on 2 October 2012
This is an impressive book on a serious subject which at times really is a matter of life and death. It can be read by anyone interested in the pharmaceutical industry, and doesn't require any previous knowledge of medicine or even science in general.
The tone is chatty enough to keep you interested, while remaining relatively well structured. I think you will get an idea of whether you would enjoy this book by first watching either of Ben Goldacre's TED talks: if you finish watching them and think "I want to know more" then this book is going to be just the thing for you.
There is no hint of conspiracy theory in this book. Goldacre sticks to a sober recounting of the problems, and he is meticulous about backing up what he says with references, with particular emphasis on systematic reviews, which is important given the subject matter of the book. He never gets into politics, but concentrates on actual, proven real-world harms and benefits.
I also appreciate that despite the massive size of the problems he's describing, he manages to avoid despair and gives recommendations appropriate for the different sections of his readership. I thought the section on conflicts of interest was subtly thought-out and proves that Goldacre is not simply "anti-pharma" and has considered carefully how things could actually be changed in practice.
It's by no means an uplifting and easy read, but it is a fantastic book and fully worth the effort. And who knows, even if you're not a healthcare professional, you may be able to contribute to solving these problems by raising awareness.
on 6 November 2012
I approached this book with an expectation that it would have a similar feel to Goldacre's book Bad Science, an informative wry view of how bad science and particularly erroneous statistics are used to misinform the public on science and health issues in the media and particularly the popular press. How wrong I was.
This is a tour de force attack on the dishonesty and manipulative behaviour of the drugs industry. It is a serious, dense investigation into all aspects of the ways this industry interacts with the NHS on many levels. It is an indictment of its relationships with health professionals, particularly GPs, academics, professional publications and academic institutions as well as the international medicine regulation agencies.
No punches are pulled and if Ben is not sued by almost every drug company in the next few months one can only conclude that everything in this book is true. That being the case then he is shining a light on a truly terrifying situation.
Every MP with an interest in health issues, every aspiring medic and all GPs should treat this book as compulsory, required reading. As far as patients are concerned it will almost certainly make you think differently when you accept a prescription at your next surgery visit. Its a must for all health campaigners.
It might not be as humorous as Bad Science but it really is a page turner.
A new drug is developed. You want to find out if it works. How can you tell? The answer is that you count. You take two groups of people with the illness, which you hope your drug will treat. You give one of them the drug and the other with a sugar pill. You count and compare the results. Who gets better and who stays ill in each group? Then you know - as much as one can know for sure - whether the treatment in question actually works.
Well, you do have a good idea if you have done the test fairly. Remember: you must count. If you want to rig the result, then you do not count properly. In science, you must keep a record of the misses as well as the hits. If you want to cheat, then don't count the misses. Only count the hits. Count those who seem to get well after being given your new drug but don't count those who don't. Worse, you don't count bad hits - side effects, for instance, which suggest that your new drug harms rather than cures. Hide unflattering data and only publish the data that make your drug look good.
But that's not all. You can compare your new drug against a placebo as opposed to a decent version of the same drug. You can stop the trial early if you get a run of good results before any bad results spoil things. You can measure surrogate outcomes - i.e. changes in blood pressure - rather than whether people live longer if they get your drug or not. You can pay ghost writers to write up the biased results from your trials and then get academics and medics to rubber-stamp them. You can get your marketing reps to assiduously cultivate doctors who are prepared to promote your particular drug. Those doctors may have already formed a positive view of your particular company's drug independently of your blandishments, but you will make sure they get heard, and the sceptical ones aren't. These are just some of the tricks the book describes. It's not about peddling untruths but half-truths. But the practical effect of this is to debase the evidence upon which doctors must base their decisions.
This book's message is not that the drugs don't work. They do work - sometimes. Or they don't work - sometimes. Or they sometimes work or sometimes don't work, depending on all sorts of factors. But we need evidence to know if they do or if they don't work, or if they only work some of the time. Outright fraud is not the problem (mostly). It's methodological dishonesty, which makes it impossible to tell in all too many cases whether the drug a doctor prescribes has good evidence to tell you whether it is likely to cure or to kill. It does not follow from this dismal state of affairs that quack remedies have been vindicated. They haven't. But the tricks of bad pharma practices are a lot more sophisticated, and harder to detect. Above all else, the scientific method, properly applied can tell us (as far as we can know) whether a given remedy is efficacious or not. It is not the method which is at fault, but its distorted application.
