Budget constraint and vaccine dosing: a mathematical modelling exercise

BackgroundIncreasing the number of vaccine doses may potentially improve overall efficacy. Decision-makers need information about choosing the most efficient dose schedule to maximise the total health gain of a population when operating under a constrained budget. The objective of this study is to identify the most efficient vaccine dosing schedule within a fixed vaccination budget from a healthcare payer perspective.MethodsAn optimisation model is developed in which maximizing the disease reduction is the functional objective and the constraint is the vaccination budget. The model allows variation in vaccination dosing numbers, in cost difference per dose, in vaccine coverage rate, and in vaccine efficacy. We apply the model using the monovalent rotavirus vaccine as an example.ResultsWith a fixed budget, a 2-dose schedule for vaccination against rotavirus infection with the monovalent vaccine results in a larger reduction in disease episodes than a 3-dose scheme with the same vaccine under most circumstances. A 3-dose schedule would only be better under certain conditions: a cost reduction of >26% per dose, combined with vaccine efficacy improvement of ≥5% and a target coverage rate of 75%. Substantial interaction is observed between cost reduction per dose, vaccine coverage rate, and increased vaccine efficacy. Sensitivity analysis shows that the conditions required for a 3-dose strategy to be better than a 2-dose strategy may seldom occur when the budget is fixed. The model does not consider vaccine herd effect, precise timing for additional doses, or the effect of natural immunity development.ConclusionsUnder budget constraint, optimisation modelling is a helpful tool for a decision-maker selecting the most efficient vaccination dosing schedule. The low dosing scheme could be the optimal option to consider under the many scenarios tested. The model can be applied under many different circumstances of changing dosing schemes with single or multiple vaccines.

[1]  Á. Gentile.  The need for an evidence‐based decision‐making process with regard to control of hepatitis A , 2008, Journal of viral hepatitis.

[2]  P. De Wals,et al.  Benefits and costs of immunization of children with pneumococcal conjugate vaccine in Canada. , 2003, Vaccine.

[3]  G. Krishnarajah,et al.  Rotavirus vaccine series completion and adherence to vaccination schedules among infants in managed care in the United States. , 2012, Vaccine.

[4]  三澤吉雄.  In Canada … , 1980, Current History.

[5]  John W. Glasser,et al.  Understanding Reduced Rotavirus Vaccine Efficacy in Low Socio-Economic Settings , 2012, PloS one.

[6]  S. Madhi,et al.  Efficacy and immunogenicity of two or three dose rotavirus-vaccine regimen in South African children over two consecutive rotavirus-seasons: a randomized, double-blind, placebo-controlled trial. , 2012, Vaccine.

[7]  M. Ciblak.  Influenza vaccination in Turkey: prevalence of risk groups, current vaccination status, factors influencing vaccine uptake and steps taken to increase vaccination rate. , 2013, Vaccine.

[8]  Baudouin Standaert,et al.  Can a Multi-Criteria Decision (MCD) Optimisation Model Help Decision Makers in the Optimal Selection of Vaccines When Expanding Their Universal Mass Vaccination Programme? The Case of Poland , 2013 .

[9]  M. O'Ryan,et al.  Rotarix®: vaccine performance 6 years postlicensure , 2011, Expert review of vaccines.

[10]  R. Black,et al.  International Journal of Epidemiology 2010;39:i56–i62 , 2022 .

[11]  Manish M Patel,et al.  Post-licensure experience with rotavirus vaccination in high and middle income countries; 2006 to 2011. , 2012, Current opinion in virology.

[12]  S. Madhi,et al.  Human rotavirus vaccine Rotarix™ provides protection against diverse circulating rotavirus strains in African infants: a randomized controlled trial , 2012, BMC Infectious Diseases.

[13]  Stephanie R Earnshaw,et al.  Integer/linear mathematical programming models: a tool for allocating healthcare resources. , 2003, PharmacoEconomics.

[14]  P. Kristensen,et al.  ...or in Norway , 1994, BMJ.

[15]  Manish M Patel,et al.  Remaining issues and challenges for rotavirus vaccine in preventing global childhood diarrheal morbidity and mortality , 2012, Expert review of vaccines.

[16]  G. Irimu,et al.  Factors influencing immunisation coverage in Mathare Valley, Nairobi. , 2010, East African medical journal.

[17]  Sheng-I Chen,et al.  Maintaining Vaccine Delivery Following the Introduction of the Rotavirus and Pneumococcal Vaccines in Thailand , 2011, PloS one.

[18]  Baudouin Standaert,et al.  Selecting a Mix of Prevention Strategies against Cervical Cancer for Maximum Efficiency with an Optimization Program , 2012, PharmacoEconomics.

[19]  F. Lucht,et al.  Determinants of vaccination coverage for children and teenagers. , 2011, Medecine et maladies infectieuses.

[20]  S. Madhi,et al.  Effect of human rotavirus vaccine on severe diarrhea in African infants. , 2010, The New England journal of medicine.

[21]  M. Levine,et al.  Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in Asia: a randomised, double-blind, placebo-controlled trial , 2010, The Lancet.

[22]  K. Neuzil,et al.  Efficacy of human rotavirus vaccine against severe gastroenteritis in Malawian children in the first two years of life: a randomized, double-blind, placebo controlled trial. , 2012, Vaccine.

[23]  M. Santosham.  Rotavirus vaccine--a powerful tool to combat deaths from diarrhea. , 2010, The New England journal of medicine.

[24]  B. Robberstad,et al.  Economic evaluation of second generation pneumococcal conjugate vaccines in Norway. , 2011, Vaccine.

[25]  T. Cherian,et al.  Rotavirus vaccines in developing countries: the potential impact, implementation challenges, and remaining questions. , 2012, Vaccine.

[26]  F. Binka,et al.  Immunogenicity of the pentavalent rotavirus vaccine in African infants. , 2012, Vaccine.

[27]  M. Postma,et al.  Impact of Rotavirus Vaccination on Hospitalisations in Belgium: Comparing Model Predictions with Observed Data , 2013, PloS one.

[28]  Shawn T. Brown,et al.  The impact of making vaccines thermostable in Niger's vaccine supply chain. , 2012, Vaccine.

[29]  Meeting of the immunization Strategic Advisory Group of Experts, April 2009--conclusions and recommendations. , 2009, Releve epidemiologique hebdomadaire.

[30]  T. Vesikari.  Rotavirus vaccination: a concise review. , 2012, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.