LCDR Marisol Martinez, PharmD Fort Sam Houston, TX A Peek at the PEC: An Overview of Formulary Management at the Department of Defense (DoD) TRICARE Management Activity (TMA) Pharmacoeconomic Center (PEC) LCDR Marisol Martinez, PharmD Fort Sam Houston, TX

Objectives Discuss the Department of Defense (DoD) TRICARE pharmacy benefit and the role and responsibility of the PEC in formulary management Discuss the lessons learned from the DoD P&T process for conducting drug class reviews to determine clinical and cost effectiveness Review the functions of the Pharmacoeconomic Outcomes Research Team (PORT) and the implications of formulary decisions on military treatment facilities (MTF)

Outline TRICARE Pharmacy Benefit Roles of the PEC Process Timeline Determining Clinical Effectiveness Determining Cost Effectiveness Functions of the PORT Implications of P&T’s decisions Conclusion Questions

TRICARE Pharmacy Benefit Background Points of service MTF Retail Mail Order Population – 9.7 million beneficiaries Active duty, retired Uniformed Service members, and family members Expenditures – $7.5 billion dollars Uniform Formulary Rule P&T Committee mandated by Congress Military Treatment Facility Retail pharmacy network Mail Order Pharmacy Serves a diverse population of 9.7 million beneficiaries -The majority being retirees and family members <65 yrs Mandated by congress that we have a P&T committee to review clinical and cost effectiveness of drugs

Extended Core Formulary TRICARE Formulary Uniform Formulary Basic Core Formulary Extended Core Formulary Non Formulary This is example of how our formulary looks in the MTF In mail and retail it is different, there is only UF and NF Just bc something is NF, doesn’t mean it’s not available In mail and retail, in most situations, generics are $3, brands are $9, and NF is $22 Examples of ECF=biologics, drugs for Multiple Sclerosis, Hemophilic drugs

TRICARE Pharmacy Benefit – Points of Service FY09 POS Rxs 30-day Rxs* 30-day Rxs (%)* % Dollars Total Dollars MTF 48,101,964 80,252,540 44% 19% $1.43 B Retail 71,414,850 73,753,775 40% 67% $5.06 B Mail Order 10,454,703 30,148,634 16% 14% $1.05 B 30-day Rxs-equalized through the different points of service Mail=90 days Retal, MTF=30 days *Normalized based on 30-day supply of medications

The PEC Staff The PEC staff includes Army, Navy, Air Force, Public Health Service, and civilian personnel. Comprised of pharmacists, physicians, pharmacy technicians, data analysts, pharmacoeconomists, customer service representatives, and support personnel.

Responsibilities of the PEC Evaluate the clinical and cost effectiveness of drug therapy to support the DoD P&T Committee formulary decision-making process Implement and maintain the DoD pharmacy benefit Assess the outcomes of drug therapy to improve patient care and provide a feed-back loop for the DoD P&T Committee

Process Timeline Drug Class Selection PEC completes Clinical and Economic Analysis Consult with PORT DoD P&T Meeting Beneficiary Advisory Panel TMA Director Decision Implementation

Drug Class Selection High expenditures across Military Health System (MHS) “20/80 Rule”: 20% of the drugs comprise 80% of the expenditures Market competition within a class Expiration of existing DoD or DoD/VA contracts Impending generic competition Newly approved drug likely to impact existing class The 20/80 rules just describes the way we focus on 20% of the drugs that make up 80% of our cost We can’t review 100% of the drugs, so this is how we focus our efforts. Example of big classes: anti-inflammatory drugs, the cholesterol drugs, drugs for hypertension (the biggest classes with the most impact on the beneficiaries get the most attention) Market Competition: example: We haven’t done anything yet with plavix, but now, prasugrel is out and a direct competitor

