Towards Maximizing the Scientific Return on the Women's Health Initiative Biological Resource

BACKGROUND The Women's Health Initiative (WHI) has unique features that make it extraordinarily valuable for laboratory studies aimed at enhancing understanding of the role of genetic and blood markers in disease etiology. It is very large (enrolling 161 thousand women), it is diverse, it comprises the largest cohort of older women (~30,000 are now over age 80), it has a long follow-up (up to 19 years), serially collected and stored bloods, extensive phenotyping, carefully adjudicated data on large numbers of clinical outcomes, and it includes three clinical trial exposures. The latter feature leverages opportunities to study mechanisms of treatment effects on disease outcomes, both short-term and long-term. The WHI program has set aside bloods (serum and plasma) and DNA samples for the purpose of this acquisition. Archived bloods are available at baseline, and either 1 year for clinical trials participants or 3 years observational study participants. In addition, follow-up bloods and clinical examination data will be obtained from 8000 participants aged 78+ in 2012, which provides an important opportunity to study questions related to aging including absence or presence of cardiovascular disease and/or risk factors, maintaining good physical and cognitive function, and the predictors of change in biomarkers, DNA methylation and RNA expression, telomere length and the interrelationships of markers in their association with health status. It is anticipated the laboratory assays may include newer high-throughput technologies such as those from genomics, proteomics, and metabolomics. ACQUISITION PLAN This acquisition will employ a Broad Agency Announcement (BAA) to seek proposals that will maximize the scientific yield from the biologic resource and associated participant exposure and outcome data in the Women's Health Initiative (WHI), by soliciting the best ideas for laboratory-based research studies to apply to the WHI biologic resource. This BAA is the third of a series. Altogether 22 contracts were awarded in 2007 and in 2009. This BAA will differ from the previous ones in several respects: it will focus on study questions relevant to the NHLBI mission and in particular factors leading to an increased risk of CVD in older women (and conversely factors leading to healthy aging with absence of CVD); it will encourage the application of multiple technologies (using biospecimens) in an integrated fashion; and it will explicitly require involvement of early stage investigators. The BAA mechanism encourages wide access to the bio-specimens, while still allowing for coordination of specimen use, achieving programmatic balance, and wide data sharing. This mechanism is in addition to the regular ancillary study mechanisms mostly funded through ROIs where access to the resource is governed by study investigators. Study investigators welcome wide collaboration and details of procedures for establishing collaborations can be found at www.whiscience.org. EVALUATION PLAN Awards will be made based on the weighted evaluation factors of technical merit, programmatic balance, and funds availability. It is anticipated that the individual award amounts will vary depending on the scope and capacity of the technical objectives for the award. Two to four awards are anticipated, in the range of approximately $1.5 to $3.5 million each in early calendar year 2013. Costs are anticipated to be somewhat lower during the first year which includes planning, finalizing sample selection, receiving samples, and preliminary laboratory analyses. Higher costs are likely to be incurred during the second year when samples are run at full capacity. During the third year costs are likely to be somewhat lower as laboratory data are finalized and statistical analyses and manuscript preparation are done. At the sole discretion of the NHLBI, meritorious proposals that cannot be funded within the amount currently available under this BAA may be forwarded to other Institutes and/or Centers under the National Institutes of Health (NIH), for their consideration.