The real Avandia story – Glaxo knew the drug was a killer in 1999

This from CBS bnet:
GlaxoSmithKline (GSK)’s decision to settle most of the litigation over its Avandia diabetes drug for $460 million means that former CEO Jean-Pierre Garnier will never testify about why he sent an email in 1999 raising concerns that his diabetes drug had “a high number of CV [cardiovascular] deaths while other glitazones [similar drugs] did not.” Avandia had only been on the market for one month at the time the email was sent, according to a deposition transcript in which the email was read aloud.

The email is one reason why GSK decided today — 11 years after Garnier raised the issue with his staff — to settle about 10,000 cases for $46,000 apiece. The FDA is reviewing the drug’s record for heart attacks and other cardiovascular problems; it will probably be withdrawn from the market or the terms of its use will be severely restricted.

So Garnier and Glaxo knew in 1999 that Avandia was a killer – but it didn’t stop them pushing the drug for 11 more years.

The next thing we need to know is just what data did Glaxo supply in order to get Avandia licenced by the MHRA and FDA?

How did Glaxo manage to pull the wool over the regulators’ eyes?

I’m just asking….


European Regulator Suspends Glaxo’s Diabetes Drug Avandia

Just in:

The European Medicines Agency Thursday suspended marketing authorization for GlaxoSmithKline PLC’s (GSK) controversial diabetes drug rosiglitazone saying the risks of taking the drug don’t outweigh its benefits and that the medicines containing it will stop being available in Europe within the next few months.

The EMA — the decentralized European body responsible for licensing rosiglitazone in 2000 and which held an extraordinary expert meeting earlier this month to review the drug’s safety — said in a statement that “the availability of recent studies has added to the knowledge about rosiglitazone and overall, the accumulated data support an increased cardiovascular risk” from the drug.

The regulator said it therefore decided that “the benefits of rosiglitazone no longer outweigh its risks” and recommended the suspension of the marketing authorization of the medicines.

The decision affects the rosiglitazone-containing anti-diabetes medicines Avandia, Avandamet and Avaglim.

Pressure has increased for the London-based European body to pull the drug, which has been linked to heart failure, after U.K. regulators this month said the risks from taking Avandia were greater than the benefits. The Medicines and Healthcare products Regulatory Agency (MHRA) said it believed the risks of rosiglitazone outweighed its benefits and that “it no longer has a place on the U.K. market.”

Full story here at the Wall Street Journal

Ricky Hatton in rehab to fight his depression

The boxer, Ricky Hatton, is in rehab – but I bet none of his doctors will think about stopping his medication – I’d bet my house on the fact that Ricky will have been prescribed an SSRI or an SNRI.

It’s a classic story – his errant behaviour will have been caused to a great degree by the very drugs that doctors thought might help him

“His father has already been talking to the specialists over the last few weeks,” Max Clifford said. “He and others have been increasingly concerned about his depression and his drinking.

“He met with the specialist today and he was told that his depression is severe depression and that he has a drink problem. The drugs are quite recent.”

“The problem is depression and the drink has been a problem for some time,” Mr Clifford said. “From everything they’ve said, the drugs are a far more recent thing and very much superficial alongside the drink and depression.

“They are very confident if he does what they tell him with the treatment, therapy and advice, he can sort himself out. And he will do what they tell him.”

If only Ricky or Max Clifford could read this blog, they might begin to understand.

I’m sure Ricky has very real problems, but it seems to me like his medication will only be harming him and not helping him get better.

Five years on and the MHRA has made no changes

Below are extracts from The House of Commons Select Committee Report of March 2005 on the The Influence of the Pharmaceutical Industry…

March 2005 – that’s a long time ago and the UK drugs regulator, the MHRA, has made none of the changes recommended.

The Select Committee summed up:

“The MHRA, like many regulatory organisations, is entirely funded by fees from those it regulates. However, unlike many regulators, it competes with other European agencies for fee income… dangers of the present arrangements…. During this long inquiry we became aware of serious weaknesses in the MHRA. Worryingly, in both its written and oral evidence the Agency seemed oblivious to the critical views of outsiders and unable to accept that it had any obvious shortcomings, except those that could be remedied by more transparency. The Agency’s attitude to its public health responsibilities suggested some complacency and a lack of requisite competency, reducing our confidence in its ability to undertake the reforms needed to earn and deserve public trust.

The consequences of lax oversight is that the industry’s influence has expanded and a number of practices have developed which act against the public interest.”

Download the full report here, in the meantime here are a few choice extracts:

Page 4: The industry is by no means solely to blame for the difficulties we describe. The regulators and prescribers are also open to criticism.

Page 8: The industry is hugely influential ….Its influence in Parliament is extensive. The Annex lists the All-Party Groups the pharmaceutical industry supports.

