Peter A Glassman, MBBS, MSc VA Greater Los Angeles Healthcare System

1. Developing an Essential Medicines List for Palliative Care: Some Lessons from the VA Experience Peter A Glassman, MBBS, MSc VA Greater Los Angeles Healthcare System

2. Goals • Brief background • Discuss Pharmacy Benefits Management (PBM) • Relate VA experience • Consider congruency with essential medicines list for palliative care

3. Palliative Care: Some Basic Issues • Prevalence of advanced illness • High rate of symptoms • Adverse effects on quality of life • Many effective treatments exist • Guidance available for treating patients and symptoms

4. Palliative Care: Medicine-related Issues • Medicines not universally available: • Healthcare system deficiencies • Patient access • Drug availability • Drug costs • Ineffective treatments may be substituted • Evidence is not well developed

5. What Is to Be Done? • Address essential medicines • By selected conditions/symptoms • By drug or drug class

6. Developing an Essential Medicines List for Palliative Care • What lessons can be gleaned from VA (and others) to assist in developing an essential palliative medicines list?

7. WHO Essential Medicines List • Core list: • “a list of minimum medicine needs for a basic health care system, listing the most efficacious, safe and cost-effective medicines for priority conditions.” • Complementary list: • “essential medicines for priority diseases, for which specialized diagnostic or monitoring facilities, and/or specialist medical care, and/or specialist training are needed. In case of doubt medicines may also be listed as complementary on the basis of consistent higher costs or less attractive cost-effectiveness in a variety of settings.” • [Essential Medicines. 14th Edition. March 2005].

8. Pharmacy Benefits Management • Managed care activities devoted to assuring safe and effective (and cost-effective) prescribing and use of pharmaceuticals and related products

9. Components • Include • Formulary and Non-Formulary Development • Pharmaceutical Use Management • Product Storage, Dispensing, Delivery • Outcome Monitoring

10. Formulary • A “Formulary” is a comprehensive pharmaceutical benefits package • Oversight by Pharmacy & Therapeutics (P&T) Committee or similar • Dynamic process that requires assessment of evidence to determine included agents

11. Formulary • Open: Broad package • Some exclusions • access relatively equal among items • Restricted: • preferred drugs not on equal footing with non-preferred drugs: • non-formulary (waiver/exemption) • Restricted (“prior authorization”) • Tiered (different co-payments): “Preferred List”

12. Formulary Decision-Making • Explicit review (drug or drug class) of efficacy/effectiveness, safety profile and costs • Comparative to other treatments • Relevance to population • Expert and unbiased assessment

13. Evidence: Efficacy/Effectiveness • Efficacy/effectiveness: • Ability to achieve specified clinical endpoint(s) • For a condition • For a population • Comparative efficacy: • Ability of a set of drugs to achieve similar specified clinical endpoints • efficacy/effectiveness descriptors: • Relative benefit (relative risk reduction) • Absolute benefit (absolute risk reduction) • Number needed to treat (NNT) to achieve benefit

14. Safety • Safety • “Safe” is a relative term • Safety Profile is most relevant (cataloguing of adverse effects) • Adverse effects are known or described • Can be anticipated and, if possible, prevented • When they occur are recognized and mitigated. • Comparative safety: • the profile of one agent viewed in context of its pertinent comparators. • Safety descriptors: • Relative harm (relative risk increase) • Absolute harm (absolute risk increase) • Number needed to harm (NNH) for an event

15. Evidence Based Policy and Practice • Requires a systematic assessment of cumulative literature • Evidence of benefit (greater than harm) • Quality of evidence • (e.g., RCT vs. retrospective cohorts, case control studies, epidemiological data) • Grading systems are available to help evaluate the quality of evidence (e.g., AHRQ)

16. Evidence Based Policy: Some Common Mistakes • Using methodologically flawed studies • Incomplete reviews: using selected studies • Epidemiological data applied to therapy (e.g. HRT) • Singularizing combined endpoints • Using intermediate health outcomes for efficacy • Applying evidence of safety or efficacy from approved to unapproved uses

17. Quality of Evidence and Quality of Practice: An Example • Hormone replacement therapy (HRT) • Epidemiological data and interim outcome studies (e.g., lipids) pointed to favorable outcomes • 1985  post-menopausal HRT  less CHD • 1998  post-menopausal women had increased events in early HRT but this still did not dampen enthusiasm for therapy • 2002  Women’s Health Initiative stopped • Increased risks: CHD, stroke, invasive breast cancer, pulmonary emboli • Benefit: hip fractures, colorectal cancer • JAMA.2002; 288:321-323

