an autodidact meets a dilettante…

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Posts Tagged ‘Elizabeth Finkel

The statin controversy

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Never edit your own writing! Brian J Ford.

one thing thing you can be sure of – this claim (posted by a British chiropractor) is meaningless bullshit

I read Ben Goldacre’s quite demanding book Bad pharma some years ago, and that’s where I learned about statins, but I don’t recall much. I do recall that, not long after I read the book, I was at a skeptics meet-up when Dr Goldacre’s name came up. The man next to me started literally spitting chips at the mention – he was eating a massive bowl of chips and was grossly overweight (not that I’m assuming anything from this – just saying, haha). He roolly didn’t like Dr Goldacre. What went through my head was – some people may be really invested in having a magic pill that allows them to live forever and a day no matter what their diet or lifestyle.

I’ve just discovered that Goldacre has a new book out, entirely on this topic, which I intend to read, but my current decision to explore the issue is based on listening to Dr Maryanne Demasi’s talk, ‘statin wars – have we been misled by the evidence?’, available on YouTube. I very much recall the massive Catalyst controversy a few years ago, when a two-part special they did on statins led finally to the demise of the program. Without knowing any details, I thought this was a bit OTT, but when I heard Dr Norman Swann, a valued health professional and presenter of the ABC’s Health report, railing about the irresponsibility of the statin special, I frankly didn’t know what to think.

So statins are lipid-lowering medications that come in various flavours, including atorvastatin, fluvastatin, lovastatin and rosuvastatin. Lipitor, a brand name for atorvastatin manufactured by Pfizer, is the most profitable drug in the history of medicine. I’ve never taken statins myself, and I’m starting this piece as a more or less total beginner on the topic. I’ve read the Wikipedia entry on statins, which is quite comprehensive, with a very long reference list. Of course it’s not entirely comprehensible to a lay person, but that’s not a criticism – immunobiology and related research fields are complex. It’s also clearly pro-statin. It includes this interesting sentence:

 A systematic review co-authored by Ben Goldacre concluded that only a small fraction of side effects reported by people on statins are actually attributable to the statin.[63]

It’s interesting that Goldacre, and nobody else, is mentioned here as a co-author. It makes me wonder…

My only quibble, as a lay person, is that the positive effects of these statins, and their relatively few side-effects, seems almost too good to be true. I speak, admittedly, as a person who’s always been ultra-skeptical of ‘magic bullets’.

Which brings me to issues raised in Dr Demasi’s talk, and not addressed in the Wikipedia article. They include the idea, promoted by an ‘influential group’, that statin use should be prescribed for everyone over 50, regardless of cholesterol levels. Children with high cholesterol levels are being screened for statin use and Pfizer has apparently designed fruit-flavoured statis for use by children and adolescents. Others have suggested using statins as condiments in fast-food burgers, and even adding statins to the public water supply. It’s easy to see how such ‘innovations’ involve making scads of money, but this isn’t to deny that statins are effective in many if not most instances, and we should undoubtedly celebrate the work of the Japanese biochemist Akiro Endo, who pioneered the work on enzyme inhibitors that led to the discovery of mevastatin, produced by the fungus Penicillium citrinum.

But Demasi made some other interesting points, firstly about how drug companies like Pfizer might seek to maximise their profits. One obvious way is to widen the market – for example by lobbying for a lowering of the standard level of cholesterol in the blood considered dangerous. From the early 2000s in the US, ‘high cholesterol’ was officially shifted down from as high as 6.5 down to below 5, moving vast numbers of people onto having a ‘need’ for these cholesterol-lowering drugs. Demasi points out that this lowering wasn’t based on any new science, and that the body responsible for these decisions, the National Cholesterol Education Program (NCEP), was loaded with people with financial ties to the statin industry. To be fair, though, one might expect that doctors and specialists concerned with cholesterol to be invested, financially or otherwise, in ways of lowering it. They might also have felt, for purely scientific reasons, that the level of cholesterol considered dangerous was long overdue for adjustment.

Another change occurred in 2013 when two major heart health associations in the US decided to abandon a single number in terms of risk factors for heart disease/failure. Instead they looked at cholesterol, blood pressure, weight, diabetes and other factors to calculate ‘percentage risk’ of cardiovascular problems. They evaluated this risk so that if it was over 7.5% in the next 10 years, you should be prescribed a statin. A similar percentage risk system was used in the UK, but the statin prescription started at 20%. Why the huge discrepancy? Six months later, the Brits brought their threshold down to 10%. The US change brought almost 13 million people, mostly elderly, onto the radar for immediate statin prescription. The method of calculation in the US was independently analysed, and it was found that they over-estimated the risk, sometimes by over 100%. Erring on the side of caution? Or was there a lot of self-interest involved? It could fairly be a combination. The term for all this is ‘statinisation’, apparently. It’s attributed to John Ioannidis, a Stanford professor of medicine and a noted ‘scourge of sloppy science’. If you look up statinisation, you’ll find a storm of online articles of varying quality and temper on the issue – though most, I notice, are five years old or more. I’m not sure what that signifies, but I will say that, while we’ll always get the anti-science crowd baying against big pharma, vaccinations and GM poison, there’s a clear issue here about vested interests, and the need to, as Demasi says, ‘follow the money’.

