1 Boring Old Man

^{So do I think that editors and researchers sit around thinking, "We’ve got to keep them from nailing down the process to insure that there’s some official copy of the a priori Primary and Secondary Outcome variables publicly available"? I kind of doubt it. I expect there are some people inside the walls of Pharma whose understanding of this is more intentional, who consciously know that if they don’t keep this question always open and unresolved, they will lose an extremely valuable tool to market their drugs. But editors? I expect they think the reformers are just being too picky or are anti-pharmacology types or something like that. Maybe they feel like the lady outside the gala whose mink coat has just been sprayed with red paint by some unwashed hippie activist. Or maybe they don’t buy the scientific explanation for preregistration [see de Groot]. I doubt that it occurs to them that there was some savvy ghost·organizer in the background carefully orchestrating what Outcomes got presented in the article they published. But the net result is the same – the issue of the a priori Primary and Secondary Outcome variables just never gets resolved…}

So here we are with the powerful publication editors, an astute investigative editor [Peter Doshi], and a preeminent clinical trial researcher [Ben Goldacre] engaged in a tête-à-tête about Clinical Trial preregistration, a priori variables, and "Outcome Switching" [that’s occurring after the fact, disconnected from the specific trial reports]. The clinicians who read all of those trials in their journals likely have no idea that this debate is taking place, and even more to the point, they didn’t and don’t know that the paper they read had the "Outcome Switched" [a selective reporting that may well have painted a picture of the results through rose colored glasses]. The discussion in Is this trial misreported? Truth seeking in the burgeoning age of trial transparency by the editors is focused on COMPare’s methodology, whether the prespecifieded Outcome Variables are the best choice, or whether Goldacre’s team made an "accurate, complete and nuanced evaluation of the published trial reports."

We have to wonder "Why are they talking about that?" Only the BMJ editor seems to have responded to the cogent question, "Did you know you were publishing an article where the Outcome Parameters had been switched?" The editors of the Annals of Internal Medicine and the New England Journal of Medicine either denied the facts or said that it didn’t make any difference – essentially ignoring the question. And Doshi’s article doesn’t address the Sponsors who submitted the articles or ask them the pertinent questions: "Why did you switch the Outcomes?" and "Why didn’t you tell us that you switched the Outcomes?"

the first step

“COMPare objects to the format in which the data are communicated, but COMPare is silent about whether they dispute the key clinical message of the article,” NEJM editor Jeffrey Drazen said through a spokesperson.

Annals echoed this sentiment: “COMPare’s methodology suggests a lack of recognition of the importance of clinical judgment when assessing pre-stated outcomes.”

"Our gold standard for finding pre-specified outcomes is a trial protocol that pre-dates trial commencement, as this is where CONSORT states outcomes should be pre-specified. However this is often not available, in which case, as a second best, we get the pre-specified outcomes from the trial registry entry that pre-dates the trial commencement. Where the registry entry has been modified since the trial began, we access the archived versions, and take the pre-specified outcomes from the last registry entry before the trial began."

The Goldacre et al COMPare study in a frenzied match of ping pong… seems straightforward. Find the Outcome Variables they said they were going to use and see if they used them. They frequently didn’t. But finding those preregistered [a priori] Primary and Secondary Outcome variables in the first place is no minor task. In fact, the COMPare team had to develop an algorithm for just that problem [see the COMPare full Protocol and the Adhering to the original plan section in the previous post]. It’s often ambiguous with either nothing to go on or several versions [Protocol, clinicaltrials.gov]. Some of the editors criticized COMPare‘s methodology. But the unclarity isn’t with COMPare. It’s with the inconsistent record keeping of the Sponsors. That shouldn’t be the problem it is. These Outcome Variables are a required part of the Protocol submitted to the Institutional Review Board that approved the study – before registration.

With the exception of the BMJ, the editors’ responses to the letters from COMPare pointing out the inconsistencies were either critical or dismissive. They talked about COMPare‘s methodology or intent, denied wrong-doing, brought up exceptions, etc. They did everything except flesh out the reason for the identified inconsistencies in their articles that COMPare was asking about. When we [Bernard Carroll, John Noble, Shannon Brownlee, the Lown Institute, and yours truly] were first beginning to work on turning Dr. Carroll’s Proposal into a Petition, I had written Peter Doshi with several questions about these matters. He responded but was similarly confused – said he was writing about this too [I presume this article]. He was finding the same mess we were trying to address.

