Lateral thinking on diagnostics can help tackle antibiotic resistance

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(Originally published on Health Service Journal Blog, 18th Nov 2014, available here)

New diagnostic technologies can help improve patient outcomes, support changes to our habits and improve surveillance systems to tackle antibiotic resistance, writes Anna Williams

The rising use for antibiotics was linked with the growing prevalence of antimicrobial resistance in a Public Health England report, published last month. To most health professionals this is not groundbreaking news. Nevertheless, our understanding of the development mechanisms of resistance pales in comparison to the magnitude of the problem it presents.

Thankfully, this year there has been much very vocal activity about antimicrobial resistance, such as the publicity surrounding the Longitude Prize. Projects such as these should make us all re-examine our own relationship with antibiotics and look at what can be done to help slow resistance. There is no “magic bullet” for this problem but more can be done to help both from a technical and a social perspective.

Today marks the launch of the Longitude Prize, so it is fitting that we should open the competition for entries on the same occasion as European countries come together for Antibiotics Awareness Day. There is no better time to spread the message about prudent use of antibiotics and reflect on the global problem of antibiotic resistance.

Focus on the future

The Longitude Prize 2014 is a competition with a £10m fund to tackle antibiotic resistance.

I work as a researcher in the team developing the prize at Nesta. We are asking people from across the globe to come up with a point of care diagnostic to detect and understand infections to enable the prescription of the right antibiotics at the right time.

We hope entrants produce new and innovative diagnostics that will ultimately help to slow the rate of antimicrobial resistance and enable us to safeguard antibiotics for the future.

Tools and tests are one way to help us slow resistance by providing healthcare professionals with information to help make accurate clinical decisions. They can help definitively rule in or out bacterial infection, directly informing the decision to prescribe antibiotics.

However, there remains a technical challenge in developing a diagnostic that is rapid and sufficiently accurate to inform antibiotic prescriptions at the point of care, as well as being cost effective.The diagnostics the Longitude Prize seeks to develop may also go one step further by providing all of the necessary information to identify an effective antibiotic or combination of antibiotics.

This would allow clinicians to use a targeted, narrow spectrum of antibiotics that perhaps they wouldn’t normally use on the first occasion, thereby minimising the use of broad spectrum antibiotics. There are some exciting diagnostics out there already – for example, Spectromics is in the patent application stage for its urinary tract infection diagnostic. The test monitors phenotypic change that occurs between a urine sample and different candidate antibiotics to provide guidance on the most effective treatment. Up to 70 per cent of urinary tract infections are resistant, so Spectromics and other innovators in the field have the potential to inform accurate diagnosis and treatment, thereby improving care for a large proportion of patients.

Swelling numbers

Inflammation can be an indicator for bacterial infection and there are several tests that have been developed to detect biomarkers for inflammation. There are a variety of blood based tests for procalcitonin levels that are able to detect sepsis in patients. A recent systematic review of these tests showed that they may be effective in informing the initiation and termination of antibiotic treatment for respiratory infection, reducing overall exposure to antibiotics. This is encouraging news.

However, the relative benefits of inflammatory tests such as procalcitonin and C-reactive protein are widely debated, so there is a need for further research into their use in primary care settings. There has been innovation in the range of tests for bacterial infection, but they generally are unable to fully demonstrate cost effectiveness, accuracy and usability in comparison with the best available alternatives. The Longitude Prize is pushing innovators to address such inadequacies and calling for a more ambitious test than anything currently available.

Surveillance tactics

Better surveillance techniques to collate data on bacterial resistance will help us better understand its spread and underlying mechanisms. The more we understand the situation facing us, the better we can deal with the issue head on. Surveillance is needed in all environments where resistance can occur and diagnostics can act as a tool for collecting information.

At a national level, hospitals are best equipped to carry out surveillance. However, more and more care is being delivered in the community by multiple organisations providing more than one services and this may lead to difficulty in implementing standards for surveillance. Explicit infection control policies need to be developed by each organisation responsible for the care of individuals, which are specific to the settings of care. This should include all care settings, from hospitals to homes, community transport and day centres.

The standardised collection of data through diagnostic devices presents a simple way to increase surveillance in these settings. The 2011 chief medical officer’s annual report asserts that NHS England is well placed to collect, collate, analyse and disseminate information from surveillance. The UK needs to develop methods to ensure consistency and standardisation of data collection, but we also need to understand how this data will be used, so we collect the most useful information.

