Six not-so-simple steps toward protecting people from dangerous drugs

Over the past two years there has been a steady diet of books and media reports about the disturbing influence the pharmaceutical industry has on medical research and doctors' prescribing patterns. Not a week goes by without a new report on the marketing muscle of the industry and the pervasive ties between the industry and the doctors upon whom we rely for supposedly objective medical advice.

A recent addition to this growing body of literature is The Risks of Prescription Drugs, which explains why the number of Americans taking prescription drugs has soared 72 percent in the last decade, with the result that an estimated 46 million Americans suffer from adverse side effects and 2.2 million are hospitalized every year. The book is co-written by five health policy experts and for the most part coalesces what has been written about in other places, including Marcia Angell's The Truth about Drug Companies, Jerome Kassirer's On the Take, Howard Brody's Hooked, Melody Petersen's Our Daily Meds, Peter Conrad's The Medicalization of Society and Side Effects, along with many newspaper reports.

However, The Risks of Prescription Drugs, published by Columbia University Press, does two things particularly well. First, it explains in a clear concise fashion why, despite the fact most new drugs offer little or additional benefit over existing meds, so many doctors prescribe these new drugs, exposing patients to serious side effects and adding billions in wasted costs to an already overburdened health care system.

Second, in the final chapter, the book offers comprehensive solutions to the problem, such as:

* Prohibit direct to consumer advertising by drug companies (because advertising to patients conveys inherently commercialized, biased information). Read more about this here.
* Create a stronger more independent Food and Drug Administration by more fully funding this federal agency so that it is no longer reliant on drug company user fees. (As reported in Side Effects, drug company money now accounts more than half of the FDA's entire drug-review budget.
* Change FDA policy so that new drugs are tested against existing drugs rather than against a placebo or sugar pill. (Right now, most drugs only need to show they are more effective than a placebo to win FDA approval).
* Reduce the commercial influence on doctors. While some medical schools such as Harvard have enacted strict policies prohibiting doctors from accepting free gifts, lunches and lucrative consulting and speaking deals from drug companies, too many others continue to allow such conflicts, all of which have been shown to bias doctors' judgment as researchers and clinicians).
* Get Big Pharma out of medical education. The Carlat Psychiatry blog makes a persuasive, ongoing case for why drug companies should not be allowed to fund continuing medical education.
* Limit the prescribing of unapproved uses of drugs, since such off-label uses are responsible for many of the adverse side effects seen in patients. See more about this here and here.
* Create and fund a new federal institute of medical science that can run clinical trials of new medications free of the drug industry's commercial interests. This institute could also be charged with doing objective research that compares the effectiveness of new products with existing drugs. As reported here, in the economic stimulus bill passed last year, President Obama included $1.1 billion for just this kind of comparative effectiveness research, but that should only be the beginning of a much larger, more comprehensive effort).

While all of these solutions are crucial if we want to improve our health care system and protect the public from dangerous and unnecessary drugs, the reality is that they will require the kind of political will that is in short supply on Capital Hill these days. That doesn't mean, however, that we should stop working toward such reforms. If anything, books like The Risk of Prescription Drugs are more important than ever -- in getting the truth out.

Mount Holyoke journalism class gains real-world experience

At the risk of tooting my own horn, I thought I'd post this video that was produced by Mount Holyoke College about the multimedia journalism class I teach there and our collaboration with the local newspaper, The Daily Hampshire Gazette. The video talks about how Mount Holyoke students are gaining real world journalism experience and helping a local newspaper gain a bigger footprint in its own community.

Government oversight agency calls on NIH to ban ghost-writing

Much has been written about the insidious practice of ghost-writing in medical research in this and other blogs and news articles. Even Dr. Francis Collins, the director of the National Institutes of Health (NIH), expressed dismay over the problem in a C-SPAN interview last year, calling it a threat to the "integrity of science." So far, however, not much has been done to curb such abuses.

In an open letter to the NIH yesterday, the Project on Government Oversight dialed up the pressure on Collins and the NIH by calling attention to several particularly egregious examples of ghost-writing. In the first, two psychiatrists, Dr. Charles Nemeroff and Dr. Alan Schatzberg, (whose ties to the pharmaceutical industry and conflicts of interest have been well-publicized) signed their names to a psychiatric textbook for primary care physicians that was in fact ghost-written by a contractor for SmithKline Beecham, now known as GlaxoSmithKline. As Duff Wilson reports in The New York Times, not only did SmithKline pay for the contractor to develop the outline and text for the two named authors but in emails obtained by PGO and the Times, the contractor also said it planned to show drafts and page proofs of the book to the drug company for sign off and final approval. Yet such company control was never disclosed in the textbook, which doesn't come as any particular surprise, since Nemeroff and Schatzberg have a history of failing to fully disclose their ties to the drug industry; see here.

