Posted on Thursday 23 October 2014
by Mark KesselNature Biotechnology 2014 32:983–990.
It wasn’t that long ago that the pharmaceutical industry was considered among the most respected industries and Merck the most admired corporation in the United States.
This is in sharp contrast to consumer attitudes today, when the industry’s reputation is not much better than that of the financial sector or tobacco companies. Why has an industry in the business of developing lifesaving drugs garnered such a negative reputation, and how should it go about fixing it?
Big pharma and big business: To some extent, reputational decline can be attributed simply to the fact that many pharma companies are large multinational corporations that are now facing strategic issues that require an adjustment to the traditional business model. The increasing price and cost pressure, patent expirations on blockbuster drugs leading to aggressive generic competition, public policy and changes in how consumers access medicine are leading to erosion of profit margins. Big pharma, like other industries, is not immune from the pressure of having to meet Wall Street quarterly earnings expectations; indeed, today’s companies are measured on how well their stock performs and boards of directors incentivize management accordingly to meet Wall Street’s demands. The needs of patients are secondary.
Kessel makes an eloquent plea for the value of corporate reputation, and outlines changes that would, indeed, improve both the company’s image and function. But I expect most of the multinational PHARMAs already have a "workgroup" "tasked" with the same thing. GSK has Sir Andrew Witty out front carrying a banner of reform while his Chinese division is bribing physicians to prescribe their drugs. Alex Gorsky of Johnson & Johnson masterminded Risperdal®’s meteoric rise, and now an army of lawyers works to keep him out of a courtroom as they try to cut their losses in the aftermath. In the legal actions, PHARMA settles the government suits rather than allowing them to go to a jury, and later "denies any wrong-doing" – no matter what they admit in the settlement agreements. In the Civil suits, they play the legal chess in the appeal courts when they lose – much like the culture of jail-house lawyers inhabiting our crime dramas.
According to Alexander Brigham and Stefan Linssen of the consulting firm Ethisphere Institute, over the past three decades, the percentage of a company’s value attributable to tangible assets has dropped from 90% to just 25%. Other estimates also suggest that it is the intangible assets of a company [including reputation] that currently represent as much as 40–60% of a corporation’s market capitalization. Thus, a company’s reputation is among its most valuable assets.
My read is that these major pharmaceutical corporations have completed the move from being drug·discovery and drug·manufacturing companies, part of the legitimate health care effort, to being drug·selling cash·cows in the business of "doing business" [in the Bernie Maddof/Enron tradition]. I would suspect any moves they made in the reform arena would be called "brand·building" in their meetings – illusions they definitely know how to create [that should probably be followed with mumbles like at the end of the DTC ads as we watch the cured patients and colorful butterflies]. Meanwhile, here‘s the Forbes’ version of a PHARMA argument lest you’re hoping for anything but the business of "doing business."
Posted on Wednesday 22 October 2014
by Mark KesselNature Biotechnology 2014 32:983–990.
