No. A Letter of Intent (LOI) is not required, but it is highly encouraged for R34 applications and U01 applications that have budgets under $500,000 in direct costs per year.
A Letter of Request (LOR) is only required for U01 applications that will have budgets of $500,000 or greater in direct costs in any given year. A Letter of Request (LOR) requires substantially more detail than a LOI and must be submitted for the NIAMS’s consideration at least 10 weeks in advance of the application due date. You will be notified by the NIAMS if your LOR is accepted and you may submit a U01 application (Note: permission is only needed if the application has a budget requesting direct costs equal to or greater than $500,000 in direct costs in any given year).