1. Caitlin Rothermel, MA, MPH 1 Writing Effective Academy of Managed Care Pharmacy (AMCP) Dossiers The Medical and Health Economics Writing Group

2. Today’s Objectives – U.S. Market Access and the AMCP Dossier – AMCP Dossiers and Value Communication – The AMCP Dossier Format (with Updates to Version 4.0) – Payers and AMCP Dossiers – The E-Dossier System – Some Practical Issues When Developing AMCP Dossiers In this presentation, you will learn about:

3. 3 U.S. Market Access and the AMCP Dossier The Medical and Health Economics Writing Group

4. Market Access In the U.S. In the U.S., the key healthcare payers are a mix of governmental and private organizations U.S. Centers for Medicare and Medicaid Services Managed Care Organizations Indian Health Service Department of Veterans Affairs Pharmacy Benefit Management Consortia, Employers Individual Market 4

5. What Is the AMCP Dossier? The U.S. standard by which managed care organizations request evidence-based information to evaluate pharmaceuticals, biologics, and vaccines for formulary placement, coverage, and reimbursement decisions Provides a standardized template to present clinical and economic evidence AMCP: Academy of Managed Care Pharmacy – Developed to encourage a clear, transparent, 2-way communication process between manufacturers and healthcare decision-makers – Users include national and regional health insurers, pharmacy benefit managers, federal agencies, hospital systems, and state Medicaid agencies—representing >150 million Americans 5

6. How Are AMCP Dossiers Distributed? The Unsolicited Request Process FDAMA Section 114 allows manufacturers to respond to an unsolicited request from the health plan or equivalent—product dossiers cannot be sent to/viewed by a health system without an unsolicited request Processes for unsolicited requests established by the U.S. FDA; key elements of manufacturer’s safe harbor to provide medical information in response to an unsolicited request – Must be truly unsolicited, without prompting, suggestion, or solicitation by the drug manufacturer or its employees – Focus on data rather than company-generated discussions of data – Prepared by individuals with scientific and medical training – Does not deliberately go beyond the scope of the request – Does not include promotional materials – Objective, balanced, and scientifically rigorous 6 AMCP/FDA Letter. March 26, 2012. AMCP: Academy of Managed Care Pharmacy; FDA: Food and Drug Administration; FDAMA: Food, Drug, and Cosmetic Act

7. 7 AMCP Dossiers In Value Story Communication The Medical and Health Economics Writing Group

8. Dossiers In Value Story Communication A value story communicates unmet treatment needs and shows how a specific product can fill those needs; a dossier assembles this scientific information and messaging into a single reference document Disease state, practice patterns Why should payers & providers care about this disease? Current treatments What do payers & providers need to know about current treatment? Product effectiveness & economic value Why should payers & providers cover your product? 8

9. AMCP Dossier Preparation and the Value Story “The quality and comprehensive of evidence within the dossiers remains an issue. Plans are warning that if the evidence dossiers are hijacked by commercial interests in the companies or from outside, they will not use.” Sean Sullivan, PharmD, University of Washington AMCP Dossier Format Co-developer The AMCP Dossier Format has been designed to maintain a high standard of objectivity and credibility It provides manufacturers with a vehicle to articulate and promote their product’s value Value messaging can be incorporated into the Format, as long as it is scientifically accurate. But always keep in mind that the Format is primarily a scientific document

10. 10 The AMCP Dossier Format Version 4.0 The Medical and Health Economics Writing Group

11. AMCP Dossier Format Update History 1999 – Academy of Managed Care Pharmacy (AMCP) Committee organized 2000 – AMCP Format Version 1.0 2002 – AMCP Format Version 2.0 2005 – AMCP Format Version 2.1 2009 – AMCP Format Version 3.0 – Substantial format revisions from version 2.0 to 3.0 2013 – AMCP Format Version 3.1 – Updated to include: Companion Diagnostic Tests (CDT) Comparative Effectiveness Research Specialty Pharmaceuticals 2016 – AMCP Format Version 4.0 – Update includes : Biosimilars More detailed CDT section Medical devices (directly related to use of drug) Expanded economic model guidance Pre-approval dossier guidance Jackson J. AMCP Format for Formulary Submissions (slide presentation). February 2014. 11 New!

