Ben Goldacre: Here’s the foreword to my new book, Bad Pharma
badscience.net
badscience.net
Platitudinous and evasive answers from the industry rep while referring to Goldacre's 'extremist' views. He's hit a nerve and they don't appear to have a good rebuttal.
For those with iPlayer access you can here it again here: http://www.bbc.co.uk/programmes/b01mw2d4
Edit: Ben Goldacre piece was at 08:34. Excerpt of just that section is here: http://news.bbc.co.uk/today/hi/today/newsid_9754000/9754505....
I would assume they are also contained in the print version.
The last few pages have a large number of references in them, and made me think for a few seconds that the book was longer than it actually was :)
As usual, I have to recommend here the edited group blog Science-Based Medicine,
http://www.sciencebasedmedicine.org/
which like any blog includes some daily articles that are duds, but which also features some of the best discussion in popular language by statistically astute medical researchers on what needs to be reformed in regulation of new drugs, and what is already working better than some possible alternative approaches. A recent post there, in this instance by a lawyer,
http://www.sciencebasedmedicine.org/index.php/stem-cell-ther...
is a thoughtful discussion of some of the regulatory trade-offs.
AFTER EDIT: Two things to add here. The clinical trials registry
hosted by the U.S. National Institutes of Health is one response to some of these concerns that precedes the publication of Goldacre's new book (which I intend to read cover to cover). It has a lot of information about human patient clinical trials being conducted all over the world.
Reviewing another recent post to Science-Based Medicine,
http://www.sciencebasedmedicine.org/index.php/news-flash-doc...
I see it mentions Goldacre's new book (favorably) and also analyzes a very recently published study about physician influence by drug companies. I have submitted that here to HN
http://news.ycombinator.com/item?id=4569970
for thoughtful comments by all of you.
At least judging from this example, the majority of his book is sourced from two earlier books that were written about the FDA and the American drug system:
The Truth About Drug Companies by Marcia Angell
Overdosed America by Jonathan Abrams
Those were published in 2004 and 2005, so there are a few studies published since then on the influence of pharma funding on trial outcomes, but nothing that contradicts the earlier results.
In general though the problems are exactly the same between the US and the UK. There are a couple drugs that are legal here and not there and vice versa, but the underlying system corruption is identical, because it's literally the same studies (or at least the same methodology) that is used to get the drugs approved in both countries.
Also, as I've said before, that science-based medicine blog is mostly industry propaganda. There is overwhelming evidence that drug companies have a massive influence on doctor's prescribing habits, e.g. http://jama.jamanetwork.com/article.aspx?articleid=192314
Here they are literally arguing that doctors aren't influenced by the file drawer effect because doctors can tell the difference in methodological rigor between good studies and bad studies. That has to be one of the dumbest and most intellectually dishonest arguments I have ever heard. Science-Based Medicine (the blog) reminds me a lot of Brawndo. Their basic argument in every article is just "but it's what plants crave!!1"
http://news.ycombinator.com/item?id=4245571
I would submit that the underlying system corruption is probably stronger among enterprises that sell schedule I controlled substances here in the United States than among those that sell government-regulated, physician prescribed medications. Both regulatory systems, the system that makes some drugs I've seen you speak up for contraband, and the system that makes some newly invented drugs legal items of commerce, may indeed need further reform. But it's an exaggeration (contradicted by thoughtful comments by drug industry researchers who have already posted replies in this thread) to say that the enterprises that develop new drugs for prescribed medical treatment are corrupt in general beyond what Goldacre claims with specific evidence.
edit: Response moved to pastebin: http://pastebin.com/cniysd82
(Didn't realize how long that was going to get.)
Your arguments regarding non psychiatric medicines are weaker. For example, in oncology trials you state that the practice of excluding patients who are elderly or frail is 'not a good way to find out how to treat most cancer patients.' The reality is that it is very difficult to show any evidence of benefit in patients that aren't fit to start off with. This is because not being fit is a strong determinant of poor outcome. If you include them in the trial then it will be negative, and even those patients who might benefit won't ever get the treatment. This isn't bad science, it is just the required degree of pragmatism when resources for running trials are scarce. The way the research is done in reality is first you give the drug to the people most likely to benefit, and then if it works for them, test it in other groups less likely to benefit by running trials specifically in the elderly or frail groups. When these trials don't exist, and they often don't, the oncologist discusses the options with the patient and family based on the available evidence. They don't, as you seem to imply, give chemotherapy to everyone that walks in the door because Pfizer took them to lunch.
