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


Journal

Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602

Informations de publication

Date de publication:
21 06 2021
Historique:
received: 21 11 2020
accepted: 29 05 2021
entrez: 22 6 2021
pubmed: 23 6 2021
medline: 30 6 2021
Statut: epublish

Résumé

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. 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. 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. 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. DRKS, DRKS00016045. Registered 01 March 2019, http://www.drks.de/DRKS00016045.

Sections du résumé

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.
TRIAL REGISTRATION
DRKS, DRKS00016045. Registered 01 March 2019, http://www.drks.de/DRKS00016045.

Identifiants

pubmed: 34154622
doi: 10.1186/s13023-021-01899-x
pii: 10.1186/s13023-021-01899-x
pmc: PMC8218507
doi:

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

282

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Auteurs

Janina Grau (J)

Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am Main, Germany.
Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany.

Johann Philipp Zöllner (JP)

Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am Main, Germany.
Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany.

Susanne Schubert-Bast (S)

Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am Main, Germany.
Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany.
Department of Neuropediatrics, Goethe-University Frankfurt, Frankfurt am Main, Germany.

Gerhard Kurlemann (G)

St. Bonifatius Hospital, Lingen, Germany.

Christoph Hertzberg (C)

Department of Neuropediatrics, Vivantes Klinikum Neukölln, Berlin, Germany.

Adelheid Wiemer-Kruel (A)

Epilepsy Center Kork, Clinic for Children and Adolescents, Kehl-Kork, Germany.

Thomas Bast (T)

Epilepsy Center Kork, Clinic for Children and Adolescents, Kehl-Kork, Germany.

Astrid Bertsche (A)

Department of Neuropediatrics, University Hospital for Children and Adolescents, Rostock, Germany.

Ulrich Bettendorf (U)

Neuropediatric Practice, Hirschaid, Germany.

Barbara Fiedler (B)

Department of General Pediatrics, Division of Neuropediatrics, University Hospital Münster, Münster, Germany.

Andreas Hahn (A)

Department of Neuropediatrics, Justus-Liebig-University Gießen, Gießen, Germany.

Hans Hartmann (H)

Department of Neuropediatrics, Clinic for Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany.

Frauke Hornemann (F)

Department of Neuropediatrics, Leipzig University Hospital for Children and Adolescents, Leipzig, Germany.

Ilka Immisch (I)

Epilepsy Center Hessen and Department of Neurology, Philipps-University Marburg, Marburg (Lahn), Germany.

Julia Jacobs (J)

Department of Neuropediatrics and Muscle Disorders, Center for Pediatrics, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg i.Br., Germany.
Department of Pediatrics and Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Matthias Kieslich (M)

Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am Main, Germany.
Department of Neuropediatrics, Goethe-University Frankfurt, Frankfurt am Main, Germany.

Karl Martin Klein (KM)

Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am Main, Germany.
Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany.
Departments of Clinical Neurosciences, Medical Genetics and Community Health Sciences, Hotchkiss Brain Institute & Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Kerstin A Klotz (KA)

Department of Neuropediatrics and Muscle Disorders, Center for Pediatrics, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg i.Br., Germany.
Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Freiburg i.Br., Germany.

Gerhard Kluger (G)

Clinic for Neuropediatrics and Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schön Clinic Vogtareuth, Vogtareuth, Germany.
Research Institute, Rehabilitation, Transition and Palliation, PMU Salzburg, Salzburg, Austria.

Markus Knuf (M)

Department of Pediatrics, Klinikum Worms, Worms, Germany.
Department of Pediatrics, University Medicine Mainz, Mainz, Germany.

Thomas Mayer (T)

Epilepsy Center Kleinwachau, Dresden-Radeberg, Germany.

Klaus Marquard (K)

Department of Pediatric Neurology, Psychosomatics and Pain Management, Klinikum Stuttgart, Stuttgart, Germany.

Sascha Meyer (S)

Department of Neuropediatrics, Children's Hospital at University Medical Center Homburg, Homburg, Germany.

Hiltrud Muhle (H)

Department of Neuropediatrics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Karen Müller-Schlüter (K)

Epilepsy Center for Children, Brandenburg Medical School, University Hospital Neuruppin, Neuruppin, Germany.

Anna H Noda (AH)

Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am Main, Germany.
Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany.

Susanne Ruf (S)

Department of Neuropediatrics, University Hospital Tübingen, Tübingen, Germany.

Matthias Sauter (M)

Klinikum Kempten, Klinikverbund Allgäu, Kempten (Allgäu), Germany.

Jan-Ulrich Schlump (JU)

Department of Neuropediatrics, University of Witten/Herdecke, Herdecke, Germany.

Steffen Syrbe (S)

Division of Pediatric Epileptology, Centre for Paediatrics and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.

Charlotte Thiels (C)

Department of Neuropediatrics and Socialpediatrics, University Hospital of Ruhr University Bochum, Bochum, Germany.

Regina Trollmann (R)

Department of Neuropediatrics, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany.

Bernd Wilken (B)

Department of Neuropediatrics, Klinikum Kassel, Kassel, Germany.

Laurent M Willems (LM)

Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am Main, Germany.
Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany.

Felix Rosenow (F)

Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am Main, Germany.
Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany.

Adam Strzelczyk (A)

Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am Main, Germany. strzelczyk@med.uni-frankfurt.de.
Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany. strzelczyk@med.uni-frankfurt.de.
Epilepsy Center Hessen and Department of Neurology, Philipps-University Marburg, Marburg (Lahn), Germany. strzelczyk@med.uni-frankfurt.de.

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