Pseudoevidence-Pseudoevidence-Based MedicineBased MedicineThe New Threat to The New Threat to Evidence-Based Evidence-Based MedicineMedicine

Wally R. Smith, MDWally R. Smith, MDProfessor and Chairman, Division of Quality Professor and Chairman, Division of Quality Health CareHealth CareVirginia Commonwealth UniversityVirginia Commonwealth UniversityRichmond, VirginiaRichmond, Virginia

Corrupt?Corrupt?

Corrupt?Corrupt?

Learning ObjectivesLearning Objectives

Understand the value and premises of Understand the value and premises of Evidence-Based MedicineEvidence-Based Medicine

Understand new threats to the validity Understand new threats to the validity and appropriate dissemination and use of and appropriate dissemination and use of scientific evidence in medicinescientific evidence in medicine

Understand how to avoid, confront, and Understand how to avoid, confront, and combat these threatscombat these threats

For immediate release:11/16/200611/16/2006Sathya Achia-Abraham University News Services(804) 827-0890sbachia@vcu.edu

Antibiotics Unnecessarily Antibiotics Unnecessarily Prescribed for Acute BronchitisPrescribed for Acute Bronchitis

New England Journal of Medicine article describes critical reviewcritical review of literatureAntibiotics are routinely prescribed unnecessarily for acute bronchitis, according to Virginia Commonwealth University findings published in today's issue of the New England Journal of Medicine.Physicians for years have prescribed antibiotics for the treatment of acute bronchitis, a common condition caused by inflammation of the bronchi of the lungs that occurs in 5 percent of adults each year. The VCU School of Medicine researchers concluded there is no evidenceno evidence in current literature to support prescribing antibiotics for the treatment of short-term bronchitis as almost all the causes of such infections are viral and therefore don't respond to the therapy, according to the article.

MDs Overprescribe MDs Overprescribe Antibiotics Despite WHO Antibiotics Despite WHO and other Rec’sand other Rec’s

WHY?WHY? Pressure from:Pressure from:

patients believing in efficacy and safety?patients believing in efficacy and safety? Pharma sales reps?Pharma sales reps? Pseudoevidence-Based Medicine?Pseudoevidence-Based Medicine?

Learning GoalsLearning Goals To review the meaning and premises of Evidence-Based To review the meaning and premises of Evidence-Based

Medicine (EBM)Medicine (EBM) To define and describe To define and describe Pseudoevidence-Based Medicine Pseudoevidence-Based Medicine

(PBM)(PBM) To understand how PBM may be not only unethical, but also To understand how PBM may be not only unethical, but also

criminal. criminal. To understand that PBM may be difficult to detect by practitioners To understand that PBM may be difficult to detect by practitioners

of EBM. of EBM. To understand the To understand the motivemotive for PBM for PBM To understand the To understand the opportunityopportunity for PBM for PBM To learn of some To learn of some evidencesevidences of PBM of PBM

To understand how to oppose and combat PBMTo understand how to oppose and combat PBM

The meaning and The meaning and premises of Evidence-premises of Evidence-Based Medicine (EBM)Based Medicine (EBM)

Evidence-based medicine Evidence-based medicine (EBM) (EBM)

Dominant paradigm in clinical Dominant paradigm in clinical practice and quality improvement. practice and quality improvement.

Far exceeds opinion-based Far exceeds opinion-based medicine and other decision-making medicine and other decision-making methods methods Produces, on average, the highest quality Produces, on average, the highest quality

clinical processes and outcomes. clinical processes and outcomes.

Steps of Evidence-based Steps of Evidence-based medicine (EBM) medicine (EBM)

Understand the patient's circumstances or predicament Understand the patient's circumstances or predicament Identify knowledge gaps and frame questions to fill those gapsIdentify knowledge gaps and frame questions to fill those gaps Conduct an efficient literature search Conduct an efficient literature search Critically appraise the research evidenceCritically appraise the research evidence Apply that evidence to patient careApply that evidence to patient care

Guyatt GH, haynes RB, jaeschke RZ, cook DJ, green L, naylor CD, wilson mc,richardson WS. Users' guides to the medical literature: XXV. Evidence-based medicine: principles for applying the users' Guyatt GH, haynes RB, jaeschke RZ, cook DJ, green L, naylor CD, wilson mc,richardson WS. Users' guides to the medical literature: XXV. Evidence-based medicine: principles for applying the users' guides to patient care. Evidence-based medicine working group. Jama. 2000 sep 13;284(10):1290-6.guides to patient care. Evidence-based medicine working group. Jama. 2000 sep 13;284(10):1290-6.

Skills Required to Skills Required to Practice EBMPractice EBM

distinguish high from low quality in distinguish high from low quality in primary studies, systematic reviews, primary studies, systematic reviews, practice guidelines, and other integrative practice guidelines, and other integrative research focused on management research focused on management recommendationsrecommendations

Guyatt GH, Haynes RB, Jaeschke RZ, Cook DJ, Green L, Naylor CD, Wilson MC,Richardson WS. Users' Guyatt GH, Haynes RB, Jaeschke RZ, Cook DJ, Green L, Naylor CD, Wilson MC,Richardson WS. Users' Guides to the Medical Literature: XXV. Evidence-based medicine: principles for applying the Users' Guides Guides to the Medical Literature: XXV. Evidence-based medicine: principles for applying the Users' Guides to patient care. Evidence-Based Medicine Working Group. JAMA. 2000 Sep 13;284(10):1290-6.to patient care. Evidence-Based Medicine Working Group. JAMA. 2000 Sep 13;284(10):1290-6.

Benefits of EBMBenefits of EBM Transparent Transparent Everyone must agree on: Everyone must agree on:

Which pieces of evidence matterWhich pieces of evidence matter Which methods of assembly of medical evidence and Which methods of assembly of medical evidence and

display of medical evidence are bestdisplay of medical evidence are best What practitioner’s goals for patients are when evidence What practitioner’s goals for patients are when evidence

is applied to their care is applied to their care The values patients and clinicians are weighing when The values patients and clinicians are weighing when

making clinical decisions (6)making clinical decisions (6) Guyatt GH, Haynes RB, Jaeschke RZ, Cook DJ, Green L, Naylor CD, Wilson MC,Richardson WS. Users' Guides to Guyatt GH, Haynes RB, Jaeschke RZ, Cook DJ, Green L, Naylor CD, Wilson MC,Richardson WS. Users' Guides to

the Medical Literature: XXV. Evidence-based medicine: principles for applying the Users' Guides to patient care. the Medical Literature: XXV. Evidence-based medicine: principles for applying the Users' Guides to patient care. Evidence-Based Medicine Working Group. JAMA. 2000 Sep 13;284(10):1290-6.Evidence-Based Medicine Working Group. JAMA. 2000 Sep 13;284(10):1290-6.

Presumptions of EBMPresumptions of EBM professionalism in science and medicineprofessionalism in science and medicine evidence of the highest possible quality is evidence of the highest possible quality is

being produced, and is untaintedbeing produced, and is untainted evidence is produced by objective evidence is produced by objective

scientistsscientists those producing evidence have no pre-those producing evidence have no pre-

conceived hopes or goals for what the conceived hopes or goals for what the evidence will showevidence will show

Presumptions of EBM Presumptions of EBM (cont’d)(cont’d)

producers of evidence have no stakes in what producers of evidence have no stakes in what the evidence will showthe evidence will show

scientific evidence-production process is free scientific evidence-production process is free from corruption by from corruption by experimental or methodologic manipulationexperimental or methodologic manipulation statistical manipulationstatistical manipulation publication manipulation or biaspublication manipulation or bias misuse by consumers and stakeholders in misuse by consumers and stakeholders in

medicine medicine Evidence-Based Medicine Working Group. Evidence-based Evidence-Based Medicine Working Group. Evidence-based

medicine: a new approach to teaching the practice of medicine. medicine: a new approach to teaching the practice of medicine. JAMA 1992;268:2420-2425. JAMA 1992;268:2420-2425.

