700,000 travellers ‘at risk of typhoid due to dud jab’

More than 700,000 people who thought they were protected against typhoid may be vulnerable to the disease, because of a dud batches of a vaccine.

16 batches of the Typhim Vi vaccine for typhoid have been found to contain doses that have 'reduced potency' to fight the bacterial infection.

16 batches of the Typhim Vi vaccine for typhoid have been found to contain doses that have ‘reduced potency’ to fight the bacterial infection. Photo: ALAMY

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Stephen Adams

By , Medical Correspondent

5:46PM BST 08 Oct 2012

Manufacturer Sanofi Pasteur MSD has recalled 16 batches of its Typhim Vi vaccine – some 88 per cent of its stock – after tests found some of it was too weak.

The “reduced potency” shots could have been given to anyone immunised since January 2011.

The firm last night emphasised that defective doses of the vaccine itself were not dangerous.

However, the Medicines and Healthcare products Regulatory Agency (MHRA), which regulates drugs, said it could mean up to 729,606 had received weak vaccine.

This would mean they were more exposed to the bacterial infection that causes typhoid, than they thought.

An MHRA spokesman said: “This recall is due to concerns about the effectiveness of the vaccine in some syringes distributed from 7 January 2011 following filling problems in the manufacturing process.

“Therefore some patients who have been vaccinated with Typhim Vi may not be fully protected against the disease.

“If you received this vaccine and have recently returned from abroad, and are unwell, you should contact your doctor.”

Typhoid is a bacterial infection spread through contaminated food and water. It is rare in Britain but common throughout the tropics and sub-tropics.

Infections can cause intestinal bleeding, heart problems, pneumonia, seizures and swelling of the brain. If not treated with antibiotics, it can be fatal.

The vaccine is available free on the NHS for those travelling to high risk areas, or can be purchased through private clinics.

A spokesman for Sanofi Pasteur said the company decided to recall the batches after discovering that too many had reduced potency.

He said the cause of the problem had been identified, “but there will be a shortage” in coming months.

“We are hoping to get supplies back to normal by early 2013,” he said.

“We understand the difficulties this recall may cause for our customers and people relying upon our vaccines. We would like to offer our most sincere apologies for the inconveniences incurred.”

A Department of Health spokesman said: “Typhoid is rare in this country and is usually associated with travel to countries where sanitation is inadequate.

“The vaccine is still available and we are working with manufacturers to help ensure that current supply problems are resolved as soon as possible.

“People who have recently been immunised should seek medical advice about precautions to take whilst abroad to minimise the risk of infection, in case the vaccine has not provided full protection.”

A spokesman for the Health Protection Agency said: “Provisional data from 2011 to September 2012 do not suggest that there has been a spike in cases of Typhoid since January 2011 when the problem with the vaccine dates back to.

“Normal typhoid vaccine is 50-80 per cent effective travellers are advised to practise strict food, water and personal hygiene precautions even if vaccinated.”


The drugs don’t work: a modern medical scandal

The doctors prescribing the drugs don’t know they don’t do what they’re meant to. Nor do their patients. The manufacturers know full well, but they’re not telling.

    Ben Goldacre The Guardian,   Friday 21 September 2012 18.00 EDT


    Drugs are tested by their manufacturers,  in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that exaggerate the benefits. Photograph: Photograph: Getty Images. Digital manipulation: Phil Partridge for GNL Imaging

    Reboxetine is a drug I have prescribed. Other drugs had done nothing for my patient, so we wanted to try something new. I’d read the trial data before I wrote the prescription, and found only well-designed, fair tests, with overwhelmingly positive results. Reboxetine was better than a placebo, and as good as any other antidepressant in head-to-head comparisons. It’s approved for use by the Medicines and Healthcare products Regulatory Agency (the MHRA), which governs all drugs in the UK. Millions of doses are prescribed every year, around the world. Reboxetine was clearly a safe and effective treatment. The patient and I discussed the evidence briefly, and agreed it was the right treatment to try next. I signed a prescription.

    But we had both been misled. In October 2010, a group of researchers was finally able to bring together all the data that had ever been collected on reboxetine, both from trials that were published and from those that had never appeared in academic papers. When all this trial data was put together, it produced a shocking picture. Seven trials had been conducted comparing reboxetine against a placebo. Only one, conducted in 254 patients, had a neat, positive result, and that one was published in an academic journal, for doctors and researchers to read. But six more trials were conducted, in almost 10 times as many patients. All of them showed that reboxetine was no better than a dummy sugar pill. None of these trials was published. I had no idea they existed.