So definitely agree for antidepressant trials. But not for everything else. Although I haven't read Ben Goldacre's book. Yet.
I think this would be an extremely valid argument, except for the fact that these drugs are in fact targeted at, and mainly used by, the population that is older and more frail. And this doesn't just apply to cancer drugs, it applies to NSAIDs and all sorts of other garden variety treatments. I realize there are limited resources, but the end result is that the vast majority of the elderly (by far the biggest consumers of drugs) are taking medicines that have never been tested for safety or efficacy in people like them.
Also, it's not just SSRIs. There are a wide range of psychiatric and non-psychiatric drugs that are either no more effective than placebos or generics: SSRIs, benzos, ADHD drugs, anti-psychotics, statins, calcium-channel blockers, evergreens like nexium and clarinex, claritin, COX-2 inhibitors (now pulled from the market), etc.
Of the 20 most-prescribed drugs overall, it looks like just under half are no more effective than placebos or generics.[1] And if you look at the top 25 psychiatric drugs, something like 22 or 23 of them are no more effective than placebos or generics for longterm use, which is the vast majority of the usage.
[1] Statins are arguably useful for people who have already had a heart attack, but the vast majority of people taking them don't fall into this category, and it's not even clear whether they're really helpful for people who have had one. Meanwhile, longterm use basically causes at least mild dementia and muscle problems in everyone, meaning there is a negligible chance of benefit that's vastly lower than the benefit from giving up smoking or even moderate exercise, whereas there is basically a 100% risk of harm. Also, there is zero evidence that the new statins are better than the old statins, so even if you believe that statins are effective then my original argument still stands since there's no evidence that they're better than the generic ones.
That's beside the point.
The same trials that are used as the basis for product license applications to the FDA are used for license applications to the UK's MHRA.
The process of generating an approval and granting a product license is different, but the same data feeds into the process, giving rise to similar outcomes.
(Also: please do not confuse controlled substances with prescription-only medicines. Two different sets of law apply, one superimposed on top of the other, just to add to the confusion.)
At risk of resorting to an appeal from authority, I speak as a retired pharmacist: the process of obtaining product licenses for pharmaceuticals isn't so much broken as it's irrelevant, because as long as the submission relies on data that can be massaged by the applicant (who stands to profit from it), the outcome will reflect the inputs. (In other words: garbage studies go in, questionable product licenses come out.)
Ever look up how respected skepticism is within the larger philosophical community?
I mean look at my pastebin post: http://pastebin.com/cniysd82
And this encompasses only a small fraction of the corruption within the pharmaceutical industry, because I wanted to make it readable. There are literally dozens of book published on this.
But does SBM actually address any of the criticism? Not a single point of it, because there is no defense; in fact, it's all coming from high-level 'insiders' in the medical community -- JAMA, NEJM, the IOM, etc. Instead they just spin it in order to trick people who are predisposed to have faith in modern medicine. (And I use the term faith, because if you're familiar with these issues then it's unmistakably clear that this is really what it is.)
What science-based medicine does (again, the blog, not the concept) is really no different than what the evangelical megachurches do, it's just dressed up in different language.
I hope you don't see these questions as confrontational because I genuinely would like to be pointed in the right direction for the some of these claims. (speaking as a relatively liberal person who recently joined a host of strongly conservative forums to get a picture of "the other side"...)
> Ever look up how respected skepticism is within the larger philosophical community?
I gather this means that it's not respected? Why is that? I find it hard to believe that scientific skepticism (and not the truther/birther/moon-landing-was-a-hoax kind) can find widespread opposition in any sort of critical thinking community.
> Instead they just spin it in order to trick people who are predisposed to have faith in modern medicine.
Are there any examples of this from the blog? I was (and am) under the impression that a lot of writing is backed up by fairly solid reasoning, references and such.
> What science-based medicine does (again, the blog, not the concept) is really no different than what the evangelical megachurches do, it's just dressed up in different language.
How so? This analogy sounds suspiciously like fundamentalists' claims of "scientism" and "science is just another religion!". If you mean something else, then do elaborate.
Firstly, skepticism is basically just a new name for a discredited philosophical movement called 'logical positivism', in the same way that intelligent design is basically just a new name for creationism.
The section on positivism here has a brief summary:
http://plover.net/~bonds/nolongeraskeptic.html
I'm not sure where the best place to go for information on this would be though to be honest. Wikipedia has a brief article also but it's not especially helpful: http://en.wikipedia.org/wiki/Logical_positivism
"Are there any examples of this from the blog?"
