{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T10:51:39Z","timestamp":1740135099692,"version":"3.37.3"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T00:00:00Z","timestamp":1658707200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T00:00:00Z","timestamp":1658707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U54AG062334","U54AG062334","U54AG062334"],"award-info":[{"award-number":["U54AG062334","U54AG062334","U54AG062334"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U01HL146241","U01HL146241"],"award-info":[{"award-number":["U01HL146241","U01HL146241"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P30AI050409","P30AI050409","P30AI050409","P30AI050409"],"award-info":[{"award-number":["P30AI050409","P30AI050409","P30AI050409","P30AI050409"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR002378"],"award-info":[{"award-number":["UL1TR002378"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR070091"],"award-info":[{"award-number":["R01AR070091"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Res Methodol"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Collecting new data from cross-sectional\/survey and cohort observational study designs can be expensive and time-consuming. Nested (hierarchically cocooned within an existing parent study) and\/or Multipart (\u2265\u20092 integrally interlinked projects) study designs can expand the scope of a prospective observational research program beyond what might otherwise be possible with available funding and personnel. The Brain, Bone, Heart (BBH) study provides an exemplary case to describe the real-world advantages, challenges, considerations, and insights from these complex designs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Main<\/jats:title>\n                <jats:p>BBH is a Nested, Multipart study conducted by the Specialized Center for Research Excellence (SCORE) on Sex Differences at Emory University. BBH is designed to examine whether estrogen insufficiency-induced inflammation compounds HIV-induced inflammation, leading to end-organ damage and aging-related co-morbidities affecting the neuro-hypothalamic\u2013pituitary\u2013adrenal axis (brain), musculoskeletal (bone), and cardiovascular (heart) organ systems. Using BBH as a real-world case study, we describe the advantages and challenges of Nested and Multipart prospective cohort study design in practice. While excessive dependence on its parent study can pose challenges in a Nested study, there are significant advantages to the study design as well. These include the ability to leverage a parent study\u2019s resources and personnel; more comprehensive data collection and data sharing options; a broadened community of researchers for collaboration; dedicated longitudinal research participants; and, access to historical data. Multipart, interlinked studies that share a common cohort of participants and pool of resources have the advantage of dedicated key personnel and the challenge of increased organizational complexity. Important considerations for each study design include the stability and administration of the parent study (Nested) and the cohesiveness of linkage elements and staff organizational capacity (Multipart).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Using the experience of BBH as an example, Nested and\/or Multipart study designs have both distinct advantages and potential vulnerabilities that warrant consideration and require strong biostatistics and data management leadership to optimize programmatic success and impact.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12874-022-01675-w","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T12:03:59Z","timestamp":1658750639000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nested and multipart prospective observational studies, flaming fiasco or efficiently economical?: The Brain, Bone, Heart case study"],"prefix":"10.1186","volume":"22","author":[{"given":"C. Christina","family":"Mehta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly S.","family":"Hagen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren F.","family":"Collins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renee\u2019 H.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ighovwerha","family":"Ofotokun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,7,25]]},"reference":[{"key":"1675_CR1","unstructured":"Mehta CC, Hagen KS, Rubtsova AA, Lahiri CD, Michopoulos V, Moran CA, et al. Bone, Brain, Heart Study Protocol: A Resilient Nested, Tripartite Prospective Cohort Study of the Role of Estrogen Depletion on HIV Pathology. Under revision PLOS ONE.\u00a0in print."},{"issue":"2","key":"1675_CR2","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1093\/ije\/dyy021","volume":"47","author":"AA Adimora","year":"2018","unstructured":"Adimora AA, Ramirez C, Benning L, Greenblatt RM, Kempf MC, Tien PC, et al. Cohort Profile: The Women\u2019s Interagency HIV Study (WIHS). Int J Epidemiol. 