Francois T pointed to a post at the blog Health Care Renewal that summarizes an important insider report at the British Medical Journal on how much so-called medical research is of dubious validity, and performed to give talking points for marketing rather than to improve the lives of patients.
The reports on the corruption is big Pharma “research” are so rife that this account hardly qualifies as news. For fun, I dug up the notes from a 2004 study in which I interviewed some experts on drug company marketing. The reason? Even then, it was seen as the most effective, and a big financial services client was keen to see what techniques they could adopt from it. Even then, it was clear “research” was seen as key to effective selling. Per one interviewee, on sales reps:
Creativity is NOT what you want for this job. You do not want someone who is creative in their dealings with doctors. Everything they say is according to very strict guidelines…The words they can share with the doctor are all carefully crafted and screened by the FDA. They can’t deviate from the script. If they deviate, they get in trouble, they get the company in trouble along with them. All the scandals in the industry were the salesforce management and the company, not the sales reps.
One reason Pfizer is effective is new product introductions. There is so much revenue and expectation behind it that they get the sales force keyed up about it. They know from the FDA when a product is going to be coming to market. They have the launches in nice places. They fly all the salesforce in, 500 people to a launch in Florida. They bring in entertainment, motivational speakers. Senior management flies down. There is a rigorous presentation fo the program and the product, information on the product, its advantages and disadvantages relative to the competitors.
They also have three times a year meetings to update the sales management on all the currently marketed products. They are called POA, plan of action meetings. It is whatever that will be new from a marketing standpoint over the next six months Each brand marketing group has to come up with new material to keep the sales force interested, like new data from recent studies. If they don’t have something new, the salesforce loses its edge. It also includes promotional pieces, like notepads, pens, It may seem silly, but the doctors love this stuff. And if a doctor says, bring me 5 more of those pens, my friends like them, it does maek a difference. You don’t like to think that stuff like that influences what a doctor prescribes, but it does.
And keep in mind, the costs of manipulated research findings are real. Cathy O’Neil, aka mathbabe, wrote up one of the most deadly cases, Vioxx. The summary of her detailed post:
Madigan has been a paid consultant to work on litigation against Merck. He doesn’t consider Merck to be an evil company by any means, and says it does lots of good by producing medicines for people. According to him, the following Vioxx story is “a line of work where they went astray”.
Yet Madigan’s own data strongly suggests that Merck was well aware of the fatalities resulting from Vioxx, a blockbuster drug that earned them $2.4b in 2003, the year before it “voluntarily” pulled it from the market in September 2004. What you will read below shows that the company set up standard data protection and analysis plans which they later either revoked or didn’t follow through with, they gave the FDA misleading statistics to trick them into thinking the drug was safe, and set up a biased filter on an Alzheimer’s patient study to make the results look better. They hoodwinked the FDA and the New England Journal of Medicine and took advantage of the public trust which ultimately caused the deaths of thousands of people.
To give an idea of the significance of the Vioxx withdrawal: per O’Neill, it led to a meaningful drop in the overall death rate in the US in the following 12 months.
Nevertheless, what is chilling in this insider account at BMJ is the sense of how pervasive and institutionalized the subordination of science, and worse, concern for the public, is to pushing drugs.
I strongly urge you to read the post in full (I’d love to read the BMJ article, but it is seriously paywalled). This section is key (emphasis original):
Research Studies Designed Primarily as Marketing Vehicles
In general, the anonymous author suggested that at least some studies were done for marketing, not scientific purposes:
some of the studies I worked on were not designed to determine the overall risk:benefit balance of the drug in the general population. They were designed to support and disseminate a marketing message.
Whether it was to highlight a questionable advantage over a ‘me-too’ competitor drug or to increase disease awareness among the medical community (particularly in so called invented diseases) and in turn increase product penetration in the market, the truth is that these studies had more marketing than science behind them.
Furthermore, the studies were supervised not by physicians or scientists, but by marketers in the marketing department,
Although the medical department developed the publication plans, designed the study, performed the statistical analysis, and wrote the final paper (which when published was passed on to marketing and sales to be used as marketing material), the marketing team responsible for that product were directly involved in all stages. They also closely supervised the content of other educational ‘scientific’ materials produced in the medical department and intended for potential prescribers. Instructions from marketing to the medical staff involved were clear: to ensure that the benefits of the drug were emphasised and the disadvantages were minimised where possible.
Manipulation of Research Design, Implementation, or Analysis
The author described how the marketers manipulated research studies so they would produce the results desired from a marketing perspective, regardless of their underlying truth,
Since marketing claims needed to be backed-up scientifically, we occasionally resorted to ‘playing’ with the data that had originally failed to show the expected result. This was done by altering the statistical method until any statistical significance was found. Such a result might not have supported the marketing claim, but it was always worth giving it a go to see what results you could produce. And it was possible because the protocols of post-marketing studies were lax, and it was not a requirement to specify any statistical methodology in detail. On the other hand, the studies were hypothesis testing (such as cohort studies, case-control studies) rather than hypothesis generating (such as case reports or adverse events reports), so playing with the data felt uncomfortable.
Other practices to ensure the marketing message was clear in the final publication included omission of negative results, usually in secondary outcome measures that had not been specified in the protocol, or inflating the importance of secondary outcome measures if they were positive when the primary measure was not.
Given how much of what passes for medical research is performed by drug companies, and how much of medical education revolves around pharmaceuticals, the adulteration of research is profoundly disturbing. We’re rolling back the underpinnings of medicine to the days when quackery reigned, except this time, with the authority of the medical profession and the mysticism of science behind it.