    It got worse. The trials comparing reboxetine against other drugs showed exactly the same picture: three small studies, 507 patients in total, showed that reboxetine was just as good as any other drug. They were all published. But 1,657 patients’ worth of data was left unpublished, and this unpublished data showed that patients on reboxetine did worse than those on other drugs. If all this wasn’t bad enough, there was also the side-effects data. The drug looked fine in the trials that appeared in the academic literature; but when we saw the unpublished studies, it turned out that patients were more likely to have side-effects, more likely to drop out of taking the drug and more likely to withdraw from the trial because of side-effects, if they were taking reboxetine rather than one of its competitors.

    I did everything a doctor is supposed to do. I read all the papers, I critically appraised them, I understood them, I discussed them with the patient and we made a decision together, based on the evidence. In the published data, reboxetine was a safe and effective drug. In reality, it was no better than a sugar pill and, worse, it does more harm than good. As a doctor, I did something that, on the balance of all the evidence, harmed my patient, simply because unflattering data was left unpublished.

    Nobody broke any law in that situation, reboxetine is still on the market and the system that allowed all this to happen is still in play, for all drugs, in all countries in the world. Negative data goes missing, for all treatments, in all areas of science. The regulators and professional bodies we would reasonably expect to stamp out such practices have failed us. These problems have been protected from public scrutiny because they’re too complex to capture in a soundbite. This is why they’ve gone unfixed by politicians, at least to some extent; but it’s also why it takes detail to explain. The people you should have been able to trust to fix these problems have failed you, and because you have to understand a problem properly in order to fix it, there are some things you need to know.

    Drugs are tested by the people who manufacture them, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that are flawed by design, in such a way that they exaggerate the benefits of treatments. Unsurprisingly, these trials tend to produce results that favour the manufacturer. When trials throw up results that companies don’t like, they are perfectly entitled to hide them from doctors and patients, so we only ever see a distorted picture of any drug’s true effects. Regulators see most of the trial data, but only from early on in a drug’s life, and even then they don’t give this data to doctors or patients, or even to other parts of government. This distorted evidence is then communicated and applied in a distorted fashion.

    In their 40 years of practice after leaving medical school, doctors hear about what works ad hoc, from sales reps, colleagues and journals. But those colleagues can be in the pay of drug companies – often undisclosed – and the journals are, too. And so are the patient groups. And finally, academic papers, which everyone thinks of as objective, are often covertly planned and written by people who work directly for the companies, without disclosure. Sometimes whole academic journals are owned outright by one drug company. Aside from all this, for several of the most important and enduring problems in medicine, we have no idea what the best treatment is, because it’s not in anyone’s financial interest to conduct any trials at all.

    Now, on to the details.

    In 2010, researchers from Harvard and Toronto found all the trials looking at five major classes of drug – antidepressants, ulcer drugs and so on – then measured two key features: were they positive, and were they funded by industry? They found more than 500 trials in total: 85% of the industry-funded studies were positive, but only 50% of the government-funded trials were. In 2007, researchers looked at every published trial that set out to explore the benefits of a statin. These cholesterol-lowering drugs reduce your risk of having a heart attack and are prescribed in very large quantities. This study found 192 trials in total, either comparing one statin against another, or comparing a statin against a different kind of treatment. They found that industry-funded trials were 20 times more likely to give results favouring the test drug.

    These are frightening results, but they come from individual studies. So let’s consider systematic reviews into this area. In 2003, two were published. They took all the studies ever published that looked at whether industry funding is associated with pro-industry results, and both found that industry-funded trials were, overall, about four times more likely to report positive results. A further review in 2007 looked at the new studies in the intervening four years: it found 20 more pieces of work, and all but two showed that industry-sponsored trials were more likely to report flattering results.

    It turns out that this pattern persists even when you move away from published academic papers and look instead at trial reports from academic conferences. James Fries and Eswar Krishnan, at the Stanford University School of Medicine in California, studied all the research abstracts presented at the 2001 American College of Rheumatology meetings which reported any kind of trial and acknowledged industry sponsorship, in order to find out what proportion had results that favoured the sponsor’s drug.

    In general, the results section of an academic paper is extensive: the raw numbers are given for each outcome, and for each possible causal factor, but not just as raw figures. The “ranges” are given, subgroups are explored, statistical tests conducted, and each detail is described in table form, and in shorter narrative form in the text. This lengthy process is usually spread over several pages. In Fries and Krishnan (2004), this level of detail was unnecessary. The results section is a single, simple and – I like to imagine – fairly passive-aggressive sentence:

    “The results from every randomised controlled trial (45 out of 45) favoured the drug of the sponsor.”