Clinical Trials have been required by the FDA since 1962. ClinicalTrials.gov has been in existence since 1997, and required since 2007 for industry-funded trials. You would think that in this last 54 years with thousands of trials behind us, we’d have worked out something as simple as where to locate an accurate list of the a priori Primary and Secondary Outcome Variables for a clinical drug trial. But as this scenario clearly demonstrates, it just hasn’t happened [carefully note the use of the passive voice in this sentence]. "it just hasn’t happened" isn’t really accurate, in my opinion. I think it has been kept from happening using frenzied matches of ping pong similar to this one because it creates a heavily protected multi-billion dollar loophole in the system. So first, what is the loophole?

the multibillion dollar loophole

The FDA efficacy standards are simple. The Trial rises or falls based on results of the a priori Primary Outcome Variable[s]. They take Secondary Outcome Variables and other arguments into account in questionable cases, but the bedrock is a statistically significant result on the a priori Primary Outcome Variable[s]. And they require two such studies for approval. They have the Protocol and the results. They have the whole CSR and they either have or can have the whole IPD if they need it. None of the arguments the drug companies use to withhold information apply, since the FDA keeps their secrets. And the could potentially get in a heap of trouble if they lie, cheat, or steal. So although the standards for approval are set fairly low, one can generally accept an FDA approval as on the up and up. And that’s basically all they say, YES or NO. At some point down the line, they may [or may not] post their report on Drugs@FDA or you can get it with an FOIA request, but it takes a while. And I think those reports are generally only available for approvals drugs.

However, there’s no official oversight in published academic journal articles. Acceptance for publication is in the hands of the journal editor and editorial staff assisted by peer reviewers. They don’t have the CSR or the IPD. They don’t necessarily have the Protocol. What they have is the submitted article and a CONSORT statement. And of particular relevance, they don’t necessarily have a copy of the a priori Protocol guaranteed to be a priori – nor do they have any injunction to make any determination about the outcome of the trial. And so to the loophole. If a drug has been approved by the FDA, the company is only allowed to advertise it for the condition it was approved for [and advertising matters!]. Let’s say you do some trials for another indication and the FDA turns it down. You can’t advertise it for that indication, but you can submit it to a journal [with its different standards] and if it’s published, that’s a HUGE advertisement. The academic authors can present it at meetings. And the reprints from those publications can be disseminated far and wide.

Conclusions: Paroxetine is generally well tolerated and effective for major depression in adolescents.

And beyond that, in a published journal article, you can selectively present your data, make arguments that omit or discount contradictions, enlist the skills of trained statisticians and writers to lean the material in your direction. You can make it desirable to publish by ordering a gajillion reprints [the ones that go far and wide]. All you have to do is get it published [and having all those semi-famous authors on the byline helps with that too]. In the case of Paxil Study 329, there were over twenty such authors.

how to maintain a loophole

When someone challenges it, initiate a frenzied match of ping pong. Bring up all the exceptions, legitimate and otherwise. Discredit the critic. Ignore the critic. Make the critic’s eyes cross. In this case, do everything possible to keep all the ambiguity about the location of the bona fide a priori list of Primary and Secondary Outcome Variables alive. If they invent a ClinicalTrials.gov – ignore it. If they make it a requirement – insist on a long lag time before completely filling it out [and continue to ignore parts of it]. And if somebody like Ben Goldacre or Peter Doshi tries to nail things down, make them feel like this:

"…disputes are so detail oriented that my eyes crossed trying to follow what at times feels like a frenzied match of ping pong, each side’s latest rejoinder seeming to rebut their opponents’ last counterpoint."

The point is to either downplay the importance of these preregistered parameters or, in fact, change them to something that gives a more favorable result. And that is what has been happening in one version or another for literally decades. These arguments over whether they are a sine qua non or not have been going on that long. So…

Is this trial misreported? Truth seeking in the burgeoning age of trial transparency

by Peter Doshi, associate editor

British Medical Journal. 2016 355:i5543

Peter Doshi has, as usual, done a great job of clearly laying out an issue and exploring all of its facets. It’s certainly one I haven’t been able to stop talking about since I knew it was there to be talked about. With great restraint, I’ll avoid referencing all the times [they might just fill this whole page]. He’s talking about the question of whether one needs to absolutely define the analytic parameters of a Clinical Trial before you begin the study, or can you make changes in the outcome variables or statistical methodology along the way. Doshi is particularly focused on what’s called "Outcome Switching"  [changing either the Primary or Secondary Outcome Variables after the study has begun]. And Doshi uses Ben Goldacre’s COMPare study as his example [comparin’…]. Goldacre’s group looked at recently published trials in top journals, and found that most of them had outcomes switched post hoc:

Goldacre et al wrote the journals about their findings and catalogued their responses:

This, from Peter’s article:

Lost in a maze of detail

The disputes are so detail oriented that my eyes crossed trying to follow what at times feels like a frenzied match of ping pong, each side’s latest rejoinder seeming to rebut their opponents’ last counterpoint. In one trial, COMPare’s datasheet shows that the group counted 83 secondary outcomes.34 Yet in its letter35 to NEJM, it mentions “29 pre-specified secondary outcomes” while the last entry before patient enrolment on ClinicalTrials.gov lists just two.36 By my count—based on the protocol37 dated before patient enrolment and posted on NEJM.org—there were over 200.

