Psycho-Babble Social Thread 896175

Shown: posts 1 to 15 of 15. This is the beginning of the thread.

 

rant about 'health' and stuff

Posted by alexandra_k on May 17, 2009, at 0:21:32

The state of psychiatry really is quite frightening. I started out working on trying to justify psychiatry's status as a branch of medicine (in the face of the anti-psychiatry critique) and the more I read about the history and current state of psychiatry (by reputable theorists) the more concerned I became. But then turning to medicine more generally the more I read about the history and current state of medicine (by reputable theorists) the more concerned I became about that too. And then similarly, reading about the current state of science (and seeing it in action myself by attending seminars etc) is similarly frightening in some respects. The main driver for medical research really does seem to be extra-scientific rather than scientific concerns. I think... It basically pollutes the science and... People suffer / are harmed because of that.

Disregarding or undermining what someone has to say on the basis of who they are (or what ulterior motives they may have for their position) is known as an `ad hominum attack'. It is thought to be unjustifiable to disregard or undermine what someone has to say SOLELY on the grounds of who they are or what ulterior motives they have. It is considered reasonable, however, to examine the grounds that a person has for saying what they say when they do have some obvious stake in what it is that they are saying. If an economist makes a recommendation for a policy where they will financially profit if the recommendation is implemented that provides us grounds not for disregarding what they have to say in virtue of the stake that they have, but grounds for really examining the reasons they have for what they have to say in order to assure ourselves that the reasons are good and that the person didn't come to the view that their recommendation was best solely on the grounds that it would profit them. The obvious way to check is to employ people who are genuinely INDEPENDENT (and non-corruptable) who are knowledgeable enough in the relevant field to uncover problems with the methodology or conclusions inferred from the findings etc. People who aren't subjected to advertising and freebies. Both the FDA and the scientific peer review process are infected by the same problem, however. They watch TV. They get their freebies. They get their 'informational sessions'. They have investments. It is hard to find people who truly are independent.

There is a significant pharma investment in health research. In psychiatry, in medicine, and in science more generally (including in university contexts). That psychiatrists, medical doctors, and scientists have financial ties to pharma (in the form of free lunches, sponsored conferences, stationary, samples, and investments in companies) doesn't itself undermine their `findings' or `recommendations' or `prescriptions' but it does give us sufficient grounds to hold their opinions up for greater scrutiny. Especially because the opinions have such a significant impact on peoples lives. At the moment `undeclared' financial interests are rife (a person doesn't have financial investment in a pharma company they have some investment in some subsidiary that isn't itself a pharma company and so on). There is a historical process whereby a new `wonder drug' is invented and considerable profits are made. Problems begin to emerge and pharma dissociate themselves from the problems with their products. About 10-15 years later (once the drug is out of patient) the problems are acknowledged. Reexamination of the scientific literature that was used to support the acceptability of the product is now reinterpreted such that the considerable problems with it really were apparent all along. The problems with the product are then used as the basis of an advertising campaign for the superiority of the next `wonder drug'. Over and over and over... There is no reason to think that things have changed. I was astounded that the majority of student psychiatrists on the student doctor network thought that accepting freebies from pharma didn't have any impact on their prescribing practices and that attending pharma sponsored `informational sessions' was the best way they had of keeping up with the `current state of knowledge' in the medical field. I hope they are not representative, but my fear is that they are.

Pharma makes significant profits. They make profits to the extent that they are able to `reinvest' millions or billions of dollars every year into advertising (both to medical practitioners and to the general public). Given the considerable profits they make I'm sure they employ some of the best market researchers in the world in order to figure out the best way of them to maximize their profits by way of advertising. It really is unthinkable that they would invest so heavily in advertising if they didn't (on average) make more money from sales in virtue of that investment than they would make if they didn't invest those funds in that way. Advertising really does have the power to alter consumer (and prescriber) behavior. If it didn't companies wouldn't invest in it. It really is astounding to me that potential doctors wouldn't know that there really is `no such thing as a free lunch' and that sometimes `a pen is not just a pen'. They might think that they can simply eat their lunch and sleep through the following 'informational session' (when they aren't attempting to say that is the best contact they have with current scientific research) but the market research surely tells us that that is not the case. Similarly with the 'familiarity effects' of advertising on stationary.

It would be easy enough to manipulate advertising to the consumer and to doctors in order to see what impact that has on both consumer demand and doctors prescribing practices (and the significant relationship between them given that consumer satisfaction co-varies significantly with the patient being prescribed the brand they request). In fact such an experiment was done in New Zealand (with respect to a temporary ban on DTC - direct to consumer - advertising of medications (note: not of medical `conditions'). I think this followed some serious f*ck up with a new 'once a day' asthma inhaler that resulted either in a number of deaths or near deaths and physicians felt that their decision to switch from what was a basically effective medication to a medication where efficacy for their patient was unknown but where convenience to patient was advertised to be significantly greater was driven by consumer demand. New Zealand is often used as a test market for advertising research because it costs (relatively) a lot less to launch a nationwide advertising campaign there and it turns out to be highly predictive of consumer behavior in Australia, Canada, the UK, and the USA. A ban on DTC advertising was never trialed or implemented in those other countries because pharma profits would have been way down (due to consumers preferring and reporting higher satisfaction with either generic with their current or with alternatives to medication). Pharma was not happy with the trial and the results of it aren't widely disseminated (interestingly enough a number of doctors felt strongly that the trial should not have been done - something about `biting the hand that feeds you').

(In a similar vein 3 WHO organization studies showed that two thirds of people with a diagnosis of schizophrenia (the majority) recover from schizophrenia in 'developing nations' whereas only one third recover (a minority) in 'developed nations' where people have 'better access' to psychiatrists and to medications (the samples were matched for severity). The WHO couldn't believe the results of the first study (surely people should profit rather than suffer from living in a 'developed nation') and so they replicated the study again... And again... Then the basic decision was for the results not to be widely disseminated in order to preserve the intuitive truth that 'schizophrenia is a life long condition that people don't recover from despite our having access to the best standard of medical intervention in the world'. Perhaps that attitude... Is largely responsible for the finding....)