Page 4: The regulator, the Medicines and Healthcare products Regulatory Agency (MHRA), has failed to adequately scrutinise licensing data and its post-marketing surveillance is inadequate. The organisation has been too close to the industry, a closeness underpinned by common policy objectives, agreed processes, frequent contact, consultation and interchange of staff. We are concerned that a rather lax regime is exacerbated by the MHRA’s need to compete with other European regulators for licence application business.

Page 5: The Government, like the MHRA, has tended to assume that all is for the best… In view of the failings of the MHRA, we recommend a fundamental review of the organisation

Page 30: The MHRA is unusual in being one of few European agencies where the operation of the medicines regulatory system is funded entirely by fees derived from services to industry

Page 31: The MHRA relies on company data, presented as a series of detailed assessment reports, in its decision whether or not to licence a drug. Raw data is very rarely analysed.

Page 49: The consent forms do not inform patients that the raw data may be maintained by the industry, not made available to the general public or even reviewed by the regulatory authorities.Much of the criticism was essentially of the lack of transparency and the difficulties for doctors and others in assessing the research which is undertaken.

Page 52: The major impetus for greater transparency with medicines came from a lawsuit brought in August 2004 by the New York State Attorney General against GSK, alleging the company had concealed negative clinical trial results. As part of the settlement, GSK agreed to set up a public register of all clinical trials on all of its drugs.This breached a longstanding
convention, vigorously upheld by the regulators, whereby clinical trial results
were regarded as company property and commercially confidential.

Page 52: Too many problems appear to persist unnoticed or unacknowledged by the organisations that are central to the co-ordination, conduct and review of the clinical trials.

Page 78: The relationship between the industry and the MHRA is naturally close. There are regular interchanges of staff, common policy objectives, agreed processes, shared perspectives and routine contact and consultation. Many of the senior staff of the MHRA have previously worked with the industry …Overwhelmingly, the different parties appeared to speak the same language, with companies determined to observe the letter of the law and the regulators determined to uphold it.

Page 79: Such closeness provides the basis of the trust that the MHRA said it relied on as an integral part of the regulatory process.239 The MHRA Chairman suggested that trust underpinned the stance of the MHRA towards the companies they regulate. We inferred that this extended to the routine acceptance of companies’ summaries of the results of tests on their drugs as true reflections of the raw data on which they were based.

Page 79: Trust is critical in the relationship between regulators and industry. However, at the heart of this inquiry are the concerns of those who believe that the MHRA is too trusting. Trust should be based on robust evidence; …The evidence indicated that the MHRA examined primary (raw) data on drug effects only if it suspected some misrepresentation in the summary data supplied. It was argued that such trust in regulated companies goes too far: reliance on company summaries is neither sufficient nor appropriate, in the absence of effective audit and verification of data that companies provide. …Denial of access to information held by the [MHRA] puts the interests of pharmaceutical companies ahead of those of patients and prescribers. This is particularly indefensible in the light of evidence that regulatory agencies, supposedly established to protect the public, are acquiescing in biased later publication of the information they hold.

Page 79: Regulatory inertia was clearly illustrated through publication of the findings of the UK’s first ever public investigation into a drug safety problem:

Page 82: In setting up the review of SSRI antidepressants, the MHRA/CSM responded to another long-standing concern about regulatory activity: the possible conflicts of interest of regulators.

Page 83: user reports of often serious problems had been systematically discounted or ignored.

Page 85: In evidence to this Committee, Mr Brook expressed concerns about the influence of the industry on drug regulation, specifically the perceived threat by MHRA staff of legal entanglement resulting from regulatory action: …every time we made difficult decisions there was always this issue of: ‘We have got to be very careful because the pharmaceutical companies will sue us if we get this wrong; they will take us to court and take us through legal processes’; and it was very clear that the MRHA officials were very mindful the whole time of that dimension, to my view, more than the dimension of public health and public responsibility of the public.

Page 87: Further concerns, relating to the MHRA’s reliance on company summaries of data, rather than raw data are discussed elsewhere.

Page 96: A statement to the effect that heart problems were associated with Celebrex was issued by the MHRA in December 2004. In the statement, the Agency made it clear that it had not seen the actual data from the drug company but that its advice was based on information from Pfizer’s website.

Page 98: The regulatory authority, which is responsible for controlling much of the behaviour of the industry has significant failings. Lack of transparency has played a major part in allowing failings to continue. The traditional secrecy in the drug regulatory process has insulated regulators from the feedback that would otherwise check, test and stimulate their policies and performance. Failure can be measured by the MHRA’s poor history in recognising drug risks, poor communication and lack of public trust. Regulatory secrecy also underpins publication bias, and other unacceptable practices. The closeness that has developed between regulators and companies has deprived the industry of rigorous quality control and audit.

