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  • Nonadherence to medication is a vast and rapidly growing killer epidemic
  • The epidemic is under reported, under-treated and costs healthcare systems billions
  • No healthcare stakeholder has assumed responsibility for reducing the burden of nonadherence and so it has become an orphan issue
  • Psychological techniques used by policy makers have been shown to change peoples’ behaviours, improve healthcare and reduce costs
  • The proliferation of smartphones embedded with behavioural techniques designed to coax people to adhere to medications holds promise
  • But recent research suggests that thousands of apps devised to reduce nonadherence use behavioural techniques sub-optimally
  • There is an opportunity to significantly improve nonadherence to medication by optimally utilising behavioural techniques and digital technology
  • The challenge needs to be embraced by all healthcare stakeholders
 
Nonadherence to prescribed medication: an orphan killer epidemic
 
Nonadherence to prescribed medication for patients with chronic long-term conditions (LTCs) is an out-of-control epidemic, which is undetected and undertreated. It kills hundreds of thousands, erodes the life chances of millions, costs billions and is one of the biggest obstacles to effective healthcare in the 21st century. According to the World Health Organization (WHO), “increasing the effectiveness of adherence interventions may have far greater impact on the health of the population than any improvement in specific medical treatments”.
 
There are a number of reasons why people with LTCs stop taking their medication, which include: (i) fear of potential side-effects, (ii) lack of understanding because taking a medication every day to reduce the risk of something bad happening can be confusing, (iii) failure to see immediate improvement, (iv) too many medications that often cannot be taken at the same time, (v) patients who are depressed are less likely to take their medications as prescribed, (vi) concerns about becoming dependent on a medicine and (vii) high drug costs, particularly in the US.
 
No healthcare stakeholder - patients, doctors, carers, regulators, pharmacists, pharmaceutical companies and healthcare providers – has made nonadherence a priority, so it has become an orphan issue. We suggest that all health stakeholders have a role to play in nonadherence and would benefit  by employing psychological techniques designed to encourage people to change their behaviour. 
 
In this Commentary

Because nonadherence to medication has a significant prevalence in people living with LTCs, we begin this Commentary by describing the vast and rapid growth of LTCs and their associated eyewatering costs. The management of LTCs rests with primary care doctors, but the average doctor-patient consultation is just a few minutes and more importantly, the majority of patients do not remember most of the information provided in such consultations. Not only do primary care doctors have little time to prescribe and explain medication regimes, there is little incentive for them to address nonadherence. We raise the question of whether doctors might be part of the problem by  citing a seminal paper published in The Lancet in 1974, which suggests that doctors have a propensity to medicalise healthcare and over-prescribe medicines. This can transform reasonably healthy people into habitual patients. We then describe a trend gaining momentum both in the US and the UK, whereby community-based pharmacists are becoming a healthcare destination and are well positioned to play a significant role in denting the nonadherence epidemic.  We draw passing reference to pharmaceutical companies’ interest in reducing nonadherence. We conclude by describing a number of research studies, which examine the confluence of mobile telephony and advances in behavioural science, which facilitate the increased use of apps embedded with behavioural techniques to address nonadherence to prescribed medication. Despite the large and growing use of such apps, studies suggest that the use of behavioural techniques in mobile applications to address nonadherence is sub-optimal. Thus, there remains an  opportunity for using advances in behavioural theory and practice to promote sustained and significant lifestyle behaviour changes designed  to reduce the nonadherence to prescribed medication epidemic.
 
Impact of LTCs in the US and UK
 
LTCs, e.g. diabetes, chronic obstructive pulmonary disease (COPD), arthritis and hypertension, are diseases for which there is currently no cure and they are managed with drugs and other treatments. Each year in the US, LTCs affect about 133m people and this is projected to rise to 157m by 2025. According to a 2012  study published in the Annals of Internal Medicine, people who take prescription medicines for LTCs typically only take about half of the prescribed doses. The study’s findings were updated to estimate costs in US dollars to reflect inflation for 2016 prices and published in the March 2018 edition of theAnnals of Pharmacotherapy. The authors estimated that the, “annual cost of drug-related morbidity and mortality resulting from nonoptimized medication therapy was US$528.4bn, equivalent to 16% of total US healthcare expenditures in 2016”.  This compared to 8% and 13% in 1995 and 2008, respectively. Although this estimate accounts for overall price inflation, it does not include non-medical or indirect costs, such as lost productivity or caregiver expenses, which have been estimated to be more than the direct medical costs for many LTCs. Also, the authors estimated that nonadherence results in about 275,689 deaths each year. 

