Supplemental Information for NIDA RFAs: DA-17-014 and DA-17-023

FAQs for RFA-DA-17-014 and RFA-DA-17-023

These frequently asked questions (and answers) are designed to help applicants for the following RFAs:

RFA-DA-17-014: HIV, HCV and Related Comorbidities in Rural Communities Affected by Opioid Injection Drug Epidemics in the United States: Building Systems for Prevention, Treatment and Control (UG3/UH3)  - https://grants.nih.gov/grants/guide/rfa-files/RFA-DA-17-014.html

RFA-DA-17-023: Hepatitis C Virus (HCV) Advanced Molecular Detection in Support of Systems for Prevention, Treatment and Control of HIV, HCV and Related Comorbidities in Rural Communities Affected by Opioid Injection Drug Epidemics in the United States (U24)  - https://grants.nih.gov/grants/guide/rfa-files/RFA-DA-17-023.html

What is a cooperative agreement and how will it function here?

Cooperative agreements are a support mechanism used when there will be substantial scientific or programmatic involvement in the award by the Federal government. In practice, substantial involvement means that, after award, Federal scientific or program staff from the funding programs will assist, guide, coordinate, or participate in project activities. Under the cooperative agreement, the purpose of Federal staff is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role without assuming prime responsibility in the activities. The prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and Federal staff.  For example, the funders will encourage awardees to use common protocols across all awardee sites for data collection instruments and methods, clinical protocols, laboratory protocols, and data analysis where these steps will enhance efficiency and scientific inquiry. Federal partners also will have access to project data and may participate in publications, if warranted.  CDC will have a specific role in developing the U24 GHOST laboratory and CDC also will conduct HIV sequencing and syphilis testing. UG3/UH3 applications will need to address specimen collection, processing, and testing, including how these relate to testing conducted by CDC and the U24 GHOST laboratory. Specific roles for investigators and Federal partners are detailed under “Cooperative Agreement Terms and Conditions of Award” in each RFA.

There will be a project Executive Steering Committee (ESC) with representation from CDC, NIH and all project sites to facilitate regular communication among awardees, NIH, CDC, the Appalachian Regional Commission, SAMHSA and any other federal agencies which may have programmatic interests in the projects or that provide funding. The ESC also may engage members who provide substantive scientific, programmatic, or clinical knowledge from academia, government, private industry or other relevant sectors. The ESC will convene periodic meetings and conference calls for study coordination and management.

What are the funding roles of the Federal agencies?

NIDA and CDC are the primary funders of the RFA. NIDA has made the largest financial contribution and will be responsible for the peer review of the applications received for these RFAs, although final funding decisions will include consultation and collaboration with the other Federal partners.  NIDA and CDC will have assigned science and project officers who will have the primary role among the Federal funders for administering awards and determining transition from the UG3 to the UH3 phases. CDC will be the primary agency providing technical assistance for the development of the U24 GHOST Laboratory.  

SAMHSA is interested in supporting substance use disorder treatment and recovery support services related to RFA-DA-17-014, including evidence-based substance use disorder prevention and treatment interventions for clients living with or at high risk for HIV, HCV and related comorbidities. SAMHSA’s specific interests include client referrals and linkages to medication-assisted treatment (MAT), antiretroviral therapy (ART), hepatitis A virus (HAV) and HBV vaccination, HCV treatment and syringe service programs (SSPs) along with collecting information confirming client receipt of these types of services.  SAMHSA also is interested in supporting testing clients for HIV, HCV, HBV and other sexually transmitted infections (STIs). 

The Appalachian Regional Commission (ARC) anticipates committing up to $750,000 for first year contributions to UG3/UH3 projects in specific counties affected by changes in the coal mining and related industries (see question below re: “Other Geographic Considerations” for more details).  Although applications should reflect the budget amounts specified in the RFAs, rather than being directed at ARC or SAMHSA contributions, applications should specifically break out line items associated with these activities (ARC-supported counties, SAMHSA-supported services) in their budget justification and will need to report on these activities in their progress reports. The availability of SAMHSA and ARC funding, like other agency funding, is subject to appropriations.

What is the UG3/UH3 mechanism?

