1 Boring Old Man

The Role of Psychiatry in Health Care Reform, APA Board of Trustees Work Group and the Economic Impact of Integrated Medical-Behavioral Healthcare: Implications for Psychiatry, prepared by Milliman, Inc.have an accompanying Infographic designed to simplify and illustrate their concept of Integrated Care. Shown above is their assessment that mental health care is inordinately expensive. That was accompanied by saying that while the need for mental health care is great – the patients are underserved:

It reminds me of the opening gambit for much of the industry funded clinical trial literature from the last decade – the public health burden of mental illness. In this case, we need more services and lower costs. I felt gamed reading it. That aside, they propose this model [I’ve extracted the small print for each element below]:

^{[redrawn for clarity]}

• Makes initial diagnosis and prescribes medications • Modifies treatment based on patient preferences,needs, and psychiatrist recommendations		• Identifies goals, needs, and preferences for treatment • Participates in regular screening
• Monitors all patients in practice • Provides education • Tracks treatment response • May offer brief psychotherapy • Assures patient engagement		• Provides team leadership • Reviews caseload regularly • Educates and consults • Sees patients who are not making improvements

By my read, the care of patients with mental health problems falls to primary care physicians with review/consultation with psychiatrists. The patient is followed using rating instruments by a case managers/mental health types using some kind of rating scale. Brief psychotherapy may be offered. The psychiatrist reviews the patient’s progress and sees treatment failures. The model is obviously focused primarily on symptom reduction – objectified on rating scales.

Dr. Summergrad was on the workforce that produced this plan. He talks about it in this presentation:

• http://www.psychiatry.org/practice/professional-interests/integrated-care/integrated-care-reconnecting-the-brain-and-the-body
• http://www.psychiatry.org/File%20Library/Practice/Professional%20Interests/Integrated%20Care/BOT-Healthcare-Reform-Summary-Report.pdf
• http://www.psychiatry.org/File%20Library/Practice/Professional%20Interests/Integrated%20Care/Milliaman-APA-EconomicImpactofIntegratedMedicalBehavioralHealthcare2014.pdf
• http://psychnews.psychiatryonline.org/newsArticle.aspx?articleid=1742623

• three wishes…
• in the comments…
• other comments…
• on Psycritic: On Integrated Mental Health Care
• on Mad in America: The End of Psychiatry
• on PsychPractice: APA-thetic

• New FDA Chief Must Divest Several Stock, Fund Holdings
• Margaret Hamburg, Wikipedia
• FDA chief urges ‘new era of partnership’
• FDA commissioner defends proposal to expedite drug approval for serious illnesses
• FDA Chief Defends Approval of Controversial Painkiller
• Sen. Elizabeth Warren Takes FDA Chief To Task On Weak Antibiotics Guidance
• New Painkiller Rekindles Addiction Concerns
• Critics Oppose FDA Approval of Painkiller Zohydro
• Gov. Deval Patrick Issues Tighter Restrictions for Painkiller Zohydro
• Understanding the uproar over Zohydro ER
• Critics Question FDA’s Approval Of Zohydro
• Zohydro Update
• Zogenix Makes Moves to Concentrate on Its Zohydro Efforts, Sells Migraine Therapy Business

hat tip to jamzo…  

The amounts recovered through these suits rose so fast I had to use a log scale to even keep it on the page:

And these are just the whistleblower suits where the government was the defrauded party. There are plenty of other suits against PHARMA coming from other directions.

FDA chief defends Zohydro approval as US states rebel

by Michael McCarthy

British Medical Journal. 2014 348:g2939

Margaret Hamburg, commissioner of the US Food and Drug Administration, has defended her agency’s decision to approve the potent long acting opioid Zohydro ER, arguing that the FDA had to balance the risks of opioid prescription abuse with “the very real medical needs of the estimated 100 million Americans living with severe chronic pain or coping with pain at the end of life, which is also a major public health problem in this country.” In an address to the National Rx Drug Abuse Summit being held in Atlanta, Georgia, Hamburg said that the drug—an extended release formulation of hydrocodone bitartrate—offered an effective option to patients who required around-the-clock opioid treatment and for whom alternative treatments were inadequate. She also said that because Zohydro did not contain paracetamol (acetaminophen), it did not pose the threat of liver toxicity seen with combination hydrocodone products, such as Vicodin, which did contain paracetamol.

