*Show Me the Evidence!Identifying the Truth about Rx DrugsEnter event/location May 19, 2008

*Faculty Disclosure Your Name Here, MDDr. Your Name Here reports that he has No Conflict of Interest with this presentation.In accordance with the requirements of the Standards for Commercial Support of the Accreditation Council for continuing Medical Education adopted by the AMA and the Oregon Medical Association, each instructor is asked to disclose any affiliations with, or financial interests in, companies whose products are discussed in his/her presentation.Event/Location of Lecture CME PresentationMay 19, 2008

Learning ObjectivesRecognize cost and health impact of inappropriate or excessive utilization of prescription drugsIncrease awareness of biased information and pharmaceutical industry marketing practices. Describe strategies that can reduce the influence of biased information.

Learning Objectives, cont.Describe how evidence-based approaches can be used to guide prescribing decisions.Provide reliable sources of unbiased prescribing information and practice guidance.Provide educational resources for more in-depth information regarding pharmaceutical industry marketing and use of evidence-based methods to make prescribing decisions.

Health Affairs 2008;27(1):14-29US Health Spending in 2006$2.1 trillion or $7,026 per personHealth care inflation generally outpaces increase in GDP.When health care costs rise faster than the overall economy, affordability and range/quality of benefits decrease.

Health Life ExpectancyHealthy Life Expectancy & Per Person Medical Expenses: 22 Developed CountriesPer Person Annual Medical Expenses

HALE 2002 BY PP EXPENDITURES 20

74.9934705073

73.3228362999

73.1670461711

72.8482847534

72.7056780774

72.5857001517

72.5743950458

72.034653152

71.9946549885

71.9744620334

71.8190049456

71.510567577

71.4113158329

71.1675088293

71.1253977202

71.0921233168

71.0120675572

70.8328116546

70.617118153

69.8470502285

69.7959038633

69.2642089947

Japan

Sweden

Switzerland

United States

HEALTHY LIFE EXPECTANCY AND PER PERSON MEDICAL EXPENDITURES

Per Person Health Care Expenditures 2001

Healthy Life Expectancy 2002

HEALTHY LIFE EXPECTANCY AND PER PERSON MEDICAL EXPENDITURES FOR 22 OECD COUNTRIES

Sheet1

http://www.who.int/whr/2003/annex_4_en.xlsACCESSED 5/0904

COUNTRYHALE 2002PP EXP 2001

Japan75.0$1,984

Sweden73.3$2,270

Switzerland73.2$3,248

Iceland72.8$2,643

Italy72.7$2,212

Australia72.6$2,350

Spain72.6$1,600

Canada72.0$2,792

Norway72.0$3,012

France72.0$2,561

Germany71.8$2,808

Luxembourg71.5$2,719

Austria71.4$2,191

Netherlands71.2$2,625

Belgium71.1$2,490

Finland71.1$1,841

Greece71.0$1,511

New Zealand70.8$1,733

United Kingdom70.6$1,992

Denmark69.8$2,503

Ireland69.8$1,935

United States of America69.3$4,887

average no czech71.7

MEDIAN with czech71.5$2,350

MEAN with czech71.6$2,392

Czech Republic68.4$1,106

Sheet2

Sheet3

Trends in health care

Rx Costs Are a Large Part of Overall Health Care SpendingSource: 2007 DMAP class 07/11 expenditures (total fund, excludes rebates)http://www.oregon.gov/DHS/aboutdhs/budget/07-09budget/index.shtml (accessed 6/10/08)http://www.oregon.gov/DAS/BAM/GRB0709.shtml (accessed 6/10/08)

Prescription Drug ExpendituresIncreased at a faster rate than any other area of health care over the last 15 years Major contributor to rising health care costsResponsible for a large portion of insurance cost increases Costs increased because ofIncreased utilization (prescribing rate) Increased price per prescription

Factors Driving UtilizationIncrease in prescription drug coverageMarketingAging populationMore chronic conditionsImpact of Medicare Coverage

Increased Price Per RXPrice increases for existing drugs exceed inflationLargest driver of increased Rx spending Newer drugs replace older less expensive agentsShorter approval timeMarketing of newer agents drives market share