In the UK nonadherence to prescribed medication among people with LTCs has a similar impact. According to a 2014 UK House of Common’s Health Committee report, “Effectively managing LTCs is widely recognised to be one of the greatest challenges facing the 21st-century”.  Seventy percent of total expenditure on healthcare in England is associated with the treatment of the 30% of the population with one LTC or more, and the number of people in England with one or more such condition - currently 15m - is projected to increase to around 18m by 2025. Care for LTCs presently accounts for 55% of primary care doctors’ appointments, 68% of outpatient and A&E appointments and 77% of inpatient bed days. The cost to NHS England of people with LTCs not taking their prescribed medicines appropriately and thereby not getting the full benefits to their health is estimated at more than £500m (US$635) a year, with a further cost of £300m (US$381) on wasted medication.

 
Nonadherence is not a doctor’s problem

Despite the fact that a medical consultation is a complex and multidimensional process, which is pivotal to the health of patients, the average time spent for each consultation is short and there is little or no time for doctors to educate or motivate patients. A 2017 paper published in the British Medical Journal (BMJ) reviewed 28.6m doctor-patient consultations across 67 countries and found that, in 18 countries, which represented about 50% of the global population, on average a doctor-patient consultation is five minutes or less. On average, British patients spend just over nine minutes with their primary care doctor  during an appointment and in the US, it is  17 minutes. More significantly, a 2016 study published in Health Expectations, suggested that patients only remember about a fifth of the information discussed in a standard doctor-patient consultation.
In addition to time constraints there is little incentive for doctors to address nonadherence. In the US, fee-for-service medicine incentivizes services, not improved outcomes. Although this is changing as insurers pay for value rather than activity, pay-for-quality programmes tend to be too small to motivate busy doctors. Similarly, the UK’s public healthcare system, which is free at the point of care for all citizens, lacks incentives for health professionals to be overly concerned about nonadherence to medication. Primary care doctors view their primary responsibility as making an accurate diagnosis followed by an appropriate prescription and generally tend to be unaware of the magnitude of nonadherence to medication.

 

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The medicalization of health

Compounding the problem of nonadherence is the medicalization of healthcare, which can transform healthy people into patients. This was graphically described by Ivan Illich, in a seminal paper entitled “Medical Nemesis” published in 1974 in The LancetThe same year, Illich published a book with the same title, which opens with the sentence, “The medical establishment has become a major threat to health”. Illich continued, “The disabling impact of professional control over medicine has reached the proportions of an epidemic”, which Illich referred to as an iatrogenic  epidemic:  derived from the Greek word “iatrogenesis” (ιατρογένεση), which means “originating from a physician or treatment”.
 
Healthy people transformed into patients

In a similar vein, a paper entitled “Let’s not turn elderly people into patients” and published in the May 2009 edition of the  British Medical Journal, suggested that annual health checks, which primary care doctors are incentivized to carry out, can transform reasonably healthy older people into habitual patients. The author, Michael Oliver, Professor Emeritus of Cardiology at the University of Edinburgh, suggested  that doctors view people over 70 to be at risk of one or other LTC and insist on medical checks. These  can lead to reasonably healthy individuals being told that they have high cholesterol levels or hypertension etc. and prescribed regular medications, instead of being encouraged, in the first instance, to exercise more and adopt healthier diets and lifestyles. Thus, a number of elderly people who considered themselves healthy on the way to the doctors, return home as patients. “What kind of medicine is this?” asks Oliver rhetorically, and answers, “It is politics taking preference over professionalism, obsession with government targets superseding common sense, paternalism replacing personal advice. It seems that many Western governments regard all people aged over 75 as patients”. And such perceptions can lead to over testing, over diagnoses and over treatment.
 
Pharmacists becoming significant healthcare destinations

Over the past decade pharmacists and pharmacies have been increasingly viewed as underutilised assets well positioned to improve nonadherence. In both the US and UK retail community pharmacies are accessible on a walk-in basis, without the need for an appointment. Pharmacists are the last checkpoint before a patient takes their medication and are therefore available to provide personalized advice about health and medicine to millions of people.
 
In the US there are approximately 314,300 pharmacists, and some 67,000 pharmacies; half of which (33,000) are conveniently located within drug stores, grocery stores, department stores, primary care clinics, universities, nursing homes, hospitals and prisons. In 2019, over 4.4bn retail prescriptions were filled throughout the US. Similarly, in England, there are some 42,990 registered pharmacists; 32,000 of whom work in 11,700 community pharmacies. Every day in England, approximately 1.6m people visit a pharmacy and for 89% of them a community pharmacy is within a 20-minute walk from where they live. Each year community pharmacies in England dispense over 1bn prescriptions.
 