The European Centre for Disease Prevention and Control sets a good model for best practice in data collection, evaluation and dissemination. Such models should be considered when action is taken to federate and connect databases from health and social care in the UK.

The chief medical officer has also called for interoperability standards for health information systems, so emerging surveillance technologies can easily be integrated. This interoperability will also provide vital flexibility when actions are taken to globally integrate surveillance efforts.

Human nature

Human behaviour plays a big role in tackling resistance. The British public demonstrated their support for tackling the issue of antibiotic resistance by voting that this should be the focus of the Longitude Prize. In a new survey – published today for the prize – 78 per cent of respondents expressed concern about the issue of antibiotic resistance. However, it is interesting that public concern may not always translate into responsible behaviour, because nearly a quarter of respondents admitted to not completing a course of antibiotics prescribed to them.

Our own actions can contribute to resistance. Whether a doctor has prescribed antibiotics when not necessary or whether a patient has decided not to finish a course, all rests with the individual’s responsibility. Every time we expose bacteria unnecessarily to antibiotics, we create an environment that is favourable to the development of resistance. In another survey for the Longitude Prize, 28 per cent of British GPs prescribe antibiotics “several times a week”, even when they’re not sure they’re medically necessary.

Nearly all (90 per cent) say they feel pressure from patients to prescribe: 70 per cent do so because they’re not sure whether the patient has a viral or bacterial infection, and 24 per cent say it’s because they lack easy to use diagnostic tools. New diagnostic technologies can help improve patient outcomes, support changes to our habits and improve surveillance systems to tackle antibiotic resistance.

As well as technology to combat resistance there must be local, national and global action to innovate within healthcare systems to make effective use of existing tools and resources to tackle the problem. We hope diagnostics will play a key role in making this journey easier.

Anna Williams is a Researcher at Nesta

Widening scope to tackle antimicrobial resistance

Originally published in the National Health Executive July/Aug 2014 – available online. 

In June the public selected antibiotic resistance to be the focus of the Longitude Prize 2014. This £10m prize fund is calling for a new and innovative point of care toolkit that will help combat the growing problem of antibiotic resistance. Anna Williams, researcher on the project, explains.

Antibiotics have revolutionised medicine, adding an average of 20 years to each person’s lifetime. Penicillin alone has saved tens of millions of lives since its discovery 86 years ago but the efficacy of these life saving drugs is threatened by the evolution of resistant bacteria. This resistance is caused in part by human behaviour and prescription practices. The G8 Science Ministers’ meeting in June 2013 identified antimicrobial resistance as “humanity’s most pressing concern, transcending national boundaries and posing significant threats to societies and ecosystems”.

Taking action: Widening scope for stewardship

The effects of antimicrobial resistance on the NHS can already be seen in efforts to tackle Methicillin-resistant Staphylococcus aureus (MRSA) and C. difficile. These resistant Health Care Associated Infections, caused thousands to die at the peak of the outbreak. The highest recorded number of deaths in the UK caused by c. difficile was 8,324 in 2007.

Through better control of antibiotic prescribing, handwashing and hygiene protocols and consistent, meticulous, intravenous central line care, outbreaks of MRSA have reduced by 84.7% between 2003 and 2011 and outbreaks of C. difficile by 53% between 2008 and 2011.

There is a large evidence base for the methods used to tackle MRSA and C. difficile, success has come in part through mandatory surveillance and target-setting. However, our current infection control policies might not be best designed to tackle infections other than MRSA and C.difficile. With outbreaks of gram-negative health care associated infections on the rise, it cannot be assumed that the same methods of infection control and surveillance will be successful for these new types of resistant infection.

Gram-negative bacteria have unique features that make them harder for antibiotics to target. Gram-negative bacteria are also developing multi-drug resistance. Giving rise to infections including pneumonia, wound or surgical site infections, and meningitis in healthcare settings, they now account for the majority of blood stream infections.

Although continued monitoring is vital, perhaps we should widen the focus to infections other than MRSA and C. difficile. There are two main courses of action to be taken: prevention and control of infection, and the development of novel antibiotics. However, the number of antibiotics in the development pipelines is low, and with growing incidents of multi-drug resistance organisms, stewardship of existing antibiotics is of increasing importance.

Courses for action

Clinical Commissioning Groups can impose financial penalties upon a Foundation Trust that fails to reach targets for the reduction of MRSA and C. difficile infections. However, these penalties have been criticised because infection trajectories are difficult to predict, bringing into question the creation of specific targets. Financial penalties could be even less effective for gram-negative infections, for which less evidence for predicting trajectories is available.

