Freedom of Information Act Office
IC Directors' Meeting Highlights
April 28, 2006
| To: | IC Directors |
| From: | Director, Executive Secretariat |
| Subject: | IC Directors Meeting Highlights—March 9, 2006 |
Discussion Items
I. Update on the Genetic Association Information Network (GAIN) and the Genes and Environment Initiative (GEI)
Dr. Collins provided an overview of the newly implemented GAIN and GEI project. He compared the whole genome association 2002 view to the 2006 approach to common disease that now includes:
- Identifying an optimum set of 300,000 tag SNPs
- Collecting 1000 cases and 1000 controls
- Genotyping all DNAs for all SNPs
This adds up to 600 million genotypes plus the cost of a genotype has dropped to $0.005, which is ~$3 million for each disease (a profound drop in cost).
GAIN is a public-private partnership between NIH, the FNIH, and the private sector (Pfizer, Affymetrix, Abbot, and potentially other future partners) and was announced on February 8, 2006. Its goal is to support the laboratory costs of whole genome association studies of common disease. There are now sufficient funds to support genotyping for 6-7 common disease projects partly through funding and partly through facilities. The guiding principle of GAIN is that the greatest public benefit will be achieved if results of whole genome association studies are made immediately available. GAIN is overseen by a Steering Committee and Executive Committee with extensive support by NIH and FNIH staff. The FNIH Board of Directors has final say in policy decisions.
Several GAIN policies have been established by the Steering Committee, including the following:
- A central data repository for phenotypes and genotypes has been established at NCBI
- All GAIN data is to be coded before submission to NCBI, removing personal identifiers
- OHRP has ruled that, provided the data is coded, NCBI and the GAIN database users are not conducting human subjects research
- IRB oversight thus occurs solely at the level of the submitting investigator (speeding up access)
- Once genotyping has been quality checked, all genotype and phenotype data is made immediately available to all qualified users (no party gets an early peek)
- A Data Access Committee reviews user requests
- A Data Protection and Participant Monitoring Board (DPPMB) monitors use of the GAIN database over time
- An analysis group of the PIs of the selected studies will be formed
- During a nine-month period after the genotype and phenotype data become available in the NCBI database, only the project PI is permitted to submit a publication on the data analysis, however all other uses of the data are permitted during this time
- As part of their certification agreement, users must acknowledge that the GAIN Steering Committee wishes to keep the GAIN data in the public domain.
- To discourage premature IP claims, NCBI will post pre-computed associations, so these become prior art
The GEI is proposed as part of the FY07 President’s budget and its aim is to accelerate the understanding of genetic and environmental contributions to health and disease. This includes whole genome association genotyping of case-control studies of common diseases and development of innovative technologies to measure environmental exposures, diet, and physical activity.
Dr. Collins concluded his presentation by discussing the potential need for harmonization of policies for whole genome association studies across NIH. This would not only show that the NIH has its house in order, but it would be less confusing to the community.
Dr. Zerhouni summed up the discussion by recommending that he would like to appoint a high level ad hoc committee, chaired by an IC Director and possibly a co-chair from the OD, and asks that this group develop a recommendation regarding harmonization to bring before the NIH Steering Committee. Given the deadline for GAIN applications of May 9, it will be important for this committee to act quickly.
II. NIH Governance Model Evaluation
The evaluation team for the NIH Steering Committee consisted of Dr. Tom Insel, Dr. Story Landis, Dr. Betsy Nabel, and Dr. Allen Spiegel. Their charge was to assess this governance model’s success in identifying and providing timely recommendations on significant trans-NIH policy issues and communicating results to the IC Directors not on the Steering Committee; make course-correction recommendations; and consult with all IC Directors and Working Group co-chairs.
