A Call to Arms: Veteran NEJM Editor Takes on Big Pharma as No One Before; Calls for Sweeping Reforms

Veteran NEJM Editor Takes on Big Pharma as No One Before; Calls for Sweeping Reforms

Party Pooper

“I find it hard to imagine that a system this corrupt can be a good thing, or that it is worth the vast amounts of money spent on it. In addition, we have to ask ourselves whether it really is a net benefit to the public to be taking so many drugs. In my view, we have become an overmedicated society.”

Marcia Angell, M.D., The Truth About the Drug Companies: How They Deceive Us and What to Do About It, (Random House, 2004).

Weaning Us Off the Dope

Just as the hand-wringing PR exercise that has become the international AIDS conference was winding down halfway across the globe, this little item hit the newsstand in the states:

July 15, 2004 — Members of a government panel, which earlier this week recommended more aggressive use of statin medications for people at the highest risk of dying from heart disease, failed to disclose financial links to the companies that make the drugs.

The revised consensus guidelines were issued by none less than the American Heart Association and were drawn up by a government panel of experts in the field, convened by the NIH’s own National Heart, Lung and Blood Institute. The new rules, if sustained, would lower serum cholesterol targets to a point where 7 million more Americans would be encouraged to start taking the cholesterol lowering medications of Pfizer, Merck, BMS and AstraZeneca. (At $1,500 or so a year and 20-30% margins, we’re talking an additional $2-3 billion a year in profits — with little more than the stroke of a pen.)

New York Newsday first reported the story in its Thursday edition. Eight of the nine panel members had earned money specifically from cholesterol drug makers, including Pfizer, Merck, BMS and AstraZeneca. The NIH’s Dr. James Cleeman and Dr. Rose Marie Robertson, of the AHA, both said they felt financial disclosure had been covered because all but two of the authors had also served on the 2001 consensus panel — and that they had made their industry connections known then.

The summer imbroglio set familiar alarm bells sounding: foxes guarding the hen house, physicians and researchers as pharma shills. Of course, guidelines meddling is among the oldest tricks in the Big Pharma playbook. The wisest, perhaps privileged, clinicians routinely eschew such interference and hope nothing untoward will befall them for their brave and educated insolence. But the fact remains that guidelines of all guises in all specialties whack quite a wallop in establishing prescription patterns and the standard-of-care. And thus, not unlike the Swift Boat veterans’ media blitz in swing electoral states, efforts to influence them suck in tens of millions of dollars a pop.

Perhaps due to an historic vigilance among AIDS activists and clinician advocates (or to its infectious nature), the field of HIV medicine has so far been spared the most egregious of these marketing-masquerading-as-medicine maneuvers. In fact, the two notable revisions to HIV’s standard-of-care followed on the heels of therapeutic setbacks (results of the early vs. deferred AZT “Concorde” study, circa 1993; and the failure of the eradication hypothesis, around 1998) and resulted in retrenchment rather than new aggressivity — albeit not without sustained intervention to limit the damage.

But might that portion of the Big Pharma enthralled research and treatment establishment still be clinging onto a model of overmedicatization in order to please its generous sponsors? After all, the NIH’s hallowed Principles of Antiretroviral Therapy seem immune to re-evaluation — even though the science and hypotheses on which they were based have largely been overtaken by events. “It’s the virus, stupid” sprang from its en-coffined slumber on the wings of hope — whipped to frenzied cries by the medical marketers — and has since taken on a life of its own. But where the silver dagger to return it to its repose?

When otherwise patient friendly researchers and community docs self-satisfyingly state, with all the authority their years of furtive pharma hustling has bought them, before a conference crowd that “lifelong antiretroviral therapy is not really a problem (anymore) because easier to take, less toxic combos are now available or just over the horizon”; when Trizivir, Viread + Sustiva or Kaletra are considered treatment sparing “maintenance” regimens in virtually all the studies pretending to re-explore this approach; when patient advocates on federal panels sign off on (or instigate) sweeping prohibitions which diminish our treatment options and further bottleneck the progress of clinical care; we, my fellow HIVers, activists, clinicians, researchers, need to rediscover our activist rage and imagination.