Premiums, Earnings & InflationSource: Kaiser/HRET Survey of Employer-Sponsored Health Benefits

Implications of Current TrendsHealth care affordability continues to deteriorateHealth costs, including Rxs, expected to rise faster than economyIncreased consumer out-of-pocket costs increased premium share, deductibles, co-insurance, and co-paymentsState & Federal budget deficitsIncreased rate of uninsured/underinsured

Conclusions About CostsCurrently, the US spends more per capita on health care than any other developed country, yet is ranked near the bottom in terms of quality.Continuing on the current path has huge societal implications. How much more can we spend?The alternative is to spend more wisely.Payers are looking at all options to contain health care and pharmaceutical costs, and to get better value.This creates a great opportunity for prescribing physicians.

Quality of care issues with prescription drugsOver-medicalization (disease mongering)Treatment of non-disease or trivial entitiesPremature intervention in less severe conditions Poly-pharmacyIncreasing med side effects leading to more medicationsUnpredictable interactions and greater potential for errorsOff-label use

Selling Sickness by Moynihan and CasselsDisease MongeringUS has 5% of the worlds population but 50% of drug consumption Strategies to expand marketsPromotional campaigns change the way people think about common ailmentsMenopause becomes hormone deficiencyShyness becomes social anxiety disorderAcid indigestion becomes gastroesophageal reflux diseaseLowering thresholds for treating common conditions

What the FDA doesApproves new drugs and devices based on:The medicine or device is effectiveEndpoint may be a surrogate such as lowering cholesterol as opposed to longer lifeUsually 2 RCTs required to prove clinical efficacy for drugsThe medicine or device is safe Charged with oversight of DTC materialsSmall number of DTC materials are actually reviewedRegulatory letters are often delayed and marginally effective.

What the FDA doesnt do!Does not assess cost vs benefit for a drug or device.Does not determine whether one drug is better than another.Does not approve every use to which a product may be put.Does not require large trials that will identify all potentially rare complications.

Important Contributions by the Pharmaceutical IndustryDevelopment of new treatments that improve health and well-being Substantial contributions to educational, health care and professional organizationsProvide samples and free meds to many patientsbut, their main goal is to make profits for their shareholders and they spend enormous amounts to influence all involved, including legislators, providers, patients, and the general public, to help them maintain or increase those profits.

2007 Fortune 500 Profits

J & J21%Pfizer37%Merck20%Abbott8%Wyeth21%BMS9%Eli Lilly17%Amgen21%Schering11%

Pharmaceutical Industry Methods for Increasing Market ShareMarketing expendituresDrug repsDTC advertisingJournal adsPrescriber dataWhat can be done?

Total spending: $29 billion(Source: IMS Health, in Donohue, NEJM 2007)Promotional Spendingand Advertising, 2005

Socolar D, Sager A. Pharmaceutical marketing and research spending: the evidence does not support PhRMAs Claims.http://dcc2.bumc.bu.edu/hs/sager/pdfs/120601/DrugIndustryMarketingStaffSoarswhileReserchStaffingStagnates5Dec01.pdf; Accessed 3/6/08

Pharmaceutical RepresentativesRemains the major marketing focus ~ 100,000 reps in 2005 vs 38,000 in 19951 rep/6 MDs in US and 1 rep/2.5 targeted MDs 6 million detail visits annuallyCost estimate $12-$13K/MD for detailingIndustry spends $150K annually/primary care rep and $330K/specialty rep*

*Med Ad News 2004;23(3):1

Docs Perception vs. Brutal RealityStudies consistently show physicians do not believe that promotion affects their prescribing habits*, butStudies consistently show drug promotion increases prescribing of targeted drugs**

*Sigworth SK et al. JAMA. 2001;286(9):1024-5.McKinney WP et al. JAMA 1990;264(13):1693-7**Chren MM et al. JAMA 1994 Mar 2;271(9):684-9; Lurie N et al. J Gen Int Med 1990;5:240-243; Wazana A. JAMA 2000 Jan 19;283(3):373-80..