Threats to EBM and Threats to EBM and Solutions to the Solutions to the ThreatsThreats

1. Dearth Of 1. Dearth Of Assembled, Graded, Assembled, Graded, High-Quality High-Quality Evidence On Which To Evidence On Which To Base Practice In Base Practice In Many DomainsMany Domains

Solutions to Dearth of Solutions to Dearth of evidence threatevidence threat

Cochrane Collaboration Cochrane Collaboration [http://www.cochrane.org] [http://www.cochrane.org] database of over 4,000 published systematic database of over 4,000 published systematic

reviewsreviews accessible via MedLineaccessible via MedLine

Government AgenciesGovernment Agencies US Agency for Healthcare Research and QualityUS Agency for Healthcare Research and Quality UK—NICEUK—NICE CanadaCanada

Solutions to Dearth Problem Solutions to Dearth Problem (cont’d)(cont’d)

Private Agencies, JournalsPrivate Agencies, Journals Dedicated to successfully collecting, assembling, and Dedicated to successfully collecting, assembling, and

disseminating high-quality evidence for practitioner and disseminating high-quality evidence for practitioner and public consumption. public consumption.

Specialty societies Specialty societies Evidence-based guidelinesEvidence-based guidelines Transparent tables or reviews of medical evidence. Transparent tables or reviews of medical evidence.

Irwin RS, Baumann MH, Bolser DC, Boulet LP, Braman SS, Brightling CE, Brown KK,Canning Irwin RS, Baumann MH, Bolser DC, Boulet LP, Braman SS, Brightling CE, Brown KK,Canning BJ, Chang AB, Dicpinigaitis PV, Eccles R, Glomb WB, Goldstein LB, Graham LM, Hargreave FE, BJ, Chang AB, Dicpinigaitis PV, Eccles R, Glomb WB, Goldstein LB, Graham LM, Hargreave FE, Kvale PA, Lewis SZ, McCool FD, McCrory DC, Prakash UB, Pratter MR, Rosen MJ, Schulman E, Kvale PA, Lewis SZ, McCool FD, McCrory DC, Prakash UB, Pratter MR, Rosen MJ, Schulman E, Shannon JJ, Smith Hammond C, Tarlo SM; American College of Chest Physicians (ACCP). Shannon JJ, Smith Hammond C, Tarlo SM; American College of Chest Physicians (ACCP). Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest. 2006 Jan;129(1 Suppl):1S-23S.guidelines. Chest. 2006 Jan;129(1 Suppl):1S-23S.

2. Time and difficulty of 2. Time and difficulty of presenting evidence to presenting evidence to patients patients

to let patients insert their values into to let patients insert their values into clinical decisions, once evidence is clinical decisions, once evidence is assembled.assembled.

Solutions to Pt Solutions to Pt Interaction and Value Interaction and Value Imputation ThreatsImputation Threats

Research in the behavioral, economic, and Research in the behavioral, economic, and managerial sciences managerial sciences

Decision analysis and cost-effectiveness Decision analysis and cost-effectiveness analysisanalysis

The science of utility assessmentThe science of utility assessment assessment of patients’ relative quantitative assessment of patients’ relative quantitative

values for a given health state or outcome. values for a given health state or outcome. Sherman SN, Mrus JM, Yi MS, Feinberg J, Tsevat J. How Do Patients with Sherman SN, Mrus JM, Yi MS, Feinberg J, Tsevat J. How Do Patients with

HIV/AIDS Understand and Respond to Health Value Questions? J Gen Intern HIV/AIDS Understand and Respond to Health Value Questions? J Gen Intern Med. 2006 Dec;21 Suppl 5:S56-61.Med. 2006 Dec;21 Suppl 5:S56-61.

3. No Penalties To 3. No Penalties To Practitioners For Failure Practitioners For Failure To Practice EBMTo Practice EBM

some stick with expert opinion or other some stick with expert opinion or other forms of justification for their styles of forms of justification for their styles of practicepractice in particular when selecting applying in particular when selecting applying

therapies therapies

How To Address How To Address Enforcement ProblemEnforcement Problem

Evidence-based guidelines used to enforce Evidence-based guidelines used to enforce standards of carestandards of care

EBM based standards of care in legal cases. EBM based standards of care in legal cases. Harlan D. The implications of practice guidelines for physician medical malpractice Harlan D. The implications of practice guidelines for physician medical malpractice

liability. Physician Executive 1994 (May). Copyright 1994 American College of Physician liability. Physician Executive 1994 (May). Copyright 1994 American College of Physician Executives. Copyright 2004 Gale Group.Executives. Copyright 2004 Gale Group.

EBM standards in specialty societies EBM standards in specialty societies EBM standards by certification boards EBM standards by certification boards EBM standards by P&T committees (Oregon). EBM standards by P&T committees (Oregon).

General Reception to General Reception to EBMEBMChanges have been Changes have been

welcomed improvements to welcomed improvements to medical care.medical care.

PseudoevidencePseudoevidence--based based medicinemedicine (PBM)(PBM) can be defined as the practice of can be defined as the practice of

medicine based on falsehoods medicine based on falsehoods that are disseminated as truth.that are disseminated as truth.

Perhaps not new Perhaps not new The Latest Discovered Threat to EBMThe Latest Discovered Threat to EBM

Falsehoods may result Falsehoods may result from from corrupted evidencecorrupted evidence

Evidence that has been contrived from Evidence that has been contrived from purposely biased sciencepurposely biased science

Evidence that has been manipulated Evidence that has been manipulated and/or falsified, then published. and/or falsified, then published.

Falsehoods fm Falsehoods fm corrupted corrupted disseminationdissemination of of evidenceevidence

Misuse of otherwise valid evidenceMisuse of otherwise valid evidence Distortion of expression of evidenceDistortion of expression of evidence

(e.g., RRR vs ARR)(e.g., RRR vs ARR) A drop from 2% mortality to 1% mortality A drop from 2% mortality to 1% mortality

(ARR) is a 50% drop (RRR)!(ARR) is a 50% drop (RRR)! Dissemination of only part of the truthDissemination of only part of the truth

E.g., Drug reduces risk in one area, E.g., Drug reduces risk in one area, But But increases risk in another area, and overall mortality!increases risk in another area, and overall mortality!

How PBM Damages the How PBM Damages the Practice of EBMPractice of EBM

Falsehoods consumed as truth by Falsehoods consumed as truth by unwitting and well-intentioned unwitting and well-intentioned practitioners of EBMpractitioners of EBM

Falsehoods disseminated and adopted Falsehoods disseminated and adopted as routine practiceas routine practice results in inappropriate quality standards results in inappropriate quality standards

and processes of careand processes of care results in harms to patientsresults in harms to patients

MOTIVE for PBMMOTIVE for PBM

The Profit MotiveThe Profit Motive pharmaceutical pharmaceutical

companiescompanies device manufacturersdevice manufacturers some health care some health care

providersproviders many insurance providersmany insurance providers various middlemen and various middlemen and

brokers in health care brokers in health care not in and of itself wrong not in and of itself wrong

or dangerousor dangerous

Danger of the Profit Danger of the Profit MotiveMotive

Profit placed in direct competition with Profit placed in direct competition with protecting and prolonging human lifeprotecting and prolonging human life the precise business in which health care the precise business in which health care

stakeholders should be engaged. stakeholders should be engaged.

The Profit Motive is The Profit Motive is Armed and Extremely Armed and Extremely DangerousDangerous

Perhaps strongest motive for Perhaps strongest motive for pseudoevidence is regarding therapy pseudoevidence is regarding therapy

↓ ↓ motive for psuedoevidence about motive for psuedoevidence about etiologies etiologies and risk factors of certain diseasesand risk factors of certain diseases Exceptions: cigarettes, firearms, alcohol, and Exceptions: cigarettes, firearms, alcohol, and

excesses of foodexcesses of food ↓ ↓ motive motive for pseudoevidence purely about for pseudoevidence purely about

prognosisprognosis

Strength of the Profit Strength of the Profit MotiveMotive

In 1990, to get a candidate drug from In 1990, to get a candidate drug from laboratory to pharmacy shelf, developers laboratory to pharmacy shelf, developers were required to invest an estimated $33 were required to invest an estimated $33 million. million. strong motivation to get a return on strong motivation to get a return on

investment.investment. ROI likely calculated far in advanceROI likely calculated far in advance

A CBO Study: How health care reform affects pharmaceutical research and development, A CBO Study: How health care reform affects pharmaceutical research and development, June 1994, Congressional Budget Office, Congress of the United States. Accessed at June 1994, Congressional Budget Office, Congress of the United States. Accessed at http://www.cbo.gov/ftpdocs/48xx/doc4846/doc31.pdf http://www.cbo.gov/ftpdocs/48xx/doc4846/doc31.pdf on November 20, 2006. on November 20, 2006.

