{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T10:19:46Z","timestamp":1777544386786,"version":"3.51.4"},"reference-count":23,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2019,6,11]],"date-time":"2019-06-11T00:00:00Z","timestamp":1560211200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","award":["FD003908"],"award-info":[{"award-number":["FD003908"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005468","name":"Batten Disease Support and Research Association","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100005468","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clinical Trials"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Travel burden often substantially limits the ability of individuals to participate in clinical trials. Wide geographic dispersion of individuals with rare diseases poses an additional key challenge in the conduct of clinical trials for rare diseases. Novel technologies and methods can improve access to research by connecting participants in their homes and local communities to a distant research site. For clinical trials, however, understanding of factors important for transition from traditional multi-center trial models to local participation models is limited. We sought to test a novel, hybrid, single- and multi-site clinical trial design in the context of a trial for Juvenile Neuronal Ceroid Lipofuscinosis (CLN3 disease), a very rare pediatric neurodegenerative disorder.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We created a \u201chub and spoke\u201d model for implementing a 22-week crossover clinical trial of mycophenolate compared with placebo, with two 8-week study arms. A single central site, the \u201chub,\u201d conducted screening, consent, drug dispensing, and tolerability and efficacy assessments. Each participant identified a clinician to serve as a collaborating \u201cspoke\u201d site to perform local safety monitoring. Study participants traveled to the hub at the beginning and end of each study arm, and to their individual spoke site in the intervening weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 18 spoke sites were established for 19 enrolled study participants. One potential participant was unable to identify a collaborating local site and was thus unable to participate. Study start-up required a median 6.7 months (interquartile range = 4.6\u20139.2 months). Only 33.3% (n = 6 of 18) of spoke site investigators had prior clinical trial experience, thus close collaboration with respect to study startup, training, and oversight was an important requirement. All but one participant completed all study visits; no study visits were missed due to travel requirements.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study represents a step toward local trial participation for patients with rare diseases. Even in the context of close oversight, local participation models may be best suited for studies of compounds with well-understood side-effect profiles, for those with straightforward modes of administration, or for studies requiring extended follow-up periods.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1740774519855715","type":"journal-article","created":{"date-parts":[[2019,6,11]],"date-time":"2019-06-11T08:40:45Z","timestamp":1560242445000},"page":"555-560","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["A novel, hybrid, single- and multi-site clinical trial design for CLN3 disease, an ultra-rare lysosomal storage disorder"],"prefix":"10.1177","volume":"16","author":[{"given":"Heather R","family":"Adams","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA"},{"name":"Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Defendorf","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Vierhile","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA"},{"name":"Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan W","family":"Mink","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA"},{"name":"Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA"},{"name":"Department of Neuroscience, University of Rochester Medical Center, Rochester, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederick J","family":"Marshall","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7257-8985","authenticated-orcid":false,"given":"Erika F","family":"Augustine","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA"},{"name":"Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA"},{"name":"Center for Health + Technology, University of Rochester Medical Center, Rochester, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,6,11]]},"reference":[{"key":"bibr1-1740774519855715","unstructured":"Ceroid lipofuscinosis, neuronal, 3; CLN3, http:\/\/omim.org\/entry\/204200# (accessed 4 March 2017)."},{"key":"bibr2-1740774519855715","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90274-0"},{"key":"bibr3-1740774519855715","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9421-6"},{"key":"bibr4-1740774519855715","doi-asserted-by":"publisher","DOI":"10.1177\/0883073813494813"},{"key":"bibr5-1740774519855715","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.11.021"},{"key":"bibr6-1740774519855715","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000169019.41332.8a"},{"key":"bibr7-1740774519855715","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318237f649"},{"key":"bibr8-1740774519855715","first-page":"655","volume":"13","author":"Augustine EF","year":"2016","journal-title":"Pediatr Endocrinol Rev"},{"key":"bibr9-1740774519855715","doi-asserted-by":"publisher","DOI":"10.1007\/s100720070038"},{"key":"bibr10-1740774519855715","author":"Congress tUS","year":"1983","journal-title":"Orphan Drug Act"},{"key":"bibr11-1740774519855715","unstructured":"Center UoRM. Cellcept for treatment of juvenile neuronal ceroid lipofuscinosis (NCT01399047), 2012, www.clinicaltrials.gov"},{"key":"bibr12-1740774519855715","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2018_113"},{"key":"bibr13-1740774519855715","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2013.04.004"},{"issue":"16","key":"bibr14-1740774519855715","volume":"86","author":"Amengual T","year":"2016","journal-title":"Neurology"},{"key":"bibr15-1740774519855715","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2016.04.001"},{"key":"bibr16-1740774519855715","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70142-5"},{"key":"bibr17-1740774519855715","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1712649"},{"key":"bibr18-1740774519855715","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182a823e0"},{"key":"bibr19-1740774519855715","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-720X.2002.tb00410.x"},{"key":"bibr20-1740774519855715","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12463"},{"key":"bibr21-1740774519855715","doi-asserted-by":"publisher","DOI":"10.1097\/ACM.0000000000000562"},{"key":"bibr22-1740774519855715","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70008-X"},{"key":"bibr23-1740774519855715","unstructured":"Final NIH policy on the use of a single institutional review board for multi-site research, https:\/\/grants.nih.gov\/grants\/guide\/notice-files\/NOT-OD-16-094.html (2016, accessed January 4 2019)."}],"container-title":["Clinical Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1740774519855715","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1740774519855715","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1740774519855715","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:30:10Z","timestamp":1777397410000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1740774519855715"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,11]]},"references-count":23,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1177\/1740774519855715"],"URL":"https:\/\/doi.org\/10.1177\/1740774519855715","relation":{},"ISSN":["1740-7745","1740-7753"],"issn-type":[{"value":"1740-7745","type":"print"},{"value":"1740-7753","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,11]]}}}