I shared the case with Curtis Meinert, Johns Hopkins professor and former editor of the journal Clinical Trials. Meinert guessed that fear of future accusations of bias was driving trialists to bad practices. “They don’t want to be accused of looking at something they didn’t specify, so they specify every freaking thing.”

What is the clinical significance?

I asked COMPare to elaborate on clinical impact. Beyond the technical violations of best practices in trial reporting, did the team discover any misreporting that concerned them from a clinical perspective? For COMPare, this question was out of scope. “On clinical impact, we’ve deliberately not examined that. We set out to assess whether outcomes are correctly reported in journals listed as endorsing CONSORT,” the team told me, referring to the well established guidelines for proper reporting of randomised trials. “We deliberately steered away from any value judgments on why someone reported something other than their prespecified outcomes, because we needed our letters to be factual, unambiguous, and all comparable between trialists and journals.”

But clinical and value judgments were central to journal editors’ defence. “COMPare objects to the format in which the data are communicated, but COMPare is silent about whether they dispute the key clinical message of the article,” NEJM editor Jeffrey Drazen said through a spokesperson. Annals echoed this sentiment: “COMPare’s methodology suggests a lack of recognition of the importance of clinical judgment when assessing pre-stated outcomes”…

Adhering to the original plan

The challenge of establishing outcome “switching” begins with determining trialists’ prespecified outcomes. But which document—protocol, statistical analysis plan, registry entry, or some combination of the above—details trialists’ true intentions? COMPare’s methods prioritise protocols over registry entries, a practice that troubles Elizabeth Loder, head of research at The BMJ, which requires reporting according to the registry entry. “I see a worrying trend away from trial registries to protocols … People seem to think that as long as you’ve registered the trial and given notice of its existence, the details don’t matter so much.”

Annals said that sometimes editors are faced with “a choice between an incomplete or non-updated registry record, with a reliable date stamp, and a more detailed and updated protocol document.” Such situations deeply trouble Deborah Zarin, a long time advocate of trial registration and director of ClinicalTrials.gov, who believes that trial registration is the foundation of the trial reporting system…

Even with trialists’ last testament established, complexity remains. Having herself conducted similar analyses that compare outcomes reported across different sources, Zarin noted that a key challenge is disagreement in the community over how detailed outcome prespecification must be. “From my perspective, prespecification sets the foundation for a statistical analysis; if there is no firmly prespecified outcome measure, then it’s unclear to me what any reported P value means,” she said, noting that ClinicalTrials.gov now requires investigators to delineate “the specific metric and the time point[s]” for all outcome measures.

Yet some trialists do not sufficiently define outcomes until after the data are collected [but not unmasked] and they finalise the statistical analysis plan, a situation the FDA apparently accepts. The FDA told The BMJ that it “does not require the statistical analysis plan to be in place prior to initiation of the trial.” Annals stated that “prespecification is certainly important, but holding blindly to this prespecification may not be good science. Sometimes it becomes clear to informed clinicians and scientists who understand the area that what was prespecified is not going to provide patients and clinicians with the information they need”…

That question has an answer. As long as the confusion remains, one can do whatever makes the outcome look most like you want it to look. And you can justify your choice with the kind of discussion that has Peter’s eyes crossing, continuing to play a frenzied match of ping pong until the end of days. So if you keep from being definite about the outcomes, you can pick the one that fits your fancy, and if challenged – bring on the fog. It’s confusing on purpose…

A few years back, a woman in her mid forties showed up in the clinic "depressed" [visible from 50+ yards]. She wanted to talk about her symptoms and not her life. As it played out, one reason was because she didn’t have one [a life]. She was the housewife to her second husband, a man who worked hard, came home and ate, drank a couple of six-packs and was off to bed. His son by a previous marriage lived there and was a "freeloader druggie." Her son from a previous marriage was a college student rarely home except to eat. She worked full time as an Assistant Manager of a busy retail business. The manager often left her in charge [to run off for trists with her married boyfriend]. The patient to be was on the phone several times a day with her aging mother who lived in another state. Her mother was and always had been a "drama queen" and my future patient managed all of her affairs and money long distance. She was a "sort of therapist" for all of her siblings and her husband’s siblings in their dysfunctional marriages. Did I mention she was a full time night student taking a medical records course of study. Like I said, she didn’t have a life. Her PCP [Primary Care Physician] had plied her with various SSRIs with no effect. She didn’t tell me on that first visit, but she had a gun, bullets, and some suicidal fantasies.

