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Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×

B
Candidate Disease Profiles
1



_________________________

1 Boxes B-1 (influenza), B-2 (tuberculosis), and B-3 (group B streptococcus) were previously published in Appendix B of Ranking Vaccines: A Prioritization Framework, pp. 128–133, and they are included here with edits. Boxes B-4 (human papillomavirus), B-5 (pneumococcal infection), and B-6 (rotavirus) in this appendix describe the disease profiles for the additional vaccine candidates evaluated in Phase II.

Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×

BOX B-1
Influenza Disease Profile

Infectious Agent: Orthomyxoviruses, RNA viruses that infect birds and mammals. Three genera cause influenza: influenza A, which is the most common cause of the disease and has varying serotypes; influenza B, which has only one serotype; and influenza C, the least common.

Routes of Transmission: Airborne aerosols and direct contact with secretions or contaminated surfaces.

Health Effects: Influenza illness typically begins with chills or fever. The illness often involves cough, sore throat, nasal congestion, muscle aches, headache, and fatigue. It typically lasts for several days. In contrast with common colds, influenza usually has high fever with sudden onset and extreme fatigue. Influenza can also cause pneumonia either directly or through secondary bacterial infection.

Incidence, Prevalence, and Mortality: Influenza causes annual seasonal epidemics throughout the world as well as periodic pandemics. In the United States, influenza has been estimated to have caused an average of approximately 36,000 deaths each year from 1990 to 1999 and 226,000 hospitalizations each year between 1979 and 2001.

Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×

The incidence varies from year to year and is highest in children aged 0 to 4 years old and in the elderly aged 65 years and older. One report from the Centers for Disease Control and Prevention estimated seasonal influenza attack rates in the United States ranging from 6.6 percent in healthy young adults to 20 percent in the youngest children.

The 2009 pandemic caused by the H1N1 virus A infected an estimated 11 to 21 percent of those populations in which incidence could be studied. The highest incidence (34–43 percent) occurred in school-aged children. The severity of the disease, in terms of hospitalizations and pneumonia, was similar to that of recent seasonal influenza strains.

Prevention and Treatment: Annual influenza vaccination is the primary tool for prevention. The vaccine is reformulated each year to prevent infection from virus strains that the World Health Organization and the U.S. Food and Drug Administration predict will be most prevalent during the coming year. In addition, antiviral treatment is most effective when initiated within 48 hours of symptom onset and has typically been directed to persons at high risk of complications due to influenza or those individuals who are hospitalized.

Vaccine: In the United States vaccination has been recommended for all persons 6 months and older since 2006. Two types of vaccines are produced: inactivated (for intramuscular administration) and live attenuated (for intranasal administration).

Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×

BOX B-2
Tuberculosis Disease Profile

Infectious Agent: Tuberculosis is due to organisms in the M. tuberculosis complex, primarily M. tuberculosis, M. bovis, and M. africanum.

Routes of Transmission: Inhaling droplet nuclei in airborne aerosols generated by coughing or sneezing by individuals with pulmonary tuberculosis.

Health Effects: In a small proportion of newly infected individuals, especially infants, initial infection progresses rapidly—in weeks to months—to primary tuberculosis, which often spreads to blood, bone, brain, and other distant sites. Pulmonary tuberculosis produces cough, fever, night sweats, fatigue, and weight loss; it often goes undiagnosed for a number of months, during which time infection is transmitted to others, especially those in close contact, such as household members. However, infection in the lung can be contained by the immune system and remain latent; fewer than 10 percent of latently infected individuals subsequently develop reactivation pulmonary tuberculosis, which generally occurs when age, malnutrition, HIV infection, or other conditions suppress the immune system and thereby allow latent infection to reactivate.

Incidence, Prevalence, and Mortality: Approximately one-third of the world’s population is estimated to be latently infected with M. tuberculosis, but only a small proportion of these individuals will develop tuberculosis. The World Health Organization estimated that in 2010, 8.8 million people developed tuberculosis worldwide, yielding an incidence of 128 cases per 100,000 people. About 650,000 cases were

Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×

caused by multi-drug-resistant strains of M. tuberculosis, and 1.4 million with tuberculosis died of the disease. The incidence rate, number of cases, and deaths from tuberculosis has been declining in recent years, mainly due to the increased attention and resources devoted to diagnosing cases and ensuring that patients receive and complete the prescribed treatment regimen.

