the why of it…

Posted on Friday 31 July 2015

For as much time as I’ve spent thinking about Randomized Clinical Trials in my retirement years, I never gave them a moment’s thought in two different medical careers. I didn’t really have much of an idea how drugs became approved, or how drug patents worked. As odd as that may sound, I expect that was true for the overwhelming majority of my contemporaries. In Internal Medicine, I learned about medications from textbooks rather than journal articles. In psychiatry, a person like me practicing psychotherapy doesn’t write many prescriptions, and I still relied on textbooks or review articles rather than looking at Randomized Clinical Trials. With rare exceptions, I rode on the "trailing edge" of medications, waiting until drugs were in widespread use before learning about them or prescribing them. The concept of a "pipeline" delivering a stream of new medications wasn’t even in my consciousness. I guess I thought that new medications came along when and if they were discovered. Writing this makes me feel incredibly naive – but I think that’s just the way it was. The only class of drugs I can recall actively keeping up with were the antibiotics – and that was because of those microbes’ incredible ability to become resistant.

So, in my oft told story, five years after retiring I had started volunteering some and was completely horrified at the drug cocktails the patients were taking. Then one morning, I read this over a cup of coffee:
New York Times
By GARDINER HARRIS
October 3, 2008

One of the nation’s most influential psychiatrists earned more than $2.8 million in consulting arrangements with drug makers from 2000 to 2007, failed to report at least $1.2 million of that income to his university and violated federal research rules, according to documents provided to Congressional investigators. The psychiatrist, Dr. Charles B. Nemeroff of Emory University, is the most prominent figure to date in a series of disclosures that is shaking the world of academic medicine and seems likely to force broad changes in the relationships between doctors and drug makers…
The chairman of the department I’d been a part of for then thirty-four years? arrangements with drug makers? a crook!? So that’s when I started to learn about Randomized Clinical Trials, and drug approval processes, and PHARMA, and more corruption than I would have thought possible.

Flash forward to the present. Over the intervening seven years, I’ve learned a lot about RCTs. About halfway back, I realized that the pharmaceutical companies being able to keep the raw data secret, or being able to simply not publish results they didn’t like, were an essential ingredients in the problem and I’ve spent a lot of my time involved in the fight for Data Transparency. There’s a lot more wrong – things like the alliance between academic medicine and industry, guest authors and ghost authors, the intrusions of third party carriers into medical care, etc. But frankly, I’ve spent so much time learning the ropes [with the help of some really good teachers], that it has been hard to get far enough away from the details to have an overall perspective on the big picture.

When I first read David Healy’s book, Pharmageddon [2012], I was still learning about Randomized Clinical Trials [RCTs], and I had looked at a number of them in as much depth as I could given the inaccessibility of the actual trial data. I could see how much subtle distortion there had been in the analyses and presentations in journal articles. The book added the history of RCTs and gave me a valuable perspective on how this tangled system had come into being  over the years. But there was one point that I didn’t intuitively grasp at the time. He seemed to be saying that there was a basic flaw in the RCT system over and above the distortions. At the time, It seemed to me that if the RCTs were properly conducted, properly analyzed, and properly reported that everything would be fine. I could tell he thought otherwise, but I just didn’t get the why of it on first reading. 

And I might as well add Evidence-Based Medicine and Measurement-Based Medicine in here along with RCTs. On the one hand, what is the alternative to evidence-based medicine? Wild guesses? And yet, every time I hear Evidence-Based Medicine [EBM], I wince involuntarily. The one that gets the biggest wince is Evidence-Based Psychotherapy [which means Cognitive Behavior Therapy (CBT)]. Well, I get it now – what’s wrong with RCTs – what Healy was saying. Rather than talk about the the why of it, I’ll refer you to the horse’s mouth, because Dr. Healy is in the middle of talking about it again on his blog:
If I had thought about my own experience as a physician [that introductory italicized paragraph that I started with], I might have gotten the why of it sooner. There’s a lot to say about this point, but I’m going think about it for a bit. In the meantime, you might take a look at Dr. Healy’s blogs, or even order the book if you don’t intuitively get it [like I didn’t]…
Mickey @ 4:36 PM

on the road again…

Posted on Thursday 30 July 2015

I’ve been preoccupied with another project for a month or so, and looking at my posts, it shows. I’m afraid they’re kind of just newsy as a result. But I’m free of those distractions at last, and looked forward to catching up on the current state of play. So I headed for one of my usual resources, arriving just in time to say goodbye – again…
Pharmalot
By Ed Silverman
June 30, 2015

Once again, another working week will soon draw to a close and – along with it – the latest iteration of Pharmalot. Yes, you got that right. After a brief, but rewarding stay here at The Wall Street Journal, we are taking our act to a different theater. As our bubbe used to say – the only constant is change.

Before discussing our destination, we would like to thank the many long-standing Pharmalot readers and, of course, the more recent arrivals, who make Pharmalot an exceptionally interesting and pleasurable experience. Without your feedback – whether posted online or sent privately – this gig would not be nearly as fulfilling. You know who you are.

Over the years, in fact, we have come to regard the Pharmalot community as something of a virtual garden party, where news emerges, views are swapped and insights are gained. And we are better off having absorbed the suggestions, criticisms and, of course, the juicy tips. We would be remiss, however, if we did not thank Dennis Berman and Stefanie Ilgenfritz for their helpful stewardship during our tenure here.

As for our next step, we are shifting our Pharmalot endeavors to Stat, a forthcoming website that will devote itself to tracking the fascinating ins and outs of life sciences. For those who are unaware, Stat will emerge out from under the umbrella of The Boston Globe. Further details will become available shortly. Meanwhile, you can reach us at pharmalot@gmail.com and follow the usual @pharmalot Twitter handle.

And now, the time has come to daydream about weekend plans. Have a wonderful summer and see you online soon.
In January of 2014, Pharmalot went away from being hosted on PharmaLive [gulp…], returning to the Wall Street Journal a year ago [oh how we’ve missed our Pharmalot!…]. Now it appears Ed Silverman is on the road again. This time, he’s moving to a new Boston Globe initiative called STAT:
Talking Biz News
by Chris Roush
July 30, 2015

Ed Silverman, the Wall Street Journal reporter who runs the Pharmalot blog that covers the drug industry, is joining the Boston Globe. With the Globe, Silverman will be joining the Globe’s new health care news called Stat that debuts in the fall. He’ll be taking Pharmalot with him and writing a weekly column, too.

