Sunday, 27 September 2015

Docs blowing the whistle on Pharma. Oiling the pharma cogs, greasing the neuros pockets

#MS Research Oiling the pharma cogs, greasing the neuros pockets

Doctors have been taking a self-inflicted bashing at the end of last week, so you may be interested to read this article whilst sticking the boot in.

You may have noticed that ProfG has not been posting as often as he used to. Is it because he is adjusting his life-style or has he been knobbled by Pharma to stop posting negative things:-)

Scientists are surprised by the assistance given to Neuros in many things, so we have "ghost writers "who write the trial manuscripts for the neuros, we have pharma making the posters for many people attending ECTRIMS...Don't believe me, then look out for the corporate branding on the posters and ask how many neuros come and go with poster tubes...(Not many because the companies print and bring them).

http://multiple-sclerosis-research.blogspot.com/2015/07/eurovison-of-ectrims.html

British cardiologist Peter Wilmshurst described in 2012 by the British Medical Journal as a "successful and cheerful whistleblower" began his crusade against dishonesty in medical research in 1986. In the course of the 66-year-old's career, he conducted studies for pharmaceutical and medical devices companies, and unlike many of his colleagues, never hesitated to publish negative results. He's been the subject of multiple cases of legal action and risked bankruptcy and his reputation to expose misconduct in the pharmaceutical industry. Today he advises and supports other whistleblowers with the organization "Patients First."

Read an interview

In your early years as a researcher, a pharmaceutical company offered you a bribe equivalent to two years of your salary: They wanted to prevent you from publishing negative study results. 

"I was just a bit surprised to be offered any money, really. I was a very junior researcher and doctor, only 33 years old, so I didn't know that sort of thing happened. I didn't know that you could be offered money to conceal data".
"Initially we were talking about the results that I'd obtained: That the drug that I had been testing for them did not work and had dangerous side effects". 
"Then the company representatives asked me to leave some of the patients out of the data analysis. Without these patients, the study result would have been positive.When I said I couldn't do that, they asked me not to publish the data. And to compensate me for the work I had done in vain, they said, they would offer me this amount of money".
"They terminated the trial prematurely, and to prevent us from doing more research with the drug, a representative from the pharmaceutical company came to the hospital pharmacy and asked for the stocks. The pharmacist noticed that something was wrong and tried to call me. While he was on the phone the drug rep picked up the box with the drug in it and left."

We know know if trials are going ahead because they are registered on places like clinical trials.gov.  

However there is a publication bias for positive  results and there is no urgency placed on publishing negative results. We are still waiting to see the negative fingolimod data in PPMS. It will appear in som small journal years down the line.

Scientists are guilty of not rushing to publish negative data either. You can sometimes drop in the negative stuff with the positive stuff and am doing this as I write. Likewise last week I put some data into a manuscript that we did in 1990s. Now was the right time to publish this. I am writing a manuscript which is solely negative..it will have a hard time.

You don't want to spend resource on a dead avenue, however sometimes finding out why things don't work is the positive.

However in the clinical case above it is not about burying data about something that didnt work it is about hiding something that was dangerous.

Is research fraud like this widespread?
"I can't tell you exactly what percentage of the trials are flawed. But I think the problem is far bigger than you imagine. And it is getting worse. Because research is getting more important for a doctor's career, and it is so easy to manipulate data, conceal it or fabricate it. Or make unimportant research look like a huge success."

Flaws in trials is one thing but fraud is another and far more serious accusation. There is a move for pharma to deposit the whole trial data set into the public domain for re-analysis. This is being resisted by some pharma, but it is possible to get your hands on trial data..we have done this via a freedom of information request. However pharma could have re-dacted the information. Likewise, the suggestion that it is easy to fabricate, I doubt due to trial monitoring, multi-national nature of trials and the blinded nature of the studies. However things are spotted. I was once at a talk when we were accused of having too varied an EDSS scoring, which made something not statistically significant.

Are studies about drugs with dangerous side effects also systematically hushed up?

"Yes, absolutely." 

Graphic: The Trillion Dollar Pharmaceuticals Industry
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Graphic: The Trillion Dollar Pharmaceuticals Industry

As a hypothetical, it was asked how pharma can excerpt influence 

"Well, I think the way you should do it is to get eminent doctors on your side by paying them a lot of money. Officially they are still independent consultants or university professors, but the truth is, they lose their independence the moment they are on your payroll. What these opinion-leaders say has a lot of weight among other doctors."

What wiil ProfG say to this?...I would add it is none of our business, if you provide a service it is correct that pharma should pay for it.

However, whilst we are stirring it....Have you noticed that the same neurologists appear as leaders of trials, over and over again. Have you noticed that the same speakers present at ECTRIMS over and over again.

Pharma will get opinion leaders to do talks on their products, because they are trusted. Pharma spend money doing surveys to find out who is an opinion leader.

I once got a survey of this nature and they offered to pay £150 by paypal Yes I declared it and paid tax on it!). It was for neurologists... but the way the questions were asked, I could answer without lying..i.e. how many people with MS have you seen this year I said 3,000 because I had just got back from MS life in Manchester.
How many times did I seek a second opinion?. Never.
Which speaker would you listen to Nationally, In Europe and Internationally...ProfG of course.

Thanks for the lolly:-)

However it does back fire, because these opinion leaders can role up to present slides made for them and have not thought about the problem. e.g. If daclizumab is inhibiting CD25 interleukin two receptor it will block Treg function and as daclizumab inhibits MS, it argues that T regs are not that important. The person could not give an answer and looked a real fool in front of one or two thousand neuros.  Anyway  

"I think for many of them enough money is all they need, really. I mean, most people have a price. But of course you have to be very friendly with them, you have to go and talk to them, have lunch with them, discuss the research. They have to forget that it is your aim to make the maximum amount of money".

