I spent a whole post on just a piece of a paragraph from Tom Insel’s and Linda Brady’s piece in Neuropsychopharmacology [Translating Discoveries into Medicine: Psychiatric Drug Development in 2011, Neuropsychopharmacology Reviews 2012 37:281–283.], but I saved the rest for special consideration:
INTRODUCTION
Recent reviews have described the crisis in central nervous system drug development, especially for psychiatric disorders. As several pharmaceutical companies reduced their investments in psychiatric drug development, NIMH has asked: [1] why the retreat from one of the most important public health targets, and [2] how could we invest federal dollars to ensure that the public will have a next generation of treatments? We have heard many answers to the retreat question: abundance of generics, lack of novel validated targets, paucity of predictive animal models, absence of biomarkers, and regulatory challenges, to name a few. The business case for psychiatric drug development is not promising. CNS drugs cost more and take longer to reach the market than other types of drugs: only 8% of those that make it to clinical trials end up being approved and they tend to fail in late-stage clinical trials after a significant investment has been made…
Meaning that the drug companies are pulling out of CNS drug development, claiming that it costs too much and takes too long – too many hurdles. To understand what Insel is saying here, one has to get up to speed on Regulatory Science – the FDA/NIMH attempts to streamline the drug approval process to determine efficacy and safety in response to the pharmaceutical industry’s complaints. In fact, we’re getting a whole new Institute for just that purpose:
REGULATORY SCIENCE
Regulatory science will be the focus of the National Center for Accelerating Translational Science [NCATS], a new institute proposed at NIH, as well as a new NIH-FDA Leadership Council, which began meeting in 2010. One regulatory science area that needs to be addressed in the near term is combination therapies. It is amazing that there is so little evidence for the effectiveness or safety of combination treatments even though most psychiatric patients are on multiple medications. Multi-target therapies, add-on strategies, and/or combination therapies that include pharmacological and behavioral interventions will be critical strategies to address unmet clinical need. Targeting cellular function rather than single proteins is expected to introduce novel classes of multi-target drugs with fewer adverse effects and toxicity. However the regulatory pathway for the co-development of innovative combination treatments may not be as clear for psychiatry as for infectious diseases and cancer.
Imagine our surprise! "Multi-target therapies, add-on strategies, and/or combination therapies." What was STAR*D? CO-MED? Augmentation with Atypicals? It amounts to lowering the bar for approval by allowing combo approval. Now get ready for some double-speak. This next and final section is a challenge:
CHANGING THE CULTURE – WHERE ARE WE GOING?
In order to develop a long-term strategy to de-risk promising compounds for further development by the private sector, a new paradigm is needed to rapidly profile novel compounds and to assess proof of clinical mechanism. Experimental medicine studies are needed to bridge between animal and human studies. Studies in healthy volunteers should include pharmacodynamic biomarkers to establish the link between the optimal dose of the compound and the molecular mechanism in addition to tolerability and safety. Experimental questions should be tested in small groups of patients to establish the link between molecular mechanism and clinical effect; these data would provide confidence in biological rationale and safety to inform go/no go decisions to advance a compound for further clinical development . A network of clinical sites is needed with capabilities to apply standardized functional imaging, electrophysiological, and cognitive/behavioral technologies to address experimental medicine questions. New models are needed to tackle the inefficiencies in drug development. Pre-competitive public–private partnerships exist for biomarkers and for methods development to support innovation in drug discovery. The Biomarkers Consortium focuses on validation of biomarkers for application in translational research and drug development; examples of neuroscience projects include proteomic approaches to validate a panel of markers using plasma and CSF samples from the Alzheimer’s Disease Neuroimaging Initiative. The Innovative Medicines Initiative supports collaborative research projects and builds networks to enhance pharmaceutical innovation in Europe. One project, NEWMEDS, focuses on development of animal models, standardized paradigms for fMRI and PET imaging, pharmacogenetic markers, and trial designs for developing new medications for depression and schizophrenia. A new, open access consortium model, Arch2POCM, offers a venue to extend partnerships between government, academia, and the private sector to identify compounds that explore proof of clinical mechanism for selected diseases and targets. Most recently, the NIH is exploring opportunities to partner with the private sector for repurposing of drugs that meet toxicity and safety criteria to deliver significant value at reduced cost and in dramatically shorter time frames for diseases with unmet medical need. Successful PPPs will expedite pre-competitive collaboration between key stakeholders to advance novel targets and mechanisms into clinical development. Catalytic efforts are needed to fill the pipeline with the next generation of treatments for psychiatric disorders.
"de-risk". "Pre-competitive public–private partnerships". "… the NIH is exploring opportunities to partner with the private sector for repurposing of drugs that meet toxicity and safety criteria to deliver significant value at reduced cost and in dramatically shorter time frames for diseases with unmet medical need." Nothing like a few neologisms to throw up a smoke screen. Here’s the defogged version.
The drug companies are saying that they’ve mined the known strategies for CNS drugs. In spite of Dr. Stahl’s crazy rant [myopia – uncorrected…] that they’re being chased off by "pharmascolds," truth-be-told, they don’t have the libido to develop new strategies and drugs for CNS if they’re going to get shot down late in the game. So the FDA and NIMH are working on making it easier for them. If you read that incredibly obtuse paragraph over three or four times, you’ll begin to get the picture. They’re trying to make things a lot easier for the drug companies, including "repurposing" formerly rejected drugs. Viibryd is an example [Viibryd II…].
