AMEND study protocol: a case-control study to assess the long-term impact of invasive meningococcal disease in Australian adolescents and young adults

Helen Marshall, Mark McMillan, Bing Wang, Robert Booy, Hossein Afzali, Jim Buttery, Christopher C Blyth, Peter Richmond, David Shaw, David Gordon, Belinda Barton, Helen Marshall, Mark McMillan, Bing Wang, Robert Booy, Hossein Afzali, Jim Buttery, Christopher C Blyth, Peter Richmond, David Shaw, David Gordon, Belinda Barton

Abstract

Introduction: Invasive meningococcal disease (IMD) primarily causes disease in young children and adolescents and can cause long-term disability. Many countries are considering implementation of meningococcal B and/or meningococcal ACWY vaccines to control meningococcal disease. Estimating the cost-effectiveness of meningococcal vaccine programme is hampered due to a lack of good quality costing and burden of disease data. This study aims to address this evidence gap by assessing the clinical, physical, neurocognitive, economic and societal impact of IMD on adolescents and young adults.

Methods and analysis: A case-control study of 64 participants with confirmed IMD (15-24 years 11 months at time of disease) and 64 control participants (17-34 years 11 months) will be conducted in Australia from 2016 to 2020. All participants will undergo a neurocognitive assessment, full medical examination, pure tone audiometry assessment and complete quality of life and behavioural questionnaires. Meningococcal cases will be assessed 2-10 years posthospitalisation and a subset of cases will be interviewed to explore in depth their experiences of IMD and its impact on their life. Primary outcome measures include general intellectual functioning from the Wechsler Adult Intelligence Scale and overall quality of life from the Health Utilities Index. Secondary outcome measures include academic achievement, executive functioning, behaviour, hearing, psychological and physical functioning. Outcome measures will be compared between cases and controls using independent t-tests or ORs, or if any significant confounders are identified, adjusted analyses (analysis of covariance or adjusted ORs) will be conducted. Thematic analysis will be used to analyse transcribed interviews and a costing model will be used to project lifetime costs.

Ethics and dissemination: The Adolescent MENingococcal Disease (AMEND) study has been approved by the Human Research Ethics Committee of the Women's and Children's Health Network (HREC/14/WCHN/024). The results will be disseminated via peer-reviewed publications, conference presentations, study participants, and meningococcal and meningitis foundations.

Trial registration number: NCT03798574.

Keywords: adolescents; health economics; immunisation programs; meningococcal disease; neurocognitive; sequelae; young adults.

Conflict of interest statement

Competing interests: HM is supported by an NHMRC CDF APP1084951 and is a member of the Australian Technical Advisory Group on Immunisation, Australian Government. HM is an investigator on vaccine trials sponsored by Industry (GSK, Novavax, Pfizer). HM and MM’s institution receives funding for investigator-led studies from Industry (Pfizer, GSK). HM and MM receive no personal payments from Industry. CCB is supported by an NHMRC CDF APP1111596 and is a member of the Australian Technical Advisory Group on Immunisation, Australian Government. PR is an investigator on vaccine trials sponsored by Industry (GSK, Novavax, Pfizer). PR’s institution receives funding for investigator-led studies from Industry (Pfizer, GSK, CSL). PR has been a member of scientific vaccine advisory boards for Industry (Pfizer, GSK, Sanofi) but has not received any personal payments from Industry. DG has received research funding support from Sanofi-Pasteur for an unrelated study and has been an investigator on non-meningococcal vaccine studies sponsored by Industry (Sanofi-Pasteur). RB has received funding from Baxter, CSL/Seqirus, GSK, Merck, Novartis, Pfizer, Roche, Romark and Sanofi Pasteur for the conduct of sponsored research, travel to present at conferences or consultancy work; all funding received is directed to research accounts at The Children’s Hospital at Westmead. HA is a member of the Australian Evaluation Sub-Committee (ESC) of the Medical Services Advisory Committee (MSAC).

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure1
Figure1
Adolescent MENingococcal Disease (AMEND) study recruitment flow chart. IMD, invasive meningococcal disease.