Drug Class Selection November 2010 P&T meeting Rationale Januvia and Onglyza Rationale Not previously reviewed Significant cost to the DoD Increased utilization Safety concerns Clinical guidelines DPP4s had not been reviewed as a class From Aug 07 to September 2010, utilization had picked up Clinical guidelines: say to use metformin or sulfonylurea first before DPP-4s

Process Timeline Drug Class Selection PEC completes Clinical and Economic Analysis Consult with PORT DoD P&T Meeting Beneficiary Advisory Panel TMA Director Decision Implementation

Clinical Analysis Review Process Team Approach Drug Class Review Key Questions Background Efficacy Safety Tolerability Other Factors Formal Presentation Utilization and Spend PEC Recommendations Team Approach-at least one clinical pharmacist and 1 physician sharing the work Drug Class Review Key Questions- How does drug A differ from drug B in terms of efficacy, safety, and other factors? Background-pharmacology Efficacy-What are the drugs used for and how well do they work? Does one drug in the class work better than the others, or are the effects the same? Safety-How likely will the drugs cause harm? (number needed to harm). Is one drug more likely to cause harm than another? Pharmacokinetics Tolerability-Are patients likely to take it? Other Factors- ease of dosing, taste of nasal steroids, dosing frequency, preservatives, packaging, . We think about our population in theater (heat, sand, stability, ex. Birth control patches)

Clinical Analysis Evidence Based Medicine Goal Use the best quality evidence when determining differences within the drug class Meta-analyses and Systematic Reviews Randomized Controlled Trials Non-randomized Trials Cohort and Case Control Studies Poster Presentations Reps We try to use the highest level of evidence (no glossy brochures allowed!) Meta-analyses or systematic reviews Condense the results of several trials (10s-100s) into an understandable format Can determine differences in efficacy, safety between drugs Results shown as odds ratio or tornado plot to show differences between drugs “Number Needed to Treat” (NNT) Weighted Mean Difference Limitations of Meta-analyses and other systematic reviews Not always available for a particular drug class, especially for newly approved agents in the class Trials may include widely differing patient populations, background meds, dose of comparative drugs, that makes true comparisons difficult May include individual studies that are not of good quality May only compare Drug A to placebo and Drug B to placebo, and may not compare Drug A to Drug B Randomized, double-blind, placebo controlled trials Head-to-head trials: often not available If head–to-head trials are available, other problems In the absence of head to head trials, do other things Calculate NNT Compare hazard ratios, odds ratios and confidence intervals Indirect comparison) Non-randomized trials unequal allocation of drug treatment Cohort studies, case control studies No intervention is given, so can’t definitely say that drug A causes outcome Z Case reports / anecdotal reports: lowest level of evidence not peer-reviewed, often only incomplete data available

Clinical Analysis Evidence Based Medicine Januvia and Onglyza Evidence No meta-analysis or systematic reviews Relied on randomized controlled trials for efficacy and safety Head-to-Head trial No outcomes data with the DPP-4s, so we have to rely on A1C lowering We usually like to look at hard clinical outcomes, for example, Do these drugs decrease cardiovascular disease or death?

Head-to-Head Trial Saxagliptin vs Sitagliptin 18 week, Phase 3b, MC, DB, non-inferiority trial Saxagliptin 5mg OR Sitagliptin 100mg Stable metformin doses (1500-3000mg/day) Primary endpoint  from baseline A1c Non-inferiority concluded if upper limit of 2-sided 95% CI of the A1c difference between treatments was <0.3% Secondary endpoints % of patients achieving A1c < 6.5% and 7%  from baseline FPG, insulin, C-peptide, proinsulin, HOMA-2 Taken straight from the DoD P&T slide deck This is how we present information to the committee Diabetes Metab Res Rev 2010;26;540-549.