- "It turns out that physicians view pharma funding sources negatively"
When there is disclosure that the studies were pharma funded. Often times this isn't disclosed even though it's supposed to be. Additionally, it's been proven beyond a doubt that pharma reps, dinners, gifts, etc. influence doctor's prescribing habits, but this is never mentioned, even though the point of the blog post is supposedly to show that it's rare for doctors to be under the influence of pharma.
- "On the other hand, this study also made me wonder if perhaps we place too much confidence in research funded by the NIH. [...] NIH funding is not a guarantee of quality science by any means."
Again the research unambiguously shows that pharma-funded research is vastly for more likely to find positive results for the drug in question than NIH research.
- "For example, a recent study found a correlation with government funding of a trial and positive results, and another study found no higher likelihood of positive outcomes in industry-sponsored trials but a higher likelihood of reporting double-blinding"
Even when he mentions that pharma sponsored studies are 'associated with' increased likelihood of favorable results, he cites one or two minor studies instead of the most important meta-studies on this topic.
- "Moreover, several studies have suggested that from a methodological standpoint industry-funded studies published in peer-reviewed journals are of equivalent or higher quality than clinical trials funded by other mechanisms."
Citation needed.
- "This is not surprising, given that many clinical trials funded by pharmaceutical companies are done for the purpose of winning FDA approval for a drug, either initially or for expanded indications, and the FDA has stringent requirements for these clinical trials."
So what he's really saying is that he's comparing apples and oranges.
- "Indeed, as I mentioned, this NEJM study doesn’t tell me anything that I didn’t already know"
The classic tactic of claiming that everything negative isn't important because it's 'something we already knew'
- "I’ve come to the conclusion that most doctors, at least in this sample, probably have it about right or may even be a little more skeptical of pharma than necessary."
You've got to be freaking kidding me. Again, look at the list of the most prescribed drugs, both psychiatric and non-psychiatric. And then look at what percentage of those are actually better than placebos or generics.
> "If you mean something else, then do elaborate.
In this case I was kind of referring to how preachers will get up on stage and do the gish gallup as an attempt to discredit evolution, as well as using emotional arguments and emotional tricks rather than facts or logic.
I generally do think that a lot of science falls into the category of scientism, but that isn't what I was getting at here. I also generally think there are good reasons for considering science to be a religion, but that's also not what I was getting at.
That doesn't really shed any light. It merely asserts, without proving, that the modern skeptic movement is equivalent to logical positivism, and provides neither an argument for that, nor an argument against logical positivism. Now, I'm familiar with Popper and Quine's criticisms of logical positivism, and there are other criticisms that I'm probably not aware of, but I don't see how those criticisms relate to the modern skeptic movement.
By the way, I do agree with many of the criticisms of the modern skeptic movement from that link, but I don't think that most of it has anything to do with whether the skeptics are correct in criticizing certain treatments and advocating others.
I'm a little unclear on what point you're trying to make here. Can you clarify?
> I mean look at my pastebin post: http://pastebin.com/cniysd82
I took a look at your pastebin post. There are a lot of criticisms there of various kinds of bad practices, but not all of them have anything to do with whether the medicines actually work. For instance, the patent issue; while that's a fair issue in its own right, whether large pharmaceutical companies can prevent people from making generic equivalents by using patents does not affect whether the drug works or not. Or direct to consumer advertising; again, it may be a bad idea, but it doesn't have anything to do with whether the drugs actually work.
Many of the other criticisms here are fairly hypothetical. Yes, there are places where the system isn't ideal, where there's potential for the wrong incentives. There are places where it would be nice to do research that covered a broader spectrum. But that doesn't mean that it's all invalid. We live in an imperfect world. We should try to fight those cases when we can, try to get better results, but you shouldn't write off the entire industry merely because it's imperfect.
Here's another example. In the software industry, I see bad practices all the time. People not writing unit tests, not doing full regression tests, writing sloppy code that doesn't handle all of the error conditions, and so on. And yet, somehow, we manage to get by. Software generally works, it does what it says, it improves whatever it was setting out to improve. Sure, there are some big expensive failures you can point to. Sure, it would be nice if we did a better job at this, and should try to continue to fight for higher quality software. But just because there is some software imperfectly written doesn't mean that you should just write off the software industry.
