By me in the BMJ: the dodginess of drug company trials

December 1st, 2009 by Ben Goldacre in bad science, big pharma, hiding data, regulating research, statistics, subgroup analysis, systematic reviews, trial registers | 73 Comments »

Here’s a piece by me in the British Medical Journal this week, published online already, and in the print edition this Friday. It’s a head to head with Vincent Lawton, who until recently was head of Merck in the UK. Briefly, I set out the quantitative evidence demonstrating the scale of the problem, and he says: “oh, we’ve fixed everything now, and anyway some academic trials are dodgy too, here’s one what I found”. That’s a paraphrase, you can read his response for free on the BMJ website here, since they’ve decided that this is an important issue which deserves open access. If you’ve got something really clever to say about these pieces then you might also want to comment in the “Rabid Response” section of the BMJ version of either article.

We were going to have a debate on the Today programme on Monday morning, and then tomorrow morning, but unfortunately it’s been ditched. If you work in mainstream media and would like to cover this issue I’m always keen, and amazingly easy to get hold of, ben@badscience.net. Although I realise that your idea of a meaningful critique of the crimes of big pharma is “chemotherapy hurt my grandma that’s why I love vitamin pills and hate teh vaxxines lol freedom”.

Incidentally, if the text is too small (on any site) hold down the CTRL key and press “=” or “+” on your keyboard.

www.bmj.com/cgi/content/full/339/nov27_1/b4949

www.bmj.com/cgi/content/full/339/nov27_1/b4953

Published 29 November 2009, doi:10.1136/bmj.b4949
Cite this as: BMJ 2009;339:b4949

Head to Head

Is the conflict of interest unacceptable when drug companies conduct trials on their own drugs? Yes

Ben Goldacre, doctor and writer
1 Nuffield College, Oxford OX1 1NF
ben@badscience.net

doi:10.1136/bmj.b4330

Ben Goldacre argues that the financial interests of drug companies lead to distorted evidence, but Vincent Lawton (doi:10.1136/bmj.b4953) believes that adequate safeguards exist to keep bias in check

The practice of medicine is based on evidence. We need this evidence base to be complete, and of the highest quality, so that we can make the right decisions, but at present, drug companies produce most of the evidence we use. There is no doubt that these companies have a conflict of interest when they conduct trials: they want to sell their products, and so naturally they want a positive result from the trials they sponsor. But there is now good evidence from systematic reviews, meta-analyses, and case studies that this conflict of interest results in bad evidence, which distorts medical decision making and so harms patients.

We will start with a tangible story, from a single field. Rochon1 analysed the literature on non-steroidal anti-inflammatory drugs (NSAIDs), and found all the studies that had ever been published where one NSAID was compared to another. In every single trial, the sponsoring company’s drug was either equivalent to, or better than, the drug it was compared to: all the drugs were better than all the other drugs. Such a result is plainly impossible.

A systematic review2 found 30 studies investigating whether industry funding is associated with outcomes that favour the funder: studies sponsored by drug companies were more than four times as likely to have outcomes favouring the funder, compared with studies with other sponsors.

How does this systematic bias come about? One answer is questionable trial design. Studies are conducted, for example, where the competitor drug is given at an inadequate dose, or worse, at a higher dose, increasing the risk of side effects, and so making the sponsor’s drug appear to be preferable.3

Another common problem is that the industry can choose which data to publish, and which to leave unavailable. Much has been written on eye-catching stories, such as the difficulties in getting clear information about the number of suicide attempts in industry trials of SSRI antidepressants4 or the number of heart attacks in patients on rofecoxib (Vioxx).5

Equally concerning is the routine grind of publication bias, where disappointing negative results on the benefits of treatments quietly disappear. This phenomenon has been demonstrated in many fields, notably that of SSRIs,6 and in some areas of medicine its scale is staggering. Ramsey and Scoggins7 went to clinicaltrials.gov and found all the trials on cancer: 2028 in total. Only 17.6% of these trials could be found published on PubMed, but 64.5% of those that were published reported positive results. Restricting their analysis to only industry sponsored trials, these results became even more extreme: just 5.9% were on PubMed, but of those trials, 75.0% gave positive results.

And while disappointing results lie unpublished, positive results may be published repeatedly, in ways that are hard to spot. One group conducting a meta-analysis on the efficacy of ondansetron8 made a striking discovery: data from 3335 patients in nine trials had been published more than once, in 14 further reports. None of these duplicate publications used a clear cross reference, so there was no easy way for a casual reader to see that each was not a new trial. Crucially, and perhaps inevitably, data showing a greater benefit from ondansetron were significantly more likely to be published twice.

It is inevitable that publishing positive results more than once will cause doctors to think a drug is better than it really is, since doctors are busy, and cannot each conduct forensic checks on every trial they read. One study estimated that for physicians to read every published article relevant to primary care alone would take more than 600 hours a month.9 Duplicate publication and dubious methodological tweaks will be missed, and an illustration of how much these practices may cause doctors to overestimate a drug’s efficacy can be seen in the ondansetron meta-analysis, where including the duplicated data led to a 23% overestimation of the drug’s antiemetic efficacy.8

The problems I have described are not new, and they have been described on many previous occasions. They could be fixed, without taking research out of the hands of industry altogether, but to do so would require that the drug companies recognised the scale of this scandal, and campaigned themselves for more effective regulation: demanding full mandatory publication of all trial data from themselves and their competitors, for example.

Instead we see inertia, and the failure of regulators to engage adequately with these serious problems. In medicine, bad information leads to bad decisions: we prescribe one drug where an alternative would have been more effective, or had fewer side effects; or we prescribe an expensive drug, unnecessarily, when a cheaper alternative was equally effective, and so we deprive the community of limited healthcare resources. This is dangerous and absurd. Doctors who are making treatment decisions need access to good quality trial data, presented transparently, and all of it, not just the positive findings that drug companies choose to share.

Cite this as: BMJ 2009;339:b4949

doi:10.1136/bmj.b4330


Based on the Great Oxford Debate on 23 September 2009 at the Oxford Union, Oxford University, sponsored by PharmaTimes. Competing interests: BG has written newspaper articles and part of a book criticising questionable activities in the drug industry, and has a Clinical Research Training Fellowship from the Wellcome Trust.  

References
     

  1. Rochon PA, Gurwitz JH, Simms RW, Fortin PR, Felson DT, Minaker KL, et al. A study of manufacturer-supported trials of nonsteroidal anti-inflammatory drugs in the treatment of arthritis. Arch Intern Med 1994;154:157.[Abstract/Free Full Text]
  2. Lexchin J, Bero LA, Djulbegovic B, Clark O. Pharmaceutical industry sponsorship and research outcome and quality: systematic review. BMJ 2003;326:1167-70.[Abstract/Free Full Text]
  3. Safer DJ. Design and reporting modifications in industry-sponsored comparative psychopharmacology trials. J Nerv Ment Dis 2002;190:583-92.[CrossRef][Web of Science][Medline]
  4. Fergusson D, Doucette S, Glass KC, Shapiro S, Healy D, Hebert P, et al. Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials. BMJ 2005;330:396.[Abstract/Free Full Text]
  5. Hippisley-Cox J, Coupland C. Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. BMJ 2005;330:1366.[Abstract/Free Full Text]
  6. Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med 2008;358:252-60.[Abstract/Free Full Text]
  7. Ramsey S, Scoggins J. Commentary: practicing on the tip of an information iceberg? Evidence of underpublication of registered clinical trials in oncology. Oncologist 2008;13:925–9.[Abstract/Free Full Text]
  8. Tramèr MR, Reynolds DJ, Moore RA, McQuay HJ. Impact of covert duplicate publication on meta-analysis: a case study. BMJ 1997;315:635-40.[Abstract/Free Full Text]
  9. Alper BS, Hand JA, Elliott SG, Kinkade S, Hauan MJ, Onion DK, et al. How much effort is needed to keep up with the literature relevant for primary care? J Med Libr Assoc 2004;92:429-37.[Web of Science][Medline]

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73 Responses



  1. Veronica said,

    December 1, 2009 at 4:18 pm

    You are complaining about a problem that has already been solved, and you are looking at data that reflects past practice and not current practice. What pharma companies need, in order to discuss their results with physician customers, is data from peer-reviewed jouornals. The International Committee of Medical Journal Editors is making it harder and harder for companies to carry out clinical trials in secret and then decide post hoc whether to publish the results. They insist that trials are registered e.g. at www.clinicaltrials.gov before they start. Check the ICMJE website for the very comprehensive rules about what they will and will not accept in terms of clinical trial publications.

    www.icmje.org/

    If pharma companies do not fund clinical trials in future, then who should fund them exactly? The taxpayer? Unfortunately, the business model for the pharma industry is that it is funded from profits. That’s how all the sophisticated drugs and medical devices we have today have appeared in the physician’s armoury. No government body or charitable sector could afford these multi-million dollar studies, nor should they.

    This issue might have been broken, but it is now largely fixed.

