Meningitis B vaccine’s high price tag poses a health care conundrum

In October 2014 and January 2015, the Food and Drug Administration licensed two meningococcal serogroup B vaccines for administration in adolescents and young adults aged 10-25 years based on each vaccine's ability to elicit bactericidal antibody against the majority of invasive serogroup B strains and demonstrated safety. Each vaccine represented novel technology that overcame the challenge of both the poor immunogenicity of serogroup B polysaccharide protein conjugates and the potential cross reactivity with fetal brain tissue. In the United States, the vaccine was recommended (category A) for individuals in this age grouping with complement deficiency, anatomic or functional asplenia, outbreaks (when indicated), and for microbiologists. The Centers for Disease Control and Prevention also recommends that physicians consider the MenB vaccine for individuals aged 16-23 years who wish to obtain short-term protection against diverse strains of serogroup B meningococcal disease (category B). The American Academy of Pediatrics encouraged pediatricians to discuss the availability of the MenB vaccines with families.

The annual incidence of meningococcal disease varied between approximately 0.5-1.5 cases per 100,000 population between 1950 and 1990 - approximately 3,000 cases annually. Between 1990 and 2010, disease caused by the three common serogroups in the United States (B, C, and Y) declined to approximately 0.35 cases per 100,000. Subsequent to the introduction of a tetravalent meningococcal conjugate vaccine (MCV4) further declines - sustained over a longer time period than previously observed - have occurred, reaching a nadir of approximately 400 annual cases. Despite the absence of serogroup B component in MCV4, declines in serogroup B disease were reported in addition to vaccine serogroups C and Y. The biological explanations for the substantial decline in the overall rate of meningococcal disease are unknown. This decline in meningococcal serogroup B disease has created a controversy about implementation of Advisory Committee of Immunization Practices and the AAP and American Academy of Family Physician recommendations reflected in Shefali Luthra's writings.

There is widespread agreement about the severity of invasive meningococcal disease, the peaks of incidence in infancy and late adolescence, a 10% case fatality rate, an additional 10%-15% morbidity, and the limited number of cases (in the United States) to be prevented by adolescent immunization despite serogroup B being the most common. The effectiveness (greater than 80%) of at least one of these vaccines (MenB-4C) has been established in the United Kingdom, where it is recommended for all infants as part of a three-dose series at 2, 4, and 12 months. The value proposition (number of people immunized to prevent one death), however, is estimated at 1 million vaccinees for each death prevented.

Some experts believe the small burden of disease that might be prevented by these expensive vaccines requires thoughtful consideration in this era of increasingly limited resources. Others (as cited in the accompanying article) believe the marketing and advertising bend the truth and create fear in the public and conclude the risk is not great enough to warrant universal immunization (called category A by ACIP designation). In contrast, parent groups (especially those including parents of children who had meningococcal serogroup B disease) advocate strongly for a universal approach. For example, Alicia Stillman, director of the Emily Stillman Foundation, feels the current recommendation is "irresponsible" because it leaves so many teens and young adults vulnerable to the disease. The group believes that ACIP has made the menB vaccine to be an "optional item," but there is no requirement to provide the education to the parent and/or patient so they are aware of this option.

For me, the question is this: Who should decide how we use limited resources? I am reminded of an editorial in the New England Journal of Medicine titled, "The Meningococcal Vaccine - Public Policy and Individual Choices" by Paul Offit, MD, and Georges Peter, MD, that examined this question (N Engl J Med. 2003;349[24]:2353-6). They advocated that parents, if aware, may choose vaccination to protect adolescents and young adults from devastating infection, even if they were required to pay. I believe the CDC foresaw this as likely and moved to recommend individual choice. The wisdom of this was that category B status required MenB vaccine to be covered by insurers, thus preventing a potential divergent uptake, where families that could afford the price would recognize its value and those unable to pay for the vaccine would have no choice but to decline. This is especially relevant as there are not specific risk factors among healthy adolescents to warrant prioritizing one group over another.

MenB vaccines are valuable but costly tools for the prevention of life-threatening infectious disease. The use of increasingly limited resources, as raised by Dr. Moss and others, is a relevant and important question, and a call for a national dialogue.

As new medical breakthroughs increase, seemingly exponentially, how do we resolve the individual versus societal benefit of costly new treatments or preventions? How do we value prevention of life-threatening illness and death in mostly healthy adolescents, compared with treatment of end-stage diseases? These are important conversations that are only in their infancy.

Abraham Verghese wrote, in his book "Cutting for Stone," that American ambulance crews "salvaged people we'd never see in Missing [fictional hospital in Addis Ababa], because no one would have tried to bring them to a hospital [in Addis Ababa]. Judging someone to be beyond help never crossed the minds of police, firemen, or doctors here" in the United States. We need transparency and a national dialogue to develop consensus about priorities. We need to make sure the discussions are comprehensive and civil - not about pushing grandmothers over cliffs or death panels. Currently, ACIP and AAP have advocated for individual choice and to empower the parent and adolescent to choose after we (clinicians) communicate disease severity, the risk to the adolescent, and adverse events associated with MenB vaccine.

Stephen I. Pelton, MD, is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. Dr. Pelton disclosed that he has participated in advisory boards on meningitis B vaccines for GlaxoSmithKline and Pfizer, has research grants from Pfizer and Merck, and has spoken at CME events on meningitis B vaccines.