Another ghostwriting example that the Program on Government Oversight highlights in its letter to NIH is one that I exposed in Side Effects: that a study of Paxil, spearheaded by Dr. Martin Keller, then chief of psychiatry at Brown University, was in fact ghost-written by the same contractor that ghost-wrote the psychiatric textbook mentioned above. According to documents that I obtained and posted here, this particular clinical trial, known as study 329, was skewed to downplay the suicidal risks of Paxil in adolescents and to make the drug seem more effective than it really was. According to email correspondence obtained by a law firm suing Glaxo, the contractor also sent this study to the drug company for final approval before it was published. In Side Effects, I quote an employee of Brown's department of psychiatry saying, “Everybody knew we had to keep [SmithKline] happy and give them the results they wanted."

While Keller has stepped down as chair of psychiatry at Brown, he remains a full professor there and is still receiving lucrative NIH grants. As the PGO letter notes, "Currently, [Keller] is the primary investigator on two NIH grants, with funding in 2010 of $1,341,493. Over the last five years, the NIH has given Dr. Keller $7 million in grants."

This is unacceptable. Keller has been accused of manipulating scientific data not only in my book but in scientific journals as well; see here and here. It's high time that the NIH stepped up to the plate and did as the Project on Government Oversight asked: "implement new policies that will require institutions to ban ghostwriting and make NIH funding contingent upon periodic certification from institutions that ghostwriting is strictly prohibited..."

Emory neurologist has history of failing to disclose conflicts of interest

My blog last week on Helen Mayberg's talk at the 2010 ScienceWriters conference caused quite a stir. Paul Raeburn, writing in the Knight Science Journalism Tracker, accused me of being wrong on the facts and several commenters defended Mayberg's research in using brain surgery for the treatment of unremitting depression.

Before I get to the gist of Raeburn's accusations, let me just point out that this isn't the first time that Dr. Mayberg, a neurologist at Emory University School of Medicine, has been less than forthcoming about her conflicts of interest. Mayberg was one of the authors on a 2006 paper that touted the effectiveness of a technique known as vagus nerve stimulation (VNS) in patients with treatment-resistant depression. Eight of the authors, including Mayberg, failed to disclose they had consulting ties with Cyberonics, the maker of the device that delivers electrical pulses to the vagus nerve in the neck. (The ninth author was an actual employee of Cyberonics). Because of this egregious failure to disclose, the lead author of the study, Dr. Charles Nemeroff, then chair of psychiatry at Emory, was forced to step down as editor in chief of the journal Neuropsychopharmacology, which published the VNS paper; read about the controversy here. Indeed, Nemeroff, who brought Mayberg to Emory, was forced to step down as chair at Emory last year after a Senate investigation found that he repeatedly failed to disclose to university and NIH officials the millions of dollars he was receiving from drug companies whose products he was touting in research papers and on the lecture circuit; read more about this here.

Mayberg also did not disclose the fact that she was a consultant for Advanced Neuromodulation Systems, a company that holds the patent on her surgical technique for deep brain stimulation, when she co-authored another 2006 article with Nemeroff that reviewed possible brain mechanisms for post traumatic stress disorder and concluded that Paxil might be an effective treatment for PTSD. The study, published in the Journal of Psychiatric Research, was funded by GlaxoSmithKline, the maker of Paxil. While Mayberg wrote about the possible involvement of Brodmann's area 25 in the brain in causing symptoms of PTSD, she did not disclose that she holds a patent for deep brain stimulation of that particular section of the brain or that she was a consultant for the company that is doing clinical trials on her surgical technique.

In my blog last week, I had reported that in her keynote at the Science Writers conference, Mayberg did not disclose that she is still a consultant for ANS, which also goes by the name of St. Jude Medical Inc. She did mention that she had a patent on the technique (which involves implanting electrodes in Area 25) and she referred on one slide to being a consultant for St. Jude Medical. Now, St. Jude Medical is a nonprofit hospital in California and so I (and others in the audience) assumed she was consulting for a nonprofit, not the for-profit company that is doing clinical trials on her patented technique. According to Raeburn who got in touch with Mayberg after I posted my blog, she said that "a review of her slides show that both ANS and St. Jude were disclosed." Now, maybe the good doctor does have a slide with ANS on it, but she did not put it up on the screen Nov. 7 and she did not mention it in her talk.

In my original blog, I also said that her "talk was heavy on anecdotal examples but skimpy on any real evidence of efficacy." She did say she was writing up a paper about her latest results but didn’t disclose much in the way of specifics. After I posted my blog, a reader sent me a summary of Mayberg's most recently published work on deep brain stimulation in UptoDate, a subscription only newsletter. Here it is:

“A case series of 20 patients with major depression unresponsive to more than 4 antidepressants and ECT (17 of the 20 patients) who underwent DBS with subcallosal electrode placement found response and remission rates to be 60 and 35 percent respectively at six months [49].”

