rarely, if ever, available…

Posted on Friday 15 August 2014

But our discussions of mental illness rarely focus on this inconvenient truth: these illnesses are currently just as fatal as the “big killers.” We must continue to invest in research to develop new and more effective treatments for people with depression and other mental illnesses. The goal must be a future in which no lives are lost as a result of suicide.

“It’s very important that we stop seeing these illnesses as false and stop blaming patients and see them for what they are — which are medical conditions, genetic conditions, brain disorders that require appropriate diagnosis, treatment, care, and support,”
APA President Paul Summergrad, M.D., on NBC Nightly News

I sincerely doubt that there will come a time when some pill will come along that will quickly whisk away the kind of profound depression that Robin Williams was apparently suffering. He was no stranger to feel better pills, and chose not to take them – to his credit.  There were a myriad of risk factors we know about: waning celebrity; financial problems; a cancelled tv series; the diagnosis of Parkinson’s Disease [which can be associated with Depression over and above as a stressor]. He was sleeping 18 hours a day and had no appetite. In his last picture, his weight loss is obvious.

I don’t want to pile on with after the fact analysis. There’s plenty enough of that coming from everywhere. But there is one thing that needs saying. A mainstay of treatment for patients with this kind of profound depression is hospitalization. And one of the reasons is protection from suicide. This is the kind of depressive illness that got lost in the 1980 DSM-III Revision that lumped it in with the more usual depressive illnesses – once called neurotic depression. Independent of one’s theories about the etiology or nosological preferences, impulsive suicide is a constant risk in such severe depressions, so protective hospitalization is a big part of any rational treatment plan – or at least it was. Managed Care and the psychopharmacological revolution have essentially eliminated the kind of mental hospitalization such patients need. It’s a paradox that with all the modern talk about depression, this kind of depression with delusional hopelessness and unbearable pain has gotten lost in the shuffle.

In June, Robin Williams checked in to the Hazelden Rehabilitation facility. not because of a relapse, but for a "tune up" of his sobriety. Maybe people do that, but I’ve never heard of such a thing. My guess is that he was looking for help in the only way he knew how, but that’s not what he needed. This kind of Depression is uncommon, but in a modern world, the "diagnosis, treatment, care, and support"  that Dr. Summergrad mentions are rarely, if ever, available for these particular patients…

"…the pain of severe depression is quite unimaginable to those who have not suffered it, and it kills in many instances because its anguish can no longer be borne. The prevention of many suicides will continue to be hindered until there is a general awareness of the nature of this pain. Through the healing process of time — and through medical intervention or hospitalization in many cases — most people survive depression, which may be its only blessing; but to the tragic legion who are compelled to destroy themselves there should be no more reproof attached than to the victims of terminal cancer."
Mickey @ 9:08 AM
Filed under: politics
into the Boston Harbor…

Posted on Friday 15 August 2014

Pharmalot: WSJ
By Ed Silverman
Aug 14, 2014

The U.K. agency that evaluates the cost effectiveness of prescription drugs has recommended the government pay for the controversial Sovaldi hepatitis C treatment, although not for all patients. The move, which still requires a final endorsement, comes as the medicine causes a ruckus in the U.S. The price tag – $84,000 for a 12-week regimen – has insurers and state Medicaid directors worried that the Gilead Sciences medication will become a budget buster and helped to fuel a national debate over the rising cost of prescription drugs.

Generally, the U.K.’s National Institute for Health and Care Excellence causes a ruckus of its own by declining to recommend coverage for medications. Consequently, the agency has often butted heads with drug makers and patient groups over its decisions. Last week, for instance, NICE and Roche battled over the cost of a cancer drug, although in a rare development, patient groups sided with the agency. NICE, in fact, sent mixed signals two months ago about its Sovaldi decision. The agency asked Gilead to supply additional data about certain patient populations and maintained there were “substantial uncertainties in the evidence” that the drug maker provided to win a coverage recommendation. The request for more data prompted speculation that NICE may not recommend coverage.

After reviewing the data, though, NICE agrees that Sovaldi is an effective improvement over existing treatments. The Gilead drug, by the way, can cure nine of 10 patients. The decision was likely helped by the lower price tag in the U.K. Gilead is selling its drug for about $56,000, according to a NICE spokesman. “It’s a lot cheaper here,” he tells us. The agency is recommending Sovaldi, plus interferon and ribavirin, for adults with genotype 1, which is the most common form of hepatitis C, and accounts for 46% of all cases in the U.K., a NICE spokesman says. The recommendation also extends to patients with genotype 3, which accounts for 43% of hepatitis C sufferers…
Pharmalot: WSJ
By Ed Silverman
Aug 7, 2014

