Dureros, dar sănătos - cam ăsta a fost efectul cărții. Ben Goldacre (care e un tip foarte tare - are o rubrică în The Guardian care merită urmărită oricând - plus e medic) prezintă mecanismele prin care medicamentele ajung să fie prescrise ... mecanisme care contrar a ceea ce te-ai putea aștepta nu sunt proiectate pentru selectarea celui mai bun tratament ci pentru maximizarea profitului companiilor de medicamente, a mediilor academice (laboratoare & publicații), a medicilor și pentru liniștea (nu sănătatea) pacienților. Astfel ni se prezintă unul după altul: cum se fac "trials"-urile medicale, cum se selectează publicațiile medicale, cum sunt aprobate medicamentele, etc. Focusul cărții este pe sistemele din US și UK dar și pe cel din EU (care aparent este cel mai opac și cel mai aliniat cu interesele Pharma în contra intereselor cetățenilor EU). Este o lectură interesantă pentru că modul în care "big pharma" conlucrează cu structurile de reglementare/academice poate fi generalizat foarte "natural" la cum "big business" conlucrează cu structurile statelor în defavoarea "omului mic"/ al cetățeanului. Ușor de citit, cu multe exemple reale ce pot fi verificate - recomandat. page 3 | location 36-48 | Added on Sunday, 1 June 2014 21:48:41Drugs are tested by the people who manufacture them, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques which are flawed by design, in such a way that they exaggerate the benefits of treatments. Unsurprisingly, these trials tend to produce results that favour the manufacturer. When trials throw up results that companies don’t like, they are perfectly entitled to hide them from doctors and patients, so we only ever see a distorted picture of any drug’s true effects. Regulators see most of the trial data, but only from early on in a drug’s life, and even then they don’t give this data to doctors or patients, or even to other parts of government. This distorted evidence is then communicated and applied in a distorted fashion. In their forty years of practice after leaving medical school, doctors hear about what works through ad hoc oral traditions, from sales reps, colleagues or journals. But those colleagues can be in the pay of drug companies – often undisclosed – and the journals are too. And so are the patient groups. And finally, academic papers, which everyone thinks of as objective, are often covertly planned and written by people who work directly for the companies, without disclosure. Sometimes whole academic journals are even owned outright by one drug company. Aside from all this, for several of the most important and enduring problems in medicine, we have no idea what the best treatment is, because it’s not in anyone’s financial interest to conduct any trials at all. These are ongoing problems, and although people have claimed to fix many of them, for the most part they have failed; so all these problems persist, but worse than ever, because now people can pretend that everything is fine after all.page 35 | location 532-535 | Added on Monday, 2 June 2014 21:52:18Finally, and perhaps most shamefully, when we allow unflattering data to go unpublished, we betray the patients who participated in these studies: the people who have given their bodies, and sometimes their lives, in the implicit belief that they are doing something to create new knowledge, that will benefit others in the same position as them in the future. In fact, their belief is not implicit: often it’s exactly what we tell them, as researchers, and it is a lie, because the data might be withheld, and we know it.page 87 | location 1332-1333 | Added on Tuesday, 3 June 2014 23:06:06even during peak flu season only about one in three people with ‘flu’ will actually be infected with the influenza virus, and most of the year only one in eight will really have it. (The rest are sick from something else, maybe just a common cold virus.)page 108 | location 1647-1648 | Added on Thursday, 5 June 2014 23:09:31Of all the drugs that make it as far as these phase 1 trials, only 20 per cent go on to be approved and marketed.page 112 | location 1716-1723 | Added on Thursday, 5 June 2014 23:17:59Now you want to give it to patients who have the disease you’re aiming to treat, so you can try to understand whether it works or not. This is done in ‘phase 2’ and ‘phase 3’ clinical trials, before a drug comes to market. The line between phase 2 and 3 is flexible, but broadly speaking, in phase 2 you give your drug to a couple of hundred patients, and try to gather information on short-term outcomes, side effects and dosage. This will be the first time you get to see if your blood-pressure drug does actually lower blood pressure in people who have high blood pressure, and it might also be the first time you learn about very common side effects. In phase 3 studies you give your drug to a larger group of patients, usually somewhere between three hundred and 2,000, again learning about outcomes, side effects and dosage. Crucially, all phase 3 trials will be randomised controlled trials, comparing your new treatment against something else.page 114 | location 1745-1749 | Added on Thursday, 5 June 2014 23:25:23Clinical research organisations are a very new phenomenon. Thirty years ago, hardly any existed: now there are hundreds, with a global revenue of $20 billion in 2010, representing about a third of all pharma R&D spending.9 They conduct the majority of clinical trials research on behalf of industry, and in 2008 CROs ran more than 9,000 trials, with over two million participants, in 115 countries around the world.page 132 | location 2021-2025 | Added on Sunday, 8 June 2014 22:07:50ethical. It’s obviously wrong to put patients in a trial where half of them will be given a placebo, if there is a currently available option which is known to be effective, because you are actively depriving half of your patients of treatment for their disease. Remember, these are not healthy volunteers, giving their bodies over for financial reward: these