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‘When Suzanne Ludgate of the Medicines and Healthcare products Regulatory Agency (MHRA), the government regulator of medical devices in the UK, says she was "appalled at how many devices are brought to market with a lack of appropriate clinical data," you know there must be a problem.’

So Dr Carl Heneghan, director of the Centre for Evidence-Based Medicine at the University of Oxford, begins a blog post on The Guardian site.

The term 'medical device' covers a huge range of products that have a medical use and are not medicines. The MHRA notes that this includes anything from walking sticks and hip replacements to glucose monitors, blood pressure machines and pregnancy testing kits. Every day in the UK, millions of people safely use medical devices.

But it is the regulation of these devices that Carl and colleagues at Oxford are concerned with. They have just completed an analysis of product recalls in the UK as part of a joint investigation by the BMJ medical journal and Channel 4’s documentary series Dispatches into medical device regulation. Carl’s post explains the main findings:

‘For the past 6 months, my group at the Centre for Evidence-Based Medicine at the University of Oxford has been looking at how many devices are recalled in the UK each year and what evidence supports their clinical use ... Device recalls are rising dramatically, from 62 in 2006 to 757 in 2010: a 1,220% increase. And yet, when we asked manufacturers for clinical data related to the recalls, we were stonewalled. Of 192 manufactures we contacted, only 53% (101/192) replied, and only four (2%) provided any clinical data.’

In Europe, he writes, high-risk devices only have to establish safety and performance and do not have to prove they make a difference to patients. Carl contrasts this situation with that in the US, where approvals are undertaken by the FDA, and information held is readily available.

Carl calls for the current system of medical device regulation to be tightened so that it requires evidence of improvements in clinical outcomes for patients.

Carl is not alone in this opinion. The BMJ has published a series of commentaries from leading academics as part of its assessment of the issue, from Nick Freemantle, Stefan James, Alan Fraser, John Skinner, and C Di Mario.

The BMJ’s press release says its investigation [see articles here and here] with Dispatches raises ‘serious concerns about the regulation of medical devices and ask how well these high-risk devices are tested before they come onto the market.’ It continues:

‘[BMJ and Dispatches] explore a European approval process negotiated by private companies behind closed doors and reveal a worrying lack of public information about the number of devices being used and their potential risks. They also discuss links between surgeons paid to design devices and the companies promoting them. The investigations findings are clear. The current system is not fit for purpose and we urgently need better regulation to protect patients.’

The Channel 4 Dispatches programme was broadcast last night at 8pm.

The BMJ/Dispatches investigation also saw coverage in the Daily Mail, Independent and online in the Daily Telegraph.

Separately, in an article in the European Heart Journal, heart specialists have called for an overhaul of the system for regulating medical devices such as heart valves and diagnostic imaging equipment, Andrew Jack notes in the Financial Times.

Jack’s article in the FT also offers a comparison of the current approaches to medical device regulation in the US and in Europe:

‘[The British Medical Journal has] published a series of articles highlighting weaknesses in the EU regulatory system for medical devices at a time of growing debate on reforms on both sides of the Atlantic ... European medical device trade bodies have also called for reforms to clarify existing regulatory standards and embraced with counterparts in North America, Australia and Japan through a Global Harmonization Task Force. However, they have also cautioned that excessive regulation risked damaging the medical device sector and could delay access to patients. They pointed to the US, where medical devices are introduced more slowly than in the EU as a result of tighter regulation, while, they claimed, not improving safety.’

Jack points to examples where UK regulators were the first to identify problems, and conversely where devices were rejected in the US but accepted then subsequently withdrawn or discontinued in the EU.

An MHRA spokesperson responded to the BMJ/Dispatches investigation, saying:

‘Medical devices bring widespread health benefits for patients and the public but no product is risk-free. We ensure that the benefits always outweigh the risks. Our priority is to ensure that patients have acceptably safe medical devices. We monitor all adverse incident reports and take prompt action to address any safety or performance concerns.'

The regulators note that manufacturers of all devices are required to have clinical data to support their performance claims for the device. In most cases, and in particular for higher risk devices, this information will come from a specific clinical trial on the device itself. However clinical data may also come from a literature review of the clinical information on equivalent devices. Where a manufacturer plans to carry out a clinical trial in the UK, agreement must be obtained from the MHRA. 

The spokesperson adds: ‘What must be borne in mind is the balancing act of generating clinical data pre-market and the benefit to patients of innovative products reaching the market place.’ 

Where this balance should lie is the question that concerns all of these parties. 

Darren Mann likes nothing better than getting his hands dirty. He’s at his happiest in the field with magnifying glass and notebook, delving into a fresh pile of poo. He is an insect expert and a specialist in dung beetles, some of nature’s best recyclers. ‘They’re an amazing group of insects,’ he tells us. ‘My life revolves around my girlfriend and insects. I work 10 to 12 hours a day and half the weekend, and when I’m not working I’m out collecting.’

