The Deadly Corruption of Clinical Trials
motherjones.com
motherjones.com
But MBA-style capitalism is a technology for producing short-term wins and substantial profits next quarter. If you also care about long-term wins or negative externalities, it's an insufficient technology to apply on its own.
And of course, we hackers know that. Jeff Bezos has been telling the quarterly-profits people to go fuck themselves for 15 years. And he has been right to do so. AWS, Amazon Prime, the Kindle, and now their local delivery stuff: all impossible to achieve if you're more interested in beating quarterly profit predictions than reshaping the world.
Health care is another area where it doesn't work so well. Consider, for example, these graphs: http://www.washingtonpost.com/blogs/wonkblog/wp/2013/03/26/2...
I should note that allowing pharma companies to advertise to the public is a relatively recent change. 1997, I think. And the US is one of only two countries that allow it. We could change it back.
So, either we figure out a way to make drugs cost less or we extend the timeframe for profit. Killing the advertising just means the number sold will be less and much higher for those buying it.
Read this book: http://www.amazon.com/Selling-Sickness-Pharmaceutical-Compan...
It is an advertising problem. Big pharma makes massive profits, so you can't cite profits as a source of justification for advertising drugs to people who don't need them. Maybe you should have taken 30 seconds to google GSK's profits last year, or AstraZeneca who had a bad year last year but still make 2 BILLION dollars.
It goes beyond selling drugs to people who don't need them though, they over exaggerate and create new attractive names for illnesses. "Social Anxiety", for example, is not a thing. It's actually called "Social Phobia". A research study showed that marketing "Social Anxiety" yielded a more positive result, so big pharma called it just that. I'll leave you to figure out how much big pharma made off of that little stunt.
I know a lot of people don't like drug advertizing, but you do realize that it gets a lot of people to their doctors talking about their health right? And it's not like a patient can prescribe a drug for themselves, its the doctor who ultimately decides which treatment to pursue.
Clearly you don't know very many people in the health field. If a patient comes in asking for a specific medication, most doctors will just prescribe that medication assuming the person is suffering from the illness required for the medication. Where do they get the information for making a diagnosis? Don't worry, Big Pharma will host an info session or hand out pamphlets so that doctors know what to look for...
It may be a conversation, but it's the wrong one. Big pharma is notorious for increasing the potential number of patients for an illness by putting out advertisements that widen the net for the given illness. Social Anxiety is great example here, as is ADD. 5% of children in the US are diagnosed with ADD, only 0.5% are diagnosed with ADD in france. The issue of ADD specifically goes beyond just advertisements; it speaks to the fact that drug reps have a real impact on the treatment options doctors present. In France if a child is having a tough time concentrating in school the find the root of the problem, in the US they throw meds at the kid and shove him out the door.
The marketing strategies of big pharma are nothing but pure evil. Get people on more meds, to make more money next quarter.
I was talking to an oncologist the other day and he thought the patient education/advertising was great. Patients who would put off coming to him, make an appointment because a drug company made them aware that their symptoms may be a sign of a more serious disease.
Also, he has patients coming to him saying "Hey, I just heard about this new cancer drug, is it the right one for me?" He thinks the more you can get patients involved in their own health, the better.
Are there doctors who are too lazy to push back on a patient that demands a prescription? Of course. Look at how many patients with viral diseases get antibiotics. Are you going to blame the pharma companies for that as well?
Additionally, big pharma has had a massive impact on how we identify illnesses. The DSM is a great example of this. The more diseases we can convince people they have the more drugs we can sell them. The issue is especially true for mental illness where they continue to push the definitions of illnesses so broad that everyone has a mental illness.
Read the book I recommended. Seriously, it's a great and easy read. If you are all about patient education, then you need to understand the full picture.
In a for-profit context, is the job of the doctor to maximize revenues? Or long-term patient health? In a customer service context, the customer is always right, after all.
And that's not even counting the doctors who get paid to manipulate other doctors and their prescription habits.
I am perfectly happy to blame pharma companies for the "everything should be solved with a pill" notion. After all, that's what the advertising tells both patients and doctors. One of the major goals of advertising is demand generation.
I will also blame consumers for falling for it, of course. And for having the weaknesses of character that advertising exploits. But I'm more willing to forgive the consumers, in that pharmaceutical companies are professional manipulators, while the consumers are amateur defenders against manipulation.
1) http://www.astrazeneca.com/Investors/financial-information/F... http://www.astrazeneca.com/cs/Satellite?blobcol=urldata&...
2) http://www.mercknewsroom.com/press-release/corporate-news/me...
The total amount of money spent on pharmaceutical marketing is enormous. We would be much better served if doctors could pay for subscriptions to research companies that only take money from doctors.
"We would be much better served if doctors could pay for subscriptions to research companies that only take money from doctors."
For what purpose? If your thinking a Forrester or Gartner model, then given how bad those companies advice has been in IT, I can only imagine what would happen in medicine.