18. Costs and Cost-Effectiveness • Costs may include: • Pharmaceutical and pharmacy related costs: • Acquisition (price for medication) • Dispensing (manpower, robotics) • Delivery (refrigerated packaging) • Other associated costs • Examples range from tablet splitters to extra staffing or extra staff time or clinic visits. • Patient-related costs (i.e., indirect costs) • Examples range from missing work to additional travel time

19. Cost-Effectiveness Analysis • Cost-effectiveness analysis allows for comparing different treatment or management options: • “Cost per unit of output” • , events avoided, additional years of life, clinical endpoint. • Cost-minimization: assume that non-medication costs and outcome are similar • For example, a drug class effect • Comparative cost-effectiveness helps determine the relative hierarchy of two or more treatment options • marginal cost-effectiveness • “extra cost incurred divided by the change in outcome” Quotes: Sox et al. Medical Decision Making. Stoneham, MA: Butterworths. 1988

20. Best Value* Maximum clinical benefit, minimum adverse events, lowest possible price In other words

21. VA Pharmacy Benefits Management Strategic Healthcare Group (PBM) • Formed in early 1996 • Comprised of: • Medical Advisory Panel (MAP) • Practicing physicians from different VA’s • Primary Care/Geriatrics • Psychiatry • Medical Specialties • Pharmacists and Support Staff (Hines,IL) • Chief consultant and other staff (Wash, DC) • Work in collaboration with regions (VISNs)

22. The Mission of the PBM • Manage the VA’s comprehensive pharmaceutical benefits package • VA National Formulary • Evidence-based monographs • guidance/criteria for use • Pharmaceutical-related outcomes • Efficacy/Effectiveness • Safety: Center for Medication Safety

23. The VA National Formulary • Includes • Prescription medications • Over-the-counter medications • Medical-surgical items • Intent: • Product standardization • Portability nationwide • Reduce costs • Assure uniform access

24. Developing the VA National Formulary • The main obstacles (circa 1995): • Approximately 170 different formularies • Drug choices varied • Fierce degree of independence • Pharmacy expenditures were rising • Silo effect on budgets

25. Contemporary Issue • National Formulary • Allowed for regional variations • Current transition to a single formulary

28. Drug Monographs • Evidence-based assessments including: • Pharmacology • Approved Indications and Off-Label Uses • Formulary alternatives • Dosing • Available study data: Efficacy and Safety • Other safety issues: drug interactions, look alike, sound alike • Economic data: Costs/Comparative Costs • Conclusions and Recommendations • References • Appendices

29. 39 pages

30. Drug Use Criteria • Standardize care • Translate evidence to practical decision-making • A “how-to” guide

32. PBM-MAP Drug Use Management Process ID Areas of opportunity • Review: • RX volume • RX expenditures • New Drugs Monitor Performance Assess feasibility • Contract Participation • Utilization Management • Use of Criteria • Review: • Medical Literature • VA Prescribing • Clinical Need START Implement action(s) • One or more of: • Issue Drug Use Criteria • Conduct Solicitation • Negotiate BPA Present issue to stakeholders • Medical Advisory Panel (MAP) • VISN Formulary Leaders (VFLs) • Get input from front • line clinical staff • Chief Clinical Consultants • DoD • Pharmacoeconomic Center • P & T Committee Determine action(s) • Nothing • One or more of: • Guideline • Criteria for Use • National Contract • Blanket Purchase • Agreement Slide courtesy of M. Valentino.

33. A Seamless Package Studies Evidence Summary Criteria for Use Guidance/Guideline Use Evaluate

34. Congruency Between Essential Medicines and Formulary • Basic conceptual overlap with formulary development • Approved indications • Governmental agency (e.g., Food and Drug Administration) • Unapproved (off-label) use • Especially important for palliative care • Typically have less evidence • Examples: • Codeine Sulfate: • Approved use: Reduce Pain (mild to moderate) • Off-Label use: Ameliorate dyspnea • Scopolamine (transdermal): • Approved use: Prevention of symptoms from motion sickness • Off-Label use: Reduce secretions

35. Congruency (Continued) • Determine essential medications that are effective, safe (meaning we understand the safety profile) and “cost-effective”: • Most easily done by choosing generic medications for approved indications • Morphine sulfate for pain • Selected benzodiazepines for anxiety • And then further detail off-label use • Consider criteria for more expensive agents • E.g., fentanyl patch for those unable to take oral opioids

36. By drug Which condition is drug essential for How to use drug for various conditions/symptoms By condition Which drugs may be used How to treat condition/symptom using various drugs Listing

37. Summary • A formulary is a comprehensive list of medications • Oversight (P&T Committee) • Dynamic process • Evidence based

38. Summary (Continued) • Essential medicines list is a limited (or core) formulary of necessary drugs • Generics: • Evidence already exists for efficacy/effectiveness, safety profile • Cost-effective • Utilize additional evidence summary for conditions where drugs may not be specifically approved • Criteria as applicable