  2. brianpcurran said,

    December 1, 2009 at 4:43 pm

    Since it took a few clicks to find Ben’s thing on the BMJ site…

    Ben: www.bmj.com/cgi/content/full/339/nov27_1/b4949

    Merck guy: www.bmj.com/cgi/content/full/339/nov27_1/b4953

  3. Ithika said,

    December 1, 2009 at 5:04 pm

    @Veronica:

    This issue might have been broken, but it is now largely fixed.

    If it is fixed, and you know it is fixed, you’ll be able to point us to new data which gives you this knowledge. I presume further analyses have been done, like the ones Ben cites above, which exhibit no detectable bias under the same conditions.

  4. skyesteve said,

    December 1, 2009 at 5:04 pm

    @Veronica – so are you saying pharmaceutical companies no longer keep unfavourable data hidden from public view? Surely if the NHS is to “buy” some kind of treatment from a pharmaceutical company every single piece of info they hold relating to that therapy must be available for scrutiny. But very recent events (e.g. Cox 2 anti-inflammatories) seem to suggest that that is still not the case or am I just out of date?

  5. CoralBloom said,

    December 1, 2009 at 5:41 pm

    @Veronica

    Well if it is fixed, what is this link for on the BMJ page where I have just been reading the Lawson piece – www.bmj.com/cgi/content/extract/339/nov03_2/b4556?q=w_latest_topic

    I don’t know what the whole story is, but it surely doesn’t look too good. It may well all be innocent, though you do have to ask why the situation was created in the first place.

    For this to be fixed, all the data, historical and current should be published. Until then…

    This is a very good piece Ben, and I hope you do finally get to discuss this on the Today programme sooner rather than later.

  6. medvetenskap said,

    December 1, 2009 at 6:07 pm

    @Veronica,

    yes, in general it is required for drug companies to have registered a study in order to get it published. But this only fixes part of the problem since there is no requirement to publish (or make public) the results of a completed registered trial.

    You see how this is a problem when 2028 cancer trials are registered at clinicaltrials.gov but only 17.6% end up published.

    We need regulations which ensures that trial results are published or made public once the trial is completed.

  7. brianpcurran said,

    December 1, 2009 at 6:11 pm

    It seems like Lawton wrote his entire essay under the impression that Ben had argued to rid the world of the inherently evil industry-sponsored trial. Either he is being disingenuous and trying to placate us with platitudes about God-like regulators, or he is just not very intelligent. I’m leaning toward the former.

  8. Keo said,

    December 1, 2009 at 7:01 pm

    I totally agree that current regulatory safeguards are insufficient to eliminate financially motivated bias. I would point out to Ben that it is not unthinkable that most -if not all- clinical trial results come out positive. We have embarked in a couple of non industry clinical trials (with treatment schema, no product involved), but since these are hideously expensive and difficult, we only went forward because the preclinical data strongly pointed to a positive result. Nobody likes a negative result, and big pharma will only place its money if they believe with confidence that it will come out.
    @Veronica: “No government body or charitable sector could afford these multi-million dollar studies, nor should they.” In fact, these multi millions came out of our (the public) pockets, “their” profits are money that once belonged to the patients. I see no problem in making a pool of money from all potential recipients of health-care (i.e. everyone) to fund the research. This is a truly political, not scientific matter.

  9. Diversity said,

    December 1, 2009 at 8:18 pm

    Look at this from another angle.

    The incentives on the drug companies are to produce drugs which work in clinical practice; and over the last half-century or so tha has produced remarkably good results. The same incentives press the companies towards producing drugs which appear to work. That is the incentive which leads to bias in the publication of trial results.

    Sometimes one man’s bias is another’s fair use of judgement. There are always going to be a good number of cases where we are not sure of the significnce of the evidence. To cope with that we need a status for some new drugs which allows their clinical use under caution and under a special duty to report good and bad results in clinical practice. We need it because in these cases it is the only way we will ever assenble enough evidence to make an objective judgement.

    Sometimes one man’s bias turns out to be another’s unfair use of ‘judgement’ in his own favour. The only way to prevent drug companies run by humans from doing that is to make sure it is costly to be caught. I leave it to others to suggest how.

    On the evidence here, a high proprotion of favourable results does not mean that the clinical trial results are cooked. A drug company that knows what it is doing won’t go into expensive clinical trials unless it judges that a favourable result is likely (and/or in a minority of cases, that a favourable result would be very profitable). On the other hand, a low proportion of clinical trial results accounted for is a danger sign. For the sake of theri own reputations reputable pharma comapnies should insist on a norm of at least a very summary result of every registered clinical trial is public (e.g. ‘abandoned’, ‘weak significance of results’, ‘positive, inconclusive’ ‘positive, conclusive’, ‘side effects to study’ might cover most of them.)

  10. Jerry said,

    December 1, 2009 at 8:32 pm

    I would indeed expect there to be a majority of favourable trials, because in-house testing would remove the worst candidates before going to trial phase.

    The solution would indeed seem simple, tax the companies a specific % and use that money to have universities do trials.

  11. Veronica said,

    December 1, 2009 at 9:18 pm

    @Diversity – thanks, you’ve said what I would have said in my replies to the above. Pharma-sponsored trials carry the same criticism that (I think it was) Churchill made about Democracy – “the worst possible system apart from all the others”.

    So pharma is taking patients’ money to fund the next round of research? Well, it’s better than taking it to make chocolate, or Humvees, or Special Brew or the little toys in Christmas crackers. It gobsmacks me that those of us who work in pharma are vilified for saving and improving millions of lives. It’s a shitty job but someone’s got to do it!

    And don’t get me started on the quality of academic research. I’ve witnessed it, commissioned it, and critiqued it, and the low standards I found would have got the perpetrators fired if they had been in Big Pharma.

  12. Delster said,

    December 1, 2009 at 10:00 pm

    @Veronica

    Nowhere in any of the article’s i’ve read on badscience or elsewhere does the Pharma industry get vilified for saving or improving lives.

    What they get critisized for is cherry picking the data, not publishing negative results and generally trying to avoid anything that might reflect poorly on one of their potential money spinners.

    If you’ve read many of the badscience articles you’ll notice that it’s not only pharma that come in for this treatment. Ben is far more scathing of the Alt Med research methods (insomuch as they have any).

    However i think that anybody has to admit that a sub 20% publishing rate for trials is pretty damned poor.

    I’d far rather take a drug where all the possible negative outcomes are known by the prescribing physician than one where it’s all a bit vague. At least that way they can be weighed up against other possible problems the patient may have.

  13. Jbags said,

    December 2, 2009 at 1:50 am

    @Delster

    I think it is fair to say Big Pharma are certainly vilified, by everyone in fact, for various different reasons. By concerned medics and scientists, looking to keep pharma honest, and by quacks looking to flog their own wares instead.

    And this I think is where we have to be clear on our motives. Are we looking to work _with_ or _against_ big pharma?

    Taking a critical look at trials, methods and analysis is the bedrock of scientific investigation, and big pharma should be scrutinised as such, the system is imperfect. However, the point remains that big pharma is responsible for significant advance in medical science, and it is by working with big pharma that we will improve medicine for future generations. Criticise to keep them honest, strive for the most transparent and diligent testing methods, this is all good work.

    Just bare in mind that we need to be a help rather than a hinderance, and I think remember that there’s no alternative to big pharma to get the billions of pounds a year worth of R&D done. All we can do, is try our best to make sure its done properly.

  14. se250 said,

    December 2, 2009 at 2:30 am

    About 3-5 years ago most pharma companies posted the results of their studies on one of the trial registries. Either state or their own.

    The company I worked for at that time had theirs independently audited each year with fines of $10k for each day after the posting deadline(which was 1 year after the study completed).

    I believe that these are now a thing of the past due to litigation in the US (initiated by individual states). I’m not so sure as I moved on since then.

    I think the comments made by Jerry had some merit to them and there are a three other aspects to consider.

    1. A company that has spent 10 years developing a drug probably has a great deal of insight in to it and consequently understand how best to test it = more +ve results
    (of course, a dishonest company could use this knowledge to their advantage should they so wish. But then the dishonest academic can use their relative lack of knowledge to run a trial of the same drug to produce inconclusive results that are career making when published until the title “New super drug fails to differentiate from placebo”. dishonest is dishonest is dishonest)

    2. The point that Big Pharma (sic – is small pharma better? or just under the radar?) willfully manipulates (or withholds) trial results for commercial advantage seems to be raised without any examination of the consequences of such action. Take a look at the financial consequences to Glaxo of Avandia (4 out of 7 ? trials from the registration published) to see where that leads.

    3. To publish trials you need a publisher. Publishers are businesses too and want sexy new science to publish in their sexy scientific journals. “New SSRI very much like previous SSRIs concludes 483rd clinical trial” isn’t likely to do it for the NEJM. You’ll notice that while the journal editors have been enthusiastic (rightly so) to require registering a trial as a requirement for publication, they have been somewhat more quiet on the subject of publishing every trial ever conducted. Everyone has an agenda.

  15. Filias Cupio said,

    December 2, 2009 at 6:18 am

    I trust this “17.6% of cancer trials got published” result accounts in some way for trials which have not yet reached a publishable stage? (E.g. if the trial registry has been open for 6 years and it normally takes 5 years from registering the trial to publication, then no trials are missing.)