Page 102: Thirdly, procedures for investigating complaints about breaches of regulations are too slow, poorly enforced and weakly sanctioned.

Page 103: The MHRA does not routinely examine raw data submitted with the licence application but is dependent on summaries provided by the applicant. The Expert Working Group on SSRI’s report of December 2004 showed that summaries of information may not provide the detail required to assess drug risks adequately.

Page 106: The publication of misleading promotional material is a criminal offence and the punishment should befit such a status.

Page 106: The MHRA, like many regulatory organisations, is entirely funded by fees from those it regulates. However, unlike many regulators, it competes with other European agencies for fee income… dangers of the present arrangements….During this long inquiry we became aware of serious weaknesses in the MHRA. Worryingly, in both its written and oral evidence the Agency seemed oblivious to the critical views of outsiders and unable to accept that it had any obvious shortcomings, except those that could be remedied by more transparency. The Agency’s attitude to its public health responsibilities suggested some complacency and a lack of requisite
competency, reducing our confidence in its ability to undertake the reforms needed to earn and deserve public trust.

Page 117: The MHRA should put in place systematic procedures to randomly audit raw data.

BMJ says Avandia should never have been licensed in Britain and should now be withdrawn

Is Glaxo going to get away with it… again?

After the scandal of Seroxat – an unsafe drug with dangerous side effects, that made billions in profit and gained a licence using dodgy data supplied by GlaxoSmithKline, we now have the Avandia scandal: the story of an unsafe drug with dangerous side effects, that made billions in profit and gained a licence using dodgy data supplied by GlaxoSmithKline.

See a pattern forming?

Two days ago, the British Medical Journal (BMJ) said Avandia should never have been licensed in Britain and should now be withdrawn, after medical experts advised that its risks “outweigh its benefits”.

The drug – also known as Rosiglitazone – was approved by the European Medicines Agency ten years ago to help lower blood sugar levels in patients with type two diabetes. However, the BMJ’s investigations editor, Dr Deborah Cohen, said the European drug approval process was not rigorous enough and raised concerns about the quality of data used by Glaxo SmithKline.

The journal said that no new patients should start taking the drug, while those already taking it should consult their GP. It said that those at a higher risk of heart disease should be advised to stop taking it.

But now it has emerged that the Commission on Human Medicines advised the Medicines and Healthcare products Regulatory Agency (MHRA) in July that Avandia “no longer has a place on the UK market” and should be withdrawn, as its risks outweighed its benefits.

The Commission’s advice has been revealed following an investigation by the BMJ in collaboration with the BBC Panorama programme. Dr Yoon Loke, a clinical pharmacologist based at the University of East Anglia, told Panorama that the drug could have caused an extra 1,000 heart attacks and about 600 extra cases of heart failure in the UK last year.

However Professor Donald Singer of the British Pharmacological Society said that patients should not be concerned in the short term. In what appears to be a confused statement he says “These are not acceptable risks in the long term and you scale up in the country, clearly that could lead to many hundreds of people being affected. But from day to day, the actual risk to a given patient is quite small.”

Thanks for clearing that up Donald… ?

Glaxo shares down as agency warns against Avandia

The story below from the London Evening Standard.

It is amazing that this story has the spin that it does… talking about an “…embarrassing blow to [Glaxo’s] reputation…” and explaining how the MHRA “…warned that the heart risks associated with Avandia…”


What about the patients who have DIED because they took Avandia?

What about the way the MHRA dragged its feet over issuing the warning?

That’s where the real story is. I suggest that you all watch Panorama tonight (Monday 6 September) at 8.30pm BBC1.

Anyway – here’s the story:

GlaxoSmithKline was hit by an embarrassing blow to its reputation today when Britain’s drug regulator said its diabetes medicine Avandia should be pulled from sale because of concerns about its risk to the heart.

The Medicines and Healthcare products Regulatory Agency warned that the heart risks associated with Avandia – which was once Glaxo’s best-selling product and is still used by tens of thousands of Britons meant “it no longer has a place on the UK market”.

Avandia sales peaked at £1.4 billion in 2006, but fell to £771 million last year amid safety fears. Its value would drop off much more rapidly if the MHRA’s warning influences a special meeting the European Medicines Agency – which decides whether drugs should be used by patients in the EU – called to investigate the drug.

The MHRA said it would “robustly” put forward its position on Avandia at the meeting on Wednesday.
The latest concerns came to light after the British Medical Journal found that the Commission on Human Medicines – a group that advises Government ministers – had recommended the withdrawal of Avandia in July. At the time, the British watchdog reacted only by writing to doctors advising them to “consider alternative treatments where appropriate”.