Saxagliptin vs Sitagliptin Results SAXA + Met N = 334 SITA + Met N = 343 Mean (SE) A1c at baseline (%) 7.68 (0.052) 7.69 (0.047) Mean (SE) A1c at week 18 (%) 7.16 (0.052) 7.07 (0.051) Adjusted change from baseline A1c (%) Mean (SE) Two-sided 95% CI -0.52 (0.039) -0.60, -0.45 -0.62 (0.038) -0.69, -0.54 Difference in adjusted change from baseline A1c vs sitagliptin + met (%) 0.09 (0.055) -0.01, 0.20 - Taken straight from the DoD P&T slide deck This is how we present clinical trial data The company wanted to show noninferiority and they stated beforehand that there would be no difference between groups for A1c Each drug was stat sig vs baseline, but only by a 0.5-0.6 decrease in A1C However, when drugs were compared to each other, there was no stat sig difference SE = standard error Diabetes Metab Res Rev 2010;26;540-549.

Clinical Analysis Provider Input Developed by the clinical evaluation team Sent via email using web survey tool Questionnaire Physicians Pharmacists Other healthcare providers Summarized responses presented to the P&T Committee Missing input from civilian network providers Januvia and Onglyza: Email Invites > 500, Responses 443 To help made our recommendations, we ask for provider opinion

Provider survey summary Very little experience with saxagliptin Survey: Non-Insulin Anti-Diabetic Agents: To what extent do you agree or disagree with this statement: "In order to treat the majority of y ... Provider survey summary Very little experience with saxagliptin Clinicians would be willing to use saxa or sita Clinicians requested one agent on their local formulary

Economic Analysis Relative Cost-Effectiveness Two broad types of economic analyses Pharmacoeconomic Analysis Evaluates the outcomes and costs of interventions designed to improve health 4 types Budget Impact Analysis (BIA) Accounts for costs associated with a decision Estimates the likely impact (use and cost) of a formulary decision over 2-3 years To determine relative cost-effectiveness, the PEC uses two types of economic analyses BIA: Factors included in the model Market growth Market share migration: Change in utilization among therapeutic class agents as beneficiaries migrate from nonformulary (NF) to UF agents Costs associated with migration from NF to UF agents: Medical necessity processing fees •Provider costs associated with switching patients from NF to UF agents Cost reduction associated with NF $22.00 co

Types of Pharmacoeconomic Analysis Cost-Minimization Analysis (CMA) Treatments are equally effective Cost is only factor Cost-Effectiveness Analysis (CEA) Outcomes vary but can be expressed in a common unit Combines clinical benefits with cost efficiency Cost-Utility Analysis (CUA) Costs and consequences of different interventions in terms of the patient’s health-related quality of life and survival time Cost-Benefit Analysis (CBA) Compares the net costs of a health care intervention with the benefits as a result of applying that intervention Cost-Minimization: A type of analysis used when two treatments have been deemed equally effective, so cost is the only differentiating factor. Hence, CMA compares only costs The models typically evaluate the cost per day of treatment at conventional doses for each drug Results are reported as the weighted average cost per day of treatment. Can only evaluate therapies that produce identical outcomes Cost-Effectiveness: Usually limits its use to comparisons between treatments affecting the same condition/ patient group For example, there are several treatments for allergic rhinitis. Their effectiveness varies, but can be expressed in terms of a reduction in daily rhinitis symptoms. Could compare the cost per % reduction of symptoms. Examples statins-cost per 1mg/dL of LDL lowering; BP-cost per mm of mercury lowering. Clinicians like this because it shows how a drug works compared to the cost. Cost-Utility: Key thing is Quality of Life. This method is useful when evaluating interventions that are life-extending, yet with significant side effects, or those that produce reductions in morbidity rather than mortality. Includes patient preference in analysis of benefits. - Utility measurements are not standardized. Seldom used – controversial to assign a monetary value to health outcomes. Example=assess the Quality of life of Alzheimer's patients that have caregivers Cost-Benefit: Assessing a program or service. Valuing health outcomes on money. It is difficult to give a price on health. We tend to use the first 2 categories the most at the PEC. As you move down the list, you start to look at different interventions and a broad look of how treatments are applied.