    @JBags: “there’s no alternative to big pharma to get the billions of pounds a year worth of R&D done.”

    Taking this attitude as your starting point is just as wrong as taking “big pharma must never run drug trials” as your starting point.

    I can think of lots of alternatives. I don’t know whether they’d be better. Consider the price difference between patented and generic drugs, and how much the UK health system pays in this differential. It would be, well, billions of pounds a year (and in the USA it would be much higher, even on a per capita basis.)

    Here are just a few alternatives. I’m aware that they have problems, and possibly worse problems than the current system.

    Alternative 1: Wealthy nation governments develop new drugs with tax money, and either license the drugs to manufacturers or ‘open source’ the drugs. Paid for by lower drug costs and/or license fees.

    Alternative 2: Wealthy nations make bounties available for drugs that achieve desired results. Reduced bounties are paid if the drug has undesired side effects – the remainder could be paid later for a new drug which does not have the side effects. The contributors to the bounty own the drug and can license or open source it.

    Alternative 3: (Sort of a combination of the above.) Government funds are given as grants (in much the same way as scientific grants are given to academics) to drug development companies to attempt to develop desired new drugs. The drug development companies are generally separate from the drug manufacturing/distributing companies, which (once again) get the drug formula from the government agencies by license fee or for free.

    Alternative 4: legally enforce a separation between drug development companies and drug manufacturing/distribution companies. The development companies license formulae to the manufacturers, and by law must offer the same license terms to all comers. (I’m not sure that this one would in practise be much different from the current system.)

  16. vinnyr said,

    December 2, 2009 at 12:04 pm

    I don’t think Ben can necessarily say that the proportion of positive trials from BigPharma is due to skulduggery of some sort. It could be that once trials clearly are not going to produce positive results, they just get abandoned. What needs to be analysed is if a particular drug is goes through a trial whose results do not get published, and then subsequently a trial using the same drug is published and shown in a positive light.

    I can’t see why trials should not be abandoned once they are clearly not showing the desired results as that would be throwing good money after bad. However whatever results that have been found should be published in a summary form. Perhaps journals could have a section for abandoned trial summaries which let people know why the trial was abandoned. Or at least a final result should also be submitted to www.clinicaltrials.gov

    Too many people have criticized Ben on here for suggesting that someone else should do the trials. I don’t think he has suggested that at all – just that any trial that does take place also gets reported.

  17. chinaphil said,

    December 2, 2009 at 12:44 pm

    I guess I agree with Diversity and Veronica, but I still think there’s a problem. When a pharma company conducts a trial, it’s part of its commercial process. The question they are trying to answer is, “Can this product make us money?” It’s business, not science.
    When a university conducts a trial, the question they’re trying to answer is, “What does this drug/treatment do?” It’s science, not business.
    There’s room for both. But why does anyone think they should be put together? Medical scholarship is one thing; R&D is another. They should be published in separate journals, with the academics basically acting as a watchdog on the pharma companies.

  18. Veronica said,

    December 2, 2009 at 1:47 pm

    The question “Can this product make us money?” is an indirect one. Pharma doesn’t make money unless it helps patients, therefore the question being asked in clinical studies is “Can this product help patients?”. Nothing wrong with that, business and science are hand in hand. What we do less of is working out the mechanism of action of certain drug molecules – that is more of an academic pursuit.

    A university could not afford the sort of studies that pharma can do, and indeed has to do, both to register its products and support them commercially post-launch(by showing where they are better than other products). Phase III / IV studies can easily cost between $10 million and $100 million. They need to be run in many clinical centres worldwide. No academic department could cope with the infrastructure needed to run them.

    It’s getting worse. Regulatory agencies are now asking for outcomes studies e.g. it is not enough to show that a drug lowers blood pressure effectively and safely, pharma is now being asked to prove that high blood pressure is a bad thing – by counting up the number of heart attacks, strokes and deaths over years and years of use, as prospective, randomised studies, not retrospective epidemiology. That will cost even more. And you wonder why drugs are expensive.

  19. skyesteve said,

    December 2, 2009 at 4:17 pm

    Sorry – but I still think the big issue is that too often we are being asked to make decisions about treatment with one hand tied behind our backs because not all the data about a particular drug is made available for public scrutiny, especially when it might portray the drug in a negative light. This has happened too often to pretend it’s just a problem of the past.
    The problem with the “can this product make us money?” question is that it automatically runs the risk that corners might be cut and data may be selectively released or buried in order to maximise the chances of commercial success as money rather than benefit to the public becomes the driving force.
    That’s not to say that “academic” trials should get let off the hook. Too many of them in the past have also been subject to selective reporting/under-reporting and that’s not acceptable either.
    Until we have total and complete openess for all trials – commercial or academic – it’s impossible not to be a wee bit sceptical (well, for me anyway).
    I’m not necessarily anti “Big Pharma” per se. There are examples where their work has saved or enhanced millions of lives (though it could be argued that many of these developments had their origins in non-commercial academic research). But there are also plenty examples where they have been less than scrupulous.
    Surely all any of us can ask for is a bit of trust and honesty.

  20. Health Pain said,

    December 2, 2009 at 6:14 pm

    The medicines that are used for bone pain are narcotics findrxonline as opioids such as vicodin, Lortab, OxyContin, hydrocodone and the doctors that are usually used to combat pain they cause diseases such as homeopathy, fibromyalgia and even cancer In general, these medicines are used mostly is the United States and Europe are controlled because their use can lead to addiction.

  21. ferguskane said,

    December 2, 2009 at 9:00 pm

    @ Veronica.

    ‘If pharma companies do not fund clinical trials in future, then who should fund them exactly? The taxpayer?’

    Umm. Well in European countries with ‘socialised medicine’, it IS the taxpayer who pays the drug companies to conduct these trials. It is also the taxpayer who pays for scientists to do all the preliminary basic science that happens in universities without the involvement of drug companies. In the end patients pay for everything, including the ‘free’ lunches from drug reps.

    There is an argument that governments should take all the work in house rather than also having to pay shareholders. There are also compelling arguments against this, but the above rhetorical question demonstrates a very shallow understanding of how things really work.

    How about ‘Who should fund them if not the taxpayer?’

  22. ferguskane said,

    December 2, 2009 at 9:13 pm

    ‘I can’t see why trials should not be abandoned once they are clearly not showing the desired results as that would be throwing good money after bad. However whatever results that have been found should be published in a summary form’

    This needs to stronger. All RCTs MUST be registered and the results of all RCTs must be published, peer reviewed or not. ALL relevant information MUST be made available. This applies to both pharma and non pharma studies. As far as I can see, for the consumer, there is no downside to such regulation. Is the problem already solved? As others have said, let’s wait and see.

  23. toxman said,

    December 2, 2009 at 11:08 pm

    I fully understand Ben’s arguments, however, interpreting trial data, having time to read all the latest releases etc. can, and is done by clinical pharmacists. I work with allot of these folks, and they often complain at the lack of respect doctors and others in the medical profession hold for them, especially when they correct a doctors prescription. Perhaps by working with the experts in pharmaceutics some of these problems could be avoided?

  24. Jbags said,

    December 3, 2009 at 1:53 am

    @Filias Cupio

    I’m sorry you feel that way, but I still honestly think there’s no alternative, and that should be our driving motivation to improve the industry. I’m saying this: “because there is no alternative we have a paramount responsibility to make sure it works”, and I don’t think anyone would disagree when I say there is a lot of space for improvement in this industry (maybe people will only disagree about the degree to which that is an understatement).

    Looking at alternatives is fine, we shouldn’t lock ourselves into one course of action and ignore alternatives, but I honestly don’t think there are any that work. Taking a look at your 4,

    #1 The first problem with this one (and it applies to most of the alternatives) is that you can’t nationalise innovation in an industry. Innovation is driven by competition, as the old saying goes “necessity is the mother of invention”, if there is no competition there will be significantly less innovation, and that means less medical advance.

    Even if this were not a problem, you would never get this idea off the starting blocks for the simple reason that the pharmaceutical industry is one of the most global of industries. Nationalising drug development would find a huge amount of opposition amongst countries which owe a proportion of their GDP to pharma… i.e. the majority of the developed world. If you did implement it, you’d find trade tariffs imposed to raise the price of these drugs to be uncompetitive internationally to protect global pharma.

    There’s no way round this one, you can’t “globally nationalise” an industry like big pharma, we can’t even complete this round of Doha negotiations.

    This also raises the risk of politicising medical R&D. For example, if abortion were to become an election issue, a new government comes in and cuts all funding to medicine and technology related to abortion as part of their “hardened” stance on abortion. This is clearly a disaster waiting to happen, so how about making it independent from the government like the MPC at the Bank of England? Well suddenly we’re heading back to the lands of private business and big pharma.

    You also have the problem of monopsony. You have made the government the sole consumer of drugs research, bypassing the entire market mechanism. This gets you into a whole load of problems, since this removes the information link between consumer and producer. The government does not consume these medicines, it passes them on to the populace to consume, by removing the drug consumers from the drug producers you lose all direction in drug research and development. Since drug development is prioritised by a probability function of expected revenue, the revenue itself being a function of consumer demand… remove consumer demand and you remove a fundamental link in deciding what to actually reseach. Consumer demand links need for (or rather want for) drugs to the production of drugs, therefore the drugs that will be bought most will get developed most. this is a beneficial system because it means the companies develop the drugs that people actually wants. for over the counter medicines this system is flawed, but for prescription medicines this works rather well since you are selling to an educated consumer (the GP).