Marketing CostsMarketing Costs Pharmaceutical and Device Companies Pharmaceutical and Device Companies

spent an estimated $12.7 billion spent an estimated $12.7 billion promoting products in 1998. promoting products in 1998. Ma J, Stafford RS, Cockburn IM, Finkelstein SN. A statistical Ma J, Stafford RS, Cockburn IM, Finkelstein SN. A statistical

analysis of the magnitude and composition of drug promotion in the analysis of the magnitude and composition of drug promotion in the United States in 1998. Clin Ther. 2003 May;25(5):1503-17.United States in 1998. Clin Ther. 2003 May;25(5):1503-17.

For-Profit Middlemen For-Profit Middlemen Found along the chain of evidence productionFound along the chain of evidence production

contract research organizations contract research organizations who help write research protocolswho help write research protocols recruit patients recruit patients generate datagenerate data

scientific publishers scientific publishers want to fill their journal and book pageswant to fill their journal and book pages

health news dissemination organizationshealth news dissemination organizations who want the scoop on the latest, greatest breakthroughs.who want the scoop on the latest, greatest breakthroughs.

“ “. . . a tower of Babel that reaches to the moon. . . .” . . . a tower of Babel that reaches to the moon. . . .” Klienke JD. Oxymorons: The Myth of a U.S. Health Care System. San Klienke JD. Oxymorons: The Myth of a U.S. Health Care System. San

Francisco: Jossey-Bass, 2001. Francisco: Jossey-Bass, 2001.

Professionalism is Under Professionalism is Under Threat From the Profit Threat From the Profit MotiveMotive

Perceptions of conflicts of interestsPerceptions of conflicts of interests Actual conflicts of interests on otherwise well-Actual conflicts of interests on otherwise well-

meaning, well-intentioned clinicians meaning, well-intentioned clinicians Brennan TA, Rothman DJ, Brennan TA, Rothman DJ, Blank L, et al. Health industry practices that create conflicts of interest: a policy proposal for Blank L, et al. Health industry practices that create conflicts of interest: a policy proposal for academic medical centers. JAMAacademic medical centers. JAMA.. 2006;295:429-433. 2006;295:429-433. Poses RM, Silverstein S, Smith WR. Academic medical centers and conflicts of interest. JAMA. 2006 Jun Poses RM, Silverstein S, Smith WR. Academic medical centers and conflicts of interest. JAMA. 2006 Jun

28;295(24):2846-7; author reply 2848-9.28;295(24):2846-7; author reply 2848-9.

Direct threats from those Direct threats from those with a stake in the with a stake in the maintenance of corruption maintenance of corruption

employers or others may press us to employers or others may press us to compromise professional valuescompromise professional values

physicians feel health care dominated by physicians feel health care dominated by bureaucracy bureaucracy may not honor medicine’s core valuesmay not honor medicine’s core values contribute to health care dysfunction contribute to health care dysfunction

Poses RM. A cautionary tale: the dysfunction of American Poses RM. A cautionary tale: the dysfunction of American health care. Eur J Intern Med. 2003 Mar;14(2):123-130.health care. Eur J Intern Med. 2003 Mar;14(2):123-130.

Direct pressures to remain silent about Direct pressures to remain silent about corruption or poor carecorruption or poor care in order to boost corporate or individual profitsin order to boost corporate or individual profits

ECONOMIC INCENTIVESECONOMIC INCENTIVES Incentives work according to non-randomized studiesIncentives work according to non-randomized studies If I hold a gun to your head, you’ll do about anything”If I hold a gun to your head, you’ll do about anything” Move you from precontemplation to actionMove you from precontemplation to action

Tran s-Th eore tica l M od e l

P recon tem p la tion C on tem p la tion P rep ara tion A c tion M a in ten an ce Term in a tion

S tag es o f C h an g e

The Cost of CourageThe Cost of Courage Pittsburgh newspaper series Pittsburgh newspaper series Retributions on US physician whistleblowersRetributions on US physician whistleblowers

community hospitals community hospitals academic centers academic centers Yale, Cornell Yale, Cornell

MDs exposed unsafe conditions or a colleague’s poor MDs exposed unsafe conditions or a colleague’s poor work work

MDs were fired or dismissed from staffMDs were fired or dismissed from staff retaliation for breaking the code of silence about wrongdoing? retaliation for breaking the code of silence about wrongdoing?

(16)(16) Not protected by whistleblower lawsNot protected by whistleblower laws

Twedt, S. The Cost of Courage: How the tables turn on doctors. Pittsburgh Post-Gazette, Sunday, Twedt, S. The Cost of Courage: How the tables turn on doctors. Pittsburgh Post-Gazette, Sunday, October 26, 2003. Accessed November 20, 2006.October 26, 2003. Accessed November 20, 2006.

ED Doctors Under SiegeED Doctors Under Siege 1998 survey of 465 emergency physicians across the 1998 survey of 465 emergency physicians across the

United StatesUnited States majority reported encountering instances of substandard majority reported encountering instances of substandard

emergency medical careemergency medical care 75% felt they had been financially exploited by the 75% felt they had been financially exploited by the

emergency department contract holder emergency department contract holder 49% considered leaving their employer because of unfair 49% considered leaving their employer because of unfair

business practices. business practices. 15% had been terminated without due process/peer review. 15% had been terminated without due process/peer review.

Plantz SH, Kreplick LW, Panacek EA, Mehta T, Adler J, McNamara RM. A national survey of Plantz SH, Kreplick LW, Panacek EA, Mehta T, Adler J, McNamara RM. A national survey of board-certified emergency physicians: quality of care and practice structure issues. Am J Emerg board-certified emergency physicians: quality of care and practice structure issues. Am J Emerg

Med. 1998 Jan;16(1):1-4.Med. 1998 Jan;16(1):1-4.

Pharmaceutical and Pharmaceutical and Device IndustryDevice Industry

Most pervasive yet subtle influence Most pervasive yet subtle influence Advertising to the profession, clearly can Advertising to the profession, clearly can

influence the prescribing of individual influence the prescribing of individual physicians. physicians. Cleary JD. Impact of pharmaceutical sales representatives on Cleary JD. Impact of pharmaceutical sales representatives on

physician antibiotic prescribing. J Pharm Tech. 1992;8:27-29.physician antibiotic prescribing. J Pharm Tech. 1992;8:27-29. Orlowski JP, Wateska L. the effects of pharmaceutical firm Orlowski JP, Wateska L. the effects of pharmaceutical firm

enticements on physician prescribing patterns. Chest. 1992;102:270-enticements on physician prescribing patterns. Chest. 1992;102:270-273.273.

Some clinicians may be Some clinicians may be naïvenaïve

159 specialty residents 159 specialty residents asked to empty their pockets asked to empty their pockets

Only 21 (13%)Only 21 (13%) yes to: yes to: "If a pharma co. offered to pay you to wear a small patch "If a pharma co. offered to pay you to wear a small patch

on the chest pocket of your white coat advertising their on the chest pocket of your white coat advertising their product, would you?" product, would you?"

97%97% w/ w/ 1 item with a pharma insignia1 item with a pharma insignia Branded items = 50% of the items carried by each resident, Branded items = 50% of the items carried by each resident,

with a median number of 4.with a median number of 4. Sigworth SK, Nettleman MD, Cohen GM. Pharmaceutical branding of resident Sigworth SK, Nettleman MD, Cohen GM. Pharmaceutical branding of resident

physicians. JAMA. 2001 Sep 5;286(9):1024-5.physicians. JAMA. 2001 Sep 5;286(9):1024-5.