Arguments are sometimes made (and in fact were made) that pharma profits are important because the funds generated are reinvested in the developments of further products for 'medical breakthroughs'. I'm not at all convinced that the greatest medical breakthroughs have come or are likely to come from pharma rather than from the (relatively few) independent researchers that there are out there. A child dies every 30 seconds from malaria. How much pharma funds are invested in developing treatments for maleria compared to developing medications that inhibit the absorption of fats that people eat or giving people erections on demand or smoothing out peoples skin or giving them larger breasts? Once treatments are developed (e.g., for dehydration and HIV) how are those medications distributed to people? The majority of people who need the medications don't get it because they can't afford to pay the patients that pharma (falsely) says it *must* charge in order to remain viable at all. Hand outs are a small token of what they could do while remaining viable. It isn't about running a business that is viable so as to help people and it isn't about treatment for life threatening disorders. It is about profits at the end of the day and it simply is more profitable to persuade people by way of an extensive advertising campaign that relatively (to malaria, death by dehydration, or HIV) minor complaints are serious enough such that they should take the latest wonder drug for it (warning potential side effects include heart attack renal failure impotence and even death). It is about profits at the end of the day.

How did the world get to be in such a state? Is it an inevitable consequence of a 'free market' or a 'market driven economy' do you think? If so then should there be more restrictions on the extent to which the market (significantly altered by the absence of restrictions on advertising) is allowed to drive health research? Should medication decisions be like spaghetti sauce decisions where people are 'free' to make their choices on the basis of advertising and product placement? Or do we expect different when it comes to treatments for health conditions given that the potential harms are so very much greater? A number of people feel that our obligations to humanity don't cross national boundaries. I don't know... What does it mean to be a 'world leader' and what obligations does that confer (or is that simply about rights?)? What can one do to change all this? I simply don't know... Why is the world like this? I simply... Don't understand.

I wonder if a course (or two) in 'critical thinking' for future doctors that is aimed at covering the impact of advertising on consumer / prescriber behavior, the difference between advertising and information etc etc etc along with facts about the history of the rise and fall of wonder drugs and an examination of the (adequacy? inadequacy?) of the current checks that are supposed to prevent this would help doctors be more circumspect about this all... Looking through some of the data and seeing how it didn't support the conclusion that was claimed and that the problems with the product really were apparent in the study. There really need to be independent researchers whose job it is to disseminate quality research findings to medical practitioners (rather than relying on drug rep / former cheerleaders). But then there also need to be quality studies that are done by people who don't have pharma ties. At the moment people aren't even honest about their financial ties and there simply aren't serious consequences for this. That is unbelievable. Just because pharma claims 'the majority of doctors believe that depression is due to a chemical imbalance in the brain' doesn't mean that 1) They have actually done a survey of doctor opinion at all (but of course that isn't considered false advertising such that they aren't allowed to claim it if the study has not been done) even less done a representative one (such that they can legitimately generalize from their sample to 'all doctors') or 2) Doctors only believe this because pharma tells them so. Repeatedly. At every 'informational' session. Because the current health system really is so consumer driven this won't even be enough... It is just... A f*ck*ng mess. A f*ck*ng mess.

 

Re: rant about 'health' and stuff

Posted by manic666 on May 17, 2009, at 10:36:07

In reply to rant about 'health' and stuff, posted by alexandra_k on May 17, 2009, at 0:21:32

wow, you put that better than me , but i think we had the same idea,

 

Re: rant about 'health' and stuff alexandra_k

Posted by Phillipa on May 17, 2009, at 13:45:17

In reply to rant about 'health' and stuff, posted by alexandra_k on May 17, 2009, at 0:21:32

Oh how I agree. Getting slammed on my bioidenticals and urine transmitter testing on meds. Take a peek add your two cents. Love Phillipa

 

Re: rant about 'health' and stuff

Posted by Sigismund on May 17, 2009, at 15:25:39

In reply to rant about 'health' and stuff, posted by alexandra_k on May 17, 2009, at 0:21:32

I have a shrink who bulk bills and makes a point of not accepting anything from the pharmaceutical companies. He mentioned he had wanted to do a double blind study on ECT but the ethics committee knocked him back. Our sessions are filled with scorn at the state of something or everything, but including psychiatry. Of course their stupid pens and woeful conferences in beautiful places with tax write offs to match compromise them. It's just one of the modern world's little rackets...but it's why we get the drugs we do, because it's how the patents work. Enough to make you in favour of the free market.

 

Here's what I think.

Posted by seldomseen on May 17, 2009, at 18:16:14

In reply to rant about 'health' and stuff, posted by alexandra_k on May 17, 2009, at 0:21:32

I think there is a lot of interplay between the "independent" researcher/physician and the pharmaceutical companies and a tremendous amount of money does flow from pharma into academia/private concerns. However, it does not always translate into a financial conflict of interest, or bad science.

The facts of the matter are that big pharma has the capital to invest in large scale R&D for new therapies. Much more capital than academia - which relies, in the US at least, on the NIH, or non profit foundations for funding.

What big pharma lacks however, is the patient population and infrastructure from which to conduct large phase 3 efficacy clinical trials. Therefore, pharma will contract with institutions (not individuals typically) to conduct these trials. The monies paid to these institutions constitute the bulk of the money exchanged from pharma into the "independent" realm of research.

So, in my mind, the question then becomes, do these monies truly reflect a conflict or a simple contractual agreement? It appears to me as though public opinion would favor the former interpretation rather than the latter. However, I would maintain that, excepting the few egregious exceptions that are often cited, that this contractual arrangement is productive, beneficial and, based on my own personal experience, effective.

