Direct and indirect costs and cost-driving factors of Tuberous sclerosis complex in children, adolescents, and caregivers: a multicenter cohort study

  • Background: Tuberous sclerosis complex (TSC), a multisystem genetic disorder, affects many organs and systems, characterized by benign growths. This German multicenter study estimated the disease-specific costs and cost-driving factors associated with various organ manifestations in TSC patients. Methods: 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. Results: The caregivers of 184 patients (mean age 9.8 ± 5.3 years, range 0.7–21.8 years) 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 TSC2 were reported in 46% of patients, whereas 14% were reported in TSC1. Mean total direct health care costs were EUR 4949 [95% confidence interval (95% CI) EUR 4088–5863, 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 1027–1314, median EUR 1635) over three months. Total indirect costs totaled a mean of EUR 2813 (95% CI EUR 2221–3394, median EUR 215) for mothers and EUR 372 (95% CI EUR 193–586, 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. Conclusions: 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.

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Author:Janina GrauGND, Johann Philipp ZöllnerORCiDGND, Susanne Schubert-BastORCiDGND, Gerhard KurlemannGND, Christoph HertzbergORCiDGND, Adelheid Wiemer-KruelORCiD, Thomas BastGND, Ulrich BettendorfGND, Barbara Fiedler, Andreas Hahn, Hans Hartmann, Frauke Hornemann, Ilka ImmischGND, Julia Jacobs, Matthias Kieslich, Karl Martin KleinORCiD, Kerstin Alexandra KlotzORCiDGND, Gerhard Kluger, Markus KnufGND, Thomas Mayer, Klaus Marquard, Sascha Meyer, Hiltrud MuhleORCiDGND, Karen Müller-SchlüterGND, Anna NodaGND, Susanne Ruf, Matthias SauterORCiDGND, Jan-Ulrich SchlumpGND, Steffen SyrbeORCiDGND, Charlotte ThielsORCiDGND, Regina TrollmannORCiDGND, Bernd Wilken, Laurent Maximilian WillemsORCiDGND, Felix RosenowORCiDGND, Adam StrzelczykORCiDGND
Parent Title (English):Orphanet journal of rare diseases
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Date of Publication (online):2021/06/21
Date of first Publication:2021/06/21
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/07/12
Tag:Anti-seizure medication; Epilepsy; Everolimus; Rhabdomyoma; Seizure; mTOR inhibitor
Issue:art. 282
Page Number:16
First Page:1
Last Page:16
Open Access funding enabled and organized by Projekt DEAL. This study was supported by a LOEWE Grant from the State of Hessen for the “Center for Personalized Translational Epilepsy Research” (CePTER,, Goethe-University Frankfurt, Frankfurt am Main, Germany.
The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0