Details of Detailing: Impact on Prescribing & CostsIncreased likelihood of formulary requests for targeted drugsIncreased awareness, preference and rapid prescribing of new drugsHigher prescribing costsLess use of lower cost, but equally effective, genericsLess rational prescribing(Wazana A, JAMA 2000)

Direct to Consumer (DTC) AdsDirectly target consumers & general public1997: FDA relaxed regulationsEliminated requirement to list all side-effects by simply referring to additional sources of information, e.g., 1-800 number or websiteAs of 2005, the US and New Zealand only developed nations with DTC Rx advertising

DTC Expenditures Are Huge$4.5 billion spent on DTC in 2005* 296.4% increase from 1997-2005* 14% of total industry marketing for DTC**Hoechst spent $580K on 60-second Allegra ad***Merck spent $161M advertising on 1 drug, Vioxx, whereas total annual ad budgets: Dell ($160M), Budweiser ($146M), Pepsi ($125M) or Nike ($78M)*****Shuchman, NEJM, 2007**Donohue et al. NEJM, 2007***Eaton, Stanford University Press, 2004****Gellad et al. Amer J Med, 2007

But, DTC Ads Pay Off1998-1999: 25 most advertised drugs account for 43% growth in Rx sales compared to 13.3% for all other drugs*1998: Claritin, Allegra, and Zyrtec increase sales by 32%, 50% and 56%*2002: >53M patients discuss DTC-advertised meds with their doctors***Eaton, Stanford University Press, 2004**Rosenthal, NEJM, 2002

*

The Quantity and Quality ofScientific Info in Journal Ads1999 review of pharm ads from 10 US journals:498 unique ads (3,185 total)74 unique graphs36% of graphs: numeric distortion66% of graphs: chart junk54% list intermediate outcomesJGIM 2003;18:294-297

Big Brother (Pharma) Knows What You Are DoingIndustry has access to AMA managed databases that track prescribing patterns of most practicing providersSuch data is used to more precisely target specific providers with specific types of products or messagesAMA has an opt out option

Ann Intern Med 2007;146:742-48But You Can Opt-outPhysicians can enroll at: www.ama-assn.org/go/prescribingdataPurchasers of the data must agree to restrict prescriber profiling by reps for those who have opted out.Must be renewed every three years and manufacturers have 90 days to comply after opt-out is exercised.

Ann Intern Med 2007;146:742-48

What Clinicians Can Do To Reduce Marketing Impact?Reduce or eliminate contact with industry representativesJust say noIdentify/use unbiased and independent sources of prescribing informationOpt out of use of your data in the AMA master profile

CME: Incentives and Gifts

Free MealsPayment for attendance at lectures and conferencesStipendTimeTravelRegistration fees

Industry Support of Continuing Medical EducationIn 2006, half of the $2 billion dollars spent on CME came from industry sponsorship Medical Education and Communication Companies (MECCs)Organize meetings, find speakers for grand rounds and symposia, develop written materialsAbout 76% income from industryMedical SchoolsIndustry provides almost two thirds (62%) of CME income to medical schools (ACCME) Source: ACCME, Annual Report Data 2006

Does this Affect Prescribing?

Attending drug companysponsored CME5-19% increase in rate of prescription of sponsors drug vs. competitors drug (P

Does the Source of Funding Affect the Content of CME?Content analysis of two different CME courses sponsored by two different drug companies, each discussed 3 calcium channel blockersDrug companysponsored CME preferentially highlighted the sponsor's drug(s) compared with other CME programs2.5-3 times more likely to mention positive effects of sponsors drug and negative or equivocal effects of competitors (P

J Gen Int Med 2007;22:184-90Deal With Conflicts of InterestEliminate the conflicts whenever possibleCan be difficult and painful, especially with friendly repsEven the perception of conflicts create credibility problemsRecognize tendency to rationalizeIts an educational dinnerpatients need samplesDenialIt doesnt affect my prescribing decisionsI take it with a grain of salt

J Gen Int Med 2007;22:184-90

Sage AdviceThe best defense the physician can muster against (misleading) advertising is a healthy skepticism... cultivate a flair for spotting the logical loophole, the invalid clinical trial . . . and the unlikely claim. Above all, develop greater resistance to the lure of the fashionable and the new.