||193||criminal and civil liabilities arising from Endo’s marketing of the prescription drug Lidoderm [lido-caine]. As part of the agreement, Endo admitted that it intended that Lidoderm be used for unapproved indications and that it promoted Lidoderm to healthcare providers this way.|
|11/2013||J&J||2,200||criminal and civil allegations relating to illegal promotion of the prescription drugs Risperdal [risperidone], invega [paliperidone] and Natrecor [Nesiritide] for uses not approved as safe and effective by the FDA, the targeting of elderly dementia patients in nursing homes, and the payout of kickbacks to physicians and to the nation’s largest long-term care pharmacy provider, Omnicare.|
|12/2012||Amgen||762||criminal and civil charges that the company illegally introduced and promoted several drugs, including Aranesp [darbepoetin alfa], a drug to treat anemia. Amgen pleaded guilty to illegally selling Aranesp to be used at doses that the FDA had explicitly rejected, and for an off-label treatment that FDA had never approved.|
|Sanofi||109||Allegations that company gave doctors free units of Hyalgan [hyaluronate injection to relieve knee pain] to encourage sales, lowered the effective price by promising doctors free samples, while at the same time obtaining inflated prices for the drug from government programs by submitting false price reports.|
|10/2012||Boehringer Ingelheim||95||Allegations that company promoted several drugs including Aggrenox [aspirin/dipyridamole], Atrovent [ipratropium], Combivent [Ipratropium/albuterol] and Micardis [telmisartan] for nonmedical ly accepted uses.|
|07/2012||GSK||3,000||Civil and criminal liabilities regarding misbranding of Paxil for treating depression in patients under 18, even though the drug had never been approved for that age group as well as failure to disclose safety information about Avandia to the FDA.|
|05/2012||Abbott||1,500||illegal promotion of Depakote [divalproex] in indications for which it had never been approved: schizophrenia and control of aggression and agitation in elderly dementia patients.|
|11/2011||Merck||950||illegal promotion of Vioxx as a treatment for rheumatoid arthritis before it had been approved for that use and misrepresentation of the drug’s heart safety to increase sales.|
||520||Allegations of illegal promotion of Seroquel [quetiapine] for a variety of unapproved uses, such as aggression, sleeplessness, anxiety and depression. The company paid the fine but denied the allegations.|
|09/2009||Pfizer||2,300||Misbranding Bextra with "the intent to defraud or mislead," promoting the drug to treat acute pain at dosages the FDA had previously deemed dangerously high. Bextra was pulled from the market in 2005 due to safety concerns. The government alleged that Pfizer also promoted three other drugs illegally: Geodon [ziprasidone], Zyvox [linezolid]and Lyrica [pregabalin].|
|01/2009||Eli Lilly||1,420||Off-label promotion of Zyprexa [olanzapine] to elderly populations to treat dementia. The US government also alleged that Lilly targeted primary care physicians to promote Zyprexa for unapproved uses and "trained its sales force to disregard the law."|
Posted on Tuesday 21 October 2014
Posted on Tuesday 21 October 2014
With the American Academy of Child and Adolescent Psychiatry meeting in San Diego right now, I’m having something of a remembrance of things past period. Of course there’s Paxil Study 329 which stands in my mind as a paradigm for an infamous era, along with a other less well known Clinical Trials suggesting that the SSRIs are effective and safe in the treatment of adolescent depression [ie more Wagner et al…]. It remains a major unresolved question in my mind why the Journal of the American Academy of Child and Adolescent Psychiatry is still unwilling to retract Paxil® Study 329, or for that matter, why the American Journal of Psychiatry didn’t [and still doesn't] retract Wagner et al’s ghost written Citalopram [Celexa®] paper [collusion with fiction…]. And I continue to wonder why journals still publish the stream of papers attempting to discredit the Black Box Warning on these drugs about the uncommon but potentially fatal suicidality that the drugs sometimes cause [a betrayal…]. It’s like the ripples from that period when the pharmaceutical industry, complicit psychiatrists, and journals were publishing fiction-as-fact under the cover of darkness won’t die out.
There was one issue from that period that remains very sticky – Pediatric Bipolar Disorder. It’s sticky because the patients in question really exist, and the medications in question really work, and the treatment questions are really tricky for anyone who actually sees these cases. And whether these cases represent a distinct group or not is, itself, an open question in my mind. To use Dr. Joseph Biederman’s term, they are children with super angry, grouchy, cranky, irritability. They drive parents, teachers, siblings, psychiatrists, therapists, and themselves crazy. They usually have the clinical findings of ADHD [with a capital H] but there’s no cure with stimulants, and if you give them antipsychotics, they do become more manageable – but... These are among the kids that get drugged, often in response to pleas by parents, caretakers, psychologists, social workers, teachers, etc. – the exasperated people who deal with them. I’ll skip the many diagnoses invented for this maybe-group, except for one – Pediatric Bipolar Disorder.
When Risperda® was introduced, it came with a study of behavioral treatment for retarded children that was, of course, positive [genuinely positive] [see trial 93: a bad penny…]. Janssen’s application for FDA Approval was turned down. When Dr. Biederman began to say that these kids with super angry, grouchy, cranky, irritability had Pediatric Bipolar Disorder, this study was republished and repurposed under Dr. Biederman’s name [Risperidone for the treatment of affective symptoms in children with disruptive behavior disorder: a post hoc analysis of data from a 6-week, multicenter, randomized, double-blind, parallel-arm study] and the rest is history. Pediatric Bipolar Disorder took off like wildfire and the papers flowed from everywhere [I called it Biedermania].
