Tuesday, December 30, 2008

Pharmaceutical market failures?

This review in the New York Review of Books shows how drug companies pay bribes to medical doctors and psychiatrists to have new drugs publicly endorsed and promoted and how research activities into new drugs are given a positive spin through the input of drug company money.  Quote:
'No one knows the total amount provided by drug companies to physicians, but I estimate from the annual reports of the top 9 US drug companies that it comes to tens of billions of dollars a year. By such means, the pharmaceutical industry has gained enormous control over how doctors evaluate and use its own products. Its extensive ties to physicians, particularly senior faculty at prestigious medical schools, affect the results of research, the way medicine is practiced, and even the definition of what constitutes a disease'.
Consider Dr. Joseph L. Biederman, professor of psychiatry at Harvard Medical School and chief of pediatric psychopharmacology at Harvard's Massachusetts General Hospital.
'Thanks largely to him, children as young as 2 years old are being diagnosed with bipolar disorder and treated with a cocktail of powerful drugs, many not approved by the FDA for that purpose and none of which were approved for children below 10 years of age.
Legally, physicians may use drugs that have already been approved for a particular purpose for any other purpose they choose, but such use should be based on good published scientific evidence. That seems not to be the case here. Biederman's own studies of the drugs he advocates to treat childhood bipolar disorder were, as The New York Times summarized, "so small and loosely designed that they were largely inconclusive."
In June, Senator Grassley revealed that drug companies, including those that make drugs he advocates for childhood bipolar disorder, had paid Biederman $1.6 million in consulting and speaking fees between 2000 and 2007. Two of his colleagues received similar amounts'.
In an interesting twist after this was revealled the president of the Massachusetts General Hospital and the chairman of its physician organization sent a letter to the hospital's physicians expressing not shock over the enormity of the conflicts of interest, but sympathy for the beneficiaries! "We know this is an incredibly painful time for these doctors and their families, and our hearts go out to them."'

The conflicts of interest here are clear enough for prescribing doctors and pharmaceutical regulators to appreciate.

Update: This article in NYT records that US pharmos have agreed to stop issue branded trinkets - Vioxx pens and so on.  Quote:
“We have arrived at a point in the history of medicine in America where doctors have deep, deep financial ties with the drug makers and marketers,” said Allan Coukell, the director of policy for the Prescription Project, a nonprofit group in Boston working to promote evidence-based medicine. “Financial entanglements at all the levels have the potential to influence prescribing in a way that is not good.”

18 comments:

conrad said...

1) There's all this whinging and whining about drug companies influencing research, but this is of course not surprising -- who else is going to fund it? This type of research costs more than most universities could ever hope to fund themselves.

2) I really fail to see the difference between, say, an ARC Linkage grant and what people are complaining about. It's no surprise most universities would be happy to bring in millions of dollars. This is just a strange hate of drug companies.

3) If young kids have mental disorders and drugs help them, I don't see what the problem is. If doctors are prescribing unapproved drugs that haven't been tested, then that's poor ethics on the doctors part, not the drug company.

hc said...

I think the difficulty is that doctor preferences for prescription and for advocating drugs are related to the often undisclosed money paid to them.

Patients have poor information and this creates the opportunity for adverse outcomes.

civitas said...

"I think the difficulty is that doctor preferences for prescription and for advocating drugs are related to the often undisclosed money paid to them."

Harry, can you prove the above statement? I know it's what you believe, but this is the sort of thing one should have actual proof of before saying, isn't it?

As to patients having poor information, there is an unbelievable amount of information available to patients (in the US anyway).

hc said...

Civitas

Good to hear from you again. The article states:

'...most doctors take money or gifts from drug companies in one way or another. Many are paid consultants, speakers at company-sponsored meetings, ghost-authors of papers written by drug companies or their agents,and ostensible "researchers" whose contribution often consists merely of putting their patients on a drug and transmitting some token information to the company. Still more doctors are recipients of free meals and other out-and-out gifts. In addition, drug companies subsidize most meetings of professional organizations and most of the continuing medical education needed by doctors to maintain their state licenses'.