A remission rate of 35 percent on 20 patients doesn’t seem that encouraging to me. More to the point, why didn’t Dr. Mayberg share this data with all of us science writers on Nov. 7?

Keynote scientist at ScienceWriters conference dances around the truth

Dr. Helen Mayberg, a neurologist at Emory University, had top billing at the annual Science Writers conference in New Haven Sunday to talk about her work in using deep brain stimulation to treat depression. Nearly 500 writers, editors, public information officers and students listened as she spoke of inserting electrodes into the frontal lobes of chronically depressed patients for whom other treatments (like drugs and ECT) have failed. She spoke with wonder of being able to help "patient after patient" awake from the fog of depression and how for some patients, the difference was like "night and day."

As it turns out, Dr. Mayberg left out a few salient details. To begin with, she never mentioned how many depressed patients have actually benefited from this risky surgical technique. She did say that in the initial feasibility study she and colleagues did in 2002 while she was at the University of Toronto, electrodes were surgically implanted in six patients and four out of six "got better and stayed better." She also alluded to a slightly larger study of 20 patients she conducted at Emory in which "patients are achieving remission." But she did not how many patients are actually in remission and for what length of time, or whether the results are statistically significant, only that "we are now writing up the paper for submission." Her talk was heavy on anecdotal examples but skimpy on any real evidence of efficacy.

Of equal concern, Mayberg did not fully disclose the extent of her conflicts of interest. At the beginning of her talk, she mentioned that she held a patent for the technique and that it was now in clinical trials. She also said she was a consultant for St. Jude Medical. Now, St. Jude Medical Center is the name of a well-regarded nonprofit hospital in California and the clear implication (to many of us in the audience) was that she was consulting for a nonprofit hospital. In fact, Mayberg is a consultant for Advanced Neuromodulation Systems, which also goes by the name of St. Jude Medical Inc., a for-profit multinational company that manufactures medical devices and has annual revenues of $4.6 billion.

This is the company that holds the patent for Mayberg's surgical technique and has begun clinical trials to test it. And it has a less than stellar reputation. Last year, the FDA hit St. Jude Medical, otherwise known as ANS, with a stern warning letter alleging that the company had failed to correct known design defects in spinal cord stimulation devices it sells to treat chronic pain. The FDA letter said the manufacture and installation of these devices are not in conformity with good manufacturing practice requirements and called the company to task for failing to respond to previous warnings from FDA inspectors about the devices' defects.

Now maybe St. Jude has cleaned up its act, although as of this afternoon a phone call to its corporate headquarters in St. Paul, Minnesota had not been returned. But if I were a chronically depressed patient being recruited for the company's ongoing clinical trials, I might think twice about participating. And if I had been one of the organizers for the 2010 Science Writers conference, I might have thought twice about inviting Mayberg to speak in the first place.

Alternatives 2010 organizers reverse course on censorship

In the latest twist to the saga of Alternatives 2010, the National Empowerment Center, which organized the conference, has apparently reversed course and restored the original language to Will Hall's workshop -- see my earlier blog about the brouhaha over this.

According to a hot-off-the-presses statement from Dr. Daniel Fisher, the director of the NEC:

"Hall's original workshop title, Coming off Medications: A Harm Reduction Approach. will be restored and we are delighted Will has agreed to come to Alternatives and present on this subject as originally planned."

In his statement, Dr. Fisher, a psychiatrist, also said,

"On behalf of the National Empowerment Center, I wish to apologize to Will Hall and to the consumer/survivor community for the last-minute decision to alter the title of his workshop to remove the reference to coming off medication."

Sanity, it seems, has prevailed.

Mental Health "Alternatives" conference censors a workshop on alternatives

Less than week before the opening of Alternatives 2010, a conference dedicated to promoting alternatives for better mental health care, the organizers did a strange thing: they decided to remove any language about coming off medications from the title and description of a workshop they had approved for the conference months ago. So the workshop's creator, Will Hall, the founder of the Freedom Center, did what he had to do and cancelled his participation in the five-day conference, which starts Wednesday in Anaheim, California.

The organizers of the conference, the National Empowerment Center, a long-time advocacy group for people with mental illness based in Lawrence, MA, say they decided to change the wording of Hall's workshop out of concern for liability issues. "If someone went to the workshop and stopped medication abruptly and had a bad reaction coming off and did something horrible, it would come back to us probably," said Dr. Daniel Fisher, executive director of NEC.

Why can't I buy this explanation? Possibly because, as Fisher, who is a psychiatrist himself, also admitted, the last-minute decision had a lot to do with the fact that Hall's workshop offered an alternative to working with psychiatrists and the prevailing biomedical model. "Our concern is that people would do this without working with their psychiatrists," Fisher said in a phone interview.