“We have set three basic pricing tiers [based on a country’s per capita income and hepatitis C prevalence] that serve as the starting point for negotiations with national governments. The tiers are low-income, low middle-income and upper-middle income,” Gregg Alton, a Gilead executive vice president for corporate and medical affairs, tells the paper. Such decisions, however, have further fed a controversy in the U.S., where Sovaldi costs $84,000 for the same 12-week regimen and has become a proxy for a growing national debate over the rising cost of prescription drugs…
In the US, Sovaldi® costs $1000/day [total $84,000/patient]. Now we learn that in the UK, it will cost $56,000/patient [~$667/day]. And in India and Egypt, it’s being offered at $900/patient [~$11/day].  We once knew what to do about situations like this one:

Boston Tea Party, 1773
Mickey @ 6:36 AM
Filed under: politics
under some of the rocks…

Posted on Thursday 14 August 2014

I started writing about these topics a few years ago because I was stunned by the deceptive presentation methods in clinical trial reporting. And then I discovered that if a trial didn’t come out like they wanted and couldn’t be doctored, they just didn’t publish it. The more I looked, the worse things got. I kept running across the term CRO, one that I’d never heard before, and asked a more knowledgeable colleague what it meant. Looking into that arena lead me to a whole new level of deception. It has been a disillusioning journey, I must admit. Back in the day, there weren’t so many resources for chasing things down: Carlat, Soulful Sepulcher, Healthcare Renewal. Now there are many more, thankfully. But Dr. Roy Poses blog at Healthcare Renewal remains the gold standard when it comes to the big picture. This take on the recent article by Carl Elliot in Matter is up to his usual level and worth a full read for its editorial perspective:
Healthcare Renewal
by Roy Poses
August 13, 2014

Dr Carl Elliott seems to be one of the few people willing to investigate how modern medical research may threaten vulnerable research subjects.  His book, White Coat, Black Hat, opened with a chapter on vulnerable "guinea pigs," people willing to be clinical research subjects for money.  Such people may be desperate for money, and further may be homeless, and have psychiatric problems, including psychosis or drug or alcohol problems.  Dr Elliott just wrote another important article on the plight of vulnerable research subjects…
In Carl Elliot’s article [The Best-Selling, Billion-Dollar Pills Tested on Homeless People], he talks about making a personal hegira into the Clinical Research Center world, and he actually visited South Coast Clinical Trials, home to The Clinical Trials Guru. I first ran across South Coast back in 2011 [the clinical research industry: the CRCs…] directed by a post on Soulful Sepulcher [still active on Twitter]. In my recent take on Carl’s articles [some system…, the illusion of evidence…], I posted one of South Coast‘s many videos of their research subjects. Here‘s another oldie from South Coast, their discussion about the case of Dan Markingson, Carl Elliot’s major focus. And speaking of University of Minnesota’s bioethicist Carl Elliot, here’s his recent blog about another old friend I was also introduced to by Soulful Sepulcher some time back [selling seroquel II: into the fray…]:
Fear and Loathing in Bioethics
by Carl Elliot
August 11, 2014

Illinois has suspended the medical license of Dr. Michael Reinstein, aka The Clozaril King.  Reinstein "received ‘illegal direct and indirect remuneration’ from the maker of generic clozapine; did not consider alternative treatments for his patients; and disregarded patients’ well-being because of potentially life-threatening side effects of the drug."  

In 2009, ProPublica and the Chicago Tribune detailed how he had prescribed more of the antipsychotic clozapine to patients in Medicaid’s Illinois program in 2007 than all doctors in the Medicaid programs of Texas, Florida and North Carolina combined. Autopsy and court records showed that, by 2009, at least three patients under Reinstein’s care had died of clozapine intoxication.
Dr. Michael Reinstein was even more than the Clozaril King, he was also the psychiatrist for a Clinical Research Center next door in Chicago. I ran across this bit of information trying to run down where the Lurasidone [Latuda®] trials were conducted by looking at Google™ Maps, Street View [see hiding uptown]. Uptown Research is a CRC like South Coast, only in Chicago rather than California. They were also involved in some of the Seroquel® clinical trials:

Charles Ornstein at ProPublica has long been on the trail of Dr. Michael Reinstein:
by Charles Ornstein
Aug 11, 2014

Illinois medical regulators have indefinitely suspended the medical license of psychiatrist Michael Reinstein, who prescribed more of the most powerful and riskiest antipsychotic drug clozapine than any other doctor in the country. The decision by Illinois’ Department of Financial and Professional Regulation, signed Friday, suspends Reinstein’s license for a minimum of three years, at which time he can apply to have it reinstated.

The state’s medical disciplinary board recommended the sanction in May after determining that Reinstein, 71, received "illegal direct and indirect remuneration" from the maker of generic clozapine; did not consider alternative treatments for his patients; and disregarded patients’ well-being because of potentially life-threatening side effects of the drug. Reinstein’s motion for a rehearing was denied Friday, making the matter public.