So to summarize, the marketers would control the statistical analyses, promoting multiple analyses to attempt to come up with the “right” result that would support the marketing message (although the more kinds of analyses one tries, the more likely one is likely to come up with false results by chance alone). Presumably the marketers did not care whether or not the results were really true, which is perhaps why even they felt “uncomfortable” in some circumstances.
They would also foster the suppression of negative results, and the dredging of data for extra outcome measures when analysis showed no advantage in terms of the real primary outcomes. Suppression of negative results could be viewed as plain lying. Deliberate analysis of multiple end-points again risks identifying random error as true results.
This doesn’t mean that vaccines aren’t perfectly safe.
True. It means merely that neither you nor I may rely on the safety or even the efficacy of prescription drugs. Or vaccines.
There is zero evidence to suggest that vaccines cause autism.
….. or epilepsy or homosexuality or any other thing that is being caused by altering our genetic code. There is proof they are altering our genetic code. They have too much control over our minds and bodies. We need to stop allowing that.
Not to rain on that categorical statement, but an examination of the contents of an MMR vaccine dose would reveal the presence of Human Serum Albumin, a blood protein. The introduction of foreign proteins into the human bloodstream can cause encephalitis or other brain inflammation, which may vary in its severity. Naturally a side effect of the MMR vaccine, commonly seen in up to 15% of children vaccinated, is fever >103 degrees. While most chalk this up to an immune response, this also falls neatly into the same category of effects as encephalitis.
I would dearly love to see research on an examination of what is actually happening to the brain during this side effect period.
Given the extremely nasty effects of feeding animals to other animals (BSE, Scrapie, CWD, etc.) I posit that the effects of human derived proteins or prions such as found in the HSA (Albumin) component of the Rubella Vaccine have not been adequately studied, and the science is definitely NOT settled in the area of these classes of diseases. While feeding infected bone or blood meal as a protein filler, or transmission by infected preadator animals are known vectors, how many of you know that the Rubella component of the vaccine is cultured out Human Diploid Fibroblasts? Or that it was isolated from a congenitally rubella infected aborted fetus? As a Natural and Organic food person I care about what I put in my body. The MMR vaccine which contains human derived proteins was licensed in 1979. All others before that were animal derived.
For the knee jerk deniers: http://www.cdc.gov/vaccines/pubs/pinkbook/rubella.html
This begs a legitimate question: Has adequate non-biased research been done on this aspect of disease complications of protein based infectious vectors? Especially when such research might open the floodgates to massive liability?
Oh, thats right! Big Pharma got immunity from the consequences of harmful vaccines from Daddy Government! Woot!
There are known and real dangers of vaccines. Including autoimmune diseases.
Autism is NOT one of the dangers. There was a controlled UNIVERSITY-funded and run study which extensively examined this question.
Now, there *is* evidence that endemic hormone disrupters (such as estrogen mimics, but in this case other hormone mimics) may be causing autism. If you’re eating organic, I’m sure you’ve heard obout the hormone disrupter problem, which is well-documented. This has *not* been properly studied. The chemical companies don’t want anyone talking about that.
Again, not to rain on parades, or be conspiratorial, but where do you think universities get their funding?
Who do the grants come from?
Corporations and governments.
Who sponsors a given research line?
Corporations and governments.
How do researchers stay employed?
Their research does not rock the boat, unless the boat rocking is worth more money than they are already getting.
In short, UNIVERSITY is not a badge guaranteeing, in any way, validity of data.
My original research questions stand, in regard to Prion behavior and encephalitis effects on brain development.
Remember, PTSD was laughed at before the Iraq Wars, and TBI was not studied. Until, that is, they found that being in close proximity to a major explosions scrambled brain circuts and required brain retraining, and being in two explosions would permanently alter brain function.
These effects are real, and took a long time to become ‘officially sactioned’ because they upset the established order and mindset.
The book “Mad in America” about nails it.
“You don’t like to think that stuff like that influences what a doctor prescribes, but it does.”
the last time i went to see a doctor out of town, when visting my brother, two of those drug company door-to-door salesmen walked through the waiting room, right on back to see the quack, right in front of a room full of patients. i have no doubt that guy tries to fob off on his patients whatever those creeps are hawking. its a disgrace.
The reps are no longer allowed to come bearing “gifts” when they visit the docs. Regulations or laws or whateverwere changed about 4 years ago and the once-standard bribery practices were forbidden. Doctors have to go to Office Depot now and buy their pens and notepads just like everybody else.
I know (you can find proof in older posts) but I left that in to show how the pharma guys have studied and use every angle they have at their disposal.
The “PharmaPhoque” Seal-the-Deal model.
That is absolutely not true! Although the laws have changes, guess what….They are still getting around it. I just did two BIG events at St Luke’s Hospital, for the pharmacy dept. I charged 24.00 pp and it was a lunch! They don’t get the stupid pens. cups, pads, bags, or magnets, but they still get food and some even get wine.
I stopped working with them, because I am passionate about healthy foods and the majority of the office workers want “Italian(pasta or pizza) or they want Spanish(rice and beans). So, my hard work is wasted on them. It’s a corrupt bunch and they know how to play the sales reps. Since the sales reps are under so much pressure to sell, they will do anything to keep their jobs!
Fidel you are on to something. Hard times are made harder as people will do anything to keep their jobs. No real safety net and two paychecks away from homelessness most people do not have the luxury of being principled. Sad but true. Much pain among many decent people who are trapped. Then of course there are the sociopaths and true believers but thats another story…
The M.D.’s cop “free” Rx “samples” for friends & family.
Which would say that those MDs trust those drugs at least to use on their friends and family, then.