Hamburg’s comments came as several state governors moved to severely restrict the use of Zohydro in their states, citing concerns that the drug, which can be easily crushed for sniffing or injection, would exacerbate prescription opioid abuse in their states. On Tuesday 22 April Deval Patrick, the Massachusetts governor, issued orders to require prescribers to complete a risk assessment and agreements on pain management treatment before prescribing Zohydro. Rules issued by the Massachusetts Board of Registration in Medicine say that these agreements must address drug screening, pill counts, and safe storage and disposal.

Patrick said, “We are in the midst of a public health emergency around opioid abuse and we need to do everything in our power to prevent it from getting worse.” His order came after a court lifted an outright ban on the drug, which Patrick imposed in March. In that ruling District Court Judge Rya W. Zobel cited the Supremacy Clause of the US Constitution, which establishes that federal law supersedes state law if they conflict. Zobel wrote, “If Commonwealth [of Massachusetts] were able to countermand the FDA’s determinations and substitute its own requirements, it would undermine the FDA’s ability to make drugs available to promote and protect the public health. The Commonwealth’s emergency order thus stands in the way of ‘the accomplishment and execution of’ an important federal objective”…

The FDA’s decision to approve Zohydro last October, despite an 11-2 vote by the agency’s advisory board against approval, triggered a storm of protests from state officials and politicians in Washington. Late last year attorneys general from 29 states wrote a letter to Hamburg, calling for her to either revoke the drug’s approval or require the manufacturer to quickly produce a formulation that deterred misuse. And earlier this year Joe Manchin, a Democrat senator from West Virginia—a state that has been hard hit by the opioid abuse epidemic—introduced a bill that would force the FDA to withdraw its approval of the drug.

Back in ancient history when I first began trying my hand at deciphering the bizarre clinical trial situation in psychiatry, I looked into the strangest of stories involving a drug called Mifepristone [Corlux®][RU-486]. For the details, see my series of eight consecutive posts starting with Mifepristone 0: $tanford’s $chatzberg redux…. I was relatively new to the amount of corruption in the world of psychopharmacology, and I recall writing that series incredulous at such blatant Conflicts of Interests. The essence of the story is that Dr. Schatzberg, Chairman at Stanford, was the principle Investigator on an NIMH grant to study the effect of RU-486 [the "morning after" pill] on patients with psychotic depression.

The premise was reasonable. These patients had been shown to have hypercortisolemia, and RU-486 blocks the effects of cortisol [among other things]. What was not reasonable was that Dr. Shatzberg and Stanford got a patent on RU-486. Then Dr. Schatzberg and his associate Dr. Joseph Belanoff formed a private company, Corcept, to explore getting FDA approved with plans to capitalize on the drug. It was a bolder time then and the NIMH Study and Schatzberg’s commercial planning were virtually indistinguishable until 2008 when Senator Grassley began to look into Conflicts of Interest and unreported income in psychiatrists in high places [Dr. Schatzberg was in the highest of places – President of the American Psychiatric Association]. In the course of that investigation, he "stepped down" as chairman, and moved off of the Board of Corcept, the company he’d founded with Belanoff – though he remained an investor and advisor. In that same time frame, we learned that he and Dr. Charlie Nemeroff has guest authored a textbook, Recognition and Treatment of Psychiatric Disorders: A Psychopharmacology Handbook for Primary Care, ghost-written by Scientific Therapeutics Incorporated, financed by GSK.

Corcept Therapeutics: Fourth Time’s A Charm For Mifepristone In PMD?

SeekingAlpha

by Bay Area Biotech Investor

Apr. 15, 2014

Summary

• Mifepristone in psychotic major depression [PMD] has one positive phase 2 and three negative phase 3 clinical trials.
• Management has made important trial design changes to the current phase 3 trial, most notably regarding placebo effect and dose.
• The potential of mifepristone in psychotic major depression [PMD] is underappreciated by the market.

In this article, Bay Area Biotech Investor does an amazing thing. He goes through each of the previous failed clinical trials and deconstructs them in some detail. If only they didn’t have the European sites in the first trial, they would’ve gotten a significant result. Solution, no more European sites. In another trial, if only they included the patients with high blood levels of Mifepristone, they would’ve had the desired outcome. There was a very high Placebo response – with too many Placebo dropouts. If only that hadn’t happened … Harder to solve, but maybe having a large study would work. So now they’ve launched a trial with only US sites, a high dose of Mifepristone, and are aiming for 450 subjects [finding 450 patients that are really psychotically depressed is going to be quite a challenge]. In fact one of their problems it’s likely that the earlier studies didn’t have a true cohort because the cases are not very common. So maybe that’s why the had such a brisk placebo response.

