1 Boring Old Man

People in the know [and I consider both Goldacre and Healy to be such people] have a variety of differences on how to proceed now that it’s very clear that we can’t even consider the possibility that PHARMA will be self regulating. I defer to their judgement on how to resolve their differences [so long as PHARMA has no seat at the table]. But quite honestly, if PHARMA were out of the way, I doubt that there would be any differences to resolve. I expect we’d all be out trying to practice decent medicine instead of fighting about drug marketing and deceitful science. As a doctor, I’d be willing to just live with the drugs I can trust right now until this all gets ironed out. We’ve been blackmailed and compromised long enough.

Long ago [in the late 1970s or early 1980s sometime], a friend invited a psychiatrist who was in town to come to a journal club he chaired. The visitor was a psychiatrist/psychoanalyst who had retired from an interesting career. For years, he’d directed a public mental health center in the mornings, and then gone to his private practice in the afternoons. He was one of the early describers of "burn-out," that thing that happens to mental health personnel after working with chronic patients for too long. His topic that evening was one of his books on Schizophrenia [that he was in town to promote]. His name was Werner Mendel. He was a very personable, happy guy [with a natty bow tie] who spent his retirement sailing and writing about his time in grade. He told us about some things that have always stuck with me.

I was interested in "burn-out." I’d spent a lot of time with staff in Mental Health Centers and the Crisis Unit I was in charge of at the time, and I’d seen a lot of that. Essentially, he described something of a developmental crisis in his mental health staff. It happened at around six or seven years, when a staff member would go a little crazy – get depressed, get hostile to the boss, colleagues, or patients, any number of uncharacteristic things for that person. His explanation was simple. Success in a facility with chronic psychotic patients was not measured in their getting better, it was measured in their not deteriorating. He said he realized that he didn’t get "burned out" because his afternoon patients actually got better and said "thanks" when they moved on. His nurses across town didn’t have that luxury. Instead of getting frustrated with them when they "burned out," he had come to see as part of his job helping them move forward. Some moved "up," became administrative with less patient responsibilities; some came through it rededicated to helping chronic patients, but with new set of expectations; and some changed professions altogether. Whichever happened [speaking of Memorial Day], he thanked them "for their service." Quite something, Werner Mendel.

"You know, as I talk about it, I’m realizing that those clinic patients did better than the staff. Schizophrenic patients get better with age. I don’t know why, but there’s no question about it. Maybe it’s fueled by the passion of youth? hormones? Whatever the case, I was around for a long time, and the old patients would come in and I was amazed at how much better they were. Amazed! They outlasted my staff."

I find it fascinating to know that the innovative rehab program introduced by George Brooks at Vermont State Hospital in the 1950′s, which was the basis of Courtenay Harding’s ground breaking long term study in the 80′s [2/3′s living full lives in the community, 50% on no medications, another 25% using them intermittently], was predicated on a non-hierarchical approach. Brooks brought in the patients and asked them what THEY needed in order to be able to be well enough to leave the hospital.

• The Vermont Longitudinal Study of Persons With Severe Mental Illness, I: Methodology, Study Sample, and Overall Status 32 Years Later
• The Vermont Longitudinal Study of Persons With Severe Mental Illness, II: Long-Term Outcome of Subjects Who Retrospectively Met DSM-III Criteria for Schizophrenia

Thus, 5-10 years after release from the rehabilitation program, 70% of the patients were out of the hospital, which was considered remarkable at the time because they had been expected to live out their lives in the hospital. However, the study concluded with a warning:
Implicit in our findings is the fact that any plan for rehabilitation of the chronic patient be conceived as long-term, since all of our evidence suggests that the commitment necessary to the chronic mental patient has no foreseeable end, and that unless constant attention be given to the chronic patient, the end result may be simply that he is out of the hospital, but operating at a high level of inadequacy and a low level of employment.
It is at this point that most follow-up studies stop and most programs are discontinued. Thus, most of our understanding of the long-term outcome for severe mental disorder is derived from such shorter-term data. The question asked in the present study was, Do these patients still continue to display such impairment and disabilities 20 to 25 years later, as predicted earlier by our own research team?

