The Vaccine Formulary Selection Algorithm: A Web-Based Tool for Determining Best-Economic Value Pediatric Immunization F

1. The Vaccine Formulary Selection Algorithm:A Web-Based Tool for Determining Best-Economic Value Pediatric Immunization Formularies Daniel A. Allwine, M.S. This work is supported by Contract No. 200-2002-00789 from the Centers for Disease Control and Prevention (CDC). CDC Project Officer: Bruce G. Weniger, M.D., M.P.H. Immunization Safety Branch, NIP, CDC

2. Participants and Contributions A collaborative effort between government, industry, and academia. • GOVERNMENT: Centers for Disease Control and Prevention • Bruce G. Weniger, M.D., M.P.H. • - Project Officer, SBIR Contract No. 200-2002-00789 • - Vaccine Domain knowledge. • INDUSTRY: Austral Engineering and Software, Inc. • Enrique Medina, M.S., Daniel Allwine, M.S., M. QadeerAhmed • Software and user interface design and web implementation. • User interaction. • ACADEMIA: Southern Illinois University Edwardsville • University of Illinois at Urbana-Champaign • Edward C. Sewell, Ph.D. • Sheldon H. Jacobson, Ph.D. • - Modeling and algorithm development.

3. Motivation • The economic factors involved in establishing a cost-effective pediatric immunization formulary are not straight forward. • Some tangible and intangible costs: • Vaccines and related products • Administration, storage, and delivery • Pain and suffering (leads to avoidance) • Potential treatment for unvaccinated individuals • Combination vaccines are making the procurement landscape more complicated.

4. Objectives Assist health care professionals in making vaccine formulary choices for purchasing. • Automate determination of best-value formularies to procure. • Facilitate use of vaccine selection algorithm through a user-friendly website • Provide access to large number of users throughout the health care system. • Allow users to customize costs for their particular situation.

5. Potential Users of Website  Purchasers of Vaccine Products  Public Sector Agencies • Federal, state, and local agencies • Physician Groups • Health Maintenance Organizations • Pediatricians and Family Practitioners  Health Insurance Companies  Vaccine Manufacturers

6. Technical Content • CDC/Academia collaboration since 1996. • Operations research modeling and economic vaccine selection algorithm within the childhood immunization schedule. • Weniger, B.G., Chen, R.T., Jacobson, S.H. Sewell, E.C. Deuson, R., Livengood, J.R., Orenstein, W.A., 1998, "Addressing the Challenges to Immunization Practice with an Economic Algorithm for Vaccine Selection," Vaccine, 16(19), 1885-1897. • Jacobson, S.H., Sewell, E.C., Deuson, R., Weniger, B.G., 1999, “An Integer Programming Model for Vaccine Procurement and Delivery for Childhood Immunization: A Pilot Study,” Health Care Management Science, 2, 1-9. • Sewell, E.C., Jacobson, S.H., Weniger, B.G., 2001, “ “Reverse Engineering” a Formulary Selection Algorithm to Determine the Economic Value of Pentavalent and Hexavalent Combination Vaccines,” Pediatric Infectious Disease Journal, 20(11), S45-S56. • Jacobson, S.H., Sewell, E.C., 2002, "Using Monte Carlo Simulation to Determine Combination Vaccine Price Distributions for Childhood Diseases,” Health Care Management Science, 5(1). • Jacobson, S.H., Sewell, E.C., Allwine, D.A., Medina, E.A., and Weniger, B.G., “Designing pediatric vaccine formularies and pricing combination vaccines using operations research models and algorithms,” Special Report. Expert Review of Vaccines 2(1), 15-19, 2003. • Jacobson, S.H., Karnani, T., and Sewell, E.C., “Analyzing the economic value of the hepatitis-B - Haemophilus influenzae type B combination vaccine by reverse engineering a formulary selection algorithm,” Vaccine 2003;21:2169-2177.

7. Operations Research Model • Operations research model currently captures: • ACIP recommended childhood immunization schedule requirements. • Cost components (e.g., vaccine purchase prices, labor costs, office visit costs, injection costs). • Vaccine constraints (e.g., number of injections, age limitations, brand matching). • Vaccine wastage by expiration.

