Risperdal: yet another instance of wrongdoing and decietful science
This commentary incorporates suggestions for combatting the tidal waves of bad and dishonest science, flooding over us all via the medical journals that we read. Quite a long time ago I wrote about the dishonest practices and bad science in the field of atypical antipsychotic drugs, which have been a multi-billion-dollar source of income for big pharma for a couple of decades now. The original piece that I posted on this website about ‘Antipsychotics and Humpty Dumpty’ was republished in the Carlat psychiatry report in an abbreviated form, sometime later (1).
In that article I made passing reference to risperidone and the chicanery that had been engaged in to make it appear good (Huston et al.), better than haloperidol — which was of course going out of patent — and better than the other competing ‘newer’ drugs.
In the process of researching that commentary I contacted the Prof Leucht (2), who had written the meta-analysis relating to the relative merits of various of these drugs, including risperidone. I was enquiring of him why they had not referenced and discussed the paper ‘Redundancy, disaggregation, and the integrity of medical research’, by Huston et al. (3)*** when discussing the possibility of bias, fraud, and unpublished studies etc. His answer was that they were simply not aware of it. I do not suppose they searched the scientific data using words like fraud, dishonesty, etc. Many doctors are insufficiently ‘street-wise’ and insufficiently sceptical, or cynical. See also (4).
*** The title is a science-journal-acceptable way of saying ‘lying and cheating’.
That is an example of how even carefully done meta-analysis is often seriously flawed without anyone noticing it (except me, it seems). A sort of ‘whoops, we did not know the castle was built on sand’ moment.
I have done quite a lot of writing about bad science and fraud in science (see main menu ‘Bias in science’), but no amount of writing about it is going to change anything unless people decide enough is enough and take actions.
There are so many quotes and references one could give on this subject that it is difficult to choose: I will offer you the words of the retiring British medical journal editor of some years, Richard Smith (5, 6), that ‘Journals have devolved into information laundering operations for the pharmaceutical industry’: but see also my other commentaries on bad science, especially ‘Why Most New Antidepressants Are Ineffective: And How Pharmaceutical Companies Have Deceived Doctors’.
Part of Smith’s writing is a sort of mea culpa about why it took him so long to realize he was being duped as editor of a top medical journal. I will record the fact that I wrote to him, in response to something in the BMJ, a while before he resigned, to tell him I thought he was being duped. I like to think I may have played a small part in his ‘conversion’.
So, I wonder if this series of articles about risperidone (Risperdal™) in the ‘Huffington Post’ will precipitate anything useful? other than spreading the appreciation of the negative aspects of naked capitalism. Capitalism caught in flagrante delicto, as it were.
The big picture: information generation and dissemination
The misleading drug trials that permit big pharma to get their drugs approved are possible mainly because big pharma often has control of all the data from clinical trials (doctors have very naively allowed them to gain that control), that is but the tip of the ice-berg. Big pharma exerts considerable control over post-graduate medical education, medical journals, and the whole environment of information that doctors are exposed to on a day-to-day basis. Furthermore, big pharma has gained a strong influence over, or even control of, much of the process of legislation about drug licensing, the FDA, the formation of clinical guidelines, and more.
What are the ‘nutrients’ that have nourished this mutant growth of big pharma control?
The first essential element is getting the data. Patients, who all sign consent forms agreeing to participate in drug trials, and doctors who ‘allow’ them to do that, are giving big pharma control ‘on a plate’. It is like putting the fox in charge of the hen-house. Anyone wishing to understand that a bit more just needs to look at the Huston review (3). If they have possession of the raw data (possession is nine-tenths of the law) they can manipulate it free from control and scrutiny — and we know, beyond any conceivable doubt, they do that ruthlessly and repeatedly (see Huston), despite multi-million dollar penalties for infringements. When one is raking in billions (not millions), that is just a minor cost of doing business.
Trials cannot be carried out without the essential raw material of patients! If patients only signed ‘consent’ forms that stipulated that the raw data must be held and controlled by to an independent party, that would be the beginning of the end of the story — a knockout blow. TKO in the first round, as they say.
There are various other somewhat similar measures that could be enacted as well, perhaps another key one would be to do with the metrics of ‘success’ used to assess researchers, and which determine their chances of progress and promotion. At present the system encourages poor research, multiple small publications (salami publishing) and puts so much pressure on most, that good people do less reviewing for journals. The huge proliferation of published journal titles means that more and more less expert people are acting as ‘referees/reviewers’ and the quality of published work is declining. In my area, much of what is published is simply rubbish. The proliferation of poorer quality material makes the finding of the better stuff more and more difficult, especially now that less researchers utilize the services of independent professional librarians (Journal cost to libraries have become so great that many places can no longer afford a librarian).
So, what goes naturally, hand-in-hand with the above, is a system for ‘rating’ (post-publication), the quality and value of material. That is quite straightforward if you think about what Google have achieved with search engines and advertisements. Such a system would link in to weighing the ‘publication’ metrics of authors in a way that would enable appointments committees and funding agencies to improve their decision making.
The proliferation of 3rd rate publications makes it harder and harder to figure out who is doing good work, and easier for big pharma to artificially elevate the apparent excellence of their chosen, groomed, candidates and place them in prestigious and influential positions (there are various ways they can do that, the bottom line is ‘money talks’). There is little reliable data on this, but I am sure it is much more widespread and consequential than most doctors appreciate. This proliferation of 3rd rate publications*** also makes it hard for ‘ordinary’ doctors, who may not have the ability to accurately deduce the quality of their source, to know what to trust and rely on when they wish to inform themselves with quality information. After I retired from clinical work and began publishing and writing much more, especially about bad and fraudulent science, I went through a period of being angry. I was angry because these dishonest people had caused me to waste so much of my intellectual effort wading through lies and rubbish to reach something approaching good and true science. I could have achieved so much more if I had not so frequently been lied to and conned.