Clozapine is approved to treat patients who don’t respond to other medications. But it can have dangerous side effects, including seizures, inflammation of the heart muscle, and a drop in white blood cells. The drug is considered particularly dangerous for elderly patients…

In 2009, ProPublica and the Chicago Tribune detailed how he had prescribed more of the antipsychotic clozapine to patients in Medicaid’s Illinois program in 2007 than all doctors in the Medicaid programs of Texas, Florida and North Carolina combined. Autopsy and court records showed that, by 2009, at least three patients under Reinstein’s care had died of clozapine intoxication. At that time, Reinstein defended his prescription record, arguing that clozapine is effective and underprescribed.

Last year, as part of an investigation into Medicare’s failure to monitor problem prescribers, ProPublica reported that Reinstein prescribed even more clozapine in Medicare’s prescription drug program for seniors and the disabled. We found that the program continued to let him prescribe even after the U.S. Department of Justice accused him of fraud and Illinois’ Medicaid program suspended payments to him…

I came back Monday from a vacation trip with friends where I spent little time thinking about contemporary matters medical. When I got back Monday night, I was out of the rhythm of keeping up with the things I usually follow. What I always find when I’ve taken a break is that I feel anew the same kind of outrage I felt five or six years ago when I first began to understand how the pharmaceutical-academic psychiatry alliance had become so widely corrupting. Obviously it’s a much bigger problem than simply psychiatry, but it appears my specialty was especially vulnerable [and had some people in high places who dove in head first]. It always takes me a few days to recover my composure and get back into the state of play, rather than this just rant on and on about the myriad of absurdities like those mentioned above.

I remain awed by the tenacity of the people who have dogged this problem for years – people like Drs. Bernard Carroll and Bob Rubin, Jon Juriedini and Healthy Skepticism, David Healy and Rxisk, Stephany of Soulful Sepulcher, Danny Carlat, Dr. Poses of Healthcare Renewal, Ed Silverman of Pharmalot, Joe Friday at Pharmagossip, Carl Elliot of Fear and Loathing in Bioethics, Ben Goldacre of AllTrials, the volunteers of the Cochrane Collaboration – and the growing number of others who’ve taken up the task of shining spotlights into the dark corners of the medical industries. What’s missing, by my read, are strong stands by the various medical professional organizations and particularly their sponsored academic journals. Dr. Fiona Godlee of the British Medical Journal stands tall as an exception to the laissez-faire attitude of journal editorial staffs elsewhere.

On my trip, I returned to the Museum of Civil War Medicine in Frederick Maryland that I mentioned last Fall [in the museum…], this time with four other doctors and our wives – people we were stationed with in the early 1970s that we spend a week with every summer. In the Fall, I was impressed with the advances in medicine in the Civil War – triage, ambulances, hospitals, nursing care, anesthesia and early amputation to prevent gangrene. This time through, I found myself thinking about what was missing. About the only medication in the displayed pharmacy kits that would pass muster was opium. Everything else was either in the toxic poison or inert patent medicine category. Those were the days before Pasteur and Lister so antiseptic techniques were unknown, much less antibiotics. The real killers in the Civil War were the infectious diseases that swept through the camps in waves, killing many more than the enemy’s bullets. On the nearby battlefield at Antietam where 23,000 soldiers became military casualties in a single day, there was an unfinished stone with a small embedded brick cross among the cannons and heroic granite sculptures of soldiers. It marked the spot where Clara Barton [later founder of the American Red Cross] narrowly escaped a miniball that killed the fallen soldier she was tending to. The chief of nursing there was Dorthea Dix, the crusader for moral treatment of the mentally ill.

As we walked around the museum, I realized that among the ten of us seventy-somethings, there were any number of artificial joints, stents, lumbar fusions, early detected cancers with successful treatment, and I expect that the dopp kits back at our B&B held a number of pill bottles with medication that actually helped with something or another. I think I need periodic reminders of the advances and successes of modern medicine to counter the cloud that sometimes forms looking at the dark places under some of the rocks that dot the medical landscape…
Mickey @ 5:22 AM
Filed under: politics

Posted on Wednesday 13 August 2014

Pharmalot: WSJ
By Ed Silverman
Aug 7, 2014

India has become the latest country where the Sovaldi hepatitis C treatment will be offered for $900 per patient. The move, which was reported by The Times of India, comes a few weeks after the manufacturer, Gilead Sciences GILD +0.66%, is making the medication available for the same price in Egypt. The pricing reflects an effort by Gilead to forestall the sort of criticism the pharmaceutical industry has often encountered when selling life-saving medicines in poorer countries, which have often complained bitterly that many of its citizens have been unable to afford some treatments. An advocacy group last year formally opposed a patent for Sovaldi in India, claiming the treatment is based on “old science” and, therefore, does not deserve patent protection. An Indian generic drug maker made a similar point recently in asking Indian officials to deny the patent. If they prevail, generic alternatives could become available at low prices.