The UG3/UH3 mechanism is a Cooperative Agreement that involves two phases. The UG3 phase will support projects with specific milestones to be accomplished by the end of the first 2 years. Applications must include Transition Milestones to be assessed at the end of the UG3 phase. The UH3 phase will provide funding for up to three (3) additional years to those projects that successfully completed the milestones set forth in the UG3 phase and will be administratively considered by NIDA and CDC/NCHHSTP and prioritized for transition to the UH3 phase based on milestone performance, as well as programmatic priorities and availability of funds. Funding of the UG3 phase does not guarantee support of the UH3 phase, and it is anticipated that not all funded UG3 projects will transition to the UH3 phase. Appeals of the transition decision will not be accepted. 

What should be the focus of the UG3/UH3 projects?

RFA-DA-17-014 will support multi-component research projects that inform community response and promote comprehensive, integrated approaches to prevent HIV and HCV infection, along with associated comorbidities such as HBV infection and STDs, among people who inject drugs (PWID) in rural US communities. Opioid injection and its consequences (e.g., HIV, HCV, HBV, STDs and overdose) are the primary foci. These projects should yield evidence of the effectiveness of community response models and best practices in responding to opioid injection epidemics that can be implemented by public health systems in similar rural communities in the US.

What should the UG3/UH3 projects look like?

UG3/UH3 applications are expected to focus on Multi-Method projects with a clear plan for integrating approaches such as analysis of PWID networks, epidemiologic surveys, laboratory analyses, document reviews, ethnographic methods, program data surveys, and collection of biologic specimens. UH3 projects should propose an integrated model of service delivery and include a plan for evaluating the initial efficacy of this model with particular attention to evaluation of outcomes for interventions that fill gap areas. The plan also should address factors related to successful implementation and sustainability. There should be an estimate of the PWID population to be served and scientific justification for the study aims to be undertaken.

Efforts are encouraged to identify innovative service delivery approaches such as telehealth, justice system-based programs, integration with existing clinical infrastructure, or the use of non-traditional service delivery venues. Novel approaches to service financing are encouraged, including braiding of funding streams and incorporation of public and third-party insurance, particularly where Medicaid expansion has occurred. Collaborations with state and/or local health departments are considered to be a key factor for the successful community engagement of appropriate implementing partners, as well as for strengthening and developing local data collection systems that will sustain monitoring and response to future drug use and injection epidemics and their infectious disease consequences. Although the primary focus is on services that prevent HIV, HCV, and other consequences of opioid injection, approaches are encouraged that incorporate efforts to address structural factors which may influence drug use in these communities.

The UG3 and UH3 projects should reflect the demographic composition of local opioid injection epidemics. These epidemics have been characterized by younger individuals than in past urban opioid injection epidemics, but this may vary by locality. Recruitment is encouraged to include minors (those under the age of 18 years), as appropriate, as well as representation of all genders, sexual minorities, and racial/ethnic minorities. The local epidemics that are the focus of the UG3/UH3 projects may have social, sexual, or drug use network connections to other HIV-infected populations (e.g., gay men or sex workers) or to HIV or HCV epidemics in nearby communities---these may warrant examination in these UG3/UH3 projects (e.g., analysis of partner patterns) but these should not become the primary focus of the UG3/UH3 projects.

How should UG3 and UH3 projects fit together?

Assessments in the UG3 phase are expected to engage stakeholders and provide foundations for optimized community-based programming to facilitate: linkage to services, including SSPs (unless prohibited by law) and treatment for substance abuse; testing, care, and treatment for HIV, HCV, and HBV; detection and management of STDs; and improving surveillance to detect outbreaks. Programming to prevent new opioid use, prevent transitions to injection, and prevent overdose, also should be included. Consideration should be given to improving the quality and speed of screening and diagnostic testing for blood-borne pathogens including HIV, HCV, HBV and STDs. In short, the UG3 should provide data that can identify and address steps necessary to fill gaps in the local public health and health care systems to mitigate existing injection epidemics and prevent new ones.

The new or modified programming and the data collected to inform policy that result from the UG3 phase will be the subject of the UH3 phase and will be supported for a maximum of three years. These projects should propose an integrated model of service delivery and include a plan for evaluating the initial efficacy of this model with particular attention to evaluation of outcomes for interventions that fill gap areas. The UH3 model of service delivery should be supported by the conceptual framework and data collection methods proposed in the UG3 phase. The UH3 plan also should address factors related to successful implementation and sustainability. There should be an estimate of the PWID population to be served and scientific justification for the study aims to be undertaken.

