Family Spillover Effects in Pediatric Cost-Utility Analyses

  • Tara A. LavelleEmail author
  • Brittany N. D’Cruz
  • Babak Mohit
  • Wendy J. Ungar
  • Lisa A. Prosser
  • Kate Tsiplova
  • Montserrat Vera-Llonch
  • Pei-Jung Lin
Original Research Article



Childhood illness can impose significant costs and health strains on family members, but these are not routinely captured by pediatric economic evaluations. This review investigated how family “spillover effects” related to costs and health outcomes are considered in pediatric cost-utility analyses (CUAs).


We reviewed pediatric CUAs published between 2000 and 2015 using the Tufts Medical Center Cost-effectiveness Analysis (CEA) Registry and the Pediatric Economic Database Evaluation (PEDE) Registry. We selected studies conducted from the societal perspective and included in both registries. We investigated how frequently family spillover was incorporated into analyses, and how the inclusion of spillover health effects and costs changed CUA results.


We found 142 pediatric CUAs meeting inclusion criteria. Of those, 105 (72%) considered either family spillover costs (n = 98 time costs, n = 33 out-of-pocket costs, n = 2 caregiver healthcare costs) or health outcomes (n = 15). Twenty-four studies included 43 pairs of incremental cost-effectiveness ratios (ICERs) with and without spillover. In 19 pairs of ICERs, adding spillover changed the ICER enough to cross a common cost-effectiveness threshold (i.e., $50,000/QALY, $100,000/QALY, $150,000/QALY; values are in 2016 US$). Incorporating spillover generally made interventions more cost-effective (n = 18; 42%), or did not change CUA results enough to cross a threshold (n = 24; 56%). Including family spillover reduced ICERs by 31% ($40,000/QALY) on average.


Most pediatric CUAs conducted from a societal perspective include family costs but fewer include family health effects. Inclusion of family spillover effects tends to make CUA results more favorable. Future pediatric CUAs should aim to more fully incorporate the family burden of illness.



We would like to acknowledge Ashley Leech, PhD for her comments during the literature review process, and Peter Neumann, ScD for his comments on the manuscript.

Author Contributions

Study concept and design: Lavelle, Lin, D’Cruz, Prosser, Ungar, Mohit, Vera-Llonch; data acquisition: Tsiplova, Lin, D’Cruz, and Lavelle; drafting publication: Lavelle, Lin, D’Cruz; all authors participated in analysis or interpretation of data as well as preparation and critical revision of the manuscript.

Compliance with Ethical Standards


This study was supported by research funding from Shire Pharmaceuticals to Tufts Medical Center.

Conflict of interest

Montserrat Vera-Llonch is an employee of Shire and owns stock/options. Tara Lavelle, Brittany D’Cruz, and Pei-Jung Lin were funded by a grant from Shire during this work. Wendy Ungar reports receiving a consulting fee from Tufts Medical Center for her contribution to this work. Babak Mohit reports receiving funds from Bayer to support his post-doctoral fellowship. Pei-Jung Lin reports personal fees from Avanir and Otsuka, outside of the scope of this work. Lisa Prosser and Kate Tsiplova report no conflicts of interest.

Supplementary material

40258_2018_436_MOESM1_ESM.docx (976 kb)
Supplementary material 1 (DOCX 975 kb)
40258_2018_436_MOESM2_ESM.xlsx (42 kb)
Supplementary material 2 (XLSX 42 kb)


