AMCP PT Monograph Review

1. AMCP P&T Monograph Review Jennifer Banovic, PharmD, BCPS Drug Information Clinical Specialist November 5th 2009

2. Objectives Understand the primary sections contained in a dossier Apply the format of the AMCP monograph Design a clinical efficacy table Demonstrate how to complete a search of primary literature

3. DOSSIER

4. What is a product dossier? Clinical summary of a drug Standardized reporting format Provided by drug manufacturers Tool for formulary decision-makers MCOs, PBMs, health-systems It is NOT a sales or marketing tool It CANNOT offer precise answers guarantee better overall decisions reduce healthcare expenditures

5. The AMCP Format for Formulary Submissions Used by organizations across the country Regence Group, numerous BCBS plans nationwide, PBMs such as AdvancePCS and Cardinal Health Plans that use the Format enroll >100 million members Widely accepted by pharmaceutical industry Acknowledgment of the Format�s value at the individual P&T committee level FDA regulations require that dossiers be made available only upon request; cannot be proactively disseminated

6. The AMCP Format for Formulary Submissions Version 2.1: www.fmcpnet.org/data/resource/Format~Version_2_1~Final_Final.pdf Format for product dossiers Integrates published and unpublished data on efficacy, safety, economic impact, and other medical outcomes Permits efficient review by coverage and formulary decision-makers Goals: Improve timeliness, scope, quality, and relevance of information available to P&T committees Simplify the review process

7. Responsibilities of the drug companies Dossier ready by the time product is launched 4 primary sections Must be presented in a specific order Allows for efficient review Supporting information should also be included Provide dossier in response to unsolicited requests

8. The AMCP Format - Sections Disease and Product Information Supporting Clinical and Economic Information Cost-effectiveness and Budget Impact Model Report Product Value and Overall Cost Supporting Information Reprints, bibliography, checklist, electronic media, appendices, authors

9. Section 1 - Product Information 1.1 Product description (max 20 pages) Names, class, forms, indications, pharmacology, PK/PD, warnings, precautions, CIs, AEs, dosing, cost, access, etc. Table with comparator products 1.2 Place of the product in therapy 1.2.1 Disease description (max 2-4 pages/disease) Epidemiology and risk factors, pathophysiology, clinical presentation, societal/economic impact 1.2.2 Approaches to treatment (max 2-3 pages/indication) How is disease treated and how does the drug fit into therapy Treatment guidelines 1.3 Evidence for pharmacogenomic tests and drugs

10. Section 2 � Supporting Clinical and Economic Information 2.1 Summarizing key clinical and economic studies Pivotal efficacy and safety trials (3-4 pages/study) Systematic reviews and meta-analyses Positive and negative findings 2.1.1 Evidence table spreadsheets of all published and unpublished trials Citation, sample, design, inclusion/exclusion, treatments, endpoints, results, significance 2.2 Outcomes studies and economic evaluation supporting data 3-4 pages/study 2.1.1 Evidence table spreadsheets of all published and unpublished outcomes studies

11. Section 3 - Modeling report 3.1 Model overview (20 pages) Cost-effectiveness ideal 3.2 Parameter estimates for models Translate efficacy results to effectiveness parameters 3.3 Perspective, time horizon and discounting Primary analysis � payer perspective Secondary evaluation � societal perspective 3.4 Analyses Clear and transparent � data and calculations are visible 3.5 Presentation of model results Inputs, assumptions, costs, sensitivity analyses 3.6 Exceptions

12. Section 4 - Product Value and Overall Cost Summary of all clinical and economic information presented in the previous sections Expected cost/unit Value argument Manufacturer should justify expected expenditures Context of clinical and economic effects Clients and members Why the product should be added to formulary Max 2-3 pages

13. Section 5 - Supporting Information 5.1 References contained in dossiers List and provide copies 5.2 Economic models Spreadsheet or CD-ROM Transparent, unlocked Designed to allow individuals to review calculations Not graphical representation as presented in section 3 5.3 Formulary submission checklist

14. DRUG MONOGRAPH

15. Drug Monograph Comprehensive review of a drug or drug class Questions to keep in mind Is the drug� More effective Safer More convenient (easier to use) Cheaper

16. Drug Monograph Drug profile Manufacturer, patent expiration, labeled/unlabeled uses Dosing, administration, availability (formulations) Adjustments for renal or hepatic impairment, elderly or pediatrics Pharmacology Brief description of the mechanism of action Focus on information clinically relevant to the drug�s formulary status PK (ADME) AEs, monitoring parameters What is clinically relevant? Consider special patient populations Specific adverse effects reported in table format CIs, interactions, allergies, intolerances Drug-drug, drug-food, drug-disease state Include interaction, description, and clinical significance of interaction Consider a table format Therapeutic use Similar drugs, same drug class or same treatment indication

