David Bartram BVet Med Dip M CDip AF

David Bartram BVet. Med, Dip. M, CDip. AF, MPhil, Dip. ECSRHM, FRCVS Director Outcomes Research, Zoetis International Operations 1 1 One Health EJP Summer School, 28 August 2019, University of Surrey

WELCOME Congratulations on being selected participate in One Heath EJP Summer School Over-arching objectives of this session: Connect, Learn, Encourage, Inspire 2 2

CURRICULUM 3 3 • What is Outcomes Research: pharma industry perspective • Sources of value • Defining the value proposition • Identifying evidence gaps • Developing project proposals • Communicating value • Case studies

CURRICULUM • What is Outcomes Research? • Sources of value • Defining the value proposition • Identifying evidence gaps • Developing project proposals • Communicating value • Case studies 4 4 AGENDA • Introduction to Outcomes Research: a pharma perspective • Sources of value for One Health interventions (Workshop) • Defining the value proposition and beyond (Workshop)

PRIMARY LEARNING OBJECTIVE Able to understand potential sources of value for One Health interventions and develop project proposals to demonstrate and communicate that value communicate for different stakeholders 5 5

WHAT IS OUTCOMES RESEARCH? • OR evaluates the economic, clinical and quality-of-life outcomes of health care interventions to inform health care decision-making • OR works within the marketing/technical teams to identify meaningful value propositions for Zoetis products/ services and generate robust and compelling supporting evidence for the development of sales and marketing communication tools and to inform value-based pricing 6 6 Creating value for, communicating value to and capturing value from customers

the importance of outcomes research 7 7

VALUE-BASED PRICING VALUE CORRESPONDING TO EACH OF ‘ 3 C’ PRICE COMPONENTS 8 8

OUTCOMES-BASED PRICING / RISK-SHARING HUMAN PHARMA EXAMPLE 9 9 • Indicated for the treatment of heart failure in patients with systolic dysfunction. • OR studies showed reduced rate of cardiovascular-related death and heart failure hospitalisation compared to angiotensinconverting enzyme (ACE) inhibitor therapy but Entresto costs 10 x more per day. • Novartis offers upfront discount on the drug price in exchange for a share of downstream healthcare savings resulting from use of the drug - specifically, savings resulting from reductions in hospital stays.

OUTCOMES-BASED PRICING / RISK-SHARING ALPHAJECT Livac SRS pricing strategy • • • 10 10 Salmon Rickettsial Septicaemia Drives 80% of antimicrobial use for fish in Chile First live vaccine approved for use in sea water Customer expected a sharing of risk Value proposal: Base price USD 0. 20 per dose Additional discount up to 15% if vaccinate > 80% of fish population Additional USD 0. 10 to be paid before harvest (about 16 months later) based on two performance criteria to be negotiated with customers: a) Antibiotic use less than 200 gt-1 fish (varies by customer) b) Mortality caused by SRS less than 1. 5% (varies by customer)

DIFFERENCES FROM CLINICAL RESEARCH • OR attempts to understand explain the end results of health care interventions • Both experimental and non-experimental designs • includes observational, retrospective, meta-analysis, systematic reviews • Intervention being evaluated is not limited to medicines – includes services, policies • Considers additional parameters in addition to therapeutic efficacy and safety – cost, timeliness, ease of use, compliance, quality of life, veterinarian and owner preference/experience/satisfaction, performance of a system – effectiveness (performance in ‘real-world’ everyday setting) vs. efficacy (performance under ideal circumstances) • Often less expensive, faster, fewer animals required, concurrent interventions permitted, heterogeneous population • Seeks to inform decisions of those who participate in healthcare • More multi-disciplinary – pharmacoeconomics, epidemiology, sociology, psychometrics • Less restrictive regulatory environment • Higher external validity: better extrapolation potential due to broader population • Lower internal validity: greater likelihood of wrong conclusions because of error from bias or 11 confounder 11

OUTCOMES RESEARCH PROCESS #1 #2 #3 12 12 #4 • Integration of OR into the planning process • Identification of meaningful value proposition • Generate and collate evidence to support the value • Delivery of communication tools

DELIVERING VALUE THROUGH THE SOLUTIONS SELLING MODEL Is the value delivered consistent with expectations? Post-Call Follow-up Present supporting evidence of value Ask for the Business Tailor value message to customer needs Develop Tailored Solution(s) 13 13 Identify potential sources of value Pre-Call Planning What materials exist to demonstrate value? Open the Call Which sources of value are important to this customer? Identify and Confirm Customer Needs