The field of HIV/AIDS seems poised, once again, at a crossroads. This time, however, activism and advocacy are deafening only by their silence. While the black and white, demagogic issues such as Abbott’s notorious price gouging rampage had even the bloated pharma front men crying foul, the more insidious issues — an anachronistic treatment paradigm, a research and regulatory establishment high-jacked by industry — go entirely unaddressed. It is within this context that an important voice may have serendipitously risen to stimulate our latent activist memory cells: former NEJM editor Marcia Angell via her gutsy deconstruction of (nearly) all that ails us.

Marcia Angell wasn’t always a crusader. Some may remember her rather uncritical endorsement of the design and conduct of the seminal AZT study (at 1,500 mg a day; it’s now dosed at 600 — and 500 mg or less, outside the U.S.) when it appeared in the pages of her little journal, circa 1987. Others haven’t forgiven her tough stance against alternative medicine. But with the release of her new book late last month, The Truth About the Drug Companies: How They Deceive Us and What We Can Do About It, Dr. Angell appears to have Goliath precariously centered within the cross hairs of a populist sling shot; her rousing philippic having transformed an otherwise mild-mannered Harvard lecturer into a present day Daniel J. Goldhagen of the medical profession.

She clearly doesn’t buy the Nussbaumian “good intentions” defense; instead, she lays out the evidence like an expert prosecutor — and goads us all to cease the charade. For those among us who, over the years, have come to rely on drug company beneficence for little luxuries here and there (and maybe even some extra pocket money), implementation of the Angell agenda will not be painless. Her clear and cogently articulated vision is of a reformed medical profession as much as it is a reformed pharmaceutical industry — both of which need to return to their mission, she argues, of serving the public interest.

Angell’s epiphanal moment is said to have occurred in the spring of 2000 when newly required conflict-of-interest disclosures for authors exceeded the available page space. The study in question was of an antidepressant drug, nefazodone, developed by Bristol-Myers Squibb. All but one of the study investigators reported consultancy arrangements, speaking honoraria and membership on pharma advisory boards — in most cases, with pharma companies producing similar types of drugs. Visibly frustrated, Angell referred readers to the journal’s Web site for the complete list of pharma financial entanglements. In disgust, she penned a now legendary accompanying editorial for the issue, “Is Academic Medicine for Sale?”

If we have become inured to apocryphal tales such as that of the section chief who supplemented his income to the tune of $500,000 a year through pharma consulting gigs or the clinical trials sites paid $12,000 per patient enrolled — with a $30,000 bonus if the number reaches six, Angell’s manifesto threatens to shake us from our stupor. And in a hodge-podge effort to depict the HIV KOLs and consensus makers in this regard, three extra pages of TAGline’s back-to-school issue are dedicated to Dr. Angell, in support of her campaign to bring medicine back to the people and to save Big Pharma from its most egregious excesses.

Early reviewers of the names and numbers note that acceptance of financial goodies (not to mention the unquantifiable triumvirate of fame, friendship and flattery) is not in itself evidence of objectivity’s loss. In fact, without exception, the half dozen or so New York City HIV docs informally queried about their advisory and lecture circuit relationships with Big Pharma were eager to point out that they moonlighted for “all the major drug companies” with HIV products expressly “to avoid any question of bias.” Others note that Angell’s scorched earth solution (barring anyone with pharma ties from key panel posts) would only be self-defeating. Were financial ties to drug companies an automatic disqualifier, the argument goes, there’d be only empty chairs at empty tables. (Angell disagrees.)

For the time being, the only remedy deemed workable is that of disclosure requirements — ironically, what appears to have sparked Angell’s fiery exposé in the first place. But, as she is quick to point out, does the mere act of disclosing financial ties to industry then render them acceptable? In the best of all worlds, certainly not, but it looks like that’s all we have for now (and what made the tables below possible). While the major journals and a couple of the med-ed/CME web sites are doing a reasonable job of highlighting industry ties, professional associations, the ACTG, the FDA Antiviral Advisory Committee and some less reputable treatment information providers make it difficult if not impossible to know who’s writing what for whom. TAGline welcomes comments, corrections, updated disclosure and other information at tagnyc@msn.com.