17. Example

18. Example

19. Drug Monograph Summary of medical evidence Studies supporting efficacy Large, well-designed, head-to-head, randomized controlled trials are ideal Compile trials in tabular format 1st, then summarize evidence from clinical trials Background information needed to interpret results

20. Specific elements of efficacy table Reference: author, year, citation Trial design/duration Randomized (R), double-blind (DB), placebo-controlled (PC), parallel-group (PG), crossover (XO), etc. Use abbreviations and define at end of table n = number of patients in the study Drug regimens: list regimens and placebo (if applicable) Abbreviations may save space Demographics: patient characteristics End points Primary, secondary Single, composite outcomes Safety Results/comments Corresponding result for each endpoint Limitations of the study

21. Example

22. Drug Monograph Economic evidence Pharmacoeconomic studies and outcomes research Compare value of 1 therapy vs. another Evaluate cost and effect on healthcare resource utilization ($, efficacy, QoL) Prepare table 1st, then summarize Utilization data Formulary tier, market share, # Rxs, AWP/Rx, mean quantity dispensed Budget impact/cost-effectiveness model Type of model, key assumptions, sensitivity analyses and scenarios Model results and conclusions Projected impact of formulary addition on the plan�s drug budget Pipeline products in Phase 3

23. Drug Monograph Place in therapy Where does this product fit in? What factors do we need to consider? Overall product value and cost How much will we spend on this? Impact: member, client, PBM perspectives Formulary recommendations Reflect what was presented in the monograph Final and concise version of findings Proposed programs Authors References (correct format)

24. Issues for formulary consideration Should the drug be added to the formulary? Is there a specific therapeutic niche and/or subpopulation of patients to which its use should be restricted? If so, how to define/identify? Should the drug be declared to be therapeutically equivalent to similar drugs (those mentioned in the introduction)?

25. Study Results and NNT Absolute risk reduction (ARR) Absolute difference in rates of an outcome between groups Ex: Risk of stroke is 4% with a statin and 6% with placebo; ARR = 2% Relative risk (RR) Ratio of the risk in the treatment group to the risk in the control group Ex: RR = 0.66 Relative risk reduction (RRR) Relative risk subtracted from Ex: RRR = 0.34 or 34% Number needed to treat (NNT) Number of patients that need to be treated to prevent 1 outcome Reported as a whole number Higher numbers = more patients need to be treated Lower numbers = less patients need to be treated 1/ARR = 1/0.02 = 50

26. Practice Statin Placebo Survival 91.8% 88.5% Mortality 8.2% 11.5% ARR 11.5% - 8.2% = 3.3% RR 8.2 /11.5 = 0.71 RRR 3.3 /11.5 = 0.29 = 29% (OR 1-0.71) NNT 1 /3.3 = 30 Statin Placebo Survival 91.8% 88.5% Mortality 8.2% 11.5% ARR 11.5% - 8.2% = 3.3% RR 8.2 /11.5 = 0.71 RRR 3.3 /11.5 = 0.29 = 29% (OR 1-0.71) NNT 1 /3.3 = 30

27. SEARCHING THE MEDICAL LITERATURE

28. Medline/PubMed Database from the National Library of Medicine Biomedical/medical literature From 1950�s to present >15,000,000 records Indexes >5000 journals Available via UIC library website Linked to full-text if available - must access via UIC library to obtain

29. Steps to search Medline Access through http://library.uic.edu Click �Databases A-Z� Click on �PQ� Click on Type drug name in the search box and hit �Search�; numerous articles will appear For a more specific search enter drug name with AND the disease state To further limit the search, click �Advanced search�

30. Steps to search Medline Check the following boxes: Humans English Clinical trial and/or randomized controlled trial Click �Search� � there should be fewer hits Clicking on the title of the article to see the abstract To obtain the full-text article, click You may be able to access the full-text online; if not, obtain it from the library

31. Key points Important to complete a Medline search as there may be more data published than in the dossier Comparative trials (those that compare 1 drug to another similar drug) are valuable in establishing a place in therapy Look for well designed trials with a large patient population Article selection should be based on the quality of the study Do not base your article selection on the outcomes Only using positive outcomes creates bias

32. GOOD LUCK!