real world data: moving beyond clinical...

Real World Data: Moving Beyond Clinical Trials:The WellPoint Outcomes-Based Formulary

T Jeffrey White, Pharm.D., M.S.Director – Clinical Analytic StrategiesWellPoint NextRx

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Presentation Objectives

Provide an overview of WellPoint NextRxReview the WellPoint NextRx Outcomes-Based Formulary ProcessProvide examples of data and analyses used to support formulary decisions (emphasis on observational data)Provide highlights of the WellPoint Health Technology Assessment GuidelinesPresentation summary

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MissionMissionWe deliver integrated pharmacy and health solutions

providing exceptional value to our customers

VisionVisionWellPoint NextRx will transform our industry and become the most trusted and valued Pharmacy Benefits Manager (PBM)

Differentiating StrategiesDifferentiating StrategiesLeader in affordable quality care

Most trusted choice for consumers

NextRx Strategy

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The Value of Integration

MEDICALRx

The integration of pharmacy and medical data can provide information for the improvement of health, and better

management of total health care cost.

Pharmacy Perspective

Pharmacy and Medical

Perspective

GOAL = IMPROVE HEALTH, QUALITY OF SERVICE, AND

REDUCE TOTAL COSTS

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Provide an overview of WellPoint NextRxReview the WellPoint NextRx Outcomes-Based Formulary ProcessProvide examples of data and analyses used to support formulary decisionsProvide highlights of the WellPoint Health Technology Assessment GuidelinesPresentation summary

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Outcomes-Based Formulary Management

General ApproachGeneral ApproachConsider the complete burden

of disease

Clinical Burden

Epidemiology

Natural History of Disease

Total Cost of Care

Productivity Impact

Quality of Life Impact

Leverage the formulary process to improve patient

outcomesImprove Quality of Care(clinical status, quality of life)

Reduce Total Cost(pharmacy, medical, ancillary, home

health, nursing home, etc.)

Optimize Care(cost effectiveness)

Improve Productivity

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P & T Process and Committee Overview

Pharmacy and Therapeutics

(P&T) Committee

Clinical appropriateness

FIRST

Financial considerations

SECOND

OUTCOMES ADVISORY COMMITTEEOutcomes / Pharmacoeconomic Review

Value Assessment Committee

(VAC)

Value Assessment Committee

(VAC)

Reviews the clinical, outcome, and financial data and makes final tier placement

decisions

Clinical Review

Committee (CRC)

Critical review of the literature,

Assigns a clinical designation based on the evidence.

Recommendations sent to the VAC

ACTUARIAL SUBCOMMITTEE TO VAC (ASVAC)

Analyzes Financial and PharmacoeconomicResults

Integrated Pharmacy and Medical AnalysisIntegrated Pharmacy and Medical Analysis

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A Critical Review of Clinical Trial Data

Each clinical trial and guideline is carefully critiqued before being included in the drug monograph

• Only high quality evidence material is included in the monograph

• Many studies fall short

The focus of decision-making is based on patient-oriented clinical outcomes

• Outcomes that are understood and desired by patients (e.g. decreased risk of heart attack/stroke/death)

• Many studies fall short here too

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Common Pitfalls of Clinical Trial Data

• High-drop out rates or missing data, with no sensitivity analysis• Use of post-hoc analysis to draw cause and effect conclusions

• Subgroup analysis where subgroups were not determined in advance.

• Non-significant findings or power calculation is not clear• Non-ITT analysis (>5% of patients excluded from the primary

outcome analysis)• Inadequate dosages• Use of non-validated scoring methods • Disease oriented outcomes only (BP lowering vs. CV mortality)• Unclear quality assessment methods for meta-analysis studies• Study duration too short for endpoint (e.g. 6 weeks HbA1c)• Use of other medications that may influence or confound the effect of

the primary drug on outcomes

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Pharmacoeconomic and Outcomes Data

How well does the drug perform in the real world (effectiveness vs. efficacy)?

Are we achieving the outcomes we expect based on clinical trial data?

Is the drug being used properly (right patient, dose, duration, etc.)?

Are there quality of life or productivity benefits?

Are there medical cost offset benefits

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Efficacy vs. Effectiveness

Real-world clinical practiceControlled clinical trialSetting / Design

Medium to highLow to mediumExternal Validity (generalize to other populations)

LowHighInternal Validity

Example: Cardiovascular events, hospitalizations

Clinical endpoints (e.g. BP, HbA1c, LDL)Outcomes

Low to HighHighCompliance

Heterogeneous / any subjectsHomogenous/highly selective (stringent inclusion/exclusion criteria)Subjects

Active comparator/usual carePlaceboComparatorFlexible regimenFixed regimenIntervention or treatmentDrug performance in real-worldRegulatory approval (FDA)Purpose

Does it work under usualcircumstances

Does it work under idealcircumstancesObjective

Effectiveness (Real-World Data)

Efficacy (Clinical Trial Data)

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Alz. Dz.