If you believe otherwise, then you are mistaken. A book like this presupposes that there is a difference between truth and falsehood, and that the difference can be detected, with tried and tested means to do so. The trials do speak the truth - if they are not muzzled. To get at the truth, you need a complete picture, not a partial one. If you find a body with a knife in its back, you want to find the killer. Corrupt police may decide to frame an innocent man - but does not mean that there is no way of telling who the culprit was, or there is no such thing as the proper use of evidence in criminal justice. If there is no such thing as objective truth, there is no such thing as a lie. The same with medicine. Dodgy use of the method does not mean the method itself is to blame.
One way we can get at the truth is better collection of data. Data are the bread and butter of science, The excellent Cochrane Library does jut that - collects all the hits and misses. The Library is an entirely voluntary collaboration of doctors, which seeks to gather all the data on particular remedies (not just drugs), and score them on how harmful or helpful they are. It scrutinises all would-be remedies, both mainstream and complementary, to the same cold, objective eye. It is worth looking up (enter Cochrane Library in your search engine). This is how the scientific method is supposed to work. It is a beacon of intellectual rigour and honesty. Goldacre rightly sings its praises.
Goldacre's book is restrained and forensic in its tone. There is no bilious hyperbole, just careful analysis. If you want to read a call for the entire system to torn down, rather than fixed, then this isn't the book for you. If you decide that all mainstream medicine is a fraud and start taking quack remedies, then this also is not the book for you. You'd also be making a decision poorly supported by evidence. But the system is broke. And it's broke because the thing that should be its lifeblood - evidence - has been chocked off in too many places because of dodgy methodology.
He offers plenty of practical suggestions for reform, things we can all do and gives examples of initiatives that have worked (the US is well ahead of the UK in this respect). But this is going to take years to fix. First the fur deserves to fly. Hopefully this book will ruffle a lot of feathers, not just those in the pharma industry, but among pusillanimous regulators and complacent senior medics who really ought to know better.
It will be interesting to see what sort of discussion this book provokes in the next few months. Are the offended parties going to engage with Goldacre in print, or are they going to try and silence him in a libel courts? I'm going to put aside a few quid for his defence fund.
Disclosure: I do patient reported outcomes research for top 20 pharma companies
I love science, and I love medicine. Truly, some of the most incredible inventions of our species have been the successful development of amazing compounds from antibiotics and antiretrovirals to insulin and levodopa to modern biologic drugs which help us to lead better lives despite illness. And yet, somewhere along the way, the industry that has arguably done the most to improve life for human beings (in the developed world at least) has taken a curious deviation away from science, and lost its way. As it turns out, marketing is more effective than science in persuading doctors to write prescriptions, and it's cheaper too. Full scale clinical trials are expensive, career-making (or ending), difficult, and time-consuming, and often fail to deliver anything like the transformational benefits that older (now cheap and generic) pills once did.
In this thoroughly researched, engaging, and intensely catalytic account, psychiatrist and truth-seeker Dr Ben Goldacre systematically diagnoses the faults not just with pharma, but with the entire system of evidence based medicine, in which none of us are blameless.
The broad brush strokes are that:
* Pharma builds clinical trials with what can kindly be described as "gamesmanship", systematically biases the literature by with-holding data, drags its feet to comply with transparency measures, ensures its message is heard clearer and louder than anyone else's, and on occasion gets caught doing things it knows it shouldn't.
* Some doctors, whether through cognitive dissonance, ambition or just plain commercialism, use their own reputation to persuade their colleagues that pharma's drugs are more effective than they really are, allow themselves to be unwittingly beguiled by personable drug reps, and take advantage of free education that is systematically biased rather than pay out of their own pocket to keep up to date
* Regulators are buffeted by their own agendas and are relatively toothless in pursuing bad actors in the system or holding people to account for abusing trust
* Journal editors and peer reviewers let things through that they shouldn't - although as with many of these actors the traditions and systems within which they operate make it hard for them to do their job properly
* Patient charities repeat the lobbying policies of their pharma patrons such as protesting against generics or biosimilars or collaborating with commercial PR firms to lobby for access to expensive drugs
* Just about everyone left over outside that group is in rather an all-too-chummy relationship with the biggest pharma companies and are not well motivated to rock the boat or support whistle blowers.
