Contributed by Dr John Briffa, Aidan Goggins & Zoë Harcombe
HealthInsightUK has a number of contributors who are experts in statins. Here three of them – Dr John Briffa, Zoë Harcombe and Aidan Goggins respond to the CTT investigation. They explain why side-effect data is unreliable and disagree about whether it is in the drug companies interest that the risk of side-effects is downplayed or is that part of cunning plan?
How side effects are brushed under the carpet
As a doctor, it seems utterly perverse to me that we are in a position where bodies we entrust to advise doctors and their patients on treatment are basing their recommendations on incomplete data. We simply don’t know what the risk of harms of statins are, but somehow this is accepted as ‘just the way it is’. Quite frankly, it’s just not good enough and does us a huge disservice.
However, even if we manage to get hold of the relevant data on adverse effects, there is still a very real risk it will not accurately reflect these risks in the real world. Sometimes, before a study gets underway, individuals who are in poor health and perhaps at increased risk of side-effects are identified and eliminated.
Yet, in the real world, even people who are poor candidates in this respect may end up being prescribed a statin. Individuals with a history of problems such as muscular pain or damage to the liver or kidneys (all of which can be exacerbated by statins) are typically excluded from studies too, further reducing the chance that side-effects will arise in the study proper.
Even those who make it through this screening process, however, may be subjected to what is known as a ‘run in’ period prior to the study. Officially it is a chance for researchers to weed out individuals who are ‘non-compliant’ (do not take their medication as instructed). However, it also provides an opportunity to detect individuals who are susceptible to statin side-effects and stop them getting into the study proper.
When side-effects go missing
In other words, in formal studies participants are often at a significantly lower risk of side-effects than those in the general population.
Another problem with conventional studies is how side-effects are defined. Muscle pain is a quite-frequent side-effect of statins. In extreme cases, statins can cause a break-down of muscle tissue known as ‘rhabdomyolysis’ which can have potentially fatal consequences. In some studies, the focus has been on rhabdomyolysis, which means less severe side-effects such as muscle pain or fatigue may ‘go missing’.
Another way in which the bar for side-effects can be set very high concerns the blood parameters used to detect damage. For instance, in some studies damage was only deemed to have occurred when enzyme levels (a marker for damage) were several times higher than normal upper limits.
It’s almost as if studies are designed to have statins look as safe and non-toxic as possible. And after all this, we still rarely get to see the original data. One wonders what there is to hide.
By Zoë Harcombe
Drug company money behind downplaying side-effects
Following the announcement last month that NICE was proposing to put millions more on statins HealthInsightUK reported the conflicts of interest behind the chair and other members of the group that developed these guidelines. It’s a who’s who of the cholesterol-lowering industry.
The Guideline Development Group (GDG) for NICE not only recommended far wider use of statins, they recommended atorvastatin specifically. This was branded as Lipitor by Pfizer, earning an eye watering $125 BILLION in sales over 14.5 years.
The NICE full draft references the 2012 Lancet article produced by the CTT that advocated statin therapy for healthy people. And note the use of the word “therapy” alongside “statins”. To establish the association of healing and curative power from the outset (headline) of the article.
So did GDG manage to obtain from CTT the Serious Adverse Effects information that other medics have failed to acquire? Did they even try? We aren’t told.
In fact the CTT 2012 Lancet article dismisses “potential hazards of statin therapy” as quickly as it raises them: “a small increased risk of myopathy”; “more rarely of rhabdomyolysis” [can be fatal that one]; “statin therapy might increase the risk of haemorrhagic stroke”; “statin therapy might be associated with a proportional increase in the diagnosis of diabetes of about 10% and more intensive statin therapy [still therapy :-)] produces a bigger increase.” The latter would explain the Lipitor Diabetes lawsuit gathering pace in the US (http://statin-diabetes-lawsuit.com/).
Companies behind the CTT
Drug company studies are infamously poor at reporting the side-effects of drugs. Just as the NICE Guideline Development Group lists every drug company you can think of, so the CTT conflicts of interests report that “most of the trials in this report were supported by research grants from the pharmaceutical industry.”
