In its May edition of Peer Review Notes, the US National Institutes of Health's Center for Scientific Review reiterates how it defines a new application, in the context of an unsuccessful A1 resubmission. "A new application is expected to be substantially different in content and scope, with more significant differences than are normally encountered in a resubmitted application," CSR notes. A new application, it adds, should show "fundamental changes in the questions being asked and/or the outcomes examined" and demonstrate a "significant change in direction and approach for the research project."
When developing a new application in the context of a previously unsuccessful resubmission, CSR says it is important to consider whether the new application asks the same basic questions and expects the same set of answers. If that's the case, "your application is probably not new enough," the center says.
The center says that even after an unsuccessful resubmission, "you still have options for moving your science forward in a future application." To do this, CSR suggests that applicants deconstruct their research plans in search of new directions to take, apply for a different kind of grant ("some of the stronger research aims you originally proposed in an R01 application, for instance, may be proposed in an R21 application so long as you follow the requirements for this smaller and different type of grant," it says), or consider putting that particular project on hold, rather than resubmitting. After 37 months from A0 submission, "the same application will automatically be considered new," CSR says, adding that "of course, you'll want to update your application based on changes in the field during that time."