Key Dates

Related Announcements

• October 9, 2020 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional). See NOFO PA-20-272.

Issued by

National Cancer Institute (NCI)

Purpose

This Notice of Special Interest (NOSI) from the National Cancer Institute (NCI) announces an opportunity for administrative supplemental funding to support normative data collection and determination of test-retest reliability estimates of US-Spanish translated neuropsychological tests to enhance the diversity of Spanish speakers participating in NCI clinical trials assessing cognitive function.

Background

Neuropsychological tests are used in cancer clinical trials to objectively assess cognitive function before, during and after cancer treatment. NCORP and NCTN clinical trials frequently use three specific neuropsychological tests: 1) the Hopkins Verbal Learning Test-Revised (HVLT-R), 2) Multilingual Aphasia Examination (MAE) Controlled Oral Word Association (COWA), and 3) the Trail Making Test Parts A and B (TMT) as either primary or secondary study endpoints. Neuropsychological tests are highly complex and are needed to systematically assess cognitive functions including verbal fluency, verbal learning and memory, processing speed, and executive function. However, inadequate normative data for these tests relevant to the NCI clinical trials populations and absence of key psychometric properties for these tests limit the inclusion of non-English speaking study participants, and thus perpetuates persistent lack of diversity in these important trials. Although Spanish is the second most spoken language in the US, considerable linguistic variation exists across populations originating from Mexico, Puerto Rico, or South America. While some efforts have been made to translate these test instruments and establish norms, those efforts are incomplete (e.g., data was not collected for all critical test subscores, variable test administration procedures were utilized, limited age ranges of participants were used, test-retest reliability estimates were inadequate).

To address this problem, this NCI Moonshot^SM Initiative project seeks to enhance diverse clinical trial accrual by obtaining normative data and test-retest reliability estimates for US-Spanish versions of these instruments with the expected outcome that this effort will improve clinical trial enrollment, facilitate equitable selection of subjects, and improve the generalizability of results from clinical trials that include Spanish speaking individuals.

Specific Research Objectives

NCI has worked alongside the test’s publisher to create US-Spanish translations that will be provided and should be utilized to obtain normative data from healthy controls as well as test-retest reliability estimates. Normative testing needs to be conducted in individuals who represent various dialects, levels of education, age, and gender.  Participants need to be native, predominant, or exclusive Spanish speakers. Data from up to two administrations per participant will be used to establish critical psychometric properties of these measures.

The project should include:

• Obtaining normative data for US-Spanish versions of HVLT-R, COWA, and TMT in groups defined by sex, age, and education level.
• Obtaining test re-test reliability data for US-Spanish versions of HVLT-R, COWA, and TMT between two administrations of each test spaced approximately 3 months.

Research Bases are encouraged to work collaboratively with other Research Bases and NCORP community sites and other sites to strengthen the proposal and ensure completion of the project requirements.

Specific Requirements

• This administrative supplement requires a study team which includes a neuropsychologist with experience conducting multi-site clinical trials and/or multi-site research involving standardized cognitive testing, preferably including in non-English speaking populations.
• The applications must describe a detailed approach to fulfilling the objectives of this Supplement.
• Provide the neuropsychology expertise and the comprehensive clinical trial operations services necessary to plan, implement, and complete in person (not remotely or via telehealth) normative data collection and determination of test-retest reliability estimates of US-Spanish versions of the following tests used in clinical trials conducted in the United States:  
• Team members should be familiar with the methodology of producing 1) normative data by tabulating the means and standard deviations of the raw scores for each test defined by age, gender, and education level, 2) regression-based norms, and 3) test-specific Pearson correlation coefficients between test-retest scores.
• Study Timeline and Milestones should be included in the PHS Human Subjects and Clinical Trials Information Form
  • Hopkins Verbal Learning Test-Revised (HVLT-R)
  • MAE Controlled Oral Word Association (COWA)
  • Trail Making Test (TMT) Parts A & B
• Protocol Development: Within 60 days of award submit a fully developed protocol that follows NCORP protocol guidelines.
  • The protocol must be written to achieve sample sizes required to obtain sample standard deviations that have a high chance of being within desired margins of the true standard deviations.
  • The protocol must be written to adequately sample from several categories including 5 age categories (18-30, 31-54, 55-69, 70-84, 85+), 2 sex categories (Male and Female), and 2 categories of education level (high-school equivalent or less, and greater than high-school equivalent; more fine-grained data may be obtained and reported).
  • The protocol should be written to achieve a second administration of each test from at least 50% of the study participants recruited for the normative data collection (i.e., the main study) that parallels typical intervals (e.g. 2-3 months).
  • The protocol should allow for randomizing patients to the alternate test forms of HVLT-R and COWA in accordance with the goals of obtaining normative data and test-retest reliability estimates.
  • Country-of-origin data must be collected for later use, so protocol development should justify feasibility of accruing Spanish speakers with a variety of countries-of-origin. The five largest Hispanic populations in the U.S. by origin group in 2021 were Mexicans (37.2 million), Puerto Ricans (5.8 million), Salvadorans (2.5 million), Dominicans (2.4 million) and Cubans (2.4 million). These 4 countries of origin and one U.S. territory represent approximately 50 million people, of which approximately 74.4% are of Mexican origin. Therefore, protocols should target between 15%-35% of participants with countries of origin other than Mexico.
  • The protocol should describe the methods that will be employed to review medical, neurologic, and psychiatric histories to ensure only healthy controls are recruited, the sociodemographic data that will be collected, and the methods and procedures to ensure that the healthy controls are native, predominant or exclusive Spanish speakers, and that the bilingual test administrators are adequately bilingual in Spanish and English.
• Eligible Participants: All participants meet the following inclusion criteria: a) 18 years of age and older, b) Spanish is their native, predominant and/or exclusive language, and c) have sufficient literacy levels to participate in cognitive testing.
• Participant Recruitment: Provide a recruitment plan that ensures sufficient eligible participants are available for normative data collection and determination of test-retest reliability estimates for the battery of tests above. Develop and implement methods to contact, screen, and schedule participants and replacement participants (if needed) and provide monetary incentives to participants.
• Bilingual Test Administrators: Obtain services of a sufficient number of qualified bilingual test administrators. Conduct training and credentialing activities to ensure consistent and correct test administration. Propose a plan to monitor test administration to ensure compliance with standardized test administration procedures. The Research Base will describe the process to coordinate, manage, schedule, and budget for the test administrators.
• Test Administration Facilities: Secure the necessary number of facilities to conduct Spanish-language testing in multiple locations to meet the diverse patient population. Each facility should have adequate space to complete testing in a quiet, distraction free environment with testing resources required for these measures (e.g., appropriate table, stopwatch, pen). Proposed plans should ensure that only the participant is in the room with the test administrator; no other family members, friends, patients, or staff should be in the room during testing. 
• Post-Testing/Data Analysis Phase: Provide a plan for all test results to be centrally reviewed and scored by a neuropsychology expert(s). Provide cognitive debriefing results to NCI and participate in results review with the NCI and selected stakeholders. Provide all data from normative testing that have been de-identified and de-linked, analyzed and summarized to NCI. Research Bases will be responsible for providing the final analysis of the normative data, test-retest reliability data, and publish the results.