Ah, there's the rub. What Hall (and the nonprofit Freedom Center) espouse are treatments that don't necessarily depend on psychiatrists and drugs but on alternatives such as yoga, meditation, exercise, nutrition and access to peer-run support groups. I blogged about the Freedom Center and its goals here.

The irony in all of this is that Hall is not anti-medication. While he himself (as a psychiatric survivor -- he was diagnosed with schizoaffective disorder at one point) has been off drugs for 17 years, both the Freedom Center and the workshop he put together for Alternatives 2010 included information about how to continue on drugs, reduce drug utilization or come off medications. Hall is not saying that all mentally ill patients can or should do without their medications; he's just putting out information about possible treatment alternatives to drugs. But that apparently was too much for the psychiatric establishment who pressured the NEC into censoring Hall.

This, by the way, is the same supposedly consumer-driven organization that also rescinded an invitation to speak at its Alternatives conference to Robert Whitaker, author of Mad in America and Anatomy of an Epidemic. Whitaker was restored as a keynote speaker only after mental health advocates raised an outcry.

Sounds to me like Alternatives 2010 is not really about alternatives at all.

GlaxoSmithKline takes a big hit; the story of Avandia and Paxil

I've been experiencing a strong sense of deju vu ever since Gardiner Harris' story in The New York Times earlier this week that GlaxoSmithKline hid negative findings about a bestselling drug and misrepresented data in a clinical trial of the drug. This time, the drug is Avandia for diabetes, and there is evidence that Glaxo not only knew the drug increased the risk of heart attacks in patients and suppressed the data for 11 years. But according to The Times, the company also omitted cases of patients who were taking Avandia and suffered serious heart problems in the trial's tally of adverse events.

Where have we heard this before? As I revealed in Side Effects two years ago, GlaxoSmithKline pulled the same shenanigans with its blockbuster antidepressant, Paxil. Not only did the drug manufacturer suppress negative findings about the safety and effectiveness of Paxil in treating depression in children, but in one of the clinical trials it conducted of Paxil in the mid-90s, there is evidence that researchers actually omitted from the final study results, cases of adolescents who became suicidal after taking the drug. I revealed this pattern of deception in Side Effects and in subsequent blogs here and here.

Side Effects is essentially the story of how the New York State Attorney General's office uncovered GlaxoSmithKline's chicanery and sued the drug company, forcing it to publish the results of all of its clinical trials, negative as well as positive. Which is why it's so good to see one of the players in that 2004 drama -- Eliot Spitzer, who headed the AG's office at the time -- weigh in on the whole saga in Slate today.

The irony is that if Spitzer and his crew had not forced GlaxoSmithKline to post all of the clinical trial data on a public website, Dr. Steven Nissen, a cardiologist with the Cleveland Clinic, would never have been able to gather the data necessary to show, in a groundbreaking 2007 meta-analysis, that Avandia does cause an increase in heart problems. And the company's subterfuge would never have been revealed.

Now, of course, the ball is in the FDA's court. A split advisory panel yesterday recommended that Avandia should either be withdrawn from the market or have sales severely restricted because of its heart risks, according to The Times.

And just today, GlaxoSmithKline announced that that it would take a second-quarter charge of $2.36 billion to settle legal cases involving its drugs, Avandia and Paxil, again according to The New York Times Given that the company has been pocketing enormous profits for both of these blockbluster drugs for more than a decade -- last year alone, it made a total of $8.4 billion -- that's not exactly a ruinous sum. Even so, I'm sure GlaxoSmithKline's stockholders will not be happy with the news.

We can only hope that GSK and all the other drug companies who have practiced similar deceptive tactics over the years are finally getting the point: Crime doesn't pay.

Fighting for lower drug prices, or how to counteract Big Pharma's lobbying

At a recent talk I gave on health care, the question came up: why isn't our government negotiating with the pharmaceutical industry to lower drug prices in the US? My audience was a group of sharp-minded Mount Holyoke College alumni, and almost all of them were on some kind of prescription medicine. While private health plans (which insure most working Americans) don't have the clout to negotiate more reasonable drug pricing, the US government, which funds Medicare and Medicaid, does. Yet it doesn't use it, unlike in Canada and many European countries, where the government ensures low drug prices through tough-minded negotiations.

Why? The reason is glaringly obvious: Congress won't give the Department of Health and Human Services (HHS) the authority to negotiate lower drug prices because too many of its members are in bed with the industry. That's why HHS was expressly prohibited from negotiating lower drug prices in the Medicare Part D legislation enacted during the Bush administration.

One has only to look at the list of top industry spending on campaign contributions and lobbying in Washington to understand. This past year, the pharmaceutical/health products industry headed the list of industries spending millions of dollars to sway the opinion of Congressional and executive policy makers, according to Center for Responsive Politics, a nonpartisan, nonprofit research organization that tracks money in U.S. politics. This industry, which includes big pharma, biotech and the medical device industry, spent $263 million in 2009, ahead of the second (business associations), the third (oil and gas -- gee, could this be why BP was allowed to drill without the proper environmental review?) and the fourth highest (insurance companies) industry spenders.