Silverman had been laid off from the Journal last month…
Poynter.org
by Gurman Bhatia
July 17, 2015

The Boston Globe’s life sciences initiative led by former Politico executive editor Rick Berke now finally has a name. They want you to read the news urgently, hence – Stat. The name, which evokes urgency, is a reference to the medical term stat. Stat is derived from a Latin word that means “immediately.” The company acquired the domain www.statnews.com on Thursday. Berke later made it official with an announcement in a staff meeting Friday. “We take you inside science labs and hospital wards, biotech boardrooms and political backrooms,” Stat’s mission statement reads. “Stat will examine controversies, introduce power brokers and puncture hype.”

Stat’s leadership ranks include Gideon Gil, managing editor of enterprise and partnerships and Jeff DelViscio, who is senior editor of multimedia and creative. Gil was the former health and science editor of The Globe and DelViscio was a Web producer on the science and environment desk of The New York Times. While Stat is still hush-hush about who it has hired, Berke said the reporters’ names will be recognizable once they’re disclosed.

The company is also looking to hire for at least six senior positions for the Stat multimedia team. DelViscio’s ambition is to incorporate video, photo and interactive content within Stat’s storytelling stream. These jobs include a video editor, an interactives editor and a social media editor. DelViscio aims at integrating a full-stack multimedia team in the newsroom, drawing on its expertise from the very beginning of the storytelling process. “It is also a question of what constitutes a multimedia element,” DelViscio said. “Often something as simple as a GIF can have a little impact on the story, in sort of a teaching mentality. There is a visual quality to the life sciences that is often not utilized.”

The initiative can be expected to feature both short and longform video, be it shareable short clips focused towards social media, or mini-documentary style footage. With the interactives editor, the aim is to explore data visualization and the potential on that side right from the start. “At its core, Stat is supposed to be a watchdog,” DelViscio said. “There is so much money in the system and no people are looking at it consistently. That is the huge part of our mission. Although we are at a nascent stage right now, the possibilities also include searchable databases for public health information that aren’t otherwise readily accessible, something places like ProPublica and Center for Public Integrity do so well.”

Although the website doesn’t have a launch date yet, the team would start publishing Stat-branded content on The Boston Globe in late summer. Staffers would work towards building a national audience with that and promotion on social media. According to Berke, Stat has recruited people in Boston, New York, Washington, D.C. and the West Coast. “This will eventually be of national scope,” he said. What used to be a formal-looking publisher suite on the third floor of the Boston Globe building is now being revamped for Stat. The launch date is still several months away, but as the team works on creating an office space and reporters come in, Berke says it already has the feel of an excellent newsroom.
It actually sounds like a good move for his blog. What’s important is that Ed doesn’t go away. He’s been at it for fifteen years, and obviously has a network of information sources that almost guarantees that if something happens, he’ll be telling us about it pronto. So, in his absence, here’s a predictable offering [GSK’s bribery program is apparently up to speed]:
Reuters
By Ben Hirschler
Jul 29, 2015

Drugmaker GlaxoSmithKline, which was fined a record 3 billion yuan ($483 million) for corruption in China last year and is examining possible staff misconduct elsewhere, faces new allegations of bribery in Romania.

GSK confirmed it was looking into the latest claims of improper payments set out in a whistleblower’s email sent to its top management on Monday. A copy of the email was seen by Reuters.

The company is already probing alleged bribery in Poland, the United Arab Emirates, Lebanon, Jordan, Syria and Iraq
Mickey @ 8:26 PM

our better exports…

Posted on Tuesday 28 July 2015

Pharmalot: WSJ

U.K. doctors and public health officials may be required to report any financial ties to drug makers under plans that are being considered by U.K. government officials, The Telegraph reports. The move comes after the paper ran an undercover investigation showing how National Health Service staffers were allegedly paid by drug makers that lobby health care providers to use specific medicines.

Some staff, who say they worked as industry consultants, charged more than $23,000 to organize so-called ‘advisory board’ meetings for drug makers and many of the meetings took place in five-star hotels in other countries, according to the paper. Some attendees told the Telegraph they were taken to “flashy” restaurants and paid large sums while considering whether to “switch” drugs.

NHS staffers who participated in the advisory boards argue their involvement helps them make “best use” of government money by analyzing drugs and providing expert advice, the paper wrote. Meanwhile, a dozen NHS staffers who attended one meeting in Germany told the paper they reported the trip and payments from a drug maker to their employers, and were not involved in subsequent decisions to adopt the drugs that were discussed. Each was paid nearly $800 a day.

An NHS England spokesman tells the paper “these are extremely serious allegations so we have immediately directed NHS Protect [an investigative agency] to launch a full investigation of each and every case identified by this press report.” He adds the U.K. may want to pass a law requiring “full disclosure of any payments” made by companies to health professionals or NHS employees…
The National Health Service in England is a dramatically different species from the system of care in the US, but if you take a look at the article in The Telegraph, you’ll be struck by how familiar this story sounds – attesting to the universality of the adage, "money talks."

Personally, I find the rate at which these things are being exposed these days encouraging. There’s a momentum developing to bring the the widespread corruption in pharmaceutical clinical trials, marketing, and pricing out into the bright light of public scrutiny. I’m always amazed when such things finally happen – when some cause that seems like it will remain lost forever reaches a kindling point and bursts into the flames it has long deserved. In the UK, physicians in the NHS appear to be salaried, though after three years living there, my understanding of how all that worked was no greater that of any of their other great British enigmas like Cricket or the London Times’ puzzles. While our medical care systems differ, and the pharmaceutical games seem to be played in a different way – the impact and the rationalizations are the same on both sides of the pond:
NHS staffers who participated in the advisory boards argue their involvement helps them make “best use” of government money by analyzing drugs and providing expert advice…
From The Telegraph article:
Last night MPs on the Commons health select committee called on the NHS to investigate whether the practice was “widespread”. NHS England and Mr Hunt are looking at the merits of introducing a so-called Sunshine Act, akin to US legislation introduced in 2010 to shed light on financial relationships between pharmaceutical companies and health professionals.