I am surprised that in Australia at medical conferences such as APSAD that firms such as Reckitt Benckiser run sessions where doctors promote their drugs Subutex and Suboxone as legal opiates for maintenance treatment of opiate addiction.

See e.g. http://www.apsad2008.com/highlights.asp

The discussions are uniformly positive with doctors from the world over endorsing these drugs.

Yet the treatments themselves are controversial since they generally keep users addicted for life with a stream of paymemts accruing to RB.

I would prefer some 'distance' on these issues.

conrad said...

"I am surprised..."

I don't see why, many of the conferences I go to have promoters of one type or another (books, tests, various equipment my area uses etc.). They also sponsor sessions sometimes. The information is occasionally handy. I assume the same is true of economics.

"The discussions are uniformly positive with doctors from the world over endorsing these drugs.

Yet the treatments themselves are controversial since they generally keep users addicted for life with a stream of paymemts accruing to RB"

There's two issues here. One is whether it's ok to have people on drugs all their lives even if there are non-drug solutions. The answer to this obviously yes -- many people have less controversial drugs that combat things as easy to solve as a heroin addiction yet kill many more (i.e., hypertension drugs for the overweight or unwilling to exersize, type II diabeties drugs for those unwilling to change their diet, etc.).

The second is whether its okay for companies to get profits from these. I think this is a non-issue -- if it was an issue, we would have to get rid of all the hypertension drugs etc., which is obviously crazy.

davidp said...

How do you tell if a 2-year old has bipolar disorder? Is there a chemically based way to determine this or is it based solely on behaviour? I find it hard to imagine how such a drastic diagnosis could be made for a 2-year old based on behaviour. Though am not in medicine and am (sort of) happy to be corrected.

John said...

How do you tell if a 2-year old has bipolar disorder? Is there a chemically based way to determine this or is it based solely on behaviour? I find it hard to imagine how such a drastic diagnosis could be made for a 2-year old based on behaviour. Though am not in medicine and am (sort of) happy to be corrected.

Conrad is probably better placed to address this than I am but my understanding is that a diagnosis of ADHD should not be made until 5 years of age. As for bipolar at 2 years of age, in my view that is getting close to professional incompetence and stupidity. There would need to be very some very convincing evidence to allow such a diagnosis. If your child has been given that diagnosis, I think it would be very prudent to seek another. I have real concerns about sustained psychoactive medical interventions in children and believe that in this matter too many doctors have rushed in where angels fear to tread. It is necessary but it is used too often.

A very worrying example of pharmaceutical strategies:

I just read this yesterday. If researchers want to research a prescription drug they have to obtain it from the manufacturer. They then have to sign contracts which can include the right of the manufacturer to veto publication of any research. This should be illegal because it can substantially mask potential problems with many drugs, which may explain the spate of drug withdrawals and warning statements over the last few years.

conrad said...

"that a diagnosis of ADHD"

Actually, I'm not thrilled at all by the way most mental health disorders tend to be diagnosed -- generally people (often doctors with next to no training at all) simply use the DSM checklist (or similar), chat to the client a bit, and presto, there you have your initial diagnosis (incidentally, it's worthwhile having a look through the DSM list to see what they are like if you haven't -- basically a bunch of symptoms dreamt up by a group of psychiatrists -- many people don't even agree on some of the categories). That's no doubt why the rate of diagnosis for different things varies wildly in different places -- you can interpret what you find how you wish in many cases. Of course, that being said, there's no simple diagnosis for many things, so you have to start somewhere.

Back on topic, the idea of prescribing 2 year olds psychoactive drugs is clearly nothing to do with the drug companies -- I'm sure there is no documentation that shows they are promoting this -- I doubt you could ever get approval to do testing on those groups. This is a problem of taking a drug designed for one thing on one particular group and using it for another (which is relatively common -- partially because doing proper trials on innumerate groups is prohibitively expensive). Of course, this isn't just a problem in mental health, just look at Botox.

davidp said...