So many problems with drugs aren't uncovered until after FDA approval and large scale application. This is just the truth. Sometimes the data collection is flawed, sometimes results are buried, sometimes the FDA just ignores results. However, there is no clinical trial that could ever be big enough to discover everything about a drug - especially if the problem if rare, *or* very common in the general population. New drugs are often considered to be in phase 4 clinical testing even after FDA approval.

As far as psychiatric meds, one of the problems I see in psychiatry today is I think, very similar to a problem in the early days of cancer research. There is a very heterogeneous set of symptoms, causes and mechansms of illness, but no "gold standard" of treatment against which to compare anything. At least cancer had a "hard" outcome for the trials (remission/no remission, dead vs alive). In the field of psychiatry, even the term remission is subjective. I think rather than shotty science and corruption, the problem with psychiatric research is that it is truly in its infancy. Without a doubt, what are considered viable treatments today will be considered untenable within the next 20 years. Just as the cancer field has matured, so will psychiatry I predict.

As far as malaria, well, it is truly a killer in the underdeveloped countries of the world. However, in my opinion, the problem of malaria goes way beyond the realm of big pharma and ultimately must solved politically prior to treatment. How could one even put a drug into trials if there is no established and available health care delivery system in the countries in which malaria is endemic? Is that a problem that pharma could or should solve? Should they go into the business of health care delivery as well?

Finally, (your post was very through provoking) I am ambivalent about the consumer driven versus I suppose provider? driven state of pharmacotherapy today. On the micro (direct advertising) level, I would propose anything that engages the patient in their own care can be beneficial, but a conservative approach is usually in the patient's best interest - even if the provider has to convince the patient of that. On the macro level, these so called designer drugs do sell well and are big revenue generators. It may surprise a lot of people that sildenafil (Viagara) has broad application outside of erectile dysfunction. In fact, it is currently being investigated as a treatment for a pulmonary hypertension - a fatal condition and pregnancy-related hypertension. Guess what? The revenues from the ED sales are driving those clinical trials.

All in all, I think things could be better, of course. However, I am unconvinced that things are as bad as made out to be.

Seldom

 

Re: rant about 'health' and stuff alexandra_k

Posted by Bobby on May 17, 2009, at 21:26:21

In reply to rant about 'health' and stuff, posted by alexandra_k on May 17, 2009, at 0:21:32

Aren't fraternal organizations clever? I mean who is going to cover John Doe IV's Ivy league tuition? Perhaps the studies have shifted to the behavior of Lemmings and the potential revenues involved at the edge of the sea? I have a dear friend with a grave heart condition---he counts the days and enjoys every second. He say's--in his many years of life---he has learned one thing in life that has never failed him--"Follow the money!" What's left of his heart is pure gold and I'm sure "someone" is ready to claim every pennyweight(The honest gold buyers buy in grams). I think you're on to something--but if I agree with you --I could be declared as crazy.......I'm really really glad to see you've stayed this long Alex.

 

Re: Here's what I think.

Posted by alexandra_k on May 18, 2009, at 7:00:31

In reply to Here's what I think., posted by seldomseen on May 17, 2009, at 18:16:14

Hey. I'm very interested in what you have to say because you probably know a great deal more about this than me. I'd be interested to run a number of ideas by you and see what you think. It is a little hard for me to assess them (without doing a major study myself).

I do agree that the mere fact that there is significant financial flow from pharma to scientific researchers doesn't itself undermine the research (that would be ad hominum). So if there is a problem it must be in the details of the conditions on the financial flow or something like that.

> What big pharma lacks however, is the patient population and infrastructure from which to conduct large phase 3 efficacy clinical trials. Therefore, pharma will contract with institutions (not individuals typically) to conduct these trials.

I've heard this said in a number of places and I'd be interested to know what you think:

There is a way of designing a trial such that two outcomes are possible: The first outcome is that there is support for the efficacy of the medication (compared to placebo and alternative medication). The second outcome is that the study failed to find support for the efficacy of the medication (compared to placebo and alternative medication). The crucial thing about this is supposed to be that the second outcome DOESN'T entail or imply that the medication that was trialed is WORSE or MORE HARMFUL than either placebo or alternative medication and it also DOESN'T entail or imply that further studies (maybe 5 in 100) will find the first outcome - that there is support for the efficacy of the medication.

IF this is correct (that there are ways of designing trials such that you either show efficacy or you fail to find efficacy) THEN is it the case that researchers need to design their trials in this fashion in order to obtain pharma funding (or free / subsidized samples of expensive medications) to do the trial? If so, then this would be pharma driving scientific methodology in a way that obviously benefits them (they are required to report HARMFUL findings but they are not required to report FAILURE TO FIND POSITIVE BENEFITS). This is of course important because if you run a study often enough, well, 5 in 100 will give you the result you seek).

Deaths would be something that you would think would be hard to have not show the medication to be positively harmful. But the same studies that showed certain anti-depressants to be more effective than alternative and placebo were the studies that (pharma didn't think) showed certain anti-depressants to result in more deaths in certain age groups. Was it a genuine oversight to fail to pick up on this in the discussion section or would discussing such a thing jepordize ones future research funding?

I do understand that science quite generally really is very messy. I'm particularly interested in this added feature of complexity here, however.

I thought (could well be wrong) that the 'gold standard' of treatment for psychiatry is the last generation. So... If we want to get a new 'erectile dysfunction' medication approved then the way to go about it would be to either show it to be more effective than viagra OR show that it has less harmful side-effects (not quite sure how the latter works out - but I heard the latter was the main reason for the move from MAOI's to SSRI's, major tranquilisers to new gen anti-psychotics, and lithium to alternative mood stabilizers. That efficacy really wasn't any better, but the side-effects were less? Not sure how compatible this is with what I said before).

