Assess your field. Find out the opportunities for collaborating with a known laboratory or more experienced grantee.
Look at the competition. See which other projects in your field are being funded. Search the NIH CRISP database and Community of Science.
Check the literature to make sure the work you are considering has not been done before or to see if it has been done and its methods were judged to be inadequate. Go to MEDLINE and NLM Databases and Electronic Resources.
Evaluate yourself. How do your strengths match up with the topics you uncovered in step 1? Can you capitalize on your expertise and fill in gaps with mentors, collaborators, or consultants?
Figure out resources and support your organization has and what additional support you'll need.
Start thinking about your next application. As long as the topics are different you can apply simultaneously for as many grants as you like. Or use the same application to apply to a non-Public Health Service organization (find PHS entities at Agencies and Programs).