PEC Process for Effective PEC Process for Effective Formulary Decision-Making: Can Formulary Decision-Making: Can

This Work for the Local MTF?This Work for the Local MTF?

CDR Denise M. Graham

DoD Pharmacoeconomic Center

ObjectivesObjectives

By the end of this presentation the audience will be able to:

• Cite the analysis process used by DoD PEC clinical staff to aide in the P&T Committee’s formulary decision-making

• Explain how efficacy, safety/tolerability, other factors and price/cost are used by the PEC to assess acceptability of formulary and contracting strategies

• Explain how therapeutic interchangeability and coverage of clinical needs influence the acceptability of different formulary and contracting strategies

• State how provider input is critical to a complete evidence-based evaluation and the subsequent formulary and contracting strategy

• Describe how the Uniform Formulary Rule could affect MTFs.

Challenges within DoDChallenges within DoD

• Three venues available to beneficiaries to receive care

• Three venues available to beneficiaries to fill prescriptions

• Significant variation in size (and pharmacy budgets) between facilities

• Three individual services

• Joint VA/DoD contract strategies

• Uniform Formulary (coming soon)

Roles Within the Roles Within the Military Health SystemMilitary Health System

• Pharmacoeconomic Center (PEC)– Identify opportunities

for improved outcomes

– Perform clinical review

– Solicit and collate provider input

– Collaborate with VA PBM

– Develop and present recommended strategy and alternatives

• DoD Pharmacy and Therapeutics Committee– Evaluate clinical review

– Evaluate provider input

– Determine best clinical approach for class

– Identify clinical imperatives that must be satisfied by procurement strategy

Utilization of the Utilization of the Analysis Process Analysis Process

• Drug Reviews requested for– Basic Core Formulary (BCF) addition/deletion

– Results in review of therapeutic class

• Drug Class Reviews for procurement initiatives – BCF

• New Drug Reviews – BCF

– TMOP

Clinical Review: Clinical Review: The ESTOP AnalysisThe ESTOP Analysis

• Efficacy: The likelihood to work

• Safety: The likelihood to do no harm

• Tolerability: The likelihood to be taken

• Other: Any other factors we can think of

• Price: The denominator for value

Efficacy: Efficacy: What Works Best?What Works Best?

• Most important part of analysis

• Often most difficult to complete, especially in classes with lots of products– Differences in time to market

– Differences in design of clinical trials

– Different definitions of success

– And, often most significant…

Efficacy: Efficacy: What Works Best?What Works Best?

• A general lack of head-to-head trials comparing efficacy against other agents in the class

Efficacy: Efficacy: What Works Best?What Works Best?

• Evidence-based approach– Critical evaluation of medical literature

• Randomized clinical trials

• Meta-analyses

• Results of effectiveness/clinical outcomes studies

• Clinical Practice Guidelines

• Other studies

• Published abstracts

• Importance as part of procurement strategy analysis

• The issue of ‘efficacy’ vs. ‘effectiveness’

SSafety: afety: The likelihood to do no harmThe likelihood to do no harm

• All drugs have risks associated with their use

• Goals of safety evaluation– Determine whether all class members

have sufficient data regarding their safety

– Determine whether data indicate that all class agents are equally safe

TTolerability: olerability: The likelihood to be takenThe likelihood to be taken

• All drugs need to be taken in order to be effective

• Several things can affect the likelihood that patients will take prescribed medications– Frequency of administration

– Ease of administration

– Frequency of irritating or uncomfortable side effects

TTolerability: olerability: The likelihood to be takenThe likelihood to be taken

• Available measure: discontinuation rates during clinical trials– Often underestimates likelihood of

discontinuation during “real use”

– Must be compared to discontinuation rate in placebo arm

OOther: ther: Any other factors we can think ofAny other factors we can think of

• The kitchen sink

• Most factors considered here are nonclinical– Utilization rates

– Competitive forces

– Patent life expectancy (time to generic availability)

– Political factors (SSRI class)

– Packaging issues

– Operational considerations

PPrice: rice: The denominator for valueThe denominator for value

• Main role is in procurement strategy analysis

• This is the “irony factor”– Least considered in clinical review

– Most likely to give us the reputation of being “heartless”