“We have set three basic pricing tiers [based on a country’s per capita income and hepatitis C prevalence] that serve as the starting point for negotiations with national governments. The tiers are low-income, low middle-income and upper-middle income,” Gregg Alton, a Gilead executive vice president for corporate and medical affairs, tells the paper. Such decisions, however, have further fed a controversy in the U.S., where Sovaldi costs $84,000 for the same 12-week regimen and has become a proxy for a growing national debate over the rising cost of prescription drugs.

The U.S. price tag has prompted objections from insurers, state Medicaid programs and politicians, among others, who complain the cost for Sovaldi will bust budgets as more hepatitis C sufferers are diagnosed and seek treatment. Gilead and its supporters say this argument is, effectively, short sighted by noting that Sovaldi can cure nine of 10 patients, many of whom would require more expensive treatment over a protracted period. In other words, society saves money in the long run…
There is nothing that Gilead will ever do or say that will justify the US price tag on Sovaldi®. And they’re not alone. AbbVie’s Humira® is another example of similar price gouging. The Atypical Antipsychotics and many new cancer drugs are in the same class. These PHARMA Companies are using the patent laws not for their intended purpose. There’s no "free market enterprise" or "supply and demand" in these enterprises. It’s simply a predatory monopoly feeding on a captive audience – and in the case of Sovaldi®, a captive audience with lives on the line. After decades of jury-rigged clinical trials and false advertising campaigns, when PHARMA finally comes up with something that might actually work as advertised, they feel entitled to break the bank. Shame on them…
Mickey @ 11:00 PM
Filed under: politics
a more legitimate science…

Posted on Wednesday 13 August 2014

You’ll never know more about a disease than with those first cases in medical school. The first autopsy, the first case in the clinic, the first hospitalized patient. It’s all so new and things fall on a mind eager to see the things learned in the basic sciences manifested in a real patient. In those days, one believes everything you read in journals, textbooks, hear from valued teachers. It’s a time where one is desperate for anchors. This article is by a second year medical student, however it unfortunately veers off the track.
New York Times: Opinion
AUG 12, 2014

Edward Larkin is a second-year medical student at the University of Pennsylvania, where Irene Hurford is an assistant professor in the department of psychiatry.  

A few months ago, a patient came to our hospital, seeking help. One of us, Edward, was on the team that treated him. He was pleasant, if slightly withdrawn, and cogent. He was a college graduate in his 20s and had recently been fired from his job as a high school math teacher, because of unexpected absences. He had come to believe that government agents were conspiring against him, and he had taken to living out of a truck and sleeping in different parking lots. By the time he came to us, he was exhausted. A diagnosis became clear: he had schizophrenia. We admitted him to the hospital, and after a few days, with his symptoms under control, we released him. Unfortunately, we prescribed a medication for him that could cause significant, permanent harm, instead of an equally effective drug with milder side effects — all because he was uninsured.

Schizophrenia, which affects 1 percent of the population and emerges in the late teens to early 20s, is deeply misunderstood. People who suffer from it are often suspected of being dangerous, but this is not usually the case, and antipsychotic drugs are very effective. Our patient was exactly the kind of person who, with the right treatment, could have weakened the stigma surrounding schizophrenia. Antipsychotic drugs fall into two classes: the older ones, like Haldol, and newer ones, like Abilify and Latuda. Both classes are equally effective at treating some of the worst symptoms of schizophrenia, specifically the hallucinations, delusions and paranoia that cause social alienation. [They’re not effective for treating “negative symptoms,” like low motivation].

But the older drugs can cause a multitude of serious side effects, including a potentially devastating one called tardive dyskinesia. This condition involves unsettling, animalistic smacking and wagging of the lips and tongue. At its extreme, it can affect the entire body. It occurs in 20 percent or more of patients who take the drugs long-term, and it tends to start so mildly that patients can’t identify it in time to stop taking the drugs. It is often irreversible.

The newer drugs have lower rates of tardive dyskinesia [estimates vary, but most likely less than half or one-third the risk], although they can cause weight gain and predisposition to diabetes, among other side effects. The newest among them, however, have decreased these risks, too. And a 2006 study showed that patients were more likely to keep taking the new drugs than the older ones.
    Note from 1boringoldman: This 2006 study is from a proprietary Insurance Claims database with the following financing and ghost? authorship: "This study was supported by AstraZeneca Pharmaceuticals LP. The authors would like to acknowledge the assistance of Anusha Bolonna, PhD [PAREXEL MMS], who provided medical writing assistance on behalf of AstraZeneca."  [The article itself makes multiple pair-wise comparisons with no overall ANOVA to justify them, nor did it provide enough information to allow me to accurately estimate the overall ANOVA's significance].
As a result, most psychiatrists prefer the newer drugs, especially for younger people, and they should have been the clear choice for our patient. He didn’t have the luxury of choice, however, because he was uninsured, and he was explicit about the fact that he didn’t have much money to spend on medications. So we had to prescribe him Haldol, which costs about $20 per month, instead of one of the newer drugs, which can cost more than $600 per month. These issues will be amplified as progress is made in discovering the mechanisms of psychiatric disease, as it likely will be, thanks to the billions of dollars that are now going to neuroscience research. We can already see the results of that kind of investment in oncology, where extravagantly expensive specialty drugs are coming on the market. But as we make much-needed progress and develop new, expensive treatments that are clearly superior to old, cheap ones, we have to ask: Will those with the most to gain still receive a lower standard of care?
Good for our young medical student taking the position as a patient advocate. But the point he’s making about the drugs is unfortunately one fostered by PHARMA propaganda and filled with curve balls. First off, the study he quotes in Psychiatry Research is refuted by the NIMH and even by a more cogent prospective study conducted by AstraZeneca itself [kept hidden because of its outcome] in addition to having a flawed analysis:
[CATIENIMH on top, AstraZeneca's unpublished Study 15 below].
Perhaps an even greater omission from this article is that it fails to recognize that its logic is the logic of TMAP [the Texas Medical Algorithm Project] which was the source of numerous charges against J&J/Janssen resulting in one $158 M settlement and many other court battles. It remains a major PHARMA scam still largely unprosecuted.