    How does this happen? How do industry-sponsored trials almost always manage to get a positive result? Sometimes trials are flawed by design. You can compare your new drug with something you know to be rubbish – an existing drug at an inadequate dose, perhaps, or a placebo sugar pill that does almost nothing. You can choose your patients very carefully, so they are more likely to get better on your treatment. You can peek at the results halfway through, and stop your trial early if they look good. But after all these methodological quirks comes one very simple insult to the integrity of the data. Sometimes, drug companies conduct lots of trials, and when they see that the results are unflattering, they simply fail to publish them.

    Because researchers are free to bury any result they please, patients are exposed to harm on a staggering scale throughout the whole of medicine. Doctors can have no idea about the true effects of the treatments they give. Does this drug really work best, or have I simply been deprived of half the data? No one can tell. Is this expensive drug worth the money, or has the data simply been massaged? No one can tell. Will this drug kill patients? Is there any evidence that it’s dangerous? No one can tell. This is a bizarre situation to arise in medicine, a discipline in which everything is supposed to be based on evidence.

    And this data is withheld from everyone in medicine, from top to bottom. Nice, for example, is the National Institute for Health and Clinical Excellence, created by the British government to conduct careful, unbiased summaries of all the evidence on new treatments. It is unable either to identify or to access data on a drug’s effectiveness that’s been withheld by researchers or companies: Nice has no more legal right to that data than you or I do, even though it is making decisions about effectiveness, and cost-effectiveness, on behalf of the NHS, for millions of people.

    In any sensible world, when researchers are conducting trials on a new tablet for a drug company, for example, we’d expect universal contracts, making it clear that all researchers are obliged to publish their results, and that industry sponsors – which have a huge interest in positive results – must have no control over the data. But, despite everything we know about industry-funded research being systematically biased, this does not happen. In fact, the opposite is true: it is entirely normal for researchers and academics conducting industry-funded trials to sign contracts subjecting them to gagging clauses that forbid them to publish, discuss or analyse data from their trials without the permission of the funder.

    This is such a secretive and shameful situation that even trying to document it in public can be a fraught business. In 2006, a paper was published in the Journal of the American Medical Association (Jama), one of the biggest medical journals in the world, describing how common it was for researchers doing industry-funded trials to have these kinds of constraints placed on their right to publish the results. The study was conducted by the Nordic Cochrane Centre and it looked at all the trials given approval to go ahead in Copenhagen and Frederiksberg. (If you’re wondering why these two cities were chosen, it was simply a matter of practicality: the researchers applied elsewhere without success, and were specifically refused access to data in the UK.) These trials were overwhelmingly sponsored by the pharmaceutical industry (98%) and the rules governing the management of the results tell a story that walks the now familiar line between frightening and absurd.

    For 16 of the 44 trials, the sponsoring company got to see the data as it accumulated, and in a further 16 it had the right to stop the trial at any time, for any reason. This means that a company can see if a trial is going against it, and can interfere as it progresses, distorting the results. Even if the study was allowed to finish, the data could still be suppressed: there were constraints on publication rights in 40 of the 44 trials, and in half of them the contracts specifically stated that the sponsor either owned the data outright (what about the patients, you might say?), or needed to approve the final publication, or both. None of these restrictions was mentioned in any of the published papers.

    When the paper describing this situation was published in Jama, Lif, the Danish pharmaceutical industry association, responded by announcing, in the Journal of the Danish Medical Association, that it was “both shaken and enraged about the criticism, that could not be recognised”. It demanded an investigation of the scientists, though it failed to say by whom or of what. Lif then wrote to the Danish Committee on Scientific Dishonesty, accusing the Cochrane researchers of scientific misconduct. We can’t see the letter, but the researchers say the allegations were extremely serious – they were accused of deliberately distorting the data – but vague, and without documents or evidence to back them up.

    Nonetheless, the investigation went on for a year. Peter Gøtzsche, director of the Cochrane Centre, told the British Medical Journal that only Lif’s third letter, 10 months into this process, made specific allegations that could be investigated by the committee. Two months after that, the charges were dismissed. The Cochrane researchers had done nothing wrong. But before they were cleared, Lif copied the letters alleging scientific dishonesty to the hospital where four of them worked, and to the management organisation running that hospital, and sent similar letters to the Danish medical association, the ministry of health, the ministry of science and so on. Gøtzsche and his colleagues felt “intimidated and harassed” by Lif’s behaviour. Lif continued to insist that the researchers were guilty of misconduct even after the investigation was completed.