‘Stewardship’ initiatives aim to reduce the unnecessary prescribing of all types of antibiotics. The ‘Target Toolkit’ and ‘Start Smart, Then Focus’ campaigns give guidance on antibiotic prescriptions in primary and secondary care respectively. However, because gram-negative bacteria respond to very few classes of antibiotics, we require more than guidance on prescription practices.

Surveillance is needed in all environments where resistance can occur. As care is increasingly being delivered in the community by multiple organisations, this may lead to difficulty in implementing standards. Therefore, we require action to develop explicit infection control policies that are specific to the settings of care.

The Chief Medical Officer commented that the NHS is well equipped to collect, collate, analyse and disseminate information from surveillance. The Department of Health has stated that the UK needs to develop methods to ensure consistency and standardisation of data collection and this could be helped by opening up access to statistical information about infection for modelling. This work must be underpinned by common interoperability standards for health information systems so that emerging surveillance technologies can be integrated across national borders.

Point of care test kits

There is a role for innovation in diagnostics for infections to improve infection control and surveillance in the future. Current lab culture based techniques for the diagnosis of infection are slow, and require specific resources and expertise. The development of cheap, accurate and rapid point of care diagnostics will allow for the more targeted use of antibiotics. This in turn will lead to a reduction in the use of broad-spectrum antibiotics, curtailing the opportunity for resistance to occur. The impact on global levels of resistance could be far reaching if the test was versatile and cheap enough to be used in primary and secondary care settings. Such test kits will also provide an opportunity to collect data on infection from a much great range of care settings across the world.

The more patients that get the right antibiotic prescription the first time, the longer we can preserve the action of our existing antibiotics. This is why the Longitude Prize is offering a reward fund of £10 million, in order to incentivise innovation in point of care diagnostics for infection. Over the next 5 years, Nesta with the support of the Technology Strategy Board, will be accepting and judging submissions from innovators who are working to produce a rapid, accurate test that has the potential to identify bacterial strains and profile possible resistance to antibiotics.

Novel innovation, both in diagnostics and the production of antibacterial agents have to be supported by surveillance and data collection. Then we can develop an effective evidence base for techniques to control antimicrobial resistance with co-ordination at a local and national level. The global nature of resistance means that we must also find new ways to work internationally, share data and set standards for interoperability in order to slow this growing threat.

Anna Williams, researcher, Longitude Prize 2014

Longitude Prize: Incentivising MedTech to deliver solutions

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Originally published on MedTech Views Blog 19th June 2014, available here.

The £10 million pound Longitude Prize forms another route to funding vital medical and healthcare research, from antimicrobial resistance, to paralysis and dementia.

 

MedTech is transforming the world in which we live; we are healthier and more able than ever before. However, there are still a number of fundamental challenges that we face both locally and globally. The launch of the Longitude Prize 2014, with it’s £10 million prize fund, is seeking solutions to some of these fundamental scientific challenges. Antibiotic resistance, paralysis and dementia are on the shortlist of issues that could reap a £10m research windfall. The MedTech community has a vital and integral role to play, harnessing its power to innovate and accelerate towards the winning solutions!

The British public is being asked to cast the deciding vote to choose which challenge the Longitude Prize 2014 should focus on. Three out of a total of six challenges have implications for medicine and healthcare, that’s half the shortlisted challenges. This not only reflects the global importance of improving healthcare, but it also highlights the importance of MedTech as discipline. From dementia to antimicrobial resistance and paralysis, these challenges are diverse and require lateral thinking, which we so often see in the entrepreneurial MedTech community. Nesta, with the support of the Technology Strategy Board has developed the prize and the Longitude Committee identified these six challenges with careful consideration to ensure a science prize might be the most appropriate mechanism to stimulate innovation and collaboration that might otherwise not occur.

Antibiotics

The preservation of antibiotics and the production of novel alternatives is vital to our future survival. Many existing antimicrobials are becoming less effective, as bacterial colonies are developing resistant to treatment, while the inappropriate use and misuse of these medicines is causing an acceleration of the numbers of reported cases of resistance globally. The pipeline for the development of new antibiotics is at an all time low and initiatives to implement behavioural and education programmes are in their infancy. Most policy proposals to tackle antimicrobial resistance put forward two main points for action: Action to conserve the antimicrobials that we already have, and action to accelerate solutions in diagnosis and drug development.