References

    1. Hart CA, Thomson APJ. Meningococcal disease and its management in children. BMJ 2006;333:685–90. 10.1136/
    1. Chang Q, Tzeng Y-L, Stephens DS. Meningococcal disease: changes in epidemiology and prevention. Clin Epidemiol 2012;4:237–45. 10.2147/CLEP.S28410
    1. Jafri RZ, Ali A, Messonnier NE, et al. . Global epidemiology of invasive meningococcal disease. Popul Health Metr 2013;11:17 10.1186/1478-7954-11-17
    1. Baker CJ. Prevention of meningococcal infection in the United States: current recommendations and future considerations. J Adolesc Health 2016;59:S29–37. 10.1016/j.jadohealth.2016.03.040
    1. Edmond K, Clark A, Korczak VS, et al. . Global and regional risk of disabling sequelae from bacterial meningitis: a systematic review and meta-analysis. Lancet Infect Dis 2010;10:317–28. 10.1016/S1473-3099(10)70048-7
    1. Borg J, Christie D, Coen PG, et al. . Outcomes of meningococcal disease in adolescence: prospective, matched-cohort study. Pediatrics 2009;123:e502–9. 10.1542/peds.2008-0581
    1. Viner RM, Booy R, Johnson H, et al. . Outcomes of invasive meningococcal serogroup B disease in children and adolescents (MOSAIC): a case-control study. Lancet Neurology 2012;11:774–83. 10.1016/S1474-4422(12)70180-1
    1. Lahra M, Enriquez R. Australian meningococcal surveillance programme annual report, 2014, 2016. Available: [Accessed 16 Aug 2016].
    1. Davis KL, Bell TJ, Miller JM, et al. . Hospital costs, length of stay and mortality associated with childhood, adolescent and young adult meningococcal disease in the US. Appl Health Econ Health Policy 2011;9:197–207. 10.2165/11587330-000000000-00000
    1. Pelton SI. The global evolution of meningococcal epidemiology following the introduction of meningococcal vaccines. J Adolesc Health 2016;59:S3–11. 10.1016/j.jadohealth.2016.04.012
    1. Patton GC, Sawyer SM, Santelli JS, et al. . Our future: a Lancet commission on adolescent health and wellbeing. Lancet 2016;387:2423–78. 10.1016/S0140-6736(16)00579-1
    1. Keshavan MS, Giedd J, Lau JYF, et al. . Changes in the adolescent brain and the pathophysiology of psychotic disorders. Lancet Psychiatry 2014;1:549–58. 10.1016/S2215-0366(14)00081-9
    1. Spear LP. The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev 2000;24:417–63. 10.1016/S0149-7634(00)00014-2
    1. Sander J, Bay D, Gedde-Dahl TW, et al. . Late sequelae after meningococcal disease. A controlled study in young men. NIPH Ann 1984;7:3–11.
    1. Wang B, Santoreneos R, Afzali H, et al. . Costs of invasive meningococcal disease: a global systematic review. Pharmacoeconomics 2018;36:1201–22. 10.1007/s40273-018-0679-5
    1. Borrow R, Alarcón P, Carlos J, et al. . The global meningococcal initiative: global epidemiology, the impact of vaccines on meningococcal disease and the importance of herd protection. Expert Rev Vaccines 2017;16:313–28. 10.1080/14760584.2017.1258308
    1. Jit M, Hutubessy R. Methodological challenges to economic evaluations of vaccines: is a common approach still possible? Appl Health Econ Health Policy 2016;14:245–52. 10.1007/s40258-016-0224-7
    1. Joint Committee on Vaccination and Immunisation (JCVI) JCVI interim position statement on use of Bexsero® meningococcal B vaccine in the UK 2013. Vol 2018 UK: Department of Health and Social Care, 2013.
    1. Getsios D, Caro I, El-Hadi W, et al. . Assessing the economics of vaccination for Neisseria meningitidis in industrialized nations: a review and recommendations for further research. Int J Technol Assess Health Care 2004;20:280–8. 10.1017/S0266462304001096