… There were no subjects who could become a control group in the Vermont State Hospital, inasmuch as the entire most severely ill third of the patients in the state’s only hospital [excluding the geriatric population] was selected to participate in the program. For years an appropriate comparison sample was sought, and recently a study was undertaken in the state of Maine that matched each of the Vermont study’s subjects by age, sex, diagnosis, and level of chroniciry with a patient from the Augusta Mental Health Institute. These new subjects are being interviewed with the same protocols and instruments to determine their life courses and illness trajectories. The primary difference between the two samples is the presence or absence of rehabilitation efforts. It is hoped that the difference in outcome between rehabilitated and nonrehabilitated subjects will be helpful in the study of mediating factors in long-term course.

I recognize that in the last post [another IRT prequel…], I’ve stepped out of the general frame of Evidence-Based Medicine in that it’s the experience of a single clinician with a small number of cases. While it’s reinforced by my own teachers and patients, and from reading the writings of a lot of clinicians [Eugene Bleuler, Viktor Tausk, Kurt Schneider, John Cameron, Harry Stack Sullivan, Frieda Fromm-Reichmann, Otto Will, etc]. I acknowledge that it is a collection of opinions and observations rather than scientifically validated data – hard facts. I make no apology about that. I’m mentioning it just so you’ll know that I know I’m doing that generalizing-from-small-numbers thing that people like to criticize. I can’t think of any other way to express what bothers me when I read the Individual Resiliency Training [IRT] Manual. I expect I’ll continue in this vain in this post too.

I suspect the manualized approaches will be very helpful for some but not all and just getting the person into the room is a huge challenge… However, these manuals contain some useful guidelines on how to talk to people about psychosis other than just encouraging them to take their medications. .. Even if we hire more people to do the work, we need to give them some idea of what to do once they have their job and these manuals can help with that. In my experience, DBT worked that way. At first it was applied rather rigidly but now many of the concepts have worked their way into many aspects of what we do and the tools we try to give people to help them recover. However, if this increases resources and attention, I think that many well meaning and caring people will use the manual but end up not following it to the T; some of them are bound to look up and see the human being sitting in the room.

I agree with George Dawson. This Individualized Resilience Training [IRT] looks like a dressed-up, manualized version of training for coping skills plus supportive-psychoeducational therapy, plus case management. What’s remarkable is that it is presented as something new. …the description smacks of armchair planning of services for nice clients by nice mental health administrators. Will they do a demonstration trial within the Los Angeles County jail?

I’d be surprised if there were any consumers [service-users] involved in this. Its language and orientation is far from the material produced by consumer-led organisations such as the Icarus Project. It is very much a product of the ‘technological’ mind-set that dominates psychiatry and psychology. The assumption is that mental health problems can be analysed in the same idiom we use to analyse endocrine or cardiology problems. Even ‘fun’ is a technical issue here, patients will receive education on the ‘three stages of fun’ The writers of the manual are very much the ‘experts’. This is the starting point. The patient is rendered passive in this move. They are to come to sessions to be ‘trained’ as though they have little to contribute themselves. There is no ‘critical thinking’ in operation, no questioning of assumptions about the nature of psychosis, the limitations of medications, the questionable expertise of psychiatry etc. It is very confident in its message: ‘we know how to teach you about resilience’. There is no room for uncertainty here. In my experience, this is simply inadequate. It is much better to start with doubt, with questions, with openness. This allows the very many patients who are struggling to make sense out of their psychotic experience to make contact and to engage. The IRT approach will chase people who are questioning away. There is no mention of ‘culture’ in this document, no acknowledgment that religion, spirituality, creativity etc are often bound up with psychotic experience… Again, this is inadequate. I hope these comments make sense! They are initial observations after a quick read through. I don’t think I could face really reading the whole thing carefully!

I agree with them all. The only thing I would add is that the Individual Resiliency Training [IRT] Manual didn’t seem to me to be written with the target population in mind. They address the topics of people recovering from psychosis, but they don’t seem to know them very well. That’s why I wrote another IRT prequel… first. This is a population of patients that often don’t know what they want, where they’re headed. So starting the sessions asking them about their goals is ill advised ["That’s what I am, a blank page"]. The authors of the manual obviously are the ones with the goals. Trying to tease those goals out of the patients can reproduce a problem rather than solve it – the author’s intent. It’s a strategy, and strategies are particularly virulent here. The patients pick up on being subtly lead somewhere, often don’t intuit where, and become mistrustful [paranoid]. So with this, of all groups, communications need to be clear, direct, and honest. The basic rules "never ask a question the patient can’t know the answer to" and "don’t use questions to make statements" both apply. And then there’s the Ambivalence thing. Questions are for exploring.