There’s an old Zen Kõan that’s told in many different ways. In one version, a scholar is lecturing to his students about the moon while pointing at it in the sky, giving elaborate descriptions of its features. The Zen Master watching all of this quips, "That fellow is confusing his finger for the moon." This Seeking Alpha article approaches these three negative trials as a challenge to be overcome – assuming the problem is in the trials, not the basic hypothesis – false negatives. With the just-right design, the truth will out and all will be well in the halls of Corcept [one suspects that if the trials were positive, he would hardly be inclined to slice and dice them with such a fervor]. The question is not about the effectiveness of Mifepristone, it’s how to get a positive trial.

The remarkable thing is that the venture capitalists have been through this three times already, yet they continue to shell out the money without apparently considering the fact that Mifepristone isn’t doing very much for the cases that are being collected for their trials. Imagine the results in the world at large where any kind of depressed patient might be chosen for a pre$cription [anyone with whole lot of loose change]

So, why would reporting cortisol levels in clinical trials be informative? Published literature suggests they will be elevated in PMD patients, and mifepristone does not lower cortisol levels, it is an antagonist, it only prevents cortisol from signaling. There is no rational for them needing to validate the PMD diagnosis by elevated cortisol levels when it has already been proven that PMD patients have elevated cortisol levels during certain times of the day. Do you agree with this reasoning? They do have a stringent entry criteria: DSM-IV TR diagnosis of Major Depressive Disorder with Psychotic Features and pre-specified minimum scores on standardized psychiatric rating scales at baseline, which will be conducted by a centralized rating system Medavante. This entry criteria seems much more practical than a entry criteria based on elevated cortisol levels. Do you agree with this entry criteria or would you rather see entry by elevated cortisol levels? 

One wouldn’t have to read much here to realize that I’m no particular fan of the American Psychiatric Association or its current President, Dr. Jeffrey Lieberman. With him, it’s not anything personal. I just don’t much like people who speak and write with a conclusion that they want me to reach, and attempt to sell it. I don’t mind his having opinions, but I do mind not hearing anything that I don’t already know woven into some conclusion I can’t imagine agreeing with. But then I read something I did like yesterday in the psychiatric news. It was an article about a talk Dr. Summergrad, the APA President-Elect, gave to the Directors of Residency Training at their annual meeting recently. That’s a job I held for for a while and would’ve continued had psychiatry not gone in a direction I didn’t understand [as in "stand under"]. The articleis there for the reading, but I want to say a word about what Dr. Summergrad says [see Summergrad Addresses Training Directors on Development of Physician Identity].

There were two things on the table for the training directors. First, there’s a push for documenting and rating in training programs – some call for objective criteria, data by which to judge individual residents and their programs. Second, there was a an issue about "resident duty-hour restrictions" – putting limits on the number of hours residents can be required to work. I thought it was kind of funny that those same things were on the agenda at that same meeting thirty years ago when I was in the audience. I guess some things never change.

But it’s not the issues, but the way he approached talking about them that I want to write about. He called his talk, Going to Sea: Psychiatric Education in an Era of Accountability. He talked about the modern need for accountability and objective measures, about everything – what was good about it. And he discussed the fact that the obsession wasn’t going to go away – sort of a "don’t fight it, it’s here to stay" point of view. But the thrust of what he had to say  was music – don’t confuse these bean-counter requirements with what really matters in a training program – that the residents develop an identity as physicians focused on the needs of their patients, not their own. It’s really quite impressive what he has to say. I haven’t heard anyone in a high place in psychiatry talk like that in years. I wanted to say, "what’s a guy like you doing in a place like this?"

Maybe I like him because he did too many training programs – internal medicine, psychiatry, psychoanalysis, with some fellowships thrown in to boot [like I did]. Maybe it’s because he has a longstanding interest in Zen Buddhism [like I do]. Perhaps his watching Nordic Noir television shows [like I do] has something to do with it. But I really think it’s his ability for straight talk, and the fact that he seems to know what’s really important in a trying time that draws me towards him. There’s a badly taped presentation at the University of Florida [The Future of Psychiatry] that you might like to watch as well.

