PHARMACEUTICALS CONFERENCE NAAG, MAY 11, 2007 FINANCIAL CONFLICTS: CONSEQUENCES, PROPOSALS

PHARMACEUTICALS CONFERENCE • NAAG, MAY 11, 2007 • FINANCIAL CONFLICTS: • CONSEQUENCES, PROPOSALS • Jerome P. Kassirer, M.D. • Distinguished Professor, Tufts University School of Medicine • Editor-in-Chief Emeritus, New England Journal of Medicine

Assumption: • EVEN SMALL GIFTS INFLUENCE BEHAVIOR Principles: • FINANCIAL CONSIDERATIONS NEVER COMPROMISE MD DECISION-MAKING • MEDICAL INFORMATION FREE OF BIAS FROM FINANCIAL INDUCEMENTS • PROFESSION ACCOUNTABLE FOR INORDINATELY HIGH COST OF CARE • ALL FINANCIAL ARRANGEMENTS OPEN AND TRANSPARENT

Not all incentives are financial… • Nina Easton from FortuneMagazine was asked how she can be objective as a Fox News TV commentator when discussing John McCain’s presidential candidacy, given that her husband is McCain’s media advisor. • She replied, • “Disclosure is the great disinfectant.” • ( NPR, April 1st 2007)

Not all incentives are financial…

PHYSICIANS’ FERVENT BELIEFS IN THEIR OBJECTIVITY • TRAINED IN THE SCIENTIFIC METHOD • RELIGIOUS ADHERENCE TO EVIDENCE-BASED MEDICINE

THE CANDY EXPERIMENT AT CORNELL’S HOTEL SCHOOL • THE GIFTTHE TIP • NO CANDY • ONE PIECE • TWO PIECES • ONE PLUS ONE

THE CANDY EXPERIMENT AT CORNELL’S HOTEL SCHOOL • THE GIFTTHE TIP • NO CANDY 19.0% • ONE PIECE • TWO PIECES • ONE PLUS ONE

THE CANDY EXPERIMENT AT CORNELL’S HOTEL SCHOOL • THE GIFTTHE TIP • NO CANDY 19.0% • ONE PIECE 19.6% • TWO PIECES • ONE PLUS ONE

THE CANDY EXPERIMENT AT CORNELL’S HOTEL SCHOOL • THE GIFTTHE TIP • NO CANDY 19.0% • ONE PIECE 19.6% • TWO PIECES 21.6% • ONE PLUS ONE

THE CANDY EXPERIMENT AT CORNELL’S HOTEL SCHOOL • THE GIFTTHE TIP • NO CANDY 19.0% • ONE PIECE 19.6% • TWO PIECES 21.6% • ONE PLUS ONE 23.0%

WHEN FINANCIAL CONFLICTS TRANSLATE INTO BIAS, WHAT DO THEY “COST”?

COLLEGE LOAN SCANDAL • Financial aid officers: fees based on loan volume, expense-paid trips to exotic locations, stock in company, paid as consultants, advisory board positions. • Students steered to “preferred lists.” • Result: Students and parents ripped off.

THEY CAN INFLUENCE TREATMENT OF MILLIONS • THERAPEUTICS INITIATIVE U.B.C. • Statins have not been shown to provide an overall health benefit for primary prevention • NCEP GUIDELINES • Aggressive LDL lowering for high risk patients (primary prevention) with lifestyle changes (diet, exercise) and statins

NCEP PANEL’S FINANCIAL CONFLICTS • (Personal income - honoraria and/or consulting fees- from all 5 statin companies) • Grundy 5 Hunninghake 4 • Pasternak 5 Merz 3 • Stone 5 Smith 0 • Brewer 4 Cleeman 0 • Clark 4

FOLLOW-UP • OCTOBER 2006 • 2004 NCEP GUIDELINES QUESTIONED • EVIDENCE BASE FOR ORIGINAL RECOMMENDATIONS WAS WEAK AND BASED ON SECONDARY PREVENTION • SOME ORIGINAL AUTHORS BACK OFF (NYT) • (Ann. Intern. Med 2006;145:520-530; Lancet 2007;369:168-169)

THEY CAN AFFECT THE OBJECTIVITY OF PHYSICIANS

INTERPRETATION OF CHEST X-RAYS • 492 abnormal chest X-rays, according to 30 plaintiff-hired “B” readers (hirees). • Films re-read by 6 blinded “B” readers (independents). • (“B” readers are certified by NIOSH; all used standard DHSS form OMB No. 0920-0020) • Gitlin et al Acad. Radiol 2004;11:843-856

RESULTS • (%) • hirees independents • ------- ---------------- • Parench. abn. 96 5 • Pneumocon. 97 6 • Pleural abn 26 8 • Film normal 0 38

THEY CAN • RAISE THE • COST OF • CARE AND • INCREASE • RISK

WE PAY FOR EXPENSIVE, INEFFECTIVE, AND RISKY DRUGS NYT 5/9/07

THEY CAN JEOPARDIZE PATIENT CARE • 1997: Rezulin withdrawn from market in England because of liver failure • In U.S., cases of death from liver failure continued to increase • 1999: FDA advisory committee voted 11:1 to keep drug on the market. Nearly all members had financial ties to drug maker. • 2000: Rezulin withdrawn from market; 63 deaths in U.S. by then.