Some people will do it for the money, but some people see it as a way to make a difference and the money is incidental. (I would bet that this is the majority of cases) My company has offered ProfG some consultancy money and I don't think he has ever requested any. 

I once was offered some consultancy to attend a company meeting. It was interesting that some neuros arrived a few min before coffee and left as coffee (15min break) finished...probably cash in hand. I gave 4-5 hours of my time.

What if the professor produces results in a trial that we don't like?
You have made the principal investigator sign a confidentiality agreement beforehand, so that you have control over the data. And you may put into the contract arrangements for a bonus in case of a positive result. (grins) This may help the researcher interpret the data in a more favorable way for you.

News to me, sounds like footballers bonus, but as contracts for trials in UK is with the universities/hospitals they get any money and not the neuros. In other countries this may not be the case. 

But there's one obstinate researcher who keeps insisting on publishing negative results. And he doesn't accept the bribe that we offer him. What now?

Well, you can try and discredit him, you can try to ruin his reputation and cast doubts on his results. That's what was done with me. And then in the end you can sue him. The threat is often enough to keep him quiet.

In a phase III the data is not going to be in the hands of a single neuro as the company will get a statistician to analyse the data and even in a phase II investigator-led study it will be the statistician who analyses the data. If you don't agree with the conclusion then you remove your name from the paper

Most young people start medical school with very high ideals ...
"yes, at the beginning they all want to work for Doctors without Borders......I think it starts in a very innocent way. You go to a lecture and the pharmaceutical industry provides sandwiches for lunch. You don't think of a sandwich as a bribe, do you? And then you see other people taking more -- money for lectures, tickets to conferences. Gradually you accept bigger and bigger bribes"

The days of company sponsored jollies are being reduced year on year but there will be VIP lounges at ECTRIMS and companies will be bringing Neuros to ECTRIMS. But if I eat an apple with a companies name on it...so what..give people abit of credit.

So many senior doctors are not very good role models?

"Unfortunately not. As a junior doctor what you see is that money is very, very important. Many doctors judge their value to society by how much they earn. Like bankers. If they haven't got enough to drive a Porsche, then they're not a very good doctor"

What do you recon NDG and ProfG. Is cash the driver....I suspect not

"Colleagues and superiors don't trust whistleblowers, because they think it could be their turn to be reported next. Also, the reputation of the medical institution they work for is at risk if a whistleblower reports fraud, so loyalty to your employer is valued higher than the truth. But I think as a doctor your loyalty should be primarily to your patients. And as a scientist it should be to the truth of your research. But I think some people have forgotten what it means to be a doctor and a scientist"

Mushroom food me thinks

What in your view are the most important changes that should be made to prevent fraud?

"Research should be independently checked".

"Since it's the money of the pharmaceutical companies that controls the researchers, it would be important to put a barrier between the company and the scientific investigators. The company could pay the money that is needed to do a study to an independent body, e.g. the Department of Health. The Department of Health then suggests which researcher could do the study, and when the company agrees, pays out the money. So there is no direct contact between the company and the researcher".

So the department of Health picks the very same researchers that Pharma would pick and you have a middle man, taking their slice. The consultancy money will still need to be paid

Who pays for the MHRA, NICE, yes the pharma industry

6 comments:

  1. Great post MD.

    Re "Colleagues and superiors don't trust whistleblowers, because they think it could be their turn to be reported next. "

    The other thing is that all doctors seem to see each other as colleagues. From what I have seen they hesitate in whistleblowing even if the doctors are at different hospitals or GP surgeries.

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  2. Shortly after the diagnosis I've been invited to participate in the phase iii trial of a drug that consistently fails to show effect in ms for decade (at least at relapse reduction), but now marketed as "neuroroprotective". Long story short, but on my screening visit they gave me Edds of 2.5 (I saw that in their internal form). But two months ago when I was at the hospital with my very first relapse, I got 1.5, and i improved from this by the time I came to a screening for a trial. So it is obvious for me why the pharma company now studies this drug as neuroprotectant, because the measures of outcomes in those trials are so vague and easy to manipulate. And could you please explain, how the multi-national nature of those trials or free access to data could help with that? You can put arbitary Edds reading at screening and then lower Edds at the end of the study and voila, it would be positive no matter how many times you will double check the freely available forged data.

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    1. Not sure which drug you are talking about...the one that works by every mechanism under the sun but hasn't been shown to work in progressive MS .....most recently we had laquinimod a pretty useless DMT at controlling relapses but is it neuroprotective?

      We've had woolly outcomes in progression for years but this has not helped pharma find something that works in progressive MS.

      If the trial is in more than one site, no signal investigator is able to manipulate the trial to success of failure and the more centres the more it is easy to spot outlyers and having the data to had allows you to verify if the analysis is correct.

      Trials are blinded and so you don't know which result to fiddle and they may not have access to the before results.

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    2. P.S. trials have many results and some of the outcomes are interlinked and so success in one outcome will be a success in another outcome, if they don't tie-up alarm bells should ring

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  3. What we really need is a discussion among patients about what level of corruption and gladhanding the average MSer should expect before care and services are compromised. The most disheartening reality is that most of the MSers in the support groups I've been in, I would not trust to watch my dog, either due to poor educational background (and who can blame them for not having a uni degree in the sciences!) Or the ravages of the disease itself.

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  4. lol even john oliver is making fun of this - it's old news. question is how to change the system not that it is happening. i don't think petitioning MPs will help change this...
    Bojana

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