An NHS England spokesman said: “These are extremely serious allegations so we have immediately directed NHS Protect to launch a full investigation of each and every case identified by this press report. “These allegations also raise the question of whether this country should now legislate for a so-called Sunshine Act, requiring full disclosure of any payments made by a pharmaceutical or device company to a health professional or NHS employee”…
The Sunshine Act would actually be one of our better exports…
Mickey @ 7:53 AM

down-right unAmerican…

Posted on Sunday 26 July 2015

There are certain situations in which Free Market Capitalism simply doesn’t work. We’ve long recognized that in how we deal with things like monopolies, insider trading, etc. The Free Market works when it operates on supply/demand and competition dynamics. The way our drug patent laws have evolved, we have literally created a system that generates monopolies. It’s down-right unAmerican…
Center for Economic and Policy Research
Beat the Press blog
by Dean Baker
July 23, 2015

This NYT article [below] on various state bills calling for drug companies to reveal their spending on research for high-priced drugs might have been a good place to mention that we have alternatives to patent financing for prescription drug research. For example, the federal government already spends more than $30 billion a year on research through the National Institutes of Health. If this sum were doubled or tripled, it could likely replace the patent supported research now being done by the drug industry.

And, since the research was all paid for upfront, the great new drugs developed for cancer, AIDS, and other diseases could all be sold as generics. Then we would not face tough decisions about whether to pay for expensive drugs for people who need them. We also would have eliminated the incentive for drug companies to mislead the public about the safety and effectiveness of their drugs.


[remember this?

New York Times
By ANDREW POLLACK
JULY 23, 2015

As complaints grow about exorbitant drug prices, pharmaceutical companies are coming under pressure to disclose the development costs and profits of those medicines and the rationale for charging what they do. So-called pharmaceutical cost transparency bills have been introduced in at least six state legislatures in the last year, aiming to make drug companies justify their prices, which are often attributed to high research and development costs.

“If a prescription drug demands an outrageous price tag, the public, insurers and federal, state and local governments should have access to the information that supposedly justifies the cost,” says the preamble of a bill introduced in the New York State Senate in May. In an article being published Thursday, more than 100 prominent oncologists called for support of a grass-roots movement to stem the rapid increases of prices of cancer drugs, including by letting Medicare negotiate prices with pharmaceutical companies and letting patients import less expensive medicines from Canada.

“There is no relief in sight because drug companies keep challenging the market with even higher prices,” the doctors wrote in the journal Mayo Clinic Proceedings. “This raises the question of whether current pricing of cancer drugs is based on reasonable expectation of return on investment or whether it is based on what prices the market can bear.”

Pressure is mounting from elsewhere as well. The top Republican and Democrat on the United States Senate Finance Committee last year demanded detailed cost data from Gilead Sciences, whose hep atitis C drugs, which cost $1,000 a pill or more, have strained the budgets of state and federal health programs. The U.A.W. Retiree Medical Benefits Trust tried to make Gilead, Vertex Pharmaceuticals, Celgene and other companies report to their shareholders more about how they set prices and the risks to their businesses from resistance to high drug prices…
The place where our already weak system is at its weakest is when the first drug in a new class is introduced – like Gilead’s Solvadi®. It’s a monopoly with a customer base of desperate and/or dying people.

We’re going to have to do something about this – and soon. The only question is do we tweak the system like we’ve done over and over? or do we change it altogether like the blog above suggests? If we tweak it, we can set our clocks for how long it will take industry to find a loophole or two. To quote the famous, "How long? Not long!" The other thing to take into account is that the pharmaceutical and medical device industry has one of the most powerful lobbies in Washington, so any changes will take forever and will likely end up with loopholes already built in.

I’m neither a communist nor even much of a socialist. Our silly greedy capitalism happens to be the best of the bad options available. But in the area of medical care, I’ve become a social democrat. And the Social Democracies of the world have already figured out that some form of socialized medicine is the only solution to many other of the problems that plague medicine these days.

Right now, allowing our Free Market economy and patent monopolies is tantamount to letting industry fleece a captive audience – and we can’t tolerate that much longer. I suspect that the reason it’s such a problem right now might be that PHARMA sees the writing on the wall and is having its last hurrah [at least that’s what I hope]…
Mickey @ 6:06 PM

«my·psychiatrist/my·therapist»…

Posted on Thursday 23 July 2015

The Chronicle of Higher Learning
by Tom Bartlett
July 21, 2015

A former official at the American Psychological Association who was implicated in the controversy over the organization’s support for torture has resigned as provost and senior vice president for academic affairs at Alliant International University. The resignation of Russ Newman comes in the wake of an independent investigation, commissioned by the APA, that found that officials there coordinated with the Department of Defense to make sure psychologists could participate in often-brutal interrogations without running afoul of the association’s ethical guidelines.

The 542-page report that resulted from that investigation, carried out by David H. Hoffman, a former federal prosecutor, took Mr. Newman to task for altering wording put out by the APA in order to comport with the government’s preferences. The report also pointed out Mr. Newman’s clear conflict of interest: His wife, Lt. Col. Debra Dunivin, was at one time the lead psychologist for interrogations at the military’s base at Guantánamo Bay, Cuba. According to the report, Mr. Newman, who served as chief of the APA’s practice directorate, pushed to exclude the negative-sounding word “coercive” from a description of techniques used to extract information from detainees. When interviewed by investigators for Mr. Hoffman, Mr. Newman said he didn’t remember arguing to remove that word. But he acknowledged that Colonel Dunivin and Col. Louie Morgan Banks, then the chief psychologist with the Army Special Operations Command, wouldn’t like the word “since it suggested from the outset that interrogations per se were problematic”…

The resignation was welcome news to longtime critics of the APA’s complicity in the government’s torture program. “Alliant’s apparent action related to Russ Newman should be a sign for other academic institutions that are employing in any role other individuals implicated in this scandal that they must also consider similar action immediately,” said Nathaniel Raymond, a former director of the Campaign Against Torture at Physicians for Human Rights. “At its heart, this scandal is about the violation of the core principles of science, research, and what it means to be a scholar”.
 
So far the APA has announced that three top officials will leave the organization as a result of the Hoffman review, including the association’s chief executive officer, Norman Anderson. Critics have called for more employees to be shown the door, and also for a number of psy chologists who have served in unpaid leadership roles to be banned from governance…
I’m not sure that a Salem Witch Trial mentality is what’s needed in this particular scandal. That a number of people at the top rung of the American Psychological Association were either actively involved or complicit in keeping the Bush/Cheney torture program going with the aid of psychologists is unquestioned. People who pay attention to such matters have known that for a very long time. That the psychologists on the ground, Jim Mitchell and Bruce Jessen, were misguided entrepreneurs on the take seems fairly obvious. And that Col. Louie Morgan Banks, then the chief psychologist with the Army Special Operations Command, had lost the meaning of his professional degree is equally clear. What is less apparent is why the upper echelon of the  American Psychological Association itself was involved in this tawdry tale – and stayed involved for such a protracted period.

