Science journalist Maryanne Demasi investigates statins, one of the world’s most profitable drugs. We know statins work. What we don’t know is information about their side effects. Many leading doctors now believe statins are being overprescribed but the raw data on statins remains concealed by the pharmaceutical companies who make them, businesses which are heavily subsidised by taxpayers around the world. This two-part series is the result of an important peer-reviewed article by Demasi. It is NOT medical advice.

PART 1

The Statin Wars

Statins are the most widely prescribed cholesterol-lowering drugs in the world.

Since their introduction in the late 1980s, statins have been a particularly lucrative class of drugs, primarily for pharmaceutical giants Pfizer, Merck Sharp & Dohme and AstraZeneca.

Pfizer’s Lipitor is the most profitable drug in the history of medicine. At its peak in 2006, yearly revenue for Lipitor exceeded $ US 12 billion.

Despite their patents recently expiring, revenue for statins is still expected to rise, with total sales on track to reach an estimated $US1 trillion by 2020. Statins are very big business.

Yet this business is facing renewed calls for transparency from a growing number of doctors who pose these questions: where and what are the side effects of statins if the raw data remain hidden?

In this two-part series, I consider these questions and the responses so far. This is a war for information — The Statins War.

My full peer-reviewed article is published today in the British Journal of Sports Medicine. You can read it here.

The “Side Effects” Data

Who has them and where are the crucial data on the side-effects of statins?

The answer is it is held by the Cholesterol Treatment Trialists’ (CTT) Collaboration; the rather Orwellian title awarded to a group of researchers at Oxford University, led by Professor Sir Rory Collins.

While the CTT Collaboration periodically publishes its interpretation of the data on statins, what it does not do is permit independent researchers to verify CTT results by allowing access to the raw data.

I approached the CTT Collaboration in 2013 when doing research for the ABC’s TV program Catalyst. CTT researchers revealed that to gain access to the data from the drug companies, they would not be permitted to share the raw data with any third parties.

In a written statement, the CTT wrote:

“Such an agreement was necessary……without such an agreement the trial data could not have been brought together for systematic analysis”.

What does this mean?

It means a legal instrument which had been drafted by drug companies effectively preserves their monopoly over the raw data of side-effects of statins.

This in itself is a matter for serious concern since science, by its very nature, requires contestibility.

Further, while Professor Rory Collins has assured people that there are “few troubling side effects” associated with statin use even he publicly admits he has not seen the full data set on statin side effects.

The lack of independent scrutiny surrounding statin side-effects has ignited fresh concerns from some quarters within the medical profession.

The conclusions of the CTT Collaboration have influenced international guidelines for prescribing statins and have led to what has been called the ‘“Statinisation”of the population by Stanford University Professor, John Ioannidis.

Sharing data is essential for transparency

Sharing data with other researchers is vital for scientific transparency. It is vital for doctors, their patients and the public interest. It allows for independent scrutiny of the clinical trial results and fosters greater confidence about the true benefits and risks of a medication.

It has been shown that when drug companies sponsor their own clinical trials and withhold the raw data, the benefits of a drug are likely to be exaggerated and the harms underplayed.

Take for example the famous case of the hidden Tamiflu and Relenza data, on which I previously reported. Tamiflu and Relenza are prescription medications marketed to reduce the duration of flu symptoms and reduce hospital complications.

Based on favourable trial results released by the drug’s manufacturer, Australia’s Federal Government spent millions of taxpayer dollars stockpiling these medications in warehouses across the country, ready to dispense in the event of a flu pandemic.

However, a group of researchers demanded access to the unpublished data from the drug manufacturers, Roche and GlaxoSmithKline. A very public campaign pressured the manufacturers into handing over its unpublished data to independent researchers from the Cochrane Collaboration.

Cochrane researchers analysed all the high quality trials, including the new unpublished data and concluded the medications were “largely ineffective” in reducing hospital admissions and complications from influenza, and come with serious side-effects.

The pro transparency campaign

This secrecy has now cultivated doubt about the authenticity of the conclusions drawn by the CTT Collaboration, which may have a profound impact for the confidence of doctors prescribing statins.

“The simple fact that the raw data on statin side effects have not been made available yet, sounds alarm bells and breeds mistrust – something we can do without when heart disease is increasing now in the most statinised populations ever,” says UK cardiologist Dr Scott Murray, President of the British Association For Cardiovascular Prevention & Rehabilitation (BACPR).

