Estimating the Cost of Disease in The Vital 90 TM Days

Estimating the Cost of Disease in The Vital 90 TM Days KDDC Young Dairy Producers Meeting Bowling Green, KY February 21, 2017 Michael Overton, DVM, MPVM Elanco Knowledge Solutions Dairy moverton@elanco.com

Transition Cow DryOff Fetal growth Colostrum Hormone Changes Calving Rapidly increasing milk production -60-21 21 30 RationΔ RationΔ RationΔ RationΔ Dry Matter Intake (DMI) drop A 90 day collection of transition periods that have interrelated events influencing either productive or non-productive outcomes in the lactation Transition Period USDBUNON02052

Management in The Vital 90 Days is Critical: RISK, COST, and OPPORTUNITY RISK The metabolic adaptation required for a successful new lactation is extraordinary ALL transition dairy cows experience negative nutrient balance and immune dysfunction Many adult dairy cow diseases are related to this challenge 45-60% of cows experience one or more of the common transition cow problems such as metritis, mastitis, retained placenta, milk fever, etc 1 Energy balance and immune dysfunction are at the root of these diseases 1 Santos et al, Proc. 2013 Dairy Cattle Reproduction Council Conference, Indianapolis, IN, p 32-48.

Management in The Vital 90 Days is Critical: RISK, COST, and OPPORTUNITY Two Major Types of COSTS During The Vital 90 Days Investment Costs Dairy producers often invest heavily to mitigate the RISK associated with calving Many products and procedures are justifiably used to reduce disease and optimize performance Consequence Costs Direct and indirect costs of disease are a major source of economic loss and frustration for dairy producers Lowering consequence costs through reducing disease and refining treatment decisions is a great opportunity to improve profitability

Direct disease costs: Estimating Cost of Disease: Issues that Need to be Considered Diagnostics is there any kind of special screening or lab test that is performed? Therapeutics what are the various antimicrobials, supportives, antiinflammatories, etc that are used in treatment? Discarded milk how much milk is being discarded and for how long? What is the true value of this milk? Is it used to feed calves or discarded? Veterinary service is the vet involved with either diagnosis or treatment of this issue? Labor how much of my on-farm labor s time is used to diagnose or treat this issue? Death how many cows die as a consequence of this disease and what is the true economic impact to the dairy?

Estimating Cost of Disease: Issues that Need to be Considered Indirect disease costs: Milk production loss how much marginal milk is NOT produced throughout lactation as a result of this disease issue and what is that worth? Culling loss how many cows leave the herd prematurely as a consequence of this issue and what is the economic impact to the dairy? Reproductive loss how much is my reproductive performance negatively impacted by this issue and what could that be costing the herd? Losses due to other attributable disease issues are there any other disease issues that are impacted by the occurrence of this issue?

Management in The Vital 90 Days is Critical: RISK, COST, and OPPORTUNITY Opportunity: With improved risk management and disease prevention efforts during The Vital 90 Days Reduced disease incidence Lower treatment costs Reduced mortality and culling Higher milk production throughout lactation Opportunity for improved reproductive performance Healthier transition cows = greater profit potential

The Subsequent Data are from Dairy Herds from the Southeast that are Enrolled in Elanco s Dairy Data Access System All herds use either DC305 or PCDART Herds were from Florida, Georgia, North Carolina, Mississippi Selected an 18-month period of calvings (1/1/15-6/30/16) Eliminated herds that had unreasonably low recorded incidences of mastitis and metritis Filtered to include only Holstein Result: 42,496 lactation records REMEMBER: This is observational analyses of farm reported information

Descriptive Statistics

Descriptive Statistics Milk Production 2 nd Test p305me Milk Most Recent p305 Milk

All Cows: Disease Incidence (within 30 DIM) 8.3% 15.4% 5.7% 3% Lactation = 1: 8.6% 23.5% 4.3% 1.6% Lactation > 1: 8.1% 11% 6.5% 3.7%

Early Disease Issue (Category) Cows must have had one or more of the following within the first 30 DIM: Mastitis Metritis RP Ketosis DA Milk Fever Dystocia (Calving Ease >1) 49% 33% 41%