Unlike the Bush/Cheney Torture Lawyers [Jay Bybee, John Yoo, Doug Feith, etc], they were not part of the NeoConservative Complex of the American Enterprise Institute, the Project for the New American Century, the Federalist Society, etc. And there’s nothing about the American Psychological Association that would suggest any particular ideological alliance with that administration’s grand plan. The unstated objective of the torture program had been to extract some excuse for invading Iraq, and by the time the APA became involved [2005 – Psychological Ethics and National Security (PENS)] they were certifying what had already happened. And further, the public face of the APA was anti-torture, while privately legitimizing what was actually going on. So it seems likely that the Hoffman Report‘s analysis of motive was on the mark:
The very substantial benefits APA obtained from DoD help explain APA’s motive to please DoD. and show that APA likely had an organizational conflict of interest, which it needed to take steps to guard against. DoD is one of the largest employers of psychologists and provides many millions of dollars in grants or contracts for psychologists around the country. The history of DoD providing critical assistance to the advancement and growth of psychology as a profession is well documented, and includes DoD’s creation of a prescription-privileges "demonstration project" in which psychologists were certified to prescribe psychiatric drugs within DoD after going through a two-year training course…. And by the time of the PENS Task Force, contemporaneous internal discussions show that improving APA’s already strong relationship with DoD was a clear priority for officials working on the PENS Task Force.  In addition, at the time of the task force’s creation, DoD was in the midst of developing policy about how psychologists and psychiatrists could participate in interrogations and other intelligence-collection activities. APA wanted to positively influence DoD regarding this policy so that psychologists would be included to the maximum degree possible, and psychologists would not lose the lead role to psychiatrists…
While I don’t doubt that the overwhelming sentiment of the APA membership was and is opposed to Torture and Human Rights abuse, I’m not sure this comment in the APA’s Press Release is the whole story – a slip-up:
“Our internal checks and balances failed to detect the collusion, or properly acknowledge a significant conflict of interest, nor did they provide meaningful field guidance for psychologists,” said Dr. Nadine Kaslow, chair of the Independent Review’s Special Committee. “The organization’s intent was not to enable abusive interrogation techniques or contribute to violations of human rights, but that may have been the result…
It seems more likely to me that it’s an index of the APA’s zeal in battling for a greater share of the healthcare dollar. The American Psychiatric Association‘s DSM-III and later revisions have been publically villified by professional psychology associations, yet that code book gave psychologists access to medical insurance at a previously unparalleled level. And while the various psychology organizations have carried the anti-psychopharmacology banner, they have continued to fight for prescription privileges for themselves, and are, far and away, the major referral source to the "med check" psychiatrists they also claim to decry – actually fueling the over-medication epidemic as the driving half of the «my·psychiatrist/my·therapist» symbiosis that has become standard fare in clinical office practice.

the pot calling the kettle blackSo rather that approach this scandal as a search for a few "bad apples," the APA would do well to borrow the watchword of Cosgrove’s and Whitaker’s new book, Psychiatry Under the Influence, and take a long look at the "bad barrel" aspect of their own APA. This was a massive ethical infraction, originating in the upper levels of the APA with those in charge of setting the profession’s ethical standards, one that involved two APA Presidents. This hardly qualifies the American Psychological Association for any moral high ground in the guild wars that have plagued the mental health specialties for decades. Institutional Corruption? Sure sounds that way to me…
Mickey @ 8:25 PM

out of my league…

Posted on Thursday 23 July 2015

Pharmalot
By Ed Silverman
07/22/2015

The investors, which collectively manage about $3.8 trillion, plan to meet with drug makers in which they invest to ensure that trials are registered and results are reported, according to Sile Lane, campaign director at Sense About Science, a non-profit that launched the AllTrials campaign. In an unprecedented move, a group of 85 asset managers and pension funds is teaming with a U.K. non-profit campaign to pressure drug makers to disclose clinical trial data. The effort is likely to escalate a closely watched battle that has increasingly placed the pharmaceutical industry on the defensive as researchers and regulators call for increased disclosure in the U.K. to agitate for greater trial data disclosure.

Drug makers will be asked to retrospectively register past and ongoing clinical trials, and register all future trials before they begin; publish methods and full results of all trials, include information on adverse events; post objective summary results within one year of completing a trial, and support efforts to provide independent researchers access to anonymized individual patient data, according to a statement. “We believe this is going to be game changing,” Lane tells us. To facilitate the process, the AllTrials campaign is conducting an audit of disclosure policies for the 50 largest drug makers and will score each one. The results are expected to be published in September. “This will become a tool readily available to investors,” she says.

The move comes amid growing clamor from academics and consumer groups to press drug and device makers to release trial data. At issue is the ability for researchers to independently verify study results and, consequently, improve patient treatments that can lead to better health and lower costs. Concerns have been heightened following various safety scandals that revealed trial data for some products was never fully published or disclosed. In recent months, regulators in the U.S. and Europe have responded by releasing new rules designed to widen access. And several drug makers, in varying degrees, have taken steps to release trial data.

For instance, GlaxoSmithKline created a website where data requests are made to 10 different drug makers, Johnson & Johnson is working with Yale University to provide access to data, and Bristol-Myers Squibb will grant access to academics as part of a collaboration with Duke University. AstraZeneca formed a panel to review requests for data, although questions were raised about its independence. But critics say such efforts are few and far between. Helena Vines Fiestas, who heads sustainability research at BNP Paribas, says there is increasing concern that a lack of transparency about medicines – past and present – is having a negative impact on stock valuations. BNP got involved as an outgrowth of a broader effort to rate and benchmark companies in different industry sectors.

For instance, she says fines paid by 21 drug makers for marketing malfeasance between 2007 and mid-2015 was $40 billion, and 43% was directly related to minimizing side effects that were identified during clinical trials but not properly reported. Her team also queried analysts and discovered that an average of about 30% of drug company stock valuations directly relate to results of Phase III clinical trials.