    #2 This scheme is just a reorganisation of big pharma but it doesn’t change anything? you will get pharma companies maximising bounty revenue just like you have them maximising profit at the moment, there is exactly the same motive to make drugs that work as well as drugs that “appear to work”.

    Then there is the problem of paying the bounties. At what point do you give this bounty? When do you have enough evidence? Some drugs don’t show up to be at fault until a long time after their original development, would you demand some bounty be repaid? This leads us into a massive financial quagmire.

    It also raises the problem that, to keep the R&D in business, you will need to provide enough revenue through bounties to sustain the industry. Even if you were then to sell the drugs at their same old market price (raising the question why bother), you will still be massively out of pocket, and will need huge additional tax revenue just to pay for the running of this scheme.

    #3 You can’t grant fund R&D and expect it to remain globally competitive. Since the financial decisions to develop of drugs are based on probabilities (expected probability of favourable outcomes, risk factors, discount rates), how do you suggest giving an incentive for successful development? If the drug companies are given a grant “to attempt to develop a new drug for condition x”, there’s no incentive to actually develop it. They have received the grant up front, so why bother actually making any effort? Cynical yes, but incentives are fundemental in assessing economic pros & cons. I won’t repeat myself, but a lot of what I said in resonse to #1 applies here.

    #4 Again, a lot of #1 applies here, particularly the point about severing the link between consumer and producer of medicine research.

    This time, enforcing identical license terms to all comers will most likely result in a distributor monopoly, since they will all have exactly the same product. This creates another situation of monopsony between distributor and developer, and essentially you would have the distributor entirely dictating the work of drug developers -without having a stake in their success of failure- as they do at the moment being part of the same companies. This would be a disaster.

    I apologise for going to such length, but I hope you realise I am not throwing around idle speculation when I say “we have no alternative”, as an economist I genuinely think we really have no alternative. Which brings me back to the point: lets please spend time and effort working with big pharma to improve its running and not waste time with what ifs or unconstructive criticism.

  25. se250 said,

    December 3, 2009 at 2:07 am

    @chinaphil I think that academia being a science not a business is no longer true. Every academic relies on publications for tenure. It’s about publications in the same way that pharmaceuticals is about money. In both cases this is achieved through scientific pursuit.

    Having worked in both, I would more readily trust the science performed in a pharmaceutical company. They’re basically shit-scared of getting it wrong. Of being the next Merck/Vioxx or GSK/Avandia. They have masses to lose and have large (we’re talking hundreds of employees) in quality organisations to check and document that things are done correctly.

    The explosion of the internet and “informal” peer review – the sort of thing that Ben does – is such a healthy thing that it would be extremely foolish for companies to hide the bad news. It will be found out it’s a matter of “when” not “if”.

    When Steve Nissen’s meta analysis of Avandia found an issue it was published in NEJM – if he had found nothing do you think it would have made the NEJM?

    No. Maybe the Latvian Journal of Dull Results. (Apologies to any Latvians reading).

    Which one of those Journals would be best for the career of the academic?

    It’s not quite as simple as it first appears.

  26. tomrees said,

    December 3, 2009 at 11:04 am

    Ben’s criticisms are several years out of date. Anyone working within the pharma industry knows how the climate has shifted. All trials are now registered and the results reported, whether positive or negative. Maximal doses of comparators are used (trials using underdosed comparators are worthless, from a business perspective, because the regulators won’t let you use them in communications – let alone in drug registrations). Publications include the unique trial identifier, so post-hoc analyses of already-published data are easily identified.

    Of course trials sponsored by industry are mostly positive. That’s because they largely don’t do them to find out if their drug is better. They do them to demonstrate that their drug is better – to fulfil the requirements of evidence based medicine.

    They are not going to spend money on a trial unless they’re pretty sure that the drug will show itself to be better, and hence provide some return on investment.

  27. Veronica said,

    December 3, 2009 at 11:07 am

    @ ferguskane

    “Umm. Well in European countries with ’socialised medicine’, it IS the taxpayer who pays the drug companies to conduct these trials. It is also the taxpayer who pays for scientists to do all the preliminary basic science that happens in universities without the involvement of drug companies. In the end patients pay for everything, including the ‘free’ lunches from drug reps.”

    There are a small number of clinical studies carried out in fields of general interest by bodies such as the US National Institutes of Health. (Taxpayer money again)But studies into a particular drug, and how it performs against placebo, against standard care, or against a rival drug, are generally funded by drug companies. That is true everywhere. The company pays out of their profits. And yes, those profits are gathered from the sale of drugs. What other source of research funding would a drug company have? The National Lottery? Collection tins in the street?

    This is the business model we operate in. There is no charitable money for pharma companies (the reverse is true). There is no government grant for pharma companies. There are very few philanthropists such as Bill Gates who fund pharma endeavours. Where else should we get our research money from?

    Free lunches from drug reps are, BTW, a misnomer. If a drug rep wants to give a presentation of their company’s data on a drug or a disease state, sometimes food is provided at the meeting, otherwise the healthcare professionals would not turn up. I think it is important for doctors to learn something about the tools we are providing for them to fight disease.

  28. Veronica said,

    December 3, 2009 at 11:22 am

    and in reply to some of the early comments on this blog @me…
    it depends what you mean by “publish”.

    If a study is boring or has ambiguous or contradictory answers, it is quite possible that the company concerned will write it up and submit it to a peer reviewed journal and have it rejected as not being of sufficient interest. Journals jealously guard their own reputation and want to publish “wow” rather than “so what?”.

    A company can of course, and usually does, make the results public (rather than publish) at meetings, in poster sessions, in press releases, on their own websites.

  29. philbo said,

    December 3, 2009 at 1:46 pm

    I like the idea of an article having “rabid responses”. ’twas such a shame to find out it was a typo.

  30. wilsontown said,

    December 3, 2009 at 5:27 pm

    If you’ve seen what some of those rapid response threads are like (especially on controversial topics like CAM and vaccines), you’ll know that it wasn’t a typo…

  31. Frido Bohn said,

    December 4, 2009 at 2:15 pm

    I want to point out that the seeming contradiction between the statements about quality of clinical trials of Ben and the “Merck guy” (Vincent Lawton) might have been risen from the missing classification into “pre-marketing” and “post-marketing” clinical trials.

    During the early development phase of a new substance that is intended to acquire the honours of a medicinal product (vulgo “drug”) a quite well and strong regulated system is launched. Here, governmental authorities and local institutions like ethics committees safeguard the commonly accepted standards and regulations. From my experience, there is little space for comparative statements, like “drug A has a 2% less relative risk for the development of strokes than drug B”. The reason is simple because the aim of the pre-marketing phase is to get that “multi-million dollar baby” into the public who eventually would pay for it. Therefore, these studies look in first line at safety and tolerability according to the rule “primum non nocere” (first, do no harm), and in second line they look for efficacy. At least, contemporaneous authorities demand a proof of efficacy. But it does not go beyond non-inferiority tests. Generally speaking, this means that a newly established drug should be tested against a standard therapy and show that it is not less effective or safe than the comparator. After it was shown that the developed drug is acceptable it gains market authorisation.

    The broad spectrum of clinical trials that attract criticism is indeed situated in the post-marketing phase. Interestingly, there is no real need for “big pharma” to conduct such studies as their product has attained its main goal – to be available to the public. So, what the heck are all these post-marketing studies for? Simple answer – marketing! And is there more to say? As every product in our consumers’ world, a drug is also subject of marketing. Every effort is made to increase the sales rate. As automobiles are presented in car shows, drugs are presented on scientific meetings –a fool would take “scientific” literally.

    To make a long story short: Clinical trials, more precise – publications of clinical trials of the post-marketing phase – should be more scientific and less advertisement. As long as this is not the case, medical professionals and the general public should handle results of this class of clinical trials with care and be aware of the underlying conflict of interest. Or would you expect from the big automobile brands to disclose their weak points on a motor car show?

  32. DrJG said,

    December 4, 2009 at 11:22 pm

    @Toxman, re Clinical Pharmacists:

    “I work with allot of these folks, and they often complain at the lack of respect doctors and others in the medical profession hold for them, especially when they correct a doctors prescription.”

    Depends what they mean by “correct”. If they mean “changing a drug to the locally approved one despite the fact that the doctor has spent many consultations working out that that particular drug does not suit that particular patient”, then yes, they will lose my respect. Those pharmacists are strangely absent when the patient comes back deeply and quite legitimately unhappy that their carefully tailored therapy has been mucked about with.

  33. markwe said,

    December 5, 2009 at 1:13 pm

    Veronica

    re your comment: “It’s a shitty job but someone’s got to do it!”

