Politics, Marketing, and the Media: Do They Trump Good

Science?

Richard Deyo MD, MPHUniversity of Washington

Hope or Hype?• What’ s the Problem? Examples

• Stealth Marketing

• FDA limitations

• Political action to eliminate funding for research with unwelcome results

• Ways to Improve?

The Problem• Treatments widely used before fully evaluated

• Unfavorable results sometimes suppressed; trivial benefits presented as breakthroughs; Scientific evidence often incomplete

• Expensive new treatments sometimes prove less effective or less safe than alternatives; after avoidable harm or unnecessary expense

Example: Drug Safety Problem

• Vioxx recalled after ~140,000 avoidable heart attacks

• Most who took it would have done as well with ibuprofen.

• Cost: $2.5 billion each year

Dai C et al. Arch Int Med 2005; 165: 171

Example: Surgery Problems

• Arthroscopic Knee debridement and lavage for osteoarthritis

• No more effective than sham surgery• Cost: $3 billion/yr.

Moseley JB et al: NEJM 2002; 347: 81-8

Example: High-tech Therapy

• High-dose ChemoRx and • Bone Marrow transplant for late

stage breast cancer• Long delayed RCT’s: no more

effective than standard chemotherapy; more toxic

• 42,000 women treated • Cost: $3.4 billion

Welch HG. BMJ 2002; 324: 1088

Example: Drug Efficacy Problem

• ALLHAT: thiazides > than newer drugs at preventing hypertension complications.

• Use in favor of newer drugs at 15x higher cost. • use of diuretics: • might prevent• 70,000 MI’s/year• Cost: $1.2 billion/yr.

ALLHAT group. JAMA 2002; 288:2981

Consequences of Using Expensive, Marginal Treatments

• Costs soaring; fewer can afford insur.

• Marketing, politics, media, advocacy often trump the best science

• Health policy makers not tackling the main reason for rising costs: new technology

• Hard to practice Evidence-Based Medicine

Imagined Course of Scientific Advances in Medicine

Hypothesis

Proof of Principle

Practical application

Increasingly rigorous tests in Humans

If safer, more effective, or less expensive than other treatments, disseminate widely

More Likely: Forces That Affect Dissemination

OPINION MAKERS(marketers, media,

politicians, advocacy)

ARBITRATORS RESEARCHERS(courts, FDA, FTC) (basic, clinical

HSR, commercial)

DECISION-MAKERS(hospitals, docs, patients, insurance,

MCO’s, Government)

Magnitude of Drug Company Advertising

• 2002: $21 billion total

• Vioxx alone, 2000: $160 million on DTC ads

-More than Pepsi spent on Pepsi

-More than Anheuser-Busch spent on Bud

Direct-to-Consumer Drug Advertising

• TV ads permitted in 1997

• U.S. only country (besides NZ)

• Risk when new drugs marketed: instant widespread use. For 5 recalled drugs in ‘97/98, 20 million exposed before recall.

• Pharmaceutical Executive: ads are designed to meet “the challenge of ensuring that patients walk out of their doctor’s office with a prescription for a particular brand…”

Unrealistic Expectations

“I think the dosage needs adjusting. I’m not nearly as happy as the people in the ads.”

Stealth Marketing: 1st Convince docs and pts. there’s a major problem

Allegedly, • 32 million with chronic dry eye• 22 million with insomnia• 16 million with restless leg syndrome• 9.5 million with adult attention deficit disorder• 43 million with irritable bowel syndrome• 36 million with seasonal allergic rhinitis• 28 million with social anxiety disorder• 28 million with toenail fungus• 102 million with high or borderline cholesterol Note: There are only 215 million American adults

“It’s the wheezingest, sickest, most decrepit nation on the face of the earth. It’s amazing anyone gets out of bed.”

-Arthur Caplan Director, Center for Bioethics University of Pennsylvania

Disease-mongering

Advocacy Groups: Stealth Marketing?

National Sleep Foundation (2005):

• March 29: “insomnia awareness day”

• March 27-April 2: “National Sleep Awareness week”

• Poll by the Foundation: 50% of Am. adults have problems getting to sleep at least once a week, and 22 million rarely get a good night’s sleep.

