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, 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.
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 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 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


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.  


  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. the rim groper said,

    December 9, 2009 at 8:00 am


    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.

  2. 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.

  3. 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.”


    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.

  4. 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!

  5. 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.

  6. 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.

  7. 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.

  8. 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?

  9. 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.

  10. 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.

  11. 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:

    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.

  12. 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.

  13. quasilobachevski said,

    December 9, 2009 at 10:19 pm

    @ Guy – hear, hear.

  14. 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.”

  15. 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.

  16. 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?’

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. foofdawg said,

    December 17, 2009 at 9:50 pm

    At least on an american keyboard, the + and = signs are on the same key, you might have meant + and – keys.

    Also, if you have a scroll wheel on your mouse, you can hit CTRL and roll the wheel to zoom in and out in most windows applications (though not all)

  22. Windows 7 Professional said,

    December 21, 2009 at 8:34 am

    COME ON! Microsoft Office 2007 $110 and Windows 7 $139 on, Office 2007 Ultimate
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  23. 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.