The point of the post isn’t this patient’s case, but a paragraph or so will help get me closer to the point. Diagnosis? She met all MDD [Major Depressive Disorder] criteria. A twelve step diagnosis would’ve been [Malignant] Co-Dependency. A family systems theorist might label her with the "Executive Daughter" syndrome. But the Dx that I went for was "a Network case" [from the movie with the line, "I’m mad as hell and I’m not going to take it anymore!"].  I recall going for the anger because she didn’t seem to know she had it. But it wasn’t very hard to find. I saw her as frequently as I could and on my off weeks, she saw an LPC who was in the clinic. That’s where "Executive Daughter" dx came from. She had always essentially held her dysfunctional family together as her father’s "right hand man" – a family role. He was a soft alcoholic who appreciated her help. He had died several years ago, and the hardest anger for her to get to was directed towards him for putting her "in charge," then dying and leaving her to take care of all these "crazy f___ing" people.

It took a long while for her to figure out that the solution wasn’t making "them" change, it was in her stopping taking on their problems as if they were her own. Discovering the source of her anger helped, but changing roles is hard to do. On the other hand, not cringing every time the phone rang was a powerful reinforcer. To her surprise, when she started talking out loud, her husband got rid of his "freeloading druggie" son and drank much less himself. He said "I didn’t realize what we were doing to you." She dropped school ["just a way to get out of the house"] and moved to a better job. Progress once she got her rhythm was surprisingly swift. Recently, she showed up with a "relapse." He mother had a "light" stroke and a sibling’s husband died in a single week, and she found herself automatically sliding too far into the caretaker role once again and felt liked she was trapped again [forever].

The topic here is the PHQ-9 [Patient Health Questionnaire – 9 Item] [see how silly!…, remarkable…, simply absurd…, PHQ-9®™…]. The day this patient came back with her "relapse" was shortly after they started handing patients a routine PHQ-9 to fill out in the Waiting Room. It’s apparently a requirement for whatever certification the clinic is getting so they can take insurance. She said, "What is this shit?" I glanced at it and told her. She rolled her eyes, and then launched into what had happened.  It looked like this from what I recall in a quick glance…

[I particularly recall the "double answer" on number 9].

"showed up in the clinic ‘depressed’ [visible from 50+ yards]. She wanted to talk about her symptoms and not her life"

She felt really snookered. Her mother’s stroke wasn’t that light after all, and she really probably couldn’t live alone and take care of herself. Throw in the drama, and things were an unholy mess back home. It was the common problem of the elderly person who needed to go into care, but resists the need [with a heavy dash of lifelong Drama Queen-ness thrown in for good measure]. My patient felt sentenced to bringing her mother to Georgia to live with her, which would’ve been a fate worse than any she could ever imagine.

So the other thing that PHQ-9® measured was frustration. She had spent days calling hospitals, doctors, etc. trying to get someone to see that her mother couldn’t live alone, without success. Doctors and hospitals don’t initiate such things. Families and Social Services do. This is the reason every psychiatrist, psychologist, etc. should have as part of training a stint in a Social Agency. Her problem of an aging impaired parent, while common, is never easy. But in this case, everything was already in place – resources [check], fiscal assets [check], and an immediate cause [check]. All that’s needed is a savvy Social Worker and/or lawyer. My patient’s son [that college student I mentioned] had moved to his grandmother’s town to continue schooling, and moved in with her thinking he could "help Grandma." He ended up having to call the police when she got out of control and attacked him with a knife. "Grandma" ended up with an assault charge. He was busily looking for an apartment to get out of there. So there was a pending charge, a cause to go to the court and insist on an immediate mental competency assessment. That "other State" happened to be my home State and so I know the laws, so…

I work as a volunteer physician in a [formerly] charity clinic in a rural part of a rural State. The Clinic was started by some retired doctors and operated out of a few trailers with a large volunteer staff, seeing only uninsured patients. This is an unusual place at the beginning of the Appalachian Mountains. About ¼ of the county is occupied by gated retirement communities. The rest is home to the descendants of the settlers that came after the Cherokee were marched out on the Trail of Tears in 1838 and their land parceled off in a lottery. It’s a beautiful place that has the world’s largest piece of white marble [1 mile x 6 miles x unk. depth] that sustained the county back when people built with marble [it’s now the grit in your toothpaste]. It was also the home for the "moon shiners" of a former time, and their whiskey-runners and souped-up cars were the direct progenitors of the  modern NASCAR races.