“The lack of complete and unbiased information can mislead decisions made not only regulators and doctors, but also investors,” Fiestas tells us. “We think if the companies become more transparent and take the issue around auditing and reports more seriously that the decisions made by analysts can be more closely aligned with reality”…
So if appeals to common sense and common decency move too slowly, where else to turn but to big money. It makes an odd kind of sense, but who’d have thought it? I suppose the next question is obvious, "But will the backing of the representatives of investors’ money bring the same corrupting influence that caused the problem in the first place?" Answering that is way out of my league, that’s one thing I’m sure of…
Mickey @ 10:33 AM

still around…

Posted on Wednesday 22 July 2015

New York Times
by Richard A. Friedman
Contributing Op-Ed Writer
July 17, 2015

AMERICAN psychiatry is facing a quandary: Despite a vast investment in basic neuroscience research and its rich intellectual promise, we have little to show for it on the treatment front. With few exceptions, every major class of current psychotropic drugs — antidepressants, antipsychotics, anti-anxiety medications — basically targets the same receptors and neurotransmitters in the brain as did their precursors, which were developed in the 1950s and 1960s. Sure, the newer drugs are generally safer and more tolerable than the older ones, but they are no more effective…

At the same time, judging from research funding priorities, it seems that leaders in my field are turning their backs on psychotherapy and psychotherapy research. In 2015, 10 percent of the overall National Institute of Mental Health research funding has been allocated to clinical trials research, of which slightly more than half — a mere 5.4 percent of the whole research allotment — goes to psychotherapy clinical trials research.

As a psychiatrist and psychopharmacologist who loves neuroscience, I find this trend very disturbing. First, psychotherapy has been shown in scores of well-controlled clinical trials to be as effective as psychotropic medication for very common psychiatric illnesses like major depression and anxiety disorders; second, a majority of Americans clearly prefer psychotherapy to taking medication…

Finally, many of our patients have histories of trauma, sexual abuse, the stress of poverty or deprivation. There is obviously no quick biological fix for these complex problems. Still, there has been a steady decline in the number of Americans receiving psychotherapy along with a concomitant increase in the use of psychotropic medication in those who are treated in the outpatient setting. These trends are most likely driven by many factors, including cost and the limited availability that most Americans have to mental health practitioners. It is clearly cheaper and faster to give a pill than deliver psychotherapy…

More fundamentally, the fact that all feelings, thoughts and behavior require brain activity to happen does not mean that the only or best way to change — or understand — them is with medicine. We know, for instance, that not all psychiatric disorders can be adequately treated with biological therapy. Personality disorders, like borderline and narcissistic personality disorders, which are common and can cause impairment and suffering comparable to that of severe depression, are generally poorly responsive to psychotropic drugs, but are very treatable with various types of psychotherapy…
A couple of months ago, I had me something of a rant. It was long overdue for me:
Robert Whitaker got it started in an interview with Bruce Levine:
Truthout
by Bruce Levine
March 5, 2014

Bruce Levine’s Question: Is it really possible for psychiatry to reform in any meaningful way given their complete embrace of the "medical model of mental illness," their idea that emotional and behavioral problems are caused by a bio-chemical defect of some type? Can they really reform when their profession as a financial enterprise rests on drug prescribing, electroshock and other bio-chemical-electrical treatments? Can psychiatry do anything but pay lip service to a more holistic/integrative view that includes psychological, spiritual, social, cultural and political realities?

Robert Whitaker’s Answer: I think we have to appreciate this fact: any medical specialty has guild interests, meaning that it needs to protect the market value of its treatments. If it is going to abandon one form of treatment, it needs to be able to replace it with another. It can’t change if there is no replacement in the offing. When the APA published DSM-III, it basically ceded talk therapy to psychologists, counselors, social workers and so forth…
It’s not Bob’s fault. He didn’t mean to set me off. He didn’t know that there were a lot of psychiatrists who didn’t sign the mythic Talk Therapy Cession Decree of 1980, who didn’t sign up for the ‘complete embrace of the "medical model of mental illness," their idea that emotional and behavioral problems are caused by a bio-chemical defect of some type’, and who had reluctantly left our academic positions, and just continued doing the psychotherapy we had learned to do. And he didn’t know we didn’t need any advice about how to repurpose ourselves [because we didn’t repurpose ourselves back in 1980]. Said Robert Whitaker:
… So I don’t believe it will be possible for psychiatry to change unless it identifies a new function that would be marketable, so to speak. Psychiatry needs to identify a change that would be consistent with its interests as a guild. The one faint possibility I see – and this may seem counterintuitive – is for psychiatry to become the profession that provides a critical view of psychiatric drugs. Family doctors do most of the prescribing of psychiatric drugs today, without any real sense of their risks and benefits, and so psychiatrists could stake out a role as being the experts who know how to use the drugs in a very selective, cautious manner, and the experts who know how to incorporate such drug treatment into a holistic, integrated form of care. If the public sees the drugs as quite problematic, as medications that can serve a purpose – but only if prescribed in a very nuanced way – then it will want to turn to physicians who understand well the problems with the drugs and their limitations. That is what I think must happen for psychiatry to change. Psychiatry must see a financial benefit from a proposed change, one consistent with guild interests.
No thanks. Life without a guild is preferable. Of course there wasn’t really any Talk Therapy Cession Decree of 1980. I was just being sarcastic. But that dichotomy actually did arise in those days – the psychotherapy versus the medical model thinking Levine is talking about. Pick one or the other [how about both? or maybe the right one for the patient at hand?]. Jeffrey Lieberman just wrote a book about the horrors of the pre-1980 psychiatry he saved you from – caricaturizing psychiatrists as Freud Clones who had left real medicine for a fairy tale world, charlatans all. And a million times I’ve heard that an interest in psychotherapy doesn’t require a medical education – a wasted four years. But actually, I can’t personally imagine any better preparation than spending one’s life amid and among the suffering people that physicians attend daily. That’s what got me interested in the first place and where I learned much of what I know. And I certainly didn’t shed my medical identity, or for that matter my psychiatric identity. I prescribe medications when I think they are appropriate and might help.