“The CTT analysis has some contradictory results that raise doubts about the robustness of the findings,” says cardiologist Professor Vikas Saini, President of the Lown Institute, Massachusetts.

“We cannot trust the conclusions of research derived through a scheme that doesn’t allow us to independently examine the evidence for ourselves. The ‘trust us, we’re experts’ approach to the statin hypothesis has probably been more damaging to science and humanity than many other controversies in medicine,” says Dr Alan Cassels, Drug Policy researcher, University of Victoria, Canada.

The CTT Collaboration, a branch of the Clinical Trial Service Unit (CTSU) at Oxford, assures the public it is “independent”. However, there is growing unease about this proposition of independence as it is now known that the CTSU has received over £260 million in research funding from the pharmaceutical industry, the vast majority of it from manufacturers of cholesterol-lowering drugs.

And so it goes, a growing chorus of leaders in the medical field in a heightened state of unease, denied access to data by a data monopoly preserving agreement, drafted by the funders.

The CTT Collaboration has its say

Just as the pro-transparency campaigners are motivated to gain access, so are those wanting to protect the information.

And they seem minded to play both the man and the ball.

In 2014, Prof Rory Collins said those who spoke out about statin side effects were “far worse” and had probably “killed more people” than “the paper on the MMR vaccine”.

When the Australian Broadcasting Corporation TV Catalyst series, Heart Of The Matter, which I produced, challenged the over-prescription of statins and highlighted the limitations of industry-sponsored trials, it was labelled “biased” with some claiming “the ABC has blood on its hands” or “people will die” as a result of the programs.

One doctor later published an article postulating the program may have caused up to “2900 potentially fatal heart attacks and strokes” as around 60,000 people stopped taking their statins despite there being no fall in the number of statin drugs being dispensed by the Australia’s drug subsidy program, the Pharmaceutical Benefits Scheme (PBS) and the Repatriation Pharmaceutical Benefits Scheme.

“The whole issue is shrouded in secrecy and

riddled with huge financial conflicts of interest,

which does not instil public confidence”

In France also, following extensive media coverage of a book that challenged the widespread prescription of statins, the book was blamed for potentially causing 10,000 deaths if patients stopped taking their statins.

These claims were debunked however when the national statistics showed the actual number of deaths (not the predicted number of deaths) significantly decreased in the following year. Cardiologists later warned that it was ‘not evidence-based to claim that statin discontinuation increased mortality’ and that before scientists made alarmist claims in the future, they should assess the ‘real effects of statin discontinuation rather than making dubious extrapolations and calculations’.

A call to action

Queen Elizabeth’s former doctor of 21 years and the immediate past president of the UK Royal College of Physicians, Sir Richard Thompson says, “The statin controversy is another example of murky conflicts, misleading statistics and abuse of contrarian views that are sadly so frequent in clinical trials. The public will continue to distrust the value of their doctor’s advice if these uncertainties are not quickly resolved”.

“The whole issue is shrouded in secrecy and riddled with huge financial conflicts of interest, which does not instil public confidence,” says Professor Peter Gøtzsche of the Nordic Cochrane Collaboration.

“It’s high time the proper evaluation of [statin] harms is enforced to provide reliable data as soon as possible” says Emeritus Professor Klim McPherson, Public Health Epidemiologist, Oxford University.

Eminent cardiologists have also weighed in on the debate.

“The CTT Collaboration should share their database with independent scientists. That they refuse fosters suspicion. If you have a great result, wouldn’t confirmation make it even greater?” says cardiac electrophysiologist and Fellow of the American College of Cardiology, Dr John Mandrola.

“Unfortunately, until all data is available and discussed with patients, millions of people taking these drugs will continue to have far greater chance of harm than benefit,” says US cardiologist Professor Rita Redberg, University of California San Francisco.

The call to action is growing louder and with it the pressure is mounting on the CTT Collaboration to respond, not with criticism, but with data.

Read Maryanne’s full peer-reviewed article published today in the British Journal of Sports Medicine here.

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Dr Maryanne Demasi is an investigative medical reporter with a PhD in Rheumatology.

You can follow her on Twitter @MaryanneDemasi.

Don’t miss PART TWO tomorrow which analyses why there is such reluctance to heed these calls for transparency.