RE: NEW MODELS FOR LARGE PROSPECTIVE STUDIES: IS THERE A BETTER WAY?

American Journal of Epidemiology © The Author 2013. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Vol. 177, No. 4 Letters to the Editor RE: NEW MODELS FOR LARGE PROSPECTIVE STUDIES: IS THERE A BETTER WAY? Manolio et al. (1) proposed a “better way” for large pro- spective cohort studies based on the UK Biobank protocol, which used a novel centralized model rather than a tradi- tional distributed model to recruit a population cohort of 500,000 participants. Cost was the stated motivation for identifying a better way despite possible selection biases. Adopting the alterna- tive implied “…large anticipated costs [that] present a sub- stantial hurdle” (1, p. 859) for mounting a large cohort study in the United States. The stated contrast was dramat- ic: The $100 million for the UK Biobank “…stands in stark contrast to the roughly $400 million per year for 10 years estimated for traditional models of conducting a large cohort study in the United States” (1, p. 864). The implied absolute cost difference ($4 billion vs. $100 million) and 40:1 ratio seemed high to us. We accessed the citation for the distributed model, a 2005 report of an expert panel commissioned by the National Human Genome Research Institute (2), but we did not ﬁnd a cost estimate there. Thus, the basis of the cost estimate of $4 billion is not clear, but we assume it was provided in another report. This estimate was for an acquisition phase of longer dura- tion (10 years) than that in the UK Biobank (3 years), perhaps because the expert panel described a 10-year acqui- sition. However, an equivalent 3-year acquisition is feasible and would provide a fairer comparison. Adjusting for the difference in duration would reduce the cost ratio from 40:1 to 12:1. In addition, the per-year cost of the distributed model ($400 million) does not match our empirical cost estimate based on the National Children’s Study (NCS) Vanguard Study that used a distributed model and household-based recruitment that was very similar to the plan proposed by the expert panel. We estimate that the work required to enroll a population cohort of 500,000 persons would be much less than that for the proposed survey of about 1 million households to enroll women of childbearing age for prospective recruitment of a birth cohort of 100,000 women, and the cost per year would be substantially less than $200 million per year projected for this phase of the NCS. The actual cost ratio might be less than 4:1. Furthermore, in a joint National Human Genome Research Institute/NCS report in 2005, investigators evalu- ated the feasibility of acquiring a birth cohort of 100,000 people and a population cohort of 500,000 people at the same time, which would leverage the infrastructure of the NCS and make acquisition of the population cohort very cost- efﬁcient. We estimate that the marginal cost would be $130 per visit for each individual in the population cohort, so for a cohort of 500,000 people with 2 visits (to match the visits in the initial UK Biobank protocol), the estimated cost for this opportune distributed model would be $130 million, and sharing additional infrastructure (e.g., informed consent, biorepository, information management, etc.) would be possible. This could generate a representa- tive population sample for a cost not much more than that for the convenience sample from the “better way” de- scribed by Manolio et al. (1). However, this extraordinary opportunity may not be possible because of dramatic changes in the NCS (3, 4), which included dismantling the local data collection infrastructure of Vanguard Centers to test the “better way” of making the distributed local study centers temporary and transferring activities to a central coordinating center. We propose that by leveraging rather than dismantling the infrastructure of the NCS, a representative probability- based sample of 500,000 people could be acquired at a cost not much greater than that for the convenience sample of the UK Biobank. This might be an even better way to implement a large population cohort study in the United States. A CKNOWLEDGMENTS The authors were principal investigators on the following con- tracts from the Eunice Kennedy Shriver National Institute of Child Health and Human Development for the National Children's Study: HHSN275200503415C, HHSN267200700021C, HHSN 275200800019C, HHSN275201100007C, and HHSN2752012 00013C. However, no funding from these contracts was used for the preparation of this letter. Conﬂict of interest: none declared. R EFERENCES 1. Manolio TA, Weis BK, Cowie CC, et al. New models for large prospective studies: is there a better way? Am J Epidemiol. 2. Design Considerations for a Potential United States Population-based Cohort to Determine the Relationships Among Genes, Environment, and Health: Recommendations of an Expert Panel. Bethesda, MD: National Human Genome Research Institute; 2005. (http://www.genome.gov/Pages/ About/OD/ReportsPublications/PotentialUSCohort.pdf ) (Accessed April 7, 2012). 3. Kaiser J. Overhaul of U.S. child study concerns investigators. Science. 2012;335(6072):1032. 4. Wadman M. Growing pains for the children’s study. Nature. James Swanson 1 and Dean Baker 1,2 (e-mail: jmswanso@ uci.edu) Am J Epidemiol. 2013;177(4):371–374