So far, so doomed, right?
Not so. Each chapter (again, presented with specific case studies, footnotes, and more detail on the badscience.net website) ends with clear instructions on how each of these groups (as well as you, the reader) can do something about this. That's what transforms this from an articulate diatribe to a true call to arms, and for me the clearest set of people who can influence this are the patients.
Never will you find another group of people who are so clearly "aligned" to ensure that the entire product of the pharmaceutical industry is better outcomes, instead of higher sales volume. With the right support, patients can spot the holes in trial protocols, they can lobby their patient organisations, they can ask their doctors awkward questions, and whether they know it yet or not they're also the ones with the biggest lever here. Pharma needs patients to volunteer for trials, to be adherent to their medications, and to be engaged enough in their condition to want to be talking to their doctor about the right treatment for them. With a book like this as their guide, no empowered patient can have any doubt about where to make a start.
And everyone else? We should read this book to know how to support them, prepare institutions to mediate the new dialogue, and prepare for the rehabilitation of "bad pharma" to help the companies that really mean to do so to reassert their moral authority and honor the social contract they've been given. There really is no other path to take.
This is a magnificent and brave book. It demands full support, and I am bold enough to express this. It brings together knowledge which many of us in medicine have known for some time, but it makes clear that the problem is worse than we have realised.
This book strikes a fundamental blow to medical epistemology. We used to joke that "Half of what you learn in medical school will be of no use to you in practice- the problem is just that we don't yet know which half; After reading this book you realise the problem is deeper- too much medical knowledge is suppressed from the start- and so as doctors we do not even know what we don't know. It just never crosses our consciousness. We don't even know the half of it.
The flaws in medical knowledge Goldacre describes run wide and deep.
Too much medicine is simply never published or recorded.
Negative results "This does not work" are just as important to medical practice as "this does work." Yet routinely negative studies are ignored, filed away, unpublished, maybe never even written up. There is no journal of failed treatments and other false starts. Authors and researchers don't get promoted for showing such results. Share prices don't rise on such news.
Too much pre-selection and pre-editing goes on so that what reaches large journals and is then available to be incorporated into guidelines is rather over-optimistic, and based on a biased sample. (Most of the times a drug hasn't worked in a clinical trial the information simply vanishes into "internal company files") Goldacre points out how unethical this is- patients have been taking part in clinical trials to advance medical knowledge- and then the trial goes unpublished so no one can learn from it. Worse still some patients are at risk of harm as a result of this omission.
The way information is presented to and by journals is biased. Large positive results are welcomed by drugs companies and journals alike- good for sales of both of them. Good for authors too. (Kudos/promotions) Some doctors put their names to articles they have barely even reviewed.
Many trials are stopped too soon- so long term treatments are assessed over unrealistically short time scales. Many trials stop too soon so that later complications are missed out of the analysis.
Many trials are set up against false or misleading comparators, rather than against best current treatments.
Many journals are not robust in their peer review processes, and the possibility of obviously misleading flawed papers reaching publication (and so the credibility that goes with that) is huge. Peer review is touted as a gold standard of academic accuracy yet in reality it shows that fools seldom differ, and that great minds think alike. The misuse of reviewing by some competitive scientists to advance their own views, and to do down competition, rather than quality assure scientific results, is a blot on science's copy book. (I do peer review for some journals and sign my name to reviews- and try to be fair about a paper's merits)
National Regulators are not given the full information about candidate drugs, and have no means to compel its production. So they make their assessments of a drug's merit on partial and positively skewed information. Bodies like NICE then have incomplete information on which to base their recommendations. All the way through the deletion and distortion of the published record of medicine is weakening our ability as doctors to make good treatment recommendations to our patients. We do not know either the positive results or the negative results properly, and so no one can get a proper overall view of which drug is good for which patients. The potential for harm by ignorance is huge here- whether by missed benefits or unrecognised side effects.