Procurement Strategy AnalysisProcurement Strategy Analysis

• Therapeutic Interchangeability

• Coverage of Clinical Needs

• Provider Acceptance

Therapeutic InterchangeabilityTherapeutic Interchangeability

• Similar clinical attributes

• Same indications

• Same patient populations

• Similar clinical outcomes

Closed class contracts

– Require the highest degree of therapeutic interchangeability

Coverage of Clinical NeedsCoverage of Clinical Needs

• For closed class:

Sufficiently safe, tolerable, and efficacious to meet clinical needs of at least 90% of patients

Provider AcceptanceProvider Acceptance

• Willingness of providers to use contracted drug and refrain from using noncontracted drug

Provider AcceptanceProvider Acceptance

• Two components– New patient starts: degree of willingness to use

a particular agent in a class. Duration on the market, available safety data

– Mandated switching of therapy: degree of willingness to abandon current therapy for contract winner• Perceived likelihood of similar clinical outcome with

contracted drug

• Perceived level of work involved in making switch (i.e., supplemental visits and lab tests)

Utilization of the Clinical ReviewUtilization of the Clinical Review

DoD P&T Executive Council Determines:

• Clinically acceptable contracting/formulary strategy

• Closed class vs. open class contract

• Blanket purchase agreement (BPA)

• On or not on formulary (BCF)

• “Clinical Imperatives”• Does vs. does not require switching patients to contracted

agent

• Therapeutic agents in the class to be competed

• Indication(s) of class to be considered in procurement initiative

Oral Fluoroquinolones Oral Fluoroquinolones BackgroundBackground

• The Council previously voted to support a joint DoD/VA contract for a workhorse oral fluoroquinolone that would compete levofloxacin and gatifloxacin (Nov 01)

• DoD’s utilization has reflected a 70% marketshare for levofloxacin (94% if ciprofloxacin is excluded)

• Before proceeding to contract the PEC approached Ortho-McNeil and requested modifications to the existing BPA, specifically:– Removal of the marketshare requirements

– Price reduction

• Ortho-McNeil suspended the marketshare requirement, but did not remove them

Fluoroquinolone Fluoroquinolone EfficacyEfficacy

Gram NegativeGram Negative Clinical CoverageClinical Coverage

ORGANISM Gatifloxacin Levofloxacin Moxifloxacin

Citrobacter sp * * *

Enterobacter sp * X *

Escherichia coli X X *

Haemophilus influenzae X X X

Haemophilus parainfluenzae X X X

Klebsiella pneumoniae X X X

Moraxella catarrhalis X X X

Morganella morganii * * *

Neisseria gonorrhoeae X

Proteus mirabilis X X *

Proteus vulgaris * *

Pseudomonas aeruginosa X

Salmonella sp X * X

Serratia sp *

Shigella sp X * X

X microorganisms associated with FDA approved indications.•Exhibits in vitro MIC of <1 mcg/ml( ciprofloxacin), < 2 mcg/ml (enoxacin, gatifloxacin,levofloxacin,lomefloxacin,moxifloxacin,ofloxacin), <4 mcg/ml( norfloxacin) against >90% strains •however, the safety and effectiveness in treating clinical indications has not been established in adequate well controlled clinical trials.

Fluoroquinolone Fluoroquinolone EfficacyEfficacy

Gram Positive & OtherGram Positive & Other Clinical CoverageClinical CoverageORGANISM Gatifloxacin Levofloxacin Moxifloxacin

Gram-positive

Staphylococcus Aureus X X X

S. epidermidis X X

S. saprophyticus

Enterococcus sp X X X

Streptococcus pneumoniae X X X

S. pyogenes X X X

Other

Chlamydia pneumoniae X X X

Chlamydia trachomatis

Mycoplasma pneumoniae X X X

Legionella pneumonophilia X X

Anaerobe

Bacteroides fragilis

Peptostreptococcus sp. * *

Clostridium perfringens *

X microorganisms associated with FDA approved indications.•Exhibits in vitro MIC of <1 mcg/ml( ciprofloxacin), < 2 mcg/ml (enoxacin, gatifloxacin,levofloxacin,lomefloxacin,moxifloxacin,ofloxacin), <4 mcg/ml( norfloxacin) against >90% strains •however, the safety and effectiveness in treating clinical indications has not been established in adequate well controlled clinical trials.