I can’t speak to legality, only that the following happens a lot. The drug rep comes in and takes everyone’s lunch orders. He or she then goes out to buy it and distributes it to everyone in the office. These people are busy and this is a real help to them (although it is often phood from Arby’s so perhaps the real movtive is the creation of costumers for heart drugs!) I asked my doctor about this and he claimed, I believe truthfully, that these lunches did not effect his prescribing actions. I have read several studies which show that marketing does effect doctors actions, even when they sincerely believe it does not.
Full disclosure: I admit I asked my doctor for his viagra clock! I just love it!!
Jill, it really affects Doc Rx if he/she or family members are “invested” in the Pharma companies.
1. Do you honestly think you doctor would admit he was influenced? That’s close to asking for a lawsuit.
2. People are in massive denial about how easily they are influenced. Social psychologist Robert Cialdini reports that a gift as small as a can of soda will bias someone to be more receptive to a salesman’s pitch.
Especially at noon and midnight when both hands point up.
Their bewitching hours are all hours in between.
Ok, let’s get things straight shall we. I was a drug rep for 2 years (1999-2001) with Janssen (a subisdiary of Johnson & Johnson). There are very few doctors that are not influenced by sales reps. This is a fact. Pharma buys Rx listing from pharmacies and compiles lists of top docs, i.e. those that prescribe the most and targets those docs heavily (80/20 rule), and those docs are well aware that they are being courted and play the game accordingly. Believe me when I tell you that it’s a quid pro quo game. No one will come out and say it but it’s there. I once expensed a $3000 dinner for a few gastros at a very nice restaurant in Santa Fe, New Mexico and my number went up. They were grateful and gave me some business. And there are always loop holes. There was once a time when you could simply take docs on vacations, buy them gifts, etc.. but that was changed so avoid conflicts of interest. So what did pharma do? They simply made the docs pay their way and now pay them consulting fees to wash the taint of the bribe off. One last thing in this quick rant: a manager once bragged to me that J&J and by extension Janssen was too smart to do “too much” R&D. They were much more comfortable licensing or creating me-too drugs (e.g. Aciphex was introduced to compete with Prilosec, at the time) so that the actual clinical hurdle of proving efficacy was lowered. This was it was cheaper to introduce and capture a segment of the market than it was to truly deliver new drugs for new ailments. The fact that I was given a car, with a gas card and an expense card with limits for some docs and no real limits for other will tell you the entire story. The costs are really all marketing and doctors (not all but many) succumb to the free stuff just like any normal human being. They are bought and sold you just don’t know it. Good luck with your doc because he might seem like he’s being honest but those trips to Aspen as a consultatn just might be too nice to give up, so enjoy your marketed drugs, that just might be as effective as the science they are supposed to be based on.
(Had to rush this one out so sorry for the sloppy grammar and syntax)
Now instead of wholesale pens deliveries they include a pen and notepad in the “informational and research folders” they leave with clinics. And they usually bring lunch with them when they come as well.
Ah, Pharma lunches and dinners: what practitioners live for.
This is good to know.
The culmination of my witnessing of such tactics in my own G.P.’s office happened one day when two (very attractive, very young, female) pharmaceutical reps walked into the doctors’ waiting room within about 5 minutes of each other.
It seemed to be a relatively busy day for the Practice, and the waiting room was quite full. The first rep struggled to get the front door open but then skillfully manuevered her way to the receptionists’ desk with a huge platter of luncheon sandwiches. She announced perkily to the receptionists that she was there because she just wanted to wish “Dr. So-and-so” a Happy Birthday. She was asked politely to sit and wait.
Enter rep number two–who comes in with one of those edible fruit “creations.” She asked to see the same doctor and was also asked to have a seat and wait.
So there we all sat–the patients and the pharmaceutical reps–in a moment of common, awkward understanding.
This is definitely par for the course.
Sheesh…. Alll product marketing material from every type of business is stuffed full of contrived science.
The only things that matters are whether the customer believes it and the lawyers approve it.
For my shame. I once worked in competitive intelligence, cherry picking data and commissioning misleading “independent” reports to exaggerate weaknesses in some other poor saps product.
>>> Furthermore, the studies were supervised not by physicians or scientists, but by marketers in the marketing department <<<
I think you'll find the marketers in the marketing department *are* scientists.
Like any other businesses, Pharma companies must be able to market the products they've spent billions of dollars developing, else they'll cease investing and health-wise we'll be worse off for that. Likewise, when they overstep the mark they should be punished hard.
Whether it be Big Pharma, or Big Oil, or Big Finance (Wall St), or Big Food, or Big Whatever, the problem seems to be corporate culture generally. But until someone comes up with a radically different model for organising productive endeavour, we'd best quit moaning and instead persevere with making the best with what we have.
So, maintain regulatory pressure, punish transgressions and promote and encourage the highest ethics, but do not indulge in demonising that gets us nowhere.
Please spare us the PR.
1. Big Pharma spends more on marketing than on R&D. And having known people who’ve worked at the corporate staff level at major drug companies, they are generous in how they allocate overheads to R&D.
2. Close to 90% of new drug applications are not what a layperson would consider to be new drugs. They are modest tweaks on existing drugs (like time-released Wellbutrin, so you take it once a day rather than 3X a day) often for the purpose of extending the patents
3. The article (and other accounts, see the examples in the Health Care Renewal post) made it clear that the interventions of the marketers in research were contrary to good scientific practice. So even if they might have had “science” training in their backgrounds, they are not operating in the manner of scientists and are not deserving of the label.