> But does SBM actually address any of the criticism? Not a single point of it, because there is no defense; in fact, it's all coming from high-level 'insiders' in the medical community -- JAMA, NEJM, the IOM, etc.
Really? I just decided to take a look at SBM; I wasn't familiar with it before this thread, but decided to take a look at it. Here's an article on reducing prescriptions for elderly patients, because they may do more harm than good: http://www.sciencebasedmedicine.org/index.php/how-do-we-avoi... (addressing one of your concerns about differences in how medications effect the elderly). Or here's an example where they do address one of the concerns that you mention; they demonstrate that doctors actually are more skeptical of research funded by the pharmaceutical industry: http://www.sciencebasedmedicine.org/index.php/news-flash-doc....
> Instead they just spin it in order to trick people who are predisposed to have faith in modern medicine. (And I use the term faith, because if you're familiar with these issues then it's unmistakably clear that this is really what it is.)
You know, I do tend to be skeptical of pharmaceutical remedies, and so try to minimize them myself. But to say that you have to have faith to buy into modern medicine is a bit of a stretch. How do you explain ever increasing life expectancies? Clearly, there is something going right in modern medicine.
> What science-based medicine does (again, the blog, not the concept) is really no different than what the evangelical megachurches do, it's just dressed up in different language.
Citing actual scientific studies, which may be flawed in certain ways, is the same as merely preaching mythology from a 2000 year old book based on no science whatsoever? Remember, "science" is not some binary thing, where if there's one flaw, it's all false. It's a process, by which we attempt to come up with better models of the world, and try to reduce bias in the process. Sometimes there will still be some bias; you won't necessarily be able to eliminate it all. But that doesn't mean it's worthless.
There are definitely a lot of ways in which I wish that pharmaceutical research would be improved; but the fact that there are people now who are living perfectly normal lives while HIV positive with anti-retroviral therapies, when just 10 or 20 years ago they would have died of the same disease, leads me to believe that it's not all bad. I wish those drugs were cheaper, that they weren't so tied up with patents, and so on; but you know, I wish I had a pony too. To equate the research and development that went into such life-saving measures as equivalent to an evangelical megachurch is quite frankly ridiculous.
That's because in general I'm only interested in systemic problems, not specific case studies. There are entire books written about just anti-depressants, or statins, or whatever, which you can easily find on Amazon.
"How do you explain ever increasing life expectancies?"
Of the 30-year increase in life expectancy over the last 100 years, 25 years has come from better public health (e.g. sanitation), and another 1.5 years has come from preventive care like vaccination.
Source: Bunker JP, Frazier HS, Mosteller F. Improving health: measuring effects of medical care. Milbank Quarterly 1994;72:225-58.
What is the point that you are trying to prove? Are you merely trying to demonstrate that there are certain systemic problems? If so, then congrats, you've won, there are some systemic problems. I don't think there has ever been a wide-scale system involving humans that hasn't had a certain amount of cheating, lying, corruption, and the like. If someone tried to claim to me that there was an entire multi-trillion dollar industry that did not involve some amount of cheating, lying, and corruption, I would laugh in their face.
Are you trying to argue that the pharmaceutical industry has a net negative value; that it it something that causes more harm than good? Because that's going to be a lot harder to prove, and a bunch of little anecdotes does not make a good argument.
You seem to be fairly concerned with certain people, who discuss science based medicine, and say that they are corrupt because they advocate for modern pharmaceuticals and criticize certain alternative medicine. Your evidence seems to be that they do not talk about all of the corruption and problems that you would like them to talk about. Do you have anything more than that?
> Of the 30-year increase in life expectancy over the last 100 years, 25 years has come from better public health (e.g. sanitation), and another 1.5 years has come from preventive care like vaccination. > > Source: Bunker JP, Frazier HS, Mosteller F. Improving health: measuring effects of medical care. Milbank Quarterly 1994;72:225-58.
Hmm. That's an 18 year old source, talking about life expectancy, which is a trailing indicator. So, 25 years of life expectancy from better public health (like sanitation and nutrition) is an amazing thing. And you say that 1.5 years come from preventative care like vaccination, and dismiss the other 3.5 years. Now, 3.5 years may not sound like much out of about 75. But think about it for a bit. 3.5 years is averaged across the whole population. Not everyone has a condition that is treatable; many people die of old age, accidents, murder, suicide, and things that modern medicine has not yet made much progress in. Those 3.5 years don't really affect any of those folks. So lets say that 1 in 10 people have a treatable condition (I'm pulling this number out of my ass, by the way; this is just a hypothetical, and the numbers may differ, in which case you would scale the reasoning appropriately). That means that those 1 in 10 people have gained 35 years of their life from medicine. Look around at your family and closest friends. How much would you trade for 35 more years with one of them?