Table A: How to Save the Pharmaceutical Industry — and Get Our Money’s Worth

Seven broad problems:

1. Too many me-too drugs and too few innovative ones.

2. Key information about R&D, marketing and pricing is kept secret.

3. Drug companies have too much control over clinical research on their own products.

4. Drug companies control medical education about their own products.

5. The FDA is too much “in thrall” of the industry it is supposed to regulate.

6. Patents and other exclusive marketing rights are too long and too elastic.

7. Prices are too high and too variable.

Seven key reforms:

1. Shift the emphasis from me-too to innovation.

· U.S. patent law should be enforced in its original form.

2. Strengthen the FDA.

· Repeal the Prescription Drug User Fee Act (or allow it to expire in 2006).

· Increase public funding for the agency.

· Exclude experts with financial ties to industry from the FDA’s advisory committees.

3. Create an institute to oversee clinical trials.

4. Curb monopoly marketing rights.

· The clock on patents should not begin ticking until the drugs come to market.

· The loopholes in the Hatch-Waxman Act should be closed so that exclusivity cannot be stretched out for years.

5. Get Big Pharma out of medical education.

· Once and for all, we should clarify a simple fact: Drug companies are not providers of education — and they cannot be.

· No laws, regulations, or guidelines should be based on the idea that they are.

· The medical profession needs to take full responsibility for educating its members just as other professions do.

· There are a few simple steps to make this happen:

· Medical schools should teach students about drugs, not leave such education to industry-sponsored programs and teaching materials.

· Teaching hospitals should regard drug reps just as they do other salespeople (who are not allowed to traipse around at will, promoting their wares and offering gifts and meals to medical students and doctors in training).

· The profession needs to take responsibility for continuing medical education (CME). Just as there should be no private clinical research industry, there should be no private medical education industry hired by the drug companies.

· Professional associations need to be self-supporting.

· Direct-to-consumer advertising should be prohibited in the United States — just as it is in other advanced countries.

6. Open the “black box” of R&D and marketing costs.

· The pharmaceutical industry should be regarded as a public utility: its books should be open.

7. Establish reasonable and uniform pricing.

· Drug prices should be not only transparent but reasonable and as uniform as possible for all purchasers.

· President Bush’s Medicare reform bill (2003) should be repealed and replaced by a simple measure that guarantees all Medicare beneficiaries appropriate coverage of their drug costs, with government-negotiated payments to industry and a medically based formulary.

Source: Angell M, The Truth About the Drug Companies: How They Deceive Us and What to Do About It, (Random House, 2004).

Table B: Camel’s Nose Under the Tent

Who Evaluates and Licenses the Drugs You’re Taking?

cf. M Angell, The Hard Sell … Lures, Bribes and Kickbacks.

Angell: “The FDA’s advisory committees should not include experts with financial ties to industry. The notion that they are somehow indispensable is not credible. No one is indispensable. The truth is that experts who have deals with drug companies are being co-opted, just as the FDA is co-opted by user fees.” TTATDC, p 244.

Who Approves Your Drugs?

FDA’s Antiviral Advisory Committee (AVAC) membership and ties to industry:

Roy M. (“Trip”) Gulick, M.D., M.P.H., Chair
Consultancy fees from two pharma companies (not identified) of less than $20,000 a year; and research funding from two pharma companies (not identified) of less than $20,000 a year (per 2004 AVAC transcript). Consultancy fees from: Bristol-Myers Squibb, GlaxoSmithKline, Triangle, Trimeris; Speaking fees from: Abbott, Agouron, GlaxoSmithKline, Pharmacia-Upjohn (now part of Pfizer), Triangle (per 2000 disclosure).

Tara P. Turner, Pharm.D., Executive Secretary
“Nothing to report.”

Victor G. DeGruttola, Sc.D.
Pharmaceutical stock ownership totaling less than $5,000.

Janet A. Englund, M.D.
“Nothing to report.”

Courtney V. Fletcher, Pharm.D. , Consumer Rep
Pharmaceutical stock ownership totaling less than $50,000.

Princy N. Kumar, M.D.
Pharmaceutical stock ownership (including but not limited to Schering-Plough) totaling less than $30,000; advisory fees from Schering (per 11/02 documents).