45%

Compliance Varies Significantly by Therapeutic Category

100

0

10

20

30

40

50

60

70

80

90

61%

ARB

SOURCE: Internal Claims Database Analyses – WellPoint NextRx 2008

46%

Anti-Depressants

50%

DM ACEI

57%

49%

HMGs

69%

PlavixPsych

34%

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0

0.1

0.2

0.3

0.4

0.5

0.6

All 0.5 0.44 0.45 0.42 0.41 0.38 0.36Depression 0.52 0.47 0.47 0.44 0.42 0.4 0.48Anxiety 0.49 0.46 0.46 0.42 0.37 0.39 0.39

Drug A Drug B Drug C Drug D Drug E Drug F Drug G

Pro

porti

on o

f Day

s C

over

ed

Source: Data on file – WellPoint NextRx, 2008

Antidepressant Compliance(Proportion of Days Covered Over a 1-Year Period)

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$0

$2,000

$4,000

$6,000

$8,000

$10,000

$12,000

Rx Cost $2,249 $1,774 $1,684 $1,153 $3,597 $1,510 $1,763Medical Cost $4,486 $3,534 $3,668 $3,169 $6,546 $3,079 $3,024Total Cost $6,682 $5,290 $5,340 $4,406 $10,065 $4,581 $4,771

Drug A Drug B Drug C Drug D Drug E Drug F Drug G

1-Ye

ar C

ost


Antidepressant Total Cost(Pharmacy and Medical Cost Over a 1-Year Period)

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A Small Percentage of Patients Newly Started on Bisphosphonate Therapy are > 80% Compliant

<10% 10-20% 20-30% 30-40% 40-50% 50-60% 60-70% 70-80% 80-90% 90-100% >100%0

5

10

15

20

25

Per

cent

of P

atie

nts

Percent of Days Covered

Percent of Patients Compliant on Bisphosphonate Medication


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REAL StudyIncidence of Hip Fractures 1-Year Post Index

Cumulative Incidence of Hip Fractures

43% difference

0.21% absolute difference Fosamax

0.37

Actonel

Silverman SL, Watts NB, Delmas PD, Lange JL, Lindsay R. Osteoporos Int (2007) 18:25–34

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WellPoint Data:Incidence of Hip Fractures 1-Year Post Index

Fosamax

Boniva

Actonel

Source: Data on file, WellPoint NextRx 2008

N= 26,086

Kaplan-Meier cumulative incidence of hip fractures (1 year post-index)

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WellPoint Data:Incidence of All Fractures 1-Year Post Index

Fosamax

BonivaActonel

Source: Data on file, WellPoint NextRx 2008

N= 26,086

Kaplan-Meier cumulative incidence of all fractures (1 year post-index)

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Proportion of Patients at HbA1c Goal (<7)and Cost per Patient at HbA1c Goal

$0.00

$1,000

$2,000

$3,000

$4,000

$5,000

$6,000

$7,000

$8,000Or

al/Inj

(1)Or

al/Inj

(2)Or

al/Inj

(3+)

Ins (1

)Ins

(2)

Ins (3

+)Ins

(1) +

Oral

/Inj (1

)Ins

(1) +

Oral

/Inj (2

+)Ins

(2) +

Oral

/Inj (1

)Ins

(2) +

Oral

/Inj (2

+)Ins

(3+)

+ Oral

/Inj (1

)Ins

(3+)

+ Oral

/Inj (2

+)

Cost

per

Pt a

t Goa

l

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

70.0%

Perc

ent a

t Goa

l

Cost per GoalPercent at Goal


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Observed Percent Change in LDL-C by Different Statin Doses

4774,5896,0501,377

8416213

2,015121528

3,07211,518

21,495

Sample Size

(Obs. Data)

-46-39-35-28----55-52-46----51

-48-43

-37

Mean % LDL-C Reduction in

STELLAR Clinical Trial

-47-41-38-30-26-63-55-52-45-60

-50-43

-39

Package Insert

-30-34-32-28-21-43-37-39-30-38

-40-38

-35

Mean % LDL-C Reduction

(Observational Data)Drug and Dose

Simvastatin 80

Simvastatin 40

Simvastatin 20

Simvastatin 10

Simvastatin 5

Rosuvastatin 40

Rosuvastatin 20

Rosuvastatin 10

Rosuvastatin 5

Atorvastatin 80

Atorvastatin 40

Atorvastatin 20

Atorvastatin 10

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Simvastatin is Associated With a Lower Cost Per Percentage LDL Reduction