The fact that pharmacists are rapidly evolving from a focus on product preparation and dispensing to becoming significant healthcare destinations is welcomed by both the UK’s Royal Pharmaceutical Society (RPS), the Royal College of General Practitioners (RCGP) and NHS England. Three 2016 reports demonstrate this: two published by the RPS and one published jointly by the RCGP and NHS England.  In September 2016, a RPS report entitled, Community Pharmacy Forward Viewset out a vision to expand and improve pharmacy services by: (i) facilitating personalised care for people with LTCs, (ii) acting as a trusted, convenient first-port-of-call for healthcare advice and treatment, and (iii) providing a hub for neighbourhood health and wellbeing. The report was complemented by another, published in November 2016, entitled Frontline pharmacists: Making a difference for people with long term conditionswhich argued that the expertise and clinical knowledge of pharmacists must be fully utilised to support people with LTCs and help them to achieve the desired outcomes from their medicines, thereby making more efficient use of NHS England’s resources. Such views were echoed in the General Practice Forward View, a report published in April 2016 by the RCGP and NHS England. The report suggested that pharmacists were, “one of the most underutilised professional resources in the [healthcare] system” and suggested that there was a need to, “bring their considerable skills into play more fully” and promote the need for pharmacists to be part of the broader health practice team.

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Pharmaceutical companies

Pharmaceutical companies have an incentive to reduce nonadherence with innovative solutions. When patients fail to take their prescribed medications, not only does their health deteriorate and health providers lose money, but doctors often change medications. This translates in a potential loss to the pharmaceutical company. Some experts estimate nonadherence in the US costs the pharmaceutical industry US$30bn a year in lost revenues, which others suggest is the tip of the iceberg.
Apps using behavioural techniques to reduce nonadherence

Over the past two decade, reducing nonadherence to medication has sought solutions in smartphone apps embedded with psychological techniques to encourage users to change their behaviour. Recent studies suggest that 90% of total time on mobile phones is being spent on apps and individuals may spend an average of 30 hours per month on apps. Such preoccupation raises the possibility that apps could be utilized by healthcare providers and their patients to reduce nonadherence.
 
Behavioural science’s  signature policy is set out in the 2008 book  Nudge, which looks at how people make decisions and applies this to healthcare. Nudges are a particular type of behaviour change intervention, which steer people in certain directions while maintaining their freedom of choice. The key insight is that changing the way choices are presented to people can have a significant impact. We end this Commentary by briefly describing some studies that have examined apps embedded with ‘nudge’ techniques to address the nonadherence to medication challenge. But first, we describe the rise in the influence of behavioural techniques in health policy.
 

The rise in the influence of behavioural techniques on health policy

In the early 2000s, both the US and UK governments began to explore how psychological and behavioural techniques could be used to improve public policy and healthcare, while maintaining a significant element of personal choice. In 2003, policy makers in the US were influenced by a paper entitled ‘Libertarian Paternalism’, published in the American Economic Review. Its authors, Richard Thaler, a University of Chicago economist and Cass Sunstein, a Harvard University  Law School professor, suggested that it is both possible and legitimate for private and public institutions to influence people to make decisions about health and wellbeing without coercing them. In February 2004, the UK’s Prime Minister’s Strategy Unit, published a report entitled ‘Personal Responsibility and Changing Behaviour: the state of knowledge and its implications for public policy’, which described behavioural theories of change  and explored ways the government might employ psychological techniques to influence personal behaviour in order to improve public policy. In 2008, Thaler and Sunstein published a book entitled Nudge’, which described how behavioural techniques and mental processes could be used to ‘nudge’ people and groups, rather than ordering them, to do things expected to improve public policy and reduce costs. In 2009, the US government recruited Sunstein to head the Office of Information and Regulatory Affairs (OIRA) and streamline regulations. In 2010, UK Prime Minister David Cameron established the Behavioural Insights Team (BIT) (referred to as the ‘Nudge Unit’) in 10 Downing Street, which was headed by David Halpern, the first author of the 2004 Strategy Unit Report referred to above. This was the first formal and systematic application of behavioural insights to public policy. In 2014,  President Obama set up a similar unit - the Social and Behavioral Sciences Team - in the White House. Over the past decade, similar units have been set up by governments throughout the world, the word “nudge” and ‘Nudge Units’ have become common place in social and public policy, and the application of behavioural techniques, have become a significant aspect of public sector management. Nudge techniques  have been employed to reduce the burden of nonadherence to medication.
 
Apps to nudge people to adhere to medication

Over the past decade, there has been a plethora of apps launched to tackle nonadherence to medication. A December 2015 study published by the UK’s Health Foundation entitled Behavioural Insights in Healthcare, suggested that “nudge-type” interventions could, “improve rates of medication adherence, particularly for chronic conditions”. In September 2018, Public Health England published a similar report entitled, Improving People’s Health: Applying behavioural and social sciences to improve population health and wellbeing in England. These and other studies reflect the prominence gained in recent years of the potential benefits behavioural and social sciences can make to improving peoples’ health.
 