Fluoroquinolone Fluoroquinolone EfficacyEfficacy

FDAFDA IndicationsIndications

Site Gatifloxacin Levofloxacin Moxifloxacin

Urinary Tract X

(complicated and uncomplicated)

X

(complicated and uncomplicated)

Lower Respiratory Tract (CAP) X X X

Chronic Bronchitis X X X

Skin and Skin Structure X

(uncomplicated)

X

(Complicated and uncomplicated)

X

(uncomplicated)

Sexually Transmitted Disease X

(N. gonorrhoeae)

Acute Sinusitis X X X

Pyelonephritis X X

Fluoroquinolone Fluoroquinolone Safety/TolerabilitySafety/Tolerability

• QTc Prolongation (Moxifloxacin)– Resulted in several agents being withdrawn from the

market

– Rare but life threatening

– Moxifloxacin has been shown to prolong the QT interval in some patients

– Phase II-IV studies of moxifloxacin treatment in over 7,900 patients resulted in no cardiovascular morbidity attributable to QTc prolongation.

– Torsade de pointes• 2 cases/1,300,000 gatifloxacin patients

• 1 case/1,000,000 levofloxacin patients

Fluoroquinolone Fluoroquinolone Safety/TolerabilitySafety/Tolerability

• QTc Prolongation (Moxifloxacin)– Infectious Disease Consultants Opinion

• Thinks concerns are over-stated

• Levofloxacin time on the market substantiates it’s safety profile

Fluoroquinolone Fluoroquinolone Safety/TolerabilitySafety/Tolerability

• Dysglycemia (Gatifloxacin)– Both hypoglycemia and hyperglycemia

– Diabetic patients receiving oral hypoglycemic agents or insulin appear to be at highest risk

– Elderly patients (>75yrs) may be at higher risk due to underlying disease states and decreased renal function

• Infectious Disease Consultants Opinion– Low risk

– Should use all fluoroquinolones in the diabetic population with caution

– European Union Decision Paper • Do not use gatifloxacin in ICU patients

• Should use all fluoroquinolones in the diabetic population with caution

Fluoroquinolone Fluoroquinolone Therapeutic InterchangeabilityTherapeutic Interchangeability

• NOT sufficiently interchangeable to support a closed class contract– Different coverage between the products

– Safety/tolerability concerns are different between the products

– Infectious Disease Consultants strongly agree and voiced that opinion • “Infectious Disease Consultants from each service,

concluded gatifloxacin, levofloxacin and moxifloxacin could be used interchangeably to treat CAP and sinusitis when a fluoroquinolone is clinically indicated.”

Fluoroquinolone Fluoroquinolone Clinical CoverageClinical Coverage

• Bottom Line:– Two major indications for fluoroquinolones are CAP and

UTIs

– 4th generation fluoroquinolones (moxifloxacin and gatifloxacin)• Increased gram positive coverage

• Reduced gram negative coverage

• Gatifloxacin will cover approx. 80% of UTI infections

• Moxifloxacin does not have UTI indication

– Extensively metabolized prior to excretion

– Levofloxacin has a good range of coverage for bugs involved with CAP and UTIs

– All three agents provide good upper respiratory tract coverage for pneumonia (esp. CAP)

FluoroquinoloneFluoroquinolone PEC Recommendation PEC Recommendation

• Compete moxifloxacin, gatifloxacin and levofloxacin for BCF status as a “workhorse” fluoroquinolone for the indication of Community Acquired Pneumonia (CAP) and Acute Sinusitis.– Open class status

• If moxifloxacin or gatifloxacin wins, add generic ciprofloxacin to the BCF as preferred fluoroquinolone for UTI.– When other cost-effective antibiotics are contraindicated

or ineffective.

• If levofloxacin wins, it will remain the only fluoroquinolone needed on the BCF for all three indications.