Pharmaceutical Branding Pharmaceutical Branding of Resident Physiciansof Resident Physicians

0

10

20

30

40

50

60

70

80

90

100

%

Reflex

hammer

Calculator Datebook Calipers Stethoscope

ag

Penlight Pens Information

cards

Reference

books

Carrying the item Carrying the item With a Pharmaceutical Brand

< Should Should physicians physicians accept gifts in accept gifts in exchange for exchange for listening to a listening to a promotional promotional message?message?

< N=159N=159< 97% were 97% were

carrying at carrying at least 1 item least 1 item with with pharmaceuticpharmaceutical insignia on al insignia on it.it.

< Sigworth SK, Sigworth SK, Nettleman MD, Nettleman MD, Cohen GM. Cohen GM. Pharmaceutical Pharmaceutical branding of branding of resident physicians. resident physicians. JAMA. 2001 Sep JAMA. 2001 Sep 5;286(9):1024-5. 5;286(9):1024-5.

Ostrich MentalityOstrich Mentality toward more subtle threats toward more subtle threats

to professionalism to professionalism could very well be more could very well be more

dangerous than dangerous than physicians’ mentality physicians’ mentality toward open, direct threats toward open, direct threats Unwary clinicians could be Unwary clinicians could be

duped into representing to duped into representing to their patients that industry is their patients that industry is doing them a service with doing them a service with only altruistic motives. only altruistic motives.

OPPORTUNITY for PBMOPPORTUNITY for PBM ample opportunity for ill-motivated ample opportunity for ill-motivated

personspersons to corrupt evidence to corrupt evidence to produce pseudoevidenceto produce pseudoevidence

possibly without notice possibly without notice

The partnership between The partnership between academia and industryacademia and industry

Pervades every step of the evidence creation Pervades every step of the evidence creation processprocess bench bench

where candidate compounds or devices are discoveredwhere candidate compounds or devices are discovered

Pervades evidence dissemination processPervades evidence dissemination process journal publication processjournal publication process lecture circuitlecture circuit

Pervades application processPervades application process hospitalhospital physician exam room physician exam room

Relationship between MDs and Relationship between MDs and pharmaceutical industrypharmaceutical industry

< 538 studies retrieved, 29 included 538 studies retrieved, 29 included < Physician interactions with pharmaceutical representatives were Physician interactions with pharmaceutical representatives were

generally endorsed, began in medical school, and continued at a generally endorsed, began in medical school, and continued at a rate of about 4/month.rate of about 4/month.

< Meetings with pharmaceutical representatives were associated Meetings with pharmaceutical representatives were associated with requests by physicians for adding the drugs to the hospital with requests by physicians for adding the drugs to the hospital formulary and changes in prescribing practice.formulary and changes in prescribing practice.

< Drug company-sponsored continuing medical education (CME) Drug company-sponsored continuing medical education (CME) preferentially highlighted the sponsor's drug(s) compared with preferentially highlighted the sponsor's drug(s) compared with other CME programs.other CME programs.

< Attending sponsored CME events and accepting funding for travel Attending sponsored CME events and accepting funding for travel or lodging for educational symposia were associated with or lodging for educational symposia were associated with increased prescription rates of the sponsor's medication.increased prescription rates of the sponsor's medication.

< Attending presentations given by pharmaceutical representative Attending presentations given by pharmaceutical representative speakers was also associated with non-rational prescribing. speakers was also associated with non-rational prescribing. Wazana A. Physicians and the pharmaceutical industry: is a gift ever just a gift? JAMA. 2000 Jan 19;283(3):373-80. Wazana A. Physicians and the pharmaceutical industry: is a gift ever just a gift? JAMA. 2000 Jan 19;283(3):373-80.

Correlations between Correlations between pharmaceutical detailing and pharmaceutical detailing and physicians prescribing behaviorphysicians prescribing behavior

< Cleary JD. Impact of pharmaceutical sales Cleary JD. Impact of pharmaceutical sales representatives on physician antibiotic prescribing. J representatives on physician antibiotic prescribing. J Pharm Tech. 1992;8:27-29.Pharm Tech. 1992;8:27-29.

< Orlowski JP, Wateska L. the effects of pharmaceutical Orlowski JP, Wateska L. the effects of pharmaceutical firm enticements on physician prescribing patterns. firm enticements on physician prescribing patterns. Chest. 1992;102:270-273.Chest. 1992;102:270-273.

Quote from Richard Quote from Richard Smith, former Lancet Smith, former Lancet EditorEditor

““The much bigger problem lies with the original The much bigger problem lies with the original studies, particularly the clinical trials, published studies, particularly the clinical trials, published by journals. Far from discounting these, readers by journals. Far from discounting these, readers see randomised controlled trials as one of the see randomised controlled trials as one of the highest forms of evidence. A large trial published highest forms of evidence. A large trial published in a major journal has the journal's stamp of in a major journal has the journal's stamp of approval (unlike the advertising), will be approval (unlike the advertising), will be distributed around the world, and may well distributed around the world, and may well receive global media coverage.”receive global media coverage.” Smith R (2005) Medical Journals Are an Extension of the Marketing Smith R (2005) Medical Journals Are an Extension of the Marketing

Arm of Pharmaceutical Companies. PLoS Med 2(5): e138 DOI: Arm of Pharmaceutical Companies. PLoS Med 2(5): e138 DOI: 10.1371/journal.pmed.002013810.1371/journal.pmed.0020138

Industry paysIndustry pays

for a large number of for a large number of very expensive, very expensive, “definitive” trials of its “definitive” trials of its productsproducts Published in extremely Published in extremely

reputable journalsreputable journals Journal Supplements Journal Supplements

often paid for by industryoften paid for by industry

The opinion of several former The opinion of several former first-tier journal editors first-tier journal editors

the evidence-creation process may have been corrupted by the evidence-creation process may have been corrupted by its partnership with industryits partnership with industry

stakeholders in medicine who are more obviously motivated stakeholders in medicine who are more obviously motivated by profit have ample opportunity to corrupt scientific evidenceby profit have ample opportunity to corrupt scientific evidence

scientists, physicians, and other clinician leaders have ample scientists, physicians, and other clinician leaders have ample opportunity to succumb opportunity to succumb

journals should break free of dependency on industryjournals should break free of dependency on industry Horton R (2004) The dawn of McScience. New York Rev Books 51(4): 7–9. Horton R (2004) The dawn of McScience. New York Rev Books 51(4): 7–9. Angell M (2005) The truth about drug companies: How they deceive us and what to do about it. New York: Random Angell M (2005) The truth about drug companies: How they deceive us and what to do about it. New York: Random

House. 336 p. House. 336 p. Kassirer JP (2004) On the take: How medicine’s complicity with big business can endanger your health. New York: Kassirer JP (2004) On the take: How medicine’s complicity with big business can endanger your health. New York:

Oxford University Press. 251 p. Oxford University Press. 251 p. Barbour V, Butcher J, Cohen B, Yamey G (2004) Prescription for a healthy journal. PLoS Med 1: e22. DOI: Barbour V, Butcher J, Cohen B, Yamey G (2004) Prescription for a healthy journal. PLoS Med 1: e22. DOI:

10.1371/journal. pmed.0010022.10.1371/journal. pmed.0010022.

Humorous Quote from David Humorous Quote from David Sackett and Andy OxmanSackett and Andy Oxman

““HARLOT plc will provide a comprehensive package of HARLOT plc will provide a comprehensive package of services to discriminating trial sponsors who don’t want services to discriminating trial sponsors who don’t want to risk the acceptance and application of their products to risk the acceptance and application of their products and policies amid the uncertainties of dispassionate and policies amid the uncertainties of dispassionate science. science.

Through a series of blind, wholly owned subsidiaries, Through a series of blind, wholly owned subsidiaries, we can guarantee positive results for the manufacturers we can guarantee positive results for the manufacturers of dodgy drugs and devices who are seeking to of dodgy drugs and devices who are seeking to increase their market shares, for health professional increase their market shares, for health professional guilds who want to increase the demand for their guilds who want to increase the demand for their unnecessary diagnostic and therapeutic services, and unnecessary diagnostic and therapeutic services, and for local and national health departments who are for local and national health departments who are seeking to implement irrational and self serving health seeking to implement irrational and self serving health policies.”policies.”