Darren is Assistant Curator for Entomology at Oxford University’s Museum of Natural History [OUMNH]. He has just returned from Borneo where he and Dr Eleanor Slade of the Department of Zoology and Oxford’s WildCRU are involved in an innovative project to study the effects of logging on the various benefits provided by rainforests. Under the Stability of Altered Forest Ecosystems project [SAFE], whose sponsors include Borneo’s Sabah Forestry Department and the UK’s Royal Society, fragments of forest are being left in an area to be felled for palm oil. Dung beetles will be an indicator of the profusion of larger species in the rainforest areas that remain.

‘Dung beetles are quite sensitive to habitat change and because they feed on dung they can be used as a surrogate for mammal abundance,’ Darren explains. ‘They’re now one of the most popular groups used in ecological studies. We have the pre-logging data from Borneo and hope to go back to record any changes. It’s such a cool project and a wonderful opportunity to track change over time.’

There are more than 5,000 species of dung beetles inhabiting every continent bar Antarctica. Most belong to the sub-family Scarabaeinae and within that group, can be distinguished by their differing breeding behaviours: dwellers live in dung; rollers roll dung balls elsewhere; and tunnelers bury dung in situ. Females lay their eggs in the dung, which becomes food for emerging larvae. Some females must cling to dung balls as they are wheeled away from the main dung pile.

Dung beetles perform many useful roles, returning goodness to soil, dispersing seeds excreted by mammals and saving farmers huge sums by clearing fields of livestock manure. They were successfully imported into Australia between 1969 and 1984 because native beetles couldn’t cope with the volumes of dung produced by introduced cattle.

Beetles are caught by setting small traps baited with faeces. They are removed for identification which can mean finding new species. Darren is credited with discovering several insect species new to science and has a dung beetle, Copris manni, named after him. He has published many papers and collected specimens in several countries including Costa Rica, Pakistan, Turkey and Namibia.

When he came to the Museum of Natural History in 1997 to interview for the post of collections’ technician he was so convinced he’d be overlooked for the job that he treated his first visit as a chance to marvel at some of the site’s five million preserved insects. His passion won over the interview panel and he has won several promotions since. Darren is now responsible for insect collections some of which are centuries old. Currently he is providing specialist help to the charity Buglife, which is trying to establish the locations of Britain’s four remaining oil beetles. He is also updating the UK guide that first inspired him as a schoolboy in 1986, Dung Beetles and Chafers by L Jessop. ‘Reading it was like an epiphany, one of those life-changing moments. I’ve been hooked on dung beetles ever since.’

Darren says he was ‘a really, really bad student’ at school because so little interested him. ‘I didn’t see the point in going because they weren’t teaching me about insects.’ He forgot to attend an A level exam because he was too busy collecting. ‘I found a Rhynchites cavifrons, a really beautiful weevil,’ he recalls. He subsequently missed lectures, and turned down the chance of degree studies at Plymouth Poly, but years later still won a place on a postgraduate diploma in insect taxonomy at the University of Wales.

Darren’s favourite beetle is tattooed on his chest. It is Coprophanaeus lancifer, the giant Amazonian carrion scarab beetle. The exoskeleton of a specimen looks down from a shelf above Darren’s desk. ‘I was asked at my Oxford interview whether I’d have the same passion for entomology in 10 years time. I do. I can stare at a beetle in a microscope for four hours and not get bored but I’ve never read a novel from start to finish; I’d much rather sit in a field and watch a bee pollinate a flower.

‘I have to do natural history wherever I am. I don’t understand how people can’t do natural history or go out for a walk and not try to identify what they see.’ Mounted police officers in Richmond Park did understand and once pulled up alongside Darren as he was busy ‘dung beetling away’.

He remembers the incident well: ‘I explained what I was doing and they burst out laughing. When I’m out collecting, some people look at me in disgust but most just think I’m a bit of a weirdo. I’m perfectly at ease sticking my hands in a pile of dung and I’ve never been ill. I think I’m pretty well inoculated against anything that’s in there.’ 

The two thousand, seven hundred and eighty-fourth baby has been vaccinated today in South Africa as part of a clinical trial of a new vaccine against tuberculosis. The new TB vaccine is the most advanced in development anywhere in the world.

That’s the last baby in the trial, and marks completion of trial enrolment almost two years to the day after the study was first announced.

‘We are extremely proud of this achievement and are eager to see the study results, which are expected to be available in 2012,’ says Dr Helen McShane, who developed the vaccine at the Jenner Institute, Oxford University. ‘This milestone brings us a step closer to potentially having a new TB vaccine, from which millions of people around the world would benefit.’

It’s certainly quite a milestone, and marks a great deal of work to vaccinate all these babies under 1 year old in an area where there is one of the highest rates of TB in the world.

But why precisely 2,784 babies, not 2,500 or 3,000?

Helen explains that it is entirely down to the calculations used to plan the trial. These sums showed that 2784 babies should give enough statistical weight to be able to see a significant improvement in preventing TB over the 90-year-old (but still standard) BCG jab.

The new vaccine is designed to be given to infants after they have received the BCG vaccine, boosting the immune response further. All the babies in the trial have received the BCG vaccine, with half then getting the trial vaccine and half a placebo. ‘If successful, the next steps would be to plan a phase III trial and licensure of the vaccine,’ Helen says.