Limited use of ‘nudge’ techniques

A research paper entitled, “Behavior Change Techniques in Apps for Medication Adherence” published in the May 2016 edition of the American Journal of Preventative Medicine drew attention to the vast and growing number of apps promoting medication adherence available in the two largest app repositories: the Apple App Store and the Google Play Store. The authors identified and coded 166 medication adherence apps according to 96 established behaviour change techniques and found that the apps only used a limited number of these, and “do not appear to have benefitted  from advances in the theory and practice of health behaviour change”. The most commonly included behaviour change techniques were “action planning” and “prompt/cues,” which were included in 96% of apps, followed by “self-monitoring” (37%) and “feedback on behaviour” (36%). The authors of the study concluded that the apps did not appear to have benefitted from “advances in the theory and practice of health behavioural change”.
 
Four research studies conclude that apps are using behavioural techniques sub-optimally

Four research papers published between 2017 and 2020 in the Journal of Medical Internet Research assessed thousands of apps embedded with behavioural techniques to address medication adherence in different regions of the world and all reached similar conclusions to the 2016 paper in the American Journal of Preventative Medicine mentioned above: that apps designed to enhance medication adherence use ‘nudge’ techniques sub-optimally.
 
In the April 2017 edition of the Journal of Medical Internet Research, a paper entitled “Assessing the Medication Adherence App Marketplace from the Health Professional and Consumer Vantage Points”, identified  824 adherence apps and evaluated 645 of them. Researchers found that the quality of the apps “varied considerably”.  A 2018 review paper published in the same journal,  provided one of the first comprehensive assessments of medication adherence apps in terms of their evidence base, medical professional involvement in their development and the strategies they used to facilitate behaviour change and improve adherence. Researchers identified 5,881 apps, tested 1,486 according to predetermined criteria and concluded that there was, “a concerning lack of healthcare professional involvement in app development and evidence base of effectiveness”.  
 
A paper entitled, “Using Health and Well-Being Apps for Behavior Change” published in the July 2019 edition of the Journal of Medical Internet Research, provides a systematic review of a large sample of healthcare apps marketed in Australia. The initial search identified 212,352 apps, from which 5,018 were identified using a priori key search terms.  Of these, 344 were classified as behaviour change apps and were reviewed and rated. Conclusions suggested that only a limited number of the apps were found to be using behavioural change techniques expected to promote and sustain lifestyle behavioural change and improved health. 
 
And finally, a research paper entitled, “Quality, Functionality, and Features of Chinese Mobile Apps for Diabetes Self-Management: Systematic Search and Evaluation of Mobile Apps” published in the April 2020 edition of the Journal of Medical Internet Research evaluated apps that are available to millions of people in China living with diabetes and designed to help them self-manage essential medications they are required to take regularly throughout their lives. Among 2,072 apps identified, 199 were selected based on the authors’ criteria and 67 apps were analysed.  Conclusions were similar to those in the previous studies mentioned in this section and suggested that the, “general quality” of the apps was “sub-optimal”.
 
Takeaways
 
Nonadherence to medication is a vast and rapidly growing killer epidemic, which is under reported, under-treated and cost healthcare systems billions. This is partly because no healthcare stakeholder has assumed responsibility for denting the burden of the epidemic. Thus, nonadherence is an orphan issue. More recently, the confluence of mobile telephony and behavioural techniques has held out a promise to reduce nonadherence. However, research has suggested that while there is a proliferation of mobile apps embedded with behavioural techniques specifically designed to lower the burden of nonadherence to medication, the overwhelming majority of these are not using tried and tested behavioural techniques optimally. This suggests that there is an opportunity to significantly improve nonadherence to medication by optimally utilising behavioural techniques and digital technology.

 
#LongTermConditions #nonadherence #nonadherencetomedication #behaviouraltechniques #Nudge
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  • The CoVID-19 pandemic created an unprecedented global shock and killed hundreds of thousands
  • Nations responded by closing their borders, implementing stringent lockdowns and saying the  world is at war with a common invisible adversary
  • Responses to the outbreak diverged in the different regions of the world
  • Asian countries responded rapidly and effectively
  • The US and UK responded slowly and ineffectively
  • Observers suggested that the divergent responses to CoVID-19 signal a shift in power and influence from West to East
  • National responses alone are insufficient to effectively deal with the coronavirus
  • Only by embracing effective international cooperation will governments protect their citizens and safely exit the CoVID-19 crisis
 
National leaders have described the coronavirus CoVID-19 pandemic as “the enemy”. In attempts to protect their citizens, nations turned inwards and closed their borders, implemented stringent lockdown restrictions and suggested that the world is at war with a common adversary it cannot see. The speed and effectiveness of national responses to the new coronavirus crisis differed, but not even the wealthiest, most advanced nations were able to protect their citizens. The global coronavirus crisis made millions seriously ill, killed hundreds of thousands, destroyed industries, bankrupted thousands of companies, caused economies to nose-dive and threw societies into turmoil. Only by avoiding nationalist policies and embracing effective international cooperation will governments protect their citizens and safely exit the CoVID-19 crisis.
 