The clinic I work in was staffed by retired volunteering professionals of various ilks from the gated communities and serves the indigenous population. There’s a symbiosis between these two groups that works well – strong tax base, well stocked Thrift Shop, plenty of eager workers for building and other jobs, a better hospital than we might otherwise have, our clinic, and a  cultural mixing that’s refreshing. Both groups are mostly Republicans [for different reasons].

With the coming of the Affordable Care Act and insurance for all, the clinic changed dramatically. The old docs who founded it either died or moved on [I find myself the old man now]. Instead of volunteers, we now have a few volunteers but mostly employees. There’s a new clinic building. There are inspections and standards, a new EMR [Electronic Medical Record] system. Everyone gets vital signs and fills out a PHQ-9 in the waiting room with every visit [I wonder who looks at them? not me]. And it seems like there’s some kind of administrative snafu with almost every patient, any prescriptions. Every patient has a "primary" – a primary care-person, usually a nurse practitioner. And there are lots of "rules" from the various governments and agencies involved. The patients are confused by it all [as am I]. I actually hate that it changed, and am likely to soon move on out of frustration.

The thing that has me mentioning it here is hard to know how to say – it’s a change in attitude in both the staff and patients that I didn’t anticipate – but it’s undeniable. It’s almost adversarial. Though that word seems too harsh, it’s the best one I can think of. It’s as if there has been a shift from a hermeneutic of trust to one of suspiciousness. The staff seems often worried that the patients might be trying to game the system, and the patients are likewise concerned that something might be withheld, that the "system" is working against them. It’s bigger than the fact that there’s now money involved though the fees are quite low. In my case, because I remain a volunteer and am not a registered "provider" in any system, there’s no charge to see me. Yet the attitudinal change spills over into my office. I never anticipated anything like this happening and there doesn’t seem to be anything I can do about it.

I hope I can find a way to stay on for a while because I’ve really enjoyed my time there. It has been a good end-of-career experience. It’s an antidote to some of the disillusioning things I encounter in writing this blog. It’s a mixture of all the different ways of approaching problems help-seeking patients show up with – doing what can be done in the time alloted. I often think of the title of Adolf Meyers’ collected works "Common Sense Psychiatry" – because that’s what it comes down to. Many of the patients I see have outrageous biographies, yet have put together meaningful lives against the odds. And even with the brief and infrequent visits to the clinic, I’m often awed with the work that can be accomplished. And it’s good for a psychoanalytically oriented psychotherapist to work in a situation where the very medications I talk about here as overused can be so helpful in treatment if you’re careful.

DISSEMINATION OF INTEGRATED CARE WITHIN ADULT PRIMARY CARE SETTINGS

THE COLLABORATIVE CARE MODEL

AMERICAN PSYCHIATRIC ASSOCIATION

ACADEMY OF PSYCHOSOMATIC MEDICINE

Spring 2016

There is expert consensus that all effective Collaborative Care Models share four core elements: [1] team-driven, [2] population-focused, [3] measurement-guided, and [4] evidence-based. These four elements, when combined, can allow for a fifth guiding principal to emerge; accountability and quality improvement. Table 1 reviews the core elements of Collaborative Care implementation. Collaborative Care is team-driven, led by a PCP with support from a "care manager" [CM] and consultation from a psychiatrist who provides treatment recommendations for patients who are not achieving clinical goals. Other mental health professionals can contribute well to the Collaborative Care Model. Collaborative Care is population-focused, using a registry to monitor treatment engagement and response to care. Collaborative Care is measurement-guided with a consistent dedication to patient-reported outcomes and utilizes evidence-based approaches to achieve those outcomes. Additionally, Collaborative Care is patient-centered with proactive outreach to engage, activate, promote self-management and treatment adherence, and coordinate services.

Table 1: Essential Elements of Collaborative Care

Team-Driven: A multidisciplinary group of healthcare delivery professionals providing care in a coordinated fashion and empowered to work at the top of their professional training.

Population-Focused: The Collaborative Care team is responsible for the provision of care and health outcomes of a defined population of patients

Measurement-Guided: The team uses systematic, disease-specific, patient-reported outcome measures (e.g., symptom rating scales) to drive dinical decision-making.

Evidence-Based: The team adapts scientifically proven treatments within an individual clinical context to achieve improved health outcomes.