12. AMCP Dossier Format 3.1 vs 4.0 AMCP Format Version 4.0 was released in April 2016 – The 4.0 document is substantially shorter and more to the point than 3.1 (62 vs 108 pages) – Version 4.0 was designed to make the transition from 3.1 to 4.0 “relatively straightforward” 12 AMCP: Academy of Managed Care Pharmacy

13. What’s In the AMCP Dossier? Section 1.0 Section 1.0: Executive Summary (5 pps recommended, 8 max) Page limits have been increased 1.1 Clinical Benefits Efficacy/effectiveness and comparative effectiveness Safety/tolerability and unmet need that proposed therapy addresses 1.2 Economic Benefits Cost per unit, context of proposed costs (potential clinical/economic benefits) Shortcomings of other therapies 1.3 Conclusions Summarize value of proposed product, highlighting key clinical and economic advantages Include a statement regarding the expected impact of the product, relative to other available treatment options 13 New length!

14. Subsection 2.1: Product Description 5 pps recommended, 10 maximum Provide detailed information about the product, including: AHFS: American Hospital Formulary Service; ASP: Average Sales Price; CPT: Current Procedural Terminology; FDA: Food and Drug Administration; HCPCS: Healthcare Common Procedure Coding System; NDC: National Drug Code; WAC: Wholesale Acquisition Cost 14 What’s In the AMCP Dossier? Section 2.0, Place of Product in Therapy Generic and brand name, and therapeutic class All dosage forms, including strengths and package sizes NDC for all formulations ASP and WAC cost per unit size AHFS or other drug classification Additional codes for specialty pharmaceuticals (eg, HCPCS, CPT) U.S. FDA-approved indication(s) and date Pharmacology, pharmacokinetics/pharmacodynamics New length

15. CMS: U.S. Centers for Medicare and Medicaid Services; HEDIS: Healthcare Effectiveness Data and Information Set 15 Contraindications/warnings/precautions/adverse effects Interactions (drug/drug, drug/food, drug/disease) Dosing and administration Access, e.g. restrictions on distribution, supply; prescribing restrictions Co-prescribed/concomitant therapies Big Table: Concise comparison of prescribing information of target product and primary comparator products in same therapeutic area Describe how product may impact quality measures (eg, HEDIS scores, CMS Star rating) New! Subsection 2.1: Product Description Provide detailed information about the product, including: Section 2.0, Place of Product in Therapy

16. 16 Concise comparison of prescribing information of your product and primary comparator products, focused on safety and efficacy Include: dosing, indications, pharmacokinetic/pharmacologic profile, adverse effects, warnings contraindications, interactions, and other relevant For biosimilars, summarize the reference product (focus on “biosimilarity” – interchangeability and dosing equivalency) May include a discussion of comparator product(s) or services that proposed product will substitute for or replace If direct-head-to-head clinical trials of product vs comparators have been conducted, note this here (full coverage in section 3.0) Include a statement as to why comparators were selected (eg, guidelines, literature search) Subsection 2.1.1: Product Comparison Tabular format (the “Big Table”) Section 2.0, Place of Product in Therapy

17. Subsection 2.2.1—Disease Description 10 pages recommended, 15 max for each indication (with section 2.2.2) Should be brief and ideally formatted as bullets and tables/figures: Epidemiology and relevant risk factors, with a focus on identifiable subpopulations appropriate for the product Pathophysiology Clinical presentation Societal, humanistic, and/or economic burden OK for content to be longer for specialty pharmaceuticals or rare diseases Intent is to give reader a good overall sense of the disease and characteristics of the patients treated for the condition – Note specific subpopulations where product is expected to be most effective; include clinical markers, diagnostic, or genetic criteria used to identify these subpopulations 17 AMCP: Academy of Managed Care Pharmacy Section 2.0, Place of Product in Therapy New length

18. Subsection 2.2.2—Approaches To Treatment Should be very brief and ideally formatted as bullets and tables; do not duplicate content from later sections: How is the disease currently treated? How does the new product fit into standard or existing therapy ? 18 AMCP: Academy of Managed Care Pharmacy; FDA: U.S. Food and Drug Administration; REMS: Risk Evaluation and Mitigation Strategy Updated and reorganized Current approaches to treatment Place and anticipated use(s) of the proposed product, including targeted subpopulations Appropriate care setting(s) for administration (eg, self- administration, infusion clinic, physician office, hospital) Heterogeneity and treatment effect (ie, patient-to-patient variation) Note clinical practice guidelines Manufacturer’s proposed ancillary disease, education, or management intervention strategies Product development or post- marketing obligations required by the FDA (eg, REMS program, Phase IV trial, patient registry) Plans for drug safety monitoring post- approval Expected outcomes of therapy (eg., cure, palliation, symptom relief) Section 2.0, Place of Product in Therapy

