IOM Committee on Assessment of Studies of Health Outcomes Related to the Recommended Childhood Immunization Schedule

IOM Committee on Assessment of Studies of Health Outcomes Related to the Recommended Childhood Immunization Schedule Bruce Gellin, MD, MPH Director, National Vaccine Program Office Deputy Assistant Secretary for Health Office of the Assistant Secretary for Health Department of Health and Human Services

Title XXI Public Health Service Act (Sec 2102) National Vaccine Program Responsibilities Vaccine Research Vaccine Development Safety and efficacy testing of vaccines Licensing of vaccine manufacturers and vaccines Production and procurement of vaccines Distribution and use of vaccines Evaluating the need for, the effectiveness, and adverse effects of vaccines and immunization activities Coordinating governmental and nongovernmental activities Funding of federal agencies

2010 National Vaccine Plan Goals 1. Develop new and improved vaccines 2. Enhance the vaccine safety system 3. Support communications to enhance informed vaccine decision-making 4. Ensure a stable supply of recommended vaccines and achieve better use of existing vaccines to prevent disease, disability and death in the United States 5. Increase global prevention of death and disease through safe and effective vaccination

Scientific Opportunity and Vaccine Development

Recommended Childhood Immunization Schedule 1982

MMWR 1995;43:959-960

VACCINE Selected Recent Immunization Policy Decisions ACIP Vote Meningococcal conjugate (adolescents) February 2005 Tdap (adolescents) June 2005 MMRV October 2005 Universal hepatitis A October 2005 Rotavirus (infants) February 2006 Influenza (expanded 24 to 59 months*) February 2006 Human papillomavirus (adolescents) June 2006 Second Dose Varicella June 2006 Zoster (shingles) October 2006 Influenza (expanded 5 to 18 years) February 2008 Influenza (universal >6 months) February 2010 Pneumococcal 13-valent conjugate February 2010

Recommended Schedule for Persons Aged 0-6 Years, U.S. (2012)

Comparison of 20 th Century Annual Morbidity and Current Morbidity: Vaccine-Preventable Diseases Disease 20th Century 2011 Annual Morbidity Reported Cases Percent Decrease Smallpox 29,005 0 100% Diphtheria 21,053 0 100% Measles 530,217 212 > 99% Mumps 162,344 370 > 99% Pertussis 200,752 15,216 92% Polio (paralytic) 16,316 0 100% Rubella 47,745 4 > 99% Congenital Rubella Syndrome 152 0 100% Tetanus 580 9 98% Haemophilus influenzae 20,000 8* > 99% Source: JAMA. 2007;298(18):2155-2163 Source: CDC. MMWR January 6, 2012;60(51);1762-1775. (provisional 2011 data) * Haemophilus influenzae type b (Hib) < 5 years of age. An additional 14 cases of Hib are estimated to have occurred among the 237 reports of Hi (< 5 years of age) with unknown serotype. National Center for Immunization & Respiratory Diseases Historical Comparisons of Vaccine-Preventable Disease Morbidity in the U.S.

2010 National Vaccine Plan Goals 1. Develop new and improved vaccines 2. Enhance the vaccine safety system 3. Support communications to enhance informed vaccine decision-making 4. Ensure a stable supply of recommended vaccines and achieve better use of existing vaccines to prevent disease, disability and death in the United States 5. Increase global prevention of death and disease through safe and effective vaccination

February 2, 2012

At first glance, US vaccination rates appear reasonable; coverage among children entering kindergarten exceeds 90% for most recommended vaccines. A closer look, however, reveals substantial local variation. In Washington State s San Juan County, for example 72% of kindergartners and 89% of 6 th graders are either non-compliant with or exempt from vaccination requirement for school entry. Only 52.5% of kindergartners and 4% of sixth graders were adequately immunized against pertussis for the 2010 2011 school year. Not surprisingly, the county also has one of the state s highest incidence rates of pertussis. February 2, 2012

Socioeconomic barriers School entry requirements Ease of exemption Address misinformation Effective persuasion: Aristotle: The Art of Rhetoric Accurate information Facts - Benefit and Risks: Vaccination, opting out, or delay Trusted source Science vs. Story Communication tailored to parent/patient needs February 2, 2012

2010 National Vaccine Plan: Enhancing Informed Decision-Making Conduct research regularly to understand the public knowledge, beliefs and concerns about vaccine and VPDs Conduct research on factors that affect decisionmaking about vaccination for individuals and families, providers, and policy-makers.