April, 2005: Lunesta Released

April 2005: Lunesta Released

Was this a coincidence?

National Sleep Foundation• PR preceding poll, Insomnia Awareness Day coordinated by PR

firm: Zeno Group. Poll, press kits paid for by sleeping pill manufacturers

• 10 of 23 members of Foundation’s board have had financial ties to manufacturers

• Foundation launched in 1991 with release of sleep problem survey funded by Searle; in 1992 Ambien released; Searle gave grants for “insomnia awareness” workshops in 20 cities.

• Over half of Foundation’s contributions are from drug companies that make sleeping pills

2006: The followup• 42 million prescriptions for sleepers in 2005, up 60%

since 2000.

• $185 million on Lunesta advertising in 8 months, April-Nov, 2005; campaign linked to “Desperate Housewives”

• Ambien: doubled its ad budget from 2004 in response (to $107 million)

• Headlines on overuse of sleeping pills in Feb, 2006

FDA: Common Misconceptions

• New drug, device must be better than old ones

• Studies done for approval are likely to discover important side effects

• Device approval similar to drugs

• Only approve if good value for money

• Off-label uses of drugs well-studied

• Surgery is regulated

Consumer Misconceptions• 50% think FDA pre-approves ads

• 43% think only “completely safe” drugs can be advertised directly to consumers

• 22% think drugs with serious side effects can’t be marketed

• 21% think only “extremely effective” drugs can be marketed DTC

• Consumers with most misconceptions held the most positive attitudes toward drug advertising

Bell, Kravitz, Wilkes: J Gen Int Med 1999; 14: 651

FDA limitations in Monitoring Drug Ads

• Doesn’t approve ads before airing; after the fact (voluntary pre-review increasing)

• Cannot levy fines

• Until 2000, ~100 warning letters/year about improper claims; Now only 20-30/year

• Regulatory letters delayed 2-12 weeks due to new requirement for legal review– often the planned broadcast life cycle

• 30 reviewers for 30,000 submissions/year; all TV ads reviewed, but not all print ads

Problems with Devices: Example

• 2001: Guidant recalls Ancure aortic endograft after 12 deaths; failed to report to FDA until whistleblower.

• 2003: pleads guilty to 10 felonies, $92 million penalties

• Since June, 2005: 88,000 defibrillators recalled (7 deaths); recalls or safety warnings for 200,000 pacemakers

Device Approvals

• FDA authority only since 1976; previously, no proof of efficacy or safety required.

• 99% of devices approved by 510(k) process: “substantially equivalent” to something marketed prior to 1976

• Review focuses on safety; efficacy only in an engineering sense

• Clinical efficacy studies usually not required

• RCT’s only for the newest and highest risk devices, eg implantable defibrillators

Postmarketing Surveillance• 50% approved drugs have serious side effects not known prior to

approval; only postmarketing surveillance can detect

• FDA has inadequate mandate, money, staff for surveillance of 5,000 drugs

• Even when postmarketing studies required for approval, lax enforcement

• Spontaneous reporting by docs: < 13% of serious adverse events; company reporting mandatory, but often delayed or suppressed

Pressures for Approval

• Protect from snake oil vs. delay in cures

• Frequent criticism of review time by industry, Congress

• In 1988, only 4% of new drugs approved worldwide first approved by FDA; had advantage of safety experience in Europe

• 1998: FDA first to approve 2/3’s of new drugs; approval time decreased from 32 mos. to 12

Pressures for Approval• 1992: User fees for drug review: now half the FDA

budget for drug review

• So much of budget from industry, may be reluctant to alienate corporate “sponsors”

• Internal report: 1/3 of employees uncomfortable expressing contrary opinions; negative actions stigmatized.