    Paroxetine is a commonly used antidepressant, from the class of drugs known as selective serotonin reuptake inhibitors or SSRIs. It’s also a good example of how companies have exploited our long-standing permissiveness about missing trials, and found loopholes in our inadequate regulations on trial disclosure.

    To understand why, we first need to go through a quirk of the licensing process. Drugs do not simply come on to the market for use in all medical conditions: for any specific use of any drug, in any specific disease, you need a separate marketing authorisation. So a drug might be licensed to treat ovarian cancer, for example, but not breast cancer. That doesn’t mean the drug doesn’t work in breast cancer. There might well be some evidence that it’s great for treating that disease, too, but maybe the company hasn’t gone to the trouble and expense of getting a formal marketing authorisation for that specific use. Doctors can still go ahead and prescribe it for breast cancer, if they want, because the drug is available for prescription, it probably works, and there are boxes of it sitting in pharmacies waiting to go out. In this situation, the doctor will be prescribing the drug legally, but “off-label”.

    Now, it turns out that the use of a drug in children is treated as a separate marketing authorisation from its use in adults. This makes sense in many cases, because children can respond to drugs in very different ways and so research needs to be done in children separately. But getting a licence for a specific use is an arduous business, requiring lots of paperwork and some specific studies. Often, this will be so expensive that companies will not bother to get a licence specifically to market a drug for use in children, because that market is usually much smaller.

    So it is not unusual for a drug to be licensed for use in adults but then prescribed for children. Regulators have recognised that this is a problem, so recently they have started to offer incentives for companies to conduct more research and formally seek these licences.

    When GlaxoSmithKline applied for a marketing authorisation in children for paroxetine, an extraordinary situation came to light, triggering the longest investigation in the history of UK drugs regulation. Between 1994 and 2002, GSK conducted nine trials of paroxetine in children. The first two failed to show any benefit, but the company made no attempt to inform anyone of this by changing the “drug label” that is sent to all doctors and patients. In fact, after these trials were completed, an internal company management document stated: “It would be commercially unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile of paroxetine.” In the year after this secret internal memo, 32,000 prescriptions were issued to children for paroxetine in the UK alone: so, while the company knew the drug didn’t work in children, it was in no hurry to tell doctors that, despite knowing that large numbers of children were taking it. More trials were conducted over the coming years – nine in total – and none showed that the drug was effective at treating depression in children.

    It gets much worse than that. These children weren’t simply receiving a drug that the company knew to be ineffective for them; they were also being exposed to side-effects. This should be self-evident, since any effective treatment will have some side-effects, and doctors factor this in, alongside the benefits (which in this case were nonexistent). But nobody knew how bad these side-effects were, because the company didn’t tell doctors, or patients, or even the regulator about the worrying safety data from its trials. This was because of a loophole: you have to tell the regulator only about side-effects reported in studies looking at the specific uses for which the drug has a marketing authorisation. Because the use of paroxetine in children was “off-label”, GSK had no legal obligation to tell anyone about what it had found.

    People had worried for a long time that paroxetine might increase the risk of suicide, though that is quite a difficult side-effect to detect in an antidepressant. In February 2003, GSK spontaneously sent the MHRA a package of information on the risk of suicide on paroxetine, containing some analyses done in 2002 from adverse-event data in trials the company had held, going back a decade. This analysis showed that there was no increased risk of suicide. But it was misleading: although it was unclear at the time, data from trials in children had been mixed in with data from trials in adults, which had vastly greater numbers of participants. As a result, any sign of increased suicide risk among children on paroxetine had been completely diluted away.

    Later in 2003, GSK had a meeting with the MHRA to discuss another issue involving paroxetine. At the end of this meeting, the GSK representatives gave out a briefing document, explaining that the company was planning to apply later that year for a specific marketing authorisation to use paroxetine in children. They mentioned, while handing out the document, that the MHRA might wish to bear in mind a safety concern the company had noted: an increased risk of suicide among children with depression who received paroxetine, compared with those on dummy placebo pills.

    This was vitally important side-effect data, being presented, after an astonishing delay, casually, through an entirely inappropriate and unofficial channel. Although the data was given to completely the wrong team, the MHRA staff present at this meeting had the wit to spot that this was an important new problem. A flurry of activity followed: analyses were done, and within one month a letter was sent to all doctors advising them not to prescribe paroxetine to patients under the age of 18.

    How is it possible that our systems for getting data from companies are so poor, they can simply withhold vitally important information showing that a drug is not only ineffective, but actively dangerous? Because the regulations contain ridiculous loopholes, and it’s dismal to see how GSK cheerfully exploited them: when the investigation was published in 2008, it concluded that what the company had done – withholding important data about safety and effectiveness that doctors and patients clearly needed to see – was plainly unethical, and put children around the world at risk; but our laws are so weak that GSK could not be charged with any crime.