$0.00

$20.00

$40.00

$60.00

$80.00

$100.00

$120.00

$140.00

0% 10% 20% 30% 40% 50% 60% 70%

% LDL Reduction

Ingr

edie

nt C

ost (

30 D

ay S

uppl

y)

LOV 20

SIM 5

ZOC 5

SIM 10

ZOC 10

LOV 40

SIM 20

ZOC 20

LIP 10

SIM 40

ZOC 40

LIP 20

CRE 5VYT 10-10

SIM 80

ZOC 80

LIP 40

CRE 10VYT 10-20

CRE 20

VYT 10-40VYT 10-80

LIP 80

CRE 40

LOV 10

More favorable

Less favorable

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COPD Health Care Utilization (1)

7.4(9.5)8.7(10.3)8(10)Mean# of outpatient visits

9392100≥ 1 outpatient visit %

Outpatient visits

0.4(0.9)0.6(1)0.4(0.9)Mean# of hospital stay

313626≥ 1 inpatient stay %

Inpatient hospitalization

0.1(0.5)0.2(0.6)0.1(0.6)Mean# of ER visits

11129≥ 1 ER visit %

ER Visits

COPD-Related utilization

CombiventN=4,206

AtroventN=1,463

SpirivaN=3,030

12 months post-index date

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COPD Health Care Utilization (2)

27.5(21.8)28.6(23)28.1(22.6)Mean# of outpatient visits

10099100≥ 1 outpatient visit %

Outpatient visits

0.7 (1.2)0.9(1.5)0.6(1.2)Mean# of hospital stay

404433≥ 1 inpatient stay %

Inpatient hospitalization

0.4 (1)0.5(1.6)0.4(1.3)Mean# of ER visits

272823≥ 1 ER visit %

ER Visits

All-Cause Utilization

CombiventN=4,206

AtroventN=1,463

SpirivaN=3,030

12 months post-index date

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COPD Health Care Utilization (3)12 months post-index date

$5,224$7,226§$5,172*Total (Medical + Pharmacy)

$171¶$310§$324Pharmacy

$4,782¶$6,612§$4,317*Medical

COPD-related adjusted cost

$13,116$16,093§$13,007*Total (Medical + Pharmacy)

$1,952¶$1,927$2,584*Pharmacy

$11,182$14,316§$10,378*Medical

All-Cause unadjusted cost

CombiventN=4,206

AtroventN=1,463

SpirivaN=3,030

Adjusters are prior year cost, age, gender, health plan Charlson Comorbidity index, hypertension, depression, asthma, and stroke* p<0.05 pairvise comparison between spiriva and atrovent§ p<0.05 pairvise comparison between atrovent and combivent¶ p<0.05 pairvise comparison between spiriva and combivent

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Quality of Life Summary

Some diseases are associated with significant QoLburdenSome treatments can result in significant improvement in QoL• QoL consistent with disease in remission• QoL approaches that of the US population norm

QoL is an important endpoint from a patient perspective

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Revised WellPoint Guidelines for Formulary Submissions: 2008

Standards and Recommendations

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WellPoint Outcomes Based Formulary

Supports WellPoint’s leadership position in the provision of a high-quality pharmacy benefit that is evidence-based

Formulary decisions are based on high quality evidence focused on patient outcomes

Studies should be representative of WellPoint patient populations

Product choice and continuing formulary support should be supported by clinical evidence and product value (e.g. cost-effectiveness)

Patient focused claims are judged by their impact in a naturalistic environment and should be monitored on an ongoing basis, validated and reported on by manufacturers

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Provide an overview of WellPoint NextRxReview the WellPoint NextRx Outcomes-Based Formulary ProcessProvide examples of data and analyses used to support formulary decisionsProvide highlights of the WellPoint Health Technology Assessment GuidelinesPresentation Summary

31

Presentation Summary (1)

WellPoint NextRx strategy• Transform our industry. . .• Deliver integrated pharmacy and health solutions. . .• Leader in affordable quality care. . .

Outcomes-based formulary• Understand the complete burden of disease• Leverage the formulary process to improve patient outcomes

– Improving quality of care (clinical status, quality of life)– Reducing total cost of care (pharmacy, medical, total)– Optimize care (cost effectiveness)– Leverage both clinical trial data and observational data

Compliance challenges• Generally poor (~50%)• Leverage tier placement and other tools to drive utilization towards drugs

associated with better outcomes (quality and total cost)

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Presentation Summary (2)

Efficacy and effectiveness data to be used to make formulary decisions

There are differences in performance of drugs within the same therapeutic category• Goal is to identify the “best” performing drugs

Health Technology Assessment Guidelines• Inform manufacturers regarding information most useful to WellPoint

Expected Outcomes• A pharmacy benefit that is high quality and cost effective• Better quality of care• Improved cost-effectiveness of care

real world data: moving beyond clinical...

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