  1. 1.
    Gold MR, Siegel JE, Russell LB, Weinstein MC. Cost-effectiveness in health and medicine. Oxford: Oxford University Press; 1996.Google Scholar
  2. 2.
    Neumann PJ, Sanders GD, Russell LB, Siegel JE, Ganiats TG. Cost-effectiveness in health and medicine. Oxford: Oxford University Press; 2016.CrossRefGoogle Scholar
  3. 3.
    Guidelines for the Economic Evaluation of Health Technologies: Canadian Agency for Drugs and Technologies in Health. 2017.Google Scholar
  4. 4.
    National Institute for Health and Care Excellence (NICE). Guide to the methods of technology appraisal. London: National Institute for Health and Care Excellence; 2013.Google Scholar
  5. 5.
    NHS Scotland-Scottish Medicines Consortium. Guidance to manufacturers for completion of new product assessment form 2007. Accessed 22 Apr 2018.
  6. 6.
    Zorginstituut Nederland. Guideline for the Conduct of Economic Evaluations in Health Care. 2016. Accessed 22 Apr 2018.
  7. 7.
    Krol M, Papenburg J, van Exel J. Does including informal care in economic evaluations matter? A systematic review of inclusion and impact of informal care in cost-effectiveness studies. Pharmacoeconomics. 2015;33(2):123–35.CrossRefGoogle Scholar
  8. 8.
    Basu A, Meltzer D. Implications of spillover effects within the family for medical cost-effectiveness analysis. J Health Econ. 2005;24(4):751–73.CrossRefGoogle Scholar
  9. 9.
    Brouwer WBF, van Exel Job, Mick TJ. Incorporating caregiver and family effects in economic evaluations of child health. In: Ungar W, editor. Economic evaluation in child health. Toronto: Oxford Scholarship Online; 2010.Google Scholar
  10. 10.
    Lavelle TA, Wittenberg E, Lamarand K, Prosser LA. Variation in the spillover effects of illness on parents, spouses, and children of the chronically ill. Appl Health Econ Health Policy. 2014;12(2):117–24.CrossRefGoogle Scholar
  11. 11.
    van Oers HA, Haverman L, Limperg PF, van Dijk-Lokkart EM, Maurice-Stam H, Grootenhuis MA. Anxiety and depression in mothers and fathers of a chronically ill child. Matern Child Health J. 2014;18(8):1993–2002.CrossRefGoogle Scholar
  12. 12.
    Wittenberg E, Ritter GA, Prosser LA. Evidence of spillover of illness among household members: EQ-5D scores from a US sample. Med Decis Making. 2013;33(2):235–43.CrossRefGoogle Scholar
  13. 13.
    Winthrop AL, Brasel KJ, Stahovic L, Paulson J, Schneeberger B, Kuhn EM. Quality of life and functional outcome after pediatric trauma. J Trauma. 2005;58(3):468–73.CrossRefGoogle Scholar
  14. 14.
    Ortega-Sanchez IR, Molinari NA, Fairbrother G, Szilagyi PG, Edwards KM, Griffin MR, et al. Indirect, out-of-pocket and medical costs from influenza-related illness in young children. Vaccine. 2012;30(28):4175–81.CrossRefGoogle Scholar
  15. 15.
    Brouwer WB, van Exel NJ, van den Berg B, van den Bos GA, Koopmanschap MA. Process utility from providing informal care: the benefit of caring. Health Policy. 2005;74(1):85–99.CrossRefGoogle Scholar
  16. 16.
    Wittenberg E, Saada A, Prosser LA. How illness affects family members: a qualitative interview survey. Patient Patient Center Outcomes Res. 2013;6(4):257–68.CrossRefGoogle Scholar
  17. 17.
    Goodrich K, Kaambwa B, Al-Janabi H. The inclusion of informal care in applied economic evaluation: a review. Value Health. 2012;15(6):975–81.CrossRefGoogle Scholar
  18. 18.
    Thorat T, Cangelosi M, Neumann PJ. Skills of the trade: the Tufts Cost-Effectiveness Analysis (CEA) Registry. J Benefit Cost Anal. 2012;3:1–9.CrossRefGoogle Scholar
  19. 19.
    Ungar WJ. The Pediatric Economic Database Evaluation (PEDE) project. 2015. Accessed 22 Apr 2018.
  20. 20.
    Ungar WJ, Santos MT. The Pediatric Economic Database Evaluation (PEDE) Project: establishing a database to study trends in pediatric economic evaluation. Med Care. 2003;41(10):1142–52.CrossRefGoogle Scholar
