Between 1998 and 2003, the annual budget of the National Institutes of Health (NIH) doubled, rising from $13.7 billion to $26.9 billion per year. The doubling was the result of a concerted and purposeful commitment by the U.S. Congress to increase funding to levels commensurate with the growing opportunities and challenges in biomedical research. This generosity and trust vested on the research community by Congress are likely to have an important and measurable impact on medicine and health. Liver disease research funding grew commensurate with the doubling of the overall NIH budget, from $180 million in 1998 to $388 million in 2003.
Of course, after the 5-year period of budget doubling, growth in NIH funding is expected to return to previous levels, which had been close to or slightly above the rate of biomedical inflation. Indeed, in fiscal year 2004, the NIH budget rose to $27.7 billion, a 2.9% increase over the previous year. Furthermore, a proportion of the growth was committed to high-priority initiatives including biodefense ($1,694 million), the NIH roadmap ($237 million), and obesity research ($22 million). The sudden slowing of growth in the NIH budget has resulted in budgetary constraints that appear to be out of proportion to the actual growth, which remains substantial. The reasons for these constraints are multiple. Thus, in 2004 the number of research grant applications rose faster than the rise in funds available. Furthermore, there is the problem of the “noncompeting base.” The average duration of NIH grants is approximately 4 years, so that each year only one fourth of the ongoing budget becomes available for funding new applications, the remainder being the noncompeting base. Since the budget has been growing rapidly during the last 4 years, the one fourth of funds that became available in 2004 represented a smaller-than-average proportion of the overall budget. These complexities of the budget partially account for the decline in award rates from the range of 30%–32% during fiscal years 1998 to 2003 to an estimated 25%–27% for fiscal year 2004.
For 2004, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has developed initiatives using “Special Emphasis” program announcements. Funds are set aside to award grants in the areas described in these program announcements, and selected grants are paid even if they do not fall into the regular pay line for grant funding. These program announcements are published both in the NIH Guide to Grants and Contracts and online at http://www.niddk.nih.gov/fund/crfo/specialpas.htm.
Several of the announced areas of special emphasis are applicable to liver disease research including proteomics (PA-04-081), noninvasive methods for diagnosis and evaluation of disease (PA-04-088), development of assays for high throughput drug screening (PA-04-068), and ancillary research studies that supplement ongoing clinical research trials or networks funded by NIDDK (PAR-04-078).
In proteomics, important areas for liver disease–related research applications include analysis of the normal liver proteome and changes that occur with liver disease or liver cell injury, effects of cell signaling on liver proteins (such as with interferon alfa or cytokine therapy), and changes of the protein patterns in liver and serum associated with progressive fibrosis and development of liver cancer. In the area of noninvasive markers of disease, important topics include serum biomarkers for hepatic fibrosis, liver disease activity (particularly in chronic hepatitis and nonalcoholic steatohepatitis), allograft rejection and level of immunosuppression, and early detection of hepatocellular carcinoma and cholangiocarcinoma. In the area of high throughput screening for drugs with potential therapeutic applicability to liver disease, important areas are targets in pathways of apoptosis, fibrogenesis, fatty acid metabolism, insulin and interferon action, and liver carcinogenesis. Finally, in the area of ancillary studies, clinical trials, natural history studies, cohort studies, and databases in liver disease that currently accept applications for collaborative basic research ancillary studies include the HALT-C, Peds-C and Virahep-C trials, the Nonalcoholic Steatohepatitis Clinical Research Network, the Adult-to-Adult Living Donor Liver Transplant Cohort Study, the Biliary Atresia Research Consortium, the Drug-Induced Liver Injury Network, the Longitudinal Assessment of Bariatric Surgery Consortium, and the prospective controlled trial of high-dose ursodiol therapy of primary sclerosing cholangitis, all of which are described on the NIDDK website at http://www.niddk.nih.gov/fund/ancillary-studies/descriptions-ancillary-studies.htm.
Thus, the change in rate of growth of the NIH budget during 2004 has led to a decrease in the overall award rate of grant applications. Yet the total amount of funding and total number of liver disease grants remain at all-time highs, and important opportunities exist for future funding in liver disease research.