For the first time, antimicrobial resistance topped the agenda at the G8 meeting of science ministers last year. While solutions have been proposed to incentivise and accelerate solutions in drug development with initiatives such as, Advanced Market Agreements (AMAs) and Product Development Partnerships (PDPs), challenge prizes still have an important role to play. The Chief Medical Officer for England, Dame Sally Davies has highlighted the need to encourage a range of incentives to address the currently stagnated pipeline, primarily she proposes the use of PDPs, AMAs and Science Prizes as well as changes in patent agreements, to extend the patent period from twenty years to, say, twenty-five years.

Antibiotics underpin all modern medicine. It is vital that health professionals can make increasingly accurate prescriptions, reducing the number of broad-spectrum antibiotics used. There are several interesting MedTech and biomedical research groups already working in this area. For example, RAPP-ID are working on point-of-care test platforms for infectious diseases. But as Rangarajan Sampath mentioned in his blog yesterday, current culture based techniques are often inaccurate for bacterial diagnosis and we require innovation to improve patient care. The Longitude Prize for antibiotics will incentivise this much needed innovation, competitors will be asked to develop a cheap, rapid and extremely accurate point of care test that can enable practitioners to diagnose a bacterial infection in a variety of health care settings.

Paralysis

Paralysis can be devastating, and affects people with a range of medical conditions from stroke to nerve damage. Although some types of paralysis can be improved through intense rehabilitation, there is no effective treatment to restore the function of the nervous system. To the outside world, this limited mobility is the main symptom of paralysis. In reality, numerous secondary conditions dramatically affect the day to day life of those with paralysis. These secondary symptoms often include loss of normal bladder and bowel function, sexual function, low blood pressure, the formation of blood clots, pneumonia, neuropathic pain, spasticity and muscle spasms.

Given the multiple causes of paralysis, for example, stroke, spinal cord injury, and multiple sclerosis, a total cure for paralysis is distant goal for medical science. In the meantime, there is an extraordinary opportunity to develop incremental solutions that restore freedom to those who have been paralysed. Therefore the paralysis prize seeks solutions that could restore movement to individuals with any form of paralysis, in an easy light and useable form. The innovation must also address the secondary symptoms of paralysis.

The beauty of this prize is that there is scope for new forms of collaborations within the MedTech industry. For example, Neuroprosthetics is an area of research that has seen significant progress in the past decade, some treatments focus on replacement strategies by recording the electrical signals of neurons in the brain and translating them into the movement of devices such as robotic arms. Regenerative medicine has also made a lot of progress towards finding a cure for paralysis, but solutions are still in an early phase. Developments in robotics, bioengineering, and artificial intelligence have led to innovative technological solutions that offer support to people with paralysis. The emergence of assistive devices such as powered exoskeletons like REX, are an amazing feat of engineering, however all of the current fields of research need future refinement and could benefit from future collaboration in order to win the prize.

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Picture: REX in action

Dementia

It is estimated that 135 million people worldwide will have dementia by 2050.

In order to solve the problems posed by dementia, we need a cure, condition-altering treatment or a robust preventative intervention. New treatments, for instance anti-tau drugs, are currently being developed and could potentially improve cognitive functioning, but it could be many years before they are approved for clinical use, if at all. As with all chronic conditions, care plays a critical role in the management of dementia. This care will usually take the form of emotional, cognitive, and physical support from paid carers, but also from close family members, and friends.

Studies suggest that telecare systems and home automation have great potential to reduce the cost of chronic conditions where management is key. The largest barrier to success of the systems that currently exist is that they are not well suited to the nature
of dementia; for instance, they will often require interacting with new, unfamiliar devices or change established patterns of behavior in order to acquire meaningful information, things which many dementia sufferers would find difficult. However, there are a range of novel technologies that are in development, from simple location devices and fall sensors, to more complex ambient sensor systems such as the ambient kitchen developed by Newcastle University. Although stand-alone technologies exist, the prize for Dementia will focus on the development of assistive technologies that deliver an exceptional level of care, while rewarding innovation that provides an integrated home system of ambient technologies that support people with dementia to live independently in their own homes for longer.

Many of these issues are already being worked on by experts in a diverse range of science and technology disciplines related to medicine and healthcare. Three other non-medical challenge areas are also available to vote on: water, food and flight.Prizes open up new opportunities and we are throwing down the gauntlet to the MedTech community to provide new innovation. In Autumn 2014, we open the challenge to innovators across the world to solve the public’s chosen problem.

