GWAS Request for Proposal Review Information
Request for proposals for genome-wide investigation of late-effects using the Childhood Cancer Survivor Study (CCSS) cohort
The Childhood Cancer Survivor Study (CCSS) is an NCI-funded resource for the study of long-term survivors of cancer diagnosed during childhood and adolescence. Details regarding the cohort are available on the CCSS website. Members of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute and CCSS investigators collaborated to conduct a genome-wide association study, initially intended to study the role of genetic susceptibility in the development of subsequent neoplasms using samples from the CCSS Biorepository. Genotyping was conducted for 5739 childhood cancer survivors diagnosed 1970-1986 (5324 are of European ancestry) using the Illumina HumanOmni5Exome microarray, with over 4.1 million loci passing quality control thresholds (based on locus and sample missing rates, sample heterozygosity, and sex discrepancies).
The CCSS leadership is now broadening the scope of this initiative to study the role of genetic susceptibility in the development of non-malignant treatment-related outcomes (in addition to subsequent malignancies) in cancer survivors. Accordingly, CCSS is announcing a request for proposals to collaborate with CCSS and NCI investigators in the use of existing genome-wide association study (GWAS) data and corresponding outcomes-related data to address innovative research questions relating to potential genetic contributions to risk for treatment-related outcomes. Requests will be accepted on an ongoing basis. Requests will be reviewed three times per year, in February, June and October (cut-offs for receipt of applications will be February 1st, June 1st, and October 1st).
All GWAS data will be posted on dbGap along with limited demographic and cancer-related covariates linked to genotypes. Instructions for access to data in dbGaP can be found on the NCBI website. CCSS ID and outcome-related phenotypes will not be posted and thus researchers desiring additional covariates or linkage of genotypes to other phenotypes must submit a full application. All projects requiring use of covariates, beyond those posted on dbGaP, will be viewed as a collaboration with one or more investigators from the CCSS and NCI being part of the research team. The CCSS Data and Statistics Center will provide investigators of approved projects with selected phenotype data and variables required for linking with the genotype data on dbGaP. Data analyses may be performed by qualified individuals proposing the research, by CCSS biostatisticians, or both; however, all analyses and results must be vetted by CCSS biostatisticians prior to submission for publication.
By signing the Data Use Certification, investigators proposing to use CCSS GWAS data certify that they will comply with the following: i) Limiting use of data to the project described in Application for Data Access; ii) Not distributing data beyond those directly engaged in the analysis outlined in the Application for Data Access; iii) Not attempting to identify or contact study participants from whom phenotype/genotype data were collected; iv) Adhering to policies on timeframe for publications stemming from data (described below); and v) Providing annual detailed reports (described below). Any violation of these policies can result in withdrawal of the project with return of CCSS data.
Any researcher, or group of researchers, qualified to conduct genetic research can submit an application to request use of CCSS data in conjunction with the genotype data posted on dbGaP. There are no restrictions relative to country, institution, or prior involvement in CCSS.
Prior to preparation and submission of an application, it is recommended that investigators communicate with Dr. Smita Bhatia (chair of the CCSS Genetics Working Group, firstname.lastname@example.org) to discuss the proposed research with respect to feasibility and potential overlap.
The principal investigator proposing to use GWAS data must submit an Application for Data Access to Dr. Greg Armstrong (CCSS principal investigator, Greg.Armstrong@stjude.org). On the proposal page, you will be required to submit:
- Application for Data Access (Maximum of five pages for specific aims, background/significance, requested data elements, approach, statistical considerations and timeline. Cited literature cannot exceed 1 additional page)
- Specific Aims
- Background and significance of the research question
- Requested data elements
- Approach (methodology, technical plans for validation, functional studies)
- Statistical considerations
- Cited literature
- Investigative team and qualifications
- NIH Biosketch for each investigator
- Available resources/funding plans
- Data Use Certification
- Completed Data Use Certification form (see below)
- Completed material transfer agreement
- Applications will undergo a two-stage review process. The initial review will be conducted by the CCSS Genetics Working Group Data Access Committee (see below). Those applications approved by the Genetics Working Group Data Access Committee will be submitted to the CCSS Research and Publications Committee for review and comment.
- Review criteria for scientific merit and priority will be based upon:
- Significance/impact of the research question
- Approach (methodological, technical and statistical)
- Overlap with previous or current CCSS research
- Qualifications of the investigative team
- Concordance with CCSS priorities
- Compliance with CCSS policies
- Funding/available resources
- Timeline for manuscript submission
- Reviewed applications will be categorized as: (1) approved, (2) approved with stipulations, (3) not approved, but a revised application will be reconsidered, and (4) disapproved, no future consideration.
Post Approval Process
- Once a proposal has been approved, the principal investigator and his/her research team will work together with CCSS collaborators assigned to the project to facilitate construction of the analytic data set, establish a task-specific timeline, and agree upon both authorship and a tentative list of target journals.
- A written progress report will be required annually (due on the anniversary of the project’s approval date) until the project has been completed (i.e. publication). The CCSS will monitor the progress of the study closely with the primary goal of facilitation of the various components of the study to ensure smooth and timely execution. The CCSS reserves the right to withdraw approval for any project that fails to demonstrate adequate progress
- Review and approval of results by the CCSS Genetics Working Group Chair, CCSS Principal Investigator and the assigned CCSS biostatistician is required prior to any presentation or publication of the data from the project.
Genetics Working Group Data Access Committee
- Smita Bhatia (chair)
- Greg Armstrong
- Les Robison
- Yutaka Yasui
- Lindsay Morton
- Joshua Sampson
- Wendy Leisenring
- Stephen Chanock (ad hoc)
- Peggy Tucker (ad hoc)
- Working Group Chairs (ad hoc)
- NCI DCEG investigators (ad hoc)