Wm. Christopher Mathews, M.D.
“Nothing to report.”

Kenneth E. Sherman, M.D., Ph.D.
Pharmaceutical stock ownership totaling less than $25,000.

Lauren V. Wood, M.D.
“Nothing to report.”

Eugene Sun, M.D., non-voting industry representative
Employed by Abbott Laboratories; not required to make disclosures.

Joel Morganroth, M.D., non-voting consultant
Not required to make disclosures.

Douglas G. Fish, M.D., voting consultant
“Nothing to report.”

Peter R. Kowey, M.D.
Consultancy and speaking fees from pharma companies totaling less than $100,000 a year.

D. Roger Illingworth, M.D., Ph.D.
Consultancy and speaking fees from two pharma companies totaling less than $60,000 a year.

Rory P. Remmel, Ph.D.
“Nothing to report.”

Thomas R. Tephly, M.D., Ph.D.
“Nothing to report.”

Ronald G. Washburn, M.D.
Pharmaceutical stock ownership totaling less than $150,000.

Matthew Sharp, voting patient representative
“Nothing to report.”

Aggregate total disclosed: Less than $400,000 per year.

Source: DHHS/FDA/CDER transcript, Antiviral Drugs Advisory Committee (AVAC) Meeting, Tuesday, May 13, 2003. “NDA 21-567 and 21-568, ReyatazTM (atazanavir sulfate) capsules and powder for oral use, Bristol-Myers Squibb Company, proposed for the treatment of HIV infection in combination with other antiretroviral agents.”

Table C: Dancing With the Devil

Who Tests (and Reports on) the Drugs You’re Taking — and Formulates Your Treatment?

cf. M Angell, The Hard Sell … Lures, Bribes and Kickbacks.

Angell: “You need to know that your doctor’s decisions are based solely on what is best for you. And doctors need to be weaned from their dependence on drug company largesse.” TTATDC, p 262.

Who (at the NIH) Tests Your Drugs?

ACTG HIV Research Agenda Committee (RAC) membership and ties to industry:

Joseph J. Eron Jr., M.D.
Consulting arrangements with GlaxoSmithKline, Merck, Triangle, Trimeris. Research grants: GlaxoSmithKline, Merck, Abbott, Agouron, Triangle and Trimeris.

Roy (Trip) Gulick, M.D., M.P.H.
Consultancy fees from two pharma companies (not identified) of less than $20,000 a year; and research funding from two pharma companies (not identified) of less than $20,000 a year (FDA AVAC transcript [see source reference in preceding table]). Consultancy fees from: Bristol-Myers Squibb, GlaxoSmithKline, Triangle, Trimeris; Speakers bureau services for: Abbott, Agouron, GSK, Pharmacia-Upjohn (now part of Pfizer), Triangle.

Ann C. Collier, M.D.
Consulting arrangements with Merck. Research grants: Agouron, Merck, Hoffmann-LaRoche, Glaxo-Wellcome and Anor Med.

Eric S. Daar, M.D.
Consulting arrangements with Abbott, Boerhinger Ingelheim, GlaxoSmithKline, Gilead, Serono, ViroLogic. Speaking honoraria from: Abbott, Boehringer Ingelheim, GlaxoSmithKline, Gilead, Roche, Merck, Serono, ViroLogic, Ortho. Research grants: Abbott, Bayer, GlaxoSmithKline, Gilead, Roche, Merck, ViroLogic, Serono (Medscape disclosures, 2001).

Margaret A. Fischl, M.D.
Consultancy arrangements with and grant support (not broken out in disclosure) from: Abbott, Agouron, Bristol-Myers Squibb, DuPont, GlaxoSmithKline, Triangle (JAMA required disclosures from IAS guidelines panels, 2004 [IAS itself does not make this information available]).

Richard Haubrich, M.D.
Speakers bureau member for: Agouron, GlaxoSmithKline, Trimeris, ViroLogic; Grant support from same (Medscape disclosures, 2001).

Victoria A. Johnson, M.D.
Nothing found.