See his campaign site: http://www.alltrials.net/
His blog/news site: http://www.badscience.net/
His Ted talk: http://www.ted.com/talks/ben_goldacre_what_doctors_don_t_kno...
For those who think that drug companies need high prices for recouping R&D costs, their marketing budgets are far greater than R&D budgets, so this isn't really true. In the UK they aren't allowed to market to end-users, so the advertising costs are generally much lower here.
And how exactly do you compete when your competitors can clone your product with ease?
And the NHS spends < 10% of drugs, most of which are already available as generics, so there is not a lot of scope for cost reduction.
I'm not saying that aren't improvements that can be made, but people need to wake up and realise that there are no simple answers.
Also, their costs would be much lower because we'd be paying for the clinical trials and there wouldn't be marketing costs.
Glad to have that cleared up.
It hasn't been a free market since we created the FDA (and I'm not looking to get rid of it), and with patents and advertising law, etc, it's never going to be free.
So why don't we change the accounting? Instead of making drugs companies advertise and exploit to be able to pay the regulatory costs, and R&D, etc, why not recognize that they create drugs for us and this is our hurdle - not theirs.
We want the product, so we shouldn't dump costs on the drug companies and pretend we've dealt with them.
So we should pay for the regulatory testing. 100%.
But that leaves an inventive to push expensive and unneeded or dangerous drugs through the system because they don't pay and yet get rewarded. So we need to make these our drugs - by paying for the R&D up front, so that there's no need to game our own system.
Now there's no need for secrecy so there's no need for patents to reward letting it go, and everything gets simpler again.
When you strip the patents, the marketing, and the legal games, our drugs would get a lot cheaper and more reliable.
We'd still be paying for all, maybe even more, tests, but at least we wouldn't have to trust someone whose motive clearly (and reasonably in this system) is to rush to market.
It'll certainly reduce some gaming of the current system, but I can't see how this will materially improve the situation as a whole.
Medication compliance (people taking meds correctly) is a severe problem. The UK spends about £9bn on medication, and about half of that is wasted by non-compliance.
It's not the severity of the illness; many organ transplants fail because of med non-compliance. It's not the lack of cost of the meds; figures are similar in the US.
Getting patients to take meds correctly is a problem waiting for a solution, and there's money to be made from it.
If we really cared about rewarding invention we'd pay inventors. But instead all we do is give them a letter of marque and tell them to steal it from others.
Those who can, do. Those who can't, pass a law to confiscate it.
Companies engaging in illegal, anti-competitive behaviour such as "pay to delay"[1] need to have some realistic punishment applied.
[1] (http://www.npr.org/2013/03/25/175043758/supreme-court-hears-...)
He's writing a book about an industry that everyone loves to hate. Few people question a book when it agrees with their preconceived views.
I've seen some critical reviews that are just nonsense. I don't want to spend time wading through nonsense, but I realise that maybe he's made mistakes, so I'd welcome curated suggestions.
This is a good critique of only one aspect of Goldacre's book, but it's a good one.
However, since was written by a former pharma exec, I'm sure people will dismiss it without reading it.
I read the article and the various replies from Goldacre and the author, including Goldacre's post of the passage in question. I find Goldacre far more persuasive.
LaMattina claims that Goldacre is cherry-picking data, and gives his presumably best example. But this example isn't "data"; it's Goldacre explaining the conclusions of a govenmental report about an incident where 6 experimental subjects nearly died. In writing about science for the general public, you need to give examples. This seems like a fine example for people to understand why a culture that promotes publishing everything could save lives.
His core argument is extremely simple: If you conduct any sort of medical research, you have a moral duty to publish all anonymised data associated with that research, promptly and in full. There is absolutely no reason why that should not also be a legal duty.
I'd like to see specific examples of issues that Goldacre gets wrong, as I see his work recommended by a lot of astute doctors and medical researchers, and I'd especially appreciate you making the effort, for the community here, to link to the "critical reviews of Goldacre's work" that have public-visible links that you most recommend. I'm willing to hear you out, but please give those of us reading along in this discussion more to follow up on.
The case reported in the Mother Jones article happened at my alma mater, a state university with many biomedical research studies going on at any given time. The article author later published a follow-up piece
http://www.thehastingscenter.org/Bioethicsforum/Post.aspx?id...
in another publication. Two articles by different authors in local publications last year
http://blogs.citypages.com/blotter/2012/11/dan_markingsons_s...
and just last month
http://www.minnpost.com/second-opinion/2013/03/controversy-o...
provide further updates about this particular local case.