Thank you John and Conrad for your comments. It seems like the case of the 2-year old is probably less to do with the pharmaceutical companies and more the doctor with the cooperation (in some way) of the parents (there must be quite a story involved).

The general topic seems like the sort of thing modern microeconometrics could be applied to (though certainly is unlikely to be easy to set up the problem or get the data).

civitas said...

Harry, thanks for the reply. I read what the article states, but 1) it is one-sided, and 2) it doesn't say that doctor preferences for prescription and for advocating drugs are related to the often undisclosed money paid to them.

That may well be your opinion but it certainly is not proven. Nor was it stated in the article.

Also, in the US, much of that doctor cultivation has stopped. My sister is married to an OB-GYN and she complains constantly that the free trips have dried up several years ago. So sad for her, eh? The free meals aren't for doctors as much as the drug reps will do things like bring pizza and doughnuts by the offices for the office staff. It's hard to believe that docs would be favoring specific drugs because their office staff is enjoying the occasional free doughnut. Plus almost all the companies do it so there really wouldn't be much point in favoring one drug over another from a different company also supplying free office goodies.

Lastly, you give doctors absolutely no credit at all for being interested in the best interests of their patients and I think that's unfair.

John said...

It's hard to believe that docs would be favoring specific drugs because their office staff is enjoying the occasional free doughnut. Plus almost all the companies do it so there really wouldn't be much point in favoring one drug over another from a different company also supplying free office goodies.

A study of New York psychiatrists found a direct correlation between monies received from drug companies and the prescription practices of doctors. Doctors are human and will be influenced by such gifts. A friend of mine whose father is a psychiatrist once said to me that his father had a strict policy regarding gifts: no greater than $50.00 and even then often refused. Smart man, he knew that he was human and no matter how "ojective" he thought his opinions were he knew damned well that such gifts can impact on that objectivity.

Harry is absolutely right about that, doctors preferences are influenced. Of course they are, all of us are influenced by things like that.

3) If young kids have mental disorders and drugs help them, I don't see what the problem is. If doctors are prescribing unapproved drugs that haven't been tested, then that's poor ethics on the doctors part, not the drug company.

1.

We cannot know the long term consequences of psychiatric drugs. It is clearly established that substantial changes in gene expression occur with sustained use. The long term consequences of this are unknown.

2. Ecstasy is known to induce damage to serotonin neuron projections. The SSRI Redux, removed in 1997, clearly demonstrated substantial damage to serotonin neurons in animals at dosages hopefully matching the levels typically reached in the human brain under medication.

We need to take seriously the possibility that long term use of other SSRIs may also be causing damage that could take years if not decades to become apparent.

3.

Many patients, perhaps up to 40%, become tolerant to SSRIs. The reasons for this are unclear, I wonder if antibodies are being produced but most suspect neurological adaptations. Again, the long term consequences are unknown.

4.

Withdrawal effects can be severe and debilitating, many patients are not informed of this substantial risk. Effexor creates many horror stories in this regard.

5.

Prozac builds up to quite high levels in the brain and has a slow washout, the consequence being that sustained dosing may be over activating the serotonin neurons, thus making these susceptible to damage because serotonin metabolism involves the generation of oxyradicals, these nasties possibly explain the axonal retractions noted in regard to Redux and Ecstasy.

6. Movement disorders arising from sustained SSRI use are now recognised in DSM4. Up to 50% of patients who develop tics will have persistent tics even after cessation. Because there have been insufficient studies it is not possible to determine the total risk across a population. It can take many months for these to subside if at all. The same happened with thorazine, at first the medicos thought the EPS issues were only a very small subset of patients. Studies proved that to be very wrong.