John W. Mellors, M.D.
Consultancy fees from: Agouron, Bristol-Myers Squibb, DuPont (now part of BMS), GlaxoSmithKline, Gilead, Merck, Novirio, Pharmasett, Triangle, Virco, Visible Genetics (per JAMA 1999); Grant support: BMS, Chiron, DuPont (now part of Bristol), GlaxoSmithKline, Merck.

Andrew R. Zolopa, M.D.
Consulting arrangements with Abbott, Bristol-Myers Squibb and Merck. Research grants: Abbott, Bristol-Myers Squibb and DuPont (Medscape disclosures, 2001).

Angell: “It is impossible to know to what extent these financial deals influence judgments about … research priorities or the interpretation of results, but they certainly are cause for concern.” TTATDC, p 105.

Who Sets Your Treatment Guidelines?

International AIDS Society (IAS) guidelines panel membership and ties to industry:

(U.S. based members only. Pharma ties of the six extra-U.S. panel members (Yeni, Cooper, Gatell, Gazzard, Montaner, Vella) are extensive.)

Angell: “Increasingly, panel members and med ‘educators’ are required to disclose their financial ties. And that disclosure is supposed to make it acceptable that they have them.” TTATDC, p 140.

Scott Hammer, M.D.
Consultancy fees and grants (not broken out in disclosure): Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Roche-Trimeris, Shionogi, Shire BioChem, Tibotec-Virco, Triangle.

Charles Carpenter, M.D.
“None to report.”

Margaret Fischl, M.D.
Advisory fees and grant support (not broken out in disclosure) from: Abbott, Agouron/Pfizer, Bristol-Myers Squibb, DuPont, GlaxoSmithKline, Triangle.

Martin Hirsch, M.D.
Consultancy and lecture fees and grant support from: Bristol-Myers Squibb, GlaxoSmithKline, Merck, Schering-Plough, Takeda, Trimeris.

David Katzenstein, M.D.
Stock holdings, advisory fees, speaking honoraria and grant support (not broken out in disclosure) from: Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck, ViroLogic, Visible Genetics, patent US 5,968,730 on PCR assay (October 15, 1999).

Doug Richman, M.D.
Consultancy arrangements with Abbott, Bristol-Myers Squibb, Chiron, Gilead, GlaxoSmithKline, Merck, Pfizer, Roche, Takeda, Triangle, ViroLogic.

Mike Saag, M.D.
Grant support from or served as a consultant (not broken out in disclosure) or on the speakers bureau for Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Hoffmann-La Roche, Ortho Biotech/JNJ, Pfizer/Agouron, Pharmacia & Upjohn, Schering-Plough, Shire, TherapyEdge, Tibotec/Virco, Triangle, Trimeris and ViroLogic.

Mauro Schecter, M.D.
Consultancy fees, speaking honoraria and grant support (not broken out in disclosure) from: Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck, Roche.

Melanie Thompson, M.D. M.P.H.
Consultancy and advisory fees, lecture sponsorship, speaking honoraria and grant support (not broken out in disclosure) from: Abbott, Agouron, Agouron/Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiron, DuPont, Gilead, GlaxoSmithKline, Merck, Oxo-Chemie, Roche, Serono, Triangle, Trimeris, ViroLogic.

Chip Schooley, M.D.
Stock holdings (options), consultancy and lecture fees, honoraria and grant support (not broken out in disclosure) from: Agouron, AnorMed, Bristol-Myers Squibb, Merck, Mojave, Pan Pacific Pharmaceuticals, Hoffmann-La Roche, Tanox Biosystems, Triangle, Vertex, ViroLogic.

Paul Volberding, M.D.
Consultancy fees and honoraria from: Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithkline, Merck.

Table D: Who Provides You With Up-to-Date Treatment Information?

Popular treatment information resources for doctors and patients — and their reliance on pharmaceutical largesse:

Self-Test

Inquire for yourself from those resources you use most often.

“If you have a genuine firewall between the editorial and sales sides of your treatment magazine or Web site, you would be extremely unusual. For most journals and magazines, the pharma marketing people call the shots.”

— Interview, Marcia Angell, MD; September 2004

Medscape.com
Bangkok conference coverage on the site paid for by Bristol-Myers Squibb, GlaxoSmithKline, and Gilead.

Pharma (or pharma consultant) sign-off on CME content? Yes __ No __