So while his point holds that we aren’t taking good-enough care of Schizophrenic patients, it’s not our using the older medications that’s the problem [in fact, there are generic Atypicals now as available as the first generation antipsychotics]. Our failure is in offering little more than medications to his young patient and vague hopes for some future breakthrough medication that will fix everything.

I don’t mean to malign the student author here. Maybe I do worry about his supervisor’s mentorship. But my point is rather that he shouldn’t have to be disillusioned about the literature he found [the 2006 study] at this point in his career. Articles like that one – an industry infomercial – continue to do their damage in perpetuity. They just shouldn’t be there in the first place. I hope Edward’s patient advocacy stays with him, but is directed by a more legitimate science…
Mickey @ 9:25 PM
Filed under: politics

Posted on Saturday 9 August 2014

In my last post [the illusion of evidence…], I was playing with the phrases evidence of illusion [looking for signs that a scientific paper has used the the techniques of presentation to obscure rather than clarify data] and the illusion of evidence [valuing the mathematical/statistical results of Randomized Clinical Trials over all other sources of information]. I was trying to get at something besides simply the corruption of the Clinical Trial system – but lost track along the way. The corruption theme is so compelling and those two articles in Matter were so powerful, that they carried away my narrative. The thing that got lost, the thing I started off wanting to say, probably deserves its own separate post anyway. In a recent article [unfortunately behind a pay-wall], David Healy makes the point explicitly,
    Today, many argue that the growing crisis in health care stems from conflicts of interest and lack of access to clinical trial data. Our view is that small-print disclosure in academic footnotes and open access to trial data, important though these are, will not solve problems that stem from the notion that clinical trials provide a higher form of knowledge than knowledge borne in a clinical encounter – the realm of the experiential and the singular…
and he illustrates it with a poem:
    This ‘Trust in Numbers’ story was caught wonderfully when it was unfolding, by George Oppen, a New York poet and member of the communist party, in his 1968 volume Of Being Numerous:
      Crusoe we say was rescued.
      So we have chosen.
      Obsessed, bewildered
      By the shipwreck of the singular
      We have chosen the meaning
      Of being numerous.

I envy that eloquence. For many, this point is counter-intuitive and easy to brush off.

beyond corruption…

Even in the best of circumstances – when protocols are followed precisely, diagnosis is rigorously pursued, analyses are pristine, conflict of interest is absent – a Randomized Clinical Trial is time-limited, and constrained by the measurement instruments selected, proxies like the HAM-D scale substituting for depressive affect. In addition, statistical significance or even effect size measurements don’t necessarily parallel clinical changes that make much of a difference. Subtle adverse effects often become apparent in a time-frame that exceeds the trial’s duration. In many cases, the cleanest of clinical trials can only say that the drug may possibly be effective and may possibly be safe.

beyond limitations…

In the case of psychiatry, the limits of the clinical trial are in bas relief. Unpleasant emotions themselves are not pathological – anything but. They are a part of an essential and elaborate warning system similar to physical pain. Among those presenting with emotional difficulties, primary disorders of the emotional system [Manic Depressive Illness, Melancholia, Anxiety disorders, psychosis, etc] are in the minority. In the majority whose emotional discomfort is related to some aspect of their life or personae, the use of emotion altering medications is highly dependent on the specifics. Likewise, the capacity to manage adverse effects, addiction, withdrawal, the downside of psychoactive medications, is as variable as ripples in the stream. A physical analogy might be the use of corticosteroids. For some, short-term use can be therapeutic. For others, it can be the introduction of a medication that can be over-used with disastrous consequences.