Viruses are notoriously difficult to treat and cure

CoVID-19 has rapidly spread throughout the world with a scale and a severity not witnessed since the devastating Spanish Flu in 1918. So-called because Spain was neutral during WW1 and was one of the few countries where journalists were free to report on the outbreak. In an era before antibiotics and vaccines, the Spanish Flu claimed the lives of nearly 0.68m Americans, 0.25m Britons and between 50 to 100m people worldwide. Adjusting for population growth, that is equivalent to between 200 and 425m today.
 
At the time of writing - June 2020 - neither an adequate therapy nor a vaccine has been developed and CoVID-19 remains prevalent in populations throughout the world. Even with today’s scientific advances, infectious diseases are notoriously challenging to either treat or cure: an Ebola vaccine was more than two decades in the making; despite the first cases of the human immunodeficiency virus (HIV) presenting in 1983, we still do not have a therapeutic preventative vaccine for the disease; nor do we have a vaccine for severe acute respiratory syndrome (SARS), a killer coronavirus, which also originated in China and was unknown before its outbreak in 2002.
 
Recovery will neither be straightforward nor quick

Notwithstanding, governments have lifted lockdown restrictions in order to get their economies working again. V, U, W and L are letters of the alphabet used to describe the shape of a recovery following the economic crisis caused by CoVID-19. Stringent lockdowns forced economies into unprecedented cold storage, and no one knows what shape a recovery will take since professional forecasters have never encountered anything like the sheer magnitude of the current economic crisis.
 
The Bank of England’s Monetary Policy Report published in May 2020, warned that the coronavirus has caused the worst economic crisis in 300 years. So, emerging from this is unlikely to be either straightforward or quick. National responses to the coronavirus outbreak were mixed. Although it is too soon to know the longer-term effects of the virus, China, Singapore and South Korea are among the countries that responded early and effectively, while the US and UK, together with other Western European countries, responded late and less effectively. As of June 1, China, with a population of 1.4bn, had 83,017 confirmed cases and 4,634 deaths; South Korea with a population of 52m, had 11,537 cases and 270 deaths,  and Singapore with a population of 5.7m, had 34,884 confirmed cases and 23 deaths.
 
In this Commentary

This Commentary describes the divergent national responses to the CoVID-19 pandemic; in particular that of China, Singapore, South Korea, the US and UK. China’s more effective response might have been because Beijing benefitted from the lessons it learned after the SARS epidemic in 2002. Governments also differed in their approaches to lifting restrictions. China’s approach was slower than that of the US and more determined to make some of the unexpected benefits thrown up by the crisis permanent. Some observers perceive such variances as a difference between liberal and illiberal nations. Others view the divergences as a shift in power and influence from West to East. We suggest that the divergent responses and outcomes are a product of the capacity and legal authority of different states and reveal different mindsets and competing views about solutions. We also contend that the devastation created by the pandemic will only be resolved with effective international cooperation. However, it is difficult to see this happening in the near term as the pandemic has become a theatre for a wider political disagreement between the US and China, in which other nation states are being forced to take sides.
 
Asian nations won the battle against CoVID-19

China, Singapore and South Korea leveraged the collectivists mindset of their citizens, their centralised authority and digital infrastructures to quickly implement the gold standard “test-trace-and-isolate” strategy to reduce and control the virus. The reason for such prompt actions and the subsequent relatively low number of cases and deaths in these Asian countries is described by  Byung-Chul Han, a South Korean-born German Professor of Philosophy at the Universität der Künste in Berlin. In an article published on May 22, in the Spanish newspaper El Pais, Han suggests that Asian nations won the battle against the CoVID-19 outbreak because their citizens, “have a collectivists mindset, which comes from their cultural tradition of Confucianism. Asians are less rebellious and more obedient than people in the West. They trust the state more. Daily life is much more organised, and Asians are strongly committed to digital surveillance. The epidemics in Asia are fought not only by virologists and epidemiologists but also by computer scientists and big data specialists”.
 
Confucian mindset rather than authoritarianism

Given Iran’s response to CoVID-19 has been less effective, it seems reasonable to suggest that the Confucian mindset, rather than authoritarianism, appears to provide at least a short-term advantage. In early March, at the Shia Muslim Masumeh shrine in the holy city of Qom, pilgrims licked and kissed its gates. Qom experienced Iran’s first outbreak of the coronavirus and became the country's worst-hit city. Shortly afterwards the government closed all major Shia shrines across the Islamic republic and reopened them again in late May. As of June 1, Iran with a population of 81m, had confirmed 154,000 cases of CoVID-19 and 7,878 deaths.  