• Burnout? 15% of medical officer jobs unfilled in 2002; “sweatshop environment”

Other Conflicts of Interest

• Half the members of advisory committees had direct financial interest in drugs under review: own stock, consulting fees, research grants

• Law tries to restrict members with conflict of interest, but rule waived 800 times between 1998-2000

• USA Today: even consumer and patient reps. often receive money

FDA Constraints: Implications for Clinical Practice

• New drugs not necessarily as effective as old ones

• New drugs likely to have undiscovered side effects

• DTC ads are sometimes misleading

• Devices not as well tested as drugs

• Value for money not considered

Political Action: The Example of Spine Fusion Surgery

• fastest rising type of back surgery

• Popular technique: “pedicle screw”: adds about $13,000 per operation; $4 billion/yr

• Our findings, funded by AHCPR: o Literature synth: few validated indics.o Admin. Data: higher costs, complics. than discectomy,

laminectomyo Recommended RCT’s

AHCPR Guidelines: Advocated non-surgical treatment for most acute back problems

• Part of Congressional Mandate• 23 panel members; 4 surgeons• Advocated non-surgical Rx for most acute problems; didn’t

address chronic pain

Opponents to Research, Guidelines

• North American Spine Society (NASS): letter-writing campaign

• Center for Patient Advocacy (founded by ortho surgeon on NASS board):

o eliminate AHCPR, curtail FDA

o Sofamor Danek: injunction to block guidelines

Consequences of Attacks• 1996 House bill with $0 for

AHCPR

• Agency restored by Senate after intense lobbying in support by prof. societies

• Intimidation led AHCPR to end guideline work

• 25% budget cut: no new starts for years

The Follow-up• NASS: lawsuit alleging CME activities were promotions for

pedicle screws

• 6 of 7 subsequent RCT’s: fusion with bone graft alone has clinical outcomes equivalent to pedicle screws, fewer complications.

• But… spinal fusions rapidly increasing: new unproven implants

• Today: companies under investigation for alleged kickbacks to surgeons

Attacks on Funding or Research Agencies: Business as Usual?

• Injury Prevention Branch at CDC, from NRA and “Doctors for Integrity in Research and Public Policy”

• National Center for Health Care Technology Assessment in 1970’s (NCHCT)

• Office of Technology Assessment (OTA)

• Harassing scientists, funding agencies: disincentive to studying controversial qs.

• Eliminating public peer-reviewed funding: slow production of knowledge, push investigators toward funding with conflicts of interest

Solutions?For Doctors: Evidence-Based Medicine

Not enough to know if a treatment ought to work,

whether it makes physiologic sense,

whether it’s common practice,

whether we learned it in medical school,

whether we’ve always done it that way,

whether an expert vouches for it, or

whether it works in mice…

Evidence-based approach: what’s the best evidence that a new treatment extends lives or improves quality of life, and what are the risks?

Not practicing Evidence Based Medicine

‘Take these pills three times a day, unless you read in the paper that they’ve been proven ineffective.’

For Gov’t: regulatory approaches to disseminating medical innovations

• Direct comparisons of drugs, devices

• Pre-marketing review of ads; delay DTC ads after drug approval

• Better post-marketing surveillance

• Independent drug safety board (analogy to NTSB and FAA)

• Require RCT’s for devices

• Insurers support clinical trials as a condition of coverage (eg, Medicare and Lung Volume Reduction Surgery)

For Consumers: Shared Decision-Making

• Decision Aids: make choices explicit

• Open access to Medical records

• Avoid experimental Rx outside clinical trials; support clinical trials

• Foster skepticism, lots of questions

• “Nutritional labels” for drugs, products

Summary: Challenges in Disseminating Medical Technology

• Technology here to stay; much is good. But: main reason for rising costs

• “Latest & greatest” isn’t always the greatest; but marketing, media, and politics can obscure this

• Better info to be better shoppers; more use of EBM good for private payers, public payers, taxpayers

• Develop better “crap detectors”

• Need action by all parties; will only happen if we all insist

Other Marketing Strategies to Docs

Technology as an Income Strategy

Backlash: Alternatives to EBM• Eminence-based Medicine: gray hair & years of experience are

basis for recommendations• Vehemence-based medicine: louder and more strident, better to

browbeat• Eloquence-based medicine: fine suit and verbal eloquence

supersede evidence• Providence-based medicine: leaving decisions in the hands of

the Almighty• Diffidence-based medicine: Do nothing out of despair• Nervousness-based medicine: fear of lawsuits drives tests and

treatments• Confidence-based medicine: esp among surgeons – often wrong

but never in doubt

Prescription drug expenditures in U.S., l993-2001

Source: IMS Health

Medical Devices: Problems in Manufacturing more common

Copyright restrictions may apply.Barton, J. H. et al. JAMA 2005;294:2075-2082.