beyond groups…

After medical school and an internal medicine residency in a busy charity hospital where everyone was quite ill, I found myself in a military hospital on a base with healthy soldiers and their dependents – a very different place. My head was filled with facts and algorithms galore. But I had much to learn. The majority of patients had symptoms but rarely any of the dire illnesses that populated my mind. And I realized that a lot of my job was informed reassurance – a different role I had to learn to fill. Somewhere along those early days there, I realized that I was thinking in terms of case studies, talking less about diseases. A particular case comes to mind that goes with this topic:

    She had been diagnosed with Idiopathic Thrombocytopenic Purpura, a condition where the platelets, cells involved in clotting, all but disappeared leading to easy bleeding. The wisdom of the time was that taking out the spleen would cure cases in kids under 13, but wasn’t helpful in kids over 13. She was 13 at diagnosis, and a splenectomy had been curative. When I saw her, she was thirty something, mother of two, and had consulted a gynecologist for heavy periods. She was referred because her blood smear showed no platelets and her platelet count was essentially zero. We did the workup and started her on the recommended anti-metabolite. We were rewarded with a rising platelet count. One day, she came in "itching," a sign of liver toxicity  and we watched with dismay as she became jaundiced and quite ill from our treatment. Her platelet count rose to normal, but it took a month for her liver function to return [to our great relief].

    We sent her to the Air Force teaching hospital in Texas. When she returned, she was on another anti-metabolite [cousin to the one we used]. Our consulting hematologist sent us a stack of articles about treatment. Her platelets rose, but the itching returned, along with signs of liver failure. This time we stopped the medication more quickly and she didn’t get quite so sick. One day, I asked her about bleeding, and she said that except for heavy menses, it was no problem. I had been following protocol, and had given her two cases of liver failure chasing an abnormal lab test in an otherwise asymptomatic person, abetted by our best and brightest. We stopped the medications. Depot hormone shots eliminated her periods. And she did fine for the two years I followed her after that.
I know it’s not a Randomized Clinical Trial, but the case has always stuck with me because I was young and wanted to do the right thing, so I checked with the experts and followed recommendations precisely, but I was treating a surrogate, an abnormal lab value, and not attending to the clinical reality of the patient. I have no idea how this patient lived with such a low platelet count and no bleeding problems – but that was the way the case went for years after I stopped assaulting her with chemotherapeutic agents. I could tell such stories for hours – stories where well studied guidelines, clinical trials, or algorithms weren’t right for a given patient. I learned that the case at hand can often end up trumping the group recipe when they are at odds. Clinical medicine mirrors the Zen saying: 
    you can’t get it from books,
    you can’t get it without books.
Without the evidence-base from history, group studies, treatment guidelines, we’re lost at sea. But without careful attention to the individual case in front of  us, we can wander just as far off track. And so to the point being made by Dr. Healy:
    …small-print disclosure in academic footnotes and open access to trial data, important though these are, will not solve problems that stem from the notion that clinical trials provide a higher form of knowledge than knowledge borne in a clinical encounter…

beyond clinical trials…

The necessarily contained environment of a Randomized Clinical Trial is only a distant surrogate to that of the patients encountered in clinical practice, analogous to the relationship between the model airplane and the jumbo jet – a useful step, but hardly the full story. The cogent question is how did it come to be that the clinical trial has been escalated to some kind of gold standard for evidence based medicine rather than what it is – a minimum safety and efficacy requirement for FDA approval.

The point of the push for accurate Randomized Clinical Trials is to give practitioners a clear picture of the safety and efficacy of available medications, not to direct treatment or initiate an ad campaign. The real clinical trial is in the individual patient, and sometimes, the best medicine is in none at all.
    With the patient mentioned above, we saw her frequently. We made sure her husband’s next assignment was to a base stateside with a full hematology department [affiliated with a medical school]. He sold his Porsche and bought a Volvo after we cautioned them about car wrecks. But other than stopping her menstrual periods, it was what’s called benign neglect or watchful waiting.
Mickey @ 6:00 AM
Filed under: politics
the illusion of evidence…

Posted on Thursday 31 July 2014

One could see Matter‘s pairing of The Best-Selling, Billion-Dollar Pills Tested on Homeless People and Why Are Dope-addicted, Disgraced Doctors Running Our Drug Trials? mentioned in my last post [some system…] and by others [like Dr. Howard Brody's More on Guinea Pigging--The Quality of Pharmaceutical Research] as a walk on the wild side – disgraced professionals and professional patients making their living from the Pharmaceutical Clinical Trial scene. And certainly an inspection of the motives and practices of the involved industries [PHARMA, CROs, and the various medical economies] would reinforce that it’s a financially driven milieu increasingly distant from the its expected roots [healthcare, scientific, and academic]. Dr. Brody highlights this segment from the Peter Aldhous’ piece as the essence of the Elliot/Aldhous message:
    … “The whole thing is profit driven,” says Michael Carome at Public Citizen, a consumer advocacy organization in Washington, D.C. “You can see where corners might be cut, looking the other way when there might be concerns about an investigator.” Some experts argue that the FDA’s entire rulebook for clinical trials, with its talk of things like “institutional” review boards, reflects the academic past of clinical research — not today’s industrial juggernaut of for-profit clinical trials firms and for-hire review boards, which oversee a workforce of doctors drawn from regular medical practice. “They are regulations for a world that doesn’t exist anymore,” says Elizabeth Woeckner, president of Citizens for Responsible Care and Research, which campaigns for the safety of medical research volunteers.