THEY MAY JEOPARDIZE RESEARCH SUBJECTS • In 1999, 17 year old Jesse Gelsinger died at Penn 4 days into gene therapy experiment • Safety issues of experiment questionable • Both institution and investigator had stake in company that might profit from results • Investigator claimed money was not a factor • Some on Penn task force skeptical

THEY MUDDLE INTERPRETATION OF THE OPINIONS OF CONFLICTED EXPERTS • Are they true believers;objective? • Subconscious influences: what do they really believe? • Are their actions actually conscious?

THEY CAN BIAS PRACTICE GUIDELINES • NCEP (NIH, AHA, ACC) • ANDROPAUSE (ENDOCRINE SOCIETY) • ALTEPLASE IN ACUTE STROKE (AHA) • NKF ON USE OF EPO FOR ANEMIA • HEART RHYTHM SOC. ON ICM USE • SCCM ON XIGRIS, WITH BUNDLING

OTHER RECENT EXAMPLES • Treatment of age-related macular degeneration • Editor of Neuropsychopharmacology publishes ghostwritten paper touting Vagus nerve stimulation • MGH psychiatrists didn’t disclose industry ties in article on drugs in pregnancy • AtriCure procedure at Cleveland Clinic

THEY DENIGRATE PROFESSIONALISM Cartoons, television (ER, Simpsons)

“EPIDEMIOLOGY” • NEJM • April 26, • 2007 • Survey of • 1662 MDs • (FP, IM, Ped • Card, Anes • Surg)

MAIN POINTS • Industry used educational grants for marketing, especially for off-label uses • Excessive industry influence over content of CME programs • Lack of adequate oversight by ACCME of educational grant programs

DISCLOSURE: • “THE GREAT DISINFECTANT” • IS DISCLOSURE THE SOLUTION TO “MANAGING” CONFLICTS OF INTEREST?

THE BROUHAHA OVER LACK OF DISCLOSURE • 2003 NEJM, Annals, JAMA • 2005 Devices at Cleveland Clinic • 2006 JAMA 3 instances • 2006 Editor of Neuropsychoparmacology • 2007 PHS Guideline on drugs for smoking cessation

DISCLOSURE’S DEFICIENCIES • Disclosure is often incomplete • Difficult to detect bias even when conflict of interest is known • Naming a company may not identify drug named in print or in a lecture • Requires assessing someone’s motives

DISCLOSURE: • “THE GREAT DISINFECTANT” • LACK OF DISCLOSURE IS NOT THE PROBLEM

THEN WHAT IS THE PROBLEM? • The conflict is the real problem, not whether or not it is disclosed. • Pretending that disclosure ‘manages” the conflict doesn’t eliminate the conflict (“necessary but not sufficient”). • (Kassirer JP. A cure for public distrust. Boston Globe, July 27, 2006)

DISCLOSURE’S FLAWS • “It has become a truism on • Wall Street that conflicts of • interest are unavoidable. • In fact, most of them only • seem so, because avoiding • them makes it harder to get rich. • That’s why full disclosure is so • popular: it requires no • substantive change.” • Surowiecki J. • The talking cure. • The New Yorker • Dec. 9, 2002

IS THERE A BETTER WAY? • RELY ON UNCONFLICTED EXPERTS • INDEPENDENCE AND DIVERSITY • EXPERTISE: YES, BUT EXPERTS IN DATA ANALYSIS • MINIMIZE CONFLICTED EXPERTS • CONFLICTED EXPERTS ALLOWED TO TESTIFY

THE • SLIPPERY • SLOPE • REPRINTS FROM THE REPS • PENS AND COFFEE CUPS • TEXTBOOKS AND STETHOSCOPES • LUNCHES AND PIZZA • DINNERS AND TRAVEL • CONTINUING MED. EDUCATION • SPEAKER’S BUREAUS • STOCK AND OPTIONS • CONSULTANCIES/MARKETING • CONSULTANCIES/SCIENCE • JOINT RESEARCH

PHARMACEUTICALS CONFERENCE NAAG, MAY 11, 2007 FINANCIAL CONFLICTS: CONSEQUENCES, PROPOSALS