The current trial was a phase IIb trial, and is the first to be able to really determine whether the vaccine gives infants any protection against TB. A larger phase III trial would pin down exactly the size of any benefit and guide how the vaccine could be rolled out.

The trial in Worcester, about 100km from Cape Town, is being conducted by the University of Cape Town’s South African Tuberculosis Vaccine Initiative (SATVI), in partnership with Aeras, the Wellcome Trust, and the Oxford-Emergent Tuberculosis Consortium Ltd (a joint venture between the University of Oxford and Emergent Biosolutions Inc formed to develop the vaccine).

‘We are pleased to report that the trial has run smoothly to date,’ says Dr Hassan Mahomed, who has led the trial at SATVI.

This July an expedition will set out for the central highlands of Indonesian Borneo to sample the biodiversity of uncharted areas, track ape populations and find out how remote communities interact with their environment.

Among the 20-strong BRINCC Expedition team of conservation biologists will be Susan Cheyne of Oxford University’s WildCRU, one of the leaders of the OuTrop Project.

The team will follow the route of the Murung River, a major tributary of the Barito River, surveying the sort of wildlife – apes, birds, insects, reptiles and amphibians – essential to the health of a tropical forest ecosystem. The researchers are particularly keen to find out more about nocturnal species.

Susan is one of the team with a special interest in the area’s hybrid gibbons: a hybrid of the Bornean agile gibbon (Hylobates albibarbis) and Müller's Bornean gibbon (Hylobates muelleri) about which little is known. These apes currently have no status on IUCN, Susan explains, despite being a naturally occurring, viable and thriving population.

‘We don’t know whether orang-utans are also present,’ Susan told us. ‘This will be the first comprehensive ape survey in this area and will be combined with collecting data on the other primates throughout the course of the expedition.’

As with the OuTrop Project, involving local people in the work will be a vital part of the new mission. At several villages along the Murung the team will train people from the indigenous Dayak community how to use GPS to help accurately identify and map areas they use. It is hoped that the maps will help in both conservation and any future debates about land rights.

Susan adds: ‘The BRINCC expedition team has extensive experience working in conservation activities in Indonesia and we hope to take this knowledge and know-how into the uncharted centre of Borneo, an area which has received relatively little conservation attention compared to lowland forests.’

For more information and details of how to support the research visit the BRINCC Expedition Blog.

Dr Susan Cheyne is a member of WildCRU, part of Oxford University's Department of Zoology.

Research published last week in the journal PNAS may have identified a promising new target for developing drugs against one of the most common types of lung cancer.

Oxford University researchers have helped a team at biotech company Genentech in South San Francisco look at the role of a protein called PAK1 in the growth of tumours.

PAK1 is a protein involved in a biochemical cascade used by cells in the body to control things like cell growth, division, and survival. Other proteins in this pathway have been implicated in cancer – when these controls go wrong, they can lead to uncontrolled cancerous growth.

Dr Adrian Jubb and colleagues at the Weatherall Institute of Molecular Medicine at Oxford were able to develop a test to look at levels of PAK1 in lung tissue samples from a tissue bank in Oxford. They showed that PAK1 was found at higher levels in one type of lung cancer, specifically the squamous type of non-small-cell lung cancer.

Building on these observations, the Genentech team were then able to show that knocking out the PAK1 protein stopped the growth of cells from these human lung cancers in the lab. Similarly, inhibiting PAK1 could impair growth of these tumours in mice.

Importantly, results also showed that combining an attack on PAK1 with other targeted therapies that Genentech is developing might kill off the cancer cells.

This suggests that such combination drug therapies might be a promising new avenue in searching for new treatments for non-small-cell lung cancer.

Certainly, lung cancer (of all types) is one of the most difficult cancers to treat, and has one of the lowest survival rates of any type of cancer. Fewer than 10 per cent of lung cancer patients survive the disease beyond five years after diagnosis. It is often diagnosed at a late stage and it tends to occur in older people who may also have other medical conditions.

Non-small-cell lung cancer accounts for around 85 per cent of all lung cancer cases, with around 30,000 people are diagnosed with this form of the disease each year in the UK.

Non-small-cell lung cancers can be further divided into three types: squamous cell carcinomas, adenocarcinomas, and large cell carcinomas.

Squamous cancers are the most common type of lung cancer, and are often due to smoking. It is squamous cancers that have been identified as having raised levels of PAK1 in this study.

Beyond doing what’s already possible with surgery, radiotherapy and chemotherapy, options for drug treatments of non-small-cell lung cancer are limited.

‘Non-small-cell lung cancer is an unmet clinical need,’ says Adrian Jubb. ‘We simply need more effective treatments.

‘We have demonstrated that targeting PAK1 has antitumour activity. And we now have a platform for assessing whether PAK1 is also worth pursuing for other squamous cancers, such as head and neck cancers, or other tumours including melanoma and pancreatic cancer.’

The Oxford work was supported by Cancer Research UK, the Oxford Biomedical Research Centre and the Pathological Society of Great Britain.