Fluoroquinolone Fluoroquinolone Contract GuidanceContract Guidance

• A joint VA/DoD open class contract was awarded to gatifloxacin– Addition to the BCF

– “workhorse” fluoroquinolone for the indications of CAP and sinusitis

– All strengths of oral gatifloxacin tablets must be on their MTF formulary

• DoD P&T Executive Council does not advocate indiscriminate use of gatifloxacin for all cases of CAP and sinusitis

Fluoroquinolone Fluoroquinolone Contract GuidanceContract Guidance

• DoD P&T Executive Council 8 January 2003 interim meeting– Remove levofloxacin from the BCF

– Gatifloxacin added as per contract

• PEC strongly recommends that MTFs remove levofloxacin from their local formularies.– Use only for cases of medical necessity

– Use of more cost effective fluoroquinolone or antibiotic

• An opportunity for cost savings – Dependent upon local MTFs and their local P&T

decisions and monitoring

– Clinical outcomes and cost effectiveness monitoring by local MTF P&T

SummarySummary

• Overriding objective of PEC and P&T Committee: maximize value of drug therapy– Optimize clinical and humanistic outcomes

– Optimize economic outcome

• A complete, careful, and objective clinical evaluation is essential to success

• There are very few “no-brainers” in this process

Can this work for local MTFs?Can this work for local MTFs?

• MTF Pharmacy and Therapeutics Committees:– Objective evaluation of MTF formulary

additions/deletions based on:• Clinical effectiveness

– Therapeutic interchangeability

– Clinical coverage

– MTF provider acceptance

• Economic (cost effectiveness)

– Existing contracts

– Existing Blanket Purchase Agreements (BPAs)

– Existing FSS prices

– BPAs offered by one or more companies

PEC ReviewsPEC Reviews

• New Drug Monograph Template

• VA/DoD Drug Class Review Template

• New Drug Monographs

• Drug Class Reviews

• Posted on RxNET (www.dodrxnet.org)– Forum: File Library

• DoD P&T Library

Uniform Formulary and the MTF Uniform Formulary and the MTF Pharmacy & Therapeutics CommitteePharmacy & Therapeutics Committee

BCFMTF

Uniform Formulary

Basic Core Formulary (BCF) contains the minimum set of drugs that each MTF Pharmacy must have on its Formulary to support the Primary Care Manager enrollment sites

MTF formularies are Determined by local P&T Committees based upon Scope of health care services provided

Drugs designated as non-formularyOn the Uniform Formulary shall not be included on the MTF formulary

Uniform Formulary and the DoD Pharmacy Uniform Formulary and the DoD Pharmacy and Therapeutics Committeeand Therapeutics Committee

• Inclusion on Uniform Formulary based on:– Relative Clinical Effectiveness

• Effectiveness

• Safety

• Clinical outcome

– Relative Cost Effectiveness• Cost of drug to the government

• Impact on overall medial resource utilization and costs

• Cost-efficacy studies

• Cost-effectiveness studies

• Cross-sectional or retrospective economic evaluations

• Pharmacoeconomic models

• Patent expiration dates

• Clinical practice guideline recommendation

• Existence of BPA, contracts or incentive price agreements

Uniform Formulary and the DoD Pharmacy Uniform Formulary and the DoD Pharmacy and Therapeutics Committeeand Therapeutics Committee

• Non-formulary pharmaceutical agent classification if:– Determined not to have a significant, clinically

meaningful therapeutic advantage in terms of safety, effectiveness, or clinical outcome compared to other drugs included on the Uniform Formulary

– Determined not cost effective relative to other pharmaceutical agents in a therapeutic class

• Not available at MTF pharmacies unless medical necessity to use the non-formulary drug is validated through the special order process

Final SummaryFinal Summary

• Clinical analysis is most critical in determining formulary status and procurement initiatives

• DoD P&T Committee procurement initiatives can only provide you with an opportunity to save money

• The cost avoidance impact of the decisions made by the DoD P&T Committee is dependent upon local MTFs

• Clinical outcomes and cost effectiveness monitoring at local MTFs

Questions?Questions?