> As far as malaria, well, it is truly a killer in the underdeveloped countries of the world. However, in my opinion, the problem of malaria goes way beyond the realm of big pharma and ultimately must solved politically prior to treatment. How could one even put a drug into trials if there is no established and available health care delivery system in the countries in which malaria is endemic? Is that a problem that pharma could or should solve? Should they go into the business of health care delivery as well?

The issue is pharma setting the price that must be paid to obtain the medication in a way that is unrestricted until the patient runs out. Since it is under patient requiring much more than the cost of production. Once currency conversion gets factored in how many months or years or lifetimes worth of wages are required in order for an individual to get the treatment they need? I'm not talking about treating erectile dysfunction in developing nations I'm talking about treating HIV etc.

Yes, one needs to run a profitable business, I understand that. Yes, it costs a lot of money to develop new drugs (and there need to be lots and lots of trials when one is trying to get a good result from a number of trials from a drug that simply isn't terribly effective). Yes, it costs a lot of money to advertise the products (millions if not billions). It is kinda hard to measure 'profit' but really... Are they just making 'profits' or are they basically 'profiteers'?

> Finally, (your post was very through provoking) I am ambivalent about the consumer driven versus I suppose provider? driven state of pharmacotherapy today.

Ideally... I like to think that independent scientists would have the best ideas about where we should focus our attention on research / treatment. At the moment (as a researcher) one does need to alter what one wants to do (or recast it such that one gets funding for it). If there really was 'academic freedom' then... I think that would be a good thing, yeah. I know there are a number of scientists who work in university contexts for the explicit reason that yeah they don't make as much money as they could and yeah they don't have the nicest office or the flashiest equipment but if they develop the effective treatment for cancer or maleria they plan to write it up as a discovery for all to freely make use of rather than the discovery being patented by pharma (such that it won't be available to those who really need it).

> It may surprise a lot of people that sildenafil (Viagara) has broad application outside of erectile dysfunction. In fact, it is currently being investigated as a treatment for a pulmonary hypertension - a fatal condition and pregnancy-related hypertension.

That doesn't surprise me. Its an pretty expensive medication, there is time remaining on patient, so seems like a good business decision to look into market expansion. (Don't get me wrong I'm sure there are a variety of different scientific hypotheses about the nature of hypertension and the nature of viagra that makes such a study scientifically interesting).


 

Re: rant about 'health' and stuff

Posted by alexandra_k on May 18, 2009, at 7:14:48

In reply to Re: rant about 'health' and stuff, posted by Sigismund on May 17, 2009, at 15:25:39

I'm pretty sure there are a number of double blind studies on ECT. Troubles come when you consider that:

1) Most of the studies don't do follow up for more than 6 months after the treatment (that is a really good way of 'failing to find harms of previous generations'. Pharma didn't face up to problems with the older generation anti-psychotics until they were out of patient... I wonder what will happen in the next 10 or so years with new generation and SSRI's... Let me guess 'we have discovered that anxiety/depression and schizophrenia are chronic, seriously dehabilitating, neuro-degenerative diseases')
2) The studies that do follow up for more than 6 months after treatment tend to show relapse
3) The studies that do follow up for more than 6 months after treatment don't tend to ask / appropriately check whether the patient's spontaneously reported side effects (ability to remember new information, categorize objects, identify faces etc) continue past the 6 month period. Those that have done so show that many people report these problems persisting (but they are in the minority because THE MAJORITY OF STUDIES don't show this in that they fail to ask the question/ You would think that the number of cases of people who have ECT... It wouldn't be so hard to give them a cognitive battery (of the kinds of things patients report problems with) both before the treatment and during their relapse so they are matched for emotional state lol. Good luck getting funding for that one...).

There are stocks and shares in companies that make ECT machines, too. Newer and better frequencies etc etc etc. Deep brain stimulation is where it is at these days...

 

Re: rant about 'health' and stuff

Posted by alexandra_k on May 18, 2009, at 7:24:13

In reply to Re: rant about 'health' and stuff, posted by alexandra_k on May 18, 2009, at 7:14:48

> It wouldn't be so hard to give them a cognitive battery (of the kinds of things patients report problems with) both before the treatment and during their relapse so they are matched for emotional state lol. Good luck getting funding for that one...).

And the trouble is that it is a problem for ethics boards too (sigh).

You won't get ethical approval to do a study of the form 'hey we would like to perform this intervention on a bunch of people and what we think we are going to find is that it harms them - but you know, we would just like to check'.

I mean you can get 'effects of cat falling 50 stories' through, but probably not people anymore (seeing how long people could survive freezing temperatures was thought to be important with respect to figuring out how long the soldiers had in the water before we needed to get them out) and Harlow type experiments... Well... Still teach us much about the nature of love (and probably aren't thought to directly test the effects of deprivation). Sigh. I don't know :-(

 

Re: rant about 'health' and stuff

Posted by alexandra_k on May 18, 2009, at 7:33:16

In reply to rant about 'health' and stuff, posted by alexandra_k on May 17, 2009, at 0:21:32

i mean there is asprin and lithium and penicillin... significant medical breakthroughs. and then there are the 50 squillion varieties on the market today where... it really is unclear... actually how effective they are (given that we simply don't know how many trials were performed in order to get studies that showed efficacy out).

one scientist estimated to me (that quite aside from anything to do with health research) only about 20% of studies that were done (data that was collected) made it to being written up (and submitted to journals - where many go on to be rejected and never appear). you simply do get data that is... put down to some kind of 'noise'. polluted samples or whatever and you have another go... people often do 3 or 4 studies as part of a PhD hoping they will get 'usable' data from at least one and hopefully two of those trials.

so the issue isn't really how many trials were performed in order to show efficacy... it is 'compared to non-medical science how many trials are performed in order to show efficacy'.

i dunno... 'randomized double blind control trials' as the 'gold standard' methodology for treatment is coming under a lot of critique. it isn't the best scientific standard... and saying that this form of trial produces data that is 'worth more' or 'trumps' other forms of methodology has pharma trumping alternative treatments such as therapy (for instance) since you simply can't do that double blind. i dunno...