All this means that the medical information data base is skewed, distorted and misleading. As a doctor I try to practice evidence based medicine, and act in accordance with current assessments of best practice. What this book confirms is that my efforts are undermined before I start- all the information I need is not available at any stage of the process. I could be superbly read and up to date- and yet because of the flaws in the medical evidence base simply be moving deeper into misleading myself, and consequently my patients.
This is not a comfortable realisation. The medical information base, that can then be consolidated into reviews, guidelines, the BNF, and text books is utterly flawed. The prevalence of deletions (missing information) and distortions (spin, misleading presentations of data) mean that my personal and our collective knowledge is inaccurate right from the start.
And that's before my own prejudices and misunderstandings can even get going. Some years ago a post graduate tutor asked me to lead an EBM workshop and describe the process whereby we as doctors come to understand the evidence and then digest it and present it fairly to patients. I said I very much doubted that doctors do understand evidence very well themselves- we are easily misled by presentation effects- just as everyone else is. Ultimately the analysis of medical evidence is largely by means of detailed statistics, and few doctors understand these well. A patient of mine who was a statistician told me that his first question to a client was , "what do you want these statistics to show?" He could then work to their wish. Numbers do not speak for themselves, but can be made to sing sweetly if played right.
This book shows that the current systems of discovering new medical knowledge, and of using existing knowledge well, are severely flawed. This is not a good state for my profession to find itself in. We have grand edifices of knowledge, and this book shows that many of them are built on sand. For a profession that prides itself on being based on accurate, well defined and described knowledge this is a very poor performance.
Goldacre's book is important and raises significant questions about what we are doing as doctors, and about how we get the information we need to practice medicine well. This book shows that there are currently very widespread deep problems at every stage in the generation and distribution of medical knowledge.
His book is well written, well exampled and accurate. It should compel action by many people in medicine, the pharmaceutical industry and by those around medicine who regulate knowledge generation.
This is an important book, and it is vital for doctors to read it, no matter how uncomfortable its implications are for us.
on 27 September 2012
This is an important book, which tackles a problem that affects all of us - the development and use of effective and safe medicines. It's well researched and passionately and engagingly written. He presents a number of tricky topics clearly (I think) without losing their essence.
The case he makes for publishing the data from all trials is made in vigorously sugar rush kind of a way. But the calm measured ways have been tried (as he reports) and Ben's entertaining blunderbuss of criticism to whip up public/political pressure seems like a good plan B to me.
The section I have to comment on is the area of clinical trials. I've worked with a lot trial designers and a number of trials. You could get the impression from the book that Pharmaceutical companies have many tricks they can pull to pretty well guarantee success. They don't, most drug development project fail and they fail because their trials fail, there's roughly a 80% failure rate after a successful 'first in humans safety study', but that's across all compounds and therapeutic areas. The more novel the compound and the harder the disease is to treat, the lower success rate.
On the aspects of trials that Ben criticises many are valid criticisms, but for trials that drug companies have to run to prove that a compound is an effective drug, many of the practices are ruled out by the regulators, in particular post-hoc sub group analysis, bundling outcomes and using uninformative outcomes. I'd also like to say that in my direct experience with the pharmaceutical industry, the clinical trials were designed to elicit the truth about the compound, not make it look good, by people that are smart, honest and diligent.
As a client emailed to us today, when we commiserated with a failed trial: "Thank you ... we believe that the results were credible and while we all wanted a positive study, our job is to uncover the truth."
Ben's problem with conducting trials on 'ideal' patients, this does not make it more likely for the drug to be successful, they allow it to be shown to be successful with fewer patients. The trials aren't conducted in subjects more likely to recover and make the drug look good - the patients in the control group will be recruited from the same population and recover too making it hard to show the drug is effective. The ideal patients are those most sensitive to treatment - the `in the goldilocks zone' of neither having so mild a condition that they have a high chance or a good outcome, or so severe a condition that even a good drug is unlikely to improve matters. Being able to study the drug and prove or disprove its effectiveness in fewer patients is also an ethical thing to want to do.