What will the U24 mechanism support?

The U24 cooperative agreement will support infrastructure development for an HCV next-generation sequencing (advanced molecular detection) laboratory using Global Hepatitis Outbreak and Surveillance Technology (“GHOST”). This infrastructure development will occur in collaboration with CDC’s Division of Viral Hepatitis. GHOST will aid in establishing HCV transmission links, outbreak investigations and molecular surveillance. The GHOST laboratory will enable state and local health departments to investigate HCV outbreaks and to identify HCV transmission networks among PWID. By delineating transmission networks, these sequence data will guide public health interventions for disrupting transmission of HCV disease in PWID communities. The GHOST laboratory will support both the UG3 and UH3 research projects supported by RFA-DA-17-023. It also will provide specimen storage and processing for laboratory work to be conducted by CDC (HIV sequencing and syphilis testing). Applications for the U24 cooperative agreement should indicate how the laboratory can be sustained beyond the funding period.

How should the UG3/UH3 applications consider the U24 funded GHOST laboratory?

Projects funded for the UG3/UH3 will be expected to collaborate with the U24 funded site and the GHOST laboratory is expected to be integrated with the programs of other sites—namely to be testing specimens from them. The GHOST laboratory will enable state and local health departments to investigate HCV outbreaks and to identify HCV transmission networks among PWID. By delineating transmission networks, the selected site will provide sequence data to guide public health interventions for disrupting transmission of HCV disease in PWID communities. The funded GHOST laboratory will accept specimens from participating UG3/UH3 sites and provide viral sequences that will be automatically analyzed at each site, using the GHOST website, to identify HCV transmission links among PWID. The GHOST site also will store and process specimens that will be sent to CDC for HIV sequencing and syphilis testing.

Can I apply for both RFAs?

Applicant organizations are welcome to apply to both RFAs as long as a separate application is submitted for each RFA. Each application should include separate aims, objectives, research strategies, budgets, etc. Single applications that combine both RFAs will be considered non-responsive and will not be accepted. U24 (GHOST laboratory) applications will be scored and rank ordered separately from applications for the UG3/UH3 award. It is anticipated that only one GHOST laboratory application will be funded. No preference will be given to organizations that apply for one or both RFAs.

Are there other geographic considerations?

Applications will be accepted for all areas of the United States that meet rural criteria and demonstrate evidence of significant opioid use that have implications for HIV and HCV transmission. Applications targeting rural counties in the Appalachian Region are particularly encouraged. The Appalachian Regional Commission (ARC) has committed up to $750,000 through the multi-agency POWER 2016 initiative for first-year funding of projects. POWER 2016 targets Federal resources to help communities and regions that have been affected by job losses in coal mining, coal power plant operations, and coal-related supply chain industries due to the changing economics of US energy production. For the UG3/UH3 projects, ARC funds will be awarded only to projects serving “coal-impacted communities” in the Appalachian Region. These communities are those located within, and targeted to, communities or regions that have been impacted, or can reasonably demonstrate that they will be impacted, by employment loss in coal mining, coal power plants, or in the supply chain industries of either. Supply chain industries include, but are not necessarily limited to, manufacturers of mining equipment and parts for coal-fired power plants as well as transportation companies that carry coal. For information about ARC and the 420 counties in the Appalachian Region, see www.arc.gov/counties.

Will applications from foreign organizations be accepted?

These RFAs only will support US domestic organizations and projects. No foreign organizations or projects conducted in foreign countries will be supported.

What project areas will be considered non-responsive for the UG3/UH3 and U24 cooperative agreements?

Applications that focus on the following areas will be considered non-responsive and will not be reviewed:

• Phase III clinical trials
• Cohort studies
• Studies of communities outside the United States or its territories
• Studies whose aims are not focused on the areas identified by the RFA
• Studies that do not include collaboration with a state or local health department, as evidenced by a letter of support and description of collaborative activities in the application
• Studies not focused on rural communities
• Studies that do not include collaboration with a state or local substance abuse agency (UG3/UH3 Only)

Questions and answers primarily related to RFA-DA-17-014 (UG3/UH3 Community Response RFA)