  21. 21.
    Neumann PJ, Greenberg D, Olchanski NV, Stone PW, Rosen AB. Growth and quality of the cost-utility literature, 1976-2001. Value Health. 2005;8(1):3–9.CrossRefGoogle Scholar
  22. 22.
    Neumann PJ, Thorat T, Shi J, Saret CJ, Cohen JT. The changing face of the cost-utility literature, 1990-2012. Value Health. 2015;18(2):271–7.CrossRefGoogle Scholar
  23. 23.
    Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inf. 2009;42(2):377–81.CrossRefGoogle Scholar
  24. 24.
    Neumann PJ, Cohen JT, Weinstein MC. Updating cost-effectiveness–the curious resilience of the $50,000-per-QALY threshold. N Engl J Med. 2014;371(9):796–7.CrossRefGoogle Scholar
  25. 25.
    van der Schans J, Kotsopoulos N, Hoekstra PJ, Hak E, Postma MJ. Cost-effectiveness of extended-release methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder sub-optimally treated with immediate release methylphenidate. PLoS One. 2015;10(5):e0127237.CrossRefGoogle Scholar
  26. 26.
    Schawo S, van der Kolk A, Bouwmans C, Annemans L, Postma M, Buitelaar J, et al. Probabilistic markov model estimating cost effectiveness of methylphenidate osmotic-release oral system versus immediate-release methylphenidate in children and adolescents: which information is needed? Pharmacoeconomics. 2015;33(5):489–509.CrossRefGoogle Scholar
  27. 27.
    Al Awaidy ST, Gebremeskel BG, Al Obeidani I, Al Baqlani S, Haddadin W, O’Brien MA. Cost effectiveness of a pentavalent rotavirus vaccine in Oman. BMC Infect Dis. 2014;17(14):334.CrossRefGoogle Scholar
  28. 28.
    Bilcke J, Van Damme P, Beutels P. Cost-effectiveness of rotavirus vaccination: exploring caregiver(s) and “no medical care’’ disease impact in Belgium. Med Decis Making. 2009;29(1):33–50.CrossRefGoogle Scholar
  29. 29.
    Coyle D, Coyle K, Bettinger JA, Halperin SA, Vaudry W, Scheifele DW, et al. Cost effectiveness of infant vaccination for rotavirus in Canada. Can J Infect Dis Med Microbiol. 2012;23(2):71–7.CrossRefGoogle Scholar
  30. 30.
    Goossens LM, Standaert B, Hartwig N, Hovels AM, Al MJ. The cost-utility of rotavirus vaccination with Rotarix (RIX4414) in the Netherlands. Vaccine. 2008;26(8):1118–27.CrossRefGoogle Scholar
  31. 31.
    Imaz I, Rubio B, Cornejo AM, Gonzalez-Enriquez J. Budget impact and cost-utility analysis of universal infant rotavirus vaccination in Spain. Prev Med. 2014;61:116–21.CrossRefGoogle Scholar
  32. 32.
    Itzler R, O’Brien MA, Yamabe K, Abe M, Dhankhar P. Cost-effectiveness of a pentavalent rotavirus vaccine in Japan. J Med Econ. 2013;16(10):1216–27.CrossRefGoogle Scholar
  33. 33.
    Martin A, Batty A, Roberts JA, Standaert B. Cost-effectiveness of infant vaccination with RIX4414 (Rotarix) in the UK. Vaccine. 2009;27(33):4520–8.CrossRefGoogle Scholar
  34. 34.
    Perez-Rubio A, Luquero FJ, Eiros Bouza JM, Castrodeza Sanz JJ, Bachiller Luque MR, de Lejarazu RO, et al. Socio-economic modelling of rotavirus vaccination in Castilla y Leon, Spain. Infez Med. 2011;19(3):166–75.PubMedGoogle Scholar
  35. 35.
    Rozenbaum MH, Mangen MJ, Giaquinto C, Wilschut JC, Hak E, Postma MJ, et al. Cost-effectiveness of rotavirus vaccination in the Netherlands; the results of a consensus model. BMC Public Health. 2011;10(11):462.CrossRefGoogle Scholar
  36. 36.
    Sato T, Nakagomi T, Nakagomi O. Cost-effectiveness analysis of a universal rotavirus immunization program in Japan. Jpn J Infect Dis. 2011;64(4):277–83.PubMedGoogle Scholar
  37. 37.
    Shim E, Galvani AP. Impact of transmission dynamics on the cost-effectiveness of rotavirus vaccination. Vaccine. 2009;27(30):4025–30.CrossRefGoogle Scholar
  38. 38.
    Suwantika AA, Tu HA, Postma MJ. Cost-effectiveness of rotavirus immunization in Indonesia: taking breastfeeding patterns into account. Vaccine. 2013;31(32):3300–7.CrossRefGoogle Scholar