Ben's problem is that the medical profession needs to understand the drug in a broader population. The drug developer's problem is that drug development already costs hundreds of millions of dollars and consumed 10+ years of the drug's (nominally 20 years) patent life. Pharmaceutical companies may have been rich in the past but all are now merging, laying off staff and closing sites. So broader medical knowledge needs to come from the things Ben proposes - big simple studies using healthcare data gathered in the community and thorough and well researched meta-analyses.
Ben complains at the use of 'surrogate outcomes'. He gives the example of statins and control of cholesterol level. He gives that example because the only two 'surrogate outcomes accepted by regulators are cholesterol level and blood pressure. Perhaps giving up smoking and weight loss are also surrogate markers? Pretty much any other disease where you want to try to prove you have a drug that treats it, you have to show 'clinically meaningful' outcomes. The regulators are comfortable with cholesterol and blood pressure because of the unanimity of medical opinion that these were causes of heart problems. And studying the reduction of heart problems directly in trials requires studying thousands of patients for years.
A suggestion he makes is that trials for Diabetes treatments should be based on reducing deaths from diabetes, but diabetes sufferers also suffer from consequential liver disease, kidney disease, neuropathic pain, loss of fingers and toes and sight loss. Now I assume these are all consequences of the diabetics lack of control over their blood sugar levels, if that's correct and I was a diabetic I'd be happy with a drug proven to control sugar levels and would not want to wait until it was proven to reduce mortality. [Ben elsewhere criticises the UKPDS -trial - a big, long running study in Diabetes that is generally taken to show that stringent control of blood glucose levels and/or blood pressure reduce type 2 diabetes complications. The study is cited by many Diabetes groups. Ben's criticism is of a compound endpoint but I'm not clear if the criticism applies to the original outcome (1998) or the 10 year follow-up (2008) I could find the latter easily and they looked pretty convincing. Learning point: if Ben cites something its worth following it up.]
The biggest point I want to dispute is this business of stopping trials early. Looking at the data to in order to adapt the trial, in particular stop it is a very sane, reasonable and ethical thing to do and results in better science. Various statistical approaches to allow this to be done so that it doesn't also amount to cheating have been worked on in academia and industry for the past 25 years or so. The key aspect of all the approaches is that the rules by which decisions are to be taken are pre-specified and the consequences well understood.
Ben tells some tales of the worst behaviour by Pharmaceutical companies apart, highlighting the need for regulation and huge punishments in an industry where the rewards can be so great. But I think that is known.
More importantly Ben highlights some real and pressing problems that require pretty big changes to bring about. First pharmaceutical companies operate in a highly regulated environment, where those regulations don't always work in our best interest. Companies need to get the data on their drug necessary for licensing; this is already a big and onerous task (and much bigger and more onerous than it was 10 years ago). This data is not a good match for physician's needs - this mismatch Ben documents vividly. The best solution is to better manage drugs and their information after they've been approved, with the access to the full data, meta-analyses and big studies using public healthcare records. To move the requirement to pre-approval without also changing the patent laws will effectively make drug development unaffordable.
Secondly - and this is an area where I've no direct experience, the management and analysis of post registration trials needs management - these seem to be essential to broaden the evidence base to patient groups not studied for registration, to amass evidence for rare but serious safety issues, to study other outcome measures (such as quality of life, and long term mortality), to identify sub-population effects. From Ben's tales of clinical trial malfeasance or incompetence it would seem these aren't to the same standard as drug development trials.
Lastly this data needs collating and analysing by cool heads, in particular neither swayed by patient advocacy groups funded by the drug companies nor needing a juicy finding in order to justify publication.
on 27 September 2012
A long train ride yesterday, and the wonders of kindle, mean that I have actually read this book. I can promise you it contains no unicorns, and not a single reference to climate change.
It is, however, a very balanced exposition of many of the problems facing modern medicine and a clear manifesto on how to deal with them. In these times of austerity, it shows a way that huge amounts of money could be saved in the NHS without any reduction in quality of service.
Although he does occasionally talk about outright fraud, Goldacre is careful to point the finger at the wider professional culture which makes it acceptable, for instance, for companies to withhold data about trials which do not show their products in a good light, and for medics to accept free 'training' at flash conference centres without understanding the difference it might make to their prescribing practices. As he points out, in these days when we've seen politicians expenses and tabloid phone hacking exposed, the time is ripe for these excesses to be exposed.