Sackett DL, Oxman AD. HARLOT plc: an amalgamation of the world's two Sackett DL, Oxman AD. HARLOT plc: an amalgamation of the world's two oldest professions. BMJ. 2003 Dec 20;327(7429):1442-5.oldest professions. BMJ. 2003 Dec 20;327(7429):1442-5.

How to Cook the BooksHow to Cook the BooksBias to be exploitedBias to be exploited Strategies for applying this bias (while hiding your intentions and actions)Strategies for applying this bias (while hiding your intentions and actions) PaymentPayment

EZee-me-Too ProtocolsEZee-me-Too Protocols

11 Selective, non-systematic reviews Selective, non-systematic reviews Cite just those reports that support your product, proposal, or policy (and slag all your competitors)Cite just those reports that support your product, proposal, or policy (and slag all your competitors) £ £

22 Substituting placebos for established effective treatment Substituting placebos for established effective treatment Invoke fallacious "placebo effects" and "assay-sensitivity" arguments in order to avoid head to head comparisons Invoke fallacious "placebo effects" and "assay-sensitivity" arguments in order to avoid head to head comparisons $$

33 Unconcealed allocation to ensure better prognoses in Unconcealed allocation to ensure better prognoses in "experimental" patients "experimental" patients

Provide updatable wall posters for displaying the group to which the next patient will be allocated, see-through allocation envelope Provide updatable wall posters for displaying the group to which the next patient will be allocated, see-through allocation envelope systems, etc systems, etc

44 "Mini-max" manipulation of your competitor's product "Mini-max" manipulation of your competitor's product Give insufficient ("mini") doses of your competitor's product, accompanied by scary ("max") warnings about its (but not yours) side Give insufficient ("mini") doses of your competitor's product, accompanied by scary ("max") warnings about its (but not yours) side effects and toxicity effects and toxicity

Ocean-front property in Ocean-front property in New Jersey New Jersey

55 Incorporating irrelevant surrogate and composite end Incorporating irrelevant surrogate and composite end pointspoints

Concoct an invalid inflation of event rates (especially among control patients)Concoct an invalid inflation of event rates (especially among control patients) Lapis lazuli Lapis lazuli

66 "Shifting the goal posts" for "superiority" and "non-"Shifting the goal posts" for "superiority" and "non-inferiority" inferiority"

Require trivially better outcomes for "superiority" but massively worse outcomes for "inferiority" Require trivially better outcomes for "superiority" but massively worse outcomes for "inferiority" DiamondsDiamonds

Ethics-R-UsEthics-R-Us

77 Uninformed consent Uninformed consent Create consent forms in which study patients sign a "waiver of right to receive information" about the nature of, risk of, or alternatives to Create consent forms in which study patients sign a "waiver of right to receive information" about the nature of, risk of, or alternatives to your product your product

¥¥

RATs (Research Administration Teams)RATs (Research Administration Teams)

88 Adding efficacious co-interventions to (just) your product Adding efficacious co-interventions to (just) your product Give (just) the experimental patients additional treatments of known efficacy, find and treat their comorbidity, etc Give (just) the experimental patients additional treatments of known efficacy, find and treat their comorbidity, etc Ocean-front property in Ocean-front property in California California

99 Unblinded outcome assessment Unblinded outcome assessment Provide encouragement of (only) experimental patients' functional capacity performance or symptom scores, and ignore their minor Provide encouragement of (only) experimental patients' functional capacity performance or symptom scores, and ignore their minor strokes, heart failure, and side effects strokes, heart failure, and side effects

Insider trading before Insider trading before publication publication

1100

Repeated interim analyses Repeated interim analyses Scan repeated early analyses for spurious but favourable trends that justify terminating the trial in your favour Scan repeated early analyses for spurious but favourable trends that justify terminating the trial in your favour Rubies Rubies

FPSU (Find the Pony Statistical Unit)FPSU (Find the Pony Statistical Unit)

1111

Munchausen's statistical grid (looking for the pony) Munchausen's statistical grid (looking for the pony) Execute subExecute subnn-group analysis where n=keep going until you find a statistically significant effect in your favour -group analysis where n=keep going until you find a statistically significant effect in your favour nnxx101033 shares of stock shares of stock

1122

Overinterpretation of a positive trial Overinterpretation of a positive trial Report just the (impressive) relative risk reduction while suppressing the (unimpressive) absolute risk reduction and number needed to Report just the (impressive) relative risk reduction while suppressing the (unimpressive) absolute risk reduction and number needed to treat treat

0.5% of net sales 0.5% of net sales

1133

Overinterpretation of an indeterminate trial Overinterpretation of an indeterminate trial Report a too small trial with a huge 95% confidence interval (that includes 0) as "negative," thereby "proving" that there is "no Report a too small trial with a huge 95% confidence interval (that includes 0) as "negative," thereby "proving" that there is "no difference" between your product and the (better) one produced by your competitor difference" between your product and the (better) one produced by your competitor

0.5% of gross sales 0.5% of gross sales

Sackett DL, Oxman AD. HARLOT plc: Sackett DL, Oxman AD. HARLOT plc: an amalgamation of the world's two an amalgamation of the world's two oldest professions. BMJ. 2003 Dec oldest professions. BMJ. 2003 Dec 20;327(7429):1442-5.20;327(7429):1442-5.

And if that doesn’t And if that doesn’t work. . .work. . .

DesignationDesignation StrategyStrategy TacticTactic

SAFE (Say Anything For a Euro) panel SAFE (Say Anything For a Euro) panel of "experts" of "experts"

Provide generous research grants, first class travel, Provide generous research grants, first class travel, luxurious accommodations, exorbitant honorariums, luxurious accommodations, exorbitant honorariums, and gargantuan ongoing "consultant" fees to and gargantuan ongoing "consultant" fees to "experts" who (surprise) favour your product, "experts" who (surprise) favour your product, screening test, or programme screening test, or programme

Get SAFE experts to generate the guidelines, write Get SAFE experts to generate the guidelines, write the editorials, pick the keynote speakers, referee for the editorials, pick the keynote speakers, referee for the key journals, etc the key journals, etc

SCUM (Sick Celebrities to Use in the SCUM (Sick Celebrities to Use in the Media) Media)

Hire stars of stage and screen, famous athletes, and Hire stars of stage and screen, famous athletes, and washed up politicians who will "disease monger" and washed up politicians who will "disease monger" and tout your product or screening test tout your product or screening test

Get them on to talk shows, into gossip magazines, Get them on to talk shows, into gossip magazines, and into the front lines of parades on any issue and into the front lines of parades on any issue

PPCT (Pay the Piper and Call the Tune) PPCT (Pay the Piper and Call the Tune) Give generous "journalism" awards for articles that Give generous "journalism" awards for articles that monger your disease or praise your product in the lay monger your disease or praise your product in the lay media media

Continue to feed media new diseases and products to Continue to feed media new diseases and products to push push

RCAF (Rabid Citizens Against Facts) RCAF (Rabid Citizens Against Facts) Secretly fund "patients' action" groups to attack any Secretly fund "patients' action" groups to attack any counter-evidence that shows your product, counter-evidence that shows your product, programme, or screening test is useless or harmful programme, or screening test is useless or harmful

Denounce detractors with testimonials and threats Denounce detractors with testimonials and threats

DISARM (DIScourage Arguments with DISARM (DIScourage Arguments with Research Money) Research Money)

Disarm your critics by funding an evaluation of your Disarm your critics by funding an evaluation of your new screening test or health programme new screening test or health programme

Then stop the funding, ignore the results as out of Then stop the funding, ignore the results as out of date, or abandon the test or programme for a new, date, or abandon the test or programme for a new, equally untested one equally untested one

FYP (Foundation in Your Pocket) FYP (Foundation in Your Pocket) Build beautiful headquarters and conference centres Build beautiful headquarters and conference centres for health foundations for health foundations

Smooth the way for infiltrating SAFE experts into Smooth the way for infiltrating SAFE experts into their leadership and programme development their leadership and programme development