So, you are discounting 18 years of medical progress, as well as treating a few years of life expectancy gained as no big deal. And of course, any talk of life expectancy also ignores quality of life issues; curing something that would have been crippling but not deadly doesn't substantially affect life expectancy, but does affect quality of life.
It sounds like you are trying to argue against the value of modern medicine, which is going to be a tough thing to convince people of, given all of the demonstrable benefits it has. I can understand discussing specific criticisms, and trying to figure out how we can improve it, and that saying "all medicine is scientific progress and is great" is fallacious, but trying to prove that modern medicine has a net negative value because of a few issues of systemic corruption is not the way to do it.
I was arguing against the following statement: "But it's an exaggeration [...] to say that the enterprises that develop new drugs for prescribed medical treatment are corrupt in general beyond what Goldacre claims with specific evidence."
Or, more generally, reminding people why it is that our infrastructure is falling apart and why the federal government is at risk of collapse in the next few years, which are both in large part due to the massive amounts of fraud in the medical system. At least a third of all medical spending is waste and fraud, and that's not even counting the damages from all the needless harm it inflicts on people. Even just fixing some of the low-hanging fruit would leave us with enough money to provide healthcare to all Americans, as well as build an entire nationwide highspeed rail network every single year.
> Your evidence seems to be that they do not talk about all of the corruption and problems that you would like them to talk about.
It's mostly the intellectual dishonesty in virtually every single post that bothers me. The entire point of the blog is to 'prove' that alternative medicine is inferior to mainstream medicine because it isn't supported by science. They do this by looking at all the ways alternative medicine isn't supported by science, while completely sweeping under the rug all of the ways that mainstream medicine isn't supported by science. My concern isn't that the authors aren't mentioning specific issues, but rather that they're going out of their way to mislead their readers about the issues and the state of medicine more generally.
> That's an 18 year old source, talking about life expectancy, which is a trailing indicator.
It's the most recent data available. The fact that a lot of the data about the medical system is 20+ years old is in fact one of the biggest problems.
Also, I'm not in any way dismissing the contributions of modern medicine. As you say, modern medicine has contributed an enormous amount to society. Which makes it all the more unfortunate that many of its most vocal supporters wildly exaggerate its benefits and stick their heads in the sand when confronted with its problems. Making an intellectually honest argument in favor of modern medicine has to be one of the easiest tasks in the world, so the fact that so many of its supporters can't even do this doesn't say much for the quality of their ideas.
> Trying to prove that modern medicine has a net negative value because of a few issues of systemic corruption is not the way to do it.
I'm not trying to prove that it has net negative value. However, it's definitely not just a 'few' issues with systemic corruption.
However, I think the most important lesson in this book and other publications like it, is not in its specifics, but in its general message.
Too many people blindly trust pharmaceuticals, too many don't even consider them "drugs", because "drugs are bad" but pharmaceuticals are good. Books/Articles/etc like this are essential if people are ever going to realize that just because a doctor hands them a pill, it doesn't mean that pill is safe.
The lazy and apathetic will never shift their focus, but hopefully books like these will inspire more people to do their own research before popping an unknown,name-branded chemical into their mouths.
All it takes is a google search of "Active Ingredients of 'X'", and then five minutes of searching "Side Effects of 'X'", or "Interactions with 'X'" to prevent potentially harmful ingestion.
Another anecdote: in the 15 or so years my employer has been around, we've only seen a handful of NDAs (new drug applications) go through on the hundreds of studies to which we've supplied software.
All that said, despite receiving my paycheck from big pharma, I'm sympathetic to Goldacre's criticisms. As I mentioned, the founders of my employer (both software folks and clinical scientists) have worked to change the way trials are run in order to provide better data. Whether the sponsors properly use this data is another story.
Marketing felt that doctors would only use the product if it was simple enough, so they made it a one-size-fits-all dose.
About half the English medication budget (£4.5 billion of £9 billion) is wasted because people don't take their medication correctly. This isn't just the medication for little things either. A major cause of transplanted organ problems is people not taking the meds correctly.