But I’ll stop my rant. This blog isn’t about that old story. This blog is about honesty in science. But I guess it has been so long since someone acknowledged that psychiatrists are physicians who care for the sick, bringing to bear whatever might help – whether biologic, psychologic, sociologic, humanistic, cybernetic, etc. And that for many of our patients, psychotherapy of the kind I learned, practiced, and still practice is exactly what the doctor ordered. As for Whitaker’s thoughts about searching for a marketable skill or some new function. I guess I already have one, so I don’t need to ponder a Collaborative Care environment where I’m asked to be an expert consultant medicating patients I’ve never seen [which to me smells like malpractice].

What I came to say is that I appreciate Dr. Friedman noticing that we’re still around and that what we do fills an important need in the cosmos of care of the sick…
Mickey @ 9:54 PM

wandering, wondering, wunderink…

Posted on Wednesday 22 July 2015

If you read the blogs, you’re likely familiar with the Wunderink Clinical Trial [Recovery in Remitted First-Episode Psychosis at 7 Years of Follow-up of an Early Dose Reduction/Discontinuation or Maintenance Treatment Strategy]. It has been reviewed by many including NIMH Director Tom Insel [Antipsychotics: Taking the Long View], MedScape [Antipsychotics in First-Episode Psychosis: Less Is More], Sandra Steingard [A psychiatrist thinks some patients are better off without antipsychotic drugs], me [persistence…], and many others [see well worth reading…]. These three editorials in BJPsych Advances offer somewhat differing views on this study and its meanings:
  • Long-term effects of antipsychotics
    Joanna Moncrieff
    BJPsych Advances March 2015, 78-79. DOI: 10.1192/apt.bp.114.012591
  • Early schizophrenia: skilful management of medication
    John Cookson
    BJPsych Advances March 2015, 80-84. DOI: 10.1192/apt.bp.114.013359
  • Patients need reliable facts and figures about antipsychotics
    Stephen M. Lawrie
    BJPsych Advances March 2015, 85-87. DOI: 10.1192/apt.bp.114.013375
If I put the titles of these papers in Google®, and select the BJPA link, I get full text. But if I try to use the link, it takes me to their pay wall. I suggest you try my title·into·Google® method. The articles are short and make an interesting read as a trio.

Dr. Joanna Moncrieff is the co-chairman of the Critical Psychiatry Network, a foreign correspondant on Mad in America, and the author of The Bitterest Pills, The Myth of the Chemical Cure, and A Straight Talking Introduction to Psychiatric Drugs. Her writings are heavily referenced in the British Psychological Society‘s Report, Understanding Psychosis and Schizophrenia in the section on Medication. She regularly writes of her concern that long term use of antipsychotic medication can cause brain damage [see Antipsychotics and brain shrinkage: an update], a point she also emphasized in this editorial. After summarizing the results of the Wunderlink Trial, she concludes:
Antipsychotics can effectively reduce acute psychotic symptoms in many people, but evidence on the benefits of long-term treatment is more equivocal, and recent evidence underlines their potentially negative effect on brain volume, alongside other serious physical complications. NICE [2014] recommends more research into long-term outcomes of antipsychotic discontinuation. In the meantime, recent evidence suggests that a trial of supported antipsychotic discontinuation should be considered as one option in the routine treatment of people with psychotic conditions. This strategy may help some people to improve their functioning and quality of life, and reduce the risks to their physical health.
Dr.. Stephen Lawrie is a Neuro-Imaging researcher at thr University of Edinburgh who has done some industry-funded research. After reviewing the known risk/benefit profile of the antipsychotics and countering some of Dr. Moncrieff’s points, he presented a close reading of the Wunderink study, noting among other things that…
Only about 20% of those in the dose reduction/discontinuation group actually managed to discontinue their antipsychotic medication at all. There were no actual differences between the dose reduction/discontinuation and maintenance treatment groups in social function or quality of life, and the mean dose of antipsychotic over the previous 2 years was only about 1.5 mg different in haloperidol equivalents [~2 mg v. ~3.5 mg daily]. In the final analysis, only 8 individuals in the dose reduction/discontinuation group and 3 in the maintenance treatment group had sustained antipsychotic discontinuation during the 7-year follow-up.
He goes on to conclude…
What it actually shows is that antipsychotic discontinuation is rarely feasible and that slow tapering of the dose down to an average of about 2 mg haloperidol equivalents is associated with some measures of functional improvement. Indeed, the results are entirely in keeping with treatment guidelines which suggest that antipsychotic medication should be maintained for 2 years and then phased withdrawal attempted. What the trial suggests we really need is not new strategies for managing antipsychotic treatment after a first episode, but a way of identifying the small number of patients who can manage without antipsychotics.
Dr. John Cookson is a Consultant Psychiatrist at the The Royal London Hospital. He begins with…
The enthusiastic embrace by Moncrieff of Wunderink et al’s 7-year follow-up of a 2-year randomised controlled trial of treatment for first-episode psychosis is understandable. But any eagerness to dismiss the usefulness of long-term treatment with antipsychotics is premature. The results are counter-intuitive and seem to have puzzled the authors themselves and to invite speculative explanations.
He reviews the history of the studies supporting long term maintenance and Wunderink’s paper. I found this article’s logic harder to follow and summarize and leave it for  you to reach your own conclusions. He ends with…
The main finding of the Wunderink et al study is that after 7 years, 30 people from the original 128 with a first episode of non-affective psychosis were identified as being in recovery, with symptomatic and functional remission; of these, 25 were on no medication at that time. This group represented about half of the patients eligible for the study. The findings tell us that skilful management of medication is important in helping patients to achieve more complete remission of functional impairments after a diagnosis of schizophrenia-like illness.

It remains advisable for patients with a first episode of schizophrenia or other non-affective psychosis to continue on medication for at least 1 year after remission of the episode and/or discharge from hospital. A proportion of patients who remain well 1 year later may not require further antipsychotic medication, but there is no reliable way of identifying these, other than by a gradual discontinuation of medication. Those with a longer initial DUI or with comorbid substance misuse are less likely to remain well for long without medication. For those requiring medication to remain well, adherence is important; the medication is not effective unless it is taken, and side-effects must be recognised. The management of dosage, choice of antipsychotic and achievement of adherence require close clinician–patient relationships with skilful clinical management, as does advice to the families and carers. 
Wunderink is one of those studies that gets discussed and analyzed over and over – something of a Rorschach ink·blot for the pre-existing opinion of the reader. Those who  are opposed to maintenance antipsychotic treatment point to the greater functional recovery in the group of patients in the reduction/discontinuation group at seven years. Those who support maintenance antipsychotic treatment note that very few patients could actually get off of antipsychotics entirely in either group of this study. The patients in the reduction/discontinuation group were on a lower mean dose in the years following the original 18 month study, suggesting that the improved functional recovery might be related to the lower dosing regimens.