Early Disease Issue (Count) By Lactation Group Cows must have had one or more of the following within the first 30 DIM: Mastitis Metritis RP Ketosis DA Milk Fever Dystocia (Calving Ease >1)

Culling by 60 DIM by Lactation Group 3.3% 1.6% 2.6% 2.1% 4.6% 4.6%

Age at First Calving Category <22 mos 22-24 mos >24 mos

Statistical Approach for Primiparous Cows (Lactation = 1) First, the association between milk production and presence of disease(s) were modeled using ANOVA Outcomes were reported as Least Squares Means Milk production was modeled using two outcomes: 2 nd Test 305ME Milk projected mature-equivalent milk production at the 2 nd recorded test date 305 Milk (non-me) projected milk production over 305-d but without an ME adjustment Variables offered to the model: Herd Month fresh Year fresh Twin or singleton Age-at-Fresh category Disease issue being examined USDBUNON02052

Summarized Milk and Disease Associations for Lactation = 1 (Accounting for the other effects in the model, one disease per model) Variable 305 Milk Impact Cost Early Mastitis -951 lb -$126 Metritis -661 lb -$88 Early Disease: 1 issue -406 lb -$54 Early Disease: 2 issues -812 lb -$108 Early Disease: 3 issues -1218 lb -$162 Early Disease: 4 issues -1624 lb -$216 Early Disease: 5 issues -2030 lb -$270 Any Early Disease -545 lb -$72 Twins -186 lb -$25 AGECAT (vs. Intermediate): Early -419 lb -$56 Older 57 lb $8 Milk Cost Assumptions: Milk price = $0.18/lb Feed Price = $0.11/lb 2.33 lb milk per lb feed on the margin Early Disease Issues: Mastitis Metritis RP Ketosis DA Milk Fever Dystocia (Calving Ease >1) AGEFR Categories: Early = < 22 mos Intermediate = 22-24 mos Older = > 24 mos USDBUNON02052

Summarized Milk and Disease Associations for Lactation = 1 (Accounting for the other effects in the model, all diseases in model) Variable 305 Milk Impact Cost Early Mastitis -917 lb -$122 Metritis -570 lb -$76 Retained Placenta -365 lb -$48 Displaced Abomasum -981 lb -$130 Twins -70 lb -$9 AGEFR (vs. Intermediate): Early -410 lb -$54 Older 594 lb $79 Milk Cost Assumptions: Milk price = $0.18/lb Feed Price = $0.11/lb 2.33 lb milk per lb feed on the margin AGEFR Categories: Early = < 22 mos Intermediate = 22-24 mos Older = > 24 mos USDBUNON02052

Evaluating the Association Between Disease and Culling Cox Proportional Hazards model censoring at 60 DIM Variables offered to the model: Herd Month fresh Year fresh Twin or singleton Age-at-fresh category Disease issue being examined

First Lactation Survival Through 60 DIM

Culling by 60 DIM for Lactation = 1 and Mastitis (Total Culling Risk by 60 DIM = 4.9%) Variable Early Mastitis vs. No Early Mastitis Risk Ratio P-Value Cost 1.8 <0.01 $41 Twin vs. singleton 2.6 <0.01 Age-Fresh Category Early vs. Intermediate Older vs. Intermediate 1.2 0.23 1.4 <0.01

Demonstration of How Cost Was Estimated for Culling Using Attributable Fraction Scenario: Mastitis incidence = 8.63% Culled Not culled Total Mastitis 107 1188 1295 Culling Risk M = 107 / 1295 = 8.3% No Mastitis 628 13088 13716 Culling Risk N = 628 / 13716 = 4.6% Fresh value $ 1,800 735 14276 15011 Culling risk overall = 735 / 15011 = 4.9% Relative Risk = 8.3% / 4.6% = 1.80 Beef value $ 1,000 Attributable fraction Expected Cases (if no metritis) = 4.6% * 1295 = 59 = Sold 68% Died 32% Attributable Fraction = 44.6% = ( 8.3% - 4.6% ) / 8.3% # of Cows Value Lost Attributable Cases = 44.6% * 107 = 47.7 #Sold 32.4 $ 25,953 #Died 15.3 $ 27,479 $ 41 Avg Cost/Case

