Prioritization of Influenza Pandemic Vaccination to Minimize Years of Life Lost

The Centers for Disease Control and Prevention (CDC) has estimated that the population of the United States at increased risk for influenza is 91 million, whereas the total population targeted for vaccination is ~218 million [1], which will lead to a clear resource-allocation dilemma in the event of a pandemic. Pandemic influenza preparedness strategies focus on the prevention of severe outcomes as the guiding principle for the utilization of vaccines and therapeutics. The US pandemic preparedness draft plan provides guidance for vaccine allocation, prioritizing key government and health care workers as well as emergency responders. In the general population, seniors (those ⩾65 years of age) are prioritized over younger healthy adults in all 3 of the pandemic scenarios considered, which range from mild to severe [2]. Government officials are seeking input from the public to refine this proposed prioritization strategy. In the meantime, several bioethicists and scientists have questioned the prioritization of seniors over younger persons and sparked a recent policy debate centered around the question of whom should be vaccinated first [3–8]. Essentially, ethicists criticize the inherent axiom that any life lost has the same value, regardless of whether the deceased was 5 or 99 years old. When considering the best approach to mitigate the impact of mortality in a pandemic, the age-specific historical experience of mortality risk must be taken into consideration. Mortality during influenza pandemics has ranged from relatively mild (1968) to catastrophic (1918) [9]. Although severe influenza predominantly affects the elderly and infirm in interpandemic seasons, mortality shifts toward younger adults in pandemic years [10]. The 1918 pandemic is an extreme case, in which young adults were at highest risk of death, whereas seniors were essentially spared relative to the immediately preceding influenza seasons [11]; a similar phenomenon was seen in the 1968 pandemic [9, 12]. Decisions on vaccine allocation should also incorporate information on the decline in vaccine response with age due to immune senescence [13], an issue that has been overlooked in current pandemic plans. A recent literature review of randomized, placebo-controlled vaccine response found that influenza vaccine efficacy is reduced by 25%–50% in seniors, compared with that in younger adults [14]. Incorporating the phenomenon of declining response with age in a priority setting will also intuitively drive the priority groups toward younger ages. In this article, we propose the integration of these concepts and explore a quantitative approach to be used to set priorities for vaccination in pandemic planning. Measurement of the potential years of life lost (YLL) during influenza pandemics is a quantitative tool that integrates mortality risks in various age groups with age differences in life expectancy. The YLL measure implies a differential between the prevention of death in younger and older persons [15] and is commonly used as a metric in public health decision making, particularly for vaccination recommendations [16, 17]. Intuitively, the use of YLL instead of the customary number of deaths would generate a very different weighting of age group priorities, simply because YLL “values” the prevention of the death of a younger person more highly than that of an older individual. Although YLL measures were recently applied to the estimation of seasonal influenza economic costs [18], this important metric has not been incorporated into the current debate about optimal control of pandemic influenza thus far. Health economics analyses conventionally consider complex health outcome metrics such as quality-adjusted life years and disability-adjusted life years (DALYs) [19], which incorporates both YLL and years of life spent in poor health or with disability after a disease episode. These metrics are useful for evaluating the burdens of chronic diseases or injuries [20] but do not add much to the assessment of influenza vaccine strategies, given that influenza is an acute viral infection from which survivors usually fully recover in a week or two with no life-long sequelae. Furthermore, when death and life with disability are integrated in a single measure of DALYs, different weights on these health outcomes must be set a priori, a sometimes difficult and debated approach [21]. In addition, because the YLL metric does not put different weights on remaining years of life based on disability or societal preferences related to the value of life at different ages, it tends to overestimate disease burden in seniors compared with the DALY metric [22]. Hence, in this work, we focus on YLL, a conservative metric that captures the major health burden of pandemic influenza with no need to set arbitrary values on quality of life. Although the importance of assessing YLL has been suggested as an important consideration for vaccine allocation in pandemic situations [3, 6], here we provide the first quantitative estimates of this metric. We project the age-specific YLL and the benefits of vaccination in a future pandemic, integrating historical mortality rates, life expectancy, and age-specific vaccine efficacy. The purpose of this analysis is to provide an alternative quantitative tool to help guide pandemic vaccine priority setting and achieve the greatest possible population impact, by preventing the loss of as many years of life as possible.