SOURCES OF VALUE

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WHAT IS VALUE? • Multiple definitions – an example: – the perception (measure) of what a product or service is worth to a customer compared to the price that is paid • Not always rational/ economic 16 16

STAKEHOLDER OBSESSED OR demonstrates value as seen through the eyes of a stakeholder Recognising that different stakeholders perceive value in different ways 17 17

WHO ARE THE STAKEHOLDERS? INDENTIFY THE DIFFERENT POSSIBLE STAKEHOLDER GROUPS FROM A ONE HEALTH PERSPECTIVE • Tablet which reduces itching in dogs • Vaccine to control bacterial septicaemia in salmon • Vaccine to control E. coli in poultry • Vaccine to control rabies in dogs • Injection to control sheep scab • Diagnostic test to identify dairy cows with mastitis at dry off • Testing to identify cattle with bovine tuberculosis 18 18

POTENTIAL SOURCES OF CUSTOMER VALUE Psychosocial (Emotional) Functional 19 19 Economic

WORKSHOP - LIST POTENTIAL SOURCES OF STAKEHOLDER VALUE - NOT INTERVENTION- OR STAKEHOLDER- SPECIFIC

POTENTIAL SOURCES OF CUSTOMER VALUE Psychosocial (Emotional) Functional 21 21 Economic

POTENTIAL SOURCES OF VALUE NOT INTERVENTION OR STAKEHOLDER SPECIFIC Psychosocial (Emotional) 22 22 Functional Economic

POTENTIAL SOURCES OF CUSTOMER VALUE A NON-SPECIFIC EXAMPLE Functional • • Dosing regime/ pack size convenience Consistent effectiveness Technical support Laboratory services Industry stewardship e. g. AMR Training Reliability of supply / inventory management • Ease of administration • Health and safety • Manufacturing compatibility (feed additives) 23 • Environmental impact • Shelf life 23 Psychosocial (Emotional) • Enhanced status • Sense of belonging • Sense of assurance (reduced risk/ peace of mind) • Quality of life • Animal welfare • Relationship with supplier Economic • • Increased product margin/ revenue Increase # customers Higher ROI Increased livestock lifetime productivity Reduced production cost Reduced labour cost Reduced mortality – includes opportunity cost • Increased customer loyalty, customer satisfaction, visit frequency • Opportunity to cross-sell

WORKSHOP REPEAT PREVIOUS EXERCISE BUT, THIS TIME, DO IT FOR A SPECIFIC ONE HEALTH INTERVENTION AND FROM THE PERSPECTIVE OF A SPECIFIC STAKEHOLDER DURING FEEDBACK, SPECIFY INTERVENTION AND PERSPECTIVE

POTENTIAL SOURCES OF CUSTOMER VALUE Psychosocial (Emotional) Functional 25 25 Economic

POTENTIAL SOURCES OF VALUE SPECIFIC INTERVENTION AND STAKEHOLDER Intervention Stakeholder Economic Psychosocial (Emotional) 26 26 Functional

WHAT IS VALUE? • Value equations *e. g. Quality of life + owner experience + return to normal function * *Includes need for ongoing interventions; occurrences of treatment-related illnesses etc. • 27 27 Differences between conventional and new paradigms – Input- vs. outcome-focused – Uni- vs. multi-dimensional

VALUE PROPOSITION • A promise of the value to be delivered • Succinctly answers the question: ‘Why should I implement this One Health initiative’? ‘Why should I buy your product/service rather than a competitor’s? ’ • 28 28 What makes a good value proposition? – Relevant to customer – resonates – satisfies their needs – Quantifiable – and can be substantiated – Differentiating

Benefits sought and value ladder template Possible column headings • Animal, Human, Environment • Different stakeholders 29 29

WORKSHOP USE THE SOURCES OF VALUE (IDENTIFIED IN PREVIOUS WOKSHOP) FOR SPECIFIC INTERVENTION AND STAKEHOLDER TO CRAFT A VALUE PROPOSITION USE THE BILLBOARD TEMPLATE

VALUE PROPOSITION BILLBOARD EXERCISE Promise of value to be delivered. ‘Why should the stakeholder adopt this intervention? ’ 31 31 This is not intended to be a marketing slogan. Do not try to be clever! Explain the value in one sentence.