Not great sources, but:
(http://www.bbc.co.uk/radio4/science/casenotes_20040817.shtml)
(http://www.bbc.co.uk/radio4/science/casenotes_20060509.shtml)
But it is a million times better than medicine circa 1263 AD
I am reminded of the Google logo "Don't be evil". I always heard that and wished that I really was living in a world where evil was defined as monopolistic business practises and bad UI, instead of rape, genocide and torture.
I respect Ben Goldacre, and I understand the need for a little hyperbole. But forcing pharma and regulators to publish all trials, and fund independant on-the-job training will not lead to order of magnitude changes. Its an evolution not a revolution.
Some day someone will find cancer's penicillin. They will probably have been badly funded, and roundly ignored by the rest of Chinese medical establishment (!) and none of the prescriptions in Ben's book will have helped.
I would liken this to the car industry - If the world has not invented the internal combustion engine that is not something changing regulation will fix. Ensuring that after it is invented, the industry is honest, accountable and constantly pressured to improve - that is fixable.
Welcome to Nader-hood Dr Goldacre.
Quite unlikely, since "cancer" is simply a term we use for a great variety of different diseases.
As a tentative example, Mina Bissell's theory on micro-environment supporting cancer growth indicates a penicillin style solution would fit her category of cancer.
Please don't take this as "all cancer researchers are fools looking in the wrong direction, I know better, join Scientologists" but my utterly uninformed gut reaction is that the different cancers all have such common and overlapping indicators (uncontrolled cell growth, basically) that there being multiple different root causes that all trigger the same feature seems, unlikely without other factors.
We may spend a long time treating the different cancers differently according to which is most effective. But saying that such commonality does not or even cannot have a common cause seems too early.
I will of course defer to anyone who knows of better (hell, any) evidence to tear down my layperson POV.
No, but it will allow people to make more informed decisions about what medicine they should take, and give a more realistic picture about its effectiveness. There is no justifiable reason to withhold trial data...
However my point was that the hyperbole was a little too much - Goldacre has a difficult tightrope to walk - to stir people up enough that he (sells books and) convinces them action is necessary, and yet does not actually go over the top and accuse a generally beneficial-to-society pharma industry of being one step above arms dealers.
I think he will pull it off and look forward to putting it on my Xmas reading list.
> Despite this book being an excellent take down of the pharmaceutical industry which everyone should read it completely fails as a flickbook. I'd expect a writer of Goldacre's calibre to be able to stick small pictures in the bottom right of the book's margin creating an animated effect of himself, astride a unicorn, vigorously stroking the horn until finally, a moment of satisfaction
I can't take serious the statement "the way medecine works is ludicrously appalling" if you consider people can now live a fine life with the AIDS virus and there are hundreds of diseases that can now be managed and cured, thanks to medicine.
http://blogs.bmj.com/bmj/2012/07/03/richard-smith-medical-jo...
With so much money at stake, all this should surprise no one. And anyone with an ounce of brains should be very cautious about drugs.
(http://classic.the-scientist.com/?articles.view/articleNo/27...)
Pharmaceutical companies used to spend vast amounts promoting their medications to English GPs. (Estimates suggest over £10,000 per GP, with 40,000 GPs in England.) And, because of our tight regulation that sum was probably less than in the rest of Europe. I'm pretty sure that has now stopped.
(http://news.ycombinator.com/item?id=3700513)
> And anyone with an ounce of brains should be very cautious about drugs.
Bob is taken to hospital. Bob is unconscious. Or Bob has a learning disability. Or Bob is going through psychiatric crisis. Or Bob speaks a different language than all the clinicians. Or Bob is under the influence of drugs / alcohol. Or Bob is not that bright.
I agree that people should be careful with medication, but it's a shame that we have to do so. I trust doctors, and I sort of trust pharma (I wish there was better regulation), but I'm still wary of meds.
(In the UK about 10,000 people die each year because clinicians make mistakes with medications. Compare that figure to Road Traffic Accidents (about 3,000))
"According to the editor of the British Medical Journal, Dr. Richard Smith, 'The major journals try to counterbalance the might of the pharmaceutical industry, but it is an unequal battle -- not least because the journals themselves profit from publishing studies funded by the industry.'
The journals benefit from the publicity gained from publishing large drug company-sponsored studies. This increases the value of their advertising and enables them to sell back to the drug companies reprints of articles, which the drug companies then distribute as marketing tools to doctors. According to Dr. Smith, this can amount to more than $1 million for a single article. At the same time that medical journals are given incentives to please the drug companies, they are also given strong disincentives to go against drug company interests. According to Dr. Marcia Angell, former editor of NEJM, editors of medical journals exercise self-censorship -- trying to avoid offending their chief advertisers, the drug companies.
