Are There Additional Requirements For Category 2 LOIs and Applications?

If requesting a budget with direct costs over $5 million, up to a maximum of $10 million, applicants must highlight and justify the need for the requested material and personnel resources to support the scale and scope of the proposed study.  Potential examples include scale and scope requirements to achieve the following: inclusive, diverse, and representative participation by patients, study sites, care-delivery environments, disadvantaged patients, communities, and geographic areas; adequately powered subgroup analyses; or necessary precision of effect size(s) accounting for variation with pragmatic study design and conduct.  

Category 2 applications must:

• Examine large and diverse populations as appropriate with an overall sample size that allows precision in the estimation of the hypothesized effect sizes. The proposed sample size and analytical plan must support evaluation of at least one hypothesis related to potential differences in effectiveness among relevant patient subgroups. 
• Make use of multiple study sites offering care reflective of the diversity of US health care. Applicants proposing studies with more than $5 million in direct costs will be considered nonresponsive if only a single study site is proposed.