P.R. Garai, 1964

Conclusions About MarketingIndustry marketing is very influential and definitely impacts decision makingMarketing can lead to ineffective prescribingCurrent marketing practices are controversial and opinions varyHealth professionals can make choices to avoid undue influence

Need for evidenceFirst of all, do no harm (Hippocratic Oath)2008 version: Never offer treatment to a patient without convincing evidence that it will provide more help than harm. Shouldnt we also consider help/harm to the patients family & overall community in this equation?

Principles of Evidence-based Medicine (EBM)Decision making in clinical practice

What is EBM?

What EBM is not

Decision Making in Clinical PracticeUnfortunately, many decisions are made based on unreliable evidence

Expert opinion plays a heavy role in medical decision making

Personal observation or anecdotal experience can frequently overcome clear evidence to the contrary

Clinical Decision MakingMulrow: Ann Intern Med, Vol 126(5) 3/1/97, pp 389-91EthicsGuidelinesKnowledge

What is EBM?EBM is "the conscientious, explicit and judicious use of best current evidence in making decisions about the care of individual patients.-David Sackett

What is EBM?Evidence based medicine requires the integration of the best research evidence with our clinical expertise and our patients unique values and circumstances.Sharon E. Straus: Evidence Based Medicine 3rd Edition

What is Evidence-Based Practice?A process in which we:Ask to precisely define a patient problemAcquire figure out whats needed to answer the question, conduct an efficient search of the literature.Appraise Select the best of the relevant studies and apply rules of evidence to determine their validityApply Extract the clinical message and apply it to the patient problemAssess Determine if the action was helpfulAdjust Use the outcomes of intervention to modify the treatment

What EBM is not:The same old thing weve always doneSomething that can only be done from ivory towersA cookbook method of practice A method for administrators to save costsRestricted to randomized trials

*Study Types Evidence HierarchyLab studies and Animal ResearchCase ReportsCase Control Studies SystematicReviewsRCTsCohort StudiesCase SeriesEditorials and Opinions

David EddyEBM Decisions When there is evidence of benefit and value, do it.When there is evidence of no benefit, harm or poor value, dont do it.When there is insufficient evidence to know for sure, be conservative.

Advantages of an EBM ApproachSorts through the marketing, opinions, and theory to get an accurate assessment of the proven and comparative benefits and risks of various treatments.Supports policies that reduce variations in practice, especially expensive or inappropriate prescribing.Provides incentive to conduct research on more meaningful questions, especially comparative studies

Practical Application of Evidence-Based MethodsUnderstand terms used in research and comparative reviews, such as:Generalizability/Applicability/RelevanceNumber needed to treatTarget outcomesPublication bias

Practical Application of Evidence-Based MethodsRely on systematic or comparative reviews, rather than single studies whenever possibleRecognize factors that truly impact findings, e.g. strength of evidence and quality of research methodsFind reliable and unbiased sources of information for summary and comparative reviews

PICOTS Framework for Reviewing Evidence

ParameterExamplePopulationAdults with Major DepressionInterventionsSSRIComparatorsOther antidepressants, meds plus psychotherapy, non-pharm txsOutcomesImproved mood and other symptoms, improved fxTiming6-12 months f/uSettingsPrimary care

Web Site Examples of CERshttp://effectivehealthcare.ahrq.gov

www.ohsu.edu/drugeffectiveness

www.OregonRx.gov

Unbiased Sources on DrugsAgency for Health Care Research and Qualitys Effective Healthcare Program: http://effectivehealthcare.ahrq.govNational Institute for Clinical Excellence: www.nice.org.uk Cochrane Collaboration: www.cochrane.orgCanadian Common Drug Review: www.cadth.ca/index.php/en/cdr

Unbiased Sources on DrugsPub Med: http://www.ncbi.nlm.nih.gov/pubmed/Clinical Trials Database: http://clinicaltrials.gov/Carlat Report (Psychiatric Drugs):http://www.thecarlatreport.com/Oregon Health Policy & Research www.OregonRx.govDrug Effectiveness Review Program: www.ohsu.edu/drugeffectiveness