    I dunno, but to me it looks like there might also be a dollar in it:

    Top 3 Pharma companies 2008 (by total revenue):

    1. Pfizer Wyeth Profit US$14,111,000,000
    2.Johnson and Johnson Profit US$10,576,000,000
    3. Bayer: Profit US$ 6,448,000,000

  34. the rim groper said,

    December 5, 2009 at 3:12 pm

    What value are publications of RCTs in journals, whether pre or post-marketing, when the journals themselves are simulacra? The fake Merck and Elsevier journals demand that the oversight of clinical research should not be entrusted to pharmaceutical companies.

    It is a fair point that clinicians are not always being given the best information upon which to base their decisions about the value of any particular therapeutic measure. It should not need saying but it is also clear that informed consent from the patient is never informed, where the treating clinician is not given access to the full information.

    Notwithstanding the status of journals being compromised if they do not publish novel and innovative treatment accounts, the answer may be to ensure that every single piece of relevant information is held by a supra-authority/library and is filtered by the staff, for veracity and accuracy.

    Furthermore, that information should be available to everyone, not just clinicians, so that members of the public can forewarn themselves appropriately and not get caught in the inevitable crossfire and conflict of interests between the drug company imperative to market their product (tell lies, and obfuscate unpleasant facts) and clinicians who have a responsibility to know what they are prescribing and what the real risks and benefits are so that they can discharge their duty of care to the patient, in the knowledge that they have tried to do their best.

    Paid consultancies to pharmaceutical companies should not result in the opprobrium of the profession but… it should automatically disbar the pharmaceutical consultant clinician from publishing any research concerning medical conditions which their employing pharmaceutical company are making products to treat. On leaving such a company, the bar should remain in place for life.

    The risk of financial taint and other forms of inducement is too much of an opportunity for the pharmaceutical companies. It is difficult for a career clinician to refuse to advance themselves on foot of promises for laboratories and equipment as as well as funding for research. Drug companies are not altruistic and it is likely that they never will be. The business model to which they subscribe is mutually exclusive with altruism.

    www.the-scientist.com/blog/display/55679/
    www.the-scientist.com/blog/display/55671/

  35. Veronica said,

    December 5, 2009 at 4:46 pm

    markwe

    Yes, it is good business. So it should be, we are working hard to make something people actually need. Like every other public company, pharma companies have a duty to shareholders to give them a return on their investments. But even more important than that, where does the money come from to develop the next new medicine? Yup – out of those profits! So ask yourself how much is being ploughed back into R&D before you criticise.

    And grim roper. Nobody said drug companies have to altruistic, any more than Nike or Coca-Cola or Google. They don’t CHOOSE to subscribe to their business model, it is the only one available to them. They are not charities neither are they government funded. As I have asked further up this thread, how yould YOU suggest they should be funded? By busking?

  36. the rim groper said,

    December 5, 2009 at 11:58 pm

    @Veronica.

    I don’t particularly have a problem with any businesses making money. It is illegal to run a business and not attempt to make money. Trading below the line is fraud.

    The issue is one of trust. The vested interest of the drug company is highly likely to skew any research data that is sponsored by them… in order to present a favourable publication.

    Your sarcastic point about busking is unnecessary. What is absolutely vital is that clinical research produces clean data so that clinicians and patients can be well informed and make the best choices for themselves. Healthcare is obviously a high value business but it is immoral to disregard the health of the patient by withholding vital information and invention, to the detriment of the patient, in order to pursue the greatest return for the shareholders.

    You claim the sacred cow and the high ground of expensive R&D. Where is the result of your much vaunted R&D when Merck discovered that Coenzyme Q10 was depleted by Lovatstatin and then rushed out a patent for the prevention of the statin mediated myopathy and never provided the adjunctive treatment nor did they inform the medical profession. Lovastatin was squeaky clean and only beneficial to the patient, while depleting their CoQ10 and inducing myopathy.

    If you honestly believe that what I have described represents good pharmaceutical company business practice, then I would suggest to you that your moral compass is in need of repair. I have already linked to fake medical journals from Merck and Elsevier, no less. Merck, I would expect to be rapacious and crooked. Elsevier was a highly regarded publisher of medical literature. Now… I would not read their publications with a presumption that they were honestly produced.

    Drug company largesse has always been used to entice clinicians away from their proper field of work. When you see the papers from the clinicians who are therapeutic substance champions and then read the conflict of interests, it is like a Who’s Who of the pharmaceutical industry great and good, with so-called opinion formers being paid a retainer by 10 or 12 companies and then given research grants, lab equipment and speakers fees.

    Just who do you think you are kidding with this line about R&D? All new drugs should be compared by independent testing (free from pharmaceutical industry taint) with the existing products. If they are not substantially better, then they should not be given a product licence. Clinical research should be initiated by clinicians. Drug companies have no interest in providing curative treatments, they are only interested in money. They would prefer the patient to be just unwell enough to keep needing the proposed treatment for life.

    I am that new innovations are tested independently of the inventors interference and that the innovators should have no hand, act or part in the gathering of data, study design nor data analysis. That is the only hope I see for the medical profession getting out from under the yoke of the drug companies, who by your own admission are not altruistic. It should be a fact that is out in the open. All pharmaceuticals should carry a standard warning, something along the following lines…

    These drugs are produced by a company with no interest in whether you live or die or remain in poor health. They are provided to you so that the drug company can make obscene profits and keep their shareholders happy.

    You failed to note the fake, pharmaceutical company inspired journal links in my posting. I would like to here your defence of such blatant subterfuge.

  37. the rim groper said,

    December 6, 2009 at 12:00 am

    @Veronica.

    I don’t particularly have a problem with any businesses making money. It is illegal to run a business and not attempt to make money. Trading below the line is fraud.

    The issue is one of trust. The vested interest of the drug company is highly likely to skew any research data that is sponsored by them… in order to present a favourable publication.

    Your sarcastic point about busking is unnecessary. What is absolutely vital is that clinical research produces clean data so that clinicians and patients can be well informed and make the best choices for themselves. Healthcare is obviously a high value business but it is immoral to disregard the health of the patient by withholding vital information and invention, to the detriment of the patient, in order to pursue the greatest return for the shareholders.

    You claim the sacred cow and the high ground of expensive R&D. Where is the result of your much vaunted R&D when Merck discovered that Coenzyme Q10 was depleted by Lovatstatin and then rushed out a patent for the prevention of the statin mediated myopathy and never provided the adjunctive treatment nor did they inform the medical profession. Lovastatin was squeaky clean and only beneficial to the patient, while depleting their CoQ10 and inducing myopathy.

    If you honestly believe that what I have described represents good pharmaceutical company business practice, then I would suggest to you that your moral compass is in need of repair. I have already linked to fake medical journals from Merck and Elsevier, no less. Merck, I would expect to be rapacious and crooked. Elsevier was a highly regarded publisher of medical literature. Now… I would not read their publications with a presumption that they were honestly produced.

    Drug company largesse has always been used to entice clinicians away from their proper field of work. When you see the papers from the clinicians who are therapeutic substance champions and then read the conflict of interests, it is like a Who’s Who of the pharmaceutical industry great and good, with so-called opinion formers being paid a retainer by 10 or 12 companies and then given research grants, lab equipment and speakers fees.

    Just who do you think you are kidding with this line about R&D? All new drugs should be compared by independent testing (free from pharmaceutical industry taint) with the existing products. If they are not substantially better, then they should not be given a product licence. Clinical research should be initiated by clinicians. Drug companies have no interest in providing curative treatments, they are only interested in money. They would prefer the patient to be just unwell enough to keep needing the proposed treatment for life.

    I am in favour of the position that new innovations are tested independently of the inventors interference and that the innovators should have no hand, act or part in the gathering of data, study design nor data analysis. That is the only hope I see for the medical profession getting out from under the yoke of the drug companies, who by your own admission are not altruistic. It should be a fact that is out in the open. All pharmaceuticals should carry a standard warning, something along the following lines…

    These drugs are produced by a company with no interest in whether you live or die or remain in poor health. They are provided to you so that the drug company can make obscene profits and keep their shareholders happy.

    You failed to note the fake, pharmaceutical company inspired journal links in my posting. I would like to hear your defence of such blatant subterfuge.

  38. markwe said,

    December 6, 2009 at 5:53 am

    Veronica,

    Please don’t think that was a criticism, more so I was pointing out it’s not a shitty job, it’s usually a very good one, and a very well paying one with bonuses for targets met. Sure a huge amount goes back into research, (almost equivalent to the nett profit in some cases) they are looking for the next big thing, and more power to them! But at the end of the day, it IS primarily a target driven, profit driven business.

    1. Pfizer Wyeth research funding 2008: US$11,318,000,000
    2.Johnson and Johnson research funding 2008: NA
    3. Bayer: research funding 2008: US$3,770,000,000

  39. Terry Hamblin said,

    December 6, 2009 at 2:12 pm

    Ben

    You might want to look at the chronic lymphocytic trials. Virtually all the trials choose chlorambucil as the comparator. Chlorambucil is a 50 year old drug that is as cheap as chips. All the new drugs are very expensive, some impossibly so. Yet it is standard practice to use a dose of chlorambucil that is about half that which has been shown to be most effective.