But it’s more than simply the nomenclature and regulations that come from these academic traditions. The ersatz authors are usually listed with their academic rank and university affiliations as if either have much to do with the initiation or conduct of the studies themselves, other that as perhaps a locus for recruitment and administration [if even that]. More bizarre, in many cases, the authors don’t come into the picture in a substantive way until the final revision process. The fact that the trial was conducted by a contracted commercial enterprise, analyzed by the industrial sponsor, and written by a ghost is rarely apparent on reading the article. Likewise, the appearance of the published articles on Clinical Trials in peer-reviewed professional journals lends a further aura of academic legitimacy – rarely earned in the case of Clinical Trials. The bizarre CV’s of these authors listing hundreds of publications is no more significant than the body counts that we read about during the Viet Nam War – falsely inflated indices disembodied from their true meanings – more sales pitch than honorific.

Many of our best and brightest scientists occupy themselves these days poring over the published scientific articles of others looking for evidence of illusion – the use of scientific and statistical methodology to either enhance weak signals or misrepresent negative findings. Others, like the Cochrane Collaboration, sift through the assembled literature hoping to find the studies with enough scientific rigor to be taken seriously. This has indeed become an age of meta·analysis – porting the application of critical science from the studies themselves to a later re·analyses of a group of studies, a laudable goal but one with an unfortunate built-in lag time – a science of science once removed. Likewise, the traditional scientific debate of letters to the editor or rapid responses [BMJ] require a vigilance not practiced by the majority of clinicians. So the counter to the scientific distortions in clinical trial reporting becomes a low hum overwhelmed by the music in the foreground.

In pointing out the dark under-belly of Clinical Trials, Elliot and Aldhous aren’t just talking about a piece of the Clinical Trial world that has to do with discredited doctors and the exploitation of homeless people – something to excise. They’re talking about only the most visible symptoms of a sick system – publicly modeled on academic medical science of yore in form but not substance. Many of these trials and the publications they’ve generated give only the illusion of evidence worth attending to – a sham exercise of the scientific method. Speaking of illusions, it is unlikely that regulations per se will ever fix the problems so long as the current levels of conflict of interest remain in the system. The biggest illusion of all may well be that conflicts of interest are relative, or that they can be regulated. Almost by definition, they can either be allowed to continue to dominate this scene or be eliminated…
Mickey @ 1:55 PM
Filed under: politics
some system…

Posted on Wednesday 30 July 2014

How the destitute and the mentally ill are being used as human lab rats
By Carl Elliott
June 29, 2014
By Peter Aldhous
June 29, 2014
I don’t know Peter Aldhous, but most of us do know Carl Elliot of Fear and Loathing in Bioethics as a tireless crusader for the case of Dan Markingson and what it says about the state of Clinical Trials. As is my custom, I don’t clip out pieces for the really good articles. They deserve being read in their full original form. I think both of these articles are important, but I particularly appreciated the first one because it covers things that I ran across along the way and didn’t know what to do with. Carl actually went to the Clinical Research Centers in question and interviewed the people recruited there [see the clinical research industry: the CRCs…, hiding uptown]. When I ran across places like South Coast Clinical Trials and The Clinical Trials Guru I was at something of a loss for words. And, by the way, one has to throw in another article into this mix from three years ago, Deadly Medicine, by Donald L. Barlett and James B. Steele in Vanity Fair [still available online]. Whatever you visualize when you read a clinical trial in a journal, it’s probably not right…

Mickey @ 12:26 AM
Filed under: politics
the $1000 pill…

Posted on Tuesday 29 July 2014

Speaking of my last post and capitalism…
Mickey @ 6:48 PM
Filed under: politics
enough is long past enough…

Posted on Monday 28 July 2014

Pharmalot: WSJ
By Ed Silverman
July 28, 2014

The scandal over bribery allegations in China has taken another discouraging turn for GlaxoSmithKline with the news that both the Federal Bureau of Investigation and Securities and Exchange Commission are conducting probes of the drug maker’s activities there, according to The Wall Street Journal. The disclosure comes amid ongoing turmoil for the drug maker after Chinese authorities recently accused the former head of Glaxo operations in China of ordering subordinates, his sales team and other employees to bribe hospitals, health care organizations and others on a large scale.

The drug maker tells the paper that it is cooperating with Chinese authorities and informed the U.S. Justice Department and the SEC of the Chinese investigation. A Glaxo spokesperson declined to comment to the paper about the FBI interviews, saying talks with regulators are confidential. The interest by U.S. authorities is not surprising, given that Glaxo disclosed in 2010 that U.S. authorities contacted the drug maker about its overseas operations as part of a wider probe into dealings by the pharmaceutical industry in other countries and the Foreign Corrupt Practices Act. The agencies more recently began looking at Glaxo practices in China following the allegations, the paper writes.