• Scientists believe psychosis is caused by a chemical imbalance in the brain.
• Both stress and biology contribute to psychotic symptoms.
• Biological factors contribute to this chemical imbalance in the brain.

I won’t go on and on here. I expect I’ve really already said what I wanted to say in another IRT prequel…. I think the reason this doesn’t feel like something new is that it’s about training the patients, yet it’s not informed by the patients themselves or what we know about them. What would be new would be to organize this around learning together rather than how to train them. I agree with Dr. Steingard that these clinicians need something to go on, but I think we’d be much more effective if we tried to train the clinicians in the ways of these specific patients. The manual may offer a road-map to some of the areas in need of exploration [and some of the examples are useful]. But if the point is to teach the clinicians to do their jobs ["many well meaning and caring people will use the manual but end up not following it to the T"] and the hope is that "some of them are bound to look up and see the human being sitting in the room," why not start there in the first place?

re·cov·er·y    [] n. pl. re·cov·er·ies The act, process, duration, or an instance of recovering. A return to a normal condition. Something gained or restored in recovering. The act of obtaining usable substances from unusable sources.

In its effectiveness… I was fretting about the Individual Resiliency Training [IRT] that is part of the RAISE ETP Project. It’s a structured program for patients and families following the first episode of psychosis. Unlike the other things I write about here, I thought it was well-meaning and some people have obviously put a lot of thought into writing it. I’ve mused about what bothered me so much about it. The most obvious thing might be more about me than the point of the manual. I find myself put off when approached with that much structure – it feels distancing. It’s like talking to a drug rep who has something to sell, some direction he wants to take me in, and I feel like I’m talking to an background agenda rather than a person. But that might also be something I’ve learned about this particular group of patients, they’re always looking for the hidden meaning behind the words, even in very clear communications. And a lot of the modules have that feel – strategizing to get the patient to think some certain way. And strategies breed paranoia in this group. But that’s not all that bothers me.

Just like the word Resilience, I have some difficulty with the word recovery. I get that it means not psychotic anymore. But it implies that the patient used to be fine, normal, and then psychosis came, and the goal is to get back to fine again. I’ve seen a lot of these patients and had the privilege to follow a few for a long time [one mentioned in 1. from n equals one…. [and 2. from n equals one…, 3. from n equals one…, etc]. When I’ve gotten to hear about the patient’s experience before the overt psychosis, things may have looked fine, but they weren’t at all fine inside. And with the families, there has always been a background worry, some kind of special vigilance for this particular child – not fine. Bleuler talked about that a hundred years ago, calling it the Schizoid Personality. It’s the thing Professor McGorry and others want to be able to identify – a pre·psychotic syndrome that could be treated before the outbreak of psychosis. I agree with their premise, but I don’t think we yet know how to do that. So I’m not arguing with the word recovery itself, but with the idea that there’s been a stable place to recover to. I see the psychosis as just the outward manifestation of an ongoing condition. And my best success has come when the patient can look back on those earlier days and address them as part of the problem.

What are those qualities that are often seen before and after a psychotic episode? Bleuler described them as shy people who replaced interpersonal experience with other pursuits, and were uncharacteristically explosive when frustrated. These patients often describe a predominant feeling of inner tension and "not fitting in" that has always been present. Their intuitive compass isn’t pointed by positive emotions, or directed by desires, but is rather driven by worries and towards ways to achieve tension reduction. They may edit the school paper or be a head cheerleader, but there’s no joy in the enterprise, just relief when it’s over. And identity formation, the task of adolescence, may be remarkably stunted. The patient above was in her senior year of college about to graduate Magna Cum Laude with a Liberal Arts degree, but had no idea what came next. The family sent one of her siblings on a visit to help her. Her sister got a legal pad and pencil and asked her to write down all the things she had been interested in or had thought about doing. The patient-to-be was paralyzed, thinking, "That’s what I am, a blank page." That was two years before her first psychotic episode. Three of Bleuler’s diagnostic "A-s" are almost always there before there are any signs of psychosis: Anhedonia, the absence of pleasurable emotion; Ambivalence, problems resolving conflicting emotions; and Abstraction, problems seeing the abstract meanings – sticking to the literal. Knowing in a felt way what you want is required for that intuitive compass I mentioned, and these patients to a greater or lesser degree just don’t seen to have such a mechanism in place. You will recognize that this paragraph might fill the bill for the "negative symptoms" we often read about – the ones medication doesn’t seem to help. If you look carefully, this stuff is there before the psychotic episode, though it may be well concealed.