Non-responsive Applications 

Applications not responsive to this NOSI include:

• Applications that propose normative testing on test instruments other than those stated in the research objective.
• Applications that do not plan to fulfill the research objective.
• Proposals that cannot reasonably be completed  in one year of supplemental funding with the second year of a no-cost extension.
• Applications with a foreign component.

All applicants are encouraged to discuss their applications with the scientific/research contact listed in this NOSI (below) prior to submission.

Application and Submission Information

Applications for this initiative must be submitted using the following opportunity or its subsequent reissued equivalent:

PA-20-272 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional).

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

Eligibility

• Only existing UG1 awardees of supported by  RFA-CA-18-015 - NCI Community Oncology Research Program (NCORP) Research Bases (UG1 Clinical Trial Required) are eligible to apply.
• The proposed project must be within the scope of the parent award.  
• Only one application per NCORP Research Base will be allowed.
• For supplements to parent awards that include multiple program directors/principal investigators (PDs/PIs), the supplement may be requested by any or all of the PDs/PIs (in accordance with the existing leadership plan) and submitted by the awardee institution of the parent award.
• If the PD/PI of the supplement application is not the PD/PI of the parent award, a letter of support from the contact PI of the parent award must be provided.
• The project period for the parent award must be active, and cannot be in a no-cost extension, for the 1 year of the administrative supplement application/project/award.

Application Due Dates:

June 21, 2024 until 5:00 PM local time of applicant organization, for possible funding in FY2024.

The Expiration Date of this NOSI is June 22, 2024.

Budget:

• The budget should justify all the direct and indirect costs.
• Requests must reflect the actual needs of the proposed project.
• Allowable costs include funding for personnel including bilingual testing professionals, activities related to study conduct, all site reimbursement, and all participant reimbursement.
• Requests are permitted for one year of support with one no cost extension.
• A detailed budget is required. Modular and categorical budget are not allowed.
• The earliest anticipated start date is August 1, 2024.

Submitting Applications:

• Applicants should begin the supplement application abstract by stating “This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-24-040.”
• For funding consideration, applicants must include “NOT-CA-24-040” (without quotation marks) in the Agency Routing Identifier field (box 4b) of the SF424 R&R form. Applications without this information in box 4b will not be considered for this initiative.
• Page limits: The Research Strategy section of the application is limited to 6 pages.

Review and Selection Process:

NCI will conduct administrative reviews of applications and support the most meritorious application submitted for consideration, based on funds' availability.

Additionally, NCI program staff will evaluate applications using the following selection factors:

• The proposed technical approach demonstrates a clear understanding of the specific aims and technical details of the project.
• The recruitment and testing plan demonstrate ability to complete the project within the expected time frame.
• Proposed personnel have the knowledge, experience, and time commitment to complete the project successfully.
• Has the application demonstrated engagement with research base sites and community sites that have access to the necessary population to conduct the study in an expedited fashion.

Inquiries

Please direct all inquiries to:

Scientific Contact:
Cecilia Lee, DrPH, RN 
National Cancer Institute (NCI)
Telephone: 240- 276-7050
Email: Cecilia.lee@nih.gov

or

Research Base Program Officer:
Brandy Heckman-Stoddard, Ph D , M P H 
National Cancer Institute (NCI)
Telephone: 240-276-7048
Email: heckmanbm@mail.nih.gov