  40. thinkerhead said,

    December 6, 2009 at 6:26 pm

    The financing of drug development is based on licence fees or excess margin on sales supported by the artificial device of intellectual property [patent] protection. This protection is offered in exchange for full disclosure and active public exploitation. By selectively non-reporting clinical data, the patent holders seem not to be meeting their obligations which should call into doubt the appropriateness of patent protection.

    This patent monopoly system motivates other undesirable behaviours. Examples include:
    (1)Lack of collaboration between researchers resulting in duplication of work,
    (2)Active acceptance of costly and time consuming approvals processes by the major companies because this raises the bar against smaller competitors,
    (3)Avoidance of treatments for sub-populations and diseases of the poor,
    (4)Delay in improving side issues like purification and new delivery mechanisms so these tiny improvements can extend patent cover. (see zopiclone),
    (5)Criticism and supression of (inexpensive) drugs not on patent cover.(Read Terry Hamblin, above)
    (6)Preference for patentable recurrent treatments rather than cures.(Consider the parlous state of the vaccines industry)
    They might not all be happening, but the system motivates for them.

    On that topic, Ben, it might be revealing to see how the reported comparative efficacy/safety of drugs varies with patent cover.

    Governments can and do override patent law on military issues. Perhaps they should consider doing so on healthcare issues. State procured research could be funded by saving the ‘patent margin’ on drugs. Not a perfect mechanism, but at least it would save Veronica from too much busking.

  41. Guy said,

    December 6, 2009 at 8:28 pm

    Like Ben, I feel the situation is anything but healthy. As part of my job I often do literature searches on drugs being put forward for a UK county approval committee. The standard of evidence of efficacy in many of these drugs is very poor and often relies on evidence from tiny numbers of drug company sponsored trials. The use of multiple primary end points and cherry picking of stat. significant but clinically insignificant results is rife.

    I’d love to believe that the situation is being cleaned up. Yet what we are talking about is the best part of pharmaceutical company evidence. Drug reps pushing drugs to doctors on dubious evidence is not education, I’m sorry to say Veronica. When I occasionally see drug reps and they talk about drugs that I know the evidence for, I am often unsure if we’re talking about the same drug.

    Most doctors have neither the time nor inclination to carry out literature reviews. If the general public fully comprehended the evidence base that much of the prescribing by GP’s is based upon, I suspect they would be horrified.

  42. Veronica said,

    December 7, 2009 at 1:07 pm

    Well, thank you, Thinkerhead, for sparing me from busking. I don’t think I would make much money from it. I’m concerned that you have a problem with patents. Without the guarantee that a company can exploit its own inventions without being mercilessly and cheaply copied by others, why would anyone innovate in any field? In pharma, where the R&D for a product can cost up to a billion dollars, the impetus to spend all that money would vanish overnight if there were no hope of a return.

    There is always an argument that the third world needs cheap drugs and cant afford them. The third world could also use cheap mobile phones, cheap agricultural equipment, cheap water and energy, but nobody pillories the relevant companies for not providing them at below cost price. The trouble with pharma is that health is a very emotive subject, and people see the purchase of medicines as being different from the purchase of other goods.

    Guy – I wonder how much doctors are taught about the evaluation of clinical data, and the structure and statistical analysis of a good clinical trial. Perhaps this is an essential part of their education. More savvy consumers might lead to better quality studies and fewer opportunities for pulling the wool over their eyes.

    One thing forgotten in this debate. The people working ni pharma generally believe in what they are doing. They are excited to be making a difference to people’s health, they want to change the world for the better. It is a business full of altruists. They work inside the system because it is the only one there is, and they are not all unreformed breadheads who will push any drug at any price.

  43. the rim groper said,

    December 7, 2009 at 3:01 pm

    @ veronica who said:

    “One thing forgotten in this debate… ”

    Quite: the people who have been ruined by 2 decades of pharmaceutical company secrecy over the issue of stain induced myopathy.

  44. skyesteve said,

    December 7, 2009 at 3:39 pm

    @Veronica – I don’t doubt the sincerity of your final paragraph – for the vast majority of “coal face workers” I’m sure that it’s true.
    However, I think the point Thinkerhead was trying to make is that company’s can (and do) manipulate the patent system and that can be a wee bit annoying for clinicians.
    The typical scenario is where ethylmethyldishwater is coming off patent soon so the company withdraw it but re-introduce it – oops, sorry, replace it – as new, improved neo-ethylmethyldishwater so that people who were on the orginal are switched to the neo- before the patent on the original lapses. By then both patients and docs are uncomfortable with changing back to the old, off-patent version. I don’t think that that kind of behaviour, which does go on, is very altruistic.

  45. Jbags said,

    December 8, 2009 at 1:24 am

    @Veronica

    I agree on the point of providing cheap drugs to the third world. Health is an emotive subject, and more than that it is the main priority of provision for the third world (see the Copenhagen Consensus from 2008, although it isn’t without controversy). However, here I think the mistake is to put the onus for healthcare provision on the drugs companies.

    There is a significant cost involved in selling these drugs at prices that benefit the third world (not to mention funding the supply chain and infrastructure in the destination countries to make sure the drugs actually reach the most needy). This should not be entirely taken on by the drug companies. By all means they should contribute, but bearing in mind that the profit margin of these companies equates almost directly to research funding, you can see how counterproductive it is to take bites out of this profit margin.

    If we, as a nation, and others care about the provision of cheap medicine to the third world, then its our government and others who carry out this scheme (in conjunction with the drug companies) and we, the taxpayers, can fund it.

    If you’re not willing to spend your tax pennies on these cheap medicines for the third world, then its hollow to suggest the drug companies are at fault for not doing so.

    Oh and by the way, when I was working in East Africa, the mobile phone business was absolutely booming, and was far more developed than the pharmaceutical industry. Mobiles outnumber landlines by more than 10 to 1, and in my experience, if there was electricity, there would be someone selling mobile phone top-ups. Time for medicine to catch up?

  46. reprehensible said,

    December 8, 2009 at 2:37 am

    Having worked as a drugs rep I tried to help launch a new product for COPD which rightly got me laughed out the room a couple of years back. It effectively ruined the company who sunk £3m into marketing it. At the time some of us told senior management they were walking before they could run but they never listened. Serves em right.

    www.nelm.nhs.uk/en/NeLM-Area/Evidence/Drug-Specific-Reviews/SMC-rejects-erdosteine-Erdotin-for-symptomatic-treatment-of-acute-exacerbations-of-chronic-bronchitis/

    The real shame though was that research should have been done as there was some uninvestigated potential, particularly w.r.t. antioxidant properties. It caught the attention of one international expert who felt the same way and we got lots of good but sadly anecdotal (yeah, big deal) feedback from Dr’s at the time.I hope it’s being done now, but I doubt it.

    A 2007 analysis of 1016 systematic reviews from all 50 Cochrane Collaboration Review Groups found that “44% of the reviews concluded that the intervention was ‘likely to be beneficial’, 7% concluded that the intervention was ‘likely to be harmful’, and 49% concluded that evidence ‘did not support either benefit or harm’. 96% recommended further research.” (El Dib R, Atallah A, Andriolo R. (August 2007). Mapping the Cochrane evidence for decision making in health care. J Eval Clin Pract 13 (4): 689–92. Available at doi:10.1111/j.1365-2753.2007.00886.x [Accessed December 2009]) – yes this bit was cut and pasted from an essay.

    I’ve quite the drug rep thing now and am using what some of you will probably think of as my ill-gotten gains to do an MSc in Health Management. Last I knew the NHS spent 70% on salaries and 15% on drugs though. I’m now discovering the real issue is not so much evidence- based medicine but evidenced based application of medicine which has a much worse base, though I am biased. True the ball games different with management but science here is still possible as earlier Bad Science articles have highlighted

    The preston curve shows it takes an average yearly income of about $5000 dollar per person to effectively ‘cure’ (mitigate) all communicable disease. After than it’s essentially an expensive flat curve trying to cure chronic stuff at least the public level.

    Sure health care professionals need a good evidence to base best practice on, but I’d be inclined to say it needs to be of appropriate quality and more with a greater slant on application. The real problem we have to address is appropriate rationing, including of research.

    Wow, I’ve not even mentioned the Whitehall Study once, doh!

    @ Ben, gutted the vice chancellor wouldn’t stump up your expenses in cash out of his own pocket to come for you to come give his sold out lecture in York Uni’s biggest hall. He only makes 200 grand plus a year though and trains from London are expensive. None of the student soc’s ever had a problem paying me in cash to DJ round the uni, hope something gets sorted next yr. I’d offer you a lift from the station but the company car’s gone back.

    @ anyone who links journal articles here, cheers, they’re proving a good source of info for coursework!

  47. ferguskane said,

    December 8, 2009 at 10:04 pm

    @Veronica..

    That response is a little silly and misses the point. I know full well how the system works. I was simply pointing out that your rather snide comment about who should fund studies was illogical, as, in the end with universal health care, the taxpayer obviously pays the bill. Without universal health care it is a little more complicated, but essentially it still pans out much the same.