It's difficult for individual consumers to have much of a voice in the face of such well-oiled (forgive the pun) special interests. But it doesn't hurt to try. So I will repeat what I told the Mount Holyoke crowd: Pick up the phone or write a letter/email to your Congressional representatives telling them that you want Congress to pass a law giving HHS the power to negotiate lower drug prices for Medicare and Medicaid (and while you're at it, ask for a ban on direct to consumer advertising too).

But don't stop there. Organize a town meeting with your Congressional representative or a mass street protest in Washington. If Americans devoted an iota of the time and energy to drug pricing reform that they shower on their favorite sports team, just think what this country could accomplish!

Why statins should not be widely prescribed, or the difference between relative and absolute risk

In The New York Times yesterday, Duff Wilson did a great job of explaining why many medical experts question the growing use of cholesterol-lowering statins in people without heart problems. He reported on new studies showing the risks of otherwise healthy people taking statins, and he exposed the huge conflict of interest by the scientist who led the study that enabled AstraZeneca to win FDA approval for marketing its statin, Crestor, to people without heart problems. (The scientist, Dr. Paul Ridker, a cardiologist at Harvard and Brigham and Women's Hospital, receives lucrative royalties on the test used in the study to determine whether people without visible heart problems might benefit from Crestor, There is much dispute over whether test itself, which measures an elevated level of inflammation in the body, indicates underlying heart problems).

Wilson also performed another estimable service: he highlighted the difference between relative risk and absolute risk. Relative risk is the statistical difference in outcome between a control group and a group taking an active drug in a study, whereas absolute risk is the actual number of people who might actually benefit from the drug. Most randomized clinical trials only report relative risk, which often inflates the benefits of the drug being studied.

So, as Wilson explained:

The rate of heart attacks, for example, was 0.37 percent, or 68 patients out of 8,901 who took a sugar pill. Among the Crestor patients it was 0.17 percent, or 31 patients. That 55 percent relative difference between the two groups translates to only 0.2 percentage points in absolute terms — or 2 people out of 1,000.

And then he goes on to put the difference into even clearer context:

Stated another way, 500 people would need to be treated with Crestor for a year to avoid one usually survivable heart attack. "That’s statistically significant but not clinically significant,” said Dr. Steven W. Seiden, a cardiologist in Rockville Centre, N.Y., who is one of many practicing cardiologists closely following the issue.

Well done, Duff!

On another note, I just wanted to let readers know that I am taking a hiatus from weekly blogging. I may still wade in now and then to blog about a timely issue (when I can't resist), but it's time to turn my attention to another project.

Shining the light on drug company shell games

First the good news: The Physician Payment Sunshine Act is now law, signed by President Obama as part of the health care bill overhaul. Starting in 2012, drug and medical device companies must report all consulting, speaking and other payments to doctors and teaching hospitals in excess of $100 annually to the federal Department of Health and Human Services, which will post the payments on a public website. This is an important first step toward making transparent the pervasive financial ties between doctors who are studying or promoting specific drugs and medical devices and the companies that manufacture these products.

There is one significant loophole in the law: according to the final provisions, payments related to clinical trials or product development agreements for new products are allowed a publication delay of four years or until product approval, whichever comes first. So if a particular doctor is researching a drug that has not yet been approved for a specific condition, we will have to wait four years to find out whether he or she is on the drug company's payroll. But at least the disclosure will eventually see the light of day, and patients who are prescribed the drug in question can seek a second opinion from a doctor who is not on the drug firm's payroll and whose medical judgment can be trusted.

The Physician Payment Sunshine Act, however, only goes so far. While it covers doctors and teaching hospitals, it does not extend to all the advocacy groups and professional organizations that have substantial influence on over how particular illnesses are treated. For example, as I reported, the National Alliance for the Mentally Ill (NAMI), the most powerful advocacy group for people with mental illness, received millions of dollars in funding from drug companies for years -- a payola that no doubt spurred this group's embrace of potent psychoactive drugs over alternative methods of treating mental illness.

And now, in the current Psychiatric Times, two Massachusetts researchers tear the veil off efforts by the American Psychiatric Association (APA) to hide industry funding of its two philanthropic arms -- the American Psychiatric Foundation (APF) and the American Psychiatric Institute for Research and Education (APIRE). As Lisa Cosgrove and Harold Burszstajn report: "While the APA recently announced it would phase out the visibly industry-supported educational programs, the organization has remained curiously silent about acknowledging and monitoring industry funding" of APF and APIRE.

Why does this matter? Because the APA is not only a powerful lobbying force in Washington and the premier trade group for America's psychiatrists but it also publishes the DSM, the diagnostic bible of psychiatry, that largely determines how psychiatrists treat mental illness. As I've blogged about before, the proposed DSM-V further broadens the categories of various disorders, which will have the net effect of creating profitable new markets for drug companies.

