Amyotrophic Lateral Sclerosis (ALS) Intermediate Patient Population Expanded Access (U01 Clinical Trial Required) | RFA NS 22 071

Frequently Asked Questions (FAQs) - NIH RFA-NS-22-071 (ALS Expanded Access Real-World Data)

1) What is this funding opportunity trying to support?

This NIH funding opportunity (RFA-NS-22-071) supports research that uses real-world data generated when an investigational ALS drug or biologic is provided through an intermediate-size Expanded Access (EA) protocol. The focus is on studying outcomes, safety, and other clinically meaningful measures in people living with ALS who cannot enroll in standard clinical trials, while operating under an FDA-regulated expanded access pathway.

2) Which NIH Institute is running the program?

The program is run by the National Institute of Neurological Disorders and Stroke (NINDS) in partnership with the NIH Office of the Director.

3) What award mechanism will NIH use?

The opportunity uses a U01 cooperative agreement mechanism. This typically means NIH will have substantial involvement in project oversight and coordination, rather than acting only as a pass-through funder.

4) What does "Expanded Access" mean in the context of this opportunity?

Expanded access is an FDA-regulated pathway that allows treatment use of an investigational product (drug or biologic) outside a standard clinical trial. In this opportunity, expanded access is used to provide the investigational ALS therapy to patients who cannot enroll in existing trials, while also collecting data for research purposes.

5) What does "intermediate-size Expanded Access protocol" mean here?

It refers to providing investigational product access to an "intermediate" number of ALS patients (not just a single patient and not an unlimited large-scale program), specifically in a structured expanded-access protocol that supports consistent data collection and analysis.

6) Who is the target patient population?

The target population is people living with ALS who are ineligible for existing trials. Examples given include individuals who fail inclusion criteria, have comorbidities, are outside allowed disease stage windows, or face other barriers that prevent participation in registrational studies.

7) Is the purpose of the award simply to provide access to the investigational therapy?

No. The funded project is not simply to provide access. It is to conduct scientific research using the data collected during the intermediate expanded access protocol, with a rigorous data collection and analysis plan.

8) What kinds of data or endpoints are expected to be studied?

The announcement emphasizes studying outcomes, safety, and other clinically meaningful measures. The work is expected to generate useful and interpretable evidence while reflecting the realities of a less-controlled clinical environment than a conventional trial.

9) How is this different from a conventional clinical trial?

This initiative is built around treatment delivery under expanded access rather than a traditional controlled trial setting. The data are described as "real-world" and the environment is less controlled than a conventional trial, so applicants are expected to design rigorous methods that still work under expanded-access conditions.

10) What does NIH mean by "expanded access must not interfere with product development"?

A core requirement is that expanded access cannot undermine, delay, or compromise the clinical investigations that could support marketing approval. The EA protocol should not draw away eligible participants from a phase 3 trial, disrupt trial operations, or create confusion about endpoints and standards of evidence.

11) Is this initiative meant to replace phase 3 trials?

No. The funded work is framed as complementary to, not a substitute for, pivotal clinical trials. The goal is to responsibly generate additional knowledge while protecting the integrity and feasibility of studies intended to support FDA approval.

12) Who is eligible to apply in practice?

Eligibility is narrow in a practical sense. Applicants must be clinical trial sites that are already participating in a phase 3 clinical trial supported by a US small business, where that small business is also the FDA-designated sponsor of the investigational ALS drug or biologic and holds the relevant IND.

13) What is the required relationship to the small business sponsor?

The applicant must be a clinical trial site participating in a phase 3 trial supported by a US small business. That same small business must be the FDA-designated sponsor and must hold the IND for the investigational ALS drug or biologic.

14) Does the FOA list organizational types that can apply?

Yes. The notice indicates a wide range of organizational types can apply under NIH rules (for example, state and local governments, public and private institutions of higher education, nonprofits, tribal governments and organizations, certain community-based organizations, and for-profit entities). However, the key gatekeeper is still that the applicant must be a qualifying clinical trial site tied to the specified phase 3/IND sponsor setup.

15) Are non-US (foreign) organizations eligible to apply?

No. Non-domestic (non-US) entities are not eligible to apply.

16) Are foreign components allowed under a US applicant organization?

No. Non-domestic components of US organizations are not eligible, and foreign components (as defined by the NIH Grants Policy Statement) are not allowed. The applicant organization and proposed work must be structured to avoid foreign components.

17) What is the funding ceiling for this opportunity?

The posted award ceiling is $8,250,000.

18) What is the funding activity category and CFDA number?

The opportunity falls under the Health funding activity category and lists CFDA 93.853.

19) What were the key dates mentioned?

The original closing date listed is June 17, 2022. The FOA was expected to be published in May 2022 with applications due in June 2022, indicating a short turnaround.

20) Why did NIH provide an early notice for this opportunity?

The description emphasizes that early notice was provided so teams could form meaningful collaborations and design projects responsive to the initiative before the application deadline, especially given the short turnaround between anticipated publication and due date.

21) What scenario is this opportunity specifically aimed at?

It is aimed at a specific situation: an investigational ALS therapy already in phase 3 development under a US small business IND sponsor, with trial sites positioned to offer the product via an intermediate expanded access protocol to patients who cannot join the trial, and with NIH funding supporting the research infrastructure and analyses to learn from those expanded-access experiences without jeopardizing the development pathway toward marketing approval.