Pfizer mulls $100 bln bid for AstraZeneca – report

Reuters

Apr 20, 2014

U.S. pharmaceutical giant Pfizer has approached British rival AstraZeneca to propose a 60 billion pound [$101 billion] takeover, the Sunday Times reported on Sunday. The paper said, citing senior investment bankers and industry sources, that informal conversations about a deal had taken place between the two firms but that no talks were currently under way after AstraZeneca resisted the approach. AstraZeneca is Britain’s second-biggest pharmaceuticals group with a current market valuation of around $80 billion, compared with Pfizer, which is valued at $193 billion, according to Thomson Reuters data…

Spurning Merger Approaches, AstraZeneca Pursues Own Path

New York Times

By MICHAEL J. DE LA MERCED and ANDREW POLLACK

April 21, 2014

The British drug company AstraZeneca said no to a tie-up with Pfizer, turning down the possibility of one of the biggest drug mergers in recent history. Whether such a deal would have made sense is another matter, because the British drug maker is trying to improve its fortunes on its own and Pfizer in the past has found that big acquisitions can sometimes prove more distracting than helpful.

In recent months, Pfizer made a number of informal takeover approaches to AstraZeneca, according to a person briefed on the matter who is not authorized to speak publicly about internal discussions. One of those tentative approaches valued the smaller pharmaceutical company at about £60 billion, or nearly $100 billion, according to The Sunday Times. At that level, the deal would be one of the biggest ever in the pharmaceutical industry, surpassing Pfizer’s $90 billion takeover of Warner-Lambert…

Reading this felt a lot like a new season of The Game of Thrones. Not so long ago, Pfizer’s Zoloft® was a chart topper in the antidepressant market, and AstraZeneca’s Seroquel® was the best selling of all pharmaceuticals in its day. Zoloft® was approved only through the efforts of FDA Official Paul Leber [zoloft: the approval III…]. Similarly, Seroquel® slid under the wire, and left unpublished its most definitive study [Study 15] that showed that it was decidedly inferior to Haldol [‘this cursed study’ – more about Seroquel…]. These drugs were giants in their day and the ads were everywhere – remember the Zoloft talking head that directly spoke of the drug correcting a "chemical imbalance." Now both companies are running out of patent for another class of drugs – Crestor and Lipitor – losing their places in the statin frenzy.

For these companies, the passage through the universe of CNS drugs was a lucrative but time limited season in their endless travels through the gamespace provided by our patent laws. The companies played on two simple themes – the SSRIs and the Clozaril derivatives. But in the day, it seemed like there was so much more happening. It was only as the cycles wound down that we heard all the talk about "me too" drugs. Part of that illusion of bigness was from all the activity generated by the indication sprawl and off-label prescribing.

While waves of pharmaceutical products have swept through many medical specialties [eg antihypertensives, antibiotics, statins, anticoagulants], I’m not aware of any that have had such a profound effect on a medical specialty as the psychopharmacologic agents had on psychiatry. The first wave in the 1950s is easily understood. The drugs treated things formerly untreatable by drugs, or much else. The second wave landed on a psychiatry struggling with redefining its medical identity in an age of Managed Care. House Psychiatry and House PHARMA formed an alliance that seemed forged in steel [that fit with House Managed Care perfectly]. They thrived for twenty years while the boundaries between them became increasingly indistinct.

“There are huge unmet clinical needs in mental disorders and addiction,” said Jeffrey Lieberman, M.D., incoming president-elect of APA and chair of psychiatry at Columbia University, who moderated the morning session. “There should be tremendous interest in this area, but there is not.”

But as you can see from the articles up top, the Game of Thrones in PHARMA continues right along without bothering with psychiatry – merging and looking for new candidates for their end of the pipeline of drugs. Two former psychopharmacology giants moving along to other territories. I have come to believe that the powers that be in psychiatry were living as if PHARMA was duty bound to some kind of endless supply of new drugs because of the demand, as Dr. Lieberman implies – a loyalty that would persist. That was a very naive assumption. The pharmaceutical pipeline flows to all of medicine, and PHARMA goes where there’s a market and where they can find a product to sell. Nothing new in CNS, moving right along. In leaving psychopharmacology, they cut off a vital flow of funding that psychiatry had come to rely on in any number of ways. And psychiatry lost not only funding, but the myth of new drugs just around the corner that would be more effective – the myth I called future-think.

There was a time when I used to wonder why psychiatry was so vulnerable to the pharmaceutical industry. Why did so many KOLs race over to the dark side? Why did the specialty wrap itself almost exclusively around psychopharmacology practices? But I can feel the biases in all my answers so I’ll wait and buy the definitive history when it’s written. Another question: How does the big push for Collaborative Care fit into all of this? Surely it has something to do with responding to the exodus of PHARMA, but I’m not sure how it fits.