The first listed member of the secretariat of the CTT is Colin Baigent – the man who was in the Daily Mail the day after the NICE announcement to offer his conflicted view. Baigent’s logic was quite remarkable - half the deaths from coronary disease occur in people who have no risk factors, so we should medicate them because they have no risk factors.
The CTT Lancet article declared that the CTT collaboration has observers. The observers are Bristol-Myers Squibb, Merck, Laboratoires Fournier, Novartis Pharma, AstraZeneca and Pfizer.
Seen in this light Baigent’s response to the Australian journalist (reported in CTT: House of secrets) makes sense. “The CTT secretariat has agreement with the principle investigators of the trials … that individual trial data will not be released to third parties. Such an agreement was necessary in order that analyses of the totality of the available trial data could be conducted by the CTT Collaboration.”
Pull the other one. Such an agreement is necessary to protect the interests of the companies who stand to lose billions if unfavourable data is released. That’s why observers are present. That’s why the drug company web runs through CTT, NICE and the bodies that are supposed to be acting in public interest. And who is acting in the interests of the doctors who do not wish to inflict harm? Or the patients who do not wish harm inflicted upon themselves?
By Aidan Goggins
Why Big Pharma Want Statins to Fail
The obvious message from the investigation into CTT and Dr Briffa’s comment in this post is that we are not getting a true picture of the extent of statin side effects. Little cynicism is needed to think that vested interests may be involved in keeping the true level of side effects hidden.
After all, these drugs are stupendously profitable. In the US, during the five years between 2007 and 2012, the number of prescriptions increased by 17% to a staggering 214 million monthly prescriptions annually. And now with the new 2013 American Heart Association Guidelines classifying millions more in need of the drugs, plus talk of approving a low dose over-the counter statin, sales of the most widely prescribed drugs in the world looks set to soar again.
Protecting such a cash-cow is surely a high priority. But maybe not. Whilst this may have been true in the past, the truth is that for Big Pharma statins have served their purpose. Despite ever rising sales, these blockbuster drugs have become a drag on drug company profits. In fact the only way they can capitalise on the massively lucrative cardiovascular disease market is for statins to now fall out of favour with the medical community.
This is why. Take Pfizer, the biggest drug maker in the world, worth 200 billion it’s a bell weather pharmaceutical company that has always showed good returns and sustained growth to shareholders. Actually that was true until the end of 2011, when everything started to go wrong. Then its global revenue was over $65 billion. But in 2012 that nosedived to $55 billion and it continued dropping in 2013 to just over $51billion. A further fall is projected for 2014.
This disastrous decline can mostly be put down to a single reason; the expiry of the patent on Pfizer’s blockbuster statin drug Lipitor®, (atorvastatin) at the end of 2011. In its hay-day, worldwide annual Lipitor® sales hit $12.9 billion. In 2012 (post patent expiry) they collapsed to $3.9 billion, and in 2013 they dropped a further 41%. In the US – Pfizer’s largest market – the decline was 54%.
New more expensive drugs on the way
When a patent expires copycat (generic) drug companies can begin selling the drug at a fraction of the price so despite booming sales the company’s revenue crash and will never recover. Unless… something changes. One of these could be that data is finally released that shows statins are not as safe as we were led to believe, possibly not as effective either. As a result the risk/benefit ratio is reversed. Clinicians fall out of love with these one-time wonder drugs.
This leaves the massive market for treating and preventing cardiovascular disease without a product. The solution of course is a new drug that can be shown to be more effective and safer than statins. In fact the process has already happened. Pfizer has begun phase 3 (the last stage) trials on its new cholesterol lowering heart disease drug called Bococizumab, which it hopes to bring to market in the next few years.
I don’t know about you, but if I was Pfizer, rather than lobbying to try a maintain a sliver of the massive statin market, I think I’d much rather for statins to fall out of favour, and instead push my new drug – that comes with a new patent and a price that will recreate those sky high revenues.
So don’t be surprised if in the next year or two the CTT trial data becomes available. Don’t be surprised if it shows statins are not as great as they are claimed to be. And definitely, don’t think that this comes as a blow to Big Pharma.