I don’t buy the argument that we need to push science "to ensure that the public will have a next generation of treatments." I’ve spent a year looking at the last generation of psychoactive drugs and am underwhelmed with the idea that our standards for safety and efficacy need to be loosened. If anything, they need to be tightened. But my view is biased. I think it’s biased in the right direction, but everyone explains their bias by being right. So I’ll down-regulate my rant. All of the initiatives hidden in these few double-talk paragraphs about how to jump-start the CNS pharmaceutical industry increase the possibility of putting low efficacy, unsafe drugs on the market. We’ve just been through that with the ones we already have. I say, DANGER! DANGER! DANGER!
My concern is that the forces behind these initiatives are not just "to ensure that the public will have a next generation of treatments." It’s to perpetuate the Psychiatric-Industrial Complex that has already given us enough grief over the last several decades to warrant a time-out penalty. Tom Insel and friends are playing with fire. DANGER! DANGER! DANGER!
Indeed it is certainly what it looks like to me. All of this makes me sick, sad and certain that there is not a shred of integrity in Thomas Insel whatsoever. The idiot that “treated” my kid and has been teaching and advising other medical professionals on how to “properly” drug children, testified in a Senate hearing and when asked if he knew WHY so many kids are being drugged, he said he had no clue…As if his writing the how-to guides and teaching it at a University, and giving advice on the phone in this State’s “advice line” had no effect…
The pity of it is that this kind of systems management prose has become routine for bureaucrats like Insel and Brady. After so many repetitions it becomes verbigerative. The passages you cited confirm the saying that people who cannot think clearly cannot write clearly. Orwell would have had a field day with this pair, though you are a good pinch hitter for him!
It is a dark day for clinical science when the bureaucrats in NIMH believe it is their role to shape the field or to speak for academic psychiatry. That is the mindset that gave us expensive failures like STAR*D, CO-MED and the rest.
Much of the problem has to do with their own attempts to broaden diagnostic criteria. As you have so articulately stated, life, personality and parenting problems do not get better with drugs. We have drugs that work pretty well for the originally intended indications – e.g. true psychosis, melancholia. These are probably the conditions for which we will eventually find reliable biomarkers. The drugs now appear to be ineffective because the indications have been so diluted by conditions that need a non-drug approach. The pharma industry has shot itself in the foot and knows that it will never find drugs to treat these fabricated disorders.
It all sounds pretty insane…
In fact, it meets the classic definition of ‘insanity’ –
“Doing the same thing (over and over) and expecting a different result.”
Looks like the inmate are running the asylum.
Duane
“The pharma industry has shot itself in the foot and knows that it will never find drugs to treat these fabricated disorders.”
WOW! Excellent point Carol! Never thought of that, but it’s true.
a post of note on http://neuroskeptic.blogspot.com
http://neuroskeptic.blogspot.com/2011/12/young-canadian-and-on-antipsychotics.html
Antipsychotic use in Canadian children and teens is rising dramatically – prescriptions more than doubled in just 4 years, from 2005 to 2009.
“That’s according to a paper just out from Pringsheim et al. It’s been known for a while that broadly the same is true of the USA. The data reveal that the Canadian border is no barrier to the spread of antipsychotics.
What’s surprising is that while in the USA, some of these drugs are officially licensed for use in certain children and adolescent psychiatric disorders, in Canada all such use is off-label. That didn’t stop there being nearly 700,000 youth prescriptions for an antipsychotic in 2009, in a country with a total population of 35 million – although bear in mind that this includes multiple prescriptions for the same person.
The growth in antipsychotics is accounted for by the second-generation “atypical” antipsychotics. Risperidone (Risperdal) was the biggest success story accounting for well over half of the total.
What’s disturbing about this, as I’ve said before, is not so much the fact that these drugs are being used but the speed of the growth. It represents a fundamental shift in the way children and adolescent mental health problems are treated, one which has happened so fast that it’s hard to believe that there was time to properly think through the consequences…
Use of SSRI antidepressants and psychostimulants (mainly ADHD drug methylphenidate, Ritalin) also rose between 05 and 09, but only by about 40%. That means that there were more antipsychotic than SSRI prescriptions in children and teens by 09, which is pretty remarkable.”
The damage done by this insane model of “biochemical imbalance” is entrenched, I continue to see people who acknowledge up front they have tangible, impacting psychosocial stressors that if reduced or eliminated would help them improve, but, they still insist on medications at moment one. And more and more thanks to my non psychiatric colleagues who sell this up front in the PCP/Family Med/OBGYN/Nurse Prac’s offices.
Who has time for psychotherapy and problem solving? Obviously people who are not interested in getting it right, just getting better. Per the line I have quoted in the past, “if you want to get better, take a pill, but if you want to get it right, then face the truth.” Truth, what a bitch.
Here’s a thought for you all,the next time you write or fill a psychotropic prescription, just imagine you are writing a check for a pharmaceutical company to cash then hand a sizeable percentage to it’s CEO. It really is that true!