Hostname: page-component-848d4c4894-wzw2p Total loading time: 0 Render date: 2024-04-30T21:11:23.542Z Has data issue: false hasContentIssue false
  • English
  • Français

Value of mesenchymal stem cell therapy for patients with septic shock: an early health economic evaluation

Published online by Cambridge University Press:  16 October 2020

Kednapa Thavorn Open the ORCID record for Kednapa Thavorn [Opens in a new window] ,
Sasha van Katwyk ,
Murray Krahn ,
Shirley H.J. Mei ,
Duncan J. Stewart ,
Dean Fergusson ,
Doug Coyle  and
Lauralyn McIntyre
Kednapa Thavorn*
Affiliation:
Ottawa Hospital Research Institute, Ontario, Canada School of Epidemiology and Public Health, University of Ottawa, Ontario, Canada
Sasha van Katwyk
Affiliation:
Ottawa Hospital Research Institute, Ontario, Canada School of Epidemiology and Public Health, University of Ottawa, Ontario, Canada
Murray Krahn
Affiliation:
Toronto Health Economics and Technology Assessment Collaborative, University of Toronto, Ontario, Canada
Shirley H.J. Mei
Affiliation:
Ottawa Hospital Research Institute, Ontario, Canada
Duncan J. Stewart
Affiliation:
Regenerative Medicine Program, Ottawa Hospital Research Institute, Ontario, Canada Department of Cell and Molecular Medicine, University of Ottawa, Ontario, Canada
Dean Fergusson
Affiliation:
Ottawa Hospital Research Institute, Ontario, Canada
Doug Coyle
Affiliation:
School of Epidemiology and Public Health, University of Ottawa, Ontario, Canada
Lauralyn McIntyre
Affiliation:
Ottawa Hospital Research Institute, Ontario, Canada Department of Medicine (Division of Critical Care), University of Ottawa, Ottawa, Canada
*
Author for correspondence: Kednapa Thavorn, E-mail: kthavorn@ohri.ca
Get access Rights & Permissions [Opens in a new window]

Abstract

Background.

This study estimates the maximum price at which mesenchymal stem cell (MSC) therapy is deemed cost-effective for septic shock patients and identifies parameters that are most important in making treatment decisions.

Methods

We developed a probabilistic Markov model according to the sepsis care trajectory to simulate costs and quality-adjusted life years (QALYs) of septic shock patients receiving either MSC therapy or usual care over their lifetime. We calculated the therapeutic headroom by multiplying the gains attributable to MSCs with willingness-to-pay (WTP) threshold and derived the maximum reimbursable price (MRP) from the expected net monetary benefit and savings attributable to MSCs. We performed scenario analyses to assess the impact of changes to assumptions on the study findings. A value of information analysis is performed to identify parameters with greatest impact on the uncertainty around the cost-effectiveness of MSC therapy.

Results

At a WTP threshold of $50,000 per QALY, the therapeutic headroom and MRP of MSC therapy were $20,941 and $16,748, respectively; these estimates increased with the larger WTP values and the greater impact of MSCs on in-hospital mortality and hospital discharge rates. The parameters with greatest information value were MSC's impact on in-hospital mortality and the baseline septic shock in-hospital mortality.

Conclusion

At a common WTP of $50,000/QALY, MSC therapy is deemed to be economically attractive if its unit cost does not exceed $16,748. This ceiling price can be increased to $101,450 if the therapy significantly reduces both in-hospital mortality and increases hospital discharge rates.

