Basket Clinical Trials of Drugs Targeting Shared Molecular Etiologies in Multiple Rare Diseases (U44 Clinical Trial Required) | RFA TR 20 032

FAQs - NIH RFA-TR-20-032 (U44) Basket Clinical Trials in Rare Diseases

What is this funding opportunity?

This is a National Institutes of Health (NIH) funding opportunity announcement (FOA) identified as RFA-TR-20-032. It supports small businesses proposing to run basket clinical trials in rare diseases under a cooperative agreement mechanism (U44). The FOA is categorized under health and is associated with CFDA 93.350.

What is the overall goal of the FOA?

The goal is to speed therapy development for rare diseases by supporting clinical trials that focus on shared biology. Instead of treating each rare disease as an entirely separate clinical development program, the FOA encourages a single trial framework that evaluates a drug across multiple distinct rare diseases that share a common molecular cause or pathway.

What is a "basket" clinical trial in the context of this FOA?

In this FOA, a basket trial refers to a single clinical trial framework that tests a drug across more than one distinct rare disease, where enrollment is driven by shared molecular features (a common molecular etiology or pathway) rather than by a single diagnosis. The intent is to make development more efficient when patient populations are very small.

Does the project need to include an actual clinical trial?

Yes. The announcement is described as "Clinical Trial Required," and a project under this FOA is expected to be an actual clinical trial rather than only preparatory or preclinical work.

What types of therapeutics or targets are emphasized?

The scientific emphasis is on drugs that target a shared molecular etiology across more than one rare disease. Applicants are expected to justify why a single therapeutic approach is likely to affect a common driver across multiple conditions, supported by strong mechanistic and/or human data.

How does this FOA define the key scientific rationale for a basket approach?

The central rationale is that multiple rare diseases can share a common molecular cause or pathway, and a therapy directed at that shared biology could be tested across those distinct diseases within one clinical trial framework. This is intended to improve efficiency and accelerate development relative to conducting separate trials for each disease.

Why does the FOA prioritize shared biology rather than disease-by-disease development?

Rare-disease patient populations are often very small. The FOA frames basket trials as a way to avoid slow, expensive, or infeasible development paths that would result from splitting efforts into multiple independent trials. By pooling eligible participants across diagnoses using shared molecular criteria, the approach aims to use limited patient pools more effectively.

What advantages does the FOA associate with basket trials in rare diseases?

The FOA describes basket trials as a way to increase clinical development efficiency by enrolling patients based on molecular features that cut across diagnoses. This approach aims to generate clearer signals of activity and safety while making better use of limited rare-disease patient pools.

Is there a preference for specific disease areas or networks?

Yes. NIH states a preference for applications that focus on diseases already being studied within the Rare Disease Clinical Research Network (RDCRN).

Is collaboration with the RDCRN encouraged?

Yes. The FOA favors applications that include collaborations with RDCRN clinical investigators, signaling that use of RDCRN-related expertise and infrastructure may strengthen feasibility for launching and executing a multi-disease trial.

Why does the FOA prefer alignment with RDCRN activities?

The FOA indicates this preference is intended to reduce startup time and leverage existing infrastructure and data. Proposals aligned with RDCRN priorities, cohorts, registries, natural history data, experienced sites, and established investigator networks may be viewed as more feasible for efficient trial execution.

Who is eligible to apply?

Eligibility is limited to small businesses, consistent with the U44 mechanism described in the opportunity.

Are foreign institutions eligible to apply?

No. Foreign institutions are not eligible to apply under this FOA.

Are non-U.S. components of U.S. organizations eligible to apply?

No. Non-U.S. components of U.S. organizations are not eligible.

Can the project include any international work at all?

Possibly. The FOA notes that "foreign components" may be allowed as defined in the NIH Grants Policy Statement. This typically refers to discrete elements of the project performed outside the U.S. under specific conditions and with NIH approval, rather than a foreign applicant organization. Any international involvement would need to align with NIH policy and be clearly justified as necessary.

What is the award mechanism and what does it imply?

The award mechanism is a cooperative agreement (U44). This generally means NIH will have substantial scientific or programmatic involvement during the project compared with a standard grant.

What type of funding instrument is this?

It is a discretionary funding opportunity using a cooperative agreement instrument type.

Which federal agency issues this opportunity?

The opportunity is issued by the National Institutes of Health (NIH).

What is the CFDA number associated with this opportunity?

The opportunity is associated with CFDA 93.350.

What are the key posted dates for this FOA?

The posting indicates a creation date of September 15, 2020, and an original closing date of November 12, 2020.

Is this opportunity still open?

Based on the posted dates provided (original closing date of November 12, 2020), this opportunity appears time-bound and may no longer be open unless it has been reissued or extended under a new announcement.

How should applicants think about feasibility for a multi-disease trial under this FOA?

The FOA signals that feasibility may be strengthened by strong mechanistic and/or human data supporting a shared molecular driver across multiple rare diseases, and by leveraging existing RDCRN-related infrastructure (including cohorts, registries, natural history data, experienced sites, and investigator networks) to reduce startup time and support execution.