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.

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.

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!

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.

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.

So what’s going on? A couple of things, I think. First off, there’s a reason why drugs like Paxil, Zoloft, Prozac and Lexapro are top sellers: it’s easier to expand the criteria for who might benefit from these drugs. After all, almost everyone has experienced depressive or anxious symptoms at one time or the other, so if the makers of these drugs can reach psychiatrists and persuade them to prescribe pills for such universal symptoms, we’re talking real profits here. And what better way to influence psychiatrists’ prescribing behavior than to put their most prominent colleagues — the key opinion leaders (KOLs) — on your payroll?

Secondly, as someone who came to the talk astutely noted, psychiatrists have been squeezed by managed care into the role of pill prescribers. Unlike other medical specialties, doctors in psychiatry don’t get adequately reimbursed for treating the whole patient — by doing psychotherapy, for instance — so all they can do these days is prescribe drugs. In a sense, psychiatrists are gatekeepers for the pharmaceutical industry, much like surgeons (who put in stents and other devices) are gatekeepers for the medical device industry.

Because of these trends, partnering with the drug industry has become a pervasive part of the psychiatric culture in recent years. It has become, for example, common practice for drug companies to bankroll symposia at the specialty’s top medical conferences, at which psychiatrists on their payroll extoll the benefits of their products (without disclosing their conflicts of interest). As I reported in a previous blog, Nada Stotland, the current president of the American Psychiatric Association (APA), initially took umbrage when Sen. Charles Grassley questioned the organization’s incestuous ties with the drug industry. In a memo to APA members, Stotland wrote: “Long traditions and established practices are not only being questioned, but also criticized across the board.” As I said then, it almost sounded like Stotland’s problem was with the criticism of these longstanding practices, not the practices themselves.

And that is why I was gratified to see in the Carlat Psychiatry blog, that the APA has officially decided to phase out all industry-funded symposia that take place at their annual meetings.

That’s a good first step to reform. But there is still a long way to go, as evidenced by the news reported today in The New York Times that court documents appear to indicate that Dr. Joseph Biederman promised a drug company (Johnson & Johnson) positive results about its drug Risperdal from studies that had not been undertaken. Biederman, as has already been reported, not only earned at least $1.6 million in consulting fees from drug makers from 2000 to 2007 (the bulk of which he failed to report), but also received funding from J&J for a research center at Massachusetts General Hospital, which he headed.

Like Martin Keller, the psychiatrist I expose in my book,Biederman is one more example of how science can be skewed and public interest harmed when doctors are the beneficiaries of industry largesse. Psychiatry may be particularly vulnerable to such corporate blandishments, but I would argue that it’s time for all medical specialties to take a good look at the way they do business and start healing.

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 inThe Boston Globe today, so enervated and apathetic.

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.

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.

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 this 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.