What Parents are Concerned About (2010) It is painful for children to received so many shots during one doctor s visit (38%) My child is getting too many vaccines in one doctor s visit (36%) Children get too many vaccines during the first two years of life (34%) Vaccines may cause learning disabilities, such as autism (30%) The ingredients in vaccines are unsafe (26%) Vaccines are not tested enough for safety (17%) Vaccines may cause chronic diseases (16%) Kennedy et al, Health Affairs; June 2011 30:1151-1159

Caregiver responses about vaccines for children 6-23 months of age Vaccines are as important or more important than other things parents do to keep their babies healthy (e.g., feeding them healthy food, baby-proofing the home) (91%) Very or somewhat comfortable with the number of vaccines recommended by age two (86%) Highest number of shots comfortable with their child receiving in one well-child visit Three (32%) Two (30%) CDC telephone survey, 2010. N=1,500

Caregiver responses about vaccines for children 6-23 months of age Past or planned delay or refusal of vaccines? 75% report never refusing or delaying a vaccine when it was offered and not planning to do so in the future Includes some who are not up to date CDC telephone survey, 2010. N=1,500

Caregiver responses about vaccines for children 6-23 months of age Past or planned delay or refusal of vaccines? 75% report never refusing or delaying a vaccine when it was offered and not planning to do so in the future Includes some who are not up to date 25% report past or planned delay and/or refusal of one or more recommended vaccines This includes parents who had only ever refused the H1N1 influenza vaccine CDC telephone survey, 2010. N=1,500

National Vaccine Advisory Committee Charter Study and recommend ways to encourage the availability of an adequate supply of safe and effective vaccination products in the United States. Recommend research priorities and other measures the Director of the NVP should take to enhance the safety and efficacy of vaccines. Advise the Director of the NVP in the implementation of Sections 2102 and 2103 of the PHS Act. Identify annually for the Director of the NVP the most important areas of governmental and non-governmental cooperation that should be considered in implementing Sections 2101 and 2103 of the PHS Act. http://www.hhs.gov/nvpo/nvac/charter/index.html

National Vaccine Advisory Committee Charter Study and recommend ways to encourage the availability of an adequate supply of safe and effective vaccination products in the United States. Recommend research priorities and other measures the Director of the NVP should take to enhance the safety and efficacy of vaccines. Advise the Director of the NVP in the implementation of Sections 2102 and 2103 of the PHS Act. Identify annually for the Director of the NVP the most important areas of governmental and non-governmental cooperation that should be considered in implementing Sections 2101 and 2103 of the PHS Act. http://www.hhs.gov/nvpo/nvac/charter/index.html

http://www.hhs.gov/nvpo/nvac/

2009 NVAC: Prioritization Criteria Significance of exposure to the vaccine Burden of adverse event following vaccine Public concern Scientific concern and degree to which science warrants further study Impact on policy Feasibility http://www.hhs.gov/nvpo/nvac/

2009 NVAC Recommendations A randomized clinical trial that includes a study arm receiving no vaccine or vaccine not given in accord with the current recommended schedule is not ethical, would not pass IRB review, and cannot be done. An observational study of populations looking at natural variation in vaccination schedules may be difficult to control for confounders in a study of health outcomes of vaccinated and unvaccinated populations; the baseline health and social characteristics f these populations may be different, and meaningful results may be difficult to obtain. http://www.hhs.gov/nvpo/nvac/

2009 NVAC Recommendations an external expert committee, such as the Institute of Medicine, with broad methodological, design, and ethical expertise to consider strengths and weaknesses, ethical issues and feasibility including timelines and cost of various study designs to examine outcomes in unvaccinated, vaccine delayed and vaccinated children and report back to the NVAC. http://www.hhs.gov/nvpo/nvac/

2009 NVAC Recommendations This review should consider strengths and weaknesses, ethical issues and feasibility including timelines and cost of various study designs Consideration should be given to broad biomedical research including laboratory studies, and animal studies. http://www.hhs.gov/nvpo/nvac/

Charge to the Committee Conduct an independent assessment surrounding the feasibility of studying health outcomes in children who were vaccinated according to the CDC recommended schedule and those who were not (e.g. children who were unvaccinated or vaccinated with an alternate schedule. Review scientific findings and stakeholder concerns related to the safety of the recommended childhood immunization schedule Identify potential research approaches, methodologies, and study designs that could inform this question, including an assessment of the potential strength and limitations of each approach, methodology and design, as well as the financial and ethical feasibility of doing them. 27