John has recently moved out of his house, and he and his wife are separating. He is staying with a friend in town…

After a month on the higher dose of Prozac, the patient stops it because of jitters. They’re following him with the PHQ-9 and it goes up. The Psychiatrist suggests changing to Zoloft and has a phone conversation with the PCP about titration [the only direct contact between the Psychiatrist and the PCP recorded]. The patient doesn’t fill the Rx, and a month later, he’s worse. Contacted by the CM, he finally starts the Zoloft and the dose is gradually increased. After several months, the patient is feeling better and he and his wife are "fighting less." 5½ months after the initial contact, he’s back with his wife and feels fine [PHQ-9 is 5]. But two weeks later, he stops the Zoloft, and some of symptoms return and persist, in spite of restarting the Zoloft at a maximum dose. The psychiatrist suggests adding Wellbutrin and later increases the dose. At 9½ months from first contact, he is better and his PHQ is 4.

• The psychiatrist never saw the patient, and as best I could tell only had one direct contact with the PCP. If the PCP had contact along the way when changing the medications around, it wasn’t apparent. It appears that contact was through the CM [though surely that’s not right with changing drugs and titrating doses?].
• A PHQ-9 and some comorbidity screening  don’t a diagnosis make [did they actually make a diagnosis?].
• A PHQ-9 is hardly a precise clinimetric. I’d prefer asking, and I’m pretty sure patients prefer being asked.
• There are two instances where a high dose SSRI is stopped with no taper. Both suspect for withdrawal [particularly the first] but were interpreted as worsening!
  
• What about "John has recently moved out of his house, and he and his wife are separating. He is staying with a friend in town..." Have we just forgotten that a loss like that can cause all of these symptoms? What were the details? Who left who? Is there a clinician in the house?!
• Given that he got ill when they separated and got better when he moved back in, so I doubt that the Zoloft had much to do with anything [except maybe withdrawal]. It could he that he was just plenty glad to be home…

Robert Whitaker, one of psychiatry’s major critics had this to say about where he thought psychiatry might head in the future [see still around…]:

… 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.

John J.

John J. is a 48-year-old white male visiting his PCP, Dr. Stevens, for a follow-up visit for managing hypertension. During the visit, John’s PHQ-9 score is taken and found to be 16, in the moderate range for major depression. John was treated by Dr. Stevens 12 months ago for depression and remains on fluoxetine 20 mg daily, to which he had a fair initial response. This is John’s first PHQ-9, part of the new Collaborative Care protocol instituted by Dr. Stevens’s clinic.

Dr. Stevens discusses the test results briefly with John during their clinic appointment and introduces him to Ms. Cook, a CM/behavioral health specialist with the clinic’s Collaborative Care team. Ms. Cook is immediately available in the clinic to meet patients coming and going from appointments at the request of the PCP or other clinic staff. John agrees to speak with Ms. Cook after the appointment, and Ms. Cook runs through a few patient screens for behavioral health and substance use conditions that are often comorbid with major depressive disorder. John screens negatively for alcohol use or a history of mania. Ms. Cook discovers that John has recently moved out of his house, and he and his wife are separating. He is staying with a friend in town, and it has been hard for him to make it to work consistently. He often goes to bed late and sleeps in, missing his alarm in the morning, and eventually calls in sick. Ms. Cook shares some of this initial information with Dr. Stevens after their appointment, and Dr. Stevens increases John’s fluoxetine to 40 mg daily. She also engages him in a behavioral activation strategy to improve his mood that includes getting together with his friend Joe over the weekend.

Three days later, Ms. Cook has her weekly meeting with Dr. Brown, the consulting psychiatrist. They discuss John, the new addition to Ms. Cook’s caseload. Dr. Brown acknowledges the PHQ-9 score and the fluoxetine increase and reminds Ms. Cook of additional brief intervention techniques she has reviewed in the past with other patients. Five weeks later, during their caseload review, Dr. Brown notices John’s PHQ-9 score is unchanged. Ms. Cook notes that he stopped taking the fluoxetine the week before because of some ongoing jitteriness. Dr. Brown recommends switching to sertraline instead, and Ms. Cook conveys the recommendation to Dr. Stevens by flagging him in the electronic health record. Dr. Stevens reviews John’s other medications the following day and writes a prescription for sertraline after Ms. Cook has called John to discuss the recommendations of the consulting psychiatrist. John agrees to try the sertraline. Ms. Cook reviews the side effects with John and offers her contact information in addition to Dr. Stevens’s office if he has any problems with the medication. Dr. Stevens phones Dr. Brown and asks about the titration schedule of sertraline and starting dosage to confirm his management is appropriate. They agree to continue with increases in this medication with a target PHQ-9 of less than 5 if possible.