Find out more and vote for your chosen challenge here: http://www.longitudeprize.org/

Watch the BBC horizon documentary about the Longitude prize here: http://www.bbc.co.uk/iplayer/episode/b044mkxt/horizon-the-10-million-challenge

Twitter: @Longitude_prize

Facebook: https://www.facebook.com/longitudeprize

Antimicrobial resistance: Should a technological fix be considered?

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The Nesta project I’m currently working on is looking to identify challenges we face as a society. Under the theme of health, we have been discussing various challenges that might be solved in the future through science and technological intervention or development.

The Health panel is led by Dame Sally Davies, Chief Medical Officer for England, who has publicly stated her concern that over-prescription of antibiotics is causing antimicrobial resistance. At a G8 meeting on health in June Davies said, “If we don’t take action, then we may all be back in an almost 19th Century environment where infections kill us as a result of routine operations.”

After discussions with our expert panel last month, it became clear that a possible future ‘fix’ to this problem might be a cheap (no more than 10p per unit) test that distinguishes viral from bacterial infections.  This would reduce the number of viral infections mistreated with antibiotics. Such a testing device might even be able to tell which type of bacteria are present, reducing the probability of prescribing the wrong form of antibiotic.

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Antibiotics are also misused by patients, often forgetting to complete a full course or taking old prescriptions. A test kit will help doctors’ prescription accuracy but it isn’t going to help the patient become more responsible about finishing the course of antibiotics. However, I want to explore how the technological fix might be part of the solution. For the most effective intervention we must see the problem of misuse by patients and the problem of mis-prescription by doctors as part of a bigger problem, a socio-technical one, that can be tackled holistically.

STS scholars often take a negative view of the ‘technological fix’. Rosner suggested that the term has come to be associated with a quick cheap fix using inappropriate technology. However, for some the technological fix was everything. Weinberg was one of the first to discuss the technological fix in the 1960’s. He used the example of the intrauterine device (IUD) as a means to stop unwanted pregnancy because it avoided the need to change people’s behaviour; it “provides a promising technological path to the achievement of birth control without having first to solve the infinitely more difficult problem of strongly motivating people to have fewer children”. This intervention embodies the cause – effect relationship, connecting problem to solution, which Sarewitz and Nelson argue is one of the three rules that determine the appropriateness of a technological fix for a social problem.

The trouble with the above arguments is that they assert an all-or-nothing approach to the technological fix. Even for those critics of the technological fix, such as Burke, conceiving of social problems through engineering terms would only make problems worse, but he concludes that the technological fix is either appropriate or inappropriate for the task in hand.

I propose that the technological fix is appropriate for some social problems, however I argue the all or nothing approach set out by Burke or Weinberg is flawed. The technological fix can happen alongside a social, political or economic intervention to achieve the best outcome – the ‘techno-social fix’.

According to Sarewitz and Nelson, the key to effective innovation policy is to distinguish problems that are amenable to technological fixes from those that are not.  Using Sarewitz and Nelsons three rules we can see how part of the antimicrobial resistance problem can be solved through the ‘fix’ of the test kit.  The first rule states the ‘technology must embody the cause effect relationship connecting problem to solution’. The effectiveness of a test for bacteria is independent of the person giving it; the test kit or ‘artefact’ encapsulates the essence of what needs to be done. The second rule states ‘the effects of the technological fix must be assessable using relatively unambiguous criteria’. Test kits are trusted tools in other forms of biological analysis, such as HIV testing, or blood sugar levels. Universal agreement leads to ‘operational cooperation’. The third rule is ‘research will solve a social problem when it focuses on improving a standardized technical core’. The standardised core in this case is the antibiotics themselves, providing the foundations from which improved practice can be implemented through an intervention such as test kits.

Clearly according to the three rules stated above, the bacteria test kits are a ‘technological fix’ to the problem of misdiagnosis causing antimicrobial resistance, but do not address the problem of misuse by patients. I would assert that the technological fix is still a vital part of the solution here. From a holistic perspective the technology would have to be implemented at the same time as a concerted campaign for education/behaviour change for patients. A technological fix on its own seems to form a part of the bigger whole. In this case technological and social intervention need to act together to produce change. This idea runs counter to many of the all or nothing arguments discussed in relation to the technological fix above.