Frequently Asked Questions about Catalyzing Innovation in Late Phase Clinical Trial Design and Statistical Analysis Plans U34/X01 FOAs

The purpose of these FOAs is to invite applications for support and/or access to a consultative resource to assist with planning activities for late-phase (Phase II and beyond) single-site or multi-site clinical trials that utilize non-traditional clinical trial designs with the potential for incorporating a novel or innovative statistical analysis plan. The FOAs will facilitate the development of feasible and well-designed clinical trials utilizing consultative services provided by the Innovative Clinical Trials Resource (ICTR) (N01) that are trials within the mission of the National Heart, Lung, and Blood Institute (NHLBI).

Non-traditional clinical trials would employ designs and statistical analysis plans that are outside of the usual scope of traditional approaches that include, but are not limited to: participant randomization; blinding (masking) of participants and researchers to the study intervention(s); use of a control comparison group; and classic intent-to-treat analysis.

These initiatives encourage trials in areas of heart, lung, blood, and sleep science that include, but are not limited to, studies of rare diseases and/or therapeutics, studies in sub-populations of more common diseases (e.g. precision medicine approaches to common disorders), and late-stage implementation trials. Other examples could include trials for the study of interventions in a non-randomized study setting and clinical trials in which an optimal treatment control arm may be difficult to implement.

These FOAs are not designed for planning traditional clinical trials utilizing conventional statistical methodologies, or for the collection of preliminary data or the conduct of pilot studies to support the feasibility of a clinical trial.

The ideal stage is prior to protocol development, when the investigator is designing the trial and recognizes the diminished feasibility of the proposed clinical trial using a traditional approach to trial design and analysis.  At this juncture, the investigator should consider innovative design and analysis approaches; these FOAs provide applicants an opportunity to seek support for such activities.  The application review process will evaluate the proposed trial’s rationale and significance, the proposed trial design in its early form, the investigator’s proposed requirement for access to the innovative design and analysis expertise offered through the Innovative Clinical Trial Resource, and other factors detailed in ‘Section V. Application Review Information’ of the FOAs.

The services offered include expert assistance in developing novel/innovative clinical trial designs and statistical analysis plans, as well as guidance on regulatory issues related to innovative late phase clinical trials. In addition to specific consultative services, U34 and X01 awardees will have access to an on-line education program on the application of non-traditional clinical trial design and analysis to clinical trials. 

Yes. All awardees must utilize the design and analysis consultative services provided by the ICTR in keeping with the cooperative agreement terms of award.

These FOAs are not intended to solicit applications for funding to support the actual conduct of clinical trials or the set-up activities, per se (e.g., site recruitment, regulatory approvals, data management, etc.).  These FOAs are also not soliciting applications for the support of activities to plan Phase 0 or Phase I trials.  The purpose of these FOAs are solely to solicit applications that are requesting support of planning activities for late phase (Phase II and beyond) single-site or multi-site investigator-initiated clinical trials that address critical clinical questions within the mission of the National Heart, Lung, and Blood Institute (NHLBI) and that require non-traditional clinical trial designs with the opportunity for statistical novelty and/or innovation.

While both mechanisms provide access to the ICTR, the U34 grant mechanism (RFA-HL-18-008) will provide the investigator with funding support ($125,000) to conduct clinical trial planning activities that are not provided by the ICTR. Examples of such activities include clinical trial site identification, the development of a participant recruitment strategy, protocol finalization, clinical trial implementation, and project management planning. 

The X01 mechanism (PAR-17-294) may better serve those applicants who require access to consultative clinical trial design and analysis planning expertise, but who have already completed or have existing support for institutional activities required for planning a clinical trial that involves novel or innovative statistical techniques.

There are two application receipt dates for each FOA: October 19, 2017 and January 12, 2018, by 5:00 PM local time of the applicant organization. Applications submitted under either FOA will be reviewed jointly by the same peer review panel.

Yes, resubmission of applications submitted on the first receipt date will be accepted on the second application receipt date (1/12/18).  The FOAs are currently scheduled to expire on 1/13/18, so will not allow for resubmissions from the second receipt date.

No. The principal investigator will need to select the most appropriate mechanism and only apply to that mechanism. If you have any questions about which mechanism may be most advantageous for you, please consult the appropriate scientific contact listed on the FOAs.

Yes. Applying to a different mechanism will be considered a new application.

You may submit a clinical trial application during the U34/X01 active support period once the clinical trial design and statistical approach has been finalized.