AFTER DEFINING THE VALUE PROPOSITION… What evidence is there to support the value proposition? 32 32 What are the gaps? What additional evidence is required? Generate project proposals to fill evidence gaps

DEVELOPING PROJECT PROPOSALS INTERVENTION 33 33 STAKEHOLDER VALUE PROPOSITION EVIDENCE GAP PROJECT PROPOSAL DELIVERABLE

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EXISTING TOOLS: VALUE COMMUNICATION TOOL RUMINANT – CATTLEMASTER® GOLD – BRAZIL VALUE PROPOSITION Increases breeding performance to enhance net profit at weaning in cow-calf beef herds EVIDENCE GAP Tool to communicate financial net benefits to farmer of using Cattle. Master® GOLD compared to no vaccination DESCRIPTION OF DELIVERABLE ROI calculator User input variables enable results to be tailored to individual farms 35 35

EXISTING TOOLS: VALUE COMMUNICATION TOOL COMPANION ANIMAL – SR 12 LIFETIME VALUE AGGREGATE REPORT – AUSTRALIA VALUE PROPOSITION Increasing the number of dogs on SR-12 increases revenue and loyalty for your practice while providing excellent protection for dogs DATA GAP Aggregate Report representative of Australian practices DELIVERABLE Aggregated Data report any TBM can use 36 36

EXISTING TOOLS: VALUE COMMUNICATION TOOL SWINE: ZOETIS PCV-MH-PRRS VACCINE VS. BI – A COMPARATIVE STUDY FOR APAC VALUE PROPOSITION Gain MS quickly by converting customers to Zoetis combo vaccine, preserving the value of the market EVIDENCE GAP Data to show Fostera PCVMH & PRRS combo vaccines outperform BI against triple co-infection challenges and better financial benefits DESCRIPTION OF DELIVERABLE Peer Review Publication PPT Slides with key messages & financial data for salesforce 37 37 Peer-reviewed and published in The Canadian Journal of Veterinary Research: 2018; Issue 82, Page 39– 47

EXISTING TOOLS: VALUE COMMUNICATION TOOL SWINE: RUILAN’AN – COMPARATIVE STUDY – CHINA VALUE PROPOSITION To increase market penetration of Ruilanwen against an emerging local strain of highly pathogenic PRRSV DATA GAP Evidence of clinical protection in pigs of Ruilan’An vaccination is more efficacious and safer than Ingelvac PRRS MLV and a local JXA 1 -R vaccine against HP-PRRS TP strain (JXA 1 -R like) virus challenge DELIVERABLE Data accepted for 2018 IPVS presentation Report in China HP-PRRS Swine KOL Roundtable and Seminar 38 38

EXISTING TOOLS: VALUE COMMUNICATION TOOL PHARMAQ – ALPHA JECT® LIVAC SRS – PANGA 2 VALUE PROPOSITION Increases profitability EVIDENCE GAP Tool to communicate financial net benefits to farmer of using vaccine compared to alternatives DESCRIPTION OF DELIVERABLE ROI calculator User input variables enable results to be tailored to individual farms 39 39

CASE STUDIES RISPOVAL INTRANASAL VACCINE DRAXXIN

RISPOVAL INTRANASAL 41 41

POTENTIAL SOURCES OF CUSTOMER VALUE RISPOVAL INTRANASAL VACCINE Psychosocial (Emotional) • Pride in good stockmanship, animal welfare etc. • Acting responsibly – using AIFs as little as possible, as much as necessary • Peace of mind that profits are protected by optimising herd respiratory health • Quality of life – time management – producer has more time with family because fewer BRD cases to treat • Enhanced professional image (vet) - reinforces central role of vet in herd health and productivity Functional • Producer is better able to plan workload/ time management vs. AIF treatment of BRD outbreaks • Respiratory health tools and support services offered by Zoetis – including vet/producer education • Ease of administration (IN) 42 • Superior label claims compared to other resp. vaccines – earliest protection 42 Economic • Increased herd lifetime productivity • optimised growth rates, carcass quality, % mortality, age at first breeding, first and second lactation milk yield, longevity in dairy herd etc • Reduced labour costs (single dose) • Reduced costs of treating BRD • Opportunity for vet to cross-sell Zoetis complementary respiratory health products/services • Potential for vet practice to grow business through increasing vaccine penetration in herds