This brings up the issue of how trials of these drugs are conducted, who pays for them, and who reviews them. According to Demasi, the vast majority of statin trials are funded by manufacturers. Clearly this is a vested interest, so trial results would need to be independently verified. But, again according to Demasi (and others such as Ioannidis and Peter Gotzsche, founder of the nordic Cochrane Collaboration) this is not happening, and ‘the raw data on statin side-effects has never been released to the public’ (Demasi, 2018). This data is held by the Cholesterol Treatment Triallists’ (CTT) collaboration, under the Clinical Trial Service Unit (CTSU) at Oxford Uni. According to Demasi, who takes a dim view of the CTT collaboration, they regularly release meta-analyses of data on statins which advocate for a widening of their use, and they’ve signed agreements with drug companies to prevent independent examination of research findings. All of this is described as egregious, which might seem fair enough, but Elizabeth Finkel, in a long-form article for Cosmos magazine in December 2014, takes a different view:

.. [the CTT] are a collaboration of academics and they do have access to the raw data. It is true that they do not share that data outside their collaboration and are criticised by other researchers who would like to be able to check their calculations. But the trialists fear mischief, especially from drug companies seeking to discredit the data of their rivals or from other people with vested interests. Explains [Professor Anthony] Keech, “the problem with ad hoc analyses are that they can use methods to produce a particular result. The most reliable analyses are the ones done using the methods we published in 1995. The rules were set out before we started.” And he points out these analyses are cross-checked by the academic collaborators: “Everything is replicated.”

As a regular reader of Cosmos I’m familiar with Finkel’s writings and find her eminently reliable, which of course leaves me more nonplussed than ever. I’m particularly disturbed that anyone would seriously claim that everyone over fifty (and will it be over forty in the future?) should be on these medications. I’m 63 and I take no medications at all, which I find a great relief, especially when I look at others my age who have mini-pharmacies in their homes. But then I’m one of those males who doesn’t visit doctors much and I have little idea about my cholesterol levels (well yes, they’ve been checked and doctors haven’t raised them to me as an issue). When you get examined, they usually find something wrong….

In her talk, Demasi made a comparison with the research on Tamiflu a few years ago, when Cochrane Collaboration researchers lobbied hard to be allowed to review trial data, and it was finally revealed, apparently, that it was certainly not as effective and side-effect free as its makers, Roche, claimed it to be. The jury is still out on Tamiflu, apparently. Whether it’s fair to compare the Tamiflu issue with the statin issue is a matter I can’t really adjudicate on, but if Finkel is to be believed, the CTT data is more solid.

There’s also an issue about more side effects being complained of by general users of statins – complaints made to their doctors – than side effects found in trials. This has already been referred to above, and is also described in Finkel’s article. Many of these complaints of side-effects haven’t been able to be sheeted home to statins, which suggests there’s possibly/probably a nocebo effect at play here. But Demasi suggests something more disturbing – that many subjects are eliminated from trials during a run-in period precisely because the drug disagrees with them, and so the trial proper begins only when many people suffering from side-effects are excluded. She also notes, I think effectively, that there is a lot of play with statistics in the advertising of statins (and other drugs of course) – for example a study which found that the risk of having a heart attack on statins was about 2% compared to 3% on placebos was being advertised as proving that your heart-attack risk on statins is reduced by a third. This appears to be dodgy – the absolute percentage difference is very small, and how is risk actually assessed? By the number of actual heart attacks over period x? I don’t know. And how many subjects were in the study? Were there other side-effects? But of course we shouldn’t judge the value of statins by advertising guff.

Another interesting attack on those expressing doubts about the mass prescription of statins has been to call them grossly irresponsible and even murderers. This seems strange to me. Of course doctors should be all about saving lives, but they should first of all be looking at prevention before cure as the best way of saving lives. Exercise (mental and physical) really is a great form of medicine, though of course not a cure-all, and diet comes second after exercise. Why the rush to medicalise? And none of the writers and clinicians supporting statins are willing to mention the financial bonanza accruing to their manufacturers and those who invest in them. Skepticism is the lifeblood of science, and the cheerleaders for statins should be willing to accept that.

Having said that, consider all the life-saving medications and procedures that have preceded statins, from antibiotics to vaccines to all the procedures that have made childbirth vastly safer for women – who cares now about the pharmaceutical and other companies and patentees who’ve made their fortunes from them? They’re surely more deserving of their wealth than the Donnie Trumps of the world.

So, that’s my initial foray into statins, and I’m sure the story has a way to go. In my next post I want to look at how statins work. I’ve read a couple of pieces on the subject, and they’ve made my head hurt, so in order to prevent Alzheimer’s I’m going to try an explanation in my own words – to teach myself. George Bernard Shaw wrote ‘those who can, do, those who can’t teach (it’s in Man and Superman). It’s one of those irritating memes, but I prefer the idea that people teach to learn, and learn to teach. That’s why I love teaching, and learning…

By the way, the quote at the top of this post seems irrelevant, but I keep meaning to begin my posts with quotes (it looks cool), so I’m starting now. To explain the quote – it was from a semi-rant by Ford in his introduction to the controversial dinosaur book Too big to walk (I’ve just started reading it), about writers not getting their work edited, peer reviewed and the like, and being proud or happy about this situation. This, he argues, helps account for all the rubbish on the net. It tickled me. I, of course, have no editor. It’s hard enough getting readers, let alone anyone willing to trawl through my dribblings for faults of fact or expression. Of course, I’m acutely aware of this, being at least as aware of my ignorance as Socrates, so I’ve tried to highlight my dilettantism and my indebtedness to others. I’m only here to learn. So Mr Ford, guilty as charged.

References

Dr Maryanne Demasi – Statin wars: Have we been misled by the evidence?

https://en.wikipedia.org/wiki/Statin

https://cosmosmagazine.com/society/will-statin-day-really-keep-doctor-away

https://en.wikipedia.org/wiki/John_Ioannidis

https://www.smithsonianmag.com/science-nature/what-is-the-nocebo-effect-5451823/

http://www.center4research.org/tamiflu-not-tamiflu/

Written by stewart henderson

September 9, 2019 at 9:44 pm