The majority of grant applications received and funded by NICHD are unsolicited, submitted by extramural investigators working within the mission of the Institute. However, when NICHD program staff identify areas of research that would benefit from stimulation or that demonstrate specific gaps in knowledge that should be highlighted, a Funding Opportunity Announcement (FOA) for a focused grant solicitation may be proposed. We use two types of FOA: the Program Announcement, with no set-aside of funds, and the Request for Applications, with a specific commitment of funds.
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 an FOA with a set-aside of funds, is posted on the Council Member Website.
- Program staff present the concepts during the Open Session and are available to answer questions and lead discussion with Council Members and the public.
- Council members are welcome to indicate their opinion of each concept.
- Comments, suggestions, and Council advice are recorded by NICHD staff.
This approach to concept review:
- Provides a wide spectrum of expertise for the consideration of concepts, including scientific, policy, and advocacy perspectives. The process requires 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 the Institute the benefit of multiple perspectives in the overall planning of an NICHD research agenda.
- Meets the NIH requirement for public presentation of concepts and the opportunity for public comment.
For this meeting, one concept was reviewed.
Concept Clearance by Council
Molecular Mechanisms of the Metabolic Effect of Drugs Used in Children
A Request for Applications (RFA) is proposed entitled “Molecular Mechanisms of the Metabolic Effect of Drugs Used in Children”. The proposed RFA will use the NIH Research Project (R01) grant award mechanism.
The proposed RFA will solicit innovative, multidisciplinary investigator-initiated research to identify and elucidate the molecular mechanisms of the adverse metabolic effects of diverse drug classes used in children and adolescents.
The scope of the proposed RFA will encompass research on the processes for the unexpected and unintended metabolic adverse side effects to many drug classes that children are now taking for a variety of diseases. These adverse events can have a profound impact on growth and development in childhood and extending into adulthood. Examples of high priority branch areas include:
- Stimulating research that will identify disruptions or alterations in the metabolic and/or signaling pathways that are responsible for the metabolic toxicities that are seen with the multiple drug types, including atypical antipsychotics, antiretrovirals, seizure medications, etc..
- Providing elucidation into the role of oxidative stress, mitochondria, and apoptosis in the development of metabolic toxicities.
- Advancing scientific knowledge into the role and characterization of developmental variations in metabolic adverse effects, identifying periods of increased vulnerability to drug toxicity, such as puberty, in drug metabolizing enzymes, transporters, receptors, membrane potential.
- Foster research that will elucidate the role of epigenetic factors, such as nutrition and micronutrients, in development of the final phenotype of a person who is at risk for metabolic derangements.
- Expanding the use of genomics, metabolomics and proteomics technology to identify and characterize novel mechanisms for drug related toxicity in children
Multiple drug classes across multiple therapeutic areas have been linked to metabolic adverse events. What is lacking is an understanding of the mechanism(s) behind why these adverse effects occur, who is at risk, and how to block and/or reverse these effects early on in treatment. The ultimate goal of this RFA is to promote revolutionary discoveries of translating basic knowledge in to the development of new, innovative, and efficacious strategies and targets for the molecular diagnosis, treatment and prevention of metabolic adverse effects of drugs used in children and adolescents.
Perdita Taylor-Zapata, M.D.
Obstetric and Pediatric Pharmacology Branch
Center for Research for Mothers and Children