19. Subsections 2.3.1 to 2.3.3, for dossiers with Companion Diagnostic Testing (CDT) Use when a CDT has been co-developed with drug or is required by FDA 2.3.1 – Product information for for CDT – 5 pps recommended, 10 max – Include information on type of test and intended use, analytic and clinical validity, clinical utility, economic value 2.3.2 – Place of CDT in clinical practice – 10 pps recommended, 15 max – Include in stand-alone CDT dossiers—disease description and approaches to treatment 2.3.3 – Supporting data for CDT – 2 pps recommended per study summary, 5 max – Include studies related to CDT not covered in section 3.0 (eg, validation studies, outcomes research, patient preference, safety) 19 AMCP: Academy of Managed Care Pharmacy; FDA: U.S. Food and Drug Administration New! Section 2.0, Place of Product in Therapy

20. Section 3.0: Supporting Clinical Evidence Subsections 3.1.1-3.1.4 have been eliminated Instead, Section 3 requests summaries of all primary prospective and retrospective clinical studies that investigate any aspect of the product via research conducted directly with patients Also include meta-analyses and indirect treatment comparisons 20 New! Relevant clinical evidence includes: Comparative effectiveness FDA-approved and unapproved uses; U.S. and ex-U.S. research Published and unpublished studies, of any study design type All study results, regardless of positive, negative, or null findings Relevant data and findings from governmental agencies Ongoing clinical trials and links to their registry information Typically does not include in vitro, animal, or phase 1 studies (unless value proposition is directly tied in to this research) 20 What’s In the AMCP Dossier? Section 3.0, Clinical Evidence

21. Subsection 3.1: Study Narrative Summaries This section provides narrative summaries of all primary clinical studies that support the use and value of the product The manufacturer should grade all studies summarized in the dossier, based on a recognized method 21 New! Section 3.0, Clinical Evidence

22. Subsection 3.1: Study Narrative Summaries (2 pps per study recommended, 5 max/study) Clinical study summaries should include (template provided in AMCP guidance): 22 New! Name of the clinical trial or study, and publication citation(s) ClinicalTrials.gov ID number, sponsor/funding Study objective, location, and date(s) Trial design, randomization, and blinding procedures Setting, inclusion, and exclusion criteria Baseline patient characteristics/demographics Dropout rates and procedures for handling dropouts Treatments/interventions, including dosage regimens, washout period, concomitant medications Clinical outcome(s); delineate primary vs. secondary endpoints as well as pre- specified vs post-hoc Statistical significance of outcomes and power calculations Validation of outcomes instruments Generalizability of treated population Study limitations, as stated by study authors Section 3.0, Clinical Evidence New length

23. Subection 3.2: Evidence Tables (<1 pg per study recommended, 2 pps max/study) Evidence tables should include: 23 Study citation Treatments Sample size and length of follow-up Inclusion/exclusion criteria Design Primary endpoints Secondary endpoints Results, including an explicit statement of effect size (ie, not just relative risk reduction and/or statistical significance) Include a table of key results in the “Results” column Statistical significance Formatting guidance: landscape format, appropriate use of abbreviations. Section 3.0, Clinical Evidence

24. Subection 3.2: Evidence Tables Formatting guidance: clear, objective, concise; landscape format; appropriate use of abbreviations—template provided in AMCP guidance 24 Section 3.0, Clinical Evidence

25. It is important that the dossier is transparent, reflecting the full body of evidence for the product However, if a product has been available for several years, there may be a very large number of studies in the medical literature and inclusion of each one may be impractical In such cases, it is suggested that evidence be separated into 3 categories: 1.Include large, key studies as study summaries and evidence tables 2.Smaller, less informative, and/or less rigorous studies should be added to evidence tables only 3.Other studies that do not add substantially to product knowledge base should be identified in a bibliography only Provide objective rationale for study delineation and assignment 25 AMCP: Academy of Managed Care Pharmacy Streamlining Clinical Study Content in Section 3.0 New!