  39. 39.
    Al-Janabi H, Van Exel J, Brouwer W, Trotter C, Glennie L, Hannigan L, et al. measuring health spillovers for economic evaluation: a case study in meningitis. Health Econ. 2016;25(12):1529–44.CrossRefGoogle Scholar
  40. 40.
    Brooks R. EuroQol: the current state of play. Health Policy. 1996;37(1):53–72.CrossRefGoogle Scholar
  41. 41.
    Khanna R, Jariwala K, Bentley JP. Psychometric properties of the EuroQol Five Dimensional Questionnaire (EQ-5D-3L) in caregivers of autistic children. Qual Life Res. 2013;22(10):2909–20.CrossRefGoogle Scholar
  42. 42.
    Bhadhuri A, Jowett S, Jolly K, Al-Janabi H. A comparison of the validity and responsiveness of the EQ-5D-5L and SF-6D for measuring health spillovers: a study of the family impact of meningitis. Med Decis Making. 2017;37(8):882–93.CrossRefGoogle Scholar
  43. 43.
    EuroQol Group. EuroQol–a new facility for the measurement of health-related quality of life. Health Policy. 1990;16(3):199–208.CrossRefGoogle Scholar
  44. 44.
    Brouwer WB, van Exel NJ, van Gorp B, Redekop WK. The CarerQol instrument: a new instrument to measure care-related quality of life of informal caregivers for use in economic evaluations. Qual Life Res. 2006;15(6):1005–21.CrossRefGoogle Scholar
  45. 45.
    Al-Janabi H, Flynn TN, Coast J. Estimation of a preference-based carer experience scale. Med Decis Making. 2011;31(3):458–68.CrossRefGoogle Scholar
  46. 46.
    Prosser LA, Hammitt JK, Keren R. Measuring health preferences for use in cost-utility and cost-benefit analyses of interventions in children: theoretical and methodological considerations. Pharmacoeconomics. 2007;25(9):713–26.CrossRefGoogle Scholar
  47. 47.
    Petrou S. Methodological issues raised by preference-based approaches to measuring the health status of children. Health Econ. 2003;12(8):697–702.CrossRefGoogle Scholar
  48. 48.
    O’Brien MA, Prosser LA, Paradise JL, Ray GT, Kulldorff M, Kurs-Lasky M, et al. New vaccines against otitis media: projected benefits and cost-effectiveness. Pediatrics. 2009;123(6):1452–63.CrossRefGoogle Scholar
  49. 49.
    Prosser LA, Meltzer MI, Fiore A, Epperson S, Bridges CB, Hinrichsen V, et al. Effects of adverse events on the projected population benefits and cost-effectiveness of using live attenuated influenza vaccine in children aged 6 months to 4 years. Arch Pediatr Adolesc Med. 2011;165(2):112–8.CrossRefGoogle Scholar
  50. 50.
    Bobinac A, van Exel NJ, Rutten FF, Brouwer WB. Health effects in significant others: separating family and care-giving effects. Med Decis Making. 2011;31(2):292–8.CrossRefGoogle Scholar
  51. 51.
    Hoefman RJ, van Exel J, Brouwer W. How to include informal care in economic evaluations. Pharmacoeconomics. 2013;31(12):1105–19.CrossRefGoogle Scholar
  52. 52.
    Bobinac A, van Exel NJ, Rutten FF, Brouwer WB. Caring for and caring about: disentangling the caregiver effect and the family effect. J Health Econ. 2010;29(4):549–56.CrossRefGoogle Scholar
  53. 53.
    Prosser LA, Lamarand K, Gebremariam A, Wittenberg E. Measuring family HRQoL spillover effects using direct health utility assessment. Med Decis Making. 2015;35(1):81–93.CrossRefGoogle Scholar
  54. 54.
    Al-Janabi H, van Exel J, Brouwer W, Coast J. A framework for including family health spillovers in economic evaluation. Med Decis Making. 2016;36(2):176–86.CrossRefGoogle Scholar
  55. 55.
    Richardson JS. Assessing the Economic and Quality of Life Impacts of Grief and Suicide in the United States [dissertation]: The University of Michigan; 2018.Google Scholar
  56. 56.
    Fox M, Cacciatore J, Lacasse JR. Child death in the United States: productivity and the economic burden of parental grief. Death Stud. 2014;38(6–10):597–602.CrossRefGoogle Scholar