2018;47(2):393\u20134.","journal-title":"Int J Epidemiol"},{"issue":"2","key":"1675_CR3","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1097\/00001648-199803000-00004","volume":"9","author":"SE Barkan","year":"1998","unstructured":"Barkan SE, Melnick SL, Preston-Martin S, Weber K, Kalish LA, Miotti P, et al. The Women\u2019s Interagency HIV Study WIHS Collaborative Study Group. Epidemiol. 1998;9(2):117\u201325.","journal-title":"Epidemiol"},{"issue":"9","key":"1675_CR4","first-page":"1013","volume":"12","author":"MC Bacon","year":"2005","unstructured":"Bacon MC, von Wyl V, Alden C, Sharp G, Robison E, Hessol N, et al. The Women\u2019s Interagency HIV Study: an observational cohort brings clinical sciences to the bench. Clin Diagn Lab Immunol. 2005;12(9):1013\u20139.","journal-title":"Clin Diagn Lab Immunol"},{"key":"1675_CR5","unstructured":"White S. Basic and Clinical Biostatistics. 5th ed. New York: McGraw-Hill; 2019."},{"key":"1675_CR6","volume-title":"Epidemiology: An Introduction","author":"KJ Rothman","year":"2002","unstructured":"Rothman KJ. Epidemiology: An Introduction. New York: Oxford University Press; 2002."},{"issue":"3","key":"1675_CR7","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1097\/01.ede.0000158224.50593.e3","volume":"16","author":"JI Hudson","year":"2005","unstructured":"Hudson JI, Pope HG Jr, Glynn RJ. The cross-sectional cohort study: an underutilized design. Epidemiol. 2005;16(3):355\u20139.","journal-title":"Epidemiol"},{"issue":"12","key":"1675_CR8","doi-asserted-by":"publisher","first-page":"e031031","DOI":"10.1136\/bmjopen-2019-031031","volume":"9","author":"MH Gail","year":"2019","unstructured":"Gail MH, Altman DG, Cadarette SM, Collins G, Evans SJ, Sekula P, et al. Design choices for observational studies of the effect of exposure on disease incidence. BMJ Open. 2019;9(12):e031031.","journal-title":"BMJ Open"},{"key":"1675_CR9","volume-title":"Epidemiology Kept Simple: An Introduction to Classic and Modern Epidemiology","author":"BB Gerstman","year":"1998","unstructured":"Gerstman BB. Epidemiology Kept Simple: An Introduction to Classic and Modern Epidemiology. New York: Wiley-Liss; 1998."},{"issue":"8","key":"1675_CR10","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1093\/aje\/kwab050","volume":"190","author":"G D'Souza","year":"2021","unstructured":"D\u2019Souza G, Bhondoekhan F, Benning L, Margolick JB, Adedimeji AA, Adimora AA, et al. Characteristics of the MACS\/WIHS Combined Cohort Study: Opportunities for Research on Aging With HIV in the Longest US Observational Study of HIV. Am J Epidemiol. 2021;190(8):1457\u201375.","journal-title":"Am J Epidemiol"},{"issue":"4","key":"1675_CR11","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1097\/EDE.0000000000000664","volume":"28","author":"CR Lesko","year":"2017","unstructured":"Lesko CR, Buchanan AL, Westreich D, Edwards JK, Hudgens MG, Cole SR. Generalizing Study Results: A Potential Outcomes Perspective. Epidemiology. 2017;28(4):553\u201361.","journal-title":"Epidemiology"},{"issue":"2","key":"1675_CR12","doi-asserted-by":"publisher","first-page":"e16","DOI":"10.1097\/EDE.0000000000000770","volume":"29","author":"CR Lesko","year":"2018","unstructured":"Lesko CR, Buchanan AL, Westreich D, Edwards JK, Hudgens MG, Cole SR. Generalizing Study Results: A Potential Outcomes Perspective: Erratum. Epidemiol. 2018;29(2):e16.","journal-title":"Epidemiol"}],"container-title":["BMC Medical Research Methodology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12874-022-01675-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12874-022-01675-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12874-022-01675-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T12:06:03Z","timestamp":1658750763000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedresmethodol.biomedcentral.com\/articles\/10.1186\/s12874-022-01675-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,25]]},"references-count":12,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["1675"],"URL":"https:\/\/doi.org\/10.1186\/s12874-022-01675-w","relation":{},"ISSN":["1471-2288"],"issn-type":[{"type":"electronic","value":"1471-2288"}],"subject":[],"published":{"date-parts":[[2022,7,25]]},"assertion":[{"value":"13 September 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 July 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"BBH obtains written informed consent from all participants. The Institutional Review Board (IRB) at Emory University approved the parent WIHS protocol for the Emory site. The BBH protocol was approved by the Emory University IRB and the Grady Health System Research Oversight Committee. The parent MWCCS study protocol was approved for all sites by the Johns Hopkins University IRB and prior WIHS participants were re-recruited and re-consented into MWCCS. MWCCS reverted to individual site IRB approval and informed consent was again obtained from all participants. All BBC methods were performed in accordance with the relevant guidelines and regulations.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"203"}}