 

Smaller democracies appear to cope well

Small democracies such as New Zealand and Greece seem to raise some doubt about Han’s thesis because they too have effectively responded to the outbreak. As of June 1, New Zealand, with a population of 5m, had confirmed 1,154 cases and 22 deaths and Greece, with a population of 11m, had a total of 2,917 cases and 175 deaths.
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Notwithstanding, New Zealand’s lockdown only occurred after significant pressure was applied by civil society that suggested the government needed to change track. Both New Zealand and Greece have concentrations of political power, access for vested interest, a lack of public participation in politics and weak media. Further, Greece had no choice but to act swiftly and robustly to the coronavirus outbreak because the country has been in an almost constant state of austerity management since 2008, which has significantly reduced its resources to tackle an outbreak of this magnitude. In both countries the effect of stringent nation-wide lockdowns could further weaken already fragile civil societies, media and parliamentary systems by concentrating power in political leaders, curtailing civil liberties, adjourning parliaments and restricting the normal operations of the media.
 
The Swedish exception

By contrast to all other developed countries, Sweden exercised a radical laissez faire no-lockdown approach to the CoVID-19 outbreak. The architect of this was the Swedish State Epidemiologist Anders Tegnell, who argued that, “nothing [to do with lockdowns] has any scientific basis”, particularly decisions to close schools because there is no evidence that children are a major cause of coronavirus transmission. In Sweden, primary and secondary schools, day care centres, restaurants, bars, cafés, cinemas, theatres, shops and places of work all remained open as normal, with Swedish health authorities relying on voluntary social distancing and people choosing to work from home. Schools for over-16s and universities were closed, and gatherings of more than 50 people were banned. As of June 1, as the death toll has fallen substantially in other European countries, 4,403 people had died from CoVID-19 in Sweden, a country with a population of 10m. Its neighbours, Denmark, Finland and Norway - each with populations of about 5m - have recorded death tolls of 574, 320 and 236, respectively.
 
Not only does Sweden’s no-lockdown approach enjoy significant support among its citizens, it also has the backing of Jonathan Sumption, an historian and a former Justice of the Supreme Court of the UK. Writing in The Times of London Sumption suggests that, “The lesson of CoVID-19 is brutally simply. . . . . . Free people make mistakes and willingly take risks. If we hold politicians responsible for everything that goes wrong, they will take away our liberty so that nothing can go wrong. They will do this not for our protection against risk, but for their own protection against criticism”.
 
At the beginning of June, Tegnell conceded that Sweden should have imposed more restrictions to avoid having such a high death toll. 
 
The US and UK mindset

Compared to the responses described above, the US and UK were slow to implement testing, late to acquire essential equipment, gave confusing public health messages and delayed introducing stringent lockdowns and social distancing. For example, in mid-March, when borders were being closed and mass quarantines enforced across Europe, the US government was failing to establish a clear and focused response to the outbreak. By the time the US President declared a national emergency, several states had introduced lockdowns, universities had shifted to online learning and churches had begun to close. At the same time, schools in England largely remained open and the UK government was pursuing a strategy of exposing its population to the coronavirus in the expectation that citizens would develop a “herd immunity”. As of May 31, the US with a population of 328m, had confirmed 1.83m cases and 106,000 deaths, and the UK with a population of 67m, had 276,000 cases and 39,045 deaths.
 
Signs of danger ignored

Neither the US nor the UK government appeared to have been influenced by well publicised signals of pending dangers, which included: (i) CoVID-19 being a highly contagious ‘novel’ coronavirus without either a therapy or a cure, (ii) around January 23, after the discovery of the outbreak and before the lockdown of Wuhan, the city in China where the virus originated, some 5m people left the city and were potential super spreaders, (iii) by February 4, the coronavirus had spread to 24 countries, (iv) also on February 4, China had opened the first of two mega hospitals in Wuhan, both built from scratch in a couple of weeks specifically to cater for patients affected by the fast-spreading coronavirus. Together, the two hospitals had a 2,600-bed capacity and were staffed with over 3,000 health professionals.
 
Mixed messages

Inside the US messages about CoVID-19 were mixed. Main media outlets reported the acceleration of the virus internationally and state governors independently started to take emergency actions. Notwithstanding, on February 26, at a White House briefing, President Trump urged Americans to take the same precautions for coronavirus as they would for normal flu, and US Health and Human Services Secretary Alex Azar advised that the coronavirus only posed a low risk to the American public. On February 25, the Centers for Disease Control and Prevention (CDC) confirmed that there were 60 CoVID-19 cases in the US and warned Americans that “it's a question of when, not if” the virus, which had killed thousands, would spread within the US.
 
Convinced of a rapid V-shaped recovery

In late February, in tune with White House messaging, many US business leaders from sectors not seriously affected by CoVID-19, were convinced that the coronavirus outbreak would be a relatively short-lived regional issue, concentrated in China with some limited transmission through supply chains to other parts of Asia, Europe and the US. They believed the outbreak would only have a temporary impact on global GDP and trade and weigh modestly on US business activities in Q1 2020. Although it might be difficult to contemplate now, in late February some US business leaders were suggesting that their companies and the American economy would bounce back in Q2 2020 after a modest V-shaped dip.
 