    After this episode, the MHRA and EU changed some of their regulations, though not adequately. They created an obligation for companies to hand over safety data for uses of a drug outside its marketing authorisation; but ridiculously, for example, trials conducted outside the EU were still exempt. Some of the trials GSK conducted were published in part, but that is obviously not enough: we already know that if we see only a biased sample of the data, we are misled. But we also need all the data for the more simple reason that we need lots of data: safety signals are often weak, subtle and difficult to detect. In the case of paroxetine, the dangers became apparent only when the adverse events from all of the trials were pooled and analysed together.

    That leads us to the second obvious flaw in the current system: the results of these trials are given in secret to the regulator, which then sits and quietly makes a decision. This is the opposite of science, which is reliable only because everyone shows their working, explains how they know that something is effective or safe, shares their methods and results, and allows others to decide if they agree with the way in which the data was processed and analysed. Yet for the safety and efficacy of drugs, we allow it to happen behind closed doors, because drug companies have decided that they want to share their trial results discretely with the regulators. So the most important job in evidence-based medicine is carried out alone and in secret. And regulators are not infallible, as we shall see.

    Rosiglitazone was first marketed in 1999. In that first year, Dr John Buse from the University of North Carolina discussed an increased risk of heart problems at a pair of academic meetings. The drug’s manufacturer, GSK, made direct contact in an attempt to silence him, then moved on to his head of department. Buse felt pressured to sign various legal documents. To cut a long story short, after wading through documents for several months, in 2007 the US Senate committee on finance released a report describing the treatment of Buse as “intimidation”.

    But we are more concerned with the safety and efficacy data. In 2003 the Uppsala drug monitoring group of the World Health Organisation contacted GSK about an unusually large number of spontaneous reports associating rosiglitazone with heart problems. GSK conducted two internal meta-analyses of its own data on this, in 2005 and 2006. These showed that the risk was real, but although both GSK and the FDA had these results, neither made any public statement about them, and they were not published until 2008.

    During this delay, vast numbers of patients were exposed to the drug, but doctors and patients learned about this serious problem only in 2007, when cardiologist Professor Steve Nissen and colleagues published a landmark meta-analysis. This showed a 43% increase in the risk of heart problems in patients on rosiglitazone. Since people with diabetes are already at increased risk of heart problems, and the whole point of treating diabetes is to reduce this risk, that finding was big potatoes. Nissen’s findings were confirmed in later work, and in 2010 the drug was either taken off the market or restricted, all around the world.

    Now, my argument is not that this drug should have been banned sooner because, as perverse as it sounds, doctors do often need inferior drugs for use as a last resort. For example, a patient may develop idiosyncratic side-effects on the most effective pills and be unable to take them any longer. Once this has happened, it may be worth trying a less effective drug if it is at least better than nothing.

    The concern is that these discussions happened with the data locked behind closed doors, visible only to regulators. In fact, Nissen’s analysis could only be done at all because of a very unusual court judgment. In 2004, when GSK was caught out withholding data showing evidence of serious side-effects from paroxetine in children, their bad behaviour resulted in a US court case over allegations of fraud, the settlement of which, alongside a significant payout, required GSK to commit to posting clinical trial results on a public website.

    Nissen used the rosiglitazone data, when it became available, and found worrying signs of harm, which they then published to doctors – something the regulators had never done, despite having the information years earlier. If this information had all been freely available from the start, regulators might have felt a little more anxious about their decisions but, crucially, doctors and patients could have disagreed with them and made informed choices. This is why we need wider access to all trial reports, for all medicines.

    Missing data poisons the well for everybody. If proper trials are never done, if trials with negative results are withheld, then we simply cannot know the true effects of the treatments we use. Evidence in medicine is not an abstract academic preoccupation. When we are fed bad data, we make the wrong decisions, inflicting unnecessary pain and suffering, and death, on people just like us.

    • This is an edited extract from Bad Pharma, by Ben Goldacre, published next week by Fourth Estate at £13.99. To order a copy for £11.19, including UK mainland p&p, call 0330 333 6846, or go to guardian.co.uk/bookshop.


    New rules to end secrecy over safety of medical implants

    New rules to end the secrecy over the safety of devices such as hip replacements and breast implants are being drawn up after a series of scandals.