 

Re: Here's what I think.

Posted by seldomseen on May 18, 2009, at 8:50:49

In reply to Re: Here's what I think., posted by alexandra_k on May 18, 2009, at 7:00:31

"I do agree that the mere fact that there is significant financial flow from pharma to scientific researchers doesn't itself undermine the research (that would be ad hominum). So if there is a problem it must be in the details of the conditions on the financial flow or something like that."

***IMO there is a significant problem when the investigators have a vested interest (other than patient safety and treatment) in the outcome of the study.****

***Regarding study outcomes, statistics and deaths. Most of the time, big pharma is not exclusively responsible for the design of the large clinical trials, but the principal investigators at the performance sites are intimately involved as well. In my opinion, most studies are designed with the premise in mind that there is no difference in the drug, placebo, or gold standard of treatment. The data have to demonstrate that there is a statistical difference. The kicker there is that statistical significance may or may not translate into clinical difference.

Now, having said that it is very difficult to design a trial to specifically determine that there is no difference. In fact, it is virtually impossible scientifically (not statistically) to establish no difference or to say that something doesn't happen. Now, having said this, in the US historically the FDA really didn't pay close attention to efficacy, only that the drug was safe. This *is* changing. It is true that negative results, for the reasons indicated above, are harder to publish - that's why most drugs just simply fade away and we never hear about them again.

Now about deaths. I don't know about all the studies, only those that failed to catch the increase risk of suicide in young adults on some anti-depressants. Soemtimes when a side effect is relatively common in a population (like suicide in depressed individuals) it is very difficult to show a difference in that side effect between placebo and drug unless the increase is very very big. It takes a huge study (usually phase 4) to show a statistical difference. Likewise, the increased incidence of stroke with COX2 inhibitor administration would have been very difficult to catch in phase 3 clinical trials, because the population tested had a high baseline incidence of stroke.

"I thought (could well be wrong) that the 'gold standard' of treatment for psychiatry is the last generation."

*** See, that's the problem I'm talking about. A lot of patients fail treatment with the last generation of psych meds. The gold standard, well, isn't.****

***As far as the cost of medications, as distasteful as it may seem, pharma is well within their rights to set the price as they see fit. I am in agreement with you that the price for HIV (life saving) drugs is perhaps unethical, maybe even considered artifical inflation, due to the emergent need for the drug. However, again, the solution there can also be political. Gov'ts can negotiate with companies to set the price of the drug in that country. Also, as in the case of malaria, the delivery of these drugs into the regions of the world where they are most needed is significantly complicated by lack of infrastructure.***

***This may be very very surprising to hear coming out of my mouth, but, I am opposed to total academic freedom when it comes to medical research. I truly think there *should* be market pressures on scientists and that applied science should be emphasized and funded accordingly. In my experience, most scientists, left to their own devices, are interested in the solving problems and not in the application of their work. Even then, at present, these independent researchers need big pharma for the scale up and mass production of any newly discovered drugs. Again, it's a cooperation between the two.****

***Personally, I am very grateful that sildenafil was developed. Regardless of its original intent, it may prove to be of genuine clinical benefit and turn into a life saving drug.

Seldom.

 

Re: Here's what I think. alexandra_k

Posted by Larry Hoover on May 18, 2009, at 11:25:41

In reply to Re: Here's what I think., posted by alexandra_k on May 18, 2009, at 7:00:31

> There is a way of designing a trial such that two outcomes are possible: The first outcome is that there is support for the efficacy of the medication (compared to placebo and alternative medication). The second outcome is that the study failed to find support for the efficacy of the medication (compared to placebo and alternative medication). The crucial thing about this is supposed to be that the second outcome DOESN'T entail or imply that the medication that was trialed is WORSE or MORE HARMFUL than either placebo or alternative medication and it also DOESN'T entail or imply that further studies (maybe 5 in 100) will find the first outcome - that there is support for the efficacy of the medication.

The simplest methodology is drug against placebo. The underlying assumption is that there is no difference, called the null hypothesis. The methodology is designed to standardize everything they think might be relevant, such that going into the study, both groups are identical as can be. If the results of the study indicate that the two groups differ significantly after the treatments, then the null hypothesis is rejected. If that is the case, it is generally hoped that the drug was found to be superior, rather than the other way around.

The methodology you describe has three arms, investigational drug, placebo, and active comparator. In such a trial, any one arm could be found to be significantly different from one or both of the other arms. There are three null hypotheses which may be rejected.

It is quite correct that acceptance of the null hypothesis, i.e. no significant difference found, is not evidence that there is no difference. It is an aphorism in scientific research, "Absence of evidence is not evidence of absence."

Now, with respect to the repetitious testing of the null hypothesis after non-significant results, there is a financial penalty for continuing with further trials. If the first trial(s) showed a strong trend toward efficacy, then further trials, usually with more subjects, might be warranted. But 90-95% of investigational psych drugs simply don't pan out, more often at Phase 1 (safety), than at Phase 2 (dose-ranging), or Phase 3 (efficacy).

> IF this is correct (that there are ways of designing trials such that you either show efficacy or you fail to find efficacy) THEN is it the case that researchers need to design their trials in this fashion in order to obtain pharma funding (or free / subsidized samples of expensive medications) to do the trial? If so, then this would be pharma driving scientific methodology in a way that obviously benefits them (they are required to report HARMFUL findings but they are not required to report FAILURE TO FIND POSITIVE BENEFITS). This is of course important because if you run a study often enough, well, 5 in 100 will give you the result you seek).

I don't know of any other way to do it, other than I described. No company is going to fund 100 studies to get 5 good ones. All research is now registered and in the public domain, so there can be no hiding of negative outcomes.