Five weeks after his last appointment, John remains depressed. He did not return Dr. Stevens’s last call regarding some recent lab results, and he no-showed one appointment. During their weekly caseload review, John is eighth on Ms. Cook’s list of 58 patients when sorted by PHQ-9 score severity which leads to a case review. Their registry of patients also has flagged John’s PHQ-9 as overdue and above their target. As she and Dr. Brown are reviewing all the patients, they review John’s score and with the information in the registry are able to quickly recall his latest treatment plan, including the sertraline recommendations. Dr. Stevens did write the prescription, but Ms. Cook is unsure what happened after that. She attempted to call John about 1 week after the sertraline was prescribed and left him a message that wasn’t returned. Ms. Cook and Dr. Brown agree that John needs increased outreach given his recent depression and lack of engagement, and Ms. Cook takes on this task over the next week. They then move on to Sue after spending about 5 minutes discussing John…

The following day, Ms. Cook writes a letter from the clinic to John offering assistance and begins to call more frequently. Three days later, John calls back, and he discloses that he never picked up the sertraline and was not sure he was worth the attention of the team. He reports that he didn’t want to feel like a failure again or let anyone down. John’s PHQ-9 score over the phone is 18, and Ms. Cook screens John for suicidal ideation, which is negative. She provides some education around depressive symptoms, the role of the team, and their desire to help him feel better. John agrees to pick up the sertraline from the pharmacy and check-in with Ms. Cook before the weekend to report on how he’s tolerating it.

John, the patient, calls Ms. Cook, the CM, on Friday and reports that he picked up the sertraline and is taking it without side effects but doesn’t feel much different after 2 days. Ms. Cook reassures John that this is not unusual, and that he needs to stick with the medication for 4-6 weeks at the right dose sometimes before his mood may change. They make a plan to check in once a week. In 4 weeks, John’s PHQ-9 score has gone from an 18 to a 15, and he is tolerating the sertraline without any problems. Dr. Brown, the consulting psychiatrist, recommends they titrate the dose to a higher level and continue to monitor John’s response. Dr. Stevens, the PCP, writes a new prescription for John; Ms. Cook confirms that he picks it up at the pharmacy and takes it; and after another 4 weeks, his PHQ-9 is 13. John reports that he is feeling better and has applied for a new job. He and his wife are fighting less, and they are talking about having him move back in. In spite of these gains, however, Ms. Cook discusses John’s remaining symptoms of prominent guilt and negative self-worth and poor quality sleep, energy, and concentration coupled to overeating—all of which contribute to his current score. They formulate a plan to begin more regular exercise. Because his PHQ-9 is still above 5, Dr. Brown’s advice is to continue to titrate the sertraline to the maximum daily dosage, noting his steady improvements.

Four weeks later, John’s PHQ-9 score is 5. He reports that he feels like his old self again, has moved back in with his wife, is exercising more regularly now, and starting to lose some excess weight. Two months after John achieved early remission from his depression, Ms. Cook calls him for a routine check-in. He notes that he stopped taking the sertraline for a couple of weeks right after their last conversation and had a relapse of some of his symptoms. His PHQ-9 score has jumped from 5 to 13, and John is feeling embarrassed and shameful.

He resumed his sertraline at 200 mg about a month ago but still struggles with energy and has stopped his workout routine. Dr. Brown suggests that they augment the sertraline with bupropion, and Dr. Stevens writes the prescription for John. One month later, John’s PHQ-9 score is 10, and Ms. Cook engages him with Behavioral Activation focused on his exercise regimen again. They discuss the cycle of inaction, guilt, and depression, and John agrees to experiment with a different workout regimen and assess his mood. Dr. Stevens automatically adjusts his bupropion to a higher level since he is tolerating it well, and 1 month later John’s PHQ-9 score is 4.

`

Tradition is forgetfulness of origins…

Edmund Husserl

"For Merleau-Ponty, the fact that geometry propagates itself from generation to generation in an anonymous sense as a set of human operations that began at no particular time in the past and which will be developed further in the present in order to arrive at a more developed science in the future is precisely what tradition is. “Tradition is forgetfulness of origins as empirical origins in order to be an eternal origin”. So tradition, according to Merleau-Ponty, essentially involves forgetfulness of empirical origins with the formation of a sense that can be transmitted over time and involving no conception of an origin...

Husserl’s account, as we have laid it out, however does not seem to necessitate such a reading. It is certainly not clear whether Husserl means to say that tradition essentially involves forgetfulness. Husserl does suggest that in order to uncover the structure of traditionality one does not have to concern oneself with empirical facts involving the names of the first geometers and the dates of their achievement. Traditions can develop in the absence of any factual knowledge of the founders of the tradition and the time of its founding. But this certainly does not imply that traditions necessarily require a forgetfulness of the empirical origins of that tradition. Husserls account does not seem to support the stronger claim made by Merleau-Ponty, in this regard…

"If the whole material medica, as now used, could be sunk to the bottom of the sea, it would be all the better for mankind — and all the worse for the fishes."

