Goal 4. Objective 3: Advance basic science knowledge and conduct applied prevention and treatment research to improve health and development
HHS conducts, funds, and supports a broad and diverse portfolio of biomedical research in a range of scientific disciplines, including basic and translational research, to augment scientific opportunities and innovation for public health needs. HHS works to strengthen basic and applied science and treatment pipelines to assess potential health threats and bolster the fundamental science knowledge in these risk areas to expedite the development of therapies. As described in Strategic Objective 4.2, Expand the capacity of the scientific workforce and infrastructure to support innovative research, HHS conducts research is conducted ethically and responsibly.
The Office of the Secretary leads this objective. The following divisions are responsible for implementing programs under this strategic objective: ACL, AHRQ, CDC, FDA, NIH, and OASH. In consultation with OMB, HHS has determined that performance toward this objective is progressing. The narrative below provides a brief summary of progress made and achievements or challenges, as well as plans to improve or maintain performance.
Objective 4.3 Table of Related Performance Measures
By 2023, develop, optimize, and evaluate the effectiveness of nano-enabled immunotherapy (nanoimmunotherapy) for one cancer type (Lead Agency - NIH; Measure ID - SRO-2.1)
|FY 2018||Optimize properties of three nanoformulation for effective delivery and antigen-specific response in immune cells.||Developed, tested, and optimized, in animal models, three unique nanodelivery systems for effective anti-cancer immunotherapeutics||Target Met|
|FY 2019||Further optimize top two candidate nanoformulation for co-delivery of multiple antigens to enhance anti-tumor response in one animal model.||Further optimized two unique nanodelivery systems for effective anti-cancer immunotherapeutics in different animal models and showed promising results for consideration in clinical trials||Target Met|
|FY 2020||Further optimize the top candidate nanoformulation for co-delivery of antigens, adjuvants and immuno-modulators and evaluate its efficacy and long-lasting immunity (over 3 months) in preclinical models with established tumors.||12/31/20||In Progress|
|FY 2021||Further optimize the top candidate nanoformulation for co-delivery of antigens, adjuvants and immuno-modulators and evaluate its efficacy towards near and distance metastatic lesions in preclinical models with established tumors.||12/31/21||In Progress|
Nanoparticles are extremely tiny particles that can coat, attach to, or encapsulate drugs. Scientists use nanoparticles in drug delivery systems to enhance the effectiveness of cancer drugs, which include immunotherapies. NIH supports research to enhance existing immunotherapies with nanotechnologies and facilitate the development of new, more efficacious nano-based immunotherapies.
Results from recent studies have shown that optimizing nanoparticle drug delivery systems improves the effectiveness of cancer immunotherapy. The optimization process of both drugs and delivery systems involves many different steps, which include testing the drug systems in different animal models and in different stages of disease (e.g., localized tumors and tumors that have spread to other parts of the body). In FY 2019, two NIH-funded research teams further optimized two unique nanoparticle drug delivery systems. Their work provides additional evidence that these systems are effective in delivering drugs to different tumor types and at different stages of disease, which include stages when the tumors have spread to other parts of the body.
In FY 2020 and FY 2021, NIH will support the optimization and evaluation of the top-candidate nanoparticle drug delivery system in animal models of advanced stages of cancer. These efforts will lay the groundwork for obtaining FDA approval to begin evaluating the system in human studies.
By 2022, evaluate the safety and effectiveness of 1-3 long-acting strategies for the prevention of HIV (Lead Agency - NIH; Measure ID - SRO-2.9)
|FY 2017||Strategy 1: Continue enrolling participants into two studies to test the safety, tolerability, and effectiveness of VRC01 as an intravenous prevention strategy.||Enrollment of participants continued for both studies.||Target Met|
|FY 2018||Strategy 2: Analyze primary results of a Phase 2a study examining the long-acting injectable, cabotegravir, for the prevention of HIV||Analysis of primary results has been conducted and results are in press.||Target Met|
|FY 2019||Strategy 3: NIH-funded investigators complete final analysis of an open-label extension study that builds on the findings of an earlier trial and aims to assess the continued safety of the dapivirine vaginal ring in a more real-world context and study participants' adherence||NIH-funded investigators completed final analysis of an open-label extension study that built on the findings of an earlier trial and aimed to assess the continued safety of the dapivirine vaginal ring and study participants' adherence to its use.||Target Met|
|FY 2020||Strategy 1: Complete follow-up of participants in studies testing the safety, tolerability, and effectiveness of VRC01.||12/31/20||In Progress|
|FY 2021||Strategy 1: Analyze data of two studies testing the safety, tolerability, and effectiveness of VRC01 broadly neutralizing antibody (bnAb).||12/31/21||In Progress|
NIH-funded research has led to the identification of highly effective, non-vaccine prevention strategies that have the potential to significantly reduce HIV infection rates around the world. However, adhering to daily or near-daily dosing has proved challenging for both HIV-infected and uninfected individuals. Women in particular have limited HIV prevention options that they can initiate and that are discreet and long-acting. To address this issue, NIH funded a study to gather additional data on the safety of a vaginal ring infused with a drug to prevent HIV, as well as new data on whether and how women used it in a real-world setting. The ring is inserted once a month and slowly releases the antiviral drug. Overall, the ring was found to be safe and have moderate levels of HIV protection. Additionally, the majority of study participants accepted and were willing to use the ring to protect themselves against HIV infection. These and related efforts represent some of the building blocks that NIH is laying toward the goal of providing women with a range of HIV prevention tools from which they can make informed choices.