Prevention: In most wealthy countries with low incidence rates, the prevention of tuberculosis rests primarily on prompt diagnosis, correct multi-drug treatment, and ensuring the completion of treatment among those with pulmonary tuberculosis. Latently infected individuals, especially those at high risk of reactivation tuberculosis, such as HIV-infected individuals, are also treated with drugs. In poor countries with high incidence rates of tuberculosis, infants are given a single dose of the vaccine given shortly after birth. However, effective TB prevention in those cases also depends on prompt diagnosis, correct treatment, and ensuring the completion of treatment.

Treatment: Successful treatment of tuberculosis requires multiple drugs (at least three) given for a lengthy time period (9 to 12 months), even though the patient is usually asymptomatic (and non-infectious) after a few weeks of treatment. Treatment of latently infected individuals to prevent reactivation tuberculosis is generally accomplished with a single drug (e.g., isoniazid), also given for an extended period of time (6 to 12 months).

Vaccine: The Bacille Calmette-Guerin (BCG) vaccine is widely used at birth throughout many countries, including South Africa. BCG is given to all newborns as soon as possible after birth to protect infants from M. tuberculosis infections.

Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×

BOX B-3
Group B Streptococcus Disease Profile

Infectious Agent: Group B streptococcus (Streptococcus agalactiae) is a gram-positive bacterium found as a normal inhabitant of the gastro-intestinal and genital tract of humans. The majority of cases of the disease are caused by five serotypes.

Routes of Transmission: Transmission from mother to infant occurs at the time of vaginal delivery through a colonized birth canal. Exposure to Group B streptococcus in the hospital, at home, or in the community may result in late-onset disease.

Health Effects: Group B streptococcus is a leading cause of disease in young children. There are two distinct presentations: Early-onset disease(days of life 0–6) is the result of vertical transmission from a colonized mother, while late-onset disease (days of life 7–89) is acquired from either the mother or environmental sources. Early-onset disease is characterized by sepsis or meningitis with a high mortality rate. Late-onset disease often presents as meningitis with a somewhat lower mortality rate but with prominent sequelae.

Incidence, Prevalence, and Mortality: Group B streptococcus is the most common cause of sepsis and meningitis in infants from developed countries and is one of the most common causes of these conditions in infants globally. The mean invasive GBS disease incidence is

Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×

0.53 per 1,000 live births. The mean incidence of early-onset disease is 0.43 per 1,000 live births, with the highest incidence reported from Africa: 0.53 per 1,000 live births. The mean incidence of late-onset disease is 0.24 per 1,000 live births. Incidence is again highest in Africa, at 0.7 per 1,000 live births. Typically, early-onset disease is more likely to cause mortality (case fatality rate of 12.1 percent) than the late-onset disease (case fatality rate of 6.8 percent).

Prevention: Currently, intra-partum antibiotics are administered to pregnant women who are infected or who have known risk factors for group B streptococcus. This approach was widely adopted in the United States and many developed countries and resulted in substantial declines in disease in infants younger than seven days. In the United States, culture-based screening is used to identify candidates for chemoprophylaxis, but implementing this strategy has been difficult in low- and middle-income countries.

Treatment: Supportive care and antibiotics are needed for the successful treatment of GBS in infants. Benzylpenicillin or amoxicillin combined with aminoglycosides is provided as therapy for infants with signs of severe infection before infection has been confirmed. Treatment duration for sepsis is generally 10 days, but meningitis is treated for a minimum of 14 days, with more prolonged therapy in complicated cases.

Vaccine: A vaccine is not currently available for group B streptococcal infection but is under development.

Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×

BOX B-4
Human Papillomavirus Disease Profile

Infectious Agent: Papillomaviruses are non-enveloped DNA viruses. Approximately 100 types of papillomaviruses have been described; types 6 and 11, the most common types of human papillomavirus (HPV), cause genital warts, while types 16, 18, 31, and 45 are associated with the overwhelming majority of cases of cervical dysplasia and cervical cancer.

Routes of Transmission: HPV is primarily transmitted through sexual contact, especially genital contact; mother-to-infant transmission can occur during passage through an infected birth canal.

Health Effects: HPV infection is clinically silent, but after a latent period it is the cause of cervical dysplasia (low- and high-grade squamous intraepithelial lesions) and cervical cancer in women. HPV also causes ano-genital and other types of warts in men and women as well as recurrent respiratory papillomatosis in young children. The virus is also associated with squamous cell cancers of the vagina, vulva, anus, and penis and possibly with squamous cell cancers at other mucosal and skin sites.