MTM (Move the Ministry) MTM (Move the Ministry) Lobby to shift responsibility for the approval of new Lobby to shift responsibility for the approval of new drugs and devices from the Ministry of Health to the drugs and devices from the Ministry of Health to the Ministry of Industry Ministry of Industry

Shift the objective from healthy patients to healthy Shift the objective from healthy patients to healthy national economies national economies

GFGC (Get the Fox to Guard the GFGC (Get the Fox to Guard the Chicken house) Chicken house)

Purchase a pharmaceutical benefits management Purchase a pharmaceutical benefits management organisation organisation

Control the selection and purchasing of drugs while Control the selection and purchasing of drugs while preserving the illusion of a market preserving the illusion of a market

BOSS (Bureau Of Secret Surveillance) BOSS (Bureau Of Secret Surveillance) Buy confidential information from pharmacists as to Buy confidential information from pharmacists as to exactly who is prescribing exactly what exactly who is prescribing exactly what

Tailor drug reps' visits to focus on just the prescribing Tailor drug reps' visits to focus on just the prescribing habits that need to be changed to your benefit habits that need to be changed to your benefit

SOW (Save/Sacrifice Our Workers) SOW (Save/Sacrifice Our Workers) Threaten to move your product development and Threaten to move your product development and manufacture to another country manufacture to another country

Launch media and lobbying blitzes that exaggerate Launch media and lobbying blitzes that exaggerate how many jobs will be lost if you leave (see cigarette how many jobs will be lost if you leave (see cigarette manufacturers' ploys) manufacturers' ploys)

SHARKS (Striking Horror And Retreat SHARKS (Striking Horror And Retreat through Killer Solicitors) through Killer Solicitors)

Hire all the really good lawyers Hire all the really good lawyers Use them to threaten nay-sayers, members of drug Use them to threaten nay-sayers, members of drug review boards, etc with frivolous but expensive libel review boards, etc with frivolous but expensive libel lawsuits. Suppress negative health technology lawsuits. Suppress negative health technology assessment reports until you've met your sales targets assessment reports until you've met your sales targets

Sackett DL, Oxman AD. HARLOT plc: Sackett DL, Oxman AD. HARLOT plc: an amalgamation of the world's two an amalgamation of the world's two oldest professions. BMJ. 2003 Dec oldest professions. BMJ. 2003 Dec 20;327(7429):1442-5.20;327(7429):1442-5.

The Fox is Guarding the The Fox is Guarding the Chicken CoopChicken Coop

Few with the requisite dispassion or Few with the requisite dispassion or objectivity are monitoring the evidence objectivity are monitoring the evidence creation process regarding therapies. creation process regarding therapies.

Companies are in charge of monitoring Companies are in charge of monitoring their own processes, drugs for ill effects their own processes, drugs for ill effects Opportunity for corruption especially Opportunity for corruption especially

abounds abounds

The Impotent FDAThe Impotent FDA Center for Drug Evaluation and Research (CDER) at the Center for Drug Evaluation and Research (CDER) at the

Food and Drug Administration (FDA) Food and Drug Administration (FDA) asked Institute of Medicine to assess the U.S. drug safety systemasked Institute of Medicine to assess the U.S. drug safety system

in response to CDER lack of authority in response to CDER lack of authority to force companies to complete agreed-upon post-marketing safety to force companies to complete agreed-upon post-marketing safety

monitoring studies of their productsmonitoring studies of their products to require companies to initiate new monitoringto require companies to initiate new monitoring

CDER requests companies to monitor at company CDER requests companies to monitor at company expense, in their own time expense, in their own time hundreds of agreed-upon post-marketing studies are never hundreds of agreed-upon post-marketing studies are never

carried out. carried out. Psaty BM, Burke SP. Protecting the health of the public — Institute of Medicine Psaty BM, Burke SP. Protecting the health of the public — Institute of Medicine

recommendations on drug safety N Engl J Med 2006:355;1753-55. recommendations on drug safety N Engl J Med 2006:355;1753-55.

A survey of FDA’s CDER A survey of FDA’s CDER Reviewers Reviewers

Two-thirds “lacked confidence in the Two-thirds “lacked confidence in the FDA’s safety monitoring of marketed FDA’s safety monitoring of marketed prescription drugs.” prescription drugs.”

A fifth of reviewers had felt pressure to A fifth of reviewers had felt pressure to approve a drug though they questioned approve a drug though they questioned its quality, efficacy, or safety. its quality, efficacy, or safety. FDA's review process for new drug applications: a management review. Washington, FDA's review process for new drug applications: a management review. Washington,

DC: Department of Health and Human Services, 2003. (Publication no. OEI-01-01-DC: Department of Health and Human Services, 2003. (Publication no. OEI-01-01-00590.)00590.)

It is a wonder that It is a wonder that anyany of the of the evidence we see evidence we see about new drugs or about new drugs or devices is both devices is both believable and believable and true. true.

EVIDENCE for PBMEVIDENCE for PBM Not surprisingly, there is now emerging data in Not surprisingly, there is now emerging data in

support of a corrupted evidence creation support of a corrupted evidence creation process. process.

The amount of pseudoevidence cannot be The amount of pseudoevidence cannot be quantifiedquantified the oversight process of evidence creation is so the oversight process of evidence creation is so

weakweak Anecdotes of apparent pseudoevidence Anecdotes of apparent pseudoevidence

creation are weaved through the literature. creation are weaved through the literature.

Corruption of Evidence Corruption of Evidence Creation: Rofecoxib Creation: Rofecoxib

Withdrawn from the worldwide market in Withdrawn from the worldwide market in 20042004

Was originally compared with ibuprofen Was originally compared with ibuprofen oror diclofenacdiclofenac appeared toappeared to have a more favorable have a more favorable

gastrointestinal-side-effect profilegastrointestinal-side-effect profile appeared to produce no increase in appeared to produce no increase in

cardiovascular risk. cardiovascular risk.

““The Report Contained The Report Contained only Half the Data”only Half the Data” “ “this report contained only half the data (from only six this report contained only half the data (from only six

monthsmonths of a one-year study). . . .” of a one-year study). . . .” Excess cardiovascular risk was indeed discovered upon full Excess cardiovascular risk was indeed discovered upon full

analysis and further studyanalysis and further study the advantage of a more favorable gastrointestinal profile the advantage of a more favorable gastrointestinal profile

disappeared. disappeared. ““The rofecoxib story . . . reflects poorly on the process thatThe rofecoxib story . . . reflects poorly on the process that

leads to drug approval.” (31)leads to drug approval.” (31) FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med 2001;345:433-442.  FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med 2001;345:433-442.  FitzGerald GA. COX-2 and beyond: approaches to prostaglandin inhibition in human disease. Nat Rev Drug FitzGerald GA. COX-2 and beyond: approaches to prostaglandin inhibition in human disease. Nat Rev Drug

Discov 2003;2:879-890.Discov 2003;2:879-890. Fitzgerald GA. Coxibs and cardiovascularFitzgerald GA. Coxibs and cardiovascular disease.disease. N Engl J Med. 2004 Oct 21;351(17):1709-11.N Engl J Med. 2004 Oct 21;351(17):1709-11.

Corruption of Evidence Corruption of Evidence Dissemination--Dissemination--Drug-eluting Drug-eluting stents for coronary artery diseasestents for coronary artery disease

Post-marketing evidence that was unfavorable Post-marketing evidence that was unfavorable may have been ignored or not aggressively may have been ignored or not aggressively disseminateddisseminated

Recent meta analysis showed substantially Recent meta analysis showed substantially higher rates of deathhigher rates of death and myocardial infarction and myocardial infarction from a drug-eluting stent than those with a bare-from a drug-eluting stent than those with a bare-metal stent. metal stent. Camenzind E, Steg PG, Wijns W. A meta-analysis of first generation drug eluting stent Camenzind E, Steg PG, Wijns W. A meta-analysis of first generation drug eluting stent

programs. Presented at Hotline Session I, World Congress of Cardiology 2006, Barcelona, programs. Presented at Hotline Session I, World Congress of Cardiology 2006, Barcelona, September 2–5, 2006.September 2–5, 2006.

Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005;293:2126-2130.after successful implantation of drug-eluting stents. JAMA 2005;293:2126-2130.

What Was Done with Evidence What Was Done with Evidence Prior to the Meta Analysis?Prior to the Meta Analysis?

After the meta-analysis presentation, a member of the team said to reporters After the meta-analysis presentation, a member of the team said to reporters that his results were consistent with that his results were consistent with [required but not very accessible] registry data[required but not very accessible] registry data randomized clinical trial datarandomized clinical trial data an earlier observational study.an earlier observational study. (33) (33) All indicated late stent thrombosis and hardAll indicated late stent thrombosis and hard events occurring later with drug-eluting events occurring later with drug-eluting

stents compared tostents compared to bare-metal stentsbare-metal stents ““Why company didn't discover and report the increased risk sooner?”Why company didn't discover and report the increased risk sooner?”

‘‘It's a phenomenally-low-frequency event.’ It's a phenomenally-low-frequency event.’ But the meta analystBut the meta analyst pointed out that access to data is more restricted in devicepointed out that access to data is more restricted in device

trials than in drug trialstrials than in drug trials FDA Circulatory System Devices AdvisoryFDA Circulatory System Devices Advisory Panel meetingPanel meeting . . . to discuss crucial . . . to discuss crucial

issues such as independent investigators' accessissues such as independent investigators' access to data and control of analyses. to data and control of analyses. (34)(34)

Shuchman, M. Trading restenosis for thrombosis? New questions about drug-eluting stents. N Engl J Med 2006:355(19);1949-Shuchman, M. Trading restenosis for thrombosis? New questions about drug-eluting stents. N Engl J Med 2006:355(19);1949-1952.1952.

High-Level Scientists May High-Level Scientists May Participate in Evidence Participate in Evidence CorruptionCorruption

The National Institutes of HealthThe National Institutes of Health several of its chief scientists, in charge of whole branches of several of its chief scientists, in charge of whole branches of

evidence creation, were accepting payments from evidence creation, were accepting payments from pharmaceutical companies, without disclosing such while they pharmaceutical companies, without disclosing such while they were working on the very products the NIH was evaluating. were working on the very products the NIH was evaluating.

On July 8, 2005, Dr. Elias A. Zerhouni, NIH director, On July 8, 2005, Dr. Elias A. Zerhouni, NIH director, sent a letter to the House Energy and Commerce sent a letter to the House Energy and Commerce CommitteeCommittee

Cmte investigating conflicts of interest by government researchersCmte investigating conflicts of interest by government researchers forty-four government scientists may have violated ethics rulesforty-four government scientists may have violated ethics rules nine may have criminally misbehaved during such violations. nine may have criminally misbehaved during such violations.

An alarming harbinger of An alarming harbinger of NIH Fraud and AbuseNIH Fraud and Abuse

NIH policy regarding outside income NIH policy regarding outside income changed under Harold Varmuschanged under Harold Varmus NIH had in 1995 confidentially aban- doned NIH had in 1995 confidentially aban- doned

strict rules about outside incomestrict rules about outside income letting employees accept corporate consulting letting employees accept corporate consulting

payments, including stock options. payments, including stock options.

Anecdotes of impropriety reported in a letterAnecdotes of impropriety reported in a letter physician writing letter to editor of to the Providence physician writing letter to editor of to the Providence

(Rhode Island) Journal in 2003. (Rhode Island) Journal in 2003. Poses RM. Corruption, incompetence in health care. Wednesday, Poses RM. Corruption, incompetence in health care. Wednesday,

December 17, 2003.December 17, 2003.

Industry Pays--Again Industry Pays--Again

NIH leaders -- ranging from laboratory to institute NIH leaders -- ranging from laboratory to institute directors -- had received hundreds of thousands of dollars in directors -- had received hundreds of thousands of dollars in consulting fees and stock-option proceeds from the consulting fees and stock-option proceeds from the pharmaceutical and biotechnology industries. pharmaceutical and biotechnology industries.

These NIH leaders often made decisions that affected the These NIH leaders often made decisions that affected the companies that employed them as consultants.companies that employed them as consultants.

Corruption in Medicine?Corruption in Medicine?

Prevalence of Scientific Prevalence of Scientific Corruption?Corruption?

Anecdotal and incomplete list of offenses Anecdotal and incomplete list of offenses is numerator leading to PBMis numerator leading to PBM

What is the denominator of unexposed What is the denominator of unexposed cases? cases? UnknownUnknown Where there is smoke. . . .Where there is smoke. . . .

How to respond to How to respond to Pseudo-evidence Based Pseudo-evidence Based MedicineMedicine

Let the Buyer BewareLet the Buyer Beware

Accept evidence with Accept evidence with even more cautioneven more caution

Can’t exclude certain forms of evidence-Can’t exclude certain forms of evidence-tampering simply by certifying that a tampering simply by certifying that a given analysis in a manuscript was given analysis in a manuscript was appropriate, or that the methods section appropriate, or that the methods section in that manuscript elucidated and in that manuscript elucidated and minimized all easily detectable forms of minimized all easily detectable forms of bias. bias.

Check the Source of Check the Source of Evidence Evidence

Most articles now state the sources of Most articles now state the sources of funding for research on new treatmentsfunding for research on new treatments

Check whether potential and actual Check whether potential and actual conflicts of interest have been conflicts of interest have been acknowledged by the authors of the acknowledged by the authors of the manuscript. manuscript.

Look For Evidence Of Look For Evidence Of PseudoevidencePseudoevidence

Check for the “cook the books” or “after-Check for the “cook the books” or “after-care” methods outlined above. care” methods outlined above.

Expensive and time-consumingExpensive and time-consuming Failure to find Pseudoevidence, while not Failure to find Pseudoevidence, while not

ensuring the safety of evidence for ensuring the safety of evidence for consumption, is at least somewhat consumption, is at least somewhat assuring to readers. assuring to readers.

Who’s Out There Fighting Who’s Out There Fighting PBM?PBM?

Individuals, organizations Individuals, organizations Foundation for Integrity and Responsibility Foundation for Integrity and Responsibility

in Medicine (FIRM), [in Medicine (FIRM), [www.firmfound.orgwww.firmfound.org], ], blog sponsored by FIRM blog sponsored by FIRM

[[http://hcrenewal.blogspot.comhttp://hcrenewal.blogspot.com] ] already performing a voluntary watchdog already performing a voluntary watchdog

function over the evidence creation processfunction over the evidence creation process particularly when it goes wrongparticularly when it goes wrong

Who’s Out There Fighting Who’s Out There Fighting PBM?PBM?

Trial registries, in particular, Trial registries, in particular, ClinicalTrials.gov [ClinicalTrials.gov [www.clinicaltrials.govwww.clinicaltrials.gov] ] voluntary registry of federally and privately voluntary registry of federally and privately

supported clinical research in human supported clinical research in human volunteersvolunteers

could be useful even without federal could be useful even without federal mandates to report ongoing trialsmandates to report ongoing trials

Look for corruption Look for corruption around youaround you

Examination your practice and scientific Examination your practice and scientific work (if applicable) for evidence of work (if applicable) for evidence of corruption or evidence tampering. corruption or evidence tampering.

VCU Conflicts of VCU Conflicts of Interest (COI) PoliciesInterest (COI) Policies

VCU COI Policy: http://www.vcu.edu/provost/univ_policies/conflict.htm

VCU Overview of COI: http://www.hr.vcu.edu/policies/COI%20Oveview.pdf

Office of Research COI policy: http://www.research.vcu.edu/p_and_g/coi.htm

Office of Research COI Disclosure Form: http://www.research.vcu.edu/forms/ConflictofInterestDisclosureForm.doc

[you will need to complete this to accompany every grant proposal on which you are listed - any level of involvement]

Office of Research guidelines on Industry Agreements: http://www.research.vcu.edu/p_and_g/agreements.htm

Mello Study Methods

884 U.S. medical school faculty active in 884 U.S. medical school faculty active in clinical research clinical research views about the acceptability of provisions in views about the acceptability of provisions in

contracts for industry-sponsored clinical trials that contracts for industry-sponsored clinical trials that would restrict investigators' academic freedom and would restrict investigators' academic freedom and control over trials control over trials

compared responses to results from a similar compared responses to results from a similar survey of research administrators at 107 survey of research administrators at 107 medical schools medical schools Account Res. 2005 Jul-Sep;12(3):163-91. Account Res. 2005 Jul-Sep;12(3):163-91.

