Concept Review by Council

Concepts for proposed Requests for Applications (RFA) are reviewed during the Open Session of Council. These are the features of the process:

• A brief concept description, written by the program staff proposing a grant solicitation, is posted on the Council website.
  
  
• Dr. Alexander will present the concepts during the Open Session. Program staff will be available to answer questions if called upon but, in general, will not participate in the presentation.
  
  
• Following brief presentation and discussion, Council members will be asked to indicate their opinion of each concept.
  
  
• Comments, suggestions, and Council advice will be recorded by NICHD staff.

This approach to concept review:

• Meets the NIH requirement for public presentation of concepts and the opportunity for public comment.
  
  
• Provides a wide spectrum of expertise for the consideration of concepts, including scientific, policy, and advocacy perspectives. The process should encourage the presentation and evaluation of broad concepts, without detailed or in-depth discussion of the specific science. Such discussion, typical when concepts are reviewed by a group with more narrowly focused expertise, goes well beyond the purpose of this review. Indeed, it places those involved in a potential conflict of interest situation that would prevent them from responding to a resultant RFA should they choose to do so.
  
  
• Enables the full Council to consider individual initiatives within the broader context of many planned initiatives, giving us the benefit of multiple perspectives in the overall planning of an NICHD research agenda.
  

For this meeting, three concepts were reviewed:

Pharmacokinetic Research and Optimization of Treatment in Pediatric HIV/TB Co-infection
Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN)

Pharmacokinetic Research and Optimization of Treatment in Pediatric HIV/TB Co-infection

May 2009

A Request for Applications entitled “Pharmacokinetic Research and Optimization of Treatment in Pediatric HIV/TB Co-infection”. The proposed RFA will solicit research project grant (R01) and exploratory/developmental research grant award (R21) applications, with co-funding from NIMH.

Purpose
The purpose of the proposed RFA is to stimulate research to evaluate the pharmacokinetics of anti-TB drugs and pharmacokinetic drug interactions of clinical significance between anti-TB drugs and anti-HIV medications in children with HIV/TB co-infection. The proposed RFA will also solicit research examining the relationship between pharmacokinetics and treatment outcomes.

Scope
The proposed project will support investigator-initiated grants to increase knowledge of how to optimize the treatment of TB/HIV in children. Specific examples of research may include: pharmacokinetic studies of new or existing anti-TB drugs in children with HIV; evaluation of CNS penetration of anti-TB agents, including the effects of co-administration of antiretroviral therapy and the effect of TB meningitis and/or CNS HIV-infection on blood-brain barrier permeability for anti-TB agents; pharmacokinetic studies to define interactions of anti-TB drugs with antiretroviral drugs to define appropriate dosing in children; and pharmacokinetic studies of second-line anti-TB drugs in HIV-infected children with suspected or proven multi-drug or extensively drug resistant TB.

Objective
Pediatric HIV and TB co-infection is a significant problem in resource-poor populations in international settings which has for the most part remained unaddressed. This initiative is part of a research agenda that will help to reduce health disparities among children by generating a body of data upon which future clinical trials of HIV/TB co-infection may be based.

Program Contact:
Carol J. Worrell, M.D.
Pediatric, Adolescent, and Maternal AIDS Branch
Center for Research for Mothers and Children

Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN)

May 2009

A Request for Applications entitled “Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN)” as a competing renewal using the U01 mechanism is proposed. Current collaborating co-funding ICs are NIDA and NIMH and are both expected to continue. Ongoing discussions with NIAID indicate interest to co-fund and collaborate.

Purpose
The proposed RFA is a competing renewal, using the U01 mechanism, to provide support for continuing a multi-center basic science and clinical research network with 15 clinical sites across the US and Puerto Rico whose scientific mission is to conduct independent and collaborative research that evaluates interventions for treatment and management of HIV infection and its complications among youth, as well as the prevention of HIV transmission and that explores promising behavioral, microbicidal, prophylactic, therapeutic, and vaccine modalities in HIV-infected and HIV at-risk adolescents, ages 12 through 24 years. The recently developed collaboration between NICHD, ATN and CDC to improve the identification, linkage and engagement to care of such minority youth with undiagnosed HIV infection will significantly expand ATN’s mission and is a major priority area identified by the White House and the Office of AIDS Research (OAR). This mechanism operated extremely well during the first and second funding cycles and recompetition under the same mechanism affords the optimally efficient means of continuation.

Scope
This initiative calls for the continuation and further expansion of a broad array of interventional studies aimed at the primary, secondary and tertiary prevention of HIV infection and its consequences. Primary prevention studies will focus on efforts to interrupt HIV transmission in uninfected populations by further cultivating and expanding the primary prevention infrastructure established in the previous project period to be able to support clinical trials evaluating HIV preventive biomedical modalities such as vaccines, microbicides, PrEP and others as part of its menu of prevention strategies. Secondary prevention studies will continue to evaluate behavioral, nutritional and therapeutic interventions to preserve health in HIV-infected young people. Tertiary prevention studies will continue examining strategies to restore full or improve function among HIV-infected youth.

Progress thus far shows over 13,000 enrollments in 6 years (2003-2009) among 45 ATN studies reflected by overall accrual and retention rates among completed studies of 90%. Among only 18 studies with completed analyses, there have been 32 manuscripts published with 19 more in review and 34 abstracts published with 7 more in review. The ATN has successfully forged collaborations with the CDC, ACTG, HVTN, IMPAACT and MTN evidenced by 6 co-endorsed protocols.

Objective
The objective of this Request for Applications (RFA) is to continue the infrastructure required for a network of 15 clinical sites, one data and operations center and one scientific leadership group with discipline-specific subgroups to expand research capacity and be able to increase enrollment of a much needed and underrepresented ethnic minority population. The ATN, as the sole domestic network focused on youth, will continue to design, develop and conduct multiple clinical trials as well as pertinent formative and translational research studies and will maintain accrual of the required numbers of subjects into rigorously designed common protocols to address pressing research questions in this population with such critical need more expeditiously than individual centers acting alone.

Program Contact:
Bill G. Kapogiannis, MD, FAAP
Pediatric, Adolescent and Maternal AIDS Branch
Center for Research for Mothers and Children