Keywords

Early economic evaluationeconomic analysismaximum reimbursable pricemesenchymal stem cellseptic shock
Type
Assessment
Information
International Journal of Technology Assessment in Health Care , Volume 36 , Issue 5 , October 2020 , pp. 525 - 532
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adhikari, NK, Fowler, RA, Bhagwanjee, S, Rubenfeld, GD. Critical care and the global burden of critical illness in adults. Lancet. 2010;376:1339–46.10.1016/S0140-6736(10)60446-1CrossRefGoogle ScholarPubMed
Angus, DC, van der Poll, T. Severe sepsis and septic shock. N Engl J Med. 2013;369:840–51.10.1056/NEJMra1208623CrossRefGoogle ScholarPubMed
Torio, CM, Moore, BJ. National Inpatient Hospital Costs: The Most Expensive Conditions by Payer, 2013. 2016. Accessed: Nov. 28, 2016. Available from https://www.hcup-us.ahrq.gov/reports/statbriefs/sb204-Most-Expensive-Hospital-Conditions.jspGoogle Scholar
Lalu, MM, Sullivan, KJ, Mei, SH, Moher, D, Straus, A, Fergusson, DA et al. Evaluating mesenchymal stem cell therapy for sepsis with preclinical meta-analyses prior to initiating a first-in-human trial. eLife. 2016;5:1–28.CrossRefGoogle ScholarPubMed
Zheng, G, Huang, L, Tong, H, Shu, Q, Hu, Y, Ge, M et al. Treatment of acute respiratory distress syndrome with allogeneic adipose-derived mesenchymal stem cells: A randomized, placebo-controlled pilot study. Respir Res. 2014;15:39.10.1186/1465-9921-15-39CrossRefGoogle ScholarPubMed
Wilson, JG, Liu, KD, Zhuo, H, Caballero, L, McMillan, M, Fang, X et al. Mesenchymal stem (stromal) cells for treatment of ARDS: A phase 1 clinical trial. Lancet Respir Med. 2015;3:24–32.CrossRefGoogle ScholarPubMed
Galstian, GM, Parovichnikova, EN, Makarova, PM, Kuzmina, LA, Troitskaya, VV, Gemdzhian, E et al. The results of the Russian clinical trial of mesenchymal stromal cells (MSCs) in severe neutropenic patients (pts) with septic shock (SS) (RUMCESS trial) [abstract]. Blood. 2015;126(23).CrossRefGoogle Scholar
McIntyre, LA, Stewart, DJ, Mei, SHJ, Courtman, D, Watpool, I, Granton, J et al. Canadian Critical Care Trials Group; Canadian Critical Care Translational Biology Group. Cellular immunotherapy for septic shock. A phase I clinical trial. Am J Respir Crit Care Med. 2018;197:337–47.CrossRefGoogle ScholarPubMed
McAteer, H, Cosh, E, Freeman, G, Pandit, A, Wood, P, Lilford, R. Cost-effectiveness analysis at the development phase of a potential health technology: Examples based on tissue engineering of bladder and urethra. J Tissue Eng Regen Med. 2007;1:343–49.10.1002/term.36CrossRefGoogle Scholar
Bouchie, A. Tissue engineering firms go under. Nat Biotechnol. 2002;20:1178–79.CrossRefGoogle ScholarPubMed
Angunawela, RI, Mehta, JS, Daniels, JT. Ex-vivo ocular surface stem cell therapies: Current techniques, applications, hurdles and future directions. Expert Rev Mol Med. 2013;15:e4.CrossRefGoogle ScholarPubMed
Staton, T. Docs blame reimbursement, complexity, cost-benefit for Provenge uptake. FirecePharma, 2011. Accessed: Nov. 28, 2016. Available from http://www.fiercepharma.com/pharma/docs-blame-reimbursement-complexity-cost-benefit-for-provenge-uptakeGoogle Scholar
NICE. NICE issues final guidance on azitinib (Inlyta) and sipuleucel-T (Provenge). 2015. Accessed: Nov. 28, 2016. Available from https://www.firstwordpharma.com/node/1265415?tsid=17Google Scholar
Girling, A, Lilford, R, Cole, A, Young, T. Headroom approach to device development: Current and future directions. Int J Technol Assess Health Care. 2015;31:331–8.CrossRefGoogle ScholarPubMed
Vallejo-Torres, L, García-Lorenzo, B, Castilla, I, Valcárcel-Nazco, C, García-Pérez, L, Linertová, R et al. On the estimation of the cost-effectiveness threshold: Why, what, how? Value Health. 2016;19:558–66.CrossRefGoogle ScholarPubMed
Husak, L, Marcuzzi, A, Herring, J, Wen, E, Capan, DD, Cernat, G. National analysis of sepsis hospitalizations and factors contributing to sepsis in-hospital mortality in Canada. Healthc Q. 2010;13(Sp):35–41.CrossRefGoogle ScholarPubMed
The Ottawa Hospital, The Ottawa Hospital Data Warehouse.Google Scholar
Dick, A, Hangsheng, L, Zwanziger, J, Perencevich, E, Yoko Furuya, E, Larson, E et al. Long-term survival and healthcare utilization outcomes attributable to sepsis and pneumonia. BMC Health Serv Res. 2012;12:432.CrossRefGoogle ScholarPubMed