    New rules to end secrecy over safety of medical implants

    The rules are being drawn up by the European Commission in the wake of the PIP breast implant fiasco Photo: ALAMY
    Laura Donnelly

    By , Health Correspondent

    7:50AM BST 09 Sep 2012

    The changes will mean that for the first time the public will be able to access details of the clinical research behind the products, and their safety record since coming on to the market.

    The rules are being drawn up by the European Commission in the wake of the PIP breast implant fiasco and the scandal of metal-on-metal hips, which were found to poison the body and suffer failure rates of up to 50 per cent.

    Under the current system, the clinical evidence to support devices, and the records of adverse incidents linked with them are kept behind closed doors.

    Manufacturers must share some information with a “nominated body” of their choice, which authorises their products for use, yet it cannot be seen by the public, nor by independent scientists because of draconian European Union regulations.

    British regulators run a voluntary system so surgeons can report concerns about medical devices, yet the EU confidentiality rules mean their data is not published, with patients and doctors told nothing – unless the situation deteriorates so badly that a safety alert is issued.

    Last December it emerged that more than 40,000 British women received substandard breast implants, made by Poly Implants Protheses (PIP), with some made from industrial silicone, instead of the medical substance which had been authorised.

    In January, The Sunday Telegraph disclosed that thousands of Britons had been given metal-on-metal hip implants which were found to poison the body, with some devices having failure rates of up to 50 per cent.

    Weeks later, regulators the Medicines and Healthcare products Regulatory Agency (MHRA) issued a warning that 49,000 people with the implants should undergo checks throughout their lifetime and undergo further operations to replace the devices if problems were found.

    The new proposals from the European Commission, due to be published within weeks, are expected to recommend that three directives on medical devices, passed during the 1990s, are rewritten.

    Under the plans, a duty of confidentiality which is currently placed on all organisations which handle clinical data would be erased, in a bid to make the system more transparent.

    The current rules were intended to protect the commercial interests of manufacturing companies, but safety campaigners and regulators believe they have gone too far in putting the interests of business ahead of patient safety.

    Professor Sir Kent Woods, chief executive of the MHRA, which has called for the change, said: “The evidence should be out there – so that scientists can look at it, so that patients can look at it and so the public can look at it.”

    He said it had now become “widely accepted” in the pharmaceutical industry that companies had to make the data from their clinical trials public after drugs were licensed, and that reports of adverse reactions to drugs were documented and published.

    Medical devices and implants should follow the same direction, he said.

    Because of the single European market, devices used in this country can be manufactured elsewhere, then authorised by a “notified body” in any of the 27 EU member states.

    That meant that in the case of the PIP implants, a company in Germany was responsible for the quality of devices produced in France and imported for use in 300,000 women around the world, including Britain.

    British regulators the MHRA accredit the six notified bodies which operate in this country and can audit them to check their processes – but have little control over the quality of checks done abroad.

    The MHRA has urged the European Commission to change the system, so that accreditation is done by representatives from several countries, in order to ensure that all countries are working to the same standards.

    Prof Woods said he felt confident about the expertise of the organisations it inspects but said: “I can’t be confident that notified bodies in every one of the 27 countries are working the same way”.

    He said the rules of a single market in Europe meant it was not possible for British regulators to check all the devices used in this country.

    The MHRA is also calling for more rigorous standards to ensure that the clinical evidence to support the application for a licence is more consistently and robustly scrutinised.

    The commission is considering how information should be better shared across EU member states, which Prof Woods said could have helped regulators to detect the PIP scandal sooner.

    “If we had been able to easily share adverse incident data across Europe I think we would have picked up an increased signal about rupture rates – though not that the filler was fraudulent,” he said.

    The Commission is also considering whether an “implant card” should be given to all patients who receive an implant, with details of the date, name of device, batch, lot and serial number.

    The MHRA said it became clear when problems arose over breast implants and metal-on-metal hip replacements that most patients given implants were not aware what type of device they had.

    Sir Bruce Keogh, the Department of Health medical director, is leading a review of cosmetic surgery which is considering whether details of all operations should be held on a central register, to help detect problems with particular types of implants.

    30 per cent of drugs prescribed to under-18s – and up to 95 per cent of drugs given to babies in intensive care – have never been tested on children. (U.K.)

    One third of junior drugs are not tested on children sparking demand for  probe

    • Official study calls for urgent  investigation after ‘high number of drug errors’
    • 95 per cent of all hospital medicines for  babies affected

    By Jo Macfarlane

    PUBLISHED:16:00 EST, 1  September 2012| UPDATED:16:00 EST, 1 September 2012

    Untested: A third of medicines for children are not tested on minors
    Untested: A third of medicines for children are not  tested on minors

    Children are being prescribed unlicensed  medicines that could be causing harm, a report has warned.