CMA Results MTF Retail $0.00 $0.50 $1.50 $2.50 $3.00 Drug A Drug B $1.00 $2.00 $1.75 $1.55 $0.00 $0.50 $1.50 $2.50 $3.00 Drug A Drug B (1 of 1 UF) (1 of 2 UF) (1 of 2 UF/BCF) Cost ($)/Day Weighted average cost for all 3 POS standardized to drug A market share (46% MTF; 30% RET; 24% MAIL) The DPP-4 Inhibitors have similar A1c lowering effect when used as monotherapy. Since, this was our conclusion (assuming cost was the only factor), we could then use the cost minimization analysis We can’t show the prices made by the drug manufacturers, but this is an example of what the P&T Committee would see when looking at a Cost-Minimization Analysis (1 of 1 UF, 1 of 2 UF, etc= contracting strategies)

Economic Analysis Decision Criteria Rejection threshold Cost NO MAYBE Increase Acceptance threshold Worse Better Effect To wrap things up for economic analysis, we try to find the drug with the best clinical outcomes that will also cost the MHS the least amount of money. Decrease MAYBE YES

Process Timeline Drug Class Selection PEC completes Clinical and Economic Analysis Consult with PORT DoD P&T Meeting Beneficiary Advisory Panel TMA Director Decision Implementation

Pharmacy Outcomes Research Team (PORT) Co-located in DC and San Antonio 3 pharmacists 2 pharmacoeconomists Data analyst Technical writer Improve the outcomes of drug therapy and enhance the quality of the TRICARE pharmacy benefit Support the DoD P&T Committee and assess the effects of formulary changes on DoD beneficiaries PORT is comprised of researchers based both at the PEC in San Antonio and at the Pharmaceutical Operations Directorate (POD) main office in Falls Church, VA.

Estimated new users/year Total unique utilizers/yr “First-line Use”: New Antidiabetic Users No Antidiabetic Rxs Prior 12 Months, Combos w/ Parent Agents X12 July 10 Jul 09 – Jun 10 New users Jul10 Estimated new users/year Total unique utilizers/yr Jul09-Jun10 % new users DPP-4 No antidiabetic Rx 495 5940 93,661 6 GLP-1 98 1176 23,053 5 TZD 460 5520 140,156 4 Insulin (any) 1177 14,124 159,665 9 SU 1449 17,388 222,537 8 Metformin 5959 71,508 423,224 17 Other antidiabetics 60 720 16,513 New metformin users represent 17% of all metformin users Example of what kind of questions the PORT can answer for us How many patients with no other antidiabetic scripts are given DPP-4s and what percentage are new users. The PORT conducted this analysis to see whether or not our providers were starting patients on more validated treatments vs less validated treatments Note: This method counts individuals who received an Rx for a given drug or drug class during a given month (e.g., Jul10) but NOT during the previous 12-month period (e.g., Jul 09 to Jun10); all POS

“First-Line” Use of DPP-4s 93,661 unique users Jul 09 – Jun 10 Estimated new users per year (n) No antidiabetics at all, last 12 months = 5940 No DPP-4 last 12 months = 35,364 No DPP-4, had Met or SU, last 12 months = 27,636 ~22% of new DPP-4 users had no Met or SU last 12 months Of these, about 1/3 (1788) had antidiabetics other than Met or SU prior to DPP-4s So, the percent of new DPP-4 users with no prior antidiabetic use is ~17% Sample PORT slide for DPP-4s We are not going to go over the data in detail, but here is an example of the results we got from our pharmacies From here, they found out how many patients would be affected by step-therapy Overall, we felt that our provders appear to be using this class of medications appropriately They are not abandoning metformin and sulfonylureas for newer therapies So , we will watch and continue to monitor DoD Pharmacy Outcomes Research Team