1. If no GHOST site is awarded, must specimens be shipped by the UG3/UH3 sites directly to CDC?
   The specimens collected by the UG3/UH3 sites must be shipped to the GHOST laboratory, if a GHOST laboratory is awarded---or to CDC, if no GHOST laboratory is awarded.
2. Shipping budgets. Who pays for the specimens to be shipped to the GHOST laboratory (or to CDC)?
   The UG3/UH3 sites will pay for the shipment of specimens to the GHOST laboratory (or to CDC, if no GHOST laboratory is awarded). If a GHOST laboratory is awarded, the GHOST laboratory will pay for the shipment of leftover specimens to CDC for HIV and other testing. The GHOST site will only do HCV sequencing. Sites should consider the most feasible way to process, store and ship specimens from their site and consider how this will effect shipping costs (e.g., batches versus individual participants).
3. Are specimens to be collected in the first 2 years (UG3 phase of the study)?
   It will depend on the design of individual UG3 projects, but it is anticipated that some specimens may be collected during the UG3 phase, although it is expected that the bulk of the specimens will be collected and shipped during the UH3 phase for most projects.
4. Can you give examples of Go/No-Go milestones for the transition from the UG3 to the UH3 phase?
   Examples of possible milestones are included in the RFA (see “Research Strategy” section of RFA-DA-17-014, including the “Timelines” subsection). It will be up to each applicant to provide detailed and measurable milestones.
5. It appears that in order to reach the objectives of the UG3/UH3 study, we will need to perform clinical trials. However, the RFA seems to prohibit clinical trials?
   The RFA does not allow Phase III clinical trials. NIH has a relatively specific definition for Phase III clinical trials that may be found here: https://www.nlm.nih.gov/​. Other activities that may be defined as clinical trials by NIH are permissible, as long as they do not meet the definition of Phase III clinical trials.   
6. It appears that in order to reach the objectives of the UG3/UH3 study, we will need to follow people longitudinally. However, the RFA seems to prohibit cohort studies?
   The RFA permits research that can supplement existing epidemiology, particularly in the UG3 phase, as well as research that evaluates the outcomes of the UH3 activities. Particularly in the UH3 phase, this may involve repeated measurements with the same individuals. These kinds of activities are permitted. On the other hand, the RFA does not support traditional cohort studies whose primary purpose is to follow the mortality and morbidity of a sample for its own sake. Longitudinal follow-up data need to address the objectives of the RFA.
7. What are the expectations for common protocols?
   The RFA mentions examples of harmonization that might be expected under “Resource Sharing Plans” and “Areas of Joint Responsibility”, which include protocols and data collection instruments, particularly core assessments. The RFA also recognizes that local conditions (including local laws and policies) may determine what is proposed in any one application (see “Special Topics of Research Interest” and “Research Strategy”). The RFA seeks demonstration projects that may be applicable to locales like those of an individual applicant. Harmonization will be facilitated by the Executive Steering Committee which will include funders and representatives of the funded sites.
8. What are the expectations for the geographic scope of individual applications?
   The funders recognize that the organization and funding of substance use and public health services varies widely across states and that these are likely to define the geographic areas of interest, along with available epidemiologic data and resources available through the RFA. It will be up to each applicant to define their geographic scope and to provide a rationale for choosing their geographic scope.
9. How is “community” being defined for the community response projects? Is it based on geography or demographic categories of people who may be similar in some way?
   The population of interest here is opiate injectors.  The services that are of major interest tend to be defined by the catchment areas and other geography determined by local funding mechanisms. Stakeholders including community coalitions, providers, etc. tend to cluster around public services and follow similar patterns of geography to the organization of services. It is anticipated that applicants will define their communities of interest taking into account how services are organized, as well as the spatial distribution of opiate injectors and stakeholders, as well as the resources available through the RFA.  