Hence, Cosgrove, a clinical psychologist at the University of Massachusetts, and Bursztajn, a psychiatrist at Beth Israel Hospital and Harvard Medical School, decided that the public has a right to know about any hidden financial ties between the APA and the pharmaceutical industry. So they investigated and found that the boards of both APF and APIRE were stuffed with high-level executives from companies that make drugs recommended by the APA and with psychiatrists who have financial ties to these drug companies. They discovered, for example, that nine of 16 board members of APIRE had industry ties.

Yet neither organization requires disclosure of financial conflicts of interest. Nor is there much information as to how much money Big Pharma is giving these organizations. In their Psychiatric Times piece, Cosgrove and Bursztajn ask the valid question:

Has industry removed the transparent and visible shell of professional education programs and replaced it with the more opaque shells of foundations such as APF and APIRE?

The authors go onto recommend that individuals serving on APF and APIRE's boards post disclosure statements and that the total amount of industry funding given to these organizations be posted. They also suggest that the boards of both groups be reorganized to more genuinely reflect a patient-centered focus. They conclude:

Steps need to be taken to lift the cloak of silence that surrounds the issue of indirect or covert ties exerting undue industry influence.

I couldn't have said it better.

Why tort reform isn't on the table: hard lessons about special interest money in Washington

Every semester, I do an in-class competition to show my students the power of the Web in digging up data for stories. I separate them into groups and ask them to find the answers to specific questions about current sociopolitical trends. Two questions I always ask are: one, what are the top industries in terms of campaign contributions to Congress and two, which are the top industry spenders on lobbying Congressional and federal officials. (These are two very different ways of influencing policy decisions).

The answers this year were instructive, particularly in the light of the ongoing battle to pass a health care bill.

Not surprisingly, the pharmaceutical/health products industry topped the list of industries spending millions of dollars to sway the opinion of Congressional and executive policy makers, according to Center for Responsive Politics, a nonpartisan, nonprofit research organization that tracks money in U.S. politics. This industry, which includes Big Pharma, biotech and the medical device industry, spent $263 million in 2009, far ahead of the second (business associations), third (oil and gas) and the fourth highest (insurance companies) spenders on the list. This ranking comes as no surprise, since the pharma/health industry has dominated the list of big spenders on lobbying for more than a decade, which goes a long way toward explaining why Big Pharma almost always gets its way in Congress and with the FDA as well.

What may come as more of a surprise is the industry that of late has topped the list of big spenders on Congressional campaign contributions: lawyers and law firms. In the 2009-2010 election cycle, lawyers gave Congress $27 million and the top recipient of their largesse was none other than Harry Reid, the Majority Leader for Democrats in the Senate. In the 2008-2009 election cycle, Barack Obama was the top recipient of their money, and in 2007, it was Hillary Clinton, then considered the front runner as the Democratic presidential candidate, again according to the Center for Responsive Politics, which culls its data from government records.

Such over-the-top spending explains why tort reform has been consistently excluded from each version of the health care bill, despite the fact that it's a favorite cause of Congressional Republicans. There's an ongoing debate over just how much money tort reform, or putting caps on the amount of money plaintiffs and their attorneys can reap from malpractice lawsuits, would actually save. For example, it's debatable whether tort reform would generate much savings in malpractice insurance, but there's no question that if doctors were less afraid of getting sued for big bucks, they might order fewer tests and procedures for patients and that could generate considerable savings, particularly if it was linked with real changes in the way doctors are reimbursed for care (i.e. being paid by salary rather than fee for service).

But what I haven't understood until now is why the Democrats haven't been using tort reform as a bargaining chip to bring some moderate Republicans into the fold on the health care bill.

Now that I (and my students) see how much big money lawyers have been throwing at Congress and our current President, I understand why tort reform is not on the table. And that's a damn shame. If capping monetary damages in medical malpractice suits were part of health care reform, some Republicans might just break rank and vote for it.

Instead, we see special interests once again calling the shots. No wonder the American public is, as Neal Gabler says in The Boston Globe today, so enervated and apathetic.

Financial conflicts and other problems with the proposed DSM-V

I have hesitated to weigh in on the debate raging over the proposed changes to the DSM-V (psychiatry's diagnostic bible), in large part because others more literate in psychiatric minutiae have already done so. To wit: Dr. Allen Frances in the Psychiatric Times, Dr. Edward Shorter in the The Wall Street Journal, and Dr. Daniel Carlat on his blog.