Mello Study ResultsMello Study Results Relatively large % of trialists willing to give Relatively large % of trialists willing to give

industry sponsors considerable control over industry sponsors considerable control over dissemination of research results dissemination of research results

Significant diff’s in perceptions Significant diff’s in perceptions Clinical trial investigators vs other recently published clinical Clinical trial investigators vs other recently published clinical

researchersresearchers investigators w/ high vs low % research support from industryinvestigators w/ high vs low % research support from industry junior versus senior facultyjunior versus senior faculty investigators at institutions w/ high vs low NIH funding ranks.investigators at institutions w/ high vs low NIH funding ranks.

Significant divergence of views between clinical trialists Significant divergence of views between clinical trialists and research administrators who negotiate clinical trial and research administrators who negotiate clinical trial contracts on their behalf. contracts on their behalf.

The Medical The Medical Professionalism Charter Professionalism Charter

Published in several US and European Published in several US and European journals in 2002-2003. journals in 2002-2003. Blank L, Kimball H, McDonald W, Merino J; ABIM Foundation; ACP Foundation; European Blank L, Kimball H, McDonald W, Merino J; ABIM Foundation; ACP Foundation; European

Federation of Internal Medicine. Medical professionalism in the new millennium: a physician Federation of Internal Medicine. Medical professionalism in the new millennium: a physician charter 15 months later. Ann Intern Med. 2003 May 20;138(10):839-41. charter 15 months later. Ann Intern Med. 2003 May 20;138(10):839-41.

ABIM Foundation; ACP-ASIM Foundation; European Federation of Internal Medicine. Medical ABIM Foundation; ACP-ASIM Foundation; European Federation of Internal Medicine. Medical professionalism in the new millenium: a physician charter. J Am Coll Surg. 2003 Jan;196(1):115-professionalism in the new millenium: a physician charter. J Am Coll Surg. 2003 Jan;196(1):115-8. 8.

ABIM Foundation; ACP-ASIM Foundation; European Federation of Internal Medicine. Medical ABIM Foundation; ACP-ASIM Foundation; European Federation of Internal Medicine. Medical professionalism in the new millennium: a medical statute Rev Clin Esp. 2002 Aug;202(8):451-4. professionalism in the new millennium: a medical statute Rev Clin Esp. 2002 Aug;202(8):451-4.

ABIM Foundation; ACP-ASIM Foundation; European Federation of Internal Medicine. Medical ABIM Foundation; ACP-ASIM Foundation; European Federation of Internal Medicine. Medical professionalism in the new millennium: a physician charter. Obstet Gynecol. 2002 Jul;100(1):170-professionalism in the new millennium: a physician charter. Obstet Gynecol. 2002 Jul;100(1):170-2. 2.

Medical Professionalism Project. Medical professionalism in the new millennium: a physicians' Medical Professionalism Project. Medical professionalism in the new millennium: a physicians' charter. Lancet. 2002 Feb 9;359(9305):520-2.charter. Lancet. 2002 Feb 9;359(9305):520-2.

Prologue-editorial to Prologue-editorial to Charter, Ann Intern Med Charter, Ann Intern Med

Changes in the health care delivery systems in countries throughout Changes in the health care delivery systems in countries throughout the industrialized world the industrialized world threaten the values of threaten the values of professionalismprofessionalism.. The document conveys this message with The document conveys this message with chilling brevity. The authors apparently feel no need to defend this chilling brevity. The authors apparently feel no need to defend this premise, perhaps because they believe that it is a universally held premise, perhaps because they believe that it is a universally held truth. The authors go further, stating that the truth. The authors go further, stating that the conditions of conditions of medical practice are tempting physicians to medical practice are tempting physicians to abandon their commitment to the primacy of abandon their commitment to the primacy of patient welfarepatient welfare.. These are very strong words. Whether they These are very strong words. Whether they are strictly true for the profession as a whole is almost beside the are strictly true for the profession as a whole is almost beside the point. Each physician must decide if the circumstances of practice point. Each physician must decide if the circumstances of practice are threatening his or her adherence to the values that the medical are threatening his or her adherence to the values that the medical profession has held dear for many millennia... . profession has held dear for many millennia... .

ABIM Foundation. American Board of Internal Medicine; ACP-ASIM Foundation. American College of Physicians-American Society of ABIM Foundation. American Board of Internal Medicine; ACP-ASIM Foundation. American College of Physicians-American Society of Internal Medicine; European Federation of Internal Medicine. Medical professionalism in the new millennium: a physician charter. Ann Internal Medicine; European Federation of Internal Medicine. Medical professionalism in the new millennium: a physician charter. Ann Intern Med. 2002 Feb 5;136(3):243-6. Intern Med. 2002 Feb 5;136(3):243-6.

Commitments of Professionalism Commitments of Professionalism Charter that Relate to PBMCharter that Relate to PBM

maintain appropriate relations with inherently maintain appropriate relations with inherently vulnerable, dependent patients who could be vulnerable, dependent patients who could be exploited for personal financial gain or other exploited for personal financial gain or other advantagesadvantages

maintain the integrity and appropriate use of maintain the integrity and appropriate use of scientific knowledge and technologyscientific knowledge and technology specifically condemns the creation and use of specifically condemns the creation and use of

pseudoevidence. pseudoevidence.

Commitments (cont’d)Commitments (cont’d)

Acknowledge the presence of conflicts of Acknowledge the presence of conflicts of interestinterest

Do not allow personal or corporate interests to Do not allow personal or corporate interests to compromise your duty to protect the patientcompromise your duty to protect the patient ““Such compromises are especially threatening in the Such compromises are especially threatening in the

pursuit of personal or organizational interactions pursuit of personal or organizational interactions with for-profit industries, including medical with for-profit industries, including medical equipment manufacturers, insurance companies, equipment manufacturers, insurance companies, and pharmaceutical firms.” and pharmaceutical firms.”

Lobby For Overhaul of The Lobby For Overhaul of The Evidence Creation ProcessEvidence Creation Process

IOM Recommendations on Drug Safety IOM Recommendations on Drug Safety sweeping changessweeping changes

British House of Commons British House of Commons recommended realignment of relationships between the recommended realignment of relationships between the

pharmaceutical industry and government, regulators, pharmaceutical industry and government, regulators, doctors, the health service, and patients.doctors, the health service, and patients.

Smith R (2005) Curbing the Influence of the Drug Industry: A British View. PLoS Med 2(9): e241 Smith R (2005) Curbing the Influence of the Drug Industry: A British View. PLoS Med 2(9): e241 DOI: 10.1371/journal.pmed.0020241DOI: 10.1371/journal.pmed.0020241

““a fundamental review of drug development, marketing, and a fundamental review of drug development, marketing, and prescribing practices.” prescribing practices.”

House of Commons health Committee (2005) The influence of the pharmaceutical industry. Available: House of Commons health Committee (2005) The influence of the pharmaceutical industry. Available: http://www.parliament.the-stationery-office.co.uk/pa/cm200405/cmselect/cmhealth/42/42/pdf. Accessed 15 http://www.parliament.the-stationery-office.co.uk/pa/cm200405/cmselect/cmhealth/42/42/pdf. Accessed 15 June 2005June 2005..

SUMMARYSUMMARY PBM is a realityPBM is a reality When possible, PBM must be discovered, When possible, PBM must be discovered,

opposed, and preventedopposed, and prevented We must preserve EBMWe must preserve EBM

a welcomed and strong advance in the application of a welcomed and strong advance in the application of scientific advances to clinical care. scientific advances to clinical care.

Awareness of subtle methods of producing Awareness of subtle methods of producing pseudoevidence should improve the evidence pseudoevidence should improve the evidence creation processcreation process