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

被引：18

作者：

Grau, Janina ^{[1
,2
,3
]}

Zollner, Johann Philipp ^{[1
,2
,3
]}

Schubert-Bast, Susanne ^{[1
,2
,3
,4
]}

Kurlemann, Gerhard ^{[5
]}

Hertzberg, Christoph ^{[6
]}

Wiemer-Kruel, Adelheid ^{[7
]}

Bast, Thomas ^{[7
]}

Bertsche, Astrid ^{[8
]}

Bettendorf, Ulrich

Fiedler, Barbara ^{[9
]}

Hahn, Andreas ^{[10
]}

Hartmann, Hans ^{[11
]}

Hornemann, Frauke ^{[12
]}

Immisch, Ilka ^{[13
,14
]}

Jacobs, Julia ^{[15
,16
]}

Kieslich, Matthias ^{[1
,2
,4
]}

Klein, Karl Martin ^{[1
,2
,3
,17
,18
,19
,20
]}

Klotz, Kerstin A. ^{[15
,21
]}

Kluger, Gerhard ^{[22
,23
]}

Knuf, Markus ^{[24
,25
]}

Mayer, Thomas ^{[26
]}

Marquard, Klaus ^{[27
]}

Meyer, Sascha ^{[28
]}

Muhle, Hiltrud ^{[29
,30
]}

Muller-Schluter, Karen ^{[31
]}

Noda, Anna H. ^{[1
,2
,3
]}

Ruf, Susanne ^{[32
]}

Sauter, Matthias ^{[33
]}

Schlump, Jan-Ulrich ^{[34
]}

Syrbe, Steffen ^{[35
]}

Thiels, Charlotte ^{[36
]}

Trollmann, Regina ^{[37
]}

Wilken, Bernd ^{[38
]}

Willems, Laurent M. ^{[1
,2
,3
]}

Rosenow, Felix ^{[1
,2
,3
]}

Strzelczyk, Adam ^{[1
,2
,3
,13
,14
]}

机构：

[1] Goethe Univ Frankfurt, Epilepsy Ctr Frankfurt Rhine Main, Schleusenweg 2-16 Haus 95, D-60528 Frankfurt, Germany

[2] Goethe Univ Frankfurt, Dept Neurol, Schleusenweg 2-16 Haus 95, D-60528 Frankfurt, Germany

[3] Goethe Univ Frankfurt, Ctr Personalized Translat Epilepsy Res CePTER, Frankfurt, Germany

[4] Goethe Univ Frankfurt, Dept Neuropediat, Frankfurt, Germany

[5] St Bonifatius Hosp, Lingen, Germany

[6] Vivantes Klinikum Neukolln, Dept Neuropediat, Berlin, Germany

[7] Epilepsy Ctr Kork, Clin Children & Adolescents, Kehl, Germany

[8] Univ Hosp Children & Adolescents, Dept Neuropediat, Rostock, Germany

[9] Univ Hosp Munster, Dept Gen Pediat, Div Neuropediat, Munster, Germany

[10] Justus Liebig Univ Giessen, Dept Neuropediat, Giessen, Germany

[11] Hannover Med Sch, Dept Neuropediat, Clin Pediat Kidney Liver & Metab Dis, Hannover, Germany

[12] Leipzig Univ Hosp Children & Adolescents, Dept Neuropediat, Leipzig, Germany

[13] Philipps Univ Marburg, Epilepsy Ctr Hessen, Marburg, Lahn, Germany

[14] Philipps Univ Marburg, Dept Neurol, Marburg, Lahn, Germany

[15] Univ Freiburg, Fac Med, Dept Neuropediat & Muscle Disorders, Ctr Pediat,Med Ctr, Freiburg, Germany

[16] Univ Calgary, Cumming Sch Med, Dept Pediat & Clin Neurosci, Calgary, AB, Canada

[17] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada

[18] Univ Calgary, Hotchkiss Brain Inst, Dept Med Genet, Calgary, AB, Canada

[19] Univ Calgary, Hotchkiss Brain Inst, Dept Community Hlth Sci, Calgary, AB, Canada

[20] Univ Calgary, Cumming Sch Med, Alberta Childrens Hosp, Res Inst, Calgary, AB, Canada

[21] Univ Freiburg, Fac Med, Berta Ottenstein Programme, Freiburg, Germany

[22] Schon Clin Vogtareuth, Epilepsy Ctr Children & Adolescents, Clin Neuropediat & Neurorehabil, Vogtareuth, Germany

[23] PMU Salzburg, Res Inst, Rehabil Transit & Palliat, Salzburg, Austria

[24] Klinikum Worms, Dept Pediat, Worms, Germany

[25] Univ Med Mainz, Dept Pediat, Mainz, Germany

[26] Epilepsy Ctr Kleinwachau, Dresden, Germany

[27] Klinikum Stuttgart, Dept Pediat Neurol Psychosomat & Pain Management, Stuttgart, Germany

[28] Univ Med Ctr Homburg, Childrens Hosp, Dept Neuropediat, Homburg, Germany

[29] Christian Albrechts Univ Kiel, Dept Neuropediat, Campus Kiel, Kiel, Germany

[30] Univ Hosp Schleswig Holstein, Campus Kiel, Kiel, Germany

[31] Univ Hosp Neuruppin, Brandenburg Med Sch, Epilepsy Ctr Children, Neuruppin, Germany

