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

The Golden Ticket

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The shiny envelope contained a cheque – a multimillion pound prize to reward science and technology innovation.  It’s the science equivalent of Willy Wonka’s Golden Ticket. The process of prizes seems simple; offer a monetary reward to incentivise science or technology innovation.  Yet the lavish nature of past science prizes has been criticised. Some have suggested that prizes feed the ego of billionaire funders more than they advance science or produce role models.

Longitude 2014 is Nesta’s first multimillion-pound science and technology prize to solve a major societal problem. As we get swept along in the hype around science and technology prizes, should we look at the small print before we say ‘yes’ to the golden ticket and the invitation to the chocolate factory?

The situation is complex.  First we need to establish that there are different types of prize. We can simply spilt prizes into two categories. There are more complex ways of categorizing prizes, and the people who design prizes would probably growl at us for this. Anyway, onwards…

The first and probably the most famous prize type is the recognition prize. The most well known is probably the Nobel Prize. A reward made for amazing achievements in science, technology and the humanities after the innovation has taken place.  For some these are perceived to raise the profile of science, for others these seem to provide valuable tokenism; an effective way of rewarding certain scientists, reflecting society’s appreciation for science. In some respects this type of prize allows science to stick to its Mertonian norms. One central facet of Merton’s argument was that scientist should behave disinterestedly with no emotional or financial attachments to their work. Despite the glamorous ceremonies, these prizes are good at preserving this view of the scientist; where the people ‘doing’ science are on a quest to solve a problem. Their view is unclouded by personal opinion or monetary gain, they do it for the love of science. Recognition prizes reward achievements without making scientists look unprincipled.

The second category is the inducement prize, which is a different kettle of fish. They seek to capture existing and new interest in a pursuit to achieve a given goal set out by the prize designers. It’s a bit like bounty hunting – catch this piece of science through your data, hand it to us safely and in exchange we will give you a monetary reward.

Inducement prizes

Inducement prizes generally can be split into two domains. The first are those that look to achieve ‘moonshot’ thinking, a phrase used by Google’s Solve For <x>. These prizes look to accelerate solutions through science and technology. These solutions appear so far off that its worth having a prize to hurry things along. A good example is the Virgin Earth Challenge.  The second are those prizes that address a particular societal problem, in areas of science that may be less desirable or profitable, where scientists would have little incentive to find solutions.

The prize design

Alexandra Hall, Senior Director of the Google Lunar XPrize told me, “The most effective part of the process for us is ‘visioneering’, a process whereby we get lots of people in the room, from scientists to designers and musicians.” This process allows the development of prize design, which is vital to achieving eventual successful innovations.  Visioneering brings together people from both the creative and scientific fields to scope possible future challenges which science and technology innovation could address.

This is an important step in the prize design process, the visualising of the future, the knowing what might come next, especially when the scope of your prize might be looking 10-20 years into the future. A prize must be both achievable but also not too achievable based on current scientific knowledge. The Archon XPrize is a good example of how easy it is to misjudge the scale of scientific challenge. The prize was announced in 2006 and offered $10 million to the first team that could rapidly and accurately sequence 100 human genomes, at a cost of $10,000 or less dollars per genome. The expected pace of research has accelerated so much so that a genome can now be sequenced for less than $5,000 dollars, therefore the Archon Genomic XPrize was recently cancelled.

This raises questions about the value to science of inducement prizes; how do we accurately predict the future and set realistic goals? Do prizes stifle innovation through strict criteria? After all, lots of good science has happened by accident, from the synthetic dye and the ink jet printer, to penicillin and vulcanized rubber. Should we rule out inducement prizes because they won’t let us advance further than our imagination will allow?

It’s easy to design a challenge with a set metric or a specific achievement by which it can be judged. For example the Lunar XPrizes have a requirement to successfully land a spacecraft on the moon and subsequently send back two “mooncasts” to the earth. The question remains of how we design a prize to address a significant societal problem. Indeed more generally academics such as Nelson have asked why science has found it so difficult to solve major societal issues, when we have successfully put men on the moon.

Here ideas of innovation and the way in which knowledge is produced and utilized come into question. The concept of an ‘innovation system’ to describe the organisation of institutions and polices that direct technological change, has been used to better frame ideas around how science and technology come into being.

In his 2011 paper Nelson goes on to suggest that reorientation of innovation systems is a positive step towards allowing science and technology to address complex societal needs. However a fundamental barrier to innovation is limited knowledge and this needs to be highlighted. Indeed this problem can be seen in prize design, often the objective is to incentivise innovation, yet the judging criteria can be restrictive and exclude certain groups from entering.

Nesta’s multimillion-pound Longitude 2014 prize is seeking to reward innovation to solve particular societal problems. The Prize is currently under development, and it’s interesting to observe the intricacies that Nelson mentions being playing out.

Science could be seen as socially constructed, a process of interaction, sharing and validation, however setting specific science metrics to win prizes adheres to the empiricist view that science is in the pursuit of solid evidence. Jasanoff argued that science is a process of co-construction of knowledge. Nelson highlights that barriers in solving societal problems grow from limited knowledge. Belief replaces evidence, and there are divergent beliefs about the effects of various proposed solutions. Nelson uses an example of drug addiction and drug-related crime where lack of knowledge about solutions results in valued based conflicts within the scientific community. This is true today and I see challenges arising in the design of the Longitude Prize that follow the same pattern. There is disagreement in the scientific community about how we might tackle certain future societal problems.

Therefore it is imperative, that the Longitude Prize allows for unforeseen ‘moonshot’ thinking, and this must happen in the prize design phase. ‘Reoreintation’ of the innovation system with respect to inducement prizes would begin with flexibility in setting winning criteria. If we broaden our horizons the answer to solving the problem of drug addiction is as likely to come from a drug company as an artist or a designer.