I’ve reviewed all of this ad nauseum. And I ended up wondering if Pediatric Bipolar Disorder even exists, or if it does, thinking it’s uncommon. In my opinion, the reason Pediatric Bipolar Disorder caught on was that Child Psychiatrists and Pediatricians who were seeing these extremely difficult kids were previously guiltily treating them with antipsychotics for behavior control [unable to place them in the tough love token economy environments of the past], and that the diagnosis of a disease treated with a medicine for that disease took away the guilt. I was volunteering in a child clinic for a time, and I ultimately quit working there because of this very issue. The pressure to medicate with antipsychotics was overwhelming because there were no rational alternatives, and that’s just not my cup of tea. It’s simply a do no harm thing for me. But I felt some empathy for my colleagues who were and are in that double bind, and couldn’t just say, "No thanks."
I wish I knew the contents of numbers 1 and 3, just wondering what they’re saying about Pediatric Bipolar Disorder and the use of the SSRIs in depressed adolescents. But that roster is not intended to be an indictment of the AACAP. Compared to my remembrance of things past, it’s a remarkable improvement. Even the topics are more benign and rational. But they’re all ripples nevertheless. It’s time for the ripples from that time in our history to stop…
Posted on Monday 20 October 2014
Pharmalot: WSJBy Ed SilvermanOctober 20, 2013
Responding to the ongoing controversy over the prices for new hepatitis C treatments, U.S. Sen. Bernard Sanders [I-Vt.] will probably hold a hearing – possibly before the year ends – to examine how the cost is affecting the U.S. Department of Veterans Affairs, according to his spokesman. Sanders is chairman of the Senate Committee on Veterans’ Affairs.
His interest in a hearing comes as the expense of these medicines helps fuel a national debate over the rising cost of prescription drugs. New hepatitis C treatments, in particular, have caused a ruckus, because they promise cure rates exceeding 90%, which is prompting a sudden surge in prescribing – and subsequent concerns over the effect on insurance budgets. For the past several months, pharmacy benefit managers and state Medicaid programs have complained that the cost of Sovaldi, a treatment sold by Gilead Sciences, may become unsustainable. Sovaldi costs $1,000 a pill, or $84,000, for a 12- week regimen. Gilead maintains the treatment is a cheaper alternative to older forms of care that may be less successful and involve costly hospitalization.
Federal programs may feel the pinch, as well. A recent forecast from the Veterans Department indicated that Sovaldi will cost the department about $1.3 billion over the next two years. And that’s after a discount the VA receives that brings the cost per pill down to about $543, according to department documents provided earlier this year to the U.S. Senate Committee on Veterans’ Affairs. A Veterans Affairs spokeswoman writes us that the department added Sovaldi to its national formulary, or list of drugs for which coverage is provided, last March. As of October 1, more than 5,300 veterans have received treatment with Sovaldi, she writes, adding that about 225 patients are started on the treatment each week.
And so, Sanders “is interested [in holding a hearing,] among other reasons, because of the impact on the VA,” his spokesman tells us. The timing for a hearing, however, remains uncertain. The spokesman says a hearing may occur following the upcoming midterm elections on Nov. 4, “but it’s really up in the air.” This is not the first time Congress has responded to concerns over the cost of hepatitis C medicines. Last July, two members of the U.S. Senate Finance Committee asked Gilead to provide financial information about the $11 billion deal in which it acquired the treatment, R&D costs and subsequent pricing forecasts. A committee spokesman tells us the probe remains under way, but could not offer an update.We asked Gilead, which has more recently received FDA approval to sell a newer, fixed-dose combination treatment called Harvoni that includes Sovaldi and another compound, for comment and will update you accordingly. [UPDATE: A A Gilead spokeswoman later sent us this note: "We are not aware of a hearing but we are cooperating with the Committee and responding to their questions."] This is the second time in recent weeks that Sanders has indicated concerns about prescription drug costs. Earlier this month, he was one of two members of Congress who launched an investigation into generic drugs and asked 14 drug makers to provide data on what was called the “escalating prices they have been charging” for some medicines.