The topic is the RAISE  Individual Resiliency Training [IRT] modules. They are trying to design a program that will help the patient manage or even make progress in these areas, to recognize the earliest signs of an impending psychotic episode, and to live more pleasure-driven and fulfilling lives. So what are the stressors that predispose to psychosis? It’s not just any old stress. It’s things in their areas of vulnerability – situations that require understanding abstract meanings or things that can only be resolved with emotional intuition. From my experience, emotionally ambiguous situations with other people top the list. And learning to recognize the signs of impending psychosis is hard work, because the signs invariably feel ego-syntonic – an integral part of personal experience. The patient I’m referring to came in one day several years down the road and announced her discovery. Whenever something in nature felt like it carried a special meaning for her – specifically for her – she was in trouble. For some of us, the thought, "It’s a beautiful day and that means I’m going to have an absolutely great day today!" might occur as a benign happy thought. But for her, it meant get on the phone [and she was absolutely right about that]. The reason I say "emotionally ambiguous situations with other people top the list" is that when we went back over the lead in to either psychotic episodes or "near misses" with this and other patients, that’s what we usually found.

As I said earlier [the end game…], as a member of the RIAT team who was granted access to the Data from Paxil Study 329 to do an independent reanalysis by GSK, we’ve now had months of experience working with their "remote desktop" interface as a portal to their information. It is a single windowed multiple document interface, totally self contained that can’t be accessed by any software other than that provided inside the window. Multiple passwords are required multiple times for access, and on some days, one is frequently thrown from the system without warning, necessitating repeated logins. There’s another internal window from SAS that contains the data and allows one to run SAS programs to analyze the data. The data is also provided as text-based CSV files that can be moved outside the internal SAS window and displayed in spreadsheets [Open Office is provided]. The open source statistical program, "R" is also provided. In our case having no-one fluent in SAS procedures and programming, we are using "R" which has the necessary statistical functions. Getting the data into the proper format required by "R" means using multiple spreadsheets – which is very difficult in the cramped space provided – sometimes taking days and involving many "start-overs." Once the data is analyzed, one can only export non-data containing files with results, and that’s only by application for approval. Using the primitive graphing functions of Open Office or "R’ in the "remote desktop" is very difficult and the graphs can’t be exported. That finally lead us to copy the information for the graphs by hand to get it into the computer proper to create our images. The process of using this interface for analysis is unnecessarily maddening and a severe obstruction to the task.

The original hand written CRFs are provided as PDF documents. In our case, there are some 275 subjects, many with several pdfs, each pdf containing 200+pages. In the interface provided, we can see only one page at a time of the nearly 60,000 pages. Tallying the adverse events from the pdfs is hard enough work, but doing to without being able to make printed copies and referring back and forth is a double nightmare, requiring days of wasted time, and delegation is impossible. Working inside of this little window brings home how important it is to have a workspace that allows simultaneous display of lots of information, and this isn’t it. One of our team has lost one assistant already over this interface. The EMA’s decision to even consider using this kind of interface is at best, ill advised, and a negation of the initial promise of Data Transparency. If I weren’t retired and instead had a job to do, I don’t think I could do it. If I were a graduate student given the task, I might go to the chairman of the department and ask for another major professor. It’s impossible to imagine that anyone contemplating this decision who knows the ins and outs of data analysis has tried it out in this kind of environment. As I said before, it’s like going to sea to see the world in a submarine, looking through a periscope.