This is not a book for conspiracy theorists or those who simply think that all modern medice in bad, but if you are a patient, or every expect to be, you should read it, and buy a copy for your doctor.
on 3 November 2012
Bad Pharma, a book by Ben Goldachre concerning the working practices of some pharmaceutical companies, is the most informative book I have read this year.It's content is detailed, well explained and of great interest to people like myself who are taking medication for a specific, incurable, life changing disease. At first I downloaded it to my kindle from Amazon but I found aspects of the content quite shocking and needed to constantly backtrack and confirm that I had read the text correctly. This I find tedious with my kindle so I decided to order the paperback and I am very glad I did as there are so many footnotes and references to follow through with. I am now on my second reading. To a former scientist trained in scientific method it is hard to believe that industry lead research has proved to be so unscrupulous, biased and basically dishonest. Ben Godacre writes a most convincing and compelling argument and with conviction. How can GPs and patients make informed decisions unless presented with truthful data about medications and, clearly, in many cases we have been sold a pack of lies. This book should be read by health professionals.
on 25 February 2013
I'd already read "Bad Science" and been very impressed by Ben's sceptical, sardonic style - this book is much more important: if you take medicines, might ever take them, have relatives taking them, or prescribe them, you should read this book. He outlines clearly, in detail, and with much evidence, the scams, lies, ploys & practices of drug companies and their promoters. I've been a doctor for 34 years so have experienced much of the companies' propaganda & promotions listed in the book. I've seen many new drugs pushed onto prescribers, thence to patients, which have subsequently been found to be dangerous or just ineffective, when sometimes the companies knew beforehand. It's all in this book. It is seriously sad that it's taken so long for what is written here to leak out into the medical, let alone wider public, domain. There's a lot of science, argument and statistical jargon here, but it's accessible to anyone at least of "A" level or above education. And please, if you are offered anything from your doctor, ask some hard questions about your prescription before you take it...
on 25 July 2014
Goldacre has a way of making complex science subjects accessible to the wider public. His first book, Bad Science, highlighted the way that the media dealt with reporting science, and in this book he concentrates his ire onto the $600 billion global pharmacy industry, now dominated by a handful of behemoths.
And what he reveals is frankly terrifying. He details the way that the industry hides a large majority of the trial data, the way that the legislation requiring data to be published is ignored by companies, and in the EU it is still secret in some cases. There is loads of detail on the way that the data is cherry picked to demonstrate that a particular drug is so much better than the competition. There is lots of detail on the appalling way that the industry is regulated, even though it is very heavily regulated, most of it is ineffective and not enforced, and where the regulation could be improved to help patients and save lives these are not enforced or are not enacted on after lobbying from the industry.
The biggest chapter though is on the marketing that these companies employ. Their budgets for marketing are normally twice the R&D budgets, which gives you some idea of where their priorities lie. He explains how they sponsor various ‘conferences’ and provided sweeteners to medical professionals at all levels, from lunches to flights to what most people would consider bribes. The nefarious dealings of the drugs rep are dealt with too, from the pressure that they put onto doctors to use their medicines and the way that they collect data directly from surgeries and pharmacies. A lot of academic papers are ghost written, and a leading figure puts their name to it, shocking really.
There is some details on NICE, but not a huge amount. He looks at the way that they select the drugs for use in treatment, noting that even they do not have access to all the trail data for each medicine that they consider.
He also writes about how a lot of the drug companies fund patient groups either overtly with cash donations or covertly by funding particular conferences and so on. They have been proven to use them to exert pressure on national agencies (FDA and NICE) to supply the latest drugs regardless of the cost; i.e. £50K spent with a group means that they get their £21k per patient drug treatment approved, even though the trial evidence is not there or is at best not proven to be any more effective than the current items on the market. A real scandal.
Throughout the book he does give suggestions on how the situation can be improved but he does realise that they is an endemic problem and powerful vested interests do hold sway. Even just enforcing the current rules would make a difference, but it seems unlikely at the moment.
The phrase for illegal drugs used to be: Just Say No. Perhaps it should apply to legal drugs too...