Posted on Monday 20 October 2014
Mental health civil wars leave patients in desperate lurchPsychology Today: Saving Normalby Allen J. Frances, M.D.October 20, 2014
Posted on Monday 20 October 2014
PsychiatricNewsOctober 17, 2014
As development of drugs to treat psychiatric disorders lags behind that of drugs for other illnesses, a recent study published in Psychiatric Services in Advance sheds light on why the pipeline for psychotropic medicines is nearly empty.
Researchers from Brandeis University and Truven Health Analytics led an investigation of the current state of psychotropic drugs in the pipeline and potential barriers that may keep these drugs from reaching distribution in the United States… The analysis showed that the pipeline for psychotropic drug development — 99 clinical trials were included — is limited, with little product innovation evident. Most of the examined drugs were a combination of existing of U.S. Food and Drug Administration-approved medicines or individually approved medicines that were being tested for new indications or delivery-system approaches [such as an injectable version that is similar to an approved oral form]. Only three drugs differed substantially from existing drugs…In an interview with Psychiatric News, Alan Schatzberg, M.D., a professor of psychiatry at Stanford University and former APA president, said that the departure by pharmaceutical companies to develop innovative psychotropic medicines could result in serious problems for the field of psychiatry, especially for patients. “There is a number of initiatives by various organizations to help with this problem, including the European College of Neuropsychopharmacology, which is working with companies to provide investigators with compounds that have been shelved, and NIMH’s Research Domain Criteria [RDoC], which promotes research on specific [and new] biological targets," he said. Schatzberg emphasized that it will take a concerted effort on the parts of governmental agencies, industry, as well as APA to advocate for investment and innovative psychiatric drug development. “Silence will not be helpful to our patients,” he concluded…
Med CheckPsychiatricNewsby Vabren WattsOctober 17, 2014
According to the National Institutes of Health [NIH], as many as 3,000 genes express proteins whose molecular actions could be altered by medicines, yet only 10 percent of these “druggable genes” are targeted by drugs that have been approved by the Food and Drug Administration [FDA].
The NIH recently announced the launch of Illuminating the Druggable Genome [IDG], a three-year pilot project to explore poorly understood genes that have the potential to be modified by medicines. The IDG will target understudied genes of four important protein families that may be affected by medications — nuclear receptors, ion channels, protein kinases, and G-protein coupled receptors.
“We have a gap in the drug-development pipeline between what gene activities we know could be modified by medication and what currently is targeted,” said James Anderson, M.D., Ph.D., director of the NIH Division of Program Coordination, Planning, and Strategic Initiatives. “By focusing on understudied genes, we hope to find potential targets for medications to treat or cure some of our most burdensome diseases — and then share what we learn so that all can build on this knowledge.”Primary funding for pilot awards is coming from the NIH Common Fund, which supports high-impact pioneering research in all divisions of NIH. Institutions granted awards will thoroughly investigate potential gene targets and share what they learn on a public resource that will help the larger scientific community build on the findings through basic research and clinical translation.
Results from the Human Genome Project revealed that the human genome contains 20,000 to 25,000 genes. A gene contains [encodes] the information that each cell uses to make [express] a protein, which is essential for the body to function properly. Abnormal protein expression is associated with many human diseases, which makes proteins key targets for therapeutic agents…
Approximately 3,000 genes are considered part of the “druggable genome”, a set of genes encoding proteins that scientists can or predict they can modulate using experimental small molecule compounds. Yet, only about 10 percent of these genes encode proteins that have been targeted successfully by an approved drug. Therefore, a large number of proteins remain for scientists to explore as potential therapeutic targets. The vast majority of the druggable genome encodes four key protein families: G-protein-coupled receptors, nuclear receptors, ion channels and kinases…By expanding the potential therapeutic space through the IDG program, NIH is clearing a path for more efficient disease-related research and more effective treatments for patients.