During my working years, I never watched much serialized television drama – those things like The West Wing that captivated the interest of so many. I preferred my entertainment as films or stage productions. There was an exception, three years in the 70s in a tiny rural village in England where those things just weren’t available, so I kept up with some of the shows on television – mostly mysteries. Now, in retirement, I’m again in a tiny rural village on this side of the pond, but armed with the wonders of modern technology – DVDs, Netflix, and the like. So over the years, I’ve watched the same things as before – the various British Inspector series [Lewis, Morse, Frost] and branched out into the Swedish Walander, Annika Bengtzon, etc. Right now, I’m watching the Danish Borgen series [it means Castle]. I’ll have to say, it’s a cut above the sophisticated pulp fiction of the cops and robber shows, more in the category of serious theater. The premise is the election of the first female Prime Minister of Denmark, with the goings on in the cabinet, the press, and the world providing the backdrop for the private dramas of the characters.

[spoiler alert] In the last episode I watched, the Prime Minister’s 14 y/o daughter has been put on an antidepressant for an anxiety disorder [developed after her parent’s divorce caused by her mother’s preoccupation with her position]. Was she going to develop akathisia? I wondered. No, but then she begins to "cheek" her meds. In the midst of her mother’s triumph in stopping a war in Africa, the daughter ends up in a heap locked in the bathroom. Diagnosis? Alto? You guessed it – SSRI withdrawal. Ultimately, the Prime Minister takes a leave of absence to be with her daughter and stop the media harassment of her child.

Well, life is never simple. Here’s an extract from the European Medicines Agency’s reply yesterday to the European Ombudsman’s letter [see the end game…]:

Clearly there’s a discrepancy somewhere. All I can say at this late hour is, "I don’t know what to say."

No matter how often I’ve thought about the analogy between the board game of chess and the world of politics and business where the moves people behind the scenes make have an enormous impact on the lives of real people, it’s never hit home so poignantly as when it’s something that affects me personally. The release of the DSM-III in 1980 was like that. Within a short period of time, my career was completely changed in a direction I couldn’t have previously imagined. The current situation I’m referring to has to do with the recent decision of the European Medicines Agency to radically restrict their policy on access to the data in clinical trials.

For four years, the EMA has said that it will release all clinical trial data to qualified researchers essentially opening the door to the kind of Data Transparency vital to insure the integrity of Clinical Trial reporting. It was a hard won fight involving the Cochrane Collaboration, the BMJ, the AllTrials campaign, those working on the Tamiflu issue, etc. Even some of the drug companies came on board. But then it came to a halt when two drug companies, AbbVie and InterMune, sued the EMA and the court ordered a temporary stay on data release. And then, on April 3rd, we got the news [AbbVie drops legal action in EU drug secrecy case]. My post about that was called a sunny day…, but I recall feeling wary…

EMA’s data sharing policy—towards peeping tom based medicine?

BMJ Blogs

by Tom Jefferson, Peter Doshi, and Trudo Lemmens

May 22, 2014

… We had been part of EMA’s clinical trials advisory groups responsible for advising EMA on its proactive release policy: how, going forward, EMA is to share clinical trial data from trials of pharmaceuticals that had been through the regulatory process. Everything seemed to proceed smoothly. Then Trudo, on 24 April, and Tom on 8 May, received warning of a “meeting with academics” to discuss the finalization of the EMA policy. The meeting was scheduled for 10 am GMT, a time that was very awkward for the North-Americans who were included. Peter never received an invitation despite serving on two of the EMA advisory groups. Because of the short notice Tom and Trudo could not reschedule to be at the EMA meeting in London. Tom relied on phone attendance, very much second best, to follow what was going on.

When Tom and Trudo opened the background documents [admittedly two days before the meeting] they got a shock. No clinical study reports would be proactively released. The companies are apparently being put in the driver’s seat: they will prepare special redacted reports for public use and negotiate their content with the EMA. But no one will be allowed to download even these redacted reports. Screen-only viewing will be allowed without screen capture. The Terms of Use document also contains a list of further transparency exceptions. A noticeable exception is that “novel statistical or other analytical methods and exploratory endpoint results about potential new uses of a medicine” could be commercially confidential. Safety and efficacy data about off-label prescribed drugs could thus be kept out of third party view.