*** There has been a burgeoning of the number of journals devoted to publishing case reports (from < 10 on 2005 to nearly 200 in 2016 (7).
Therefore, any measures that facilitate the better quality science getting a more prominent exposure to doctors will do a lot of good. The IT technology to achieve this already exists and could be applied tomorrow. Let me outline an illustration of this. An algorithm like the ones used in search engines, and to decide on the adverts you are shown, could give a score to published papers weighed by factors like: how long people have spent reading the material, what their professional and publication ranking in the field is, what score they give it on a scale (a more sophisticated version of ‘like’ feature), etc. Not exactly rocket science. So, if I spend a long time reading a paper on ST (as a world expert in that field) that should have a much bigger influence on its’ rating than if a nurse-practitioner from Woop Woop gives it a five-star rating. Such a system does not involve any kind of suppression of ‘non-mainstream’ ideas or any ‘censorship’, it just enhances people’s ability to know what has rated as good science by those more expert.
Big pharma is the predominant influence over clinical drug trials. Those who control clinical trials also control clinical guidelines, and clinical practice and most importantly, healthcare expenditure on drugs. They also strongly influence the general emphasis of healthcare spending. That pretty much covers all bases!
By, ‘the general emphasis of healthcare spending’ I mean, for instance, allocating money to anti-depressants drugs, rather than social and psychological services for the huge numbers of people classified as having ‘depressive illness’. Or, cardiac drugs, rather than sending people to the gym and teaching them to eat healthily.
Another thing many people would not even dream was happening is big pharma’s influence over classification of illness via DSM. That much expands their market.
I could go on: but, the point is that a lion’s share of the problem starts with patients giving-up their data unconditionally, which has allowed big pharma to high-jack the whole process, with very profitable results.
Doctors have acted as pathetic, wimpish bystanders and I am ashamed to call myself a doctor (well, I don’t, I am a clinical neuro-pharmacologist!).
The first step in the campaign to correct this awful & crazy situation is to retain control of the data! This would require some sort of umbrella patient-trials organisation to protect and represent patients, who could supervise the ‘data-collection/protection’ process.
It would be simple to form an independent board of non-pharma research scientists, and other representatives (e.g. community, law etc.), to hold all the ‘raw’ trial data, and provide it to any bona fide researcher to analyse. There are many other similar changes that could be made — but the above is the first essential step.
That idea requires no new laws, no government intervention (although that could help), just the concerted action of individuals. Stop agreeing to participate in clinical trials (stop giving money to the church): things will change very quickly. If patient advocacy and support organizations pick up that baton, and run with it there would be trembling hands, pale faces, and hyper-active descending colons, in big pharma boardrooms over-night.
The message: ‘if patients give their data away unconditionally, they are asking to be screwed, and they have been screwed, and they will continue to be screwed’. Just like people who give money to, or support, the Catholic church (except in that case they are asking for their children to be screwed).
Perhaps I will talk another time about what academia could do, along the same lines, to change the way papers are assessed, and academic promotion regulated. But I am afraid there are many wimps in that camp, so someone may have to put a bomb under them. And indeed, the bomb is the above. If they do not implement such changes then they could be ‘black-listed’ from participating in clinical trials. Patients could achieve that change without any help from laws, government or anyone else.
You have the power, if you wish to use it.
Sadly, my colleagues in the medical profession are somewhat naive and/or lacking in moral fortitude. Or are they just greedily taking big pharma money (If you think I am exaggerating, there is a web site that tells you how many $$$$$ your doctor has got from big pharma (for giving ‘education talks’ to nurses, para-medical staff of all sorts, and even their colleagues).
And we wonder why doctors have not been leaders in dealing with these crucial ethical and scientific issues.
PS. The dogma of RCTs as a gold standard
The dogma of RCTs as the gold standard has contributed greatly to the present situation in which those who control trials control clinical practice, via ‘clinical guidelines’, and aided by the pseudo-science of ‘meta-analysis’, which I now call the phrenology of the third millenium.
Healy D, Cattell D. Interface between authorship, industry and science in the domain of therapeutics. British Journal of Psychiatry (2003) 183: 22-27 & Charlton BG. Conflicts of interest in medical science: peer usage, peer review and ‘CoI consultancy?’ (editorial). Medical Hypotheses. 2004; 63: 181-186.
1. Gillman, PK, Atypical antipsychotics: where is the science, where is the evidence. The Carlat Psychiatry Report, 2013. 11(1): p. 3-5.
2. Leucht, S, Kissling, W, and Davis, JM, Second-generation antipsychotics for schizophrenia: can we resolve the conflict? Psychol Med, 2009. 39(10): p. 1591-602.
3. Huston, P and Moher, D, Redundancy, disaggregation, and the integrity of medical research. Lancet, 1996. 347(9007): p. 1024-6.
4. McLaren, N, Psychiatry as Bullshit. Ethical Human Psychology and Psychiatry, 2016. 18(1): p. 48-57 http://theaimn.com/psychiatry-as-bullshit/.
5. Smith, RL, Medical Journals Are an Extension of the Marketing Arm of Pharmaceutical Companies. PLoS Med, 2005. 2: p. e138.
6. Smith, R, Travelling but never arriving: reflections of a retiring editor. Br. Med. J., 2004. 329(7460): p. 242-244.
7. Akers, KG, New journals for publishing medical case reports. Journal of the Medical Library Association: JMLA, 2016. 104(2): p. 146 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816468/.