Pharma isn’t doing much research in the traditional drug arena anymore, that’s common knowledge in the industry. As Yves mentioned, its mostly tweaking of existing products, where it costs little but gets them new patents. There is a mindset that most everything has already been discovered. Do we need another new medication that lowers blood pressure?
Much of any real research is now being done in biologicals. These are drugs that target specific disease processes rather than the entire body, thus typically have fewer side effects and better results. There are only a few on the market right now, e.g. Humira for rheumatoid arthritis, but are seen as the “drugs of the future”. And they’re expensive and enjoy more and longer patent protections than regular medications so the drug companies see more opportunity to recoup their cost and make profits.
Just to be a bit more specific, having worked for some years in a large non-profit research institute, it’s pretty common knowledge that Big Pharma basically preys on 2 things now : academic/non-profit research + buying successful start-ups. They don’t do their own research anymore (I think some of these big companies actually have totally gotten rid of their R&D department, the only new “research” they do is find new applications from already approved drugs, which means they can skip human testing and FDA approval processes altogether saving tons of work, time and money… but obviously producing nothing new).
Real research gets done in academic/non-profit, from the money obtained in grants from large foundations (Bill Gates’ for example) or government (NIH, NIAID, etc…), OR from start-up companies that can get private investments. You’ll have reps from Big Pharma that will scout around in seminars, read research coming out of these academic organizations, etc. until they find something they can profit from. Then they can do test trials with the drugs found by academia (usually the animal testing part was already done by the previous research), and get a patent. They might recruit the scientists responsible for the discoveries to go do the final steps with them sometimes.
The other thing they can do is swallow-up successful start-up that managed to do everything up to human-test trials (which is very expensive to do and usually they will not have the funds for). So if a start-up has something very promising, Big Pharma will buy them, do human trials and get the patent for the new drugs. Note that this is what start-ups actually wish for usually, because they know they will not have the funds to go all the way to having a drug on the counters (which is a long and ridiculously expensive process, pretty much insuring that only Big Pharma will ever get something out that you can buy). But it also means that Big Pharma doesn’t have to pay anything for all the unsuccessful start-ups where it’s just the investors losing money.
The one very frustrating ‘flaw’ in the system for me it’s that again, it comes back to the same damn thing with privatization. A good part of the risk and the losses are paid by the public (grants for unsuccessful research, etc.), but when Big Pharma gets their hand on the good results leading to some new direct application, they will keep all the profits. You can be sure they won’t send the money back to the non-profits that actually did all the research necessary for them to get their new drug.
It’s a racket. Advertisement/advertorials/PR presentations for pharmaceuticals really should be forbidden. It’s the same model for “persuasive” corruption used in corporate politics and finance. Only in America, thanks to shill SCOTUS.
Yep, there are people trained in science in pharma just like there are people trained in law at the SEC and Justice Department. We place too much faith in credentials in the U.S. and too little on actual practices.
Also, exponential price rise in pharmaceuticals since “Medicare” captivity.
Once again, from Richard Feynman’s lecture on cargo cult science. Most scientists would agree that Feynman qualifies as a “real scientist,” no matter the precise definition.
There is one feature I notice that is generally missing in “cargo cult science.” It’s a kind of scientific integrity, a principle of scientific thought that corresponds to a kind of utter honesty — a kind of leaning over backwards. For example, if you’re doing an experiment, you should report everything that you think might make it invalid — not only what you think is right about it; other causes that could possibly explain your results; and things you thought of that you’ve eliminated by some other experiment, and how they worked — to make sure the other fellow can tell they have been eliminated.
Details that could throw doubt on your interpretation must be given, if you know them. You must do the best you can — if you know anything at all wrong, or possibly wrong — to explain it. If you make a theory, for example, and advertise it, or put it out, then you must also put down all the facts that disagree with it, as well as those that agree with it. There is also a more subtle problem. When you have put a lot of ideas together to make an elaborate theory, you want to make sure, when explaining what it fits, that those things it fits are not just the things that gave you the idea for the theory; but that the finished theory makes something else come out right, in addition.
In summary, the idea is to try to give all of the information to help others to judge the value of your contribution; not just the information that leads to judgment in one particular direction or another.
Marketing may indeed be a science – the science of propaganda and manipulation for profit – but let’s not delude ourselves into thinking it’s serving any kind of useful purpose other than the corporate bottom line. And continuing to lead the many sheep to their collective slaughter one “white lie” at a time.
James, the best M.D.’s used to follow these principals, writing for medical journals. But those were the days when the finest diagnosticians were deeply informed, experienced, ethical human beings whose purpose in Medicine was to heal and live comfortably, not to live high on the hog while forfeiting diagnoses (and the responsibility for the same) to machines.
That was before “ambulance chasers” and Third Party Administrators multiplied.
Edit: NOT “principals” BUT “principles”
Hate to say this but medicine is now just another racket and one of the very worst ones. For years I have avoided all drugs except aspirin and remained remarkably healthy. Don’t even have a doctor where I live most of the time, which forced me to an emergency room for an infection, where I was given a sulfa drug. The infection disappeared but side effects have laid me up for two weeks, occasionally making me wish I was dead. I still have incredible weakness, gastrointestinal symptoms, insomnia. This drug has been around 40 years!
Feeling crushed by my drug side effects, I tried to make an appointment with a doctor I actually respect, a guy who lived next door to me twelve years ago and was a friend who ate dinner at my house. (He no longer lives next door, I moved) The first appointment I could get was delayed a month. His office had no interest in what was wrong, just sent me a twelve page disclaimer form to keep me company. Can’t wait to hear his advice, if I’m still alive in two more weeks.
