Tag Archives: clinical trial

Guidelines kill 800,000

A few days ago a friend sent me this headline by e-mail.

‘Guideline Based on Discredited Research May Have Caused 800,000 Deaths In Europe Over The Last 5 Years.’

I would replace the word ‘May’ with these two words ‘almost certainly.’ You would think, would you not, that if any other event in the world, at any time, had killed eight hundred thousand people, this would be front page headlines around the world for weeks, probably months, maybe even years.

Governments would spring into action, those guilty dragged into court. Thousands would protest in the streets, petitions would be signed, laws passed.

The reality is, I am willing to bet, that you have never even heard of this gigantic scandal. It will not have appeared in any national television programme, or newspaper. The blogosphere is also, almost totally silent.

Eight hundred thousand people. Please let that figure sink in for a few moments. If you dropped a major thermonuclear device on Manchester (UK) and killed every single living person, this would be roughly equivalent. If you laid the corpses end to end, the line of dead people would stretch from John O Groats to Land’s End (the entire length of the UK). Walking briskly each day, it would take you two months to pass them.

Think on that.

To an extent the actual guidelines themselves are not the most important thing here. They are now in the process of being changed (although they have not yet been changed). Nobody can be brought back to life, those who could have died – are dead. The issue here is that the processes leading to the creation of guidelines, that have almost certainly killed 800,000 people, are still in place, with no prospect of any change.

Those who have read this blog may be aware of my distaste for medical guidelines, and my concerns about their impact. I wrote an earlier blog called ‘Who shall guard the guardians.’ This outlined some of the problems, but even I was overwhelmed by the sheer scale of deaths involved when guidelines go wrong. I could have worked it out, but never did.

Guidelines are based on evidence, and evidence is based on clinical trials. And major clinical trials are, almost without exception, paid for, run, and controlled by the pharmaceutical industry. The great and good of medicine, the ‘Key Opinion Leaders’ KOLs, who put together the guidelines will almost all have very close connections with the industry. In some cases they will have been paid millions by pharmaceutical companies.

Whether they think so, or not, these opinion leaders are biased. Biased in favour of pharmaceutical products that are promoted through biased research, and launched on an unsuspecting world. And there is no-one out there to check what these KOLs and guideline committees are doing. If, to pluck a name from the air, the European Society of Cardiology (ESC) decides to create a guideline committee, how do they do it?

They choose a chairman, who will be on one of their committees. A well regarded, sound chap, with expertise in the area. He, very rarely she, will then decide on which of his friends and colleagues would be most suitable to be committee members.

They will have a few meetings, gather the evidence together, decide on what best practice should be, and produce their guidelines. No other organisation checks on them, or their decision making, or their conflicts of interest. Or, indeed, the evidence itself.

Yet, when the guidelines come out, many countries will slavishly follow them. They will form the basis for instructions to their medical services. Doctors who fail to follow the guidelines can be censured, or lose their jobs. They virtually carry the force of law.

Something this powerful and important and critical to medical care is dealt with in an almost completely cavalier fashion. Which is, frankly, inexcusable.

I suppose you are wondering what these guidelines were? Well, they were on the use of beta-blockers to protect the heart during surgery. To see more on this story go to the Forbes website

I cannot send you to the article published in the European Heart Journal, because one hour after going up on their website, it was pulled. Here is the comment from the authors of this paper, Graham Cole and Darrel Francis, on the decision of the Editor to disappear the article.

‘Our article is a narrative of events with a timeline figure and a context figure. We had not considered it to contain scientific statements, but we admit that it does multiply together three published numbers.

It is not an analysis of individual trials considering design, molecule, dose and regimen. We published last year the formal meta-analysis under stringent peer review in Heart and addressed the questions, including dosing, in that paper and associated correspondence.

The first of our two EHJ articles merely says that our community, which races to take credit when research-led therapy improves survival, must be equally attentive to the possibility of harm.  The leverage of leadership means the magnitude of either may be far from trivial.

Where our article relayed numbers, we made clear that alternative values were possible. The focus for readers was on how serious the consequences can be when clinical research goes wrong.

We thank Prof Lüscher for highlighting the scientifically important point that the pivotal trial, DECREASE I, has not been retracted by NEJM because the investigative committee did not recommend this. Unfortunately the committee could not have done so, because DECREASE I was outside its brief, displayed on the first text page of the first committee report. Can readers suggest why DECREASE I, from the same trial family, was exempted from inquiry?

We admire Prof Lüscher’s diligence in sending for peer review what we thought was merely multiplication. We await the review of the pair of articles. The first narrated one instance of a pervasive problem. The second suggests what each of us can do to reduce recurrences.

We respect the process Prof Lüscher has set in motion. We ask readers to join with us, and the journal, in maximizing the reliability of clinical science for the benefit of patients.’

Well, I am really glad that this article is being sent for peer review, because – as we know – peer review is a jolly good thing. To quote Richard Horton, Editor of the Lancet:

‘The mistake, of course, is to have thought that peer review was any more than a crude means of discovering the acceptability — not the validity — of a new finding. Editors and scientists alike insist on the pivotal importance of peer review. We portray peer review to the public as a quasi-sacred process that helps to make science our most objective truth teller. But we know that the system of peer review is biased, unjust, unaccountable, incomplete, easily fixed, often insulting, usually ignorant, occasionally foolish, and frequently wrong.’

Let me just repeat that last bit. Peer-review is:

….biased, unjust, unaccountable, incomplete, easily fixed, often insulting, usually ignorant, occasionally foolish, and frequently wrong.

Frankly, I wouldn’t hold my breath waiting for peer-review on this matter.

I suppose you may also be wondering how the problem with these guidelines came to light. Well, it turns out that the chairman of the guidelines committee was Prof Don Poldermans. A man who has now been booted out of his job at Erasmus Hospital in the Netherlands for making up his research. The very research that was used to create these guidelines.

Don Polderman’s also had financial conflicts of interest with Merck, Pfizer, Novartis and Medtronic. To name but four. (One conflict of interest statement can been seen here).

Anyway, here is a summary of what has happened:

      • Don Poldermans had financial conflicts of interest with several pharmaceutical companies
      • Con Poldermans carried out corrupt research, supporting the use of pharmaceutical products
      • Don Poldermans was the chairman of an ESC committee that recommended widespread use of drugs to protect the heart during surgery
      • Widespread use of drugs to protect the heart during surgery has killed 800,000 people over 5 years in Europe (alone)
      • The paper outlining the scale of deaths has been pulled by the ESC

I hope the hell there are no more Don Poldermans out there…..but you would have to be a brave man to think so. Personally, I believe there is an endemic problem with bias and corruption in medical research, and we should be very afraid indeed.