> Deaths would be something that you would think would be hard to have not show the medication to be positively harmful. But the same studies that showed certain anti-depressants to be more effective than alternative and placebo were the studies that (pharma didn't think) showed certain anti-depressants to result in more deaths in certain age groups.

Where are you getting the idea that there were deaths? For example, there were no deaths ever recorded in adolescent antidepressant trials.

I well recall when the lay press first reported some statistic that adolescent trials of Paxil had demonstrated a seven-fold increase in suicidality (not completed suicide). I dug up the actual clinical trial data, some 500 or 600 pages of records (if I recall correctly), rather than the 6 or 7 pages in the published report. On examining the raw data, the reported increase in suicidality was absolutely false.

The methodology for the study in question had detailed requirements for the reporting of side effects and misadventure. The category which included suicidality was called "extreme emotional lability." But it also included other violations of study protocol. I clearly recall three such reports which you might find revealing.

In the drug group, one such report was of a young lady who took more of the drug than she should have. For some strange reason, each participant was supplied with 20 foil-pack capsules every two weeks, even though they were to take one capsule per day. They were to turn in the remainder when picking up the next batch. One young lady turned in less than the expected amount of unused capsules, and she was warned to follow the protocol. Four weeks later, it happened again. Because she was warned, it was coded as "extreme emotional lability", according to the a priori reporting guidelines. The individual improved significantly on the medication, and went on to complete the continuation phase of the study.

Another female randomized to the drug arm lied about numerous prior para-suicidal behaviours (an exclusionary factor) on the study application. She stopped taking the medication on her third day, but did not report that to the study investigators, which would have led to her being recorded as withdrawn. Three weeks later, she had a fight with her mother, and swallowed a small overdose of Tylenol (her preferred para-suicidal behaviour). Even though she had lied to get into the study, and lied about taking the study medication, because she had not formally withdrawn, her behaviour was recorded as a suicidal attempt in the medication group.

The only real suicidal act, IMHO, was recorded in the placebo group. Another female participant had failed to respond to her treatment, and had slashed her wrists. Upon being admitted to hospital, her blind was broken so as to provide her with appropriate care. She was administered an antidepressant (not the study med), and recovered thereafter.

I just don't recall all the other incidents that were lumped into this category, but in my interpretation, the score should have read 0 reports of suicidality in the medication arm, and 1 in the placebo arm. Or, at most 1 and 1, as the liar was a participant that might have been randomized to either group. By a flip of the coin, it could have been 0 and 2. In any case, I found no evidence of the reported "seven-fold increase in suicidality" trumpeted in the lay press.

> Was it a genuine oversight to fail to pick up on this in the discussion section or would discussing such a thing jepordize ones future research funding?

I have never known such outcomes to not be reported, but I have not read every similar study.

> I thought (could well be wrong) that the 'gold standard' of treatment for psychiatry is the last generation. So... If we want to get a new 'erectile dysfunction' medication approved then the way to go about it would be to either show it to be more effective than viagra OR show that it has less harmful side-effects (not quite sure how the latter works out - but I heard the latter was the main reason for the move from MAOI's to SSRI's, major tranquilisers to new gen anti-psychotics, and lithium to alternative mood stabilizers. That efficacy really wasn't any better, but the side-effects were less? Not sure how compatible this is with what I said before).

The active comparator and placebo methodology is generally preferred because if the active comparator also fails to show superiority over placebo, the study methodology needs a much closer look. Phase 3 is efficacy, so that is the primary consideration. If reported side effects are also lesser, then that is a bonus for marketing thereafter. If reported side effects are higher, then approval might be withheld, nothwithstanding efficacy.

The move towards SSRIs was generally due to lower toxicity vis a vis tricyclics, with the lower side effect profile being an added feature.

> Yes, one needs to run a profitable business, I understand that. Yes, it costs a lot of money to develop new drugs (and there need to be lots and lots of trials when one is trying to get a good result from a number of trials from a drug that simply isn't terribly effective). Yes, it costs a lot of money to advertise the products (millions if not billions). It is kinda hard to measure 'profit' but really... Are they just making 'profits' or are they basically 'profiteers'?

Without profits, then new research will not be conducted by that company. I don't see anything more than that. Pricing is always what the market will bear, for any commodity.

> Ideally... I like to think that independent scientists would have the best ideas about where we should focus our attention on research / treatment. At the moment (as a researcher) one does need to alter what one wants to do (or recast it such that one gets funding for it). If there really was 'academic freedom' then... I think that would be a good thing, yeah. I know there are a number of scientists who work in university contexts for the explicit reason that yeah they don't make as much money as they could and yeah they don't have the nicest office or the flashiest equipment but if they develop the effective treatment for cancer or maleria they plan to write it up as a discovery for all to freely make use of rather than the discovery being patented by pharma (such that it won't be available to those who really need it).

I think that's a pretty naive viewpoint. Prior to receiving funding from the public sector, there is always some sort of 'property rights' clause in the funding contract. Often, the institution holds those rights, or they share them with an agency of government. If funding is received from the private sector (most university research is funded by the private sector), then rights generally revert to the funder or are shared. Primary research outcomes, e.g. a new mechanism, end up being in the public domain. But any specific process arising from that new mechanism (or whatever) end up being patented. I can't think of an exception, outside of natural health products, which cannot be patented.

Even if that scenario of discovering a treatment for cancer or malaria would come to pass, there would still be huge expense in demonstrating all the things that would need to be demonstrated: safety, dose, efficacy. And then how would it be produced and distributed? Who would pay for that?

My observations of the real-life process run something like this.....Researcher makes fundamental discovery (public domain). Researcher develops specific approach to utilizing the discovery (patent). Researcher leaves academia and starts a company with private funding, or sells it to a private company outright, or the university does similar. Vast monies are spent in testing and development. There is a loss of some ideas at each step following the first, and maybe 1 in 1000 make it to the public.