LBR said; “But those were the days when the finest diagnosticians were deeply informed, experienced, ethical human beings whose purpose in Medicine was to heal and live comfortably, not to live high on the hog while forfeiting diagnoses (and the responsibility for the same) to machines.”
I’m pretty sure that there’s a lot of good doctors perfectly capable of doing the same as the good old days. However greed and money get in the way of doing medicine. Where would you possibly find the time for medicine when there’s more money to be found elsewhere? The problem is our tax rate. If there was an effective cap to income there would be no need to chase money instead of your real job.
TINA!!!! TINA!!!! TINA!!!!
When the paid shills are cornered by the truth, then their fallback is always:
TINA really gets around.
” maintain regulatory pressure, punish transgressions and promote and encourage the highest ethics,”
You are stating that with a straight face? A government, at all levels that is owned by the major monied interests, is going to punish transgressors? Just like in the $ multi-trillion scandal that destroyed our world’s economy saw hundreds of highest ranking execs jailed? Or like the punishment meted out to the companies that recently destroyed the Gulf of Mexico?
Which one of the towering representatives in ethics should this creature known as the U. S. Government strive for-Al Capone’s or Carlo Gambino’s ?
Dr Ben Goldacre has been all over this.Writing about the need for better regulations of big pharma. He was on radio 4’s Today this morning parsing GSK’s PR over their latest fines.
his blog is Bad Science at http://www.badscience.net/
To be clear, this post is referring to post-marketing studies, i.e. studies done after the drug has been approved by the FDA and released. The clinical tests required by the FDA remain pretty rigorous. However, if a company is willing to fudge the data, I’m not sure what can be done, other than severe sanctions should they be caught. Our tort system tends to do pretty well in the economic sanction department, manages to (barely) cover funeral costs for the injured parties, and makes some attorneys very wealthy.
That doesn’t mean the company won’t highlight benefits and downplay any drawbacks though. BigPharma are corporations (not people) and big money, and have suffered from the same greed and short-term profit seeking behaviors that the financial industry and our other large corporations have. Merck had invested a lot of money on R&D on Vioxx, getting FDA approval, and bringing it to market. They had already counted the billions they would make. They didn’t want to see their investment evaporate.
Why let a few pesky deaths ruin the fun for others?
LL, what would BigPharma do without FDA “seal of approval?” Isn’t this their back-up “release from liability” guarantee?
Also, aren’t Academic slaves to Name Profs still doing the first tier of research, paid for by “University Grant” from NIH and such? Shouldn’t the “Public Purse” investment in the potential Pharma product get a cut of the take when Pharma starts to rake in the cash from its “patented pharmaceutical?”
What a good racket. Make a drug that does something (anything, really, including placebo), then invent a designer disease to match it.
Take me. I’m hopeful and cheerful. I vibe enthusiastic. I practically radiate joy, 24/7.
Bad news, Patient 424. Results indicate you have Malaise Deficiency Disorder.
Contracted how or when (or why?), who knows, but your mental health requires that you become more compatible with our generally, quite melancholy population. Therefore, I’m proscribing our next generation pro-depressant, Raque-XX.
A Six Months to Life Double X Regimen will level you out and do you good. Trust me. As always, warning garble side effects minimal to maximal (depending). Take three times daily, or as required.
I don’t think this is what’s happening in actual scientific medicine. I think the myriads of diseases we have are real.
The new DSM IV is a different story altogether.
Now Max. Telling tales out of school, a no-no.
In junior high school health class, some sixty years ago, we were told “alcohol is a good servant but a poor master.” This would apply to capitalism as well.
ED, excellent contribution. We should put it on physical & digital billboards.
Back when I worked in such things was always perplexed by the methodological choices of the pharma “researchers”. Very simple thing which became standard practice was the sugar pill test. They would test a drug against a sugar pill and then report the benefits. They would not test against an existing drug devised for the same condition or heaven forbid a drug produced by a competitor. Busy doctors saw the amazing results (better than nothing essentially) and viola a new product gains cred….Uggh. One frigging scam after another in this country. Ives should rechristen naked capitalism to Scam Nation or have a egregious item featured in “Scam of the Week”.
CR, indeed: A Nation of Grifters. MAD Magazine’s “shrinking cereal box” told this fundamental truth so any kid could laugh at it (kids already “got it” at home).
If funding doesn’t come from big Pharma, from where shall it come?
Government sponsored research used to be the gold standard alternative (such as NIH grants) but now I am not so sure. It is hardly worth reading medical journals these days. BMJ seems to be better than most.
He who has the gold writes the rules-and big Pharma has the gold.
I worked with the pharmaceutical companies. I would supply them with lunches and mainly food. I became friendly with some of the sales reps. and they would tell me and I was witness to some of this, what the doctors would ask for. Some asked for Plasma TV’s, box seats, at the Garden, I saw a Yankees Game ion the best seats ever….Spike Lee, was only three seats away. You can imagine how expensive these tickets were. Gift cards (AMX), Expensive wines or liquor, strippers, and one even remodeled his office in Jersey City.
Some of the reps had a term for some doctors offices….”Rep Whores”
Fidel, and these “gifts” were tax-deductible! The fix is in, big time. So, “Corporations are people” but they have much better tax-relief than human people do, and they’ll never enter the Texas Prison System for crimes.