Process Timeline Drug Class Selection PEC completes Clinical and Economic Analysis Consult with PORT DoD P&T Meeting Beneficiary Advisory Panel TMA Director Decision Implementation

DoD P&T Meeting Uniform Formulary placement Basic Core Formulary (BCF) additions Medical necessity criteria for NF drugs Prior authorization requirements Quantity limits Minutes of each meeting include recommendation summaries and supporting documentation P&T meets quarterly: Feb/May/Aug/Nov

DPP-4 Inhibitors Relative Clinical Effectiveness DoD P&T Committee Recommendation on the Relative Clinical Effectiveness (vote) Motion: The DoD P&T Committee agrees with the relative clinical effectiveness analysis of DPP-4s as presented Vote Slide from the meeting; the committee has the opportunity to challenge any presented material and we do have lots of discussion sometimes. We take an anonymous vote

BCF Decision PEC Recommendation Januvia and Janumet BCF Justification Budget impact analysis showed more cost effective when placed on the BCF Questionnaire results showed preference for a BCF agent Slide from meeting: Our recommendation BCF=Basic Core Formulary

Medical Necessity vs Prior Authorization Requirement when drugs are made Non-formulary Five criteria to meet medical necessity CI, ADR’s, Tx failure, stable patient and unacceptable risk if change to UF drug, no UF alternative Retail/Mail Order: Fulfilling MN reduces co-pay from $22 (NF) to $9 (UF) MTF: Fulfilling MN allows pt to receive NF drug at MTF Prior Authorization Drug with PA can be in a UF-reviewed class (PDE-5s, biologics for RA), or class not previously reviewed Assist with ensuring appropriate use There are 5 ways a pt cal still get a NF drug: Administratively, we can assign a PA to a drug if we have reviewed it or have not reviewed it. This can be for safety reasons, or overuse in off label use, or other reasons. example PDE-5s: have to be male, and if you are male, you have to be a certain age to get a PDE-5 for erectile dysfunction example Byetta: You have to have Diabetes Mellitus to get this bc it cannot be used for weight loss NF=Non-formulary MTF=Military Treatment Facility UF=Uniform Formulary

Step Therapy Automated Prior Authorization = Step Therapy Applies to Retail Network/Mail Order, where computer can look back at patient’s profile Requires use of preferred agent first, then can try others in the class that are UF PPIs , BPH drugs, Insomnia Manual Prior Authorization When automated PA fails Physician initiates a call or fills out form Example of the PPI step therapy: Example of BPH step therapy: Manual PA (don’t say this, just FYI): Happens when the automated PA fails. The rejection comes back and the pharmacist gets a phone # that the dr has to call. Or, the Dr. Can fill out a PDF online and fax in (usually get an answer by the end of the day). Or, the dr can call in and answer question to a verbal script (will get results over the phone). If approved, then it’s entered into the system. If not approved, the dr or patient can appeal up to 2 times. The patient can call anytime to check the status of the manual PA.

Step Therapy Automated review of patient profile. Has the patient previously received the preferred product? Rx pays and is dispensed YES Prescription written Pharmacy processes prescription PDTS checks patient profile NO Rx does not pay Prior Authorization required Or, Patient must try the preferred product

Process Timeline Drug Class Selection PEC completes Clinical and Economic Analysis Consult with PORT DoD P&T Meeting Beneficiary Advisory Panel TMA Director Decision Implementation We also call this the “BAP”

The Beneficiary Advisory Panel (BAP) Washington DC Congress established Focus on implementation of UF decisions Enhance transparency to beneficiaries Members Active duty family members Retirees and their family members 2 clinical experts outside of the DoD Pharmacist from the US Family Health Plan Physicians or pharmacists from the TRICARE regional contractors After the P&T meeting ends, and the minutes are written, we communicate our decisions to the BAP Congress established the Uniform Formulary Beneficiary Advisory Panel (BAP) to review and comment on the recommendations from the Department of Defense Pharmacy and Therapeutics (DoD P&T) Committee.  The conversation at the BAP is public information (anyone can attend), it’s on the Federal Register. LTC Spridgen’s notes: BAP - speak about their perview, UF recommendation, PA criteria, and implementation..... integral part of the DoD UF process, this group sets our process apart. Both sets of minutes go to the TMA Director to approve