are real patients, often with serious medical problems, hoping for treatment and exposing themselves to some inconvenience (but hopefully no more than that) in order to advance the state of medical knowledge for other sufferers in the future.page 135 | location 2067-2073 | Added on Sunday, 8 June 2014 22:13:54Probably the most dramatic and famous comes from the Cardiac Arrhythmia Suppression Trial (CAST), which tested three anti-arrhythmic drugs to see if they prevented sudden death in patients who were at higher risk because they had a certain kind of abnormal heart rhythm.20 The drugs prevented these abnormal rhythms, so everyone thought they must be great: they were approved onto the market to prevent sudden death in patients with abnormal rhythms, and doctors felt pretty good about prescribing them. When a proper trial measuring death was conducted, everyone felt a bit embarrassed: the drugs increased the risk of death to such a huge extent that the trial had to be stopped early. We had been cheerfully handing out tablets that killed people (it’s been estimated that well over a hundred thousand people died as a result). Even whenpage 151 | location 2313-2317 | Added on Tuesday, 17 June 2014 22:09:58But however rich you are, if you become sick you can’t innovate new medicines overnight, because that takes time, and more money than even you have. And you can’t know the true effects of the medicines we have today, because nobody does, if they’ve not been properly tested, and if some results go missing in action. The most expensive doctors in the world don’t know any better than anyone else, since any trained person can critically read the best systematic reviews on a given drug, what it will do to your life expectancy, and there is no hack, no workaround, for this broken system.page 161 | location 2457-2462 | Added on Wednesday, 18 June 2014 22:12:57A regulator and a doctor are trying to make two completely different decisions about a drug, even though they are using (or in doctors’ case would like to use) the same information. A regulator is deciding whether it’s in the interests of society overall that a particular drug should ever be available for use in its country, even if only in some very obscure circumstance, such as when all other drugs have failed. Doctors, meanwhile, are making a decision about whether they should use this drug right now, for the patient in front of them. Both are using the safety and efficacy data to which they have access, but they both need access to it in full, in order to make their very different decisions.page 170 | location 2594-2595 | Added on Wednesday, 18 June 2014 22:28:43independent academics are bit players in this domain. Ninety per cent of published clinical trials are sponsored by the pharmaceutical industry. They dominate this field, they set the tone, and they create the norms.page 203 | location 3108-3112 | Added on Thursday, 19 June 2014 22:38:11Lastly, the ISIS-2 trial compared the benefits of giving aspirin or placebo for patients who’d just had a suspected heart attack. Aspirin was found to improve outcomes, but the researchers decided to do a subgroup analysis, just for fun. This revealed that while aspirin is very effective overall, it doesn’t work in patients born under the star signs of Libra and Gemini. Those two signs aren’t even adjacent to each other. Once again: if you chop up your data in lots of different ways, you can pull out lumpy subgroups with weird findings at will.page 206 | location 3152-3154 | Added on Friday, 20 June 2014 13:41:37 Sometimes, trials aren’t really trials: they’re viral marketing projects, designed to get as many doctors prescribing the new drug as possible, with tiny numbers of participants from large numbers of clinics.page 228 | location 3489-3493 | Added on Friday, 20 June 2014 14:20:00But more than that, I worry that these regulations express an implicit fantasy about normal clinical practice, which has never been adequately challenged: that of spurious over-certainty. Perhaps if all doctors were forced to admit to the uncertainties in our day-to-day management of patients, it might make us a little more humble, and more inclined to improve the evidence base on which we base our decisions. Perhaps if we honestly told patients, ‘I don’t know which of these two treatments is best,’ whenever that was the case, patients would start to ask questions themselves. ‘Why not?’ might be the first, and ‘Why don’t you try to find out?’ might follow shortly afterwards.page 233 | location 3567-3573 | Added on Friday, 20 June 2014 14:31:06Often, if you ask a doctor whether they know if one particular treatment is best for a particular medical condition, they’ll tell you they certainly do, and name it. But if you ask them how they know it is the best, their answer might scare you. They might say: that’s what I learnt at medical school; that’s what the person in the office next door told me she uses; that’s what I see the local consultant prescribing in his letters on patients I’ve referred; that’s what the local drug rep told me; that’s what I picked up on a teaching day two years ago; that’s what I think I read in a review article somewhere; that’s what I remember from some guidelines I looked up once; that’s what the local prescribing guidelines recommend; that’s what a trial I read said; that’s what I’ve always used; and so on.page 237 | location 3626-3630 | Added on Friday, 20 June 2014 14:38:29Because when you pull away from the industry’s carefully fostered belief that this marketing activity is all completely normal, and stop thinking of drugs as being a consumer product like clothes or cosmetics, you suddenly realise that medicines marketing only exists for one reason. In medicine, brand identities are irrelevant, and there’s a factual, objective answer to whether one drug is the most likely to improve a patient’s pain, suffering and longevity. Marketing, therefore, exists for no reason other than to pervert evidence-based decision-making