I did notice along the way that the last new better drug became the next old obsolete drug with some regularity. And with that came the illusion that the drugs were improving [I would now see it as more determined by patent life and advertising]. And in those salad days, psychiatry had developed a sizable commentator class – a group of academics who commented on the drugs, talked about what was coming next, wrote about the neurobiology of this or the psychobiology of that regularly. In my mind, I called it future-think, with the good stuff always lying just around the corner, but it never occurred to me that a house of cards might tumble if the march of the new ever came to an end. So now we’re illuminating the druggable genome, repurposing existing drugs, building neuro-chips for in vitro assays, and revising diagnoses to fit drug effects [RDoC] in an attempt to revitalize the previous flow of new treatments.
There was another quote in that article about the 2012 Pipeline Summit that has also stayed with me:
I thought that was an incredibly naive comment. One could say that about a million things in medicine. The comment implies that "if you need it, it will come". Most scientific discovery doesn’t work that way. It’s closer to, "don’t push the river, it runs by itself." There are places where mounting a huge effort in science speeds up the process, but those are areas where there’s a clear direction, and the task is working out the practical details [Manhattan Project, NASA, Salk Vaccine, DARPA, etc]. Their quest for genuinely new psychopharmacology starts from near zero. And the pharmaceutical industry has a tremendous interest; has been at it for years; and just couldn’t find a thread to pull that lead them anywhere. So whether you agree that new symptomatic CNS drugs are a critical national priority or not, the likelihood of locating them [if they indeed exist] may not be enhanced by NCATS, the RDoC, or any other directed research under NIH/NIMH martial law. In fact, this forced march might squeeze out the guy who would notice something odd on a dirty petri dish [Alexander Fleming Discovers Penicillin].
Posted on Saturday 18 October 2014
"We look forward to welcoming you to sunny San Diego for AACAP’s 61st Annual Meeting!
Gabrielle Carlson, MD, AACAP’s Program Chair, welcomes you to San Diego from the USS Midway, the site of the Welcome Reception on Wednesday, October 22. All are invited to attend!"
In the spirited video from the deck of the USS Midway, Gabrielle Carlson sporting a sailor’s cap, welcomes us to the AACAP Annual Meeting, ending with the words, "Get here however you can!" You may not recognize her name right off. Here’s a reminder:
The Dramatic Rise in Neuroleptic Use In Children:
Why Do We Do It and What Does It Buy Us?
Theories from Inpatient Data 1988-2010by Gabrielle A. Carlson, MDJOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY 2013 23:144-147.
…It is ironic that the most noxious and impairing behavior, namely explosive outbursts in children, has no ‘‘home’’ in the DSM no- sology. Recognizing that explosions can occur in many conditions, neither intermittent explosive disorder nor, if it is accepted into DSM-V, DMDD, allows the diagnosis if the explosions are ‘‘better explained by’’ another condition. There is not even a consistent way in which one can find information about rage outbursts. In PubMed, there are almost completely different databases for terms like rages, rage outbursts, anger outbursts, rage attacks, explosive outbursts, and meltdowns. Irritability, the term that seems increasingly to be adopted, like aggression, may sub- sume these behaviors, but is not synonymous. Therefore, we speculate that the behavior that most drives the most use of AAPs does not even have a label that can be consistently used, and will certainly, without a "home," never be an indication for FDA approval….
In conclusion, the meteoric rise in the use of AAPs in children with ADHD and ODD reflects the fact that the traditional evidence-based treatments (stimulants and parent training/behavior modification) are either unsupported by providers and insurance (at least in terms of the intensity they require) or that these treatments are insufficient, because of the severity of the conditions being treated.AAPs may be expensive, and clearly have important adverse effects. The question is whether society (and insurance companies) want to support the alternatives. If they do not, I feel that the rhetoric is disingenuous. I, for one, would be grateful if the AAPs could compensate for what we have lost in terms of other treatments, and were as powerful as the media imply.
However, I not only think that haunting these authors is justified, but is actually an imperative. Twenty of the twenty-two authors of Study 329 are still alive, six are in significant leadership positions in the American Academy of Child and Adolescent Psychiatry, and others dot the by-lines of other ghost-written industry-funded experimercials like this one. Gabrielle Carlson is AACAP’s Program Chair welcoming the attendees to the meeting. It is likely that many of the named authors were on the by-line of that article only because they were site primary investigators for the clinical trial itself and little involved in the writing or the extensive data manipulation involved in creating this masterpiece of deceit – now a monument to an era yet to be fully acknowledged.
