by Hannah Sutter
So several million more people are going to be prescribed statins but the vigorous campaign to inject some sanity into statin use has bought into sharp focus the conflict of interests at the heart of our health system.
One is whether the risks of these drugs when taken by healthy people actually outweigh the benefit? What we do know is that the only data on this comes from the manufacturers themselves. Think banks being the sole source of information about payment protection insurance or relying entirely on energy company data to choose the best tariff.
Then there are questions about the commercial interests swirling round the decision making process. If you believed (hoped) that decisions about which drugs will be suitable for prescription under the NHS was free of commercial influence , then you may find the Statin process rather shocking.
For instance 8 out of the 12 members of the NICE committee that recommended doubling the number of prescriptions have financial ties to the companies that make them. The respected Oxford organisation (the CTT) that ran the big analysis that triggered the recent proposal by NICE to recommend statins for healthy people has received hundreds of millions of funding from drug companies, but we know little about the details. And the highly respected research body – the MRC (the Medical Research Council) – that is known to fund the CTT also receives hundreds of millions from unspecified commercial interests.
Any one of these links, which until very recently were never talked about in public, would raise at least a suspicion that the decision about the best way to avoid heart disease was not entirely free of bias, but taken together it’s hard to see how the notion could be avoided.
1) Why do we still not know for sure whether statins are safe and effective?
Remarkably, after twenty five years and at least thirty large scale trials, we still don’t have reliable data either on how effective they are for people who haven’t had a heart attack or what percentage of this group suffer side effects. For those who pin their colours to the evidence based medicine mast, this points to a much wider problem in the way we evaluate treatments.
What makes it impossible at the moment to decide if statins are worth taking when you are healthy is that the only data you have got to go on is not what the drug companies have found out in their trials but only the bits of information they are prepared to publish in journal articles, such as the one published in the Lancet that is driving the NICE proposal. All the rest is a commercial secret.
A handy summary of the problem was set out in a letter to the BMJ this month by professor of public health epidemiology Klim McPherson of New College Oxford. He points out that there is a ‘strong bias in published results’ that it cannot be safe to promote a drug for millions “when almost all the data comes from commercial studies that are not available for public scrutiny.’
2) How to make the CTT transparent and accountable?
At the centre of the relentless expansion of statin prescribing has been the CTT (Cholesterol Treatment Trialists’ Collaboration) a virtually unknown academic body which for years has produced heavyweight meta-analyses of statin trials that regularly found they were safe and effective. What has become clear since independent academics have been challenging these findings is just how conflicted the CTT is.
Thanks to a deal done in the early 1990’s with all the drug companies making statins they hold data from nearly 30 large statin trials which form the basis of their meta-analyses. However a crucial part of the deal was that no other researchers were to see this data.
Do they have all the data from the trials? We don’t know. Do they have all the trials that have been done? We don’t know that either. What we do know is, bizarrely, that they do not hold data on side effects. Instead they rely on the information contained in published commercial trials which are well known to be highly unreliable about side-effects.
With that in mind the attack by Professor Sir Rory Collins on independent researchers who claimed that the CTT studies significantly underestimated statin side effects was chutzpah of a high order. He even claimed in the press that raising doubts about statin safety was killing patients. What about the risks of expanding the use of statins without accurate figures on side-effects?
3) How far is the CTT in bed with the drug companies
As well as revealing the CTT ‘s total lack of transparency the other fall-out from the rumble between Sir Rory and the BMJ has been slew of questions about where the CTT funding comes from. Their website says the British Heart Foundation, the MRC (Medical Research Council) and Cancer Research – all impeccably respectable charities and apparently government funded organisations.
But research by HIUK contributors shows that this is highly misleading. Digging into the financial arrangements of these organisations has not been easy as the CTT is not a specific legal entity but is a division of the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU) which is a division of the Nuffield Institute Department of Clinical Medicine which is part of Oxford University.
So because neither the CTT nor the CTSU are legal entities, as such, it is almost impossible to find out how they are funded or any details of their internal operations. They also don’t publish any annual audited accounts. The CTSU’s official funders are primarily charities who have no obligation to declare any detailed financial information and are not subject to the Freedom of Information Act.
