Public health impact and cost effectiveness of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in India: model based analysis

Abstract

Objectives: To examine the public health impact of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in a birth cohort in India, and to estimate the cost effectiveness and affordability of such a programme.

Design: Decision analytical Markov model encompassing all direct medical costs. Infection risk and severity depended on age, number of previous infections, and vaccination history; probabilities of use of inpatient and outpatient health services depended on symptom severity.

Data sources: Published clinical, epidemiological, and economic data. When possible, parameter estimates were based on data specific for India. Population Simulated Indian birth cohort followed for five years.

Main outcome measures: Decrease in rotavirus gastroenteritis episodes (non-severe and severe), deaths, outpatient visits, and admission to hospital; incremental cost effectiveness ratio of vaccination expressed as net cost in 2007 rupees per life year saved.

Results: In the base case, vaccination prevented 28,943 (29.7%) symptomatic episodes, 6981 (38.2%) severe episodes, 164 deaths (41.0%), 7178 (33.3%) outpatient visits, and 812 (34.3%) admissions to hospital per 100,000 children. Vaccination cost 8023 rupees (about pound100, euro113, $165) per life year saved, less than India's per capita gross domestic product, a common criterion for cost effectiveness. The net programme cost would be equivalent to 11.6% of the 2006-7 budget of the Indian Department of Health and Family Welfare. Model results were most sensitive to variations in access to outpatient care for those with severe symptoms. If this parameter was increased to its upper limit, the incremental cost effectiveness ratio for vaccination still fell between one and three times the per capita gross domestic product, meeting the World Health Organization's criterion for "cost effective" interventions. Uncertainty analysis indicated a 94.7% probability that vaccination would be cost effective according to a criterion of one times per capita gross domestic product per life year saved, and a 97.8% probability that it would be cost effective according to a criterion of three times per capita gross domestic product.

Conclusions: Across a wide range of assumptions, mass RIX4414 vaccination in India would probably prevent substantial morbidity and mortality at a cost per life year saved below typical thresholds of cost effectiveness. The opportunity costs of such a programme in this or similar settings, however, should be weighed up carefully.

Fig 1 Schematic of Markov model. Each individual begins life in the well state and thereafter resides in either the well, symptomatic, or dead state during each one month cycle for a total of 60 cycles. Individuals can receive doses of live attenuated human rotavirus vaccine at months two and four only. At the end of each cycle, each individual’s risk for rotavirus infection is determined by number of vaccine doses received, time since receiving most recent dose, and number of previous rotavirus infections. If infected, individuals might develop symptoms in which case they will begin the next cycle in symptomatic state. In symptomatic state, gastroenteritis can be non-severe (Vesikari score <11) or severe (Vesikari score ≥11). Symptom severity dictates probability that each individual will receive hospital care, outpatient care, or no formal treatment. Those with severe disease who receive no formal treatment are at risk for death. Each month, there is an age dependent background risk of death from non-rotavirus causes (not shown). M in circle represents Markov node; branches emanating from a Markov node represent possible states of being. Open circle represents chance node; branches emanating to right represent possible outcomes of probabilistic process. Left pointing triangle designates terminal node; here, the state in which next cycle should begin is given. [+] signifies that portion of tree has been collapsed because it replicates portion already shown. “Get dose” signifies contingency that individual receives dose of vaccine, “no dose” signifies that they do not

Fig 2 Model projections for cumulative incidence of first, second, and third rotavirus infections during first five years of life in children receiving no vaccination

Fig 3 Individual parameters with greatest influence on incremental cost effectiveness ratio, expressed in rupees per life year saved (LYS), in univariate sensitivity analysis. Solid vertical line represents base case incremental cost effectiveness ratio of 8023 rupees per life year saved

Fig 4 Acceptability curve for strategy of vaccination with live attenuated human rotavirus vaccine (RIX4414) compared with no rotavirus vaccination. Curve represents probability that vaccination would be cost effective over range of threshold incremental cost effectiveness ratios (ICERs)