But today fresh fears arose that the drug could be recalled from the market, sending Glaxo shares down 7.5p to 1254p. Analysts had hoped that the Brentford-based drugmaker’s Avandia headaches were over after Glaxo took a record legal charge of £1.57 billion in July, with a significant part going to settling patients’ lawsuits against Avandia.

Panorama, the MHRA, GlaxoSmithKline and… Avandia

Regular readers of this blog will know all about Glaxo, the MHRA and Seroxat.

But Glaxo, bless ’em, clearly don’t feel any shame about the Seroxat scandal, because they went and did it all again with Avandia, their killer diabetes drug… details here

This coming Monday, 6 September at 8.30 pm (in the UK), Panorama is airing its latest programme – all about Avandia:

We’re in the grip of a diabetes epidemic. The NHS spent more than half a billion pounds on medication for it in 2009. Patients trust that these drugs are safe, but does one come with a hidden cost to health? Shelley Jofre investigates the rise and fall of Avandia, until recently one of the UK’s best-selling diabetes drugs, and asks whether the medicine’s regulator is putting the interests of the drugs industry before patients.

You can read ALL about Avandia on this link

Glaxo and the MHRA – a marriage made in heaven? Read more here.

Paxil researcher falsified clinical trial data – gets 13 months in jail

Isn’t it always the way – the little fish get caught but somehow the big fish get away.

Key opinion leaders (KOLs) whose reputations are for sale can be relied on to say whatever a drug company tells them to, providing they are paid enough. The big fish I mean are ‘doctors’ such as Nemeroff and Keller in the USA and Montgomery in the UK. And the entire board of GlaxoSmithKline. Why no jail time for these people?

This is the way drug companies go about their business. They are happy to manipulate trial data to suit their own ends (while hiding the negative data) then they buy KOLs to talk up what can only be described as dangerous drugs.

Then they set aside billions of dollars in their accounts for the payment of fines and out of court settlements, and I, for one, am convinced they simply see this as just another part of the marketing cost of a new drug.

As long as the drug companies make more money than they pay out in fines (and they do, by a LONG way) then that’s good business – patients don’t come into the equation.

This story from Lawyers and Settlements:

GlaxoSmithKline is the subject of more bad publicity after a researcher was allegedly found to have falsified data in trials about Paxil. Meanwhile, the drug maker faces lawsuits alleging newborns suffered Paxil Birth defects when they were exposed to Paxil prior to birth.

The psychiatrist who reportedly falsified clinical data, Dr. Maria Carmen Palazzo, was a clinical investigator on studies conducted by SmithKline Beecham (doing business as GlaxoSmithKline). According to CNBC on 8/20/10, Palazzo has now pleaded guilty to 15 counts of failing to prepare and maintain records with the intent to defraud and mislead.

Palazzo reportedly included children in a study that involved diagnoses the children did not have. Prosecutors claimed that Palazzo also reported symptoms that her study subjects did not exhibit. She was sentenced to 13 months in prison, which she is serving at the same time as an 87-month term for healthcare fraud.

According to BNET (08/19/10), Palazzo was charged after the Federal Drug Administration (FDA) accused her of enrolling children in studies of obsessive-compulsive disorder and major depressive disorder even though the children she studied did not have the proper diagnosis for inclusion in the study.

Paxil now carries a black box warning about the risk of suicide in children. It also carries a warning about the risk of birth defects in babies exposed to the antidepressant prior to birth.

Lawsuits filed against GlaxoSmithKline allege the company did not adequately warn patients about the risk of birth defects, resulting in babies being born with serious health problems, including heart defects and persistent pulmonary hypertension of the newborn (PPHN).

GlaxoSmithKline reportedly settled a number of Paxil birth defect lawsuits, although the financial terms of the settlement were not disclosed. In announcing the settlement, the drug company said via e-mail that it “has reached agreement to settle certain cases involving the use of Paxil during pregnancy. The details of those settlements are confidential. Other cases remain pending.”

It is currently not known how many cases were settled, for what amounts or how many cases are pending. Bloomberg reported on 7/20/10 that Paxil agreed to pay more than $1 billion to settle more than 800 lawsuits that alleged Paxil was responsible for birth defects. Bloomberg further noted that the settlement works out to approximately $1.2 million to families and leaves around 100 lawsuits pending.

Remember, Glaxo has a track record of hiding negative clinical trial data that would knock sales of its drugs – the story of Seroxat and Study 329 is truly shocking.

Read more about Seroxat here:
More on Paxil and suicide – “Glaxo was aware of this risk, and hid it”

and here:
Glaxo fails in its responsibility to patients and it hid Seroxat data – it’s official

And what happens in the UK when the MHRA  undertakes a criminal investigation into Glaxo and the withholding of clinical trial data?… and finds Glaxo guilty…?

The answer is nothing happened to Glaxo – nothing at all.

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