A group blog post about medical research from 6 January 2012, "Why Do We Really Need Clinical Trials?"
http://www.sciencebasedmedicine.org/index.php/why-do-we-real...
examines some of the trade-offs involved in the still flawed, but still necessary, process of conducting clinical trials of proposed new treatments. Human beings who propose new treatments often have a bias to suppose that the new treaments are more safe and more effective than previous treatments--especially if they have a financial interest in the new treatment. People who have a financial interest in other treatments, or in not seeking effective treatment at all (e.g., faith healers) may have a bias that runs in the other direction. The way to check the safety and effectiveness of a treatment is to run an honest clinical trial with adequate justification from known science and sufficient statistical power. But keeping the trial honest involves human beings disciplining themselves not to jump to conclusions. As Richard Feynman said to graduates of Caltech: "The first principle is that you must not fool yourself--and you are the easiest person to fool."
The Emperor of All Maladies gives a candid and almost frank overview on how clinical drug trials are performed "from the inside".
Aspirin the Story of a Wonder Drug is also a nice account of "drug development" in practice.
How do they bias the results in that case?
Merck-funded researchers trivialised the problems of Vioxx. Those researchers were not evil or stupid. Subtle influences are hard to spot in yourself.
When you look at the data there's a remarkable gap between independently funded studies and company funded studies. It's very clear that studies funded by companies more often show benefits and less often show harm. (There are several published studies on this.)
And even if the blinding and randomising is effective there's no requirement to publish. Thus, a company can run ten trials and only publish the one that's positive.
Some explanation and citations here, along with many other statistical tricks:
http://www.refsmmat.com/articles/statistics.html#truth-infla...
There's also a well-known problem called "vibration of effects" where you can play with controlling different variables, using different analyses methods, and so on, resulting in an estimate of a drug's effects that oscillates by a factor of two. Look for John Ioannidis' paper "Why Most Discovered True Associations Are Inflated".
http://www.bmj.com/content/344/bmj.d7373
The results are simply buried if they're not sufficiently favorable. There have been a number of meta-analyses which dig up unpublished results (which is very difficult) and demonstrate that medications no longer have statistically significant effects when you include the unpublished data. For example:
http://www.bmj.com/content/341/bmj.c4737
(Both these papers are open access, so you can read them if you'd like.)
I think the biggest lesson to learn from this case is that there has to be a independent entity in double-blind studies which knows the relation between test subject and the substance and has the power to interrupt or terminate a study when people's lifes are at risk.
Again, another fine example of how capitalism does not take unforeseen issues into account - to refuse to drop out Dan of the study program is "manslaughter by neglicence" for me (not by malice, as the responsible actors could not have definite knowledge that Dan would kill himself).
Next up: criminals are not really responsible for crime, since "government entities" like municipal police forces supposedly "strictly enforce" criminal conduct.
I'm going to take a wild guess here and assume you've never had anything whatsoever to do with a clinical trial, because the modern FDA has almost nothing to do with the way a clinical trial is conducted.
A pharma company (the capitalists) writes the protocol the way they want, and hires a university/researcher to run the study. They file a simple two page form with the FDA to apply for an "indication" to study a treatment. The university/researcher gets the university IRB to sign off on the study protocol. Sometimes, if the IRB is any good at all, they'll tweak the protocol to try to protect the research subjects. But guess who picks the IRB members? The university/researcher making money off the capitalist pharma company. Guess how that influences an IRB.
The FDA has no input. There is no supervision in any meaningful sense by the FDA. The capitalists - researcher and sponsor - run every aspect of the study. Each decision is theirs.
The decisions spelled out in the article were made by the capitalists - the pharma company and researchers.
Barring some complete misstep like all the active arm study patients suddenly dropping dead, the FDA will eventually (read: years after the study is completed) examine the data (typically highly massaged by the capitalists) from the study to make a determination on whether to approve a medication for sale.
But pretending that the FDA (especially after years of being stripped of regulatory powers by, you guessed it, capitalists who buy and sell legislators) has much of anything to do with the way a clinical trial is conducted is complete bullshit.
How do you explain the clinical holds the FDA puts on clinical studies? The FDA does monitor clinical studies and stops the bad ones. The often stop them before a trial is over.
I'm guessing you minimal experience with how clinical trials are run. Most drug companies walk on egg shells around the FDA since they know how much power their yield.
I don't see any solution short of doing this. A study can't be considered truly blind unless the study design itself is done by researchers who do not know the "desired" outcome.
Regulatory capture has always been a bug of advanced, sufficiently honest societies. This is important because it tells us that well-intentioned rule of law is insufficient for running a democracy if you're not paying attention. I don't think anyone at the FDA wakes up and says, "I think I'll spend today getting in the way of good medical care and helping big pharma make money."
To quote the last sentence of the article: "Many academic physicians are required by their universities to generate a substantial portion of their salaries by obtaining research grants."
Healthcare, basic transportation, energy and water distribution as well as basic telecommunication infrastructure must be in the hands of the state. The free market has massively failed in each of these areas, everywhere in the world. Just look at the US electricity grid, the Berlin water privatization disaster (less service, more expensive), the US (and partially, German too) broadband Internet service, the Berlin S-Bahn problems, the (recently HN frontpaged) problems in the US healthcare system...
Why can't we learn from the countless mistakes made all over the world?!