7. SSRIs do develop dependency and withdrawal symptoms.

8. Psychiatry has a long history, beginning with Freud and cocaine, of extolling the latest wonder drug, only to find years down the track that it aint that wonderful.

9. Recent studies on mice found that when given SSRIs at young ages they developed depressive like symptoms in childhood. Again, this suggests damage to serotonin neurons.

10. Now then, how many times to pharma companies, in their advertisements to the general public and their approaches to the medical profession, fully divulge all the potential problems that can arise?

--------

I am not against psychiatric drugs, in fact I perceive these as being amongst the greatest of medical advances beginning with the Melbourne based psychiatrist, John Cade(1949-lithium). I am against misrepresentation by both the medical profession and pharma companies as to the true therapeutic value and potential dangers of these drugs.

As a matter of epistemology, who in their right mind trusts the judgment of the seller? Doctors don't need to do this, there is abundant literature out there so why the hell do they even risk their objectivity by taking so many gifts?

A golden rule of markets is good information. You don't get that from the seller.

Oh and ... . Recent studies have indicated that psychotherapy can be very effective in treating depression. In fact in recent years there has been a shift away from the heavy prescribing of antidepressants.

And ... just recalled, pharma companies have been recruiting doctors to provide favourable write ups of their latest product. Biederman is not the exception, this is a worrying practice that doctors en masse should not tolerate.

conrad said...

John,

I think there's no doubt that many psychoactive drugs have consequences. However, what you really need to consider is that some consequences of drugs are better than the client topping themselves (or other destructive behavior).

I also agree with you that the main thing that is ignored are alternative therapies (CBT and other behavioral modifications), which have historically got very little funding, since you can't make money out of them (and it's not just helpful for depression -- it's for all sorts of disorders). However, the government did try to fix that with their new scheme, but that is not working well as (a) doctors are rorting it (50% of the money actually when to the GPs who do almost nothing);(b) most of the rest of the money has been going to middle class people living in rich areas who could have paid for it anyway. That's not to say middle class people don't have various mental health issues (for example, the highest rate of alcoholism in middle aged females in Melbourne is in one of the richest areas (Hawthorn, Kew -- Burundoora) -- think bored mothers at home with rich husbands) but it's clearly missing important groups; and (c) the clinical college of the APS is trying to set themselves up as an AMA style mafia so that they can rort the system as well as possible also.

observa said...

Streuth Harry, you're not intimating that men of rational science and careful observation could have that rationality and care swayed by the hand that feeds them are you? Careful Harry or you might start finding curious correlations with global warmenista theorists, bailout Keynesian economists and the hand that feeds too, or perhaps more succinctly venerable institutions where they congregate together in large numbers. Perish the thought Harry or you may leave the Enlightment and fall into.. gulp!..the dark side and uncertainty.

Well if some of us are a little skeptical of the exactitude of climate and global economic sciences just at present, when it comes to the biology and the 'ecology of man', we're even less certain and more confused about some of the gatherings of certainty we see around us so regularly.

It was a budding chemist young O who had a salutary lesson in munitions manufacture and OHS, as well as the perils of mixing alchohol with motorcycles that quickly had blind faith in modern medicine to pick Humpty up and put him back together again amazingly quickly and with few lasting pertubations to his lifestyle.(as my poor dead mother would say-I never had any grey hairs before I met you son- wise words which I'm fond of relaying to the fruit of my loins today) That blind faith was rudely shattered after a work accident and an 18 month stint of acute sciatica, learning about the interaction of acute physical pain and keeping mind and body together to overcome it, whilst being bombarded with conflicting medical and pharmacological remedies.

Thanfully it was not until the birth of MasterO that I had to deal with the vagaries of modern medicine again. Having mastered mind over matter with extreme pain, I was in the perfect position to teach MrsO how to cope with the brief discomfort of natural childbirth, much to the amazement of nursing staff, who seldom saw it with firstborns then. That was after initial contractions and hospital attendance, upon which the gyny wanted to administer a drip to 'help things along' after knowing full well our preferences beforehand. No thanks and we came back 24 hours later for 8 hours of the real thing.

