3 bernie cadth 2016
TRANSCRIPT
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