Meanwhile, bribery allegations concerning Glaxo operations have spread to other countries. Last week, Syria was added to a list that now includes Lebanon, Jordan, Iraq and Poland, according to a report that recounted information sent to Glaxo executives by a whistleblower. The scandal in China, of course, endangers Glaxo’s ability to build its business in a crucial market, but also undermines a pledge by Andrew Witty, the Glaxo chief executive, to transform the drug maker into a leading progenitor of improved business practices in the pharmaceutical industry…
Already being investigated by the Chinese government and Britain’s Serious Fraud Office, GSK has now been targeted by the FBI and SEC in the US, not to mention their recent settlement here [with their usual denial of any wrongdoing statement following close behind, an echo of the $3 B US settlement two years ago]:
by Jack Friday
June 5, 2014

GlaxoSmithKline has confirmed it is going to pay a massive fine after admitting it mis-promoted a range of drugs in the US. The pharmaceutical company stated that it will pay $105 million [£63 million] settlement with 44 US states and the District of Columbia following the way the firm promoted anti-depressants Paxil and Wellbutrin and asthma medication Advair.

However, GSK did not admit any wrongdoing regarding the promotion of the medication and insisted that the money it is paying out is in relation to previous issues. "We don’t feel like this is who we are today," GSK spokeswoman Mary Anne Rhyne told the BBC. "These are historic matters – they relate back to the federal government settlement in 2012 so some of these events are as long ago as 14 years"…
While we recently read of the sins of GSK in off-label promotion and bribing doctors to use their products in other countries, but we often forget what was happening in my home turf, Emory University in Atlanta Georgia for over a decade. Shortly after Dr. Charlie Nemeroff became Chairman of the Psychiatry Department, Sally Laden of STI recruited him in 1993 to chair their pre-launch meeting [see PAXIL ADVISORY BOARD MEETING] for Paxil, their new antidepressant at the time. That was the beginning of a long and lucrative association. He was their advisor for 14 years [further instruction…] as well as an active speaker on behalf of their drugs [up to 14 speaker trips per month in his prime] and author of their ghosted papers/books. One of his faculty, Dr. Zach Stowe, was a full time promoter of using Paxil/SSRIs during pregnancy and was busted for being paid by GSK shortly after Nemeroff. And the NIMH financed a joint NIMH/GSK grant for Emory to test new GSK drugs that still bleeds several million a year from the NIMH coffers [and produces nothing]. One might claim that Emory was a Department "that GSK built," but there were so many others in the mix, it would be more accurate to say "that PHARMA built."

My point is that when Mary Ann Rhyne says "These are historic matters," She means to imply that they are part of a distant past and no longer true. More accurately, these matters are the history of GSK since it came into existence in 2000 through merger, and persist to the present – obviously. Since the $3 B settlement in 2012, we’ve heard the "turning over a new leaf" routine over and over, but the truth is that it should have been "turning over new rocks" and finding some dark creature underneath each and every one of them. Is that a GSK problem, or a PHARMA problem? Is that a GSK history or a PHARMA history? Is corruption the history of PHARMA?

I would find it very hard to answer that question with a "No." Personally, I think I must’ve come into things during a lull period. I started medical school in 1963 right after the major reform of the Kefauver/Harris Act. I had a Lilly doctor bag, stethoscope, tuning fork, and reflex hammer. I learned a lot of anatomy from the CIBA atlases drawn by F. Netter. All pens and prescription pads had some pharmaceutical company’s name somewhere. I even knew a few detail men. But I don’t recall having any idea what company made what drug through medical school, through a medicine residency, through the Air Force, or during psychiatric training.That may be an artifact of training in big charity hospitals. My first awareness of what company made what drug came when Prozac came along in 1987 [and thereafter]. I never saw detail reps once in practice, and at medical meetings, I snunk through the exhibit areas collecting pens, pads, and rubber body parts [office supplies] while the pretty [and handsome] reps were otherwise engaged. I’ve learned that was an idiosyncratic way to be.

But I think, as I said, I came in a lull. It appears that the forces of regulation in the universe have been chasing the Pharmaceutical Industry from its origins in the days of Patent Medicines to the present, only to be periodically thrown off the scent by good behavior after one or another reform movement. But when things settle down, they’re up to their old tricks. We put up with their walks on the wild side because we count on them for new drug development. My own take on all of this is that it’s always a Faustian Bargain guaranteed to come to no good end, and we’d best rethink the whole thing. This may well be an area where capitalism can never work. It is really not a "free enterprise" in that patients, and to some extent doctors, are a captive audiences under the current system. And as for GSK, enough is long past enough…
Mickey @ 10:43 PM
Filed under: politics