In my first 20 years in medicine [1963-1983], I can’t recall any physicians I knew or worked with having a financial relationship with a pharmaceutical company. The first time was a Grand Rounds that was what I would now call an Infomercial – shortly before I left the University [1983-ish]. Checking back in 25 years later, it seems like everyone had multiple such connections. I have no sense of how that happened. It was the same with industry sponsored clinical trials in mainstream academic journals – from never to every. Of course there were doctors who worked for industry, but they weren’t the same ones that populated academic departments. I never recall thinking about it, but I think I assumed it was a "tradition" of medicine. I’ve looked around for some account of how all of that changed, and haven’t found a thing.

Similarly, I’ve tried to find some history of where "Conflict of Interest is not a problem if it is acknowledged" specifically came from. While I agree that if a financial COI is present, acknowledged  is better than secret. But "not a problem"? Not hardly! Whether a guest·author, an employee·author, or a ghost·writer, the problem is the same. None of those categories are synonyms for the meaning of the word "author" that includes "originator" or "creator" – that implies an independent opinion. I might even be willing to go along with "Conflict of Interest is not always a problem if it is acknowledged and there is no money or other direct or indirect benefit involved."

In medical education, one doesn’t start out feeling like you’re a doctor. You’re an outsider looking in. The identity part arrives much later, if it does, indeed, arrive at all. It’s not easy to describe what I mean by that. I know I’m not talking about Evidence-Based Medicine, or the Biological Medical Model of Disease as, for example, the anti-biologists or anti-psychiatrist might explain. It has to do with an ethical tradition that is learned largely through example, by apprenticeship. While it may seem a paradox, the loudest criticisms of physicians come when that ethical tradition is absent – criticisms I find myself agreeing with most of the time. And there is simply no room in that ethical tradition for "Conflict of Interest is not a problem if it is acknowledged" no matter what argument follows.

Rather than further lament the lost idealism of a former time when the integrity of academic physicians could be assumed, where there was an ethical tradition that more or less assured us that our literature could be trusted, it’s time to accept the fact that it has eroded to a point where it’s time to rethink the system. We can no longer look at the name, academic rank, or institutional affiliation of the author of an article [or the publishing journal] and use that as evidence for the opinion it expresses. The obvious solution is a regulatory system that has enough ongoing oversight to insure that it’s not being gamed. We think our Petition fits the bill in the area of industry funded clinical trials [which is why I can’t seem to stop talking about it]. We back up primum non nocere with oversight and laws. Time to put similar teeth into the tradition of academic medical integrity…

"He who controls the narrative, controls the debate."

It was after retiring when I first became aware of how unreliable the information I had about the psychiatric medications I was being asked to prescibe as a volunteer physician had become. So I went to the medical resources traditionally available to me. I bought the latest textbooks, read the PDR, began to read review articles and the original articles reporting on the clinical trials of the drugs themselves. I got to know ClinicalTrials.gov and Drugs@FDA. I read the blogs available at that time – furious seasons, soulful sepulcher, carlat, etc. And I read about Conflicts of Interest and learned about Speaker’s Bureaus, Key Opinion Leaders [KOLs], and Senator Grassley’s findings of payola. It was a sadly disillusioning landscape.

That had never happened to me in Medicine. I had the conviction that when I hit a bump in the road I could hit the books and find my way. And this time it didn’t happen. I couldn’t find an anchor, some still point that I could count on. In a forty year medical career, I had counted on the academic literature to be a guide and it just wasn’t there this time. The chairman of the department I was affiliated with was removed from his post for unreported pharmaceutical income. The same was true for the President of the American Psychiatric Association. Such goings on in Medicine were unparalleled in my experience.

Flash forward six or seven years. It’s taken me that long to accept that things just aren’t like they used to be. In the past, I could count on the academic medical literature because of a covenant of integrity that was part of medicine’s academic tradition – embedded in its historic narrative. But there’s something now that really is different, and I credit Alastair Matheson for making it clear, though he did it in slightly different context [see rebranding…]. This is now part of academic medicine’s narrative:

"Conflict of Interest is not a problem if it is acknowledged."

That’s what is different now. And by the way, it’s an absurd declaration. Of course it’s a problem. How could it be otherwise? In the past, that covenant of integrity was the unseen force that allowed me to count on the literature. It’s not there any more, or maybe sleeping very soundly. And the time for lamenting its absence or trying to force it to come back has passed. It’s a time to accept that we’re in a different place now, and have to make adaptations to the world we actually live in. To hold people accountable directly. That false statement is currently controlling the narrative. That’s why we need for the FDA to actively certify, actively offer surveillance, actively intervene. The implicit checks and balances of historic medicine are no longer operating as they have in the past.