Such optimism might have been influenced by the SARS outbreak, which also originated from China, spread to 37 countries, infected more than 8,000 people and killed about 800. The impact SARS was to reduce China’s GDP growth by about 1% and it only had a limited effect on world GDP and trade. Although the SARS epidemic did not register much with US business leaders, it prompted Beijing to overhaul its healthcare system and prepare China for another potential virus epidemic. After SARS China invested in systems for disease surveillance and reporting, as well as epidemic prevention and control. Centres for disease control were built across the country and public insurance programmes were expanded to provide affordable care for the rural population. Arguably, this strengthened China’s preparedness for its response to CoVID-19.
 
By contrast, the US and UK did not appear to perceive a threat of a pandemic as serious. In May 2018, President Trump disbanded the US Global Health Security and Biodefense unit responsible for pandemic preparedness, which was established in 2015 by Barack Obama’s National Security Advisor. The UK did something similar. According to Professor Sir Ian Boyd, the UK’s Chief Scientific Adviser between 2012 and 2019, the nation’s biological security strategy, which Boyd partly wrote and published in 2018 to address the threat of a pandemic, was not properly implemented because of a lack of resources.
 
Commercial impact

As a consequence, on March 11, when the World Health Organization (WHO) declared the coronavirus CoVID-19 as a pandemic the US and UK were unprepared. The WHO pointed to Europe as the “epicentre” of the outbreak and, by the end of March, the outbreak had a significant effect on most industries in the developed world. Transportation, manufacturing and wholesale trade sectors were substantially affected by disrupted supply chains and travel restrictions. In many countries retail and hospitality sectors experienced sharp falls in demand and were closed. However, sectors differed in their ability to respond flexibly to supply disruptions and falls in demand. For example, business as usual continued for many professional services if their employees were able to work from home.
 
Impact on healthcare

The impact on healthcare was mixed. Demands on hospitals increased significantly as they shifted their resources and efforts to treating CoVID-19 patients. Policy responses were aimed at managing the increased capacity demands on hospitals by ‘flattening the curve’ of infection. The impact of the coronavirus outbreak on the MedTech sector was bifurcated. The vast and increased demand for critical care devices and personal protective equipment (PPE) significantly advantaged some manufacturers, while others, particularly orthopaedics, were disadvantaged as hospitals dedicated capacity to treating infected coronavirus patients and deferred non urgent surgeries. Sector forecasts suggested a reduction in medical device use in the Q1 and Q2, and a moderate recovery in the second half of 2020. But this hinged on successful efforts to halt the virus' spread. The global economic slowdown and the shift in healthcare resources toward fighting CoVID-19 dented MedTech sales and triggered a hit to their stock valuations.

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CoVID-19 weakens the ‘Western brand

Some commentators perceive the CoVID-19 crisis as a test of the competing claims of liberal and illiberal states to better manage significant social and economic shocks. According to Stephen Walt, Professor of international affairs at Harvard University's John F. Kennedy School of Government, the slow and diffident responses to the outbreak from US, UK and some other European governments could potentially weaken the dominance of the Western brand, and “accelerate the shift of power and influence from west to east”.
China building on the response to SARS

Despite China’s endeavours to be ready for a pandemic after the SARS outbreak, CoVID-19 exposed cracks in China’s preparedness, which Beijing swiftly sought to fix. This included enhancing the nation’s healthcare system’s cost management by further centralizing procurement, purchasing drugs in bulk and implementing a two-invoice policy to eliminate layers of bureaucracy in the nation’s distribution channels. Beijing also encouraged product innovation from local and foreign companies by fast-tracking approvals for medicines and medical devices. And, like many other countries, China increased its digitalization strategies by accelerating the integration of big data, artificial intelligence, telemedicine, online pharma retail and more. The coronavirus impact in China and elsewhere in the world prompted a massive shift in patients and doctors using Internet-based options for diagnosis and treatment. This shift to digital necessitated by the coronavirus outbreak is well positioned to become the ‘new normal’, which could help healthcare providers, hospitals, health systems and clinicians optimise their use of resources.
 
G7’s response to CoVID-19

Between March and April, G7 nations (Canada, France, Germany, Italy, Japan, the UK and the US) injected US$2.5tn of new money into financial markets through quantitative easing and liquidity programmes to help nations recover from the economic crisis caused by CoVID-19. Notwithstanding, only about US$1 in US$10 lent by British banks went to non-financial service companies. Most of the new credit supported financial trading. A similar pattern occurred in other G7 countries. As these nations navigate their way out of the crisis, there is little evidence of any industrial strategy being linked the CoVID-19 shock. For economies to recover, they will need financial markets to do something similar to what they did following WWII when banks worked closely with governments and used the increased liquidity for committed long-term financing that created jobs, enhanced productivity and stimulated innovation.