All these wonders of science in pharma! In banking and well technology of all sorts we have twiiter and are so advanced. Despite the blather half of the nations capital was without electricity for several days. Even in tony maryland and northern va. Make excuses all you want but hey if you don;t invest in real things like say eclectrical grids and bridges things fall apart in the real world. Too much propaganda and techno fantacism. Electrical systems, public health and transit too hard to “monetize” and yield VC deals I guess……
There is a fundamental distinction that must be made here. That is, when a drug company uses the word “research,” it means conducting the requisite studies to bring a drug to market. It’s linear and product driven – and, as noted, can spin straight into the marketing department. When academics use the word, they mean generating new knowledge within a recognized area of study. It is neither market driven nor linear. It’s ivory tower. In the US, the system is set up for NIH and other agencies to support studies for this cost-ineffective science. Once a compelling lead has been developed, typically at the point of a Phase I or II clinical study, the scientific baton is passed to industry to commercialize the lead. The process breaks down on various levels, including a drug company’s profit-driven need to have IP protections at the frontend. In their view, publicly funded research is too open to their competitors. Thus, academic research certainly has its warts. But the BMJ article refers to specifically to other side of the research spectrum. This distinction really must be made.
using the word science sounds fairly authoritative. Its a commerical process not a scientific process you note. Academic research is useful to society but not useful in s strict sense to a product launch that is over priced due to political fixes. Its all really gaming the regulatory system.
In recent years the european and japanese pharma firms have made great innovations that are life saving, done in a truly cost effective manner and subject to greater rigor–and far less marketing. Also, the outcomes for say oh regular people are much better. There is research to substantiate my statement. Why americans are so provincial who knows. Ever since Part D the U.S Pharma firms have been on level one mulcting of seniors and government…
If I understand you correctly, I would have to disagree about the word “science.” The drug companies do indeed conduct science. In fact, their scientific capabilities are daunting. I referred strictly to the word “research,” not science. Most people don’t understand the research continuum that exists in our society. But that’s semantic housekeeping. The real issue remains: How deeply rooted in the scientific method are the end points of corporate research? Abstracting upwards a level or two, I firmly believe in the idea of the public commons. It has served the US and many nations well. But what we see again and again is how business melded to the various branches of the public common (health care, law enforcement, education) corrupts absolutely. The theme is so obvious, and yet we have such tremendous difficulty as a society honing in on it. It’s both fascinating and sad.
Indeed you are correct….corporatism is both highly effective and destructive. Yes the capabilities in data mining, sequencing, etc, etc are indeed amazing. Sadly they are harnessed to serve narrow interests.
Model: Transfer of Common Wealth to Private Wealth. It’s a long con, from well before the implementation of The Shock Doctrine-Disaster Cap model.
I would like to correct the misunderstanding about the degree to which academia contributes to a lead. Academic contributions are a germ of an idea, usually through the identification of a target. Rarely does academia provide a lead. That’s what we used to do. We verified the target, developed the assays, screened the compounds and optimized the lead before it was passed off to development. The idea that a lead compound comes straight from an academic lab to industry and proceeds to development unscathed is a fantasy. There is plenty of research to do in the industrial lab and it takes many years, if we’re lucky, to get it to development stage.
I have no doubt that the corporate overlords would like for it to happen as you suggest but that’s just not how it works in the real world. In the real world, academic scientists get jobs in industry and quickly realize that research is much more demanding than they think.
Just my two cents because I have been there.
It is difficult. The fellows who did mathematical models for derivative trading and credit defualt swaps were often math and physics PhD’s from top universites. Many probably certifiable geniuses who worked long hours in demanding conditions. All well and good–but still a scam. A scam is not elevated because smart people worked really hard to get it going….
CR, you mean if you’re “really smart,” your crimes are not crimes?
Absolutely not. Riverdaughter seems to imply that though…
Excuse me, but I don’t consider what I did for 20+ years to be a scam. It’s unfortunate that any comparison is made between what those assholes on Wall street do and real scientists in pharma labs.
I designed cancer drugs for the last 8 years and CNS drugs before that. I think I have a bit more insight to this than you think. The level of demonization and mythmaking in this thread is appalling and unfair to the labrats who didn’t go into science for the money.
Here’s how it really happens:
1.) some academic group finds a target or biological pathway and *maybe* the barebones of a therapeutic agent. They publish.
2.) the therapeutic heads pick the targets and set about validating them.
3.) if the target looks druggable, a project team is assembled to try to find a lead compound that can be turned into a drug.
Along the way, it is frequently the case that the biology of the target is more complex than the academic group first understood. It is the scientists in industry that make the real discoveries with respect to the system biology because they have to in order to show efficacy and safety. This is just as creative, intense and enjoyable as any academic research. It happens more quickly than academic research as well. Most PhDs have no idea how complicated it really is until they do it and I have had to bring more than one PhD up to speed right out of academia.
The problem is that we can no longer easily meet the FDA safety standards, which are increasing every year. We all want to produce the perfect drug but this may be impossible.
I would love to describe exactly how it is that we look like we’re not producing anything original because once people understand how “me too” drugs happen, it doesn’t sound nearly as sinister. I can also tell you what the future of drug discovery is going to look like and you are not going to like it but by that time, it won’t be any fault of the labrats, as if it ever has, because none of us will be around any more. And that’s something you really don’t want.
Here’s my counter two cents having been “there” for about 30 years. True, many startups today take an idea and run with it. But (a) the idea probably came from academia and almost certainly went well beyond just identifying a target, and (b) the scientific infrastructure in the US is a far from seamless. I can go on ad nauseum about leads that are fairly well developed but are in need of venture capital or an academic scientist who knows how to commercialize a good idea, not write a grant. Here’s the flipside. NIH recently started a program to develop new leads for Big Pharma compounds that never made it through the developmental pipeline. Why won’t Big Pharma do it? There is no financial incentive. And that goes back to my original point about research. Big Pharma commercializes; academia conducts the cost-ineffective research.
I’d like to know what academic groups you’re working with because I have never seen that scenario play out.