Dr. Robert Fletcher learned about this firsthand. In 1992, he was editor of the Annals of Internal Medicine when it published an article reporting that 44 percent of drug ads in medical journals were written in a way that would lead doctors with no other source of information to prescribe improperly. The article also reported that 92 percent of those ads were in some violation of FDA rules. Writing in The Lancet in 2003, Dr. Fletcher said that as punishment for publishing this article, the pharmaceutical industry 'withdrew many adverts' and showed that it was 'willing to flex its considerable muscles when it felt its interests were threatened.' This is a price that medical journal editors would prefer not to pay." Source: Overdosed America, p. 113
About a year ago, I began an (overly) ambitious project to build a database of the scientific evidence behind the use of herbal supplements to treat a variety of conditions. I sank my nights and weekends into it for a couple of months but only got as far as one test section. It's sat more or less derelict ever since.
Aside from a mostly ignored Reddit submission, no-one has ever really seen it. If you have a minute, take a look and please let me know any thoughts you have about it at all.
http://herbevidence.com/data/Erectile_Dysfunction
(Forgive me, the section on ED happens to be one I wrote up as a test section because I was researching it anyway as a writing gig. Click on the name of each supplement in the first table to go to the full page for it.)
With my project, the basic taxonomy was always per-complaint (or per-illness if you prefer). It doesn't presuppose the user has ever heard of any particular supplement. The idea is the user can browse to the page that documents their condition and quickly see a summary of all the evidence for all the different tested herbal treatments.
Now, I'm not at all sure that this difference in structure justifies starting all the research etc. from scratch. It may be the case that examine.com could trivially switch over to the structure I used. But I do think that my structure is superior.
Just want to be in touch :)
One of my uncle is a nephrologist in the US. He recently came to India for a vacation and my talks with him were all about these issues. About how doctors work, their protocols, procedures and ethics etc and things like that. From what I could decipher doctors are not super humans how have miracle cures for every disease to exist on earth. What doctors are generally taught in medical school is to first learn about healthy bodies so that they can later to distinguish between a healthy and unhealthy body. Then they are taught pathology, stuff like dissecting dead humans and learning their internals. And then there are things like anatomy, metabolism, physiology etc. After all this they then go on to diseases and their cures.
In an ordinary medical school course. With all that heavy syllabus the actual disease-cure part is taught in a no more procedure than if-then-else decision tree scenarios. Its something like this, Imagine you are taught 100 different symptoms for fever. Combination of all those 100 scenarios in 'OR' and 'AND' conditions lead to various conditions of fever with various diseases. That's what we are talking about here. Imagine you having to remember all this, will it really possible? May be for an year or two but with time that sort of knowledge erodes quickly.
On top of this they are taught nothing much about the root cause of these diseases. Their cures. Are they addressing the root causes or just managing symptoms.
When they go on to their MD. Then comes little special training and details with investigation, practice and learning about a specific organ/part of the body. This is still understandable.
But in general most doctors work like a software cache. The diseases and cures they pull out are the ones cached with the recent patients they are treating.
So yes in general most doctors really work only like decision trees at the most abstract levels. Most don't have people skills, most just don't listen to patients completely. Its all working at the most abstract levels with guess work at times.
The break through stuff happening in medical science is not your physicians clinic. Its in things like vaccinations, surgical sciences, diagnosis and stuff like that.
Really you're just having a few hundred people take a pill and monitor their progress. I always wonder why that should cost more than 10 or 20K per patient even with overhead.
No one knows exactly because drug companies are allowed to count many of their marketing expenses are part of their R&D. For example, phase IV trials are mostly done as marketing as an excuse to bribe doctors with tens of thousands of dollars to put patients on the drugs in exchange for answering one or two questions about their opinions on the drug that are completely unscientific and unpublishable.
That said to get a drug through phase III trials shouldn't cost more than about $20 million. You can go to MAPS webpage and see their budget and how much they are projecting it's going to cost to get MDMA approved. The reason the pharma companies claim that it takes billions per new drug to develop is that they're basically counting marketing expenses, other failed drugs, regulatory fines, etc.
Not likely, MAPS is already as lean as you can get. And they have a big advantage since there have already been dozens or hundreds of previous studies done on MDMA to establish safety.