    And yes, I know free drug lunches are a misnomer, because in the end, not only does the taxpayer pay for the lunches, they also pay the drug reps’ salaries. If Doctors need a new lunch to be interested in advances in medicine, I think we have a problem. As a psychologist who willingly, but not unquestioningly accepts the value of pharmaceuticals, I will attend a talk if I think it will be useful, balanced and fair, or at least thought provoking. I have attended drug rep talks, and they do not generally meet those criteria.

  48. Guy said,

    December 8, 2009 at 10:38 pm

    Veronica,
    you state “They are excited to be making a difference to people’s health, they want to change the world for the better. It is a business full of altruists”.
    I’m afraid that I don’t recognise that industry that you describe. I have worked in and know too many people in the pharma industry to regard it as packed with altruists. It’s a business like any other. Slightly more careful these days but still a business. Lets not pretend otherwise.

  49. the rim groper said,

    December 8, 2009 at 11:33 pm

    hmmm… no Veronica. What does that portend?

    You make your points then wont respond to the rebuttals. Medical practice has been in thrall to empty pharmaceutical promises for rather longer than I care to remember.

    The promise of a quick fix for a medical problem is hardy different to the peddling of heroin and the promise of removing all of life’s trials and problems. Justify the selling of pharmaceuticals in return for empty promises and set it against the dealer selling a hit of heroin in return for empty promises. Why is one a criminal act and not the other?

  50. Jbags said,

    December 9, 2009 at 1:23 am

    @49

    You compare the other side to a heroin dealer and you’re surprised when a response is not forthcoming? Smooth.

  51. the rim groper said,

    December 9, 2009 at 8:00 am

    @Jbags.

    Thanks. :)))

    It may have escaped your notice that the lack of response to which I was referring was prior to No. 49 but why let the facts obscure an empty point, eh?

    I have seen pharmaceutical publications (for the drug industry) which encourage pharmaceutical sales on a global scale. The scope of those plans is truly breathtaking and the tip of that iceberg is listening to clinicians advocate putting drugs in the water supply or creating a polypill that we must all take for life to ensure our good health!

    Lawks a mercy! Clinicians, please wake up!

    Until medicine and clinicians stop this blanket prescribing of panaceas that are positively harmful, I don’t see much hope for the poor patient. I for one am glad to see that good information is getting past the gatekeeping system of white coats and “we know what is best for you” paternalism.

    It was George Bernard Shaw who had written – “All professions are a conspiracy against the laity” and he just may have been correct.

  52. Guy said,

    December 9, 2009 at 8:28 am

    Well said Jbags. There is something between a beautific vision of white labs filled with altruists and one packed with sleazy dope dealers. Sometimes they do make a drug that makes a real difference. But then they know that and the marketing becomes about education. Most are not as good as made out or simply ME TOO drugs. We should however make a distinction between the marketing people and the research people. Certainly more altruism in the later even if they work for the same company.

  53. the rim groper said,

    December 9, 2009 at 10:31 am

    @ Guy,

    who said: “We should however make a distinction between the marketing people and the research people. Certainly more altruism in the later even if they work for the same company.”

    qv www.medpagetoday.com/MeetingCoverage/AHA/7267

    Dr. Grundy disclosed possible conflicts of interest with Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Fournier, GlaxoSmithKline, Kos Pharmaceuticals, Merck & Co., Merck/Schering-Plough, Schering-Plough Pharmaceuticals, Pfizer, Sankyo, and sanofi-aventis.

    Dr Scott Grundy is a leading light of both the AHA and the NCEP and he recommends statins while being paid by all of the pharmaceutical companies that produce or sell statins.

    Altruisim of research people? You are most definitely having a rather large laugh.

    Mute witness is the perennial catfight among the junior clinicians, who fight to publish any old tat just to get their name on worthless pieces of paper, which they attempt to dignify with the ascription, research.

    At Grundy’s level it is about his status and the perception that he is an opinion former (albeit wrong) and the largesse that accompanies that status… from speaker’s fees, research grants, free holidays (scientific conferences) and lab equipment (personal toys). To pretend otherwise is avert one’s gaze from the trough in which many clinicians actively seek to become embroiled.

    Certainly this is not the aim of every clinician nor every research clinician but the rewards that accompany success in the field of medical research are sufficiently attractive as to override all other considerations for a large number of aspiring clinicians.

    I don’t object to people making money however they choose. I do object to the notion that their research is worth reading.

  54. bodenca said,

    December 9, 2009 at 1:23 pm

    TRG (#52 and others), you’re OTT. This is a messy world for researchers. Attack bad science when it happens, but don’t attack scientists merely because they are shown temptations.
    I commend a point Veronica made way back (and checking, I see it was addressed to you then). “Drug companies … … don’t CHOOSE to subscribe to their business model, it is the only one available to them.” If a company chose to pull out of the pharma business, would it improve matters?
    Now you attack the individuals involved. Researchers have a rotten choice. In simplistic terms, would you choose to work for the money boys, whether in pharma, oil, economics, or whatever, or be irrelevant? Yes, it is a good idea that they should be kept aware of the seamier side of the business, and sites such as this can help with examples and arguments. But attacking motives of people you don’t know isn’t going to attract Veronica’s colleagues here.
    Also, you can include universities in that same rotten choice. Staff have been sacked for not demonstrating that they have been invited “speakers”, brought in “research grants”, contributed to “scientific conferences” and obtained funding for the “lab equipment” that you complain of. They are no more to blame for this than pharma scientists.
    Some of their work is still worth reading!

  55. the rim groper said,

    December 9, 2009 at 3:03 pm

    bodenca, I am suggesting that the work is effectively worthless once it has been motivated by huge payments… commissioned by pharmaceutical companies.

    I too have been wined and dined, with no expense spared, back in the days when I thought that clinical research was all that mattered. I believed that I had the best of motivations but really, it was all merely another aspect of the sometimes subtle marketing and I was supposed to be a pliant tool of the pharmaceutical companies concerned.

    Extended stays in hotels at £600 per night in Geneva, first class flights in small private jets to anywhere required, international travel as a perquisite of the research. the only time I was happy with my published research was when it appeared as novel research in a high impact journal and I only had to give my time to the project. No money or external influences were at risk.

    It is a mealy-mouthed argument to state that drug companies don’t choose their business model. Of course they do. They don’t CHOOSE to do anything for the benefit of mankind, unless it is profitable. Not for nothing are drug companies the world’s leader in profit making. No other business enterprise comes anywhere near the vast profits made by drug companies.

    I know of one particular patient who was actually deriving benefit and life extension from a particular treatment and when the clinical trial ended so did the treatment. Distraught relatives wanted to pay the drug company to have a chance to continue the treatment and the drug company’s answer was… “we are not a charity”, so the patient was consigned to die.

    Nice ethics.

  56. Jbags said,

    December 9, 2009 at 3:50 pm

    Your anecdote is neither here nor there. these companies aren’t charities, and that sucks for huge numbers of people – especially those in the third world who can’t afford basic courses of antibiotics. But that’s got nothing to do with anything.

    Yes, they are motivated by profit maximisation. Luckily, by maximising their profits, they are benefiting mankind (through drug provision and development), this is nothing new – I wrote essays on this back in university. The existence of imperfections does not equal a broken system.

    I also beg you to look at the Oil and Banking industries for record level profits, both outstrip big pharma. JP Morgan alone controls over $88tn in assets, over 120 times the global spending on prescription drugs. A measely average one percent return on its assets would account to profit in excess of global prescription drug -revenues-. Big pharma… small fry.

  57. Jbags said,

    December 9, 2009 at 3:56 pm

    Edit: on double checking my figures, I misremembered the table, it is not only JP Morgan’s assets but Banking Industry Assets.

  58. Guy said,

    December 9, 2009 at 4:44 pm

    Rim Groper, I started out disagreeing with Veronica describing pharma as packed with altruists. Then you seemed to cast me as an apologist for the drug industry. The rabid scatter gun approach that you throw at them is to my mind, way over the top.

    Yes there is a lot wrong with the way that research is produced and disseminated. We want to improve the system in many ways, but it’s not really within our power to overthrow the capitalist way of doing business.

    I’d prefer to treat people like Veronica, who I disagree with but welcome her input, with more respect. Otherwise a forum like this just becomes a rabid rant against big pharma and nobody actually discusses anything.

    Sorry to moan. What do others think?

  59. ferguskane said,

    December 9, 2009 at 5:23 pm

    Others think you’re right, at least this one does. The point about business models is valid. As taxpayers, we have a responsibility to make sure our money is spent well. We can specify and impose regulations should we have the will. We could even propose and support a new model of clinical research. We can do a lot. If we have the will.

    For instance: We could ban the drug company sponsoring of conferences and we could ban drug reps. This could all be done directly and perhaps in the process drive down the cost of conferences. Too radical? We could make sure that registration of trials is mandatory, not self-regulated. We could make business leaders directly responsible for corporate crimes. We can certainly make things work better within a capitalist system.

  60. jcmacc said,

    December 9, 2009 at 8:22 pm

    From #52
    “Dr. Grundy disclosed possible conflicts of interest with Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Fournier, GlaxoSmithKline, Kos Pharmaceuticals, Merck & Co., Merck/Schering-Plough, Schering-Plough Pharmaceuticals, Pfizer, Sankyo, and sanofi-aventis.” Dr Scott Grundy is a leading light of both the AHA and the NCEP and he recommends statins while being paid by all of the pharmaceutical companies that produce or sell statins.”