    1. European Centre for Disease Prevention and Control Expert opinion on the introduction of the meningococcal B (4CMenB) vaccine in the EU/EEA. Stockholm: ECDC, 2017.
    1. Ladhani SN, Ramsay M, Borrow R, et al. . Enter B and W: two new meningococcal vaccine programmes launched. Arch Dis Child 2016;101:91–5. 10.1136/archdischild-2015-308928
    1. Australian Technical Advisory Group on Immunisation National immunisation program schedule. Vol 2019 10th edn Canberra: Australian Government Department of Health, 2018.
    1. Pharmaceutical Benefits Advisory Committee Meningococcal polysaccharide conjugate vaccine serogroups A, C, W-135 and Y(adolescents): Pre-filled syringe, 0.5mL; Nimenrix® Pharmaceutical Benefits Scheme. Canberra: Department of Health, Australian Government, 2018.
    1. Larg A, Moss JR. Cost-of-illness studies: a guide to critical evaluation. Pharmacoeconomics 2011;29:653–71. 10.2165/11588380-000000000-00000
    1. Byford S, Torgerson DJ, Raftery J. Economic note: cost of illness studies. BMJ 2000;320:1335 10.1136/bmj.320.7245.1335
    1. Durand-Zaleski I. Why cost-of-illness studies are important and inform policy. Vasc Med 2008;13:251–3. 10.1177/1358863X08091738
    1. Chisholm D, Saxena S, Van Ommeren M. Dollars, DALYs and decisions: economic aspects of the mental health system. Geneva: World Health Organization, 2006.
    1. International statistical classification of diseases and related health problems. 10th edn Geneva: World Health Organisation, 2018.
    1. The SAGE encyclopedia of social science research methods. Thousand Oaks, California: Sage Publications, Inc, 2004.
    1. Wechsler D. Wechsler adult intelligence Scale-4th edition (WAIS-IV) Australian and New Zealand adaptation. Sydney, NSW: Pearson, 2008.
    1. Furlong WJ, Feeny DH, Torrance GW. Health utilities index® mark 2 and mark 3 (hui2/3) 15-item questionnaire for Self-administered, self-assessed "four week" health status assessment. Dundas ON Canada: Health Utilities Inc, 2016.
    1. Kennedy ITR, van Hoek AJ, Ribeiro S, et al. . Short-term changes in the health state of children with group B meningococcal disease: a prospective, national cohort study. PLoS One 2017;12:e0177082 10.1371/journal.pone.0177082
    1. Buysse CMP, Raat H, Hazelzet JA, et al. . Long-term health status in childhood survivors of meningococcal septic shock. Arch Pediatr Adolesc Med 2008;162:1036–41. 10.1001/archpedi.162.11.1036
    1. Kostanjsek N. Use of the International classification of functioning, disability and health (ICF) as a conceptual framework and common language for disability statistics and health information systems. BMC Public Health 2011;11:S3 10.1186/1471-2458-11-S4-S3
    1. Mathers C, Smith A, Concha M. Global burden of hearing loss in the year 2000. Global burden of Disease 2000;18:1–30.
    1. Al-Janabi H, Manca A, Coast J. Predicting carer health effects for use in economic evaluation. PLoS One 2017;12:e0184886 10.1371/journal.pone.0184886
    1. Al-Janabi H, Van Exel J, Brouwer W, et al. . Measuring health Spillovers for economic evaluation: a case study in meningitis. Health Econ 2016;25:1529–44. 10.1002/hec.3259
    1. Erickson LJ, De Wals P, McMahon J, et al. . Complications of meningococcal disease in college students. Clin Infect Dis 2001;33:737–9. 10.1086/322587
    1. Koomen I, Grobbee DE, Jennekens-Schinkel A, et al. . Parental perception of educational, behavioural and general health problems in school-age survivors of bacterial meningitis. Acta Paediatr 2003;92:177–85. 10.1111/j.1651-2227.2003.tb00523.x
    1. Oostenbrink R, A Moll HA, Essink-Bot M-L. The EQ-5D and the health Utilities index for permanent sequelae after meningitis: a head-to-head comparison. J Clin Epidemiol 2002;55:791–9. 10.1016/S0895-4356(02)00448-1