[32] Univ Hosp Tubingen, Dept Neuropediat, Tubingen, Germany

[33] Klinikverbund Allgau, Klinikum Kempten, Kempten, Allgau, Germany

[34] Univ Witten Herdecke, Dept Neuropediat, Herdecke, Germany

[35] Univ Hosp Heidelberg, Ctr Paediat & Adolescent Med, Div Pediat Epileptol, Heidelberg, Germany

[36] Ruhr Univ Bochum, Univ Hosp, Dept Neuropediat & Socialpediat, Bochum, Germany

[37] Friedrich Alexander Univ Erlangen Nurnberg, Dept Neuropediat, Erlangen, Germany

[38] Klinikum Kassel, Dept Neuropediat, Kassel, Germany

来源：

ORPHANET JOURNAL OF RARE DISEASES | 2021年 / 16卷 / 01期

关键词：

mTOR inhibitor; Everolimus; Seizure; Rhabdomyoma; Epilepsy; Anti-seizure medication; HEALTH-CARE UTILIZATION; RETROSPECTIVE COHORT; ECONOMIC BURDEN; ILAE COMMISSION; POSITION PAPER; EPILEPSY; PREVALENCE; RECOMMENDATIONS; MANIFESTATIONS; CLASSIFICATION;

D O I：

10.1186/s13023-021-01899-x

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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,

引用

页数：16

共 48 条

[1] Economic burden associated with tuberous sclerosis complex in patients with epilepsy [J].

Betts, Keith A. ;

Stockl, Karen M. ;

Yin, Lei ;

Hollenack, Kelly ;

Wang, Min-Jung ;

Yang, Xiaoran .

EPILEPSY & BEHAVIOR, 2020, 112

[2] Calculation of Standardised Unit Costs from a Societal Perspective for Health Economic Evaluation [J].

Bock, J-O. ;

Brettschneider, C. ;

Seidl, H. ;

Bowles, D. ;

Holle, R. ;

Greiner, W. ;

Koenig, H-H. .

GESUNDHEITSWESEN, 2015, 77 (01) :53-61

[3] Prevalence, mortality and healthcare economic burden of tuberous sclerosis in Hong Kong: a population-based retrospective cohort study (1995-2018) [J].

Chu, William Ching-Yuen ;

Chiang, Lorraine Lok-Wing ;

Chan, Dorothy Chi-Ching ;

Wong, Wilfred Hing-Sang ;

Chan, Godfrey Chi-Fung .

ORPHANET JOURNAL OF RARE DISEASES, 2020, 15 (01)

[4] Neurological and neuropsychiatric aspects of tuberous sclerosis complex [J].

Curatolo, Paolo ;

Moavero, Romina ;

de Vries, Petrus J. .

LANCET NEUROLOGY, 2015, 14 (07) :733-745

[5] The use of the bootstrap statistical method for the pharmacoeconomic cost analysis of skewed data [J].

Desgagne, A ;

Castilloux, AM ;

Angers, JF ;

LeLorier, J .

PHARMACOECONOMICS, 1998, 13 (05) :487-497

[6] Incidence of tuberous sclerosis and age at first diagnosis: new data and emerging trends from a national, prospective surveillance study [J].

Ebrahimi-Fakhari, Daniel ;

Mann, Lilian Lisa ;

Poryo, Martin ;

Graf, Norbert ;

von Kries, Ruediger ;

Heinrich, Beate ;

Ebrahimi-Fakhari, Darius ;

Flotats-Bastardas, Marina ;

Gortner, Ludwig ;

Zemlin, Michael ;

Meyer, Sascha .

ORPHANET JOURNAL OF RARE DISEASES, 2018, 13

[7] Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology [J].

Fisher, Robert S. ;

Cross, J. Helen ;

French, Jacqueline A. ;

Higurashi, Norimichi ;

Hirsch, Edouard ;

Jansen, Floor E. ;

Lagae, Lieven ;

Moshe, Solomon L. ;

Peltola, Jukka ;

Roulet Perez, Eliane ;

Scheffer, Ingrid E. ;

Zuberi, Sameer M. .

EPILEPSIA, 2017, 58 (04) :522-530

[8] Burden of disease and unmet needs in tuberous sclerosis complex with neurological manifestations: systematic review [J].

Hallett, Lindsay ;

Foster, Talia ;

Liu, Zhimei ;

Blieden, Marissa ;

Valentim, Joice .

CURRENT MEDICAL RESEARCH AND OPINION, 2011, 27 (08) :1571-1583

[9]

Hein L., 2019, ARZNEIVERORDNUNGS RE, P531, DOI [10.1007/978-3-662-59046-1, DOI 10.1007/978-3-662-59046-1_19, 10.1007/978-3-662-59046-1_19]

[10] Tuberous sclerosis complex [J].

Henske, Elizabeth P. ;

Jozwiak, Sergiusz ;

Kingswood, J. Christopher ;

Sampson, Julian R. ;

Thiele, Elizabeth A. .

NATURE REVIEWS DISEASE PRIMERS, 2016, 2

← 1 2 3 4 5 →