    Bit of a stretch this allegation, and it is an allegation that Grundy is corrupt. Think sensibly and where’s the dangerous corruption here? If he was paid by one company and he pushed their drug alone, I could see the issue. That could be a company paying a medic to advise people to buy their drug.

    The fact loads of Pharma pay him consultancy fees tends to imply he’s an genuine expert in Statins and they are happy to pay to access his guidance.

    It takes a bizarre mindset to see Abbott, for example, paying someone to “push” a drug class in general when more than 12 of their competitors sell their own versions. It’s pretty indirect corruption.

  61. Veronica said,

    December 9, 2009 at 9:39 pm

    Gosh sorry I’ve been missed, been away toiling in the service of medicine again. Thanks jbags for your supportive comments.

    Medicine in thrall to empty promises, huh? What could it be that is extending our life expectancy then? Better diet? Less poverty? More exercise? LOL. We are not saints in white coats nor are we snake oil salesmen. In all disciplines (R&D, manufacturing and sales and marketing) there are those who are more interested in solving intellectual problems than in saving lives. Get real. I do think there is a lot of altruism in this business. In fact there attractive careers because we combine altruism with intellectual interest and the chance of a decent salary. The people I’ve met in over 20 years in this business? Yes there are a few dipsticks like everywhere else, but generally there is integrity and a sense of commitment to making somebody’s else’s life better.

    jcmacc is right about the doctors who get paid by pharma companies, they are generally very respected doctors who are given small grants (a few hundred $) to attend conferences or maybe asked to review our scientific direction at an advisory board. Or else they act as clinical trial investigators. We pay their modest, economy-class expenses and give them a very modest recompense for their valuable and highly-trained time. If you want to check the rules, see:
    www.abpi.org.uk/press/press_releases_05/051116b.asp

    Would you advise a company for free? Why should they? We are very constrained now, can’t give so much as a pen and some post-it notes to a doctor in some countries. We sponsor conferences without being able to choose or brief the speakers, we provide lunch in order to get busy doctors to attend seminars so we can talk to them about the latest research. What villains we are!

    Why would we ban drug reps? Why is it worse for a drug company to talk to a doctor about its product than for a car salesman to talk to you about buying a new beemer? Why shouldn’t trained professional people be able to help you understand the features of the products you want to use? Doctors don’t know overything (Oh Noes!) and sometimes it does them good to have their memories refreshed about the tools they are employing on our bodies and minds. Is that inherently wrong?

    And rim groper. Many companies do make drugs available for patients to continue at the end of a clinical trial. It is called compassionate use. But no, we are not charities and sooner or later a fair price for what we have made would be nice.

    Trouble is, these little pills look so simple, don’t they, like M&Ms? You have no idea that you are swallowing more high technology than you’ll ever find in your i-phone. But you are.

  62. Veronica said,

    December 9, 2009 at 9:55 pm

    @ ferguskane

    As a psychologist, who pays your salary? Oh. The taxpayer. In fact, the taxpayer pays for all the infrastructure of the country out of his or her tax £, and for all other discretionary goods out of what they have left.

    Wow. We are all paid for by our customers, either directly or indirectly. That’s a revelation.

  63. quasilobachevski said,

    December 9, 2009 at 10:19 pm

    @ Guy – hear, hear.

  64. Veronica said,

    December 10, 2009 at 5:56 pm

    I left a lovely long and well argued post yesterday responding to many of your messages. Alas, it did not appear (cansorship!!! – or ineptitude on my part). I haven’t the heart to try to reconstruct it from scratch. Bleh.

    The first line was… “Gosh, sorry I have been missed, I have been out toiling in the service of medicine.”

  65. the rim groper said,

    December 13, 2009 at 5:04 pm

    @ jcmacc who said:

    “Bit of a stretch this allegation, and it is an allegation that Grundy is corrupt. Think sensibly and where’s the dangerous corruption here?”

    Bit of a stretch? How many statin producing drug companies paying on clinician, does it take to skew the benefits of statins? I have not found the relevant conflict of interests declaration in the NCEP annual report but Grundy calimed that he only received $100,000 for his consultant work that year, although he was also awarded 3 separate research grants.

    You may feel this an unwarranted smear but it appears to me that his wholehearted recommendation of statins is not based in science but based in pecuniary gain. for now, my question is this, how do you become an asset to your employers while not doing what they ask?

    If Grundy was a genuine expert in statins, he would counsel every clinician to stop prescribing them immediately. Indirect or direct corruption is the same to my mind. The semantic game of one form of corruption being better than another is for those who have no wish to acknowledge the truth. If you are being rewarded by a drug company it is because they see benefit in your endorsement not because they like to throw away money to no good purpose.

    The links with the pharmaceutical are a canker in the practice of medicine and I have never heard a valid reason for the close ties that exists between clinicians like Grundy and the masters he serves so well.

  66. ferguskane said,

    December 14, 2009 at 12:23 am

    @ Veronica.

    Again, this is silly, it seems to be a revelation for the person who earlier said:

    ‘If pharma companies do not fund clinical trials in future, then who should fund them exactly? The taxpayer?’

  67. Veronica said,

    December 14, 2009 at 10:13 pm

    @ ferguskane. An extrapolation too far. Government has not got the resources to spend on these studies and they have little incentive to do so. So the pharma companies (whose customers happen to also be taxpayers) can fund them, but direct payment out of taxation would not and does not work. The quality of academic trials is usually not so good. I once had to persuade an academic investigator that buying Sigma-Aldrich lab grade chemicals, putting them through a 0.22 micron filter and injecting them into students was probably not an example of Good Manufacturing Practice.

  68. Henryk said,

    December 15, 2009 at 3:52 pm

    #

    I don’t think Ben can necessarily say that the proportion of positive trials from BigPharma is due to skulduggery of some sort. It could be that once trials clearly are not going to produce positive results, they just get abandoned. What needs to be analysed is if a particular drug is goes through a trial whose results do not get published, and then subsequently a trial using the same drug is published and shown in a positive light.

    I can’t see why trials should not be abandoned once they are clearly not showing the desired results as that would be throwing good money after bad. However whatever results that have been found should be published in a summary form. Perhaps journals could have a section for abandoned trial summaries which let people know why the trial was abandoned. Randi.org

  69. the rim groper said,

    December 15, 2009 at 6:17 pm

    @ Henryk who said:
    “It could be that once trials clearly are not going to produce positive results, they just get abandoned”

    and Henryk also said:
    “I can’t see why trials should not be abandoned once they are clearly not showing the desired results”:

    In both sentences you have used the phrases ‘positive results’ and ‘desired results’ and it is clearly this search for positive results that is the root of pharmaceutical companies engaging in presenting their results in the best light… after all it is just marketing.

    Examine the exclusion criteria for many RCTs and then see how many people are excluded because of their potential to mess up a neatly arranged row of pharmaceutical company ducks.

    Genuine scientific inquiry does not have an endpoint that only looks for ‘positive’ or ‘desired’ results. The negative results are frequently more revealing but when seeing only fulsome high praise for a newly manufactured and presented preparation, my index of suspicion is raised.

    Thalidomide, Cerivastatin, Atorvastatin/Torcetrapib or Vioxx anyone?

    Please see if you can find anything in the literature that supports the reduction of moderate essential hypertension by whatever pharmaceutical means you care to name? I am not talking about the actual reduction by the drug concerned. I am talking about the science behind the rationale for the reduction of blood pressure in cases of moderate essential hypertension.

  70. ferguskane said,

    December 15, 2009 at 10:48 pm

    @ Veronica.

    Again, my point was that in the end, the consumer (taxpayer) pays. However, I think your underlying assertion is that private companies provide better value for money than academia. I’m agonistic on this, in that I still believe there is a role for both.

    I agree that the standard of academic research can be poor, but it can also be excellent. Pharma research may (or may not) be to a higher standard, but Pharma has been caught out manipulating results in a variety of fascinating ways. I’m afraid that I may see the worst of it, working as I do in mental health. I do accept as well that academic research is also sometimes less than ethical and that there is always an agenda that may distort publications.

    In the end however, I think governments owe it to their electorates to commission independent trials to check those of private companies. So yes, governments should commission trials – where prudent.

    As for drug reps, I think the comparison to BMW salesmen is perfect.

  71. foofdawg said,

    December 17, 2009 at 9:50 pm

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  73. Ben Vail said,

    August 6, 2010 at 4:46 am

    @Veronica, “Pharma doesn’t make money unless it helps patients”

    Would you care to justify this claim? Pharma makes money by selling drugs, helping people is often incidental, but it’s by no means necessary…

    Certainly some of the money earned by Pharma comes from it’s products helping people, quite probably most of it… but there’s nothing inate in selling drugs that means you can’t make money doing it if the drugs do nothing; Homoeopathy anyone?

    The world would be a wonderful place if the way to make the most money always was to provide the best service, but sadly, this is not the case. Sometimes they overlap, but if profit is the primary goal, then by definition, optimal service is no longer the primary goal.