Summarized Culling and Disease Associations for Lactation = 1 (Accounting for the other effects in the model) Variable Impact (RR for Culling) Cost Early Mastitis 1.8 $41 Metritis 1.25 $13 Early Disease: 1 issue 1.34 Early Disease: 2 issues 1.78 Early Disease: 3 issues 2.37 Early Disease: 4 issues 3.15 Early Disease: 5 issues 4.19 Any Early Disease 1.9 $34 Twins 2.1-2.6 Early AGEFR vs. Intermediate Older AGEFR vs. Intermediate 1.35 1.13 (N.S.) Early Disease Issues: Mastitis Metritis RP Ketosis DA Milk Fever Dystocia (Calving Ease >1) AGEFR Categories: Early = < 22 mos Intermediate = 22-24 mos Older = > 24 mos

Reproductive Performance First Lactation Cows Evaluated univariate Time-to-Pregnancy curves through 250 DIM for each disease variable of interest Performed Cox Proportional Hazards Models for Time-to- Pregnancy Variables offered to model: Herd Month fresh Year fresh Twins or singleton Age Fresh Category Disease variable of interest

Time to Pregnancy Through 250 DIM for Lactation = 1 and Metritis Metritis was associated with 21 additional median days open Variable Risk Ratio P-Value Cost Metritis vs. No Metritis 0.73 <0.01 $42 Twin vs. singleton 0.65 <0.01 Age-Fresh Category Early vs. Intermediate 1.05 0.16 Older vs. Intermediate 0.87 <0.01

Time to Pregnancy Through 250 DIM for Lactation = 1 and Any Early Disease Issue (Count) Limited the number of issues to 3 or less to limit the business of the graph Notice the increasing negative impact on time to pregnancy with additional issues Each additional Early Disease Issue, the Odds of Pregnancy by 250 DIM decreased by 15% (p<0.01)

Summarized Reproduction and Disease Associations for Lactation = 1 (Accounting for the other effects in the model) Variable Impact (RR for Pregnancy) Cost Early Mastitis 0.9 $20 Metritis 0.73 $42 Early Disease: 1 issue 0.85 Early Disease: 2 issues 0.73 Early Disease: 3 issues 0.61 Early Disease: 4 issues 0.52 Early Disease: 5 issues 0.44 Any Early Disease 0.82 $16 Twins 0.6 0.65 Early AGEFR vs. Intermediate Older AGEFR vs. Intermediate 0.88 1.04 (N.S.) Early Disease Issues: Mastitis Metritis RP Ketosis DA Milk Fever Dystocia (Calving Ease >1) AGEFR Categories: Early = < 22 mos Intermediate = 22-24 mos Older = > 24 mos

Statistical Approach For Mature Cows was Similar Association of milk production and presence of disease outcome were modeled using ANOVA Outcomes were reported as Least Squares Means Milk production was modeled using two outcomes: 2 nd Test 305ME Milk - projected mature-equivalent milk production at the 2 nd recorded test date 305 Milk (non-me) projected milk production over 305-d but without an ME adjustment Variables offered to the model: Herd Lactation Group (2 vs. 3+) Month fresh Previous lactation 305ME Milk Year fresh Disease issue being examined Twin or singleton USDBUNON02052

Summarized Milk and Disease Associations for Lactation > 1 (Accounting for the other effects in the model, one disease per model) Variable 305 Milk Impact Cost Early Mastitis -1522 lb -$202 Metritis -1012 lb -$134 Early Disease: 1 issue -581 lb -$77 Early Disease: 2 issues -1162 lb -$154 Early Disease: 3 issues -1743 lb -$231 Early Disease: 4 issues -2324 lb -$309 Early Disease: 5 issues -2905 lb -$386 Any Early Disease -888 lb -$118 Twins -286 lb -$38 Milk Cost Assumptions: Milk price = $0.18/lb Feed Price = $0.11/lb 2.33 lb milk per lb feed on the margin Early Disease Issues: Mastitis Metritis RP Ketosis DA Milk Fever Dystocia (Calving Ease >1) USDBUNON02052

Summarized Milk and Disease Associations for Lactation > 1 (Accounting for the other effects in the model, all diseases in model) Variable 305 Milk Impact Cost Early Mastitis -1485 lb -$197 Metritis -869 lb -$115 Retained Placenta -233 lb -$31 Displaced Abomasum -1862 lb -$247 Twins -125 lb -$17 Milk Cost Assumptions: Milk price = $0.18/lb Feed Price = $0.11/lb 2.33 lb milk per lb feed on the margin USDBUNON02052