    The Government study is demanding an urgent  investigation into  the ‘unacceptable’ fact that almost a third of drugs  given to sick children are officially approved for only adult use.

    It warns of ‘a high number of drug errors’ in  which children may be wrongly prescribed too much of a medicine because the  doses are meant for adults.

    Historically, pharmaceutical companies have  not had an obligation  to test medicines on youngsters. The law  changed in  2007 and new drugs coming to market must now be tested on  children before they  can be used on them.

    But this still means about 30 per cent of  drugs prescribed to under-18s – and up to 95 per cent of drugs given to babies  in intensive care – have  never been tested on children.

    These include common antibiotics,  painkillers, asthma inhalers and cancer medicines.

    The use of unlicensed drugs is so common that  many parents will  not even  be told that their child  is receiving  medication ‘off-label’.

    Over-the-counter medicines designed for  children – such as Calpol and Nurofen for Children – which parents can buy from  high street pharmacies are not affected.

    The report, commissioned by the  Department  of Health and written by leading child health experts, warns  that unlicensed  medicines may be causing side effects that could be  going unreported.

    It is  calling for an investigation by the  drugs watchdog, the Medicines and  Healthcare products Regulatory Agency,  because it is not known how many  children may potentially have been harmed – or  how much it is costing  the NHS.

    Open wide: Junior medicines face new questions after the Government study
    Open wide: Junior medicines face new questions after the  Government study

    The report, from the Children and Young  People’s Health Outcomes Forum, says: ‘New medicines account for a relatively  small percentage of those used by children, and those introduced before [the  2007] legislation largely remain unregulated and, critically, therefore possibly  untested formally in children.

    ‘This contributes to the high number  of drug  errors and leads  to wider implications – including  the fact  that  the National Institute for Health and Clinical Excellence will not  give advice  on unlicensed medicines and this limits the guidance that  they can offer on  care for children.’

    It goes on to caution: ‘The Forum believes  that the situation with  regard to the absence of licensing for the majority of  children and  young people’s medicines in this country is  unacceptable.’

    Historically, it has been difficult  to  test medicines on children because regulators have made it hard for  drugs  companies to get ethical approval to do so.

    Safe: Over-the-counter medicines such as Calpol are not affected
    Safe: Over-the-counter medicines such as Calpol are not  affected

    There has also been no legal responsibility  for the pharmaceutical industry to conduct the tests once they have a licence  for their drug to be used in adults, which is more commercially  beneficial.

    In the past, doctors have waited  up to  ten years after a drug is introduced before giving it to children, to make sure  there are no serious side effects. But this has left children’s medicine at a  disadvantage.

    The medics’ and pharmacists’ bible, the  British National Formulary for Children, publishes recommended dosages for  licensed and unlicensed medicines based on evidence from doctors and regulators.

    Warren Lenney, professor of respiratory child  health at Keele University and chair of the paediatric formulary committee at  the BNFC, said: ‘The people who say we shouldn’t prescribe unlicensed or  off-label medicines don’t know what they’re talking about.

    ‘By no means are we using dangerous  medicines. If a medicine has been on the market for 30 years, no company is  going to spend millions of pounds testing it on children.

    What has been shown is that using an  unlicensed medicine in children does increase the risk of side effects. We don’t  know why. It is one possibility that we are really underestimating the number of  side effects – but I don’t want to scaremonger.’

    The Children and Young People’s Health  Outcomes Forum was set up this year to look at how the reorganisation of the NHS  could improve the health of children.

    Co-chair Professor Ian Lewis, medical  director of Alder Hey Children’s NHS Foundation Trust, said: ‘Most of the drugs  we use in children’s cancer like leukaemia have not been formally tested in  children but have cured many of them.

    ‘It’s very expensive for pharmaceutical  companies to do this additional testing, and the question that must be asked is  whether there’s enough incentive for them.’

    But Dr Helen Sammons, vice chair of the  medicines committee of the Royal College of Paediatrics and Child Health, said: ‘Parents shouldn’t be concerned that children are being treated with unlicensed  and off-label medicines.

    ‘We know what we should be  giving  children and that it works based on our experience and evidence, but there’s no  legal drive to update the licences sometimes.’

    A spokesman for the MHRA said: ‘We’re fully  aware of the recommendations outlined in the report and are working closely with  the Department of Health to best take forward these recommendations.’

    A spokesman for the Department of Health said  it would have a formal response to the recommendations later this  year.