  57. 57.
    Lichtenthal WG, Corner GW, Sweeney CR, Wiener L, Roberts KE, Baser RE, et al. Mental Health services for parents who lost a child to cancer: if we build them, will they come? J Clin Oncol. 2015;33(20):2246–53.CrossRefGoogle Scholar
  58. 58.
    Ungar W. Economic evaluation in child health. Oxford: Oxford University Press; 2009.CrossRefGoogle Scholar
  59. 59.
    Lavelle TA, Weinstein MC, Newhouse JP, Munir K, Kuhlthau KA, Prosser LA. Economic burden of childhood autism spectrum disorders. Pediatrics. 2014;133(3):e520–9.CrossRefGoogle Scholar
  60. 60.
    Bos JM, Rumke H, Welte R, Postma MJ. Epidemiologic impact and cost-effectiveness of universal infant vaccination with a 7-valent conjugated pneumococcal vaccine in the Netherlands. Clin Ther. 2003;25(10):2614–30.CrossRefGoogle Scholar
  61. 61.
    Coyle D, Barbeau M. Cost effectiveness of Elidel in the management of patients with atopic dermatitis in Canada. J Cutan Med Surg. 2004;8(6):405–10.CrossRefGoogle Scholar
  62. 62.
    Barton GR, Stacey PC, Fortnum HM, Summerfield AQ. Hearing-impaired children in the United Kingdom, IV: cost-effectiveness of pediatric cochlear implantation. Ear Hear. 2006;27(5):575–88.CrossRefGoogle Scholar
  63. 63.
    Coco AS. Cost-effectiveness analysis of treatment options for acute otitis media. Ann Fam Med. 2007;5(1):29–38.CrossRefGoogle Scholar
  64. 64.
    Bergman A, Hjelmgren J, Ortqvist A, Wisloff T, Kristiansen IS, Hogberg LD, et al. Cost-effectiveness analysis of a universal vaccination programme with the 7-valent pneumococcal conjugate vaccine (PCV-7) in Sweden. Scand J Infect Dis. 2008;40(9):721–9.CrossRefGoogle Scholar
  65. 65.
    Luce BR, Nichol KL, Belshe RB, Frick KD, Li SX, Boscoe A, et al. Cost-effectiveness of live attenuated influenza vaccine versus inactivated influenza vaccine among children aged 24–59 months in the United States. Vaccine. 2008;26(23):2841–8.CrossRefGoogle Scholar
  66. 66.
    Talbird SE, Brogan AJ, Winiarski AP, Sander B. Cost-effectiveness of treating influenzalike illness with oseltamivir in the United States. Am J Health Syst Pharm. 2009;66(5):469–80.CrossRefGoogle Scholar
  67. 67.
    Tan SS, van Linschoten RL, van Middelkoop M, Koes BW, Bierma-Zeinstra SM, Koopmanschap MA. Cost-utility of exercise therapy in adolescents and young adults suffering from the patellofemoral pain syndrome. Scand J Med Sci Sports. 2010;20(4):568–79.CrossRefGoogle Scholar
  68. 68.
    Hoshi SL, Kondo M, Okubo I. Economic evaluation of vaccination programme of 13-valent pneumococcal conjugate vaccine to the birth cohort in Japan. Vaccine. 2013;31(25):2762–71.CrossRefGoogle Scholar
  69. 69.
    Shiragami M, Mizukami A, Leeuwenkamp O, et al. Cost-Effectiveness evaluation of the 10-valent pneumococcal non-typeable haemophilus influenzae protein D conjugate vaccine and 13-valent pneumococcal vaccine in Japanese children. Infect Dis Ther. 2015;4(1):93–112. Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Tara A. Lavelle
    • 1
    Email author return OK on get
  • Brittany N. D’Cruz
    • 1
  • Babak Mohit
    • 1
  • Wendy J. Ungar
    • 2
    • 3
  • Lisa A. Prosser
    • 4
  • Kate Tsiplova
    • 2
  • Montserrat Vera-Llonch
    • 5
  • Pei-Jung Lin
    • 1
  1. 1.Center for the Evaluation of Value and Risk in Health, Institute for Clinical Research and Health Policy StudiesTufts Medical CenterBostonUSA
  2. 2.Program of Child Health Evaluative SciencesThe Hospital for Sick Children Research InstituteTorontoCanada
  3. 3.Institute for Health Policy, Management and EvaluationUniversity of TorontoTorontoCanada
  4. 4.Child Health Evaluation and Research Unit, Department of PediatricsUniversity of MichiganAnn ArborUSA
  5. 5.Global Health Economics Outcomes Research and EpidemiologyLexingtonUSA

Personalised recommendations