> That doesn't surprise me. Its an pretty expensive medication, there is time remaining on patient, so seems like a good business decision to look into market expansion. (Don't get me wrong I'm sure there are a variety of different scientific hypotheses about the nature of hypertension and the nature of viagra that makes such a study scientifically interesting).

Actually, Viagra was first studied as a possible treatment for hypertension and angina. It didn't do so well at those things, but it was noted that penile erection was a ....errrr prominent side effect. The fact that the drug was being tested using standard methodology was what allowed this result to achieve notice.

Lar

 

Re: rant about 'health' and stuff alexandra_k

Posted by Amelia_in_StPaul on May 18, 2009, at 16:27:01

In reply to rant about 'health' and stuff, posted by alexandra_k on May 17, 2009, at 0:21:32

YES. They should be required to take a class in critical thinking, and a class in philosophy of science, with heavy doses of critical thinkers about the "objectivity" of science in there--some feminist thinkers (the history of science and medicine is rife w/damage to women), some critical race theorists, some marxists.

I'm sick and tired of my current pdoc's attitudes--much of it coming from his wholehearted belief in the objectivity of science. Baaaaah!

Since I live in a state that requires those in the field to reveal their pharma funding, we know quite a lot about the ties the uni psychiatrists have to big pharma. One pdoc in particular is coming under scrutiny for making misleading statements about Seroquel in his AMA presentation and in marketing materials.

It sucks. It's hard to know what to do. I want so badly to be free of the psychiatric system, tell the whole thing to f$ck off, yet when I try to get off these d@mn meds, I tank. Funny how I am worse off now when I am off them than I was when I was first put on them.

My rankling is raised. Consider me resentful right along side you.