Other Information SourcesConsumer Union: www.prescriptionforchange.orgNo Free Lunch: www.nofreelunch.org/ Pharmed Out: http://www.pharmedout.org/DUR Newsletter:www.pharmacy.oregonstate.edu/drug_policy/pages/dur_board/newsletter DHS Pocket Drug Guide:www.pharmacy.oregonstate.edu/drug_policy/prescriber_tools.html

Thank youThis work was made possible by a grant from the state Attorney General Consumer and Prescriber Education Program which is funded by the multi-state settlement of consumer fraud claims regarding the marketing of the prescription drug Neurontin.

***These two slides are also the table of contents for the talk, in the order in which the presentation proceeds.*These two slides are also the table of contents for the talk, in the order in which the presentation proceeds.

***Define OECD*Source: NYTimes Dec 30, 2006In 2006, health care spending reached a total of $2.1 trillion, or $7,026 per person, up from $6,649 per person in 2005, according to a report by the Centers for Medicare & Medicaid Services (CMS). This accounts for 16% of Gross Domestic Product.

****

The need to improve prescription drug use

Prescription drug spending growth accelerated from 5.8 percent in 2005 to 8.5 percent in 2006, but stillwell below the average annual growth of 13.4 percent per year that occurred between the years 1995 and 2004.Total prescription drug spending in 2006 was $216.7 billion, compared to $199.7 billion in 2005*Projected Increases in Pharmaceutical Expenditures for 2008:Outpatient Rx5-7%Hospital4-6%Clinic (e.g., chemotherapy)12-14%

*Some increases are appropriate, i.e., reduced clinic visits and hospital stays***Trend over last 20 years; dip reflects managed care**These are the summary points for the first section of the presentation.*Disease mongering is the selling of sickness that widens the boundaries of illness and grows the markets for those who sell and deliver treatments. It is exemplified most explicitly by many pharmaceutical industryfunded disease-awareness campaignsmore often designed to sell drugs than to illuminate or to inform or educate about the prevention of illness or the maintenance of health. Some different forms of disease mongering: aspects of ordinary life, such as menopause, being medicalised; mild problems portrayed as serious illnesses, as has occurred in the drug-company-sponsored promotion of irritable bowel syndrome, and risk factors, such as high cholesterol and osteoporosis, being framed as diseases.***Over-medicalization more and more we see problems (that may for a few people be severe and need treatment) being marketed as severe problems for everyone. People come to think they must have a disease process if their toenails arent clear or their sex life isnt perfect or leg occasionally twitches, or theyre unable to row a boat like Dr. Jarvik because they lack Lipitor.**See Deyo, R. Gaps, Tensions and Conflicts in the FDA Approval Process: Implications for Clinical Practice. JABFP March-April 2004, vol 17 no 2.The ad review problem is related to both budget limitations and apparent administrative priorities (e.g., foot-dragging).

Quotes from the GAO May 2008 report:As of 2006, FDA reviewed a small portion of the increasingly large number of DTC materials it received. .the agency could not ensure that it was identifying or reviewing the materials that were the highest priority.despite FDA agreeing in 2002 that it is important to issue regulatory letters more quickly, the amount of time it takes to draft and issue letters has continued to lengthen. We believe that delays in issuing regulatory letters limit FDAs effectiveness in overseeing DTC advertising and in reducing consumers exposure to false and misleading advertising.At the time of our 2006 report, we found that FDA regulatory letters were limited in their effectiveness at halting the dissemination of false and misleading DTC advertising materials. We found that, from 2004 through 2005, FDA issued regulatory letters an average of about 8 months after the violative DTC materials they cited were first disseminated, by which time more than half of the materials had already been discontinued. Although drug companies complied with FDAs requests to create materials to correct the misimpressions left by the cited materials, these corrections were not disseminated until 5 months or more after FDA issued the regulatory letter. Furthermore, FDAs regulatory letters did not always prevent drug companies from later disseminating similar violative materials for the same drugs.