10. Can you give us a definition of rural communities?
    The emphasis of this RFA is on rural communities from the perspective that they are characterized by a low density of services and low population densities, overall, as well as limited access to specialty services. These areas also have been characterized by substantial increases in opiate injection drug use in recent years and typically do not have histories of injection drug epidemics. Suburban communities are not included, inasmuch as they have access to a variety of services and higher population densities, overall, than rural areas and are more likely to be near urban areas, with histories of injection drug use epidemics. The federal government has multiple definitions for rural which are included in the RFA and easily accessed (see “Specific Topics of Research Interest”). There may be situations where a target area is part of a large, multi-state metropolitan area, but distinct from most of that area because of where publicly-funded services are available and because the adjacent areas meet one or more federal criteria for “rural”. Scott County, Indiana—site of a recent and well documented rural opiate use epidemic--is an example of this. Applicants are asked, in the RFA, to provide a rationale for how their projects address rural opioid epidemics and are asked to make use of the various definitions of rural, as well as the other allowances (i.e., inclusion of Micropolitan Statistical Areas and Metropolitan Statistical Areas of 250,000 persons or less).
11. Are applicants required to include subjects under the age of 18?
    The RFA does not specifically require the study of persons under the age of 18, but projects should reflect the major demographic dimensions of local epidemics. From the RFA (under “Specific Topics of Research Interest”): “The UG3 and UH3 projects should reflect the demographic composition of local opioid injection epidemics. These epidemics have been characterized by younger individuals than in past urban opioid injection epidemics, but this may vary by locality. There is also particular concern about minors and young adults because of the chronic, relapsing nature of opioid misuse and injection and the long-term effects of these conditions on physical, psychosocial and neurocognitive development. These epidemics especially have been characterized by affecting young, non-Hispanic white and rural PWIDs who have transitioned from use of prescription oral opioids to heroin and other opioid injection. Recruitment is encouraged to include minors (those under the age of 18 years), as appropriate, as well as representation of all genders, sexual minorities, and racial/ethnic minorities.” The inclusion or exclusion of minors, as well as minorities and women, will be reviewed during the scientific review (see NIH “Additional Review Criteria”) and it will be determined if inclusion or exclusion is justified in terms of the scientific goals and research strategy that have been proposed.
12. (Directed to RFA-DA-17-023, but also applicable here): In the Research Strategy section of RFA-DA-17-023, it asks for “a description of the language to be used in informed consent forms to allow testing of de-identified samples by the CDC”.  Will the GHOST laboratory be responsible for obtaining informed consent or contributing to the informed consent documents?
    The GHOST site will receive samples without identifiers but the UG3/UH3 sites should be able to link these to the information they have. The UG3/UH3 sites will need to develop informed consent documents that will allow shipment of de-identified specimens to the GHOST site, if a GHOST site is awarded, or to CDC, if a GHOST site is not awarded. All participating sites will need to have IRB approval for their participation in the research – either for sample collection (UG3/UH3 sites) or to obtain IRB approval or appropriate exemptions, if receiving de-identified specimens/data (GHOST site/CDC). The extent to which a site needs to be involved in the development of informed consent forms will be determined by the institutional IRB.
13. Can allowable expenses include procurement of HIV, HCV or other relevant clinical tests?
    Yes, NIH grant funds may be used to pay all costs (whether usual care costs or research care costs) for research tests or services for individuals who would not have received such tests or services except for their participation in the research study.
    