Incidence, Prevalence, and Mortality: Genital infection with HPV is very common among sexually active men and women. More than 80 percent of sexually active individuals will acquire genital HPV infection by age 50. The prevalence of genital HPV infection is also very high, exceeding 25 percent in U.S. women of ages 20–24 years. Nearly 6.2 million new HPV genital infections occur each year in the United States among

Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×

individuals 14–44 years of age. However, 70 percent of these infections are cleared by the immune system within 12 months, and 90 percent within 24 months. Persistent infection with high-risk HPV types leads first to low-grade and then to high-grade squamous intraepithelial lesions of the cervix in women. In the United States it is estimated that 1,250,000 women develop low-grade squamous intraepithelial lesions and 300,000 women develop high-grade squamous intraepithelial lesions annually. If undetected and untreated, high-grade squamous intra-epithelial lesions can progress to cervical cancer, of which there are approximately 11,800 new cases in the United States each year, which lead to 3,700 deaths annually. The incidence and prevalence of HPV infection are similar in most geographic regions of the world, but the incidence of and mortality from cervical cancer vary greatly, depending on the availability and use of pap smear screening for cervical dysplasia.

Prevention and Treatment: There is no treatment for HPV infection itself. Low- and high-grade squamous intraepithelial lesions can be managed using various modalities whose aim is to prevent the development of cervical cancer. Correct and consistent use of male condoms may reduce the incidence of genital HPV infection by about 70 percent.

Vaccines: Two formulations of HPV vaccine are licensed and approved for use in the United States: a bivalent vaccine containing types 16 and 18 and a quadrivalent vaccine containing types 6, 11, 16, and 18. HPV vaccine is recommended for all girls 11–12 years of age in three doses; it can be administered to girls as young as 9 years of age, and “catch-up” vaccination is recommended for girls and women 13–26 years of age if they have not previously been vaccinated or have not completed the full three-dose series. It is also recommended routinely for males.

Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×

BOX B-5
Pneumococcal Disease Profile

Infectious Agent: Streptococcus pneumoniae organisms are lancet-shaped, gram-positive, facultative anaerobic bacteria. Based on their polysaccharide capsules, more than 90 different pneumococcal serotypes have been identified, although most disease is caused by a limited number of serotypes.

Routes of Transmission: Transmission of S. pneumoniae occurs as the result of direct person-to-person contact via respiratory droplets and by autoinoculation in persons carrying the bacteria in their upper respiratory tract. Its spread among family groups is influenced by crowding, the season of the year, and the presence of other upper respiratory infections.

Health Effects: In the United States, S. pneumoniae infection is the most common community-acquired bacterial pneumonia, estimated to affect approximately 100 out of every 100,000 adults each year. Pneumonia, febrile bacteraemia, and meningitis are the most common manifestations of invasive pneumococcal disease; bacterial spread within the respiratory tract may result in middle-ear infection, sinusitis, or recurrent bronchitis. Compared with the invasive disease, the manifestations of the non-invasive form, such as acute otitis media, sinusitis, community-acquired pneumonia, empyema, and conjunctivitis, are usually less severe and more common.

Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×

Incidence, Prevalence, and Mortality: Although all age groups may be affected, the highest rates of pneumococcal disease occur in young children and in the elderly population. As many as 175,000 adult hospitalizations occur due to S. pneumoniae annually in the United States. The case-fatality rate is 5 to 7 percent and may be much higher among elderly persons. According to the World Health Organization, S. pneumoniae kills close to 1 million children under 5 years of age worldwide every year, and most of these are in developing countries. Even in economically developed regions, invasive pneumococcal disease carries high mortality; for adults with pneumococcal pneumonia the mortality rate averages 10 to 20 percent, while it may exceed 50 percent in the high-risk groups. The risk for one or more of these manifestations is much higher in infants and elderly people. In addition, persons suffering from a wide range of chronic conditions and immune deficiencies are at increased risk. In developing countries, infants under 3 months of age are at particularly high risk, especially for pneumococcal meningitis.

