A new study from the Institute of Medicine (IOM) presents important information to help the research community set domestic vaccine priorities for the future. "Vaccines for the 21st Century: A Tool for Decisionmaking," commissioned by the National Institute of Allergy and Infectious Diseases (NIAID), employs a new quantitative model to compare the cost and health benefits of developing more than two dozen different candidate vaccines, including, for the first time, therapeutic vaccines against chronic diseases.
Based on this analysis, the report divides 26 candidate vaccines into four groups, from most to least favorable for development (see page 4). But the IOM report stresses that this ranking is not a recommendation about which candidate vaccines should be developed. Rather, it provides a framework to consider along with other key factors such as technical feasibility and public health urgency when making decisions about vaccine research and development.
"We expect that the NIH and other policy makers in government, academia and industry will find this report and the model it proposes to be extremely valuable tools for guiding vaccine research priority-setting," comments Anthony S. Fauci, M.D., director of NIAID. Anyone with a computer and spreadsheet software will be able to access the model from the IOM free-of-charge and adapt it to other conditions or candidate vaccines.
NIAID - the major supporter of vaccine research nationwide - requested the report in 1995 as a follow-up to two IOM reports issued a decade earlier. A 1985 report focused on priorities for vaccine development in the United States, and a second report, published in 1986, focused on vaccine development in developing countries.
Like the 1985 project, the new report considers only health conditions of public health importance in the United States, except HIV/AIDS, which already is a national priority. However, the new report differs in two significant ways from the 1985 project. First, it includes vaccines not only for infectious diseases, but also therapeutic and preventive vaccines for chronic conditions such as cancer and autoimmune diseases. Second, it evaluates both short-term (10 years) and long-term (20 years) priorities.
As requested, the committee limited their analysis to no more than 30 vaccines that would be feasible to license within 20 years. The quantitative model they created uses health indexes and other analytical methods developed by researchers within the past decade. Vaccine candidates are evaluated according to two primary criteria: anticipated health benefits and expected net savings of health care resources. As new data emerge, specific elements of the model can be changed or new candidate vaccines can be assessed.
"We are pleased that this model provides U.S. policy makers with a common tool to compare vastly divergent health conditions that might be treated or prevented by vaccines," comments N. Regina Rabinovich, M.D., chief of the clinical and regulatory affairs branch in NIAID's Division of Microbiology and Infectious Diseases. Although vaccines against diseases of primarily global importance were not assessed, the report notes that these diseases must be considered in setting research priorities.
The seven vaccines in the top tier include a cytomegalovirus vaccine given to adolescents; a universal influenza vaccine; a Group B streptococcus vaccine for high-risk adults and pregnant women; and a Streptococcus pneumoniae for infants and seniors. In addition, this most favorable group includes therapeutic vaccines for three chronic diseases: rheumatoid arthritis, multiple sclerosis and insulin-dependent diabetes mellitus. Dr. Rabinovich says it is not surprising that these three vaccines fared well in the model. The diseases they target affect large numbers of people; a therapeutic vaccine has a well-defined target population (those ill with the disease); and in this economic model, health benefits accrue more quickly with a therapeutic vaccine than a preventive one. That some therapeutic vaccines appear cost-effective bodes well for vaccine strategies targeted to certain non-infectious, chronic conditions, she says.
The report notes that considerable progress has been made since the 1985 IOM study. Six of 14 vaccines listed in that study as domestic priorities for development are now licensed. These include an acellular pertussis (whooping cough) vaccine and vaccines against hepatitis A and B, Haemophilus influenzae type b (Hib), formerly a major cause of childhood meningitis, varicella zoster (chickenpox), and rotavirus, a leading cause of serious infant diarrhea.
Despite these advances, the report cites legal and other barriers to progress that remain. For example, the Vaccine Injury Compensation Program covers adverse events caused only by vaccines mandated for children. The IOM report lists a striking number of vaccines for use in adolescent or adult populations, vaccines that currently would fall outside this program. Manufacturer liability also is a potential disincentive to developing vaccines for pregnant women to prevent infections such as Group B streptococcus in newborns and young infants.
In addition, to garner public support for the growing number of vaccines, researchers must develop more combination vaccines, rational vaccine schedules and friendly alternatives to injectable vaccines, for example, oral drops and nasal sprays. Finally, the report notes, successfully introducing vaccines into adolescent populations will require acknowledging that that this age group may be sexually active and at risk for certain infectious diseases.
Vaccines are one of the few health care measures that save money, and the cost-effectiveness of all the vaccines in the top three groups compares favorably with that of currently licensed vaccines. However, for the so-called "orphan diseases" in the lowest tier, the report says this expectation needs to shift. In some cases, the health benefits of a vaccine might be worth a higher cost. The report also emphasizes that stable, sufficient funding of basic research by the federal government is crucial to developing vaccines.
Robert S. Lawrence, M.D., associate dean for professional education and programs and professor of healthy policy and management at The Johns Hopkins School of Hygiene and Public Health in Baltimore, chaired the 14-member IOM committee. NIAID drafted the project proposal with input from other institutes at the National Institutes of Health (NIH), which funded the project.
To obtain a printed copy of the full report, call the IOM at 1-800-624-6242. The executive summary of the report is available on the Web at http://www2.nas.edu/hpdp.
NIAID is a component of the NIH. NIAID conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.
Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.
VACCINE RANKINGS (alphabetically ordered within categories)
MOST FAVORABLE -Cytomegalovirus vaccine given to 12-year-olds. -Influenza virus vaccine given to the general population. -Insulin-dependent diabetes mellitus therapeutic vaccine. -Multiple sclerosis therapeutic vaccine. -Rheumatoid arthritis therapeutic vaccine. -Group B streptococcus vaccine to be administered to pregnant women and high-risk adults. -Streptococcus pneumoniae vaccine to be given to infants and 65-year-olds.
MORE FAVORABLE -Chlamydia vaccine given to 12-year-olds. -Heliobacter pylori vaccine given to infants. -Hepatitis C virus vaccine given to infants. -Herpes simplex virus vaccine given to 12-year-olds. -Human papillomavirus vaccine given to 12-year-olds. -Melanoma therapeutic vaccine. -Mycobacterium tuberculosis vaccine given to high-risk populations. -Neisseria gonorrhoeae vaccine given to 12-year-olds. -Respiratory syncytial virus vaccine given to infants and 12-year-olds.
FAVORABLE -Parainfluenza virus vaccine given to infants and women in their first pregnancy. -Rotavirus vaccine given to infants. -Group A streptococcus vaccine given to infants. -Group B streptococcus vaccine given to high-risk adults and either 12-year-old girls or women during their first pregnancy.
LESS FAVORABLE -Borrelia burgdorferi vaccine given to resident infants and migrants of any age in high-risk geographic areas. -Coccidiodes immitis vaccine given to resident infants and migrants of any age in high-risk geographic areas. -Enterotoxigenic Escherichia coli vaccine given to infants and travelers. -Epstein-Barr virus vaccine given to 12-year-olds. -Histoplasma capsulatum vaccine given to resident infants and migrants of any age in high-risk areas. -Neisseria meningitidis type b vaccine given to infants. -Shigella vaccine given to infants and travelers, or travelers only.