    Also, please note that incentive payments to volunteers or patients participating in a grant-supported project or program are allowable. Incentive payments to individuals to motivate them to take advantage of grant-supported health care or other services are allowable if within the scope of an approved project.
14. How can salaries and other costs of state and local health departments, as project collaborators, be addressed in project budgets?
    The federal government can pay salary and benefit costs for employees of state and local health departments, but not those costs for federal employees. State and local governments’ direct and indirect costs can be included in project budgets. Indirect costs should reflect F & A rates that have been negotiated with the federal government.

Questions and answers primarily related to RFA-DA-17-023 (U24 GHOST RFA)

1. Other than the next generation sequencing data files and the transmission network results, is the GHOST site expected to collect or provide any additional data?
   No.
2. Can informatics technology be developed at the GHOST lab?
   The primary purpose of the GHOST laboratory is the sequencing of samples received from the UG3/UH3 sites. The GHOST laboratory is expected to be a full scientific partner in the cooperative agreements, but development of bioinformatics should be clearly linked to the primary objectives of the laboratory and the UG3/UH3 projects.
3. Is the GHOST site allowed to do research other than being a servicing component for the UG3/UH3 sites?
   Although the primary purpose of the GHOST site is to provide HCV sequencing, the GHOST site is expected to be closely integrated with the activities funded under RFA-DA-17-014. The GHOST site is expected to be a participating partner in the collaborative efforts of both RFAs and, as such, will participate in data exchange and analysis, in regularly scheduled conference calls, grantee meetings, and other interactive discussions involving the UG3/UH3 grantees, and in the initiation and development of publications, as appropriate. The GHOST site also will provide representation on the Executive Steering Committee that coordinates all activities for both RFAs. GHOST sites will be welcome to initiate research activities that support the GHOST laboratory mission and that are consistent with the larger objectives of the UG3/UH3 programs, as long as the primary use of resources available under this RFA is to provide HCV sequencing.
4. The GHOST laboratory will upload the NGS sequence files into the GHOST system. Does the GHOST site need to maintain long-term storage of NGS sequence data on-site?  If yes, for how long?
   This RFA falls under NIH Guidelines for data sharing https://sharing.nih.gov/ and the RFA contains a link (under “Additional Review Considerations”) that may provide additional help in formulating a data sharing plan for after completion of the study. Refer also to the “Resource Sharing Plan” text in the RFA under Section IV.2. 2. Content and Form of Application Submission: “Consistent with achieving the goals of the program, finished, de-identified datasets are expected to be made available for the research community at the close of the study through deposit at the National Addiction and HIV Data Archive Program: https://www.icpsr.umich.edu/icpsrweb/content/NAHDAP/about.html  or another site to be determined by the Executive Steering Committee of the cooperative agreement. Steps also are expected that enable sharing of research findings with the broader research and, public health, and health services communities.” The NAHDAP site referenced here is funded by NIDA. As noted elsewhere in this subsection, the Executive Steering Committee for the two RFAs may make changes regarding the specific data repository, but applications should include an initial plan that is consistent with NIH policy. 
5. Is there a minimum or maximum number of specimens required or expected for the GHOST laboratory to process?
   The RFA does not specify a minimum or maximum number of specimens for the GHOST laboratory site to process. This will be dependent on the number of UG3/UH3 sites funded under RFA-DA-17-014 and the specific plans they propose. It is anticipated that startup of the laboratory and related activities (e.g., SOPs, training) will be the initial activities of the GHOST laboratory and that the flow of specimens will increase over time, particularly as the UH3 phase of projects under RFA-DA-17-014 commences. Applicants should consider their local costs for processing specimens, the number of sites anticipated to be funded under RFA-DA-17-014 and the recent epidemiology of HCV in the most affected states to justify their estimated throughput and costs.
6. What kind of qualifications must the staff have to conduct the sequencing for the GHOST laboratory? What are the expectations for the quality and depth of the sequencing?
   Please carefully read the review criteria under Section V.1 (“Application Review Information”) of RFA-DA-17-023. Staff should meet the qualifications listed under the heading for “Investigator(s)” and the quality and depth of the sequencing should meet the qualifications listed under the heading for “Environment”.
7. Will there be a side-by-side comparison of specimens tested at CDC and at the GHOST laboratory?
   Yes, there will be GHOST validation testing at CDC. It is expected that CDC will test at least 10% of the specimens for QA/QC purposes.
8. What are the expectations for the GHOST laboratory applications regarding experience with rural settings?
   Applicants are expected to have experience working with rural sites and to demonstrate an understanding of issues commonly encountered in conducting health-related research in rural communities (e.g., smaller or more intermittent flows of specimens).
9. How do we calculate the cost of shipping specimens for the GHOST laboratories?
   This will be up to each applicant. Items that may help with this calculation include the number of UG3/UH3 sites that are expected to be awarded and an estimate of how many samples each site will collect to achieve significant results.
10. In the Research Strategy section of RFA-DA-17-023, it asks for “a description of the language to be used in informed consent forms to allow testing of de-identified samples by the CDC”.  Will the GHOST laboratory be responsible for obtaining informed consent or contributing to the informed consent documents?
    The GHOST site will receive samples without identifiers but the UG3/UH3 sites should be able to link these to the information they have. The UG3/UH3 sites will need to develop informed consent documents that will allow shipment of de-identified specimens to the GHOST site, if a GHOST site is awarded, or to CDC, if a GHOST site is not awarded. All participating sites will need to have IRB approval for their participation in the research – either for sample collection (UG3/UH3 sites) or to obtain IRB approval or appropriate exemptions, if receiving de-identified specimens/data (GHOST site/CDC). The extent to which a site needs to be involved in the development of informed consent forms will be determined by the institutional IRB.