Vaccines: Currently, there are two general types of pneumococcal vaccines: pneumococcal polysaccharide vaccine and pneumococcal conjugate vaccine. In the United States, the pneumococcal conjugate vaccine PCV13 is currently recommended for all children under 5 years of age. Pneumovax, a 23-valent polysaccharide vaccine, is currently recommended for use in all adults who are older than 65 years of age and for persons who are 2 years and older and at high risk for disease (e.g., sickle cell disease, HIV infection, or other immune-compromising conditions). It is also recommended for use in adults 19 through 64 years of age who smoke cigarettes or who have asthma.

Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×

BOX B-6
Rotavirus Disease Profile

Infectious Agent: Rotavirus is a double-stranded RNA virus of the family Reoviridae. In the United States from 1966 to 2005, five strains of rotavirus (G1–4, G9) have accounted for 90 percent of isolates from children younger than 5 years, with the G1 strain accounting for more than 75 percent of the isolates.

Routes of Transmission: Transmission is by fecal–oral spread, both through close person-to-person contact and by fomites. Rotaviruses are also probably transmitted by other modes, such as fecally contaminated food and water and respiratory droplets.

Health Effects: Clinical manifestations of infection vary and depend on whether it is the first infection or reinfection. The first infection after 3 months of age is generally the most severe. Infection could result in watery or severely dehydrating diarrhea with fever and vomiting. Up to one-third of infected children have a temperature greater than 102°F (39°C). Gastrointestinal symptoms generally resolve in 3 to 7 days. Clinical features and stool characteristics of rotavirus diarrhea are nonspecific.

Incidence, Prevalence, and Mortality: Rotavirus occurs throughout the world, and prevalence of rotavirus strains varies by geographic area. The disease is less seasonal in tropical climates than in temperate areas.

Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×

Incidence of rotavirus is similar in developed and developing countries, suggesting that improved sanitation alone is not sufficient to prevent the infection. In 2008 approximately 453,000 child deaths due to rotavirus gastroenteritis infection occurred worldwide, accounting for about 5 percent of all child deaths.

Rotavirus is highly communicable, with near universal infection of children by age 5. Spread within families, institutions, hospitals, and childcare settings is common. In the pre-vaccine era in the United States, about 3 million rotavirus infections occurred annually, with 95 percent of children experiencing at least one rotavirus infection by 5 years of age. In the United States, rotaviruses are responsible for 5 to 10 percent of all gastroenteritis episodes in children less than 5 years old. Rotavirus accounts for 30 to 50 percent of all hospitalizations for gastroenteritis among U.S. children younger than 5 years of age.

Prevention and Treatment: Rotavirus vaccination is recommended for all national immunization programs. No specific therapy is currently available against rotaviruses. Fluid replacement is required to prevent dehydration. Promotion of early and exclusive breastfeeding, hand washing, improved water supply, and sanitation is part of a comprehensive strategy to control diarrheal disease.

Vaccines: Two live attenuated oral rotavirus vaccines are presently licensed for use in the United States. RV5 (RotaTeq) is given in three doses, while RV1 (Rotarix) is given in two doses. The vaccination series for both vaccines may be started as early as 6 weeks of age. The maximum age for vaccine doses varies by country.

Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×

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Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×
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Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×
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Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×
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Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×
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Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×
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Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×
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Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×
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Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×
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Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×
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Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×
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Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×
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Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×
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Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×
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Suggested Citation:"Appendix B: Candidate Disease Profiles." Institute of Medicine. 2013. Ranking Vaccines: A Prioritization Software Tool: Phase II: Prototype of a Decision-Support System. Washington, DC: The National Academies Press. doi: 10.17226/13531.
×
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SMART Vaccines--Strategic Multi-Attribute Ranking Tool for Vaccines--is a prioritization software tool developed by the Institute of Medicine that utilizes decision science and modeling to help inform choices among candidates for new vaccine development. A blueprint for this computer-based guide was presented in the 2012 report Ranking Vaccines: A Prioritization Framework: Phase I.

Ranking Vaccines: A Prioritization Software Tool,Phase II extends the proof-of-concept presented in the Phase I report, which was based on multi-attribute utility theory. This report refines a beta version of the model developed in the Phase I report and presents its next iteration, SMART Vaccines 1.0.

Ranking Vaccines: Phase II discusses the methods underlying the development, validation, and evaluation of SMART Vaccines 1.0. It also discusses how SMART Vaccines should--and, just as importantly, should not--be used. The report also offers ideas for future enhancements for SMART Vaccines as well as for ideas for expanded uses and considerations and possibilities for the future.

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