Clinical trial research driven by marketing, not evidence

Those of you in the mood for a serious read might want to check out an article in the Journal of Bioethical Inquiry about the way in which many drug companies use their marketing muscle to mislead physicians and consumers about the safety and effectiveness of their products.

This is not news, of course. In recent years, the mainstream media and blogs like this one have spotlighted specific examples where drug companies have achieved blockbuster profits through such smarmy tactics as ghostwriting, the suppression of negative findings, the publication of journal articles that report only positive findings, and paying prominent physicians to convince their peers of the drugs' benefits. Indeed, the illicit marketing campaigns that antidepressant makers like Pfizer, Eli Lilly and GlaxoSmithKline developed to make drugs like Prozac, Paxil and Zoloft look safer and more effective than they really were are the subject of several books, including Side Effects.

What's worthwhile about the article in Bioethical Inquiry is that it makes very clear how widespread this practice of "marketing-based medicine" is and how unreliable our so-called "gold standard" of medical research -- randomized clinical trials -- really is. In too many cases, drug companies, which fund these trials and cherrypick the researchers whose names appear on them, not only ghostwrite the results to hide negative data and overstate the positive. But they also make sure that any truly negative trials never see the light of day. And then once the misleading results are published in supposedly reputable journals, the drug companies use prominent physicians (on their payroll) to market the hell out of them.

In their roundup, the authors, Glen Spielmans and Peter Parry, show how all this worked -- not only with the antidepressant campaigns but also in the way that Eli Lilly and AstraZeneca went about promoting their antipsychotic drugs, Zyprexa and Seroquel and suppressed the drugs' negative side effects to increase market share.

Spielmans and Parry suggest an interesting, if radical, solution: that journals should cease publication of clinical trials, since the much-vaunted process of peer review doesn't seem very effective in weeding out erroneous trial results. Instead, they suggest that trial results could be published in some form of online registry, and that journal articles could focus on the validity of these trial results. Of course, this would deprive the journals of a major source of revenue: reprints of positive trial results (which the drug companies use in their marketing blitzes), as well as lucrative advertising revenue. So don't look for this kind of systematic reform any time soon.

Doctor on Glaxo payroll tells Harvard Sayonara

Remember Dr. Lawrence DuBuske, the Harvard Medical School allergist whom I outed as the highest paid doctor on GlaxoSmithKline's payroll for the second quarter of last year? Rather than give up his lucrative speaking and consulting gigs for Glaxo and myriad other drug companies, DuBuske has decided to part ways with Brigham and Women's Hospital and Harvard Medical School, according to The Boston Globe.

Can't say I blame him. DuBuske, after all, earned a whopping $99,375 from just Glaxo in only three months last year, as I reported here. He also was getting speaking bucks from Schering-Plough, Merck and Sanofi-Aventis. Indeed, as the disclosures in a March 2009 journal article show, DuBuske is basically on the speaking payroll of every pharmaceutical company that makes or markets allergy drugs in this country.

So when DuBuske was notified that his speaking gigs are now in direct violation of Partners' new conflict-of-interest policy, he chose to keep the income and dispense with the titles. He only saw patients at Brigham's on a consult basis, after all, and was a part-time instructor at Harvard Medical School.

DuBuske, however, is also director of the Immunology Research Institute of New England, a nonprofit Gardner-based organization that works with medical researchers throughout Eastern Europe on educational programs and clinical studies of new allergy drugs. It is no doubt his work with this institute and all those bargain-priced clinical researchers in Eastern Europe that makes DuBuske so valuable to allergy drug makers. You can bet he's not giving that gig up.

Why the FDA is more probusiness than ever

It's nice to see that Massachusetts anesthesiologist Scott Reuben has plead guilty to faking medical research and agreed to pay restitution fees for his fraud. But there is one aspect of his plea agreement with federal prosecutors (which he signed last week in the hopes of a more lenient sentence) that troubles me: why is he paying $420,000 in restitution fees to the very drug companies that benefited handsomely from his faked research and rewarded him with speaking fees? (Reuben's plea deal was first reported in The Day).

To recap, Reuben, an anesthesiologist at Baystate Medical Center in Springfield, fabricated positive data on at least 21 studies of drugs, mostly painkillers such as Vioxx, Bextra and Celebrex; background here. Reuben received research grants from the makers of these drugs, and he was also getting lucrative speaking fees from at least two of the companies: Pfizer (which makes Bextra and Celebrex) and Merck (Vioxx). And now he is required to pay Pfizer $296,000, $16,000 to Wyeth, (now owned by Pfizer), and $49,375 to Merck, all in restitution for taking their money and then faking positive findings about their drugs. Rich, huh? I'm sure these companies are laughing all the way to the bank.

On an equally disturbing note: Jim Dickinson, the editor of FDA Webviews, an industry newsletter that follows the agency, has concluded that the FDA is more pro-business than at any time in 35 years. According to Gooznews, Dickinson writes:

It has taken almost a generation, but by now, the pro-industry infiltration of FDA's culture is firmly entrenched. Not only is collaboration in product reviews officially encouraged, but good relationships across the regulatory fence hold the prospect of a possible future career in a well-paid industry job.

And what does Dickinson blame for this tectonic shift in the federal agency's culture? The same culprit I singled out in Side Effects: the Prescription Drug User Fee Act, passed in 1992. I reported that industry user fees now account for more than than half of the FDA's entire drug review budget and as a result, the agency has become increasingly beholden to the very industry it is supposed to regulate. Or, to quote Dickinson:

User fees at FDA are the primary villain, because they allowed the industry to dictate the changes at the FDA in programs, procedures and practices. It will be impossible for the Obama administration to reverse the trend because as long as the user fees are in place the industry has the upper hand.

New study finds that extended price protections on drugs do not spur innovation

As Congressional committees work to meld the House and Senate versions of the health bill and Republicans launch a last-minute effort to scuttle the entire enterprise, one unsavory element of the legislation seems to have escaped much public attention. That's the provision permitting developers of biomedical drugs (known as biologics) an additional 12 years of protection from generic competition, despite the fact that a similar price protection measure in Europe did not spur innovation or benefit patients in any way.

Currently, federal law allows makers of all drugs (including biologics) to extend their patent protection for an additional five years after their patents expire. By allowing generic manufacturers to develop and sell generics after five years, this time limit saves American consumers roughly $10 billion a year, according to a recent column in The Los Angeles Times.

But last summer, an amendment was inserted into the House and Senate versions of the health care reform bill that provides the makers of biologic drugs up to 12 years of patient protection (an extra three years every time they tweak the drug formula slightly). One of the legislators who sponsored the amendment, Anna Eshoo (whose Palo Alto district is home to lots of venture capitalists), says the additional protection is necessary to encourage biotechs to pursue new innovative drugs. (Eshoo, by the way, is the top recipient of the biotech industry's campaign donations to Congress, according to LA Times columnist Michael Hiltzik.)

However, a new study in current Journal of Health Politics, Policy and Law finds that a similar 10-year measure extending price protections for drugs developed in Europe did not spur innovation in drug development there. The main effect of the European extension on drug price protections was to raise prices and drug company profits, according to one of the study's co-authors, Don Light, a visiting professor at Stanford University. Light's study also spotlights how the European Parliament, under pressure from pharmaceutical lobbyists, rushed the measure through before less affluent countries from Easter Europe could join the European Union (in 2004) and oppose the price protections.

As Light notes, "most affected are developing countries, where [price protections] makes drugs for cancer, AIDS and other serious conditions prohibitively expensive."

What's that French saying? Plus ca change, moins ca change. The more things change, the more they stay unchanged. How apt!