More often, the academics only have a small piece of the puzzle that gets fleshed out once we get our hands on it. Many a project has been put on hold while we do the work that the academics didn’t have time/resources to do to verify a target or structure activity relationships.
I’ve seen projects drag on for years because we needed to lay additional ground work before a lead was discovered or optimized. In fact, I worked on a kinase that was supposed to be for MS that was later turned over to oncology. I worked on a 5Ht agonist that was initially supposed to be for appetite suppression that was later switched to schizophrenia. I’ve seen many crystal structures that looked like low hanging fruit that turned into decade long ordeals. The real therapeutic benefits or difficulties weren’t determined until we had to actually do the work to optimize the leads.
What academia provides is the 1% inspiration and what industry provides is the 99% perspiration. Like I said before, the corporate overlords would very much like to believe this isn’t true so they can exploit cheap graduate student labor. If that’s their attitude, they have a rude awakening coming their way.
Oh and about those pharma compounds that didn’t get developed? Every compound that gets made at a pharma lab goes into the compound library and depending on its compound diversity has an opportunity to be tested in a wide variety of screens. The reason why some drugs are abandoned usually has to do with patent coverage, hERG issues or other ADME properties, toxicity, or they just weren’t very efficacious in the target. If it’s a patent issue, the compounds can be used as tool compounds to flesh out the structure activity relationships of a target. If it’s a hERG issue, it’s not going to make it past the FDA anyway. Some ADME properties can be fixed, some can’t. Sometimes, the therapeutic area has been covered already and god forbid we make another “me too” compound. New and Improved is perfectly fine for laundry detergent but you don’t want to put a better product in your body because someone else might already be on the market with something.
But the bottom line is that all compounds have an opportunity to be retested and there are groups that constantly revisit the compound library looking for new ways to use old compounds within pharma.
What is good about letting other groups have access to these older compounds is that people like me, sitting at home, could potentially do a virtual screen on them and use them as a starting point to design new compounds, something the internal scientists are already busily doing.
I just went back and read through the thread again. My original point was academia conducts ivory tower research; industry brings products to market. You commented, “The idea that a lead compound comes straight from an academic lab to industry and proceeds to development unscathed is a fantasy.” I never said that, nor did I imply it. In fact, I pointed out that industry labs have daunting scientific resources, and that goes right to your point. Industry labs blow academic labs out of the water. That’s why you get to perspire in ways that academic scientists simply can’t. But I think you overstate the limitations of academic researchers as mere 1 percent dreamers. You are correct that some academics still can cobble together careers publishing a string of gee-whiz discoveries without much followup. But many academics do hammer away, too, to get larger second and third grants. But they typically have no plans to commercialize anything. That’s not what they do. So back to my point, industry is limited financially in the non-directed research that it can conduct. True, that has changed in recent years as bioinformatic and screening tools have improved. You also make that point well. But Glaxo isn’t NIH. Glaxo wants to move forward, not backwards or sideways. Your point is well take that it’s not all full steam ahead at drug companies. Lots of perspiration is needed. But again, the perspiration is to move forward. In academic labs, it’s to position yourself for the next grant. Anyway, we’ve covered a lot of territory here. I started out trying to halt the broadbrush implication that all research is industry funded. Now, I’m stuck defending academic research. But I’d also like to defend industry research as well. The science is phenomenal.
Ok, you’re not quite right on the academic side either. I know academic labs in two local universities. One has a much bigger endowment and can be more pie in the sky than the other but in *both* cases, they are now actively trying to commercialize what they discover in their academic labs. The grant money is drying up and is being supplanted by private grants from big corps and smaller startups. The whole thing is getting to be very incestuous. And while academic labs are well positioned to discover breakthrough technology and science, they are coming under increasing pressure to pull their own weight, which means jumping into bed with big pharma. Big pharma will call the shots and, yes, they are expecting graduate students and former industrial scientists who are getting paid a fraction of their former salaries to do all of the work. Afterwards, the Mercks and Pfizers will swoop down on anything that comes out of these “collaborations” with a 400 page licensing agreement drawn up by the best corporate attorney’s money can buy.
The scientific infrastructure in this country is broken. Neither academia or industry is doing well. The money is drying up and only the projects that some marketing department sees as profitable will be funded.
You don’t need to flatter us in industry. We know we do good science, just as our partners in academia does. But we are all still victims of Wall Street. As long as they have the money and are sitting on it, the financiers will call the shots in the lab whether it is academia or industry. All of the rest of the arguments about pharma are just window dressing around that central fact. Science in this country is dying.
“NIH recently started a program to develop new leads for Big Pharma compounds that never made it through the developmental pipeline. Why won’t Big Pharma do it? There is no financial incentive.”
Yes. Important example: betulinic acid, a surprisingly nontoxic compound easily extracted from birchbark and several other botanical sources, which appears to be VERY effective against melanoma and some other human cancers.[check Wikipedia]
Problem: its activity was discovered by a government program in the mid-1990s, and nobody could get a patent on a natural product, much less one whose key use has already been published.
Result: 15 years of research on derivatives, none of which looks as good as the natural product, and not worth starting clinical trials on. How many lives could have been saved if there had been a mechanism to bring ordinary betulinic acid to market earlier?
I would never have known about this except for my job at the time, writing summaries of medical reasearch for (then) Adis International’s journal Inpharma.
I’m looking for my own source of birchbark right now, but I can’t import it into New Zealand from the US (biosecurity!) and I may actually plant my own. Likely an extract can be marketed as a natural product like some herb tea.