Evaluating the Association Between Disease and Culling in Mature Lactation Cows Cox Proportional Hazards model censoring at 60 DIM Variables offered to the model: Herd Month fresh Year fresh Twin or singleton Lactation Group (2 or 3+) Previous Lactation 305me Disease issue being examined USDBUNON02052

Summarized Culling and Disease Associations for Lactation > 1 (Accounting for the other effects in the model) Variable Impact (RR for Culling) Cost Early Mastitis 1.6 $50 Metritis 1.15 $36 Early Disease: 1 issue 1.34 Early Disease: 2 issues 1.78 Early Disease: 3 issues 2.37 Early Disease: 4 issues 3.15 Early Disease: 5 issues 4.19 Any Early Disease 2.25 $74 Twins 1.6-2.3 Previous Lactation 305ME 0.99998 Lactation Group (3+ vs. 2) 2.25 Early Disease Issues: Mastitis Metritis RP Ketosis DA Milk Fever Dystocia (Calving Ease >1)

Reproductive Performance Lactation > 1 Cows Evaluated univariate Time-to-Pregnancy curves through 250 DIM for each disease variable of interest Performed Cox Proportional Hazards Models for Time-to- Pregnancy Variables offered to model: Herd Month fresh Year fresh Twins or singleton Lactation Group (2 or 3+) Disease variable of interest

Time to Pregnancy Through 250 DIM for Lactation > 1 and Any Early Disease Issue (Count) Limited the number of issues to 3 or less to limit the business of the graph Notice the increasing negative impact on time to pregnancy with additional issues For each additional Early Disease Issue, the Odds of Pregnancy by 250 DIM decreased by 17% (p<0.01)

Summarized Reproduction and Disease Associations for Lactation > 1 (Accounting for the other effects in the model) Variable Impact (RR for Reproduction) Cost Early Mastitis 0.89 $38 Metritis 0.70 $88 Early Disease: 1 issue 0.83 Early Disease: 2 issues 0.69 Early Disease: 3 issues 0.57 Early Disease: 4 issues 0.47 Early Disease: 5 issues 0.39 Any Early Disease 0.76 $62 Twins 0.67-0.79 Lactation Group (3+ vs. 2) 0.86 Early Disease Issues: Mastitis Metritis RP Ketosis DA Milk Fever Dystocia (Calving Ease >1)

Even the Best Economic Models are Severely Limited in Utility if the Input Data is Inconsistent or Inaccurate Disease records are extremely variable. Inconsistencies may preclude us from making faster advances in understanding the impact of disease on cow performance understanding the relationship between diseases rate of genetic progress What if the disease definition used was different? What if the detection approach used was different? What if the herd inconsistently recorded it? It is CRITICAL that we work towards more consistent disease definitions, detection and recording Disease treatment protocols with standardized recording can really help this effort

How Much Does the Failure to Record Disease Affect the Measurable Impact of Disease? Introduces bias into the system Types of bias/recording issues: Failure to record any disease Failure to correctly distinguish mild from severe Failure to record mild disease Misclassification of a normal cow as diseased

Metritis Severity Score Misclassification Under Predicts Consequence Cost Of Disease* Convenience sample of DC305 data from 1 Mid-Western Holstein herd 1 year of calvings (n = 3,485) Herd chosen because it does an excellent job of recording metritis incidence & severity No metritis recorded (NR) Mild metritis Severe metritis *McCarthy and Overton, Abstract 16288 presented at 2016 ADSA, Salt Lake City

True Disease Severity (TS) Normal herd recorded data 1. No metritis recorded 2. Mild metritis 3. Severe metritis Inconsistent Disease Recording (IR) Randomized 40% of mild cases to not recorded 1. No metritis recorded 2. Mild metritis 3. Severe metritis Poor disease recording (PR) All mild metritis cases reclassified as not recorded 1. No metritis recorded 2. Severe metritis

Statistical analysis TS, IR, and PR datasets analyzed separately in JMP 12.1.0 ANOVA conducted for second test 305 day mature equivalent (2nd305ME) Lactation group (1, 2, 3+), month fresh, early lactation mastitis (+/-), and DA (+/-) were included in all models

