NIH/NCI 451 – Rapid and Affordable Point-of-Care HPV Diagnostics for Cervical Cancer Control

Fast-Track proposals will be accepted.

Direct-to-Phase II proposals will be accepted.

Number of anticipated awards: 3-5

Budget (total costs, per award):

Phase I: up to $400,000 for up to 12 months

Phase II: up to $2,000,000 for up to 2 years

Proposals that exceed the budget or project duration listed above may not be funded.

Summary

Cervical cancer is the fourth most common cancer and cause of cancer-related mortality in women. In low- and middle-income countries (LMIC), cervical cancer is typically the first or second most common cancer and cause of cancer-related mortality in women due to poor access to preventive services. When pre-cancer or cancer is diagnosed early it is one of the most preventable or treatable forms of cancer. As a result of complex and expensive cytology-based programs in high-income countries, cervical cancer has become a cancer that defines health disparity populations and one that is still a major cause of morbidity and mortality in low-resource settings globally, where a cytology-based screening program may not be feasible.

The World Health Organization (WHO) Global Cervical Cancer Elimination strategy calls for twice-in-a-lifetime screening of at least 70% of women globally with a high-performance test. Realization of that goal given the current commercially available HPV tests is unlikely without new tests coming to market that can be performed and analyzed outside of traditional healthcare settings and are at a price point that is affordable for going to scale in low-resource settings. Fortunately, emerging test chemistries, including those based on isothermal amplification of HPV DNA, have shown significant promise for the design of highly accurate HPV diagnostics at lower cost than existing tests. Additionally, numerous studies have shown that women across diverse settings can properly collect their own samples for HPV-based cervical cancer screening and that HPV DNA can be detected in a way that is non-inferior to clinician-collected samples.

The overarching goal of the work to be supported by this initiative is therefore to bring needed new alternatives for HPV testing to the market that are both in a form factor and at a price point that will enable testing programs to be established globally.

Project Goals

Projects in response to this FOA should first develop a functioning prototype for a portable HPV diagnostic designed for nearpatient use. The device should enable rapid detection and genotyping for HPV. Projects should establish initial clinical performance for the device using clinician-collected samples before moving to a larger prospective validation of the device using self-collected specimens. Applicants to this FOA can propose to modify an existing device such that it can be used for HPV diagnostics at the point-of-need; simplify or add new features to a device to enable the device to operate outside a laboratory; and/or apply existing or emerging technologies that have not been previously used for HPV diagnostics. Supported work includes both the development of the device as well as approaches for simplifying sample preparation and reducing training needs for its use.

The proposed technologies/devices are expected to provide clear clinical utility at the point-of-need. To that end, supported activities should include end-user design as well as usability studies centered around minimally trained health workers at the community level. The technology must comply with the applicable regulations and international standards/guidelines [such as Good Laboratory Practice (GLP), Good Manufacturing Practice (GMP), WHO guidelines, FDA Investigational New Drug (IND), FDA Investigational Device Exemption (IDE), and local regulations at project sites outside the US].

Investigators must explicitly consider affordability and cost-effectiveness design criteria for technologies proposed in applications responding to this FOA. Considerations of cost and affordability should include disposables. Technologies should be sustainable and affordable by local providers (either low enough in cost to easily replace, have easily replaceable parts/be easy to repair, and/or use parts, reagents, and consumables that are locally available in LMIC supply chains).

Note: This FOA specifically focuses on development of an affordable point of care (POC) HPV diagnostic device to enable scaling up cervical cancer screening programs globally and does not support development of associated devices for self-collection and transport/storage of cervicovaginal specimens.

Phase I Activities and Deliverables:

Using end-user design principles, develop the prototype diagnostic device with the following characteristics:
- Ease of use: the device must be suitable for use by local caregivers with minimal training in its operation and maintenance.
- Operable in locations with limited clinical infrastructure (i.e., design for use outside of laboratory settings).
- Designed for use at the community level and in non-traditional healthcare settings.
- Intended for use with either provider or self-collected cervicovaginal specimens obtained with one of the current commercially available kits. Note: Showing that the test works only with provider collected specimen is not sufficient for this deliverable.
Demonstrate a working relationship with the site(s) where the clinical validation study will take place.
Conduct studies to establish analytical performance (analytical sensitivity, specificity) and other performance characteristics (e.g., limit of detection, consistency, reproducibility) with self-collected samples.
Conduct studies to evaluate and test user acceptability and feasibility in both average-risk and high-risk (e.g., women living with HIV) populations.
Conduct initial cross-validation with at least one of the current FDA-approved HPV testing assays to determine the clinical performance measures.

NOTE: Phase I activities likely require a collaboration or partnership with a research group or medical facility that can provide relevant patient access; As such, the offeror should provide a letter of support from the partnering organization(s) in the proposal to that end.

Phase II Activities and Deliverables:

Develop a well-defined diagnostic device under good laboratory practices (GLP) and/or good manufacturing practices (GMP).
Perform manufacturing scale-up and production for multi-site and multi-test evaluations, including sites both in the U.S. and at a site in a resource-limited setting.
Demonstrate the clinical sensitivity and specificity of the device for provider-collected and self-collected specimens by performing multi-site and multi-test evaluations.
Develop a training plan for healthcare delivery users, to help assure progression toward clinical utility and benefit from the validated technology.
Report on the sustainability/durability of the device/assay.
Establish a strategy for FDA regulatory approval and insurance and/or CMS reimbursement

Receipt date: November 4, 2022, 5:00 p.m. Eastern Daylight Time

Apply for this topic on the Contract Proposal Submission (eCPS) website.

For full PHS2023-1 Contract Solicitation, c lick here.