Real-World Evidence Informing Decision Making

C. Bernie Good MD MPHDepartment of Veterans Affairs

University of Pittsburgh

CADTH 2016April 12, 2016

Chair Medical Advisory Panel for Pharmacy Benefits Management, U.S. Department of Veterans Affairs

Co-Director VA Center for Medication Safety FDA Drug Safety Oversight Board Member No COI with industry

Disclosures

Comprehensive health care system◦Direct provider of care◦Physicians are employees◦Prescription drug benefit is integrated

2014 Statistics◦6.3 M veterans treated, 4.8M pharmacy users◦271 million outpatient Rxes (30-day Eqv)

A Few Words about VA

EMR◦ Clinical data◦ Pharmacy data◦ Adverse drug events

VA Center for Medication Safety◦ Dedicated group of pharmacists, data analysts, programmers,

and statisticians to support VA PBM Routinely do data monitoring, rapid cycle analyses, and

full studies as indicated Work closely with FDA and other U.S. Federal Agencies

Tools for Gathering Real World Data for VA Pharmacy Benefits Management

Drug/Drug Class

Issue Potential Impact

Real World VA Data

Outcome or Action

TZDs Rosiglitazone CV Safety?

166,000 pts on TZD (2006)

VA Data: Rosi > Pio for MI

Rosi removed as preferred

Zoster Vaccine Inc SAE’s in Clinical Trial

~ half VA patients >65 yo

No inc in SAEs in VA patients

Relaxed criteria

Varenicline Inc Neuropsych ADE, suicide comp NRT

24% VA smoke (17% U.S. > 18 yrs)

No sig signal Relaxed criteria

DOACs Safety, effectiveness v. warfarin in VA

307,000 VA pts with AF

Safety, effectiveness ~ clinical trials

3 DOACs on VA formulary

Hepatitis C Comp. Eff; safety of meds

170,000 VA pts with HCV

Real world < Clin Trials

Use info for contracting

Empagliflozin Comp Eff;Safety

> 1M VA pts on DM Rx

To Be Determined

Reassess Recs

Real-World Data: Assessments and Outcomes- VA Examples

Hep C Registry: Every VA patient with HCV◦ Genotype, viral load, prior treatment, advanced liver disease

(ALD)◦ Treatment response, adverse events, discontinuation, etc

Weekly reports for new starts, by drug◦ National, Regional, and site facility level◦ Track new starts also by presence/absence of ALD◦ Feedback to facilities for ALD starts, drug choice, with

benchmarking Hep C data is used for contracting, CER among agents,

and feedback to facilities to manage appropriateness

Hepatitis C Real World Data

> 50,000 VA Pts treated with DAA

FY1999 FY2000 FY2001 FY2002 FY2003 FY2004 FY2005 FY2006 FY2007 FY2008 FY2009 FY2010 FY2011 FY2012 FY2013 FY2014 FY2015 $-

$100

$200

$300

$400

$500

$600

$700

$800

$900

$599FY 1999

$752

$697 $794

FY 2005

41% increase3 Yrs

2013-2015

13% increase14 Yrs

1999-2013

$672

$680

$752

$959

Annual Cost per Pharmacy Unique Patient in VA/ with and without Hep C

Post-marketing surveillance◦ FDA warnings for neuropsychiatric adverse events, and suicide

VA had reports of Varenicline related suicide As a result, VA developed criteria for use that

restricted use of Varenicline as a third line treatment, with many safety measures

Use of Varenicline dropped dramatically in VA Risk <<<< Benefit??

Varenicline for Smoking Cessation

VA Unique Varenicline Users by Year

FY 2006 FY 2007 FY 2008 FY 2009 FY 2010 FY 2011 FY 2012 FY 2013 FY 2014 FY0

10000

20000

30000

40000

50000

60000

70000

80000

Varenicline Peak 2008 > 74,000 pa-tients/ year

Currently < 20,000 patients/ year

Propensity-matched study in the era *prior to FDA warnings*

NRT vs. Varenicline◦ Primary Outcome: Psychiatric adverse events

Subgroups: Patients with and without psychiatric diagnoses◦ Inpatient admissions, outpatient visits◦ Suicide

Results (pending publication)◦ No significant increased adverse outcomes with Varenicline

VA has changed criteria for use- significantly relaxed◦ Education efforts to increase use in appropriate patients

VA Varenicline Study

DOACs- Clinical Trials: Better outcomes outcomes strongly associated with INR control in the warfarin

comparison patients- for both safety and efficacy Greater patient convenience

Far more expensive than warfarin VA Utilizes Pharmacy-based Anticoagulation Clinics

TTR’s in VA excellent 3 DOACs on VA Formulary- does comparative

effectiveness warrant significantly greater cost?

DOACs: How do they compare to Warfarin in VA?

New user cohort, propensity matched cohort for non-valvular AF

VA has done similar study, for dabigatran, rivaroxaban, and apixaban. Results show benefit >> warfarin

* Graham et al, Circulation 2014

CMS Comparative Effectiveness of Dabigatran vs Warfarin in AF*

Outcome HR (95% CI)Ischemic Stroke 0.80 (0.67-0.96)

Intracranial Hemorrhage 0.34 (0.26-0.46)

Gastrointestinal Bleed 1.28 (1.14-1.44)

Acute Myocardial Infarction 0.92 (0.78-1.08)

Death 0.86 (0.77-0.96)

Real world data can inform clinical decisions◦ Provide justification for increased expenditures based on

improved clinically relevant outcomes◦ Provide information that suggests utilization in VA should

increase, based on safety and or effectiveness◦ Provide information that drugs should be de-emphasized or

removed from formulary status based on safety concerns

Conclusions

Clinical guidance Drug Monographs Criteria for use Clinical documents

www.pbm.va.gov

Back Up Slides

> 1 million pts with DM get medications from VA Have emphasized metformin, de-emphasized other

newer oral agents without proven benefit Recent empagliflozin study indicates clinical benefit◦ VA has added drug to our formulary with criteria for use◦ Concerns regarding whether safety and effectiveness will be

similar to clinical trial data◦Will monitor use of drug carefully, and track ADE, and later

assess benefits

Diabetes Medications

Diabetes Medications, Unique Patients Veterans Affairs, FY 2000-2015

FY2000

FY2001

FY2002

FY2003

FY2004

FY2005

FY2006

FY2007

FY2008

FY2009

FY2010

FY2011

FY2012

FY2013

FY2014

FY20150

200,000

400,000

600,000

800,000

1,000,000

1,200,000

All other diabetic agentsDPP-4'sGLP1 agonistsTotal Unique Diabetic PatientsInsulin analogs onlyInsulins- (No analogs)MetforminSGLT-2 inhibitorsSulfonylureaTZD's