All three of these experts agree that the DSM-V (which, like previous DSMs, was created by psychiatrists appointed by the American Psychiatric Association) is dangerously broadening the categories of various disorders, which will have the net effect of creating profitable new markets for drug companies. As Frances, the chair of the previous DSM-IV task force, puts it:

DSM5 would create tens of millions of newly misidentified false positive “patients,” thus greatly exacerbating the problems caused already by an overly inclusive DSM4. There would be massive over-treatment with medications that are unnecessary, expensive, and often quite harmful. DSM5 appears to be promoting what we have most feared--the inclusion of many normal variants [like grief] under the rubric of mental illness, with the result that the core concept of "mental disorder" is greatly undermined.

However, the pundits seem to disagree when it comes to one particular change: subsuming Asperger's and other similar disorders under the broadened category of autistic spectrum disorders. While Shorter and Carlat think it's a good idea, Frances argues that this consolidation presents serious problems -- see again his Psychiatric Times essay. At a dinner party last night, I heard similar concerns from several mental health professionals, including allegations that the change may have been pushed for less than noble reasons -- i.e. financial gain.

But before I get to the possible conflict of interest here, let me enumerate their larger concerns:

1. There seems to be no scientific basis for subsuming Asperger's syndrome under the tent of autistic spectrum disorders.
2. Many children and adolescents with Asperger's benefit from a specially constructed type of environment (with special supports at school to bolster the social skills they lack). If these children are subsumed under the autism tent, there may be less emphasis on constructing such supportive environments and they may be more likely to be prescribed powerful anti-psychotic drugs like Abilify and Risperdal that are now approved for use with autism. Forget the fact that these drugs have significant side effects. If this happens, many Asperger's patients will not get the specialized attention they need.
3. There may be a temptation to diagnose children with mild autism as having Asperger's, thus undercutting the reality that while some people with Asperger's are highly functioning individuals, many others are severely disabled. As a result, people with severe Asperger's may also not receive the intensive care they need.

Now to the potential conflict of interest with the proposed change. As it turns out, one of the members of the DSM-V task force is Catherine Lord, a professor at the University of Michigan, who gets big royalties from a diagnostic test she helped develop (known as ADOS) that is used to diagnose autistic spectrum disorders in children. As it turns out, the subcategories for the ADOS test fit very neatly into the new criteria proposed for the autistic spectrum disorders in the DSM-V.

Now, according to an APA disclosure report I found online, Lord has agreed not to accept more than $10,000 from "industry sources" each year from the time the DSM-V is approved until its publication (the report says that will be in 2012, but recently the APA agreed to delayed publication of a new DSM until 2013).

What I want to know is: does this agreement include all the royalties Lord currently receives from the ADOS diagnostic test and the expensive bucket of toys that come with it? And if so, what happens after the DSM-V is published when all those royalties start flooding back in?

More importantly, should Lord have been allowed to sit on the DSM-TV task force in the first place and influence major policy changes in psychiatric diagnoses that will affect millions of vulnerable children? I think not.

A few questions for Judith Warner and her editors

The glowing review of Judith Warner's new book, We've Got Issues, in The New York Times this week didn't exactly catch me by surprise -- anyone who has read Warner's guest columns in recent years knows her take on psychiatric drugs -- but it did bewilder me.

Why, I wondered, did the Times choose that particular book to review so prominently in its science section; was it because Warner has such a cozy relationship with the paper, having been a guest columnist for many years?

The reviewer says that Warner "sallied forth to interview all the pushy parents, irresponsible doctors and over-medicated children she could find — and lo, she could barely find any." And that made me wonder just who did Warner actually interview for the book (which, let me admit right off, I have not read). Did she only talk to the parents of children with "issues" and the doctors who prescribed meds for them, as the review makes it sound? If so, she seems to have missed half the story. After all, parents who put their kids on psychoactive drugs and the doctors who prescribed them are probably quite earnest in believing they did the right thing. As a parent myself, I know: it's very hard to admit publicly that you may have done the wrong thing; ditto for the medical profession.

What I want to know is: did Warner bother to interview any of the folks who were forced to take powerful psychoactive drugs as children and grew up to be psychiatric survivors who have since turned to more effective, alternative methods of healing? Did she interview any of the foster children in Florida and other states where these drugs have been used for years as chemical straitjackets to control behavior caused by abuse and neglect? Did she interview the mother of four-year-old Rebecca Riley who was recently convicted of pumping her daughter full of the anti-psychotic drugs that killed her?

Did Warner interview any of the teachers or professors who deal with the detritus of inappropriately medicated children and teenagers every single day?

And where the heck did she get the information that psychiatric drugs help change the structure of the developing brain for the better? I'd like to see the evidence backing up that wild claim.

Finally, I'd like to know who orchestrated Warner's book publicity because it was a stroke of genius to postulate that this woman ever initially believed that children were being over-medicated and then changed her mind after doing the research for her book. Judging from what Warner herself has written over the years, I seriously doubt that claim. But I have to acknowledge: it's a brilliant piece of marketing.

Does aspirin really reduce the risk of breast cancer? We don't know yet...