The BAP Concerns regarding Januvia and Onglyza Does the Committee consider the mechanism of action when deciding where to place an agent? Does a patient need to go through step therapy to use metformin in combination? Can a patient get Janumet without trying a sulfonylurea or metformin first?

Process Timeline Drug Class Selection PEC completes Clinical and Economic Analysis Consult with PORT DoD P&T Meeting Beneficiary Advisory Panel TMA Director Decision Implementation

TRICARE Management Activity (TMA) Director Decision Reviews comments and approves the P&T minutes After the minutes are approved, the decisions may be made public Dr. Jonathan Woodson Assistant Secretary of Defense for Health Affairs Director, TMA Woodson oversees TRICARE expenditures

TRICARE Management Activity (TMA) Signed Minutes Example of section out of the minutes

Process Timeline Drug Class Selection PEC completes Clinical and Economic Analysis Consult with PORT DoD P&T Meeting Beneficiary Advisory Panel TMA Director Decision Implementation

Implementation 30, 60, 90, up to 180 day implementation Based on level of effort and awareness necessary to make the change Several things happen Education Operations Prior Authorization edits-testing Formulary search tool and Epocrates Monitoring DPP-4 Inhibitors - 60 day implementation We choose a 30, 60, 90, up to 180 day implementation based on the level of effort and awareness necessary to make this change and the number of affected beneficiaries   several things happen both to disseminate information on the impending change and to physically operationalize the edit: Epocrates went live with the TRICARE formulary in April 2011. We did this to increase our formulary’s visibility out in the general public Educations (after the minutes are signed): 1. Push out documents are sent out to MTFs, medical directors of network providers 2. Letters are sent out the beneficiaries who may be effected in retail/mail. 3. Our support contractors are informed of the changes so they can educate their staff who provide customer support to TRICARE beneficiaries. Operations: 1. We create the edits. The edits are tested and implemented as follows: Non-form change: a. ESI will make the change in their adjudication system. b. Emdeon will modify their records of the change so the drug will be coded at the correct tier (co-pay) level in the data repository. Step-therapy: a. Emdeon will build and test the edit set-up in PDTS since their system will perform the look-back b. ESI will set-up the PA requirements in their system and will educate their customer support staff on the PA criteria necessary for overrides. PA edits: a. ESI will setup the PA requirements in their system and educations their staff on the PA criteria b. Emdeon will set-up a PA record and will allow portability if we deem appropriate. (portability => a PA generated at an MTF will also allow a claim for that drug to pay in retail/mail) 2. We make changes to the Formulary Search Tool and Epocrates. a. All necessary forms are posted b. Rule are created to display the formulary changes. 3. Once the edits are live we monitor the adjudication system to make sure the edits are working appropriately. The tricky part of this process is building the edit especially when the PT decision support a step therapy set-up. We have to code at a hierarchy which will only include those drugs which should be represented in the step and make sure the step structure follow the PA criteria.

Summary Review of the TRICARE formulary is important to help manage a $7.5 billion dollar pharmacy benefit Formulary management is accomplished through a thorough evaluation of efficacy, safety, and cost The PEC staff assists the DoD P&T Committee with recommendations that provide the greatest value to the Military Health System

Questions

LCDR Marisol Martinez, PharmD Email: marisol.martinez@amedd.army.mil A Peek at the PEC: An Overview of Formulary Management at the TRICARE Management Activity (TMA) Pharmacoeconomic Center (PEC) LCDR Marisol Martinez, PharmD Email: marisol.martinez@amedd.army.mil