In the case of Dr. Carlson, Stony Brook was in the group of sites added to Paxil Study 329 late because of slow recruitment and accounted for only 11 subjects in the trial. She’s not mentioned in any of the subpoenaed documents that I know of. Apparently it was simply a source of revenue for Stony Book, and another paper to add to her CV. But that’s the whole point. Other than the two SKB/GSK employees who directed the show creating the paper with ghost-writer Sally Laden, the actual non-involvement was true for the twenty academic authors whose names were on that author‘s list. They lent their academic credentials and the reputations of their institutions to the paper, a ticket insuring that it would be accepted in a prestigious journal and read by colleagues who respected those honorifics, without really participating in its creation. But even worse, in the decade during which the paper has been universally vilified, not one of those authors has come forward and said a word. They continue to occupy high places, adding an obvious irony to Carlson’s comment, "Get here however you can!"
Sure, Managed Care bureaucrats have pushed atypical antipsychotics over more intensive and expensive interventions [keeping the cost of medical care down]. Of course the Pharmaceutical Industry has promoted antidepressant medications for treatment of adolescent depression [in the business of selling FDA approved drugs]. Yes the professional organizations have created guidelines that recommend these practices [evidence-based medicine from peer-reviewed journals]. But without those names on the by-line certifying the articles, the papers wouldn’t have been published that allowed those things to happen. And when the authors sit in silence in their own careers even after it becomes clear, as in this case, that they lent their names, positions, and institutions to a fictional publication, they are the main force in the center of perpetuating what’s wrong.
Posted on Friday 17 October 2014
WebMDOctober 17, 2014
A black box warning about suicide risks should remain on the anti-smoking drug Chantix® until it can be reevaluated using findings from thorough scientific studies, a U.S. Food and Drug Administration panel of experts said Thursday. Chantix® has carried the FDA’s strongest warning label since 2009 after it was linked to violent or suicidal behavior among some patients taking the drug.Pfizer asked the FDA to drop the boxed warning, citing recent studies suggesting that patients taking Chantix® were not at increased risk for psychiatric problems, the Associated Press reported. However, the 11-member FDA advisory panel voted to retain the black box warning on Chantix®. One member voting in favor of removing the warning and six favored slight changes to the label. The FDA does not have to follow the advice of its expert panels, but typically does.
Pharmalotby Ed SilvermanOctober 17, 2014
“I think Pfizer took quite a chance trying to get the box deleted. They obviously wouldn’t have done it if they thought they could convince people, but they failed completely,” says Diana Zuckerman, the president of the National Center for Health Research, a non-profit advocacy group.
“They had the best presentation money could buy – very good analyses and complicated statistics to prove their point. And the company trotted out these studies and tried to make a very strong case for why the Black Box should be deleted, but only one person voted their way."
“Pfizer took a big chance, but I think they did so because they were afraid the next study wouldn’t be so favorable and maybe they could get rid of the Black Box warning now. Remember, if it were removed, it would be hard to get it reinstated later, even if a post-marketing study showed risk.”Pfizer is not flinching. “The completion of our currently ongoing safety study will represent one more step forward in the process of accurately characterizing the neuropsychiatric safety of this important medication,” says Steven Romano, a Pfizer senior VP who heads the medicines development group.
But there’s something else to say. Pfizer’s sales of Chantix® are down. They obviously think it has something to do with the Black Box warning in the labeling. So they are spending tons of money trying to get the label removed – thinking more patients will "ask their doctor if…" and that more doctors will not be afraid to prescribe it. It’s a sign of their inflated sense that they can influence and control the world if they just play their cards right. It doesn’t occur to them that maybe their sales are down because Chantix® is only for the hardy. If you’ve prescribed it yourself, you know that it does exactly what that Black Box label says it does, and maybe more often than the label suggests. They can’t change that with a label eraser or even a piece of Robert Gibbons statistical sleight of hand [see way past time…].