26. Economic Models In the AMCP Dossier Section 4.0 26 AMCP: Academy of Managed Care Pharmacy Recommended model types for AMCP Dossiers Cost-effectiveness Assesses risk-benefit and economic value of drug in relation to other available treatments Good value for the money? Financial Minimal approach: financial impact on pharmacy budget only Budget Impact Expected changes in healthcare expenditures after adopting new intervention Is the product affordable? Section 4.0 of the AMCP Dossier Format requires a descriptive narrative and an interactive model – Enables healthcare systems to apply and evaluate based on their internal data (ie, membership, prevalence, cost estimates

27. Section 4.0: Economic Value and Modeling Report (12 pages recommended, 20 max/model) AMCP provides detailed preparation instructions/guidance based on model type (cost-effectiveness, budget impact, financial) Model summaries should include the following: – Abstract – Introduction / Background – Methods – Results – Limitations – Discussion Minimum 2 Figures, 3 Tables (detailed instructions provided) Adhere to CHEERS guidance Interactive Model (ideally in spreadsheet software) AMCP recommends subsequent peer-reviewed publication of model 27 AMCP: Academy of Managed Care Pharmacy; CHEERS: Consolidated Health Economic Evaluation Reporting Standards Section 4.0, Economic Value and Modeling Report New!

28. CHEERS Guidance (Consolidated Health Economics Reporting Standards) Report and 24-item checklist to optimize reporting of health economic interventions; developed by ISPOR (International Society for Pharmacoeconomics and Outcomes Research) 28 Download CHEERS at: http://www.ispor.org/ValueInHealth/ShowValueInHealth.aspx?issue=3D35FDBC-D569-431D-8C27-378B8F99EC67

29. AMCP Dossiers Don’t Always Include Economic Models A 2011 survey evaluated and compared the perspectives of payers and pharmaceutical manufacturers on AMCP Dossier version 3.0 – 31% of manufacturers did not include any economic model – An interactive economic model was only prepared by 2 out of 3 manufacturers – Even in cases where models were provided, they were not as user-friendly, clear, or transparent as payers would have liked 29 AMCP: Academy of Managed Care Pharmacy Medina RD et al. Evaluating the Value of Clinical and Economic Evidence-Based Information from Dossier Submissions Using the AMCP Format. AMCP 2011.

30. Consists of all other evidence types not covered in Section 3.0 This section has been reorganized and now includes information previously housed in other sections of the document 30 AHFS: American Hospital Formulary System; AHRQ: Agency for Healthcare Research and Quality AMCP: Academy of Managed Care Pharmacy; DHHS: Department of Health and Human Services; HTA: Health Technology Assessment; USP- NF: United States Pharmacopeia—National Formulary What’s In the AMCP Dossier? Section 5.0, Additional Supporting Evidence 5.1 Clinical Practice Guidelines Also, evidence-based consensus statements and clinical pathways Provide URLs/links, rationale for guidelines summarized 5.2 HTAs, systematic reviews, AHRQ, Cochrane Collaboration 5.3 DHHS-recognized compendia AHFS, USP-NF, DRUGDEX 5.4 Other economic or outcomes evidence Guidance provided to summarize economic research 5.5 Impact on Quality measures 5.6 Other evidence or information New!

31. Section 5.0: Secondary Clinical Evidence and Non-Clinical Studies This section has been reorganized and now includes information previously housed in other sections of the document 31 LYG: Life-years gained; QALY: Quality-adjusted life year What’s In the AMCP Dossier? Section 5.0 (2 of 2) 5.6 Non-clinical studies Any study that does not involve direct patient research Chart reviews, electronic medical records, administrative claims studies Also, health economic modeling studies and studies related to healthcare utilization, economic evidence, and productivity Health economics study summaries should include the following: Definition of economic endpoints (eg, mean overall costs, $/LYG, $QALY); references for standard of care costs Data sources for economic endpoints Statistical models/math used to calculate endpoints If applicable: modeling methodology, sensitivity analysis New!

32. Section 6.0: Supporting Information  6.1 References  6.2 Dossiers and Economic Models  Transparent, unlocked copy of model without a graphical interface  6.3 Product Prescribing Information  6.4 Patient Information  Eg, Patient Package Insert  6.5 Material Safety Data Sheet for product 32 What’s In the AMCP Dossier? Section 6.0 New!

33. 33 What We Know About Payers and AMCP Dossiers The Medical and Health Economics Writing Group

34. Payer Opinions on AMCP Models 34 Dymaxium (E-dossier vendor) conducted a 2015 survey (N=67 payers) to gain insight on payer’s use of economic models in AMCP dossier: – 24% never used models – 13% often used models – 63% sometimes used models Payers prefer cost-effectiveness analyses and budget impact models – Premera BCBS asks for both model types – Should be customizable to payer population – Consider using intuitively understood endpoints (lke per-member-per- month/PMPM) instead of QALYs http://www.ispor.org/health-policy_economic-models_life- sciences.pdf?utm_content=bufferf1430&utm_medium=social&utm_source=plus.g oogle.com&utm_campaign=buffer AMCP: Academy of Managed Care Pharmacy; BCBS: Blue Cross Blue Shield; QALY: Quality-adjusted Life Years

