Medicinal Chemistry 401: Immunizing Agents 2007

1. Medicinal Chemistry 401: Immunizing Agents 2007 Instructor: Valerie Daggett, daggett@u.washington.edu Download and learn Childhood immunization schedule The slide sets associated with the topics will be the basis for the lectures. Extra slides may be added and presented in lecture. You should print the slides before class and bring them to lecture. RESOURCES Childhood Immunization Schedule CDC Pink Book

2. Why Teach about immunizing agents in Pharmacy? • Important health care issue • Pharmacists can play a role with education • Efficacy • Vaccine controversies • Changing recommendations • Misinformation • Patient compliance • New vaccines

3. Why immunize? • It is effective • The widespread use of vaccines has reduced the peak-level of incidence in the US by ≥95% • Immunizing also indirectly protects other people such as infants or those with contraindications • It saves lives • Ex. Measles • Before 1963 there were >500,000 cases/yr and 400-500 deaths/yr Now, ~85 cases/yr

4. Disease Pre-vaccine Era* 2005 % change Diphtheria 31,054 0 -100 Measles 390,852 66 -99 Mumps 21,342 314 -99 Pertussis 117,998 25,616 -78 Polio (wild) 4,953 0 -100 Rubella 9,941 11 -99 Cong. Rubella Synd. 19,177 1 -99 Tetanus 1,314 27 -98 Invasive Hib Disease** 24,856 144 -99 Total 566,706 26,179 -95 Vaccine Adverse Events 0 15,803 +++ Comparison of Maximum and Current Reported Morbidity, Vaccine-Preventable Diseases andVaccine Adverse Events, United States * Maximum cases reported in pre-vaccine era ** Invasive type b and unknown serotype

5. Why immunize? • Diseases still with us Measles outbreak in 1989-1991 there were >55,000 cases and 132 deaths • It saves money • Measles outbreak -> 44,000 days of hospitalization • $3-4 million in direct medical treatment costs per 1000 cases • $3000-$4000/person • You may be administering vaccines

6. Vaccines are different • Compounds are not drugs until they are approved by a regulatory agency • Vaccines have a low rate of market entrance • It is expensive and difficult to get them to market

7. Vaccines are different • Why? • Drugs go to a small number of sick people • Vaccines are administered to millions of healthy people Higher safety expectations Fear of lawsuits

8. National Childhood Vaccine Injury Act • Passed in 1986 • Goal: Protect manufacturers of vaccines • No-fault alternative to the tort system for resolving claims resulting from adverse reactions to particular vaccines • Assumed that vaccine is responsible, which is very hard to prove in court

9. This act requires 2 things of those who administer vaccines • Maintain permanent vaccination records • Vaccination histroy, date, vaccine manufacturer, lot number, name, adverse reactions • Report certain adverse effects to the Vaccine Adverse Events Reporting System (VAERS)

10. Frist Bill • Reform to vaccine injury compensation program • Law to apply to individual components…mercury • Later, new provisions to protect health care workers with respect to smallpox vaccine administration

11. $ for act • Excise tax $0.75 - $3.00 per vaccine All childhood vaccines carry this tax Fund paid out ~$50,000,000 in 1998 $116,000,000 was taken in that year

12. Other legal issues: • There have been many lawsuits filed against physicians and hospitals for failure to immunize • All were due to ignorance usually involving either new vaccines or new guidelines

13. Examples: • Hepatitis B carrier gives birth after delivery baby did not get HBIG nor HepB vaccine. Infant became a chronic carrier • Hib. Child developed Hib disease which led to brain damage. Parents had tried to get the vaccine but told no because the doctor didn’t know about it.

14. Missed Opportunity A healthcare encounter in which a person is eligible to receive vaccination but is not vaccinated completely

15. Reasons for Missed Opportunities • Lack of simultaneous administration • Unaware child needs additional vaccines • Invalid contraindications • Inappropriate clinic policies • Reimbursement deficiencies

16. Reduction to Barriers to Immunization • Physical barriers • waiting time • distance • Psychological barriers • unpleasant experience • safety concerns • misinformation

17. Importance of Vaccine Safety • Decreases in disease risks and increased attention on vaccine risks • Public confidence in vaccine safety is critical • higher standard of safety is expected of vaccines • vaccinees generally healthy (vs. ill for drugs) • lower risk tolerance = need to search for rare reactions • vaccination universally recommended and mandated

18. Importance of Vaccine Safety • Ongoing safety monitoring needed for the development of sound policies and recommendations

19. Prelicensure Vaccine Safety Studies • Laboratory • Animals • Humans

20. Prelicensure Human Studies • Phases I, II, III trials • Common reactions are identified • Vaccines are tested in thousands of persons before being licensed and allowed on the market

21. Postlicensure Surveillance • Identify rare reactions • Monitor increases in known reactions • Identify risk factors for reactions • Identify vaccine lots with unusual rates or types of events • Identify signals

22. Postlicensure Vaccine Safety Activities • Phase IV Trials • ~10,000 participants • better but still limited • Large-Linked Databases • Clinical Immunization Safety Assessment Network

23. Vaccine Adverse Event Reporting System (VAERS) • National reporting system • Jointly administered by CDC and FDA • Passive (depends on healthcare providers and others to report) • Receives ~15,000 reports per year

24. Vaccine Safety Datalink (VSD) • Large-linked database • Links vaccination and health records • “Active surveillance” • 8 HMOs • ~2% of the U.S. population • Powerful tool for monitoring vaccine safety

25. The Provider’s Role • Immunization providers can help to ensure the safety and efficacy of vaccines through proper: • vaccine storage and administration • timing and spacing of vaccine doses • observation of contraindications and precautions

26. The Provider’s Role • Immunization providers can help to ensure the safety and efficacy of vaccines through proper: • management of vaccine side effects • reporting of suspected side effects to VAERS • vaccine benefit and risk communication

27. Benefit and Risk Communication • Opportunities for questions should be provided before each vaccination • Vaccine Information Statements (VISs) • must be provided before each dose of vaccine • public and private providers • available in multiple languages