Tamiflu isn’t much good and Roche tried to stop us showing so, says the BMJ

The BMJ has just published a whole slew of papers about Tamiflu (oseltamivir) – a key drug in the public health response against swine flu (influenza A/H1N1).

The linchpin is a Cochrane review on the efficacy of neuraminidase inhibitors – namely zanamivir (Relenza; Glaxo Wellcome) and oseltamivir (Tamiflu; Roche) – for preventing and treating influenza in healthy adults.  The review found that these two drugs were only partly effective against laboratory confirmed symptomatic influenza (oseltamivir 61% effective; zanamivir 62% effective), and no good at all against asymptomatic flu or flu-like illness.

In addition, Tamiflu did not reduce the risk of influenza-related lower respiratory tract complications – bad news for the Department of Health, which recommends using the drug to prevent secondary complications in healthy adults.  The authors conclude: “Neuraminidase inhibitors might be regarded as optional for reducing the symptoms of seasonal influenza. Paucity of good data has undermined previous findings for oseltamivir’s prevention of complications from influenza.”

In an accompanying feature, Deborah Cohen retraces the steps leading to the publication of the Cochrane review and highlights all the difficulties the authors had extracting data from Roche, the makers of Tamiflu.  The review “exposed a complex interplay between politics, public health planning, availability of trial data, publishing, and drug regulation.”

Turns out that Roche’s claims that Tamiflu reduces hospital admissions and secondary complications of influenza were based on a 2003 meta-analysis that only included two proper randomised controlled trials and was authored by several Roche employees.  When the authors of the Cochrane review tried to get their hands on the data in this paper to include them in their own analysis, they came up against all sorts of obstacles thrown up by Roche.

Peter Doshi, an author of the new Cochrane review, writes in the BMJ of his struggle to get hold of the elusive data and offers a damning verdict on the use of the drug in the swine flu epidemic. “Since August 2009, our Cochrane review team has tried to obtain the data needed to verify claims that oseltamivir (Tamiflu) lowers serious complications of influenza such as pneumonia. We failed, but in failing discovered that the public evidence base for this global public health drug is fragmented, inconsistent, and contradictory. We are no longer sure that oseltamivir offers a therapeutic and public health policy advantage over cheap, over the counter drugs such as aspirin.”

In an analysis article, Nick Freemantle and Mel Calvert look over the observational studies of Tamiflu that Roche cited in defense of their claims for the drug and found that they also do not support the use of Tamiflu to treat influenza in healthy adults. In their discussion they write: “oseltamivir may reduce the risk of pneumonia in otherwise healthy people who contract flu. However, the absolute benefit is small, and side effects and safety should also be considered. None of the studies examined the role of oseltamivir in patients with H1N1 influenza, which may be associated with higher rates of pneumonitis than seasonal influenza.”

Finally, in a linked editorial, Fiona Godlee, editor of the BMJ, and Mike Clarke, director of the UK Cochrane Centre in Oxford, rail against the obstructive techniques used by Roche and call for full data from clinical trials to be made available to the scientific community.  “Why should the public have to rely on detective work by academics and journalists to patch together the evidence on such a potentially important drug?” they ask.

All this is bad news for public health planning against swine flu – the Department of Health has already stockpiled more than 30 million doses of potentially useless Tamiflu – and even worse news for Roche.

Jefferson T, Jones M, Doshi P, & Del Mar C (2009) Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis. BMJ 339 DOI: 10.1136/bmj.b5106

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Robo-doc: Sci-Fi Surgery at the Royal College of Surgeons

Would you let a completely unmanned robot operate on you?  Or what about one manned by a surgeon thousands of miles away?  Sounds out of the question, the stuff of science fiction. But you’d be wrong, robotic surgery is here and has huge implications for medical efficiency and safety, as the Sci-Fi Surgery: Medical Robots exhibition at the Royal College of Surgeons aptly demonstrates.

A robot is “a machine – usually computer controlled – that is capable of movement and interaction with its environment”.  Robots have been used to do manual or tedious tasks in industry for almost 50 years, and now they’re being used for the same purposes in medicine – to support busy nursing staff, for example.

ProbotIn addition, robots are more accurate and have better dexterity than humans.  The reduction in incisions and trauma that can be achieved using surgical machines means a quicker recovery for patients, faster discharge from hospital and a better quality of life after surgery.  Robots also produce consistent results and produce few mistakes, if any.

The first surgical robot was the industrial machine Puma 560, which was used by surgeons in 1985 to position a needle during a brain biopsy.  Fast forward to 1991 and the PROBOT made its appearance on the scene.  The PROBOT is an autonomous device used to remove an enlarged prostate gland in a procedure called transurethral resection of the prostate.  Unsurprisingly, neither surgeons nor patients are happy using a completely “hands off” device like the PROBOT, so newer robots tend to use a “shared control” approach.

Rob017_largeAnother interesting type of robot that was developed in the 1980s is “master-slave” robots.  These robots are used to do remote surgery – that is, to perform procedures when the surgeon and the patient are in different physical locations.  The first master-slave robot was called da Vinci Surgical System and was developed by the US army for use in the field, but is now commonly used to remove prostates.  Another telemanipulator, Zeus, was first used by a surgeon in New York to remove a gallbladder from a patient in France.

I was particularly interested in the flash new capsule endoscopes on display at the exhibition.  Capsule endoscopes are pill sized cameras that are used to record images of the gastrointestinal tract in patients suspected of having diseases like colon cancer.  The patient swallows the endoscope and the doctor can view on a screen the whole of their digestive tract.  This approach is considerably more comfortable for patients than normal endoscopy, where a camera on the end of a tube is inserted either in the anus or mouth.

ARESOne problem with capsule endoscopy at the moment is that the endoscope flies down the patient’s digestive tract and the doctor has no control over its speed or where its pointing.  A doctor could spot a dodgy looking region of the gut but won’t be able to go back and get a good look at it because the endoscope is still heading down and out.

New prototype endoscopes on display at the Sci-Fi Surgery exhibition hope to solve this issue.  The Scuola Superiore Sant’ Anna in Pisa, Italy, has developed a remote control endoscope that has “legs” it can use to propel itself through a patient’s gastrointestinal tract.  The design of this particular robot is based on the motion of worms and insects.  Dr Arianna Menciassi, Associate Professor of Biomedical Robotics at Scuola Superiore Sant’Anna, Italy, explains: “We turned to biological inspiration because worms have locomotion systems suited to unstructured, slippery environments and are ideally suited for use in the human body.”

The Scuola Superiore Sant’ Anna has also developed a reconfigurable robot that researchers hope can be swallowed in separate segments that will assemble themselves in the gut into a larger device capable of carrying out surgical procedures.


By far the most disconcerting robot as far as I was concerned was the Bloodbot.  Developed by researchers at Imperial College London, the Bloodbot is designed to help doctors find a vein when taking blood samples.  A probe presses down on the patient’s arm to sense a vein, then inserts a needle under force control.  I don’t know about you, but I’m not keen on having an inanimate object sticking needles in my arm!

With processes in all industries becoming more automated, it was only a matter of time before surgery followed suit.  This little exhibition provides a great primer on the use of machines in medicine.

  • Sci-Fi Surgery: Medical Robots is running at the Qvist gallery in the Hunterian Museum of the Royal College of Surgeons until Wednesday 23rd December 2009. The museum is free and is open Tuesday – Saturday 10.00am – 5.00pm.
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