8. Problem Characteristics • Goal: Find optimal formulary • Lowest-cost set of vaccines that satisfies the Recommended Childhood Immunization Schedule • Puzzle Analogy: Put pieces together to form the picture • We know the desired picture • Each piece has a price • There are many extra pieces • A piece can be used in more than once • 100,000 to 5,000,000 ways to assemble the puzzle • We must find the least expensive way

9. Recommended Childhood and Adolescent Immunization Schedule — United States — 2005 Preadolescent Assessment Range of Recommended Ages Catch-up Immunization Age Vaccine Birth 1 mo 2 mo 4 mo 18 mo 24 mo 4-6 y 11-12 y 13-18 y 6 mo 12 mo 15 mo HepB #1 only if mother HBsAg ( - ) HepB series Hepatitis B1 HepB #3 HepB #2 Diphtheria, Tetanus, Pertussis2 DTaP DTaP DTaP DTaP DTaP Td Td Haemophilus influenzae Type b3 Hib Hib Hib Hib Inactivated Poliovirus IPV IPV IPV IPV Measles, Mumps, Rubella4 MMR #1 MMR #2 MMR #2 Varicella Varicella5 Varicella Pneumococcal6 PCV PCV PCV PCV PCV PPV Influenza (yearly) Influenza7 Vaccines below this line are for selected populations Hepatitis A8 Hepatitis A series Influenza (yearly) Approved by the Advisory Committee on Immunization Practices, the American Academy of Pediatrics, and the American Academy of Family Physicians.

10. Vaccine Selection Algorithm • Uses operations research principles to determine the best-value (lowest cost) vaccine formulary that satisfies all the constraints. • Efficiently search across all possible sets of vaccine products • There are approximately 100,000 to 5,000,000 vaccine formularies to examine for each set of cost data. • As additional vaccines (particularly combination vaccines) are added to the market, this number will grow exponentially!

11. Search Tree HBV Month 2 None GSK MRK MRK HIB-HBV DTPa DTPa DTPa DTPa Month 2 Month 2 Month 2 Month 2 AVP GSK AVP GSK AVP GSK AVP GSK HIB HIB HIB HIB HIB HIB HIB HIB Month 2 Month 2 Month 2 Month 2 Month 2 Month 2 Month 2 Month 2 • Organized procedure to examine all the possibilities • At each level, must choose a vaccine for a disease/month. • Preprocessing eliminates vaccines that cannot possibly be in best-value formulary. • Pruning eliminates useless branches.

12. Search Engine and Validation • “Back End” Search Engine is written in C++ • Typical problem • Solved in less than half a minute • 500,000 to 1,000,000 branches (partial solutions). 50,000 to 100,000 full solutions are examined • Problem was also modeled as an Integer Program (IP) • Used AMPL to generate the IP from the data, CPLEX to solve the IP • Randomly generated 1,000 test problems • Input parameters randomly chosen • Prices randomly generated • Existing vaccines randomly chosen for inclusion/exclusion • Hypothetical combination vaccines randomly created • Test problems solved using both the search engine and the IP. Same solutions were found by both methods

13. Website Architecture and User Interface • Developed in state-of-the-art Microsoft® .NET platform • Server Software: • .NET components: solver in C++ and a managed wrapper in C# • Default and user-customized vaccine data in SQL database • Middleware Software: • ASP.NET scripts generate HTML and Javascript code • Served to web browser (client) by Internet Information Server • Client software: user interface through common browsers • Best when viewed in Internet Explorer • Recently released a more friendly user interface for occasional users • Similar to common tax preparation software packages • Interview driven

14. Hypothetical AVP DTPa-HIB-IPV A hypothetical DTPa-HIB-IPV pentavalent product from AVP can be considered.

15. Closing Remarks • www.vaccineselection.com finds best-value vaccine formularies (all antigens as of today) • Enables “what-if” scenarios • Web interface supports Government, “Private”, and/or user-customized prices • Website use is currently free • Additional services available • Analysis of your particular vaccine procurement scenario • Automated what-if scenarios, price selection, model structure customization, price change notifications