> The state of psychiatry really is quite frightening. I started out working on trying to justify psychiatry's status as a branch of medicine (in the face of the anti-psychiatry critique) and the more I read about the history and current state of psychiatry (by reputable theorists) the more concerned I became. But then turning to medicine more generally the more I read about the history and current state of medicine (by reputable theorists) the more concerned I became about that too. And then similarly, reading about the current state of science (and seeing it in action myself by attending seminars etc) is similarly frightening in some respects. The main driver for medical research really does seem to be extra-scientific rather than scientific concerns. I think... It basically pollutes the science and... People suffer / are harmed because of that.
>
> Disregarding or undermining what someone has to say on the basis of who they are (or what ulterior motives they may have for their position) is known as an `ad hominum attack'. It is thought to be unjustifiable to disregard or undermine what someone has to say SOLELY on the grounds of who they are or what ulterior motives they have. It is considered reasonable, however, to examine the grounds that a person has for saying what they say when they do have some obvious stake in what it is that they are saying. If an economist makes a recommendation for a policy where they will financially profit if the recommendation is implemented that provides us grounds not for disregarding what they have to say in virtue of the stake that they have, but grounds for really examining the reasons they have for what they have to say in order to assure ourselves that the reasons are good and that the person didn't come to the view that their recommendation was best solely on the grounds that it would profit them. The obvious way to check is to employ people who are genuinely INDEPENDENT (and non-corruptable) who are knowledgeable enough in the relevant field to uncover problems with the methodology or conclusions inferred from the findings etc. People who aren't subjected to advertising and freebies. Both the FDA and the scientific peer review process are infected by the same problem, however. They watch TV. They get their freebies. They get their 'informational sessions'. They have investments. It is hard to find people who truly are independent.
>
> There is a significant pharma investment in health research. In psychiatry, in medicine, and in science more generally (including in university contexts). That psychiatrists, medical doctors, and scientists have financial ties to pharma (in the form of free lunches, sponsored conferences, stationary, samples, and investments in companies) doesn't itself undermine their `findings' or `recommendations' or `prescriptions' but it does give us sufficient grounds to hold their opinions up for greater scrutiny. Especially because the opinions have such a significant impact on peoples lives. At the moment `undeclared' financial interests are rife (a person doesn't have financial investment in a pharma company they have some investment in some subsidiary that isn't itself a pharma company and so on). There is a historical process whereby a new `wonder drug' is invented and considerable profits are made. Problems begin to emerge and pharma dissociate themselves from the problems with their products. About 10-15 years later (once the drug is out of patient) the problems are acknowledged. Reexamination of the scientific literature that was used to support the acceptability of the product is now reinterpreted such that the considerable problems with it really were apparent all along. The problems with the product are then used as the basis of an advertising campaign for the superiority of the next `wonder drug'. Over and over and over... There is no reason to think that things have changed. I was astounded that the majority of student psychiatrists on the student doctor network thought that accepting freebies from pharma didn't have any impact on their prescribing practices and that attending pharma sponsored `informational sessions' was the best way they had of keeping up with the `current state of knowledge' in the medical field. I hope they are not representative, but my fear is that they are.
>
> Pharma makes significant profits. They make profits to the extent that they are able to `reinvest' millions or billions of dollars every year into advertising (both to medical practitioners and to the general public). Given the considerable profits they make I'm sure they employ some of the best market researchers in the world in order to figure out the best way of them to maximize their profits by way of advertising. It really is unthinkable that they would invest so heavily in advertising if they didn't (on average) make more money from sales in virtue of that investment than they would make if they didn't invest those funds in that way. Advertising really does have the power to alter consumer (and prescriber) behavior. If it didn't companies wouldn't invest in it. It really is astounding to me that potential doctors wouldn't know that there really is `no such thing as a free lunch' and that sometimes `a pen is not just a pen'. They might think that they can simply eat their lunch and sleep through the following 'informational session' (when they aren't attempting to say that is the best contact they have with current scientific research) but the market research surely tells us that that is not the case. Similarly with the 'familiarity effects' of advertising on stationary.
>
> It would be easy enough to manipulate advertising to the consumer and to doctors in order to see what impact that has on both consumer demand and doctors prescribing practices (and the significant relationship between them given that consumer satisfaction co-varies significantly with the patient being prescribed the brand they request). In fact such an experiment was done in New Zealand (with respect to a temporary ban on DTC - direct to consumer - advertising of medications (note: not of medical `conditions'). I think this followed some serious f*ck up with a new 'once a day' asthma inhaler that resulted either in a number of deaths or near deaths and physicians felt that their decision to switch from what was a basically effective medication to a medication where efficacy for their patient was unknown but where convenience to patient was advertised to be significantly greater was driven by consumer demand. New Zealand is often used as a test market for advertising research because it costs (relatively) a lot less to launch a nationwide advertising campaign there and it turns out to be highly predictive of consumer behavior in Australia, Canada, the UK, and the USA. A ban on DTC advertising was never trialed or implemented in those other countries because pharma profits would have been way down (due to consumers preferring and reporting higher satisfaction with either generic with their current or with alternatives to medication). Pharma was not happy with the trial and the results of it aren't widely disseminated (interestingly enough a number of doctors felt strongly that the trial should not have been done - something about `biting the hand that feeds you').
>
> (In a similar vein 3 WHO organization studies showed that two thirds of people with a diagnosis of schizophrenia (the majority) recover from schizophrenia in 'developing nations' whereas only one third recover (a minority) in 'developed nations' where people have 'better access' to psychiatrists and to medications (the samples were matched for severity). The WHO couldn't believe the results of the first study (surely people should profit rather than suffer from living in a 'developed nation') and so they replicated the study again... And again... Then the basic decision was for the results not to be widely disseminated in order to preserve the intuitive truth that 'schizophrenia is a life long condition that people don't recover from despite our having access to the best standard of medical intervention in the world'. Perhaps that attitude... Is largely responsible for the finding....)
>
> Arguments are sometimes made (and in fact were made) that pharma profits are important because the funds generated are reinvested in the developments of further products for 'medical breakthroughs'. I'm not at all convinced that the greatest medical breakthroughs have come or are likely to come from pharma rather than from the (relatively few) independent researchers that there are out there. A child dies every 30 seconds from malaria. How much pharma funds are invested in developing treatments for maleria compared to developing medications that inhibit the absorption of fats that people eat or giving people erections on demand or smoothing out peoples skin or giving them larger breasts? Once treatments are developed (e.g., for dehydration and HIV) how are those medications distributed to people? The majority of people who need the medications don't get it because they can't afford to pay the patients that pharma (falsely) says it *must* charge in order to remain viable at all. Hand outs are a small token of what they could do while remaining viable. It isn't about running a business that is viable so as to help people and it isn't about treatment for life threatening disorders. It is about profits at the end of the day and it simply is more profitable to persuade people by way of an extensive advertising campaign that relatively (to malaria, death by dehydration, or HIV) minor complaints are serious enough such that they should take the latest wonder drug for it (warning potential side effects include heart attack renal failure impotence and even death). It is about profits at the end of the day.
>
> How did the world get to be in such a state? Is it an inevitable consequence of a 'free market' or a 'market driven economy' do you think? If so then should there be more restrictions on the extent to which the market (significantly altered by the absence of restrictions on advertising) is allowed to drive health research? Should medication decisions be like spaghetti sauce decisions where people are 'free' to make their choices on the basis of advertising and product placement? Or do we expect different when it comes to treatments for health conditions given that the potential harms are so very much greater? A number of people feel that our obligations to humanity don't cross national boundaries. I don't know... What does it mean to be a 'world leader' and what obligations does that confer (or is that simply about rights?)? What can one do to change all this? I simply don't know... Why is the world like this? I simply... Don't understand.
>
> I wonder if a course (or two) in 'critical thinking' for future doctors that is aimed at covering the impact of advertising on consumer / prescriber behavior, the difference between advertising and information etc etc etc along with facts about the history of the rise and fall of wonder drugs and an examination of the (adequacy? inadequacy?) of the current checks that are supposed to prevent this would help doctors be more circumspect about this all... Looking through some of the data and seeing how it didn't support the conclusion that was claimed and that the problems with the product really were apparent in the study. There really need to be independent researchers whose job it is to disseminate quality research findings to medical practitioners (rather than relying on drug rep / former cheerleaders). But then there also need to be quality studies that are done by people who don't have pharma ties. At the moment people aren't even honest about their financial ties and there simply aren't serious consequences for this. That is unbelievable. Just because pharma claims 'the majority of doctors believe that depression is due to a chemical imbalance in the brain' doesn't mean that 1) They have actually done a survey of doctor opinion at all (but of course that isn't considered false advertising such that they aren't allowed to claim it if the study has not been done) even less done a representative one (such that they can legitimately generalize from their sample to 'all doctors') or 2) Doctors only believe this because pharma tells them so. Repeatedly. At every 'informational' session. Because the current health system really is so consumer driven this won't even be enough... It is just... A f*ck*ng mess. A f*ck*ng mess.

 

PS alexandra_k

Posted by Amelia_in_StPaul on May 18, 2009, at 16:28:35

In reply to rant about 'health' and stuff, posted by alexandra_k on May 17, 2009, at 0:21:32

are you in grad school, alexandra? you make me yearn for the days I was in my english phd, long gone now (I am ABD; no PhD and I'm probably never going to finish)...

 

Re: rant about 'health' and stuff

Posted by Sigismund on May 18, 2009, at 22:28:38

In reply to Re: rant about 'health' and stuff, posted by alexandra_k on May 18, 2009, at 7:14:48

>. Let me guess 'we have discovered that anxiety/depression and schizophrenia are chronic, seriously dehabilitating, neuro-degenerative diseases')

That's the one.
You are less likely to hear that we are all being chronically poisoned and maintained in a state of low level emergency.

(In an Australian city the health authorities prohibited people from eating the vegetables and fruit they were growing in their back yards because of the high levels of lead and other heavy metals. That's what you do when you cut spending on public transport.)


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