****This probably means the percent of total revenues that are profits.*This is the table of contents for the succeeding section.*********from ED to improving the experience*As we know now, Dr. Jarvik has never been either a practicing physician, and doesnt row. **Numerical distortion:Improperly scaled or split axes (16%)3-dimensional objects needlessly comparing volumes instead of location, length, or area (20%)Improper baselines (12%)

Chart junk:extra grid lines (36%)meaningless background shadings (35%)color schemes that highlight 1 drug or outcome above others (21%)*******Content analysis of tape recordings of speakers. Tallied mentions of generic vs. brand, and positive vs. negative vs. equivocal clinical effects.**This quote sums up the main points of this presentation: that we have to have a healthy skepticism and a resistance to the lure of the fashionable and the new. Pierre Garai, who was quoted way back in 1964, was the head of the Ogilvie Corporation, a major marketing firm for the pharmaceutical industry. The times have not changed. Source: Garai PR. Advertising and promotion of drugs. In: Talalay P, ed. Drugs in our Society. Baltimore: Johns Hopkins Press; 1964:189-202. **David Eddy see Deans slides****Unfortunately, many decisions are made based on unreliable evidenceUse of observational studies to draw cause and effect conclusionsFocus on pharmacology, pharmacokinetics, and theory instead of clinically relevant patient oriented evidence that matters (POEM)Expert opinion plays a heavy role in medical decision makingMany experts do not have EBM trainingOpinions can vary widelyUnbiased expert opinion using EBM is very usefulPersonal observation or anecdotal experience can frequently overcome clear evidence to the contrary

****Conscientious= good faith effort to use the best treatment for patientsExplicit = theres a logical and transparent way to go about thisJudicious = clinical judgment still important to interpret and apply results within contexts.

*****From Sackett et all, EBM: What it is and what it isnt BMJ 1996;312.Too much variation in clinical behavior among clinicians. Great examples of clinical teams that have improved outcomes by explicitly using EBM principles. Facilitated by use of internetEBM is actually a bottom up approach that integrates the best external evidence with individual clinical expertise and patient values/choice.EBM is designed to identify and apply the most efficacious intervention to improved quality and quantity of life for patients; it may raise or lower costsEBM makes use of the BEST evidence available, whatever that is

*AN evidence based practitioner makes use of the highest level of evidence available.*****The first point cannot be emphasized enough. The overwhelming amount of studies available on a particular condition or type of treatment is so vast that it is generally unrealistic to expect an individual clinician to sort through and determine the best choices in most treatment situations. Likewise, it is unreliably risky to depend on the advice of someone (e.g., a pharmaceutcial rep) to provide unbiased information when there are obvious secondary, contradictory, or ulterior motivations associated with such recommendations. Systematic reviews are now becoming quite consistent in their methodological approaches and can, because of the power of pooling data from numerous studies, develop more cogent and meaningful recommendations about the effectiveness and applicability of certain treatments.*This is a crude oversimplification of the kinds of data and factors that systematic reviews will consider.**The Effective Healthcare Program is conducting comparative effectiveness reviews of many high priority conditions through the network of evidence-based practice centers throughout the US and Canada. Oregons EPC serves as the Scientific Resource Center for this project, helping to prioritize and develop topics for reviews.NICE and Cochrane are evidence-based medicine review organizations in the UK and have produced many reviews and treatment guidelines.*DERP is the Oregon originated project, involving over 15 states and Canada, that does systematic and comparative effectiveness reviews on over 25 classes of drugs. Reviews are updated on a regular basis.PubMed is creating summaries of many of the DERP reports and will have links to them in relation to individual drugs about which users may be inquiring.Clinical Trials database will be obtaining all registered clinical trials and will be including outcomes beginning in 2009.Oregon contracts with the OHSU Oregon Evidence-based Practice Center to conduct an evidence-based review of all literature available on specific drug classes. Subcommittees appointed by the Health Resources Commission then synthesize the reports to determine which drugs are most safe and effective. There are also one-page summaries of the HRC reports for consumers.

*No Free Lunch has developed a patient education leaflet entitled Why we dont have free samplesIt is available for download free of charge at www.nofreelunch.orgHelps to support clinics that choose not to accept samples

*