35. Payer Uses of AMCP Models 35 Payers were also asked the to describe what they used AMCP economic models for; most commonly: – To learn about the manufacturer’s clinical data (92%) – To scrutinize the cost-effectiveness analysis (91%) – For background information on the disease (85%) – To help conduct their own analysis (85%) – To repopulate the provided model with local data (73%) AMCP: Academy of Managed Care Pharmacy; BCBS: Blue Cross Blue Shield ISPOR 2015 http://www.ispor.org/health-policy_economic-models_life- sciences.pdf?utm_content=bufferf1430&utm_medium=social&utm_source=p lus.google.com&utm_campaign=buffer

36. When Payers Don’t Use AMCP Models 36 Payers were also asked what the main deficiencies were in AMCP models; the most commons answers were: – Biased assumptions (50%) – Timeliness of model (40%) – Not enough detail (30%) – Too much detail/too long (30%) At Premera BCBS, if model assumptions do not reflect real- world clinical practice, the model is not used 18% to 29% of payers construct their own models AMCP: Academy of Managed Care Pharmacy; BCBS: Blue Cross Blue Shield ISPOR 2015 http://www.ispor.org/health-policy_economic-models_life- sciences.pdf?utm_content=bufferf1430&utm_medium=social&utm_source=plus.g oogle.com&utm_campaign=buffer

37. 37 The E-Dossier System The Medical and Health Economics Writing Group

38. AMCP E-Dossier System AMCP supports an electronic platform to facilitate dossier distribution between manufacturers and health systems – 1,200 payers registered to use system; subscribers are 38% managed care, 21% pharmacy benefit management, 27% hospital and care facilities, 4% government institutions (eg, Veterans Affairs) – Secure, web-based platform allows formulary and/or benefit design decision-makers to easily access, review, and evaluate dossiers – Dymaxium can manage unsolicited requests from payers and dossier distribution Electronic submission is now the recommended approach for AMCP dossier dissemination – “Basic” and “Full” flat-fee annual subscription plans available for manufacturers; a free option is also available 38 http://www.ispor.org/health-policy_economic-models_life- sciences.pdf?utm_content=bufferf1430&utm_medium=social&utm_source=plus.google.com&utm_campaign=buffer

39. 39 Some Practical Issues When Developing AMCP Dossiers The Medical and Health Economics Writing Group

40. Writing AMCP Dossiers: Practical Issues Economic model section is health economics, but remainder of dossier content will be familiar to many medical writers Highly structured document, based on a defined format; plain formatting is a plus Length depends on number of indications and body of available research, (new product goal 45 to 90 pps, other products <100 pps) AMCP: Academy of Managed Care Pharmacy 40 Generally a team project—can be 400-500 hours’ work on tight turnaround Writers likely to be assigned specific sections Requires close project management AMCP Dossiers are a mix of traditional medical writing and health economics writing

41. Project Management of AMCP Dossiers: Practical Issues It is best to have 1 or 2 point people/project managers (PM) – To oversee version control, section review, and referencing – PM must have solid understanding of the AMCP Format – PM must develop strong understanding of document content – PM works closely with individual writers on content/deadline management; – PM is also main client liaison; expect regular client calls and/or contact reports AMCP: Academy of Managed Care Pharmacy 41 AMCP Dossiers require dedicated oversight

42. Project Management of AMCP Dossiers: Practical Issues It is easy to underestimate project scope and budget – The amount of content developed for AMCP dossiers varies widely based on the available evidence base Key questions to ask up front – Number of indications – Extent of existing clinical research – Number of revisions Keep concision in mind when planning dossier content – Determine ahead of time which studies will be covered, and at what level of detail – Know your value messages AMCP: Academy of Managed Care Pharmacy 42 Assess the details early in the process

43. A Final Practical Issue: When to Update AMCP Dossiers AMCP: Academy of Managed Care Pharmacy 43 When to update dossiers – New indication or changes to prescribing information – FDA advisory statement, new safety information – Important new clinical or economic evidence – Substantial changes to evidence base Updating from 3.1 to 4.0—do it now or later? – All new dossiers should be in AMCP version 4.0 – Manufacturers should make every effort to adopt version 4.0 for dossier updates AMCP: Academy of Managed Care Pharmacy; FDA: U.S. Food and Drug Administration

44. 44 Thank you! It’s time for Q & A The Medical and Health Economics Writing Group URL: medlitera.com