I must say that my own limited and anecdotal experience mirrors these results somewhat. I left training with the attitude that lower·dose or better-yet, medication·free, was the laudable goal, but wasn’t altogether able to bring it off. Getting people medication·free was invariable followed by relapse, and I settled for the lower·dose route unless directed otherwise by the patient’s choice. Those selecting medication·free either restarted medication or relapsed and ended up on a higher dose. In theory, perhaps, relapse is not necessarily a bad thing, but in practice, it was a major disruption in the interpersonal and vocational lives of the patients I followed. A couple sustained medication·free·ness, but it was way late in the game.

Wunderink’s study raises questions, but doesn’t necessarily answer them. It’s partially the reason I found that section [Section 12 on Medication] of the British Psychological Society‘s Report, Understanding Psychosis and Schizophrenia and Dr. Moncrieff’s editorial as more polemic than science-based. While I might share their sentiment, we don’t treat patients by sentiment. And one thing about Wunderink’s cohort – they were patients who came for follow-up unlike most other studies. By my reckoning, the studies that report on psychotic patients continuing on medications invariably show that most don’t [eg CATIE], in spite of what the various guidelines recommend. So while so many papers end with a call for further research, Wunderink’s final words are, in this case, mandatory in my book to adequately anchor any conclusions from this trial:
Of course, only one study indicating advantages of a DR strategy in patients with remitted FEP is not enough evidence in such an important matter. However, these results merit replication by other research groups.
Mickey @ 7:02 AM

a snail’s pace…

Posted on Monday 20 July 2015

First there was the editorial and a three  part series in the New England Journal of Medicine that advocated dropping their ban on authors with conflicts of interest writing editorials or review articles…
I  obviously didn’t care too much for that idea, and I was in good company. These posts of mine catalog many other dissenting voices…
Now we have other versions. This from the Canadian Medical Association Journal suggesting that only industry can afford to support innovation…
Part I of a series on conflicts of interest in medicine
Canadian Medical Association Journal
by Roger Collier
July 16, 2015

… In an ideal world, there would perhaps be no need for a conversation about conflicts of interest in medical research. Academic researchers with good ideas for new medications would have all the funding and resources they need to manufacture compounds and launch large-scale clinical trials without support from industry. That, however, is not reality. Today, like it or not, the expensive and risky process of getting new medications into the hands of patients requires resources unavailable in academic laboratories. "We are in the business of making patients better," said Drazen, a pulmonologist. "When you develop something and want to take it that last step, from a general idea to making a difference for patients, you really need a way to work with commercial entities"…

"The problem is that people are taking the marketing arm, where doctors are selling a drug, and they conflate it with the discovery arm, where we want to encourage interaction," said Drazen. "We need to figure out a way for researchers to work with commercial entities that won’t paint them as having sold their soul to the devil."

If negative attitudes about all financial ties between doctors and industry don’t change, they will continue to undermine innovation in medicine, according to Dr. Thomas Stossel, author of the book Pharmaphobia. Over the course of his lengthy career, the practice of medicine has improved tremendously, said Stossel. He attributes that improvement to better tools, most of which came from the medical-products industry. "We get that stuff at great difficulty and at great expense," said Stossel, director of translational medicine at Brigham and Women’s Hospital in Boston, Massachusetts. "With respect to innovation, intelligent, educated people — even doctors — have no idea. They think this stuff comes from Santa Claus"…

Next: Part II: The costs of vilifying pharma
Here’s a useful commentary that sees full disclosure of conflicts as key and also proposes that we find alternative ways of funding science…
Health Affairs Blog
by Christopher Robertson
July 16, 2015

In 1984, the New England Journal of Medicine [NEJM] began requiring authors of research papers to disclose financial relationships with the pharmaceutical or device industry. The policy was controversial then, and even a decade later still faced criticism, with noted scholars charging that it “thwarts the principle that a work should be judged solely on its merits.”

Though every respectable scientific journal has now adopted such a policy, this critical view has received new attention in a three-part series on conflicts of interest appearing in NEJM, again asking whether disclosures “foster an ad hominem approach to evaluating science.” Three former NEJM editors fired back in the pages of The BMJ, calling this a “seriously flawed and inflammatory attack” on a longstanding consensus about conflicts of interest. Who is right?

It is tempting to answer with heated rhetoric about “industry greed” and the “taint” of industry money, or with a romantic account of the “life-saving innovations” funded by industry. But both arguments miss the point. The question should be simply whether disclosures will support physician decision-making and ultimately enhance patient health outcomes. And more fundamentally, whether there are better models for funding science…
I particularly liked this framing of a dichotomy, because most commentaries fall in one or the other of these two categories: "It is tempting to answer with heated rhetoric about “industry greed” and the “taint” of industry money, or with a romantic account of the “life-saving innovations” funded by industry. But both arguments miss the point." I guess I’m usually in the heated rhetoric about “industry greed” camp. It would be hard to be a psychiatrist and end up anywhere else. To quote Richard Friedman [in the recent New York Times Op-Ed, Psychiatry’s Identity Crisis]:
"With few exceptions, every major class of current psychotropic drugs — antidepressants, antipsychotics, anti-anxiety medications — basically targets the same receptors and neurotransmitters in the brain as did their precursors, which were developed in the 1950s and 1960s."
I don’t think many [if any] of the post-50s-60s drugs were developed by academics. They came to us from the labs of the pharmaceutical industry. But it doesn’t seem reasonable to use the word "innovation" to describe them. In fact, we usually call them the "me too" drugs. And the academic professors who refer to themselves as "researchers" are in fact doctors who rarely [if ever] see a lab bench and mainly involve themselves with clinical trials [often signing on to articles about trials conducted by Contract Research Organizations, analyzed by the Pharmaceutical Company Statisticians, and written by the Pharmaceutical Company’s hired Medical Writing Firms AKA ghost-writers]. At least in psychiatry, the academics have occupied themselves talking about drugs developed by others, often up to their necks in Conflicts of Interest themselves.