The evaluation team met with the IC Directors, Working Group co-chairs, Dr. Kington, and Dr. Zerhouni to review issues pertaining to the governance model. Drs. Insel, Landis, and Nabel then discussed the subsequent findings and conclusions including:
- The SC brought discipline and efficiency to decision-making
- The SC is not considered transparent to those who are not participants
- The role change has fostered a sense of disenfranchisement for some
- The WGs are experiencing growing pains
- Succession planning is critical since rotating Steering Committee members co-chair the Working Groups
The team concluded with the following recommendations:
- Make no structural changes to the governance model but undertake fine-tuning to address issues identified
- Greater participation is needed
— Present items decided at SC to IC Directors for in-depth information
— Identify issues of “significance” for decision and elaboration at IC Directors meeting
— Regular retreats and/or IC Directors meetings to discuss policy issues - Working Groups develop “Environmental Impact Statements” to identify groups that should be consulted by WGs in development of policy; provide that info to Steering Committee when issue presented
- Working Group co-chairs meet with representatives of their counterpart committees to review Charter and revise as necessary to distinguish their respective roles
- Establish an Agenda Setting Committee (ASC) to identify corporate issues to be addressed
- Improve communication by establishing an intranet
- Provide succession planning
- Provide continuous improvement by undertaking a yearly assessment, assessing impact of proposed recommendations, and assessing success of the WGs in addressing the corporate issues identified by the AGC.
Dr. Zerhouni thanked all for their candor and reminded all that the governance model does not govern everything. He recommended that the ASC include a broad representation of the NIH community, possibly including IC Directors not on the SC but certainly not limited to IC Directors. He concluded by stating that he looks forward to the presentation of the Steering Committee implementation plan at a future IC Directors meeting.
Scientific Presentation
III. Advances in Biomedical Imaging and Progress Toward the 3Ps
Dr. Pettigrew began his presentation by sharing the ranking of the top 30 medical advances—MRI and CT are at the top of the list. He then outlined his intent to address the progress of imaging as it relates to two recent trans-NIH thematic goals:
- Translation of basic science advances into practical results for patients, and
- The new medical era where the goal is predictive, pre-emptive, and personalized information.
To define imaging, he shared the perspective from Dr. Zerhouni that, “[i]maging is the science of extracting spatially and temporally resolved information at all physical scales.”
Dr. Pettigrew discussed examples of technical progress and benefits provided by the advances in spatial resolution and time/temporal resolution over the last five years. During this time, spatial resolution has improved by a factor of 4 and temporal resolution has improved by a factor of 10 or more for MRI. These improvements are due to scientific advances such as stronger magnets, efficient data acquisition schemes using multi-channels systems, simultaneous or raw data (parallel K space) signal acquisition methods, and clever mathematically based approaches to take advantage of the temporal symmetry of the raw MRI data signals. He visually demonstrated many of these advances by comparing different techniques that have been developed and even comparing the earliest images from the 2003 Nobel Prize in Medicine winners with images obtained with these latest advances. He went on to display the practical utility of these advances in MR antiography (much less time for complete studies, now done in seconds vs. minutes) with the following examples:
- Bioimaging in identifying foci of neocortical epilepsy (60% more surgical lesions can be identified vs. 5 yrs ago)
- Identification of potential biomarkers of Alzheimer’s disease previously not seen by medical imaging
- Tracking of treatment with pharmaceuticals including anti-angiogenesis agents by using a quantitative index of MRI contrast agent transport
- Image-guided interventions in brain surgery including delineation of nerve fiber tracks (major neurological deficits have been eliminated in epilepsy surgery)
- Interactive image guidance in cardiac interventions (real-time abnormal electrical activity site identification and 3D picture guidance used for elimination of atrial fibrillation).
He also explained and illustrated that some of the more exciting advances are at the cellular level, including new approaches to detect organ rejection by tracking iron label monocytes, auto fluorescence optical imaging to detect cancer at the very early cellular stage, and neutrophil tracking in early arthritis where the genetic basis can be studied with cells from various knockout mice labeled with different frequency optical probes. He concluded by discussing three advances at the molecular level. First, he demonstrated the progress towards a more rational drug design via identification of protein structure of trans-membrane protein receptors such as GPCR using MR spectroscopic imaging. Second, he discussed the potential of an “optical biopsy” for gene expression by imaging. He used as an example a gene-based fluorescent labeled drug such as Herceptin that could be used to identify patients who have high levels of HER2 gene expression and are thus candidates for treatment with this drug. Third, he explained the use of direct imaging of angiogenesis with targeted MR sensitive nanoparticles to monitor anti-angiogenic therapy.
Dr. Pettigrew summarized his presentation with the following points:
- Imaging science has dramatically improved technical and clinical imaging performance over the last five years
- There are measurable benefits in the clinic in multiple areas
- Emerging areas at the cellular and molecular levels include:
— Risk Assessment based on imaged markers
— Ability to identify therapy targets
— Ability to monitor specific treatments and personalize therapy based on this information
Ann Brewer
cc: OD Senior Staff
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