Predicted 2 nd 305ME and Associated Losses True Severity Incomplete Recording Poor Recording -893-829 -2439-2315 -2183 Total milk loss attributable to metritis: -1,114,083 lb -751,618 lb -338,347 lb Non-identified losses attributable to metritis: -392,465 lb -805,736 lb

Implications Misclassification of metritis results in greater bias and underestimates the true association between metritis and milk production, reproductive performance and culling risk Misclassification leads to an underestimate of the consequence costs of diseases like metritis Improved definition and recording of metritis herds can lead to better interpretation of the true impact of metritis (and other diseases) on individual herds

If We Develop and Maintain Good Disease Records, What Can We Learn? Has the incidence of transition disease changed over time? Is my fresh cow mastitis risk in mature cows going down now that I have this new transition barn? Now that we are feeding this new close up diet, is the risk of RP and metritis in my heifers decreasing? What is the impact and cost of transition disease in MY herd? How much milk does a case of early lactation mastitis cost me? How much does metritis impact the herd s reproductive performance? How much does fresh cow disease actually cost my herd?

Summarization of Estimated Disease Impacts in the Southeast Data Set Variable Milk Loss Culling Loss Repro Loss Estimated Losses/Case* Incidence Lactation = 1 Early Mastitis -$126 -$41 -$20 -$187 8.3% Metritis -$88 -$13 -$42 -$143 15.4% Any Early Disease -$72 -$34 -$16 -$122 49% Lactation > 1 Early Mastitis -$202 -$50 -$38 -$290 8.1% Metritis -$134 -$36 -$88 -$258 11% Any Early Disease -$118 -$74 -$62 -$254 38% If we assume that diseases are underreported in this data set, we can also assume that these estimates of the impact of disease, both on a per case basis and overall, is also underestimated *Does not include treatment costs or full culling losses across lactation

Summarization of Estimated Disease Impacts in a Larger U.S. Data Set (using 305 Milk) Variable 305 Milk Milk Loss Early Culling Loss Repro Loss Milk, Early Culling & Repro Losses/Case* Incidence Lactation = 1 Early Mastitis -$209 -$78 -$22 -$309 4.5% Metritis -$47 -$7 -$80 -$134 22% RP -$83 -$15 -$120 -$218 4% DA -$213 -$105 -$66 -$384 0.9% Any Early Disease -$61 $28 -$42 -$131 42% Lactation > 1 Early Mastitis -$276 -$64 -$34 -$374 6.4% Metritis -$110 -$18 -$104 -$232 12.7% RP -$65 -$9 -$126 -$200 7.2% DA -$339 -$105 -$62 -$506 3.4% Any Early Disease -$133 -$53 -$66 -$252 38% *Does not include treatment costs or full culling losses across lactation USDBUNON02052

Summarization of Estimated Disease Impacts Variable SE Estimated Losses/Case* SE Incidence US Estimated Losses/Case* US Incidence Lactation = 1 Early Mastitis -$187 8.3% -$309 4.5% Metritis -$143 15.4% -$134 22% Any Early Disease -$122 49% -$131 42% Lactation > 1 Early Mastitis -$290 8.1% -$374 6.4% Metritis -$258 11% -$232 12.7% Any Early Disease -$254 38% -$252 38% *Does not include treatment costs or full culling losses across lactation

To Summarize... Research has shown the large negative impact and cost of common disease issues occurring during The Vital 90 Days Observational data from commercial Holstein herds from the Southeast reflect the research findings Mastitis, metritis, and other disease issues are costly Significant losses in milk production Significant losses due to increased culling risk Significant losses due to negative impact on reproductive performance Due to inadequate/ inconsistent disease definitions, as well as detection and recording issues, the true impact in the Southeast Dairy Industry is likely significantly higher than estimated here

Thanks For Your Attention! Michael Overton, DVM, MPVM (706) 248-4664 moverton@elanco.com Elanco, Vital 90, and the diagonal bar are all trademarks owned or licensed by Eli Lilly and Company, its subsidiaries or affiliate s. 2016 Eli Lilly and Company, its subsidiaries or affiliates. All rights reserved.