Drug Costs as a Share of Overall Health Care Costs, 1960-2002

Print ads enabled,

1985

TV & Radio Ads enabled, 1997

Ignorance is Bliss?

Consumers with the most misconceptions about the rigor of ad regulation held the most positive attitudes toward drug advertising

Conflict of interest?

“I have never been bought, I cannot be bought. I am an icon, and I have a reputation for honesty and integrity…It is true that there are people in my situation who could not receive a million-dollar grant and stay objective. But I do.”

Violations cited in warning letters

• Minimize risks

• Exaggerate efficacy

• False claims of superiority over competitors

• Promoting unapproved uses

• Promoting drug still in experimental phases

Device Approvals• Most approved by 510(k) process: “substantially equivalent” to

something marketed prior to 1976

• Why? Much less expensive than Premarket Approval process, requiring clinical data

• 2002: 3,708 approvals through 510(k); only 41 through PMA (1%)

• FDA official: “30 years later, does this make sense?”

• McClellan: “New devices are less likely than drugs to have their safety established clinically before they are marketed.”

Device Approvals

• FDA authority only since 1976; previously, no proof of efficacy or safety required. Agency overwhelmed with volume.

• Review focuses on safety; efficacy only in an engineering sense

• Clinical studies, clinical efficacy usually not required

• RCT’s only for the newest and highest risk devices, eg implantable defibrillators

Device Approvals

• Most approved by 510(k) process: “substantially equivalent” to something marketed prior to 1976

• Why? Much less expensive than Premarket Approval process• 2002: 3,708 approvals through 510(k); only 41 through PMA

(1%)• FDA official: “for first 5-10 years after 1976, made sense, but 30

years later, does it make sense?”

Professional Hype: Eliminate Death and Suffering from Cancer by 2015?

Drug Safety Problems

• Since ‘97, 15 drugs recalled, incl. Vioxx, Duract; most were “me-too” drugs

• Projection: 1 in 5 eventually get black box warning or withdrawn.

• DTC marketing increases exposure; for 5 recalls in ‘97/98, 20 million people exposed

• Cost of complications: $177 billion/year? About the same as cost of the drugs

• Preapproval testing: small numbers, short F/U, “healthy” subjects taking few other drugs

Medical Devices: Recalls

• June, ‘05: Guidant recalls 87,000 implantable defibs. after 2 deaths, inc. 21 yo college student

• July, 2005: Guidant warning on older pacemaker, 28,000 already implanted. Remove or not?

• 2004: Boston Scientific recalls 90,000 stents

• 2001: Guidant recalls Ancure aortic endograft after 12 deaths; failed to report to FDA until whistleblower. 2003: pleads guilty to 10 felonies, $92 million penalties

• 1990-2000: 28 pacemaker recalls; 300,000 devices

Other points for doctors

• EBM resources such as Cochrane Collaboration

• Use of computerized decision support

• Professionalism and resisting commercial pressures- an exhortation

Marketing and Media• Magnitude of drug marketing

• “Creating” problems to be solved medically

• Use of advocacy groups and media for marketing

• CME: marketing to physicians

• Doctors’ conflicts of interest

AHCPR Guidelines: Acute Low Back Problems

• Part of Congressional Mandate• 23 panel members; 4 surgeons, other disciplines: 2 from

UW• Exhaustive literature search, quality rating• Advocated non-surgical Rx for most acute problems;

didn’t address chronic pain

FDA

• Common misconceptions

• Limitations in drug approval, surveillance

• Limitations in monitoring drug ads

• Limitations in device approvals

• Internal tensions, conflicts of interest

Other uses of media for stealth marketing

• Reporters want Breakthroughs!