in medicine.page 237 | location 3630-3637 | Added on Friday, 20 June 2014 14:39:40This is a very powerful machine: tens of billions of pounds are spent each year, $60 billion in the US alone, on medicines marketing.3 And, most impressively, this money isn’t plucked from the air: it is paid for by patients, funded entirely from the public purse, or patients’ payments into medical insurance companies. About a quarter of the money taken by pharmaceutical companies for the drugs they sell is turned around into promotional activity which has, as we will see, a provable impact on doctors’ prescribing. So we pay for products, with a huge uplift in price to cover their marketing budget, and that money is then spent on distorting evidence-based practice, which in turn makes our decisions unnecessarily expensive, and less effective. All of this comes on top of a system for evidence-based medicine that is already gravely wounded, with poor-quality trials that are poorly communicated to doctors at the best of times. It’s magnificent.page 240 | location 3674-3677 | Added on Friday, 20 June 2014 14:50:25I’ve always been surprised by people who say that it’s doctors who force pills on patients. Doctors are generally nice people, and eager to please. They will get bounced into giving people what they want, and a lot of patients have been persuaded, through whatever social processes are at play in their world, that pills fix things. I’ll rephrase that for something that’s coming later in this chapter: a lot of people have been convinced that they’re patients.page 255 | location 3906-3911 | Added on Sunday, 22 June 2014 11:56:41resource. If we believe that the pharmaceutical industry produces these resources for the better education of doctors, without seeking to influence their practice, as they claim, then surely we would expect it still to be online (since the costs of keeping a website up, once it’s been built at great expense, are almost negligible). Instead, it seems that as soon as there’s no money to be made, these educational resources have simply disappeared. That tells a story that will recur in the rest of this chapter: information that sells drugs is given a platform; information that does not is on its own.page 265 | location 4057-4066 | Added on Sunday, 22 June 2014 15:17:47Doctors repeatedly assert, in both qualitative and quantitative research – not to mention when you chat with them socially – that drug reps have no impact on their prescribing (many claim that they improve it).55 Cheeringly, they also report that their own behaviour won’t be changed by interactions with drug reps, but that other doctors’ behaviour probably will be.56 And the more drug reps you meet, the more likely you are to think they’re not having an effect on you at all.57 This is naïve arrogance. From the most current systematic review, there have been twenty-nine studies looking at the impact of drug rep visits.58 Seventeen of those twenty-nine studies found that doctors who see drug reps are more likely to prescribe the promoted drug (six had mixed results, the rest show no difference, and none show a drop in prescribing). Doctors who see drug reps also tend to have higher prescribing costs, and are less likely to follow best-practice prescribing guidelines.page 301 | location 4601-4603 | Added on Sunday, 22 June 2014 21:31:59The Department of Health spends a few million pounds a year providing independent medicines information to doctors. The industry spends tens of billions on providing biased information. This presents a bizarre situation: doctors’ continuing education is paid for, almost exclusively, by the industry whose products they buy with public money, and by the industry that haspage 309 | location 4726-4728 | Added on Sunday, 22 June 2014 21:45:15So there you have it. Doctors around the world – except in Norway – are taught which drugs are best by the drug companies themselves. The content is biased, and that’s why companies pay for it. For decades people have stood up, shown that the content is biased, written reports against it, demonstrated that weak guidelines fail to police it; and still it continues.page 317 | location 4854-4855 | Added on Sunday, 22 June 2014 21:59:31But we have other fish to fry. Do people take a declared conflict of interest into account when they read someone’s claims? The evidence suggests that they do. In a trial from 2002, three hundred readers werepage 328 | location 5025-5030 | Added on Sunday, 22 June 2014 22:16:45Missing data is different, because it poisons the well for everybody. If proper trials are never done, if trials with negative results are withheld, then we simply cannot know the true effects of the treatments that we use. Nobody can work around this, and there is no expert doctor with special access to a secret stash of evidence. With missing data, we are all in it together, and we are all misled. I will say this only once more, but I think it bears repeating: evidence in medicine is not an abstract academic preoccupation. Evidence is used to make real-world decisions, and when we are fed bad data, we make the wrong decision, inflicting unnecessary pain and suffering, and death, on people just like us.page 342 | location 5233-5237 | Added on Sunday, 22 June 2014 22:44:55It’s hard to imagine a betrayal more elaborate, or more complete, across so many institutions and professions. This is a story of pay-offs, of course, but more than that, it’s a story of complacency, laziness, banal self-interest and people feeling impotent. You have been failed by the people at the very top of my profession, for decades now, on matters of life and death, and as with the banks, we’re suddenly discovering a terrifying reality. Nobody took responsibility, nobody was in control, but everybody knew something was wrong.
What do You think about The Drug Pushers (2012)?
Informative and important read, I just did not find it very enjoyable.
—airy
A very revealing book, and depressing as well.
—amberine