As a late adolescent, there was something in the world I lived in that was wrong in an absolute sense. Once that dawned on me, I never had a moment of doubt – the segregation of races in the South where I lived was wrong. In those times, that was not an easy realization, but there was a comfort in knowing something without reservation. My closest friends to this day are others who had that same awareness early on and involved themselves in doing something about it. But that may have been the last time I was ever completely sure about anything.

When I came to psychiatry from internal medicine, my first rotation was an acute service at an urban charity hospital – the emergency receiving facility for in-town Atlanta. It was at the wrong end of the deinstitutionalization process when all of the outpatient resources left over from the Community Mental Health initiative were disappearing along with the evaporation of inpatient beds. It seemed as if the patients that I thought needed to be in the hospital didn’t want to be there; and the patients that I thought didn’t need hospitalization were lobbying to get admitted. The same thing was true of medications. It felt as if I was always positioned against the flow, and I was never "sure" about anything.

One thing I learned in those days was to listen to people who had been there in person. An apt analogy would be the  difference between civilians and veterans. There is an intrinsic impossibility in psychotic illnesses felt by both the afflicted and their caretakers that is a required ingredient in any cogent discussion of the topic. In my case, later I ran that same service for a year or so and then spent a decade directing the training program that staffed it and several others like it. The most important part of both jobs was helping the residents learn to make sensible decisions based on the individual patient in front of them, rather than becoming polarized in the confusion of chronic impossibility. I had seen that happen to two fellow residents [in different directions], both with disastrous results.

I have nothing but respect for those who stayed in public psychiatry where most psychotic mental illness is treated. It’s a very hard road. But even those with these more informed opinions vary widely when it comes to the inevitable conflict between patients’ rights and the need for treatment and/or restraint. In fact, it’s almost impossible to find any discussion that doesn’t turn the problem of psychosis towards one or the other of these priorities, often implying that the other party is ignoring the more important side of the equation. And that’s not meant as an indictment – it’s just in the nature of the problem as I see it. An observation: among people in the business, independent of what they might say in an armchair discussion, they are usually indistinguishable in how they approach a given clinical situation or case.

There are two psychiatrists from the public sector commenting here, Dr. Dawson [Real Psychiatry] and Sandy Steingard [Mad in America]. I would recommend following what both have to say. Their views and temperments differ, but they both speak from the trenches of experience and are the kinds of people we need to be listening to. Another reference you might want to look at is the article After Newtown by E. Fuller Torrey, the author of the report Dr. Insel was referring to in the last post [lamentations · long passed…] to fully digest his point of view. That brings me back to the quote from Dr. Insel I started with: "Returning to the asylum system — which could be regarded as turning away from the goal of recovery — is not the answer." I found that odd when I first read his post, but I passed over it because I had something else I wanted to say.

The dichotomy between the asylum system and the goal of recovery uses phrases that have too many layers of meaning for that simple sentence. The asylum of Philippe Pinel or Dorthea Dix was as sanctuary for the humane treatment of the severely mentally ill. The asylum of the 1940s was an overcrowded snake pit where the severely mentally ill were essentially warehoused to keep them out of sight – forgotten people. While it’s hard for me to imagine not having the goal of recovery for all patients, that has to be defined for any given person because it varies over the a wide spectrum of possibilities. In this instance, I’m talking about the people with chronic psychotic illness who live in our prisons because there’s no other place for them that they can manage, and many are there by their own hand for that very reason.

I said at the outset that the Civil Rights Movement may have been the last time I was ever sure of anything, but I’m thinking that’s not really right. I’m sure that putting chronic mental patients in prison isn’t right – certainly not as a standard operating procedure. And that’s not an invitation for rounds and rounds of the divisive and blaming arguments that always swirl around this topic. I’m old and have heard them all. When I was suggesting a Task Force, I wasn’t thinking of the usual suspects – the mental health policy wonks from either side of any number of fences. I was thinking of people who have spent their lives among these patients and have a sense of what might work and what won’t. I would include judges, their jailers, and the patients who could participate. In my view, the blaming and arguing that invariably arises has actually interfered with any progress in the humane care of these patients. I’m sure that there’s something we can do that’s much righter than what we’re doing right now, and we’re obviously not doing it yet. I should actually say some things, because these patients are as varied as the rest of us even in their disability, and we need flexability to meet that diversity. There are templates aplenty to guide us. We are at the bottom of the heap among the countries of the developed world in this area, and I expect they’d fall all over each other trying to help us do things better.