The wonderment of new life with all its hands feet and other appendages in the right place and seemingly all functioning normally. Every parent's dream until a needle is being hastily prepared to stick into this miracle of life. Whoa what's this for? Oh nothing to worry about just some vitamin K to guard against the chance of haemorrhaging. Politely but firmly refused by me much to the consternation of staff and consequently MrsO as they make a new mum nervous. When they leave MrsO scolds she'll never forgive me if precious babyO dies of whatever it is he could possibly die of without that needle. I have the last word some years later when it's revealed that intra muscular injection can cause leukaemia in children at rates above the risk of haemorrhage. As if babies were meant to have needles stuck in them as soon as they leave the womb, I ask you? Remember the Pope and that 'ecology of Man' stuff again Harry?

MasterO grows healthily into a toddler seemingly not allergic to all the things he's supposed to be allergic to theses days, moving from the breast to the bottle and cows milk instead of goat/soy milk or whatever he's supposed to be on until a succession of flu like bouts, sneezes and wheezes which are concerning mum inordinately. For mine he's coming into cantact with other kids and just building immunity but mum is more skeptical and off to the docs. She comes home to tell me he's likely mild asthmathic and they want to treat him as such. I'm as skeptical as the vitamain K needle and forbid it with the usual protestaions from mum. He gets over the bouts of sniffles and wheezes and at 25yrs shows no sign of asthma to this day.

There's another lesson in all this for you Harry. Kids need a mum and a dad as the Pope well knows with his understanding of the ecology of man. Not that I understood any of that as a bloody know all uni student in the sexual revolution, but then that's why we elect married with kids to run the bloody country you'll notice.

John said...

However, what you really need to consider is that some consequences of drugs are better than the client topping themselves (or other destructive behavior).

Conrad, that is the terrible dilemma of the clinician. Clinicians are required to adhere to best practice and if they don't do this and something goes wrong then send in the clowns(lawyers). At present best practice is drugs.

I expect "best practice" to move from simply prescribing a pill to doing that and advising the patient to undergo CBT. Over recent years it has also been established that a number of other approaches can help: meditation, exercise, even vitamin D status may have some small bearing on depression.

I don't see any substantial risk in the considered short term use of antidepressants but have real problems when these drugs are prescribed for years on end; especially given the issues of rising tolerance and possible side effects.

Side note:

Years ago I read The Symbolic Species by Terrance Deacon. He makes an interesting point regarding the rapid encephalisation of humans. This rapid growth occurred largely in the cerebral cortex, particularly the frontal lobes. However, the transmitters ACH, Da, 5HT, nore, all arise from the brainstem, which did not increase in proportion to the neocortical expansion. These transmitters are the bogeyman in many psychiatric conditions. It may well be the case that our neocortex is stretching these brainstem nuclei to their limit.

civitas said...

John says....A study of New York psychiatrists found a direct correlation between monies received from drug companies and the prescription practices of doctors.

A study by whom, John? Could the "study" be compromised by preconcieved notions such as yours and Harry's? And what "monies" are you talking about? Monies spent on free doughnuts for office staff?

It may well be your opinion as well as Harry's that docs presecibe drugs based on doughnuts, but neither of you have proven it.

civitas said...

This NYT article supports my previous comments. It describes a moratorium on office goodies for docs. Now it may be that free pens, coffee mugs, tongue depressors and branded bandages had great influence on the prescribing habits of docs but is that really likely?

The article also supports my contention that serious goodies, like trips and free tickets to sporting events dried up several years ago, the article says in 2002. The free office lunches continue.

Paying physicians fair market value as consultants seems to be not unreasonable, after all, why should doctors be prohibited from serving as paid consultants? Who else would you like to pay as a pharmaceutical consultant, professional baseball players? Here's the article:

http://www.nytimes.com/2008/12/31/business/31drug.html?em

I have no great affection for doctors as a group, in fact, I find many of them unprofessional and just as human as the rest of us. But tarnishing an entire group with somewhat out of date thinking in unfair.

