposed by cirrhosis from chronic viral hepatitis, liver transplantation becomes the only viable option, a costly and resource intensive therapy. Even with advances in medical care, approximately 12,000 to 15,000 Americans succumb to the complications of acute or chronic viral hepatitis each year.

In January 2010, the Institute of Medicine (IOM) released the report "Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C" (http://www.iom.edu/ ). This report identified and highlighted viral hepatitis as a national health concern and outlined barriers that hinder health care delivery for viral hepatitis patients. In response to the Institute of Medicine report, the Department of Health and Human Services under the direction of Dr. Howard Koh, Assistant Secretary for Health, convened a working group that generated the report "Combating the Silent Epidemic of viral Hepatitis: U.S. Department of Health and Human Services Action Plan for the Prevention, Care and Treatment of Viral Hepatitis" (Viral Hepatitis Action Plan), which was released on May 12, 2011 (http://www.hhs.gov/ash/initiatives/hepatitis/ ). The Viral Hepatitis Action Plan represented an integrated Federal government response to the public health implications of acute and chronic viral hepatitis. Furthermore, the Viral Hepatitis Action Plan provided a framework to coordinate the Federal government wide approach to address the challenges raised in the IOM report regarding the public health implications of acute and chronic viral hepatitis.

Integrated into the Viral Hepatitis Action Plan were several action items germane to the research mission of the National Institutes of Health. The topics ranged from basic, translational, and clinical research to coordination of disseminating research findings into the clinical realm. These action items and overall progress in achieving public health objectives in viral hepatitis were recently updated in 2014. Specific research topics assigned to the National Institutes of Health can be found in the updated Action Plan for the Prevention, Care & Treatment of Viral Hepatitis (http://aids.gov/pdf/viral-hepatitis-action-plan.pdf ).

This FOA encourages small business establishments to submit applications that address any of the specific research topics in the updated Action Plan for the Prevention, Care & Treatment of Viral Hepatitis that are assigned to the NIH and germane to the research mission of the respective NIH Institutes and Centers in order to facilitate the development, evaluation, and validation of products that would be implemented in the public health efforts to reduce the burden of viral hepatitis in the United States. Applications that propose studies above a Phase I Clinical Trial will be beyond the scope of this FOA.

A sampling of research objectives and strategies appropriate for this FOA from the Viral Hepatitis Action Plan include, but are not limited to:

1. Develop point-of-care rapid screening tests that would allow for screening of patients or individuals for ongoing hepatitis virus infection (HCV, HBV, HDV, HEV) or immunity to infection (particularly hepatitis B) that could be used to screen patients or individuals, including pregnant women, for evidence of acute or chronic hepatitis or presence of immunity.
2. Develop new diagnostic tests for viral hepatitis that would aid in clinical management, such as tests that would discriminate between acute and chronic infection, identify viral hepatitis infected infants among infants born to women with viral hepatitis, or would allow for better assessment of need for treatment and monitoring, such as tests for IgM antibodies to hepatitis C, D or E, or means of measurement of HBV, HCV, HDV and HEV levels that are as reliable but less expensive and resource demanding than current molecular assays.
3. Develop non-invasive and practical tests that could be used to monitor patients for complications of chronic viral hepatitis, such as portal hypertension, esophageal varices and hepatocellular carcinoma.
4. Develop practical models of care that would be applicable to the unique issues faced by populations with viral hepatitis.
5. Develop new therapies for viral hepatitis or its complications, particularly interventions that are better tolerated and less expensive than currently licensed or late-stage investigational regimens.
6. Develop therapies that ameliorate the symptoms or complications of viral hepatitis or its antiviral therapies.
7. Develop genetic tests that might help in patient management of viral hepatitis, including tests that assess risk of complications as well as likelihood of success of specific therapies.
8. Develop computer algorithms that would help in the practical diagnosis, management, monitoring and therapy of viral hepatitis.
9. Develop candidate vaccines for hepatitis C or innovative means of prevention.
10. Develop more effective or more practical HAV and HBV vaccines and vaccine strategies.
11. Develop means of pathogen reduction for blood components that might be practical particularly for resource limited countries.
12. Develop methods for rapid, sensitive, and specific detection of hepatitis virus infections among blood donors or donations.
13. Develop vaccines, anti-viral and other strategies that can be safely used in pregnant women and their infants to prevent perinatal transmission of viral hepatitis.
14. Develop more effective or more practical HAV and HBV vaccines and vaccine strategies, candidate vaccines for hepatitis C, and therapies that ameliorate the symptoms or complications of viral hepatitis or its antiviral therapies for infants, children and pregnant women.
15. Develop tests for the frequency of aberrant hypermethylation and hypomethylation of specific genes that are associated with HCV infection and the development of HCC tumors and that may be useful in prognosis and treatment.