So I, for one think that the New England Journal’s argument is not applicable to psychiatry, and probably equally flawed in other specialties. If there are no "untainted" academics to write editorials and review articles, then I’d just as soon we do without editorials and review articles. In fact, the point being made in the CMAJ article above that only Pharmaceutical Companies have the resources to do drug research is an even stronger argument to keep academics that write editorials and reviews free of industry connections. Who else is going to counter the barrage of hype that comes when each new drug becomes available?

Truth-be-told, the field of Medicine moves much more slowly than you might imagine – at a snail’s pace. Left to my own devices, there are only two medications that I would regularly prescribe that weren’t available to me on the day I finished my psychiatric residency in 1977 – one SSRI and one Atypical Antipsychotic. That was forty years ago. And my patients and I could get by if they weren’t around. They’re just a little gentler and better tolerated than the older drugs. But, if anything, they’re also just a little less effective. Both are now available as generics.
Mickey @ 11:38 PM

and guild wars…

Posted on Friday 17 July 2015

In case you’re behind on the APA/Torture story, here are a few catch-up links. Also see Rob Purssey’s comment to the last post [UPDATE: There’s a more readable version here]:
I spent a lot of time in the period between 2005 and 2008 blogging about the misadventures of the Bush Administration and learned more than I ever wanted to know about the CIA/DoD Torture Program. Last night, I looked over some of those posts and felt the same fire in the belly I felt when I wrote them. I reread about the American Enterprise Institute, the Project for the New American Century, the Federalist Society, the Niger Forgeries, Valerie Plame, The Torture Memos, American Dominion, the Unitary Executive, etc. They wanted us to opportunize on the fall of the Communist Bloc and take over as the sole super-power. And they used the tragedy of 911 to jump·start their New American Century by invading Iraq. It was painful to read all of that again and I  stopped when I began to feel nauseated.

But there was one piece in all of what I had forgotten about those crazy times that relates to the present point. Remember that the Bybee/Yoo Torture Memos appeared quickly after 911, and the torture program at GITMO started early, almost as soon as the detainees captured in Afghanistan started arriving. In 2008, the Senate Investigation [The Treatment of Detainees in U.S. Custody] told us why [see the the why of torture…]:
When Psychiatrist Major Paul Burney arrived at Guantanamo Bay in June 2002, he was unaware that he would be assigned to BSCT [Behavioral Science Consultation Team] to support interrogations.
    [1] Three of us; [the enlisted psychiatric technician], and I, were hijacked and immediately in processed into Joint Task Force 170, the military intelligence command on the island. It turns out we were assigned to the interrogation element because Joint Task Force 170 had authorizations for a psychiatrist, a psychologist, and a psychiatric technician on its duty roster but nobody had been deployed to fill these positions. Nobody really knew what we were supposed to do for the unit, but at least the duty roster had its positions filled.

    They knew nothing of interrogation, so the psychologist contacted a psychologist he had met, LTC Banks, who was [unknown to the contacting psychologist] working with SERE. Banks set out to arrange training. BSCT thought they were going there just to learn about interrogation, but their CO wanted them to bring back SERE techniques to try.

    [2] At the time, there was a view by some at GTMO that interrogation operations had not yielded the anticipated intelligence, MAJ Burney testified to the Army IG regarding interrogations: "This is my opinion, even though they were giving information and some of it was useful, while we were there a large part of the time we were focused on trying to establish a link between al Qaeda and Iraq and we were not being successful in establishing a link between al Qaeda and Iraq. The more frustrated people got in not being able to establish this link, there was more and more pressure to resort to measures that might produce more immediate results."
They actually tortured one detainee into saying that there was an al Qaeda·Iraq connection, but he recanted as soon as they stopped drowning him every day [no big surprise]. And in case you didn’t catch it, the "LTC Banks" mentioned by Major Burney is the same "Banks" that ended up orchestrating the APA PENS Task Force in consort with Stephen Behnke, the APA Ethics Director.

The point is simply that besides being an indelible blot on the moral integrity of our country and failing to yield anything of any worth to us, the Torture Program was actually used as a tool to take advantage of our wounded and frightened state to trump up a reason to invade a sovereign country that had nothing to do with 911 by trying to link al Qaeda and Iraq, probably partly motivated to gain access to Iraq’s oil reserves and partly as a showpiece for their Project for the New American Century – AKA American Dominion on the world stage. So why did the APA Ethics Director, Stephen Behnke, and his cohort in the APA leadership do it? Was he part of the Bush Administration megalomania. No, it was something much simpler…

…to repeat «from the Hoffman Report, page 14»
APA’s motive to please DoD

The very substantial benefits APA obtained from DoD help explain APA’s motive to please DoD. and show that APA likely had an organizational conflict of interest, which it needed to take steps to guard against. DoD is one of the largest employers of psychologists and provides many millions of dollars in grants or contracts for psychologists around the country. The history of DoD providing critical assistance to the advancement and growth of psychology as a profession is well documented, and includes DoD’s creation of a prescription-privileges "demonstration project" in which psychologists were certified to prescribe psychiatric drugs within DoD after going through a two-year training course… And by the time of the PENS Task Force, contemporaneous internal discussions show that improving APA’s already strong relationship with DoD was a clear priority for officials working on the PENS Task Force.

In addition, at the time of the task force’s creation, DoD was in the midst of developing policy about how psychologists and psychiatrists could participate in interrogations and other intelligence-collection activities. APA wanted to positively influence DoD regarding this policy so that psychologists would be included to the maximum degree possible, and psychologists would not lose the lead role to psychiatrists. APA used the pro-DoD task force composition and report to show its strong support to DoD, with the hope or expectation that APA would be rewarded with a very prominent role for psychologists in this new policy. And in fact, the policy did provide a very prominent role for psychologists, a fact celebrated by the APA officials who had worked most closely on the task force…
And in response to allegations that psychologists had behaved unethically and actively participated in Torture:

«from the Hoffman Report, page 63»
Behnke failed to proceed with and actively resisted proceeding with these complaints. The evidence shows that Behnke knew that the adjudications process was not equipped to address ethical complaints regarding psychologists’ participation in interrogations — and that it would not lead to any sort of meaningful or thorough investigation.

The end result of the limited nature of the ethics investigations and the Ethics Office’s purposeful unwillingness to thoroughly investigate allegations of unethical conduct by psychologists who participated in interrogations was that the Ethics Office prioritized the protection of psychologists — even those who might have engaged in unethical behavior — above the protection of the public.

Mickey @ 2:03 PM