So, I took a look at your betulinic acid and I think I see the problem with this compound. It has multiple chiral carbons. It would be very difficult to make this sucker and once it was made, the FDA would require every disastereomer to be made as well so that the active one might be identified. They might have tried figuring out what the shape of the active form was and rescaffolding. That still might work but I suspect they’re going to run into problems with CYP enzymes and there goes the project.
Of course, if you want this stuff that badly, you might want to have it expressed by a different organism. I don’t know if anyone has looked into that. If it’s derived from a plant, maybe the gene can be isolated and inserted into something that would express the compound and you could have it purified. Provided you end up with the right diastereomer from a natural source, this might be more reasonable than trying to synthesize it in the lab. You would have to purify it and analyze it to make sure.
But just growing it and making tea out of it? Probably not very effective, not even if you got mass quantities from a natural source. For one thing, you don’t know how bioavailable it is. That is, how much of it actually passes through your stomach or gut and gets metabolized. And that depends on a lot of things like how soluble it is in water, how soluble it is in lipids, how easily it is metabolized, what its halflife is, stuff like that.
With some well known drugs, like aspirin, humans got lucky. It’s an easily obtainable extract of the willow tree. But the structure of aspirin is much simpler than betulinic acid. But who knows, maybe you will be the one person who will succeed where the other pharmas have not and will be able to overcome all of the liabilities of this compound to make it work.
Good luck with that.
RL, right, the public-to-private giveaway: like DARPA to Gates.
For more on this topic, I recommend “BLOOD FEUD
The Man Who Blew the Whistle on One of the Deadliest Prescription Drugs Ever”, by Kathleen Sharp. This book discusses anti-anemia drugs such as Procrit. It describes how drug companies (notably Johnson & Johnson – also in trouble for other medical device failurs) go about making a market for a drug and making billions of dollars doing it, while not completing the safety trials specifically requested of them by the FDA. Nor do the companies abide by the FDA recommended usage or even the product licensing agreements they have between one another.
J&J drug company sales force is urged to break the law in their sales tactics, by pursuading doctors to boost the dosage above the recommended amount and to apply the drug to off-label uses. Sales reps bribe doctors with “grants”. Beyond that doctors, hospitals and clinics are taught how to make money on the drug’s use in their clinics to de-fraud Medicare because they get the drug from the company for less than they bill Medicare for the cost. A drug rep who resists the corporate pressure is harassed and fired.
Finally after 15 years of mis-use of anti-anemia drugs, the FDA eventually figures out that epo and Procrit cause blood clots and carvioscular deaths among patients using them in excess of control subjects, but most ominously the drugs feed cancer tumors. In the final analysis, it is safer and cheaper to give an anemic patient a blood transfusion than the drug. Estimated deaths from anti-anemia drugs run perhaps as high as half a million.
It is particularly sad that doctors are so vulnerable to corruption by drug companies.
Since 1992 and the HIV/AIDS emergency, FDA regulators have been subject to new laws meant to speed drugs to market and decreasing funds to regulate and test drugs.
Eric Holder is discussed briefly toward the end of the book, but it is not a flattering mentioning. He’s caught in an industry/government revolving door conflict of interest thing.
FDA leadership is slightly strengthened since the demise of the Bush administration, but we still have a terrible problem to regulate better. Our FDA laws – first put into place in the 1930’s – have been weakened as well as the financial regulation laws instituted then.
LAS, has anyone done research on the cost/benefit of this “way of doing business?” It’s like a lobbyist for X giving $100K to Congresshill: Congresshill allows XRep to write the law that will yield to X a “ROI” of $100m on-the-ground in reality, AFTER the lobbyist and XRep gets their cut.
Whatever the “fix,” it always yields to BigCorp an exponential return.
Indeed. Odd how the advocates of free enterpirse are always lobbying to rig game in their favor….One wonders how sustainable it is…
might help someone out there….
Stem Cells Break through – Dramatic Change in Patient with ALS and MG
a propos- http://blogs.wsj.com/health/2012/07/05/a-m-vitals-dr-drew-took-glaxo-payments-promoted-drug-on-air/
pardon, the full article (shame it lacks the snappy URL): http://online.wsj.com/article/SB10001424052702303933404577505032006855076.html
It’s all about the money. We never find out the real side effects of a drug until millions of people have already taken it. Taking a new drug is tantamount to being enrolled in an informal post-marketing study.
when i see a drug company study, the game is to see how quickly i can find the way the deck was stacked. was the comparator drug overdosed or titrated too fast or just never given in adequate quantity? is the study empty in just telling me the drug in question does something i expect every drug in the class to do? were side effects actively solicited or only passively reported? it usually takes less than a minute or two to find the bs.
Big Bucks, Big Pharma-
Some folks may need medications prescribed to them but, .
Most likely a lot of folks are on meds that are not needed and may be causing harm. We all need to take a look at this. 1/3 of all medical costs are related to meds.
In medicine nowadays, the mantra is evidence-based medicine, but if the evidence is rigged, what does that make the medicine based on it?
Big Pharma continues to bring important medications to market. In an imperfect world, they do as well as anyone….Yves, why not focus on Obama’s plan to develop “…an internal security force as well funded as the military…”. Perhaps most Americans would not recognize the creation of SS troops when they see it…But my guess you would and you’d be rather concerned about it…Just a suggestion to look at Obama’s shocking admission of his long range plan.
At the beginning of my career I used to work in a medium-sized pharma advertising agency helping Big Pharma sell their Rx products to doctors. Once I met a key opinion leading doctor and had asked him what is the best medicine, he simply replied “Your body, I wouldn’t take any pills unless it is the last resort.” So get off the meds and start taking good care of yourself. Prevention is a better investment and cheaper than treatment.