Notice Number: NOT-HG-16-001

Key Dates
Release Date: November 10, 2015
Response Date: December 7, 2015

Issued by
National Human Genome Research Institute (NHGRI)

Purpose

The purpose of this Request for Information (RFI) is to solicit input regarding future opportunities in clinical sequencing.

Background

The evidence base for the use of genomic sequence to diagnose and treat patients in a clinical setting has evolved rapidly over the past several years. Since 2011, NHGRI, in collaboration with NCI, has funded the Clinical Sequencing Exploratory Research (CSER) Program to assess which clinical contexts would be best served using a genomic sequencing approach, how approaches to analysis and interpretation should be standardized, and what bottlenecks exist in developing the infrastructure needed for clinical sequencing. A broad examination of ethical and psychosocial implications of generating, interpreting and returning genomic sequencing results to physicians and patients in a clinical setting was also incorporated. CSER has enrolled nearly 5000 patients to date, and sites have individually and collaboratively disseminated scientific advances related to the integration of genomic sequencing into clinical care in areas including, but not limited to: informed consent, sequencing standards, tumor sequencing, variant interpretation, genetic counseling, return of results, display of genomic data in the electronic health record, and pediatric research (see https://cser-consortium.org/publications for examples).

On September 28, 2015, NHGRI convened a workshop to summarize and evaluate the contributions of the CSER Program and discuss scientific questions and opportunities that can substantively be addressed by a future program in clinical sequencing (agenda and archived talks available at http://www.genome.gov/27562330). The opportunities identified by workshop participants were broad and often described in the context of a complex healthcare system that includes patients, health practitioners, payers, professional societies, policymakers, regulatory agencies, and other stakeholders. As a follow-up to that workshop, and in line with NHGRI’s strategic plan that includes improving the effectiveness of healthcare (http://www.genome.gov/Pages/About/Planning/2011NHGRIStrategicPlan.pdf), NHGRI seeks input in selected areas in order to assess priorities for a potential future clinical sequencing program that broadly incorporates patient/family, practitioner, laboratory, and societal perspectives.

Information Requested

The NIH seeks input from researchers, academic institutions, professional societies, patient advocacy groups, health practitioners, payers, policymakers and other stakeholders on strategies for maximizing impact of a potential future clinical sequencing research program. We invite comments on any or all of the following areas:

1. Ideas for engaging payers, patients, professional societies, regulatory agencies and policymakers to work with researchers on optimizing design of future studies, so that outcomes of value to these groups can be measured as part of a potential future clinical sequencing program and used for decision-making by payers and policymakers. Examples of outcomes, scientific questions, or regulatory issues of interest to these stakeholders, approaches to coming to consensus on these outcomes or scientific questions, or ongoing collaborations with researchers, are encouraged.

2. Strategies that leverage existing infrastructure for data sharing, e.g., resources such as dbGaP (http://www.ncbi.nlm.nih.gov/gap) or ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/), in combination with additional data resources to facilitate the development of a shared evidence base for clinical decision-making. Additional data resources might include, but are not limited to: types of outcomes, such as health utilization data; descriptions of resources, such as case-level resources tailored to clinical data; or heterogeneous data sources, such as laboratory and pharmacy data. Strategies for individual sites to develop their own model(s), as well as those for which sites can work together to develop common models for sharing, are encouraged.

3. Areas broadly related to the integration of genomic sequencing into clinical care in which special emphasis on either an investigator-initiated approach or a consortium-based approach is needed. For the purposes of this RFI, investigator-initiated research should be regarded as research in which the aims are determined by the investigator and carried out independently. Consortium-based research should be regarded as research in which the aims are best accomplished collaboratively among multiple sites, potentially trying diverse approaches and identifying the pros and cons of each, where collective output is more than the sum of its parts. Responses can include a justification for why the proposed area falls under investigator-initiated or consortium-based research and would not likely be adequately addressed without the need for a targeted funding announcement.

4. Other issues relevant to NHGRI’s desire to maximize the impact of a potential future program in clinical sequencing.

How to Submit a Response

Responses will be accepted through 5 PM EST on December 7, 2015.

Responses must be submitted via email to [email protected].

This RFI is for planning purposes only and should not be construed as a solicitation for applications or as an obligation on the part of the Government to provide support for any ideas identified in response to it. Please note that the United States Government will not pay for the preparation of any information submitted or for its use of that information.

The NIH will use the information submitted in response to this RFI at its discretion and will not provide comments to any responder's submission. Responses to the RFI may be reflected in future funding opportunity announcements and will be used in long-term planning for NHGRI’s clinical sequencing portfolio. Responses will be compiled and shared internally and with working groups convened by the NIH, as appropriate. In all cases where responses are shared, unless the respondent indicates otherwise, the names of the respondents will be withheld. Respondents are encouraged to designate their professional role (e.g., academic researcher, payer, etc.) in their response.

Inquiries

Please direct all inquiries to:

Lucia A. Hindorff, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 240-271-1509
Email: [email protected]