The Terms of Use contract also contains highly contested clauses and strengthens companies’ control over the process. “The User acknowledges that the Information is protected by copyright and proprietary rights of the Information Owner and can be considered commercially valuable when used for commercial and regulatory purposes.” Researchers thus will have to contractually affirm companies’ legal rights in data, even if these rights are still not clearly established in law and are currently still debated in court cases, including in a case in which EMA is involved. “The User acknowledges that the Information will be made available to the User in a “view-on-screen-only” mode, after completing the registration process. The User agrees that the User is not permitted to download, save, edit, photograph print, distribute or transfer the Information. The User agrees not to access the Information using a method other than the interface provided by the EMA, or remove, bypass, circumvent, neutralise or modify any technological protection measures which apply to the Information.” Most surprisingly, the draft documents indicate that EMA will ask data users [i.e. researchers] to contractually agree that third parties [i.e. pharmaceutical companies] will have direct legal claims under UK law against them for possible violations of the Terms of Use. Infractions to the cumbersome procedural limits could thus not only be punished by withdrawal of access. Should the EMA’s draft policy be adopted as presently proposed, it appears to open up the possibility of spurious lawsuits over “misuse of data” that essentially silence critics…

• the U-Turn…
• Fucked

"Biopharmaceutical research companies are currently developing 119 medicines to help people who have some type of mental disorder, such as anxiety, depression, schizophrenia, or substance use disorders. Those medicines are either in clinical trials or awaiting review by the U.S. Food and Drug Administration (FDA), with more than 75 percent of the medicines in the earliest phases of research and development—a time when potential treatments often face difficult hurdles and setbacks."

There are a lot of words like Courage, Bravery, Cowardice, or Heroism that we use as nouns, but are really closer to adverbs describing actions rather than some intrinsic entity – some person-place-or-thing [as nouns were described by our elementary school teachers]. I’m not trying to be a grammarian here. I’m aiming at talking about another word, Resiliency. We all know that in the face of a given traumatic event, some people leave the experience perhaps shaken, but otherwise intact. Yet others may have lifelong symptoms called post-traumatic stress disorder. In the past, this difference might be described as weak versus strong, but hopefully we’re beyond that at this point in history. So there’s a new word, Resiliency, that’s in vogue to describe this difference. Again, it’s a word that can only be defined in terms of behavior, action. It’s not really a noun of the kind sweet old Ms. Bell taught me about. Those with Resiliency don’t get traumatized and those without Resiliency do get traumatized. In rhetoric, that’s called a tautology – a word that is its own definition.

Can you teach Courage, Bravery, or Heroism? We sure spend a lot of time trying. It’s called Basic Training, or Ranger School, or Special Forces Training. These are not simply didactic courses but rather rely on experiential learning. People are taught through repeated experience how to maintain control of rational thought in the face of grave danger and uncertainty; how to be simultaneously hypervigilant and emotionally detached when presented with the fog of war. Can you teach Resiliency? I expect you can teach people to be less prone to being traumatized. But the hallmark of a traumatic experience is to be unexpectedly faced with a dire situation that one has no tools to deal with, and in the face of rapidly escalating and overwhelming emotion, the mind shuts down, dissociates, whatever you want to call that process the films try to show by putting vasoline on the lens, changing the lighting to eerie, and garbling the sound. I expect there’s a limit on how much of that can actually be taught.

I originally encountered this term from students when teaching about PTSD. I couldn’t see the relevance since I was talking about patients who already had PTSD, but I went to the literature to see what they were reading. That was a few years back, but most of what I found was more wishful that "evidence-based." Read this Wikipedia article to see what I mean. I don’t question the phenomena being described. I just don’t see how the long known observation relates to the topic of what to do with the thought.

Now I see Resiliency in a new context, as part of the RAISE ETP Project [Recovery After an Initial Schizophrenia Episode]:

They are referring to a specific structuralized program called Individual Resiliency Training [IRT] outlined in the linked document [974 pages]. This was apparently created for this program specifically, and is the part that’s new, supplementing the traditional triad of education, medication, and vocational counselling already widely used. It sounds like a good idea. But we don’t yet know if it is value-added, since the results of the RAISE ETP Project are not yet available. And since this program may soon go live on a major scale through SAMHSA Block Grant funding, it’s something we need to know already.