    1. Statistical Local Area Table 2: socio-economic indexes for areas (SEIFA), data cube: Excel spreadsheet, cat. No. 2033.0.55.001, 2011. Available: [Accessed 21 Sep 2017].
    1. Pharmaceutical benefits scheme. Available: [Accessed 10 Nov 2019].
    1. Faul F, Erdfelder E, Buchner A, et al. . Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods 2009;41:1149–60. 10.3758/BRM.41.4.1149
    1. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B 1995;57:289–300. 10.1111/j.2517-6161.1995.tb02031.x
    1. Murray CJ, Lopez AD, Organization WH. The global burden of disease: a comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020: summary 1996.
    1. Pharmaceutical Benefits Advisory Committee Guidelines for preparing submissions to the pharmaceutical benefits Advisory Committee (version 5.0). Vol 2018 Canberra: Australian Government Department of Health and Ageing, 2016.
    1. Frick KD. Microcosting quantity data collection methods. Med Care 2009;47:S76–81. 10.1097/MLR.0b013e31819bc064
    1. Collins J, Alona I, Tooher R, et al. . Increased awareness and health care provider endorsement is required to encourage pregnant women to be vaccinated. Hum Vaccin Immunother 2014;10:2922–9. 10.4161/21645515.2014.971606
    1. Tariq S, Woodman J. Using mixed methods in health research. JRSM Short Rep 2013;4:2042533313479197 10.1177/2042533313479197
    1. Pharmaceutical Benefits Advisory Committee Multicomponent Meningococcal Group B Vaccine, 0.5mL, injection, prefilled syringe, Bexsero® - November 2013. Vol 2018 Canberra, Australia: Pharmaceutical Benefits Scheme, 2013.
    1. Pharmaceutical Benefits Advisory Committee Multicomponent Meningococcal Group B Vaccine, 0.5mL, injection, prefilled syringe, Bexsero® - July 2014. Vol 2018 Canberra, Australia: Australian Government Department of Health, 2014.
    1. Pharmaceutical Benefits Advisory Committee Multicomponent Meningococcal Group B Vaccine (4CmenB); 0.5 mL suspension for injection pre-filled syringe; Bexsero® - July 2015. Vol 2018 Canberra, Australia: Pharmaceutical Benefits Scheme, 2015.
    1. Wechsler D. Wechsler Individual Achievement Test- Second Edition (WIAT-II). London, UK: Psychological Corporation, 2005.
    1. Delis D, Kaplan E C, Kramer JH. Delis-Kaplan Executive Function System. San Antonio, TX: The Psychological Corporation, 2001.
    1. Gioia G, Isquith P, Guy S, et al. . Behavior Rating Inventory of Executive Function (BRIEF). Lutz, Florida: Psychological Assessment Resources, 2000.
    1. Sheslow D, Adams W. Wide Range Assessment of Memory and Learning Second Edition (WRAML2). Bloomington: Pearson, 2003.
    1. Sheehan DV, Lecrubier Y, Sheehan KH, et al. . The Mini-International neuropsychiatric interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59:22–33. quiz 34-57.
    1. Psychology Foundation of Australia Depression anxiety stress scales (DASS). Psychology Department, UNSW: UNSW, 2014.
    1. Conners KED, Sparrow E. Conners 3rd edition (Conners) manual. Canada: Multi-Health Systems Inc, 2009.
    1. Conners KED, Sparrow E. Conners’ Adult ADHD Rating Scales. Canada: Multi-Health Systems Inc, 2002.
    1. Al-Janabi H, Peters TJ, Brazier J, et al. . An investigation of the construct validity of the ICECAP-A capability measure. Qual Life Res 2013;22:1831–40. 10.1007/s11136-012-0293-5
    1. Al-Janabi H, Flynn TN, Coast J. Estimation of a preference-based carer experience scale. Med Decis Making 2011;31:458–68. 10.1177/0272989X10381280
    1. EQ-5D-5L Health Questionnaire English version for Australia. Netherlands: EuroQol Group EQ-5D, 2009.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다