John said...

To the credit of the medical profession and biomedical researchers, the issue of these monies has long been recognised. There are plenty of articles expressing deep concerns at the influence of pharmas and biomedicals on decision making by clinicians. I checked some stuff, the problem is much more widespread than I thought. Note the below:

Thorac Surg Clin. 2005 Nov;15(4):533-42.Links
Who's buying lunch: are gifts to surgeons from industry bad for patients?
Grant DC, Iserson KV.

Department of Emergency Medicine, University of Arizona College of Medicine, Tucson, AZ 85724, USA. grantdav77@hotmail.com

Why does gifting exist in the medical marketplace? It provides a sales advantage in a competitive marketplace by establishing crucial relationships with the patients' fiduciary: the physician and surgeon. Do gifts to physicians from industry harm patients? One can cite mountains of indirect evidence that they do, and maybe in the case of recalled devices and drugs there are actual corpses, but these examples are retrospective and it is impossible to prove that removing detailing eliminates the harm. Banning gifts to surgeons would not completely fix the ethical problem of pharmaceutical and device marketing. Gifts are important because they buy access and foster relationships, but inherent bias in research and the medical literature makes it very difficult to remain objective. It is a race, and education has not kept pace with advertising; only 10% of 575 internal medicine physicians thought they had had sufficient training during medical school and residency regarding professional interaction with sales representatives. Would banning gifts help at all? Would enforcing an unpopular ethical code protect patients? There might be a small improvement, but not as significant as eliminating representatives and product samples altogether. This is not likely to happen without an enormous fight against the wealthiest industry in America. The solution is education. To borrow industry's argument, physicians and surgeons are ethical creatures with capacity for judgment and integrity. They need to understand and believe the magnitude of the problem. Detailing exists because there is a market for it, empowering surgeons with ethical training reduces the demand for goodies, and at some point the popular choice will be to buy their own lunch. Business ethics are not medical ethics. Industry is behaving exactly as it must to maximize profits. Although it is painful for some surgeons, surgical residencies, and professional organizations to envision a future with diminished corporate gifts, it is every surgeon's responsibility to consider whether their dealings with the pharmaceutical and medical equipment industries withstand the harsh light of realities presented herein.

PMID: 16276818 [PubMed - indexed for MEDLINE]


Obstet Gynecol. 2007 Jul;110(1):169-73.Click here to read

Most physicians deny their professional integrity can be "bought" by something as trivial as a cup of coffee or a free lunch. In this paper, we review the social science literature arguing that "gifting" physicians in this way is, in fact, a highly successful method of boosting drug sales. Unlike ordinary consumer goods, the sale of prescription drugs does not take place directly between the producer and the consumer; rather, prescription drug sales are mediated by the physician who writes the script for the medication. Pharmaceutical sales practices are geared toward influencing physician drug recognition so that, when prescriptions are written, their drug is the first one that comes to mind. Even small gifts produce in their recipients a disproportionately powerful willingness to reciprocate in some manner. The simple act of providing food has been shown to make any message more palatable and more likely to be favorably received. We argue that physician prescribing habits should be based upon careful consideration of what medication is really in the patient's best clinical interests, not on who most recently provided the doctor with a free lunch.

PMID: 17601912 [PubMed - indexed for MEDLINE

derrida derider said...

It's pretty amusing for people to claim that getting freebies from drug companies doesn't influence how many and what sort of drugs doctors prescribe. It reminds me of the tobacco companies claiming, with a straight face, that tobacco advertising didn't cause people to smoke more "but only to swap brands".

Might I suggest that if these freebies do have no effect on doctors' fully-informed, evidence-based and objective prescribing habits, then the drug companies shouldn't mind them being banned? After all, they're obviously a complete waste of money for those drug companies.