In my health and science journalism class at Mount Holyoke yesterday, we were talking about all the questions journalists need to ask in deciding whether and how to report on a new medical finding. Two of the key questions that emerged were: 1. did the results come from a randomized clinical trial -- the gold standard of medical research -- or was it an observational study that examines people over time but has no control sample? And 2. did the study actually show cause and effect or just an association?

As it happened, the day's news furnished me with the perfect case example to illustrate the importance of these two questions. A page-one story in The Boston Globe, headlined "Aspirin may combat cancer, study suggests," trumpeted the results of a study published in the Journal of Clinical Oncology. The study in question was not a randomized clinical trial, i.e., it did not randomly compare what happened to one group who was taking the active drug (in this case, aspirin) with a control group who was taking a dummy pill or placebo. It was an observational study of more than 4,000 nurses (in the Nurses Health Study) who were diagnosed with breast cancer between 1976 and 2002, and it compared what happened with those nurses who regularly took aspirin vs those who did not. What the study concluded was that aspirin was associated with a decreased risk of death from breast cancer.

Associated is the key word here. The study did not find a cause and effect relationship, i.e. that the use of aspirin played a central role in reducing the risk of death from breast cancer. It only found an association between those two events (aspirin use and decreased risk of death). As Gary Taubes so eloquently points out in his New York Times magazine article, there can be a myriad of other reasons explaining such an association. There's something, for example, called the healthy volunteer effect. The nurses who took the aspirin in this particular study could simply be healthier and more concerned with staying healthy than the nurses who didn't, which might explain why they had a lower risk of dying from breast cancer. Until a randomized clinical trial is done, we won't know for sure whether it was the aspirin that kept more of the nurses alive or something other yet unidentified reason.

As Taubes notes, long-term prospective studies like the Nurses Health Study were among the first to show what looked to be an association between hormone replacement therapy and a reduced risk of heart disease and cancer (an association, by the way, heavily promoted by Wyeth and other companies that sold such replacement therapies). And we all know where that led us: to the routine prescribing of estrogen/progestin pills for millions of menopausal and postmenopausal women, a practice that significantly increased the risk of breast cancer for many of these women. This cause and effect and the discovery that hormone replacement therapy was not even protective of heart disease was only discovered years later when the federal government finally got around to funding a randomized clinical trial. In the meantime, thousands of women taking replacement therapies developed breast cancer and many died as a result.

Now I'm not saying that taking aspirin could produce a similarly devastating effect. Not at all. I take aspirin regularly myself to ward off bad headaches and I always keep a bottle handy. What I am saying is that the media needs to do a better job of explaining to their readers the difference between studies that find an association and studies that find an actual cause and effect. The Boston Globe article referenced above did not do a very good job of parsing this important difference and as a result, did a serious disservice to its readers.

Suing doctors who use drugs as chemical straitjackets for children

It's true that the drug industry was hard hit last year with some pretty hefty fines for the illegal off-label promotion of drugs -- $1.4 billion against Eli Lilly for its off-label promotion of Zyprexa and $2.3 billion against Pfizer for doing the same with several drugs. But such fines, many say, are still considered the cost of doing business in an industry that raked in close to $300 billion in U.S. drug sales in 2008 (and more in 2009), according to IMS Health Reports.

Now, Alaska attorney Jim Gottstein has proposed a different and potentially more effective approach toward curbing the systemic over-drugging of economically disadvantaged youngsters in this country, a sad reality which I've written about here and here. According to one recent study, children covered by Medicaid are given anti-psychotics such as Zyprexa and Seroquel (which have serious side effects) four times as often as children whose parents have private insurance. These drugs are often prescribed as chemical straitjackets to control children whose parents or foster families are unable to give them the attention and parenting they need. That was certainly the case for four-year-old Rebecca Riley, who died from an overdose of psychoactive drugs prescribed by a psychiatrist at Tufts Medical Center, Kayoko Kifuji.

Gottstein has launched an initiative to sue doctors like Kifuji who blithely prescribe potent drugs that are not approved for use in children. These lawsuits, filed under a federal Qui Tam complaint, would target not only the individual doctors but the hospitals and clinics that employ them and the pharmacies that fill their prescriptions and submit them to Medicaid for reimbursement. It is Gottstein's contention that these prescriptions constitute Medicaid fraud since they are written for uses that are not medically accepted (i.e. off-label). There is legal precedent for this kind of argument. Indeed, the Department of Justice's news release announcing its $2.3 billion settlement with Pfizer says that the drug giant caused false claims to be submitted to government health care programs for uses that were not medically accepted indications. So if the feds can succeed with this kind of argument, why not individual claimants?

Gottstein is planning to discuss his medicaid fraud initiative in a lecture webinar on Feb. 24, sponsored by the International Center for the Study of Psychiatry and Psychology. So if you know of a disadvantaged child who was slapped on drugs he or she didn't need, you might want to listen in.

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!