Starting today, nearly 6,000 students at Princeton University will be offered a vaccine against bacterial meningitis—one that is not approved for use in the United States. This highly uncommon action comes in response to an outbreak of the rare but extremely serious disease that began last spring on the New Jersey campus.
The vaccine in question, Novartis’s Bexsero, was approved this year by regulators in Europe and Australia. Its use at Princeton has been facilitated by the Food and Drug Administration and Centers for Disease Control and Prevention through a program that allows for unlicensed drugs and vaccines to be administered as a response to serious diseases when no approved alternative exists. A public-health program of this design, size, and urgency is unprecedented.
In an era in which cost-effectiveness analyses are becoming more prominent in health-policy debates, the case of meningitis vaccines illustrates the challenges and unintended consequences of efforts intended to spend limited health-care dollars most efficiently. The meningitis cases at Princeton (as well as an unrelated outbreak at the University of California at Santa Barbara) have been particularly worrisome to public-health officials because the meningitis vaccines commonly required for college students do not protect against the specific strain of bacteria causing disease on these campuses. This strain of bacteria—serogroup B—presented unique technical challenges for vaccine development. This, in turn, delayed the arrival of vaccines that could be used to prevent it, until the recent international approval of Bexsero.
Notwithstanding current outbreaks on college campuses, bacterial meningitis is quite rare in the United States (there are an estimated 800-1,200 cases annually). However, the high fatality rate among those sickened (10 to 15 percent), the rapid onset and progression of symptoms, and the large percentage of patients who are young adults living away from home for the first time all help to explain the substantial public and media attention directed even to isolated cases. These tragic disease narratives may also account for the public-health community’s strong endorsement of adolescent vaccination despite cost-effectiveness analyses that would lead most health economists to recommend against such a program.
In other words, in the case of meningitis among adolescents, the clear benefits of vaccination in preventing disease, disability, and death have justifiably trumped the cold calculus of pursuing “optimal” health spending.
A different policy exists for meningitis vaccination in infants, a group with by far the highest rate of disease. Vaccination is recommended only for a small subset of infants with specific conditions that place them at increased risk. Public-health officials justify this decision because a majority of infant disease is caused by meningitis B, the strain not included in currently licensed vaccines. The benefits of vaccinating all infants do not justify the costs and complexity of such a program, they argue.
The unmet need for protection against meningitis B would seem an ideal incentive for Novartis to pursue FDA approval for Bexsero in the United States. However, cases caused by meningitis B are extremely uncommon, failing to justify for its manufacturer the expensive, complicated, and uncertain research and approval process. Instead, Novartis hopes to develop a single new meningitis vaccine that provides the broadest protection possible against all major types of disease-causing bacteria. While a desirable goal, its pursuit will extend indefinitely the time that U.S. children and adolescents remain unprotected against meningitis B.
Concerns about an unfavorable market for these vaccines in the United States may be well founded, as vaccine advisers in Britain declined this summer to recommend Bexsero for inclusion in their national immunization program. Their view was that the costs of mass vaccination would be highly likely to exceed its public-health benefits, regardless of the final price of the vaccine.
These past and present decisions by Novartis and U.S. and international regulators have necessitated the heroic efforts by U.S. public-health officials to bring Bexsero to Princeton, where the risk of meningitis and the potential benefits of the vaccine are far greater than those of the general population. The partnership between the university and state and federal public-health agencies throughout this outbreak offers a model for effective collaboration between government and universities in response to future infectious disease outbreaks on college campuses.
Still, Princeton’s use of Bexsero comes with risks of its own. While the vaccine is similar in design to approved vaccines against other diseases, less is known about it than would be typical for products tested and approved in the traditional manner. Proceeding with vaccination amid this heightened uncertainty could be justified by the serious, continuing meningitis threat facing Princeton students and the failure of alternative measures to halt the emergence of new cases. Instead, CDC officials have pointed to the vaccine’s approval in Europe and Australia, suggesting in public statements that it should provide a level of confidence in the vaccine comparable to that if FDA itself had reached the same conclusion.
The Princeton community has been encouraged to view Bexsero’s unlicensed, investigational status in the United States as an administrative technicality instead of a meaningful statement regarding what is known and unknown about the vaccine. Effective communication in public health is challenging but essential, all the more so when responding to an unfolding outbreak. As public-health officials have worked to educate students about the grave risks of meningitis and to encourage use of Bexsero, too little has been said about the uncertainty inherent in any judgment regarding the large-scale use of an unapproved vaccine.
“This is not an experiment. It’s not a study. It’s access to a vaccine so doctors can recommend it to patients,” a CDC official told Princeton’s student newspaper last month. Yet the program by which the vaccine is being made available far more closely resembles the requirements and protections associated with clinical research than a traditional prevention or treatment program.
Even in the contentious environment around U.S. health policy, there is broad agreement that the system would be strengthened considerably by identifying interventions that provide little or no benefit to patients and allocating health resources elsewhere. Products like meningitis vaccines raise different questions, however—ones that are too easily passed over in debates about spending health-care dollars wisely.
In a system laden with waste and inefficiencies, should drugs or vaccines that can prevent permanent disability and death go unused primarily on the basis of unfavorable economic assessments?
The current inconsistent answers to this question by policy makers shape not only the use of available interventions, but, as in the case of Bexsero in the United States, the willingness of manufacturers to even pursue approval for new products. As a result, the challenges in making them available to patients when they are most needed are far greater, while less is known about their risks and benefits than is desirable.
Health officials are optimistic that this novel meningitis vaccine will slow or halt the outbreak at Princeton. A second goal for the architects of this unprecedented program should be to work to ensure that such extraordinary efforts are not required in the future, so that potentially valuable interventions can be more readily offered to patients with full confidence in their safety and potential benefits.
Jason L. Schwartz is a fellow in bioethics at the Princeton University Center for Human Values.Return to Top