    Read more: http://www.dailymail.co.uk/news/article-2196906/One-junior-drugs-tested-children-sparking-demand-probe.html#ixzz25IQ8hmKr

    Roche under investigation by UK watchdogs

    MailOnline - news, sport, celebrity, science and health stories

    Drug giant probed for not disclosing 15,000 patient death reports: Roche under investigation by UK watchdogs after 80,000 ‘adverse reactions

    PUBLISHED:16:48 EST, 7 July 2012 | UPDATED:08:20 EST, 8 July 2012

    One of the world’s biggest drug companies is at the centre of an urgent investigation after failing to disclose reports that 15,000 people died while taking its medicines.

    Swiss pharmaceutical giant Roche failed to pass on a further 65,000 reports of suspected side effects that were recorded by patients.

    All of the reactions took place in the United States over the past 15 years with medicines used to treat breast cancer, bowel cancer, hepatitis B, and skin and eye conditions.

    Roche, one of the world’s biggest drug companies, is at the centre of an urgent investigation after failing to report that people died while taking their medication

    There is no evidence so far of  any direct link between the problems and the drugs – but medicines watchdogs say they are taking Roche’s failure to disclose possible concerns ‘extremely seriously’.

    The drugs involved include Herceptin, given to about 10,000 breast cancer patients in Britain, and Lucentis, which is used to treat about 20,000 UK patients a year with age-related vision loss. The NHS pays Roche millions of pounds for these treatments every year.

    The extent of the failings were discovered when the UK medicines watchdog, the Medicines and Healthcare products Regulatory Agency (MHRA), carried out a routine inspection of Roche’s drug safety procedures at its headquarters in Welwyn Garden City, Hertfordshire.

    The company has now been ordered by the MHRA and the EU-wide regulator, the European Medicines Agency, to investigate immediately each of the total 80,000 deaths and side effects reported. Both agencies said they were ‘taking action’ over Roche’s failures.

    All of the deaths and possible adverse  reactions were reported by patients who rang a call centre run by  Roche’s US subsidiary Genentech. Staff there failed to pass on the  reports to Roche’s drug safety team – but it is not known why

    Professor Sir Kent Woods, chief executive of the MHRA, said: ‘Patients should continue to take their medicines because our investigation has currently found no evidence of a safety risk to patients.

    ‘Roche’s actions are unacceptable and our investigation has identified that its reporting systems are inadequate. We are taking urgent action to ensure that these are rectified by Roche as a matter of priority. We will take action to ensure that patients are protected now and in the future.’

    All of the deaths and possible adverse reactions were reported by patients who rang a call centre run by Roche’s US subsidiary Genentech. Staff there failed to pass on the reports to Roche’s drug safety team – but it is not known why.

    Roche, which made profits of £6.3 billion in 2010, has a legal duty to examine every suspected side effect and report them to regulators around the world so that potential safety concerns can be investigated.

    This means that each side effect reported to the patient support call centre should have been immediately sent to the safety team to be assessed.

    These must then be sent to regulators – within 15 days for the most serious reactions – even if no link between the drug and the reaction be proved.

    Some of the call centre’s records, which date back to 1997, are said to have been noted down on paper and kept in boxes.

    The European Medicines Agency, which made the findings public, said: ‘There is at present no evidence of a negative impact for patients and while the investigations and being conducted there is no need for patients or healthcare professionals to take any action.’

    A number of drugs are being investigated following the incident

    However, a spokeswoman  added: ‘It’s not often we make statements on such findings, so we do take this incredibly seriously. The numbers are huge but we’re not talking about confirmed reactions.

    ‘Some might not be related, and some may have already been reported to the regulators via other mechanisms – for example directly to us by doctors.’ But she added: ‘We cannot rule out that additional safety concerns could be discovered.’

    When asked if legal action could be taken against Roche, she said: ‘We are looking at all options. There are penalty regulations and they could be fined.’

    Other drugs being examined  include Avastin, used for bowel and breast cancer; lung cancer medication Tarceva; Rituxan, which treats non-Hodgkin’s lymphoma; the stroke drug Alteplase; Actemra for rheumatoid arthritis; Pegasys for hepatitis B; and Raptiva for the skin condition psoriasis.

    If any new safety concerns emerge after examining the data, regulators could decide to withdraw the drugs or change their guidance to doctors.

    In a statement, Roche said: ‘Patient safety is of paramount importance to Roche. We acknowledge the concerns that can be caused by this issue for people using our medicines.

    ‘The non-assessment and non-reporting of these adverse events was not intentional and we are taking comprehensive steps necessary to address the findings of the MHRA inspection. We have provided initial estimates of missed adverse events and are in the process of confirming the final number.

    ‘We expect to complete all activities related to these programmes as soon as possible.’