VALUE PROPOSITION EXAMPLE FOR RISPOVAL INTRANASAL Elements Target Cattle veterinarians (farmers) Core need/s who want to increase profitability Offering Name Rispoval IN Frame of Reference Herd health management Benefits Significant business growth opportunity (optimised lifetime productivity) Point of Difference Zoetis provides the best support for your practice to demonstrate vaccination benefits to farmers (earliest protection for improved calf performance)* 43 Supporting 43 Statement Formula attributes Intranasally-administered live vaccine; speed of onset and duration of immunity; services (materials, tools, FF support) * important to demonstrate link between calf performance and lifetime productivity

OR PROJECT • Desk research • Published evidence of effects of respiratory disease on lifetime productivity in beef and dairy calves • Applied contemporary costings 44 44

LIFETIME VALUE OF RESPIRATORY HEALTH BEEF SUCKLER CALVES 45 45

LIFETIME VALUE OF RESPIRATORY HEALTH DAIRY-BRED BEEF CALVES 46 46

LIFETIME VALUE OF RESPIRATORY HEALTH DAIRY HEIFERS 47 47

FARMER LEAFLETS 48 48

PRESS ADVERTISING 49 49

WEBSITE 50 50

E-DETAILER 51 51

VIDEO ANIMATION 52 52

ROI CALCULATORS 53 53

SHOW STAND 54 54

DRAXXIN #1 BRD treatment efficacy 1, 2 #1 BRD metaphylaxis efficacy 3 Fewer antimicrobial doses when Draxxin is used as first choice 4 55 55

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TREATMENT RISK OF RETREATMENT COMPARED WITH DRAXXIN 1 DRAXXIN TREATED CATTLE WERE THE LEAST LIKELY TO REQUIRE RETREATMENT 5 4. 44 4. 02 ESTIMATED RISK RATIO 4 3. 72 3. 03 2. 91 3 1. 87 2 1. 13 1 1. 30 57 TULA 57 1. 88 1. 59 1 0 1. 95 TRIM TILD OXY 1. 24, 9. 93 1. 23, 2. 74 0. 59, 4. 94 1. 50, 9. 76 GAMI FLOR 1. 16, 3. 06 1. 13, 2. 28 ENFO 0. 79, 1. 61 DANO CEFTS CEFTP CEFTH 0. 66, 2. 35 1, 40, 5. 62 1. 25, 11. 28 1. 08, 7. 20 CEFTH = Ceftiofur hydrochloride, CEFTP = Ceftiofur pinna, CEFTS = Ceftiofur sodium, DANO = Danofloxacin, ENFO = Enrofloxacin, FLOR = Florfenicol, GAMI = Gamithromycin, OXY = Oxytrtracycline, TILD = Tildipirosin, TILM= Tilmicosin, TRIM = Trimethoprim, TULA = Tulathromycin. Confidence interval

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METAPHYLAXIS 3 DRAXXIN HAS THE LOWEST RISK OF BRD MORBIDITY, MORTALITY AND RETREATMENT COMPARED TO CONTROLS 59 Odds ratio comparison between individual antimicrobials and with 95% credibility intervals for (a) BRD morbidity cumulative incidence d 1 to ≤ 60 of the feeding period, (b) BRD morbidity cumulative incidence d 1 to close out of the feeding period, (c) BRD mortality cumulative incidence d 1 to closeout, and (d) BRD retreatment 59 morbidity cumulative incidence d 1 to closeout.

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REFERENCES 1. O’Connor AM, Yuan C, Cullen JN, Coetzee JK, da Silva N, Wang C. A mixed treatment meta-analysis of antibiotic treatment options for bovine respiratory disease — an update. Prev Vet Med. 2016; 132: 130 -139. 2. O’Connor AM, Coetzee JF, Da Silva, Wang C. A mixed treatment meta-analysis of antibiotic treatments for bovine respiratory disease. Prev Vet Med. 2013; 110: 77 -87 3. Abell KM, Theurer ME, Larson RL, White BJ, Apley M. A mixed treatment comparison meta-analysis of metaphylaxis treatments for bovine respiratory disease. J Anim Sci. 2017; 95(2): 626 -635. 4. Poulsen Nautrup B, Van Vlaenderen I, Decker M, Cleale RM. Antimicrobial drug use for 61 control and treatment of bovine respiratory disease in U. S. feedlot cattle: A meta-analysis. Bov Pract. 2017; 51(1); 1 -13. 61

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DRAXXIN ROI CALCULATORS 63 63 METAPHYLAXIS TREATMENT