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This German multicenter study estimated the disease-specific costs and cost-driving factors associated with various organ manifestations in TSC patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A validated, three-month, retrospective questionnaire was administered to assess the sociodemographic and clinical characteristics, organ manifestations, direct, indirect, out-of-pocket, and nursing care-level costs, completed by caregivers of patients with TSC throughout Germany.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The caregivers of 184 patients (mean age 9.8\u2009\u00b1\u20095.3\u00a0years, range 0.7\u201321.8\u00a0years) submitted questionnaires. The reported TSC disease manifestations included epilepsy (92%), skin disorders (86%), structural brain disorders (83%), heart and circulatory system disorders (67%), kidney and urinary tract disorders (53%), and psychiatric disorders (51%). Genetic variations in <jats:italic>TSC2<\/jats:italic> were reported in 46% of patients, whereas 14% were reported in <jats:italic>TSC1<\/jats:italic>. Mean total direct health care costs were EUR 4949 [95% confidence interval (95% CI) EUR 4088\u20135863, median EUR 2062] per patient over three months. Medication costs represented the largest direct cost category (54% of total direct costs, mean EUR 2658), with mechanistic target of rapamycin (mTOR) inhibitors representing the largest share (47%, EUR 2309). The cost of anti-seizure drugs (ASDs) accounted for a mean of only EUR 260 (5%). Inpatient costs (21%, EUR 1027) and ancillary therapy costs (8%, EUR 407) were also important direct cost components. The mean nursing care-level costs were EUR 1163 (95% CI EUR 1027\u20131314, median EUR 1635) over three months. Total indirect costs totaled a mean of EUR 2813 (95% CI EUR 2221\u20133394, median EUR 215) for mothers and EUR 372 (95% CI EUR 193\u2013586, median EUR 0) for fathers. Multiple regression analyses revealed polytherapy with two or more ASDs and the use of mTOR inhibitors as independent cost-driving factors of total direct costs. Disability and psychiatric disease were independent cost-driving factors for total indirect costs as well as for nursing care-level costs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study revealed substantial direct (including medication), nursing care-level, and indirect costs associated with TSC over three months, highlighting the spectrum of organ manifestations and their treatment needs in the German healthcare setting.<\/jats:p>\n                <jats:p><jats:italic>Trial registration<\/jats:italic>: DRKS, DRKS00016045. Registered 01 March 2019, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.drks.de\/DRKS00016045.\">http:\/\/www.drks.de\/DRKS00016045.<\/jats:ext-link><\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-021-01899-x","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T12:03:10Z","timestamp":1624276990000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Direct and indirect costs and cost-driving factors of Tuberous sclerosis complex in children, adolescents, and caregivers: a multicenter cohort study"],"prefix":"10.1186","volume":"16","author":[{"given":"Janina","family":"Grau","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johann 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SS-B reports personal fees from Eisai, Desitin Pharma, GW Pharmaceuticals companies, LivaNova, UCB, and Zogenix. GK reports personal fees from Desitin Arzneimittel, Eisai, GW Pharmaceuticals companies, UCB, Novartis, Takeda, and Zogenix. AW-K reports personal fees from Desitin Arzneimittel, GW Pharmaceuticals companies, Nutricia GmbH, Vitaflo, and UCB. TB reports personal fees from Eisai, Desitin Arzneimittel, GW Pharma, Novartis, Nutricia, Shire, Takeda, UCB Pharma and Zogenix. AB reports personal fees from Desitin Arzneimittel GmbH, Eisai GmbH, Shire GmbH, UCB Pharma GmbH, and ViroPharma GmbH. BF reports personal fees from Desitin Arzneimittel, Novartis and UCB. JJ reports personal fees from Eisai, GW Pharmaceuticals companies, Zogenix and has been supported by the German Research Foundation (DFG; JA 1725\/4-1). KMK reports personal fees from UCB Pharma, Novartis Pharma AG, Eisai, and GW Pharmaceuticals, grants from the federal state Hessen through the LOEWE program and from the Canadian Institutes of Health Research. KAK reports personal fees from GW Pharmaceuticals companies and Zogenix and was supported by the Berta-Ottenstein-Program for Clinician Scientists from the Faculty of Medicine, University of Freiburg. TM reports personal fees and grants from Arvelle Therapeutics, Eisai, GW Pharmaceuticals companies, UCB, and Zogenix. HM reports personal fees from Desitin Arzneimittel, UCB, Novartis and Zogenix. SM reports grants from Novartis, UCB, Shire, Deutsche Forschungsgemeinschaft and Epilepsiestiftung Dr. Wolf. KMS reports personal fees from Nutricia, Desitin Arzneimittel, Shire, Medice, Novartis and UCB. MS reports personal fees from Novartis. RT reports personal fees from Eisai, Desitin, PTC Therap., Roche, Sanofi Genzyme. BW reports fees and compensation for travel expenses from Eisai, Takeda\/Shire, Ipsen and PharmAllergan. FR reports personal fees from Arvelle Therapeutics, Desitin Arzneimittel, Eisai, GW Pharmaceuticals companies, Novartis, Medtronic, and UCB, and grants from the Detlev-Wrobel-Fonds for Epilepsy Research, the Deutsche Forschungsgemeinschaft, the LOEWE Programme of the State of Hesse, and the European Union. AS reports personal fees and grants from Arvelle Therapeutics, Desitin Arzneimittel, Eisai, GW Pharmaceuticals companies, Marinus Pharma, UCB, and Zogenix. The other authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"282"}}