In FY 2020 and FY 2021, NIH will continue to support studies that assess whether giving uninfected people an infusion of VRC01, a "broadly neutralizing" (capable of stopping a wide range of HIV strains from infecting human cells) antibody, every eight weeks is an effective way to protect them against HIV infection.
By 2023, identify risk and protective alleles that lead to one novel therapeutic approach, drug target, or pathway to prevention for late-onset Alzheimer's disease (Lead Agency - NIH; Measure ID - SRO-5.3)
|FY 2014||Complete Discovery Phase whole genome sequencing and analysis of 582 family members from 111 families with late onset AD to identify genomic regions associated with increased risk of AD; sequencing of the coding regions of the DNA (whole exome sequencing) of 5,000 cases / 5,000 controls for both risk raising and protective loci; and whole exome sequencing and analysis of one individual from ~1,000 additional AD families to identify regions associated with increased risk or protection from AD.||Sequencing and an initial level of analysis were completed.||Target Met|
|FY 2015||Initiate Replication Phase to validate genes / regions of interest identified from case-control and family sequencing in ~50,000 samples from well phenotyped individuals by targeted sequencing and/or genotyping.||Sample selection for whole genome sequencing on additional multiply affected families was initiated. Planning of the Replication Phase has begun.||Target Met|
|FY 2016||Begin confirmation of genomic regions of interest identified in the Discovery Phase using samples from the Replication phase.
Begin harmonization of data from Discovery phase datasets with data from Replication Phase for confirmation of regions of interest.
|Sample selection/sequencing Discovery Extension phases completed (4,000 additional whole genomes). Data analysis for Extension Phase initiated. Genomic Center for Alzheimer's Disease funded (all ADSP quality control and data harmonization).||Target Met|
|FY 2017||Continue confirmation of genomic regions of interest in the Discovery and Replication phase datasets. Continue harmonization of Discovery Phase and Replication Phase datasets.||NIH met its target of confirming genomic regions of interest in the Discovery and Replication phase data sets and continues to harmonize the Discovery Phase and Replication Phase data sets.||Target Met|
|FY 2018||Continue confirmation of genomic regions of interest in the Discovery phase using samples from the Replication phase. Continue harmonization of Discovery Phase and Replication Phase datasets. Begin analysis of genomic regions of interest in the genomes of minority cohorts.||NIH continued confirmation of genomic regions of interest in the Discovery Phase using samples from the Replication Phase, continued harmonization of Discovery Phase and Replication Phase datasets, and began analysis of genomes of minority cohorts.||Target Met|
|FY 2019||Begin analysis of genomic regions of interest in the ADSP Discovery Follow-Up Phase using whole genome sequence data from ethnically diverse cohorts. Continue confirmation of genomic regions of interest in the Discovery Phase using samples from the Follow-Up phase. Continue harmonization of Discovery Phase and Follow-Up Phase datasets.||The ADSP Discovery Follow-Up Phase has begun to analyze genomic regions of interest using whole genome sequence data from ethnically diverse cohorts. The ADSP has continued its confirmation of genomic regions identified in the Discovery Phase of the project. Genetic data for all phases of the ADSP have been harmonized.||Target Met|
|FY 2020||Continue analysis of ADSP Discovery Follow-Up Phase in ethnically diverse cohorts. Continue confirmation of genomic regions of interest from Discovery Phase and Discovery Follow-Up Phase in ethnically diverse datasets. Compare data on genomic regions of interest by ethnicity.||12/31/20||In Progress|
|FY 2021||Continue analysis of ADSP Discovery Follow-Up Study in ethnically diverse cohorts. Continue confirmation of genomic regions of interest from Discovery Phase and Discovery Follow-Up Phase in ethnically diverse datasets. Begin harmonization of phenotypic data with ADSP genetic data across multiple types of study approaches from large epidemiology and clinical cohorts that are outside of the ADSP.||12/31/21||In Progress|
There is an urgent need for effective interventions to prevent, delay, and treat Alzheimer's disease (AD). As many as 5.5 million Americans age 65 and older are living with AD. Available treatments do not target the underlying molecular pathways believed to be involved in AD's development; thus, they neither halt nor reverse disease progression.
The overall goal of the NIH-supported Alzheimer's Disease Sequencing Project (ADSP) is to identify genetic variants associated with risk of and protection from AD. In FY 2019, the ADSP continued to reveal the complexity of the genetics of AD, and the challenges involved in genetic data analysis. The data have helped researchers understand why it has been so challenging to find and develop potential treatments. Once the ADSP has identified and confirmed genes associated with AD, their next step is to determine the genes' function and whether these genes interact to modify how the disease manifests. The availability of large amounts of data from multi-ethnic populations, made possible by the ADSP, is bringing the project closer to identifying genetic variants associated with risk of and protection from AD within specific populations.
In FY 2020 and FY 2021, the NIH-supported ADSP will continue its efforts to identify and confirm genes associated with AD and examine them in ethnically diverse populations. NIH will use this information to explore new, promising pathways for treating AD.