What we have found is a declaration of interest form published here which shows that Sir Rory together with another top statin researcher received £91 million pounds from Merck and an associated company, makers of simvastatin along with other funding. There is no suggestion of impropriety but funding has not been publicly known before. We have also seen another document that puts the drug company funding going to CTT at around 220 million. We would love to know if is accurate, whether it is a full account and any other details.
4) Why is the government’s medical research arm largely funded by drug companies?
As a way of getting more information about CTT’s funding, we looked for information about the MRC’s finances. Maybe there would be a convenient entry saying something like “funds to CTT.” We didn’t find that but we did uncover the biggest surprise so far.
Probably like most people, we assumed that the MRC was a non-commercial body funded largely by the government. An impression reinforced by the opening statement in the Annual Accounts and Report: “The MRC is a publicly funded organisation dedicated to improving human health.”This is closely followed by another on the same lines: “The MRC receives its core funding allocation from the Department of Business Innovation and Skills”
So far so independent. However as you read the Annual Accounts in detail it rapidly becomes clear that the vast majority of their income comes from the drug industry, otherwise described as “other partners and collaborative projects etc”. Their income for 2012/13 totals £194,144,000 which breaks down as follows:
£36,554,000 from the government, £62,512,000 from grants – (no details disclosed) and just £3,353,000 from other income (not disclosed).
Total £102,424,000 which is described as “external income”.
Then there is what’s called “internal income” of £91,720,000 from commercial activities – not disclosed.
So the proportions are this:
- Government Funding -18%
- Internal Commercial Activities -47%
- Grant s – 32%
- Misc. – 3%
We don’t know where the grants come from but if some, as seems likely, are from drug companies that means as much as three quarters of their income is from commercial sources.
The members of the Board of the MRC looks as if they are free of industry connections but the body making the actual strategic and commercial decisions is the Council and that has representatives from Astra Zeneca and Pfizer.
So a major funder of the CTSU (and the CTT) is another secretive organisation with a misleading public front.
5) Why are medical conflicts of interest not taken seriously
In many areas of public life conflicts of interest are taken very seriously. Lady Butler Schloss had to step down from chairing an child abuse investigation because her brother, now dead, had been administratively involved at one point. By contrast the Health Service and certainly that part dealing with decisions on drugs that involve hundreds of millions of pounds appears “intensely relaxed” about it.
The initial response of the head of NICE to the revelation about the drug company links of the statin committee was to say, in effect, they have been declared so what ‘s your problem? But in law once the interest has been declared the conflicted person cannot be involved in the debate or the subsequent decision.
An article in the BMJ last year – ‘Why we can’t trust clinical guidelines’ – set out in detail how common it was and how damaging it could be. Guidelines to use high dose steroids for acute spinal injury, for instance, were in place for nearly 25 years. The decision had been based on a single trial headed by surgeon who was a consultant to the drug manufacturer and was the only person involved in a favourable Cochrane review of the drug.
It’s an extreme example but a recent survey found that 71% of the chairs of guideline committees and 95% of co-chairs had financial conflicts. Eighty four per cent of doctors said they were concerned about industry influence over guidelines. The disconnect between the positive conclusions of a financially conflicted committee advising on the stroke drug Altephase and the findings of independent researchers had deadly consequences.
Lifting the corner of the curtain
Of course it is naïve to imagine that drug companies won’t play a significant part in medicine. But it comes as a shock to even to cynical observers just how pervasive their influence is. Lifting just a corner to the curtain that normally conceals these connections revealed how they contribute to the research, contribute to the charities funding the research body and contribute to the body drawing up the guidelines. We need drug commerce but we must also be vigilant in understanding the stretch of commerce and ensuring that our external examiners are absolutely free of influence in all respects. This should be a basic provision in all health matters.
It’s not a picture that suggests we are getting accurate information about the drugs we are offered and it explains why there is so little appetite for a serious approach to research into prevention. So many conditions can be best managed without drugs but it is the drug companies that have the cash to drive the studies to prove why drugs are best. Perhaps a more rigorous approach to drug review by truly independent experts would bring about a very different approach to Diabetes Type 2 as well as other diseases such as epilepsy.