Dellinger, RP, Levy, MM, Carlet, JM, Bion, J, Parker, MM, Jaeschke, R et al. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock. Intensive Care Med. 2013;39:165–228.CrossRefGoogle ScholarPubMed
Cheung, AM, Tansey, CM, Tomlinson, G, Diaz-Granados, N, Matté, A, Barr, A et al. Two-year outcomes, health care use, and costs of survivors of acute respiratory distress syndrome. Am J Respir Crit Care Med. 2006;174:538–44.CrossRefGoogle ScholarPubMed
Cuthbertson, BH, Roughton, S, Jenkinson, D, Maclennan, G, Vale, L. Quality of life in the five years after intensive care: A cohort study. Crit Care. 2010; 14: R6. PMC. Web.CrossRefGoogle ScholarPubMed
Whittaker, SA, Fuchs, BD, Gaieski, DF, Christie, JD, Goyal, M, Meyer, NJ et al. Epidemiology and outcomes in patients with severe sepsis admitted to the hospital wards. J Crit Care. 2015;30:78–84.CrossRefGoogle ScholarPubMed
Jones, TK, Fuchs, BD, Small, DS, Halpern, SD, Hanish, A, Umscheid, CA et al. Post-acute care use and hospital readmission after sepsis. Ann Am Thorac Soc. 2015;12:904–13.CrossRefGoogle ScholarPubMed
Chao, P-W, Shih, C-J, Lee, Y-J, Tseng, C-M, Kuo, S-C, Shih, Y-N et al. Association of postdischarge rehabilitation with mortality in intensive care unit survivors of sepsis. Am J Respir Crit Care Med. 2014;190:1003–11.CrossRefGoogle ScholarPubMed
Lee, H et al. (2002) A cost-effectiveness analysis of recombinant human activated protein C for severe sepsis in the intensive care unit. Institute of Health Economics, Working Paper 02–06.Google Scholar
Statistics Canada Mortality: Overview, 2014 and 2015; age-specific mortality rates per 1,000 population by age group and sex, Canada, provinces and territories, 2015”Google Scholar
Farrah, K, McIntyre, L, Coyle, D, Talarico, R, Thavorn, K. The long-term burden of sepsis: Attributable mortality and healthcare costs. Poster Presentation at the 2019 CADTH Symposium. Edmonton, Alberta, April 14 to 16, 2019.Google Scholar
CADTH. Guidelines for the economic evaluation of health technologies. 4th ed. Ottawa, Canada: Canadian Agency for Drugs and Health Technologies in Health; 2017.Google Scholar
Briggs, A, Claxton, K, Sculpher, M. Decision modelling for health economic evaluation. Oxford: Oxford University Press; 2006.Google Scholar
Linder, A, Guh, D, Boyd, JH, Walley, KR, Anis, AH, Russell, JA et al. Long-term (10-year) mortality of younger previously healthy patients with severe sepsis/septic shock is worse than that of patients with nonseptic critical illness and of the general population. Crit Care Med. 2014;42(10):2211–8.CrossRefGoogle ScholarPubMed
Canadian Institute for Health Information. In focus: A national look at sepsis. Ottawa, Ont.: CIHI; 2009.Google Scholar
Fan, M, Huang, Y, Chen, Z, Xia, Y, Chen, A, Lu, D et al. Efficacy of mesenchymal stem cell therapy in systolic heart failure: A systematic review and meta-analysis [published correction appears in Stem Cell Res Ther. 2019 Jul 15;10(1):206]. Stem Cell Res Ther. 2019;10:150. Published 2019 May 31.CrossRefGoogle Scholar
Shankar-Hari, M, Harrison, DA, Rubenfeld, GD, Rowan, K. Epidemiology of sepsis and septic shock in critical care units: Comparison between sepsis-2 and sepsis-3 populations using a national critical care database. Br J Anaesth. 2017;119:626–36.CrossRefGoogle ScholarPubMed
Mouncey, PR, Osborn, TM, Power, GS, Harrison, DA, Sadique, MZ, Grieve, RD et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372:1301–11.CrossRefGoogle ScholarPubMed
Cox, CE, Carson, SS, Lindquist, JH, Olsen, MK, Govert, JA, Chelluri, L et al. Differences in one-year health outcomes and resource utilization by definition of prolonged mechanical ventilation: A prospective cohort study. Crit Care. 2007;11:R9.CrossRefGoogle ScholarPubMed
Supplementary material: Image

Thavorn et al. supplementary material

Thavorn et al. supplementary material 1

Download Thavorn et al. supplementary material(Image)
Image 37.5 KB
Supplementary material: Image

Thavorn et al. supplementary material

Thavorn et al. supplementary material 2

Download Thavorn et al. supplementary material(Image)
Image 35.4 KB
Supplementary material: Image

Thavorn et al. supplementary material

Thavorn et al. supplementary material 3

Download Thavorn et al. supplementary material(Image)
Image 46.2 KB
Supplementary material: Image

Thavorn et al. supplementary material

Thavorn et al. supplementary material 4

Download Thavorn et al. supplementary material(Image)
Image 29.9 KB