Yes and no. Part of the issue is the pharma companies are only interested in testing new drugs that are under patent. Whereas these are by far the riskiest drugs to develop since much less is known about them. In contrast there are hundreds of other chemicals that have the potential to cure everything from cancer to PTSD, and they would cost only a few million dollars to turn into commercial drugs, but it's never done because there would be no profit in it. So yes failed drugs make sense to count from the viewpoint of the balance sheet of a pharma company, but it's not a very good answer to the question about how much it actually costs to develop an individual drug.
I would have to seriously disagree with that statement.
I've spoken to a number of CROs that run clinical trials. They estimate that it's somewhere between $10K and $20K per patient per year to run a phase III clinical trial (the exact number depends on what kind of data you are collecting).
For example, if we look at a cardiovascular drug where you're trying to get data to support improved patient outcomes (not just reduced cholesterol, but fewer deaths), you'd need to run a trial of 20,000 patients or more, for several (think 3 to 5) years.
For example, look at the JUPITER trial http://en.wikipedia.org/wiki/JUPITER_trial
Figure out the math on that: 20,000 patients * $10K/pt/yr * 3 years. I get $600M for ONE trial.
Keep in mind that the FDA requires TWO pivotal trials to gain approval for a drug.
Of course, this is an extreme example. CV drugs and the trial described above are pretty much the largest trials you'll ever see. However, to say that getting a drug approved through phase III should cost more than $20M is clearly wrong.
CROs pay enormous sums of money to doctors to get them to enroll patients. The reason they do this is because the patent clock is ticking, so no matter what it costs it's worth it. But if you were actually testing a drug that's not under patent, then there is no reason to pay doctors to finish the study as fast as possible. Of that 10k per patient, 8k of that could easily be the fee that the doctor gets for signing up each patient.
Also, the majority of drug approval studies only have a couple hundred patients. You'd be hard pressed to find many phase III trials with over 500 patients. IIRC the Jupiter study was a phase IV study that was done for marketing reasons to promote what was already a blockbuster drug, so it's not really relevant
$8K of the $10K is not money used to grease the wheels to get studies done. Think about it: you're treating a patient for a whole year with a new drug. You're dosing the drug, taking blood samples, monitoring the patient closely, running tests to determine endpoints, collecting and processing data. You think that would only cost $2K/yr/pt?
Pharma companies may incentivize physicians to participate in clinical trials, but that $10K-$20K is the cost of running the actual trial. Doctors, physicians, technicians, data analysts don't come cheap.
And no, the majority of drug approval studies don't have only a couple hundred patients. If you're doing research for an orphan drug or an extremely rare cancer, that might be true, but those hardly make up a majority of the drug trials that happen.
A great example, Contrave an obesity drug went in front of the FDA. The FDA wanted more data (on top of the phase III studies that were already done). How many patients for the additional trial? 10,000.
In the US the vast majority of pre-clinical work is done by universities. Pharma companies usually license the patent from the universities once it is ready for clinical testing, under the Bayh-Dohl act:
I would agree that universities do a large part of the basic science behind new drugs, but they do VERY little pre-clinical work (pretty much anything beyond simple receptor/enzyme bind studies).
Pre-clinical work is done by CROs and biotech/pharma. The resources required to do pre-clinical work is enormous. Membrane barrier penetration, microsomal metabolism of drug product require a very large investment and there aren't any universities I know of that have large enough R&D programs to support it.
However, pre-clinical has many phases, of which university research institutes only participate in the earlier ones.
Basic Research -> Lead -> Screen -> Hit -> Tox/ADME -> Formulation -> Phase I
I would argue that education research institutes only participate in the first four activities. It's very rare for them to work at all in the Tox/ADME and formulation phases, which are incredibly complex and require a lot of resources and expertise they don't have.
It's a shame; I would have bought 2 copies as Christmas gifts. He's going to lose a lot of US sales to piracy.
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If you're frustrated by later publication in other countries, register your Kindle at 1 Road Street, London W1A 1AA http://amzn.to/Uhr0p4 "
This doesn't follow at all. The difficulty of fixing a system is just one possible reason it might remain as it does; regulatory capture is another, as is well-financed lobbying at the legislative level.
Pharmaceutical companies have a very clear financial interest in seeing as broad as possible use of their products, and demonstrably have the lobbying reach to forcefully advance this interest. If reform of medical trial data regulation is not a vote-winning platform (and it's hard to argue that it's uppermost in many voters' minds), then it's perfectly plausible that a broken system would persist despite the availability of easily-implemented solutions.