• Misleading efficacy data: “Almost miraculous” 50% reduction in fractures from Fosamax (2% to 1%)

• Pre-taped, edited video “stories” directly from companies; easy to fill the news hour

• Costs, side effects, conflicts of interest rarely included in news stories

Moynihan R et al. Coverage by news media. NEJM 2000; 342: 1645-50

Problems with drug “labels”

• Unreadable print• Complex jargon• Little data on efficacy• No way to distinguish

common or serious problems from rare or trivial

Drug Facts: Nolvadex (Tamoxifen) For Preventing Breast Cancer What is this drug for? Reduce the chance of getting breast cancer Who might consider taking it? Women at high risk of getting breast cancer based on

family history, age and other risk factors. Calculate breast cancer risk at (http://bcra... What you need to do when taking 1. yearly gynecologic examination (with Pap)

2. yearly blood tests 3. Use birth control (do not get pregnant)

Tamoxifen Study facts: 13,175 women 35 and older with prev. lobular carcinoma in situ OR whose 5 year risk of breast cancer was calculated to be 1.7% or greater. 6 years FU

How drug might help? Women NOT TAKING Tam. Women TAKING Tam. Getting invasive breast cancer 2.7% 1.4%

Dying from breast cancer* 0.09% 0.05% (difference may be due to chance) How drug might harm? Life threatening side effects Blood clot 0.4% 0.8% Stroke 0.4% 0.6% Invasive Uterine Cancer 0.2% 0.5% Less serious side effects Cataracts requiring surgery 1.1% 1.7% Hot flashes 69% 81% died for any reason 1.1% 0.9% Average monthly price $103.85 (at 20 mg. a day dose)

* Learn more about Nolvadex (Tamoxifen), the study (JNCI: 1998:90: 1371-88) at http://www.drug...

Main task of drug company employees, 2000

Source: PhRMA Industry Profile 2000; percentages calculated by Sager and Socolar

CME

Another form of Stealth Marketing

Why is AstraZeneca doing CME on Lipid Management?

• AstraZeneca: Maker of newest statin drug Crestor – Approved August, 2003

• Already 5 statins on market; desperate for market share after fall in profits

“That stuff doesn’t influence me at all. I don’t even know what drug is on my pen. I just go for the food.” --Fill in your name here?

“We do marketing directly to physicians because we know it works…We do that by advertisement, by marketing, by promotion. And again I would point out it’s very effective.” --Dr. Robert Freeman, AstraZeneca

Doctors: Easy Targets?

Costs to Society

• Harassment of scientists, funding agencies a disincentive to pursuing controversial questions

• Interest groups define acceptable questions, shape range of answers

• Eliminating public peer-reviewed funding will slow production of knowledge, push investigators toward funding with conflicts of interest

Promotional spending on prescription drugs, 2002

Total spending: $21 billion

Source: IMS Health

Journal ads and corporate leverage

Suzanne and Bob Fletcher and drug ads in the Annals (Former editors Of Ann Int Med; Internists at Harvard, UNC)

Bob and Suzanne Fletcher at Ann Intern Med

• In 1992, published article by Michael Wilkes critical of drugs ads: experts reviewing ads found deficits in accuracy, compliance with FDA standards, educational value

• Dramatic drop in drug ads at Annals

• Lost $1-1.5 million in ad revenues

• Drop immediate, lasted until Jan. 1994 – when a new editor was appointed

Problems with Devices: Examples• 2001: Guidant recalls Ancure aortic endograft after 12 deaths;

failed to report to FDA until whistleblower. 2003: pleads guilty to 10 felonies, $92 million penalties

• Pedicle screws in spine surgery: 6 RCT’s indicate no advantage of instrumentation over bone grafting alone for pain or function; increase complication rate and costs: often $13K per case; $4 billion/yr.

Solutions for Insurers, Researchers: Pay now or pay more later

• Partnerships for funding earlier clinical research. Example of Lung volume reduction surgery: NIH, CMS, AHRQ

• Reporting all the research results: mandatory clinical trial registration a good start

• More support for clinical research in addition to basic biology