Interestingly, on May 30, President Trump said he will postpone the G7 meeting planned for August at the White House. He called the current group’s format , “very outdated”, suggested that it does not properly represent "what's going on in the world" and said its membership should include Russia, Australia, South Korea and India.
 
The pandemic is not over

Compared with G7 nations, China has opted for a more strategic approach to its recovery from the pandemic. Beijing has put the prevention and control of the CoVID-19 crisis as the keystone of a national strategy. Significantly, Premier Li Keqiang, did not use his annual report to China’s National Legislature on May 29 to claim victory over CoVID-19. Instead he stressed that, “The pandemic is not over” and outlined Beijing’s plans for continued vigilance against the coronavirus, which, Li said, “is a core thread in determining everything from macro-level strategy to micro-level policy for the foreseeable future in China”. Beijing committed a ¥1tn (US$138bn) rise in its fiscal deficit and ¥1tn of special governments bonds to its CoVID-19 recovery strategy, which is dedicated to: (i) securing jobs, (ii) maintaining and increasing people’s livelihoods, (iii) developing businesses, (iv) securing food and energy, (v) developing and maintaining stable industrial and supply chains, and (vi) reducing government red tape.
 
CoVID-19 strengthens the US$

Beijing’s coronavirus recovery strategy does not guarantee that China will evolve stronger than the US from the crisis. Indeed, the US may surface in better shape than analysts suggest. This is because of the strength of the US$, which remains the world’s reserve currency and is perceived as a relatively safe asset in times of crisis. The CoVID-19 crisis reinforced the US$’s strength and therefore it seems reasonable to suggest that the coronavirus outbreak may not do as much damage to the US economy as some observers suggest. Walt’s prediction, mentioned above, that CoVID-19 will accelerate the shift of power and influence from West to East will depend on whether: (i) the US successfully restarts its economy and avoids a resurgence of the coronavirus, and (ii) the US maintains its ‘America first’ approach to the pandemic or changes to its natural global leadership position, which it assumed after WWII.
 
US suspends payment to the WHO

On March 26, after a virtual G20 summit, there were encouraging signs when a joint statement said that, “Combatting this pandemic calls for a transparent, robust, coordinated, large-scale and science-based global response in the spirit of solidarity. We are strongly committed to presenting a united front against this common threat”. Despite this pledge to cooperate, little cooperation followed, and the pandemic became a theatre for a wider disagreement between the US and China. On April 20, President Trump suspended US payments to the WHO in protest at what he regards as the body’s China-centric approach, reflected, by what he suggests is the WHO’s failure to challenge China sufficiently over the origins of the CoVID-19 outbreak. On May 29, Trump said, “We will be today terminating our relationship with the World Health Organization and redirecting those funds to other worldwide and deserving urgent global public health needs”. In the near-term, before the US presidential election in November, it does not look that the US will change its ‘America first’ strategy.
 
Takeaways

CoVID-19 has created an unprecedented global crisis. Governments throughout the world responded to the crisis by closing their boarders, implementing stringent lockdown restrictions and used wartime rhetoric to rally their citizens. While this temporarily lowered the rate of infection it is not a permanent solution. Two significant takeaways from the coronavirus crisis are: (i) not even the riches and most technologically advanced nations with state-of-the-art healthcare systems were able to protect their populations and (ii) only by turning outwards and embracing effective international cooperation will nations protect their citizens and safely exit the CoVID-19 crisis.

#coronavirus #coVID-19 #pandemic #coVID-19outbreak #lockdown
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The HealthPad team extends Ramadan Mubarak to all our friends, family members and colleagues who are participating in the Holy Month of Ramadan. We very much would like to share with you a short video by DrSufyan Hussain, Consultant Physician in Diabetes and Endocrinology at Guy's and St Thomas' NHS Foundation Trust, London, UK, which we made to specifically help those who are living with diabetes and fasting.
During these unprecedented challenging times caused by the coronavirus CoVID-19 pandemic, we trust that you all stay safe and well and let the spirit of Ramadan remain in your hearts and light up your souls from within.
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The HealthPad team extends its sincerest best wishes to you, your families and loved ones during these unprecedented times caused by the coronavirus CoVID-19 pandemic. We trust that you all stay safe and well.

To everyone working long and stressful hours on the frontline of healthcare; thank you for the sacrifices you’re making every day to help others in their moments of need. Your dedication, commitment and courage have our deepest gratitude and admiration.

Also, our heartfelt thanks go to all key workers who are unselfishly providing essential services, which are helping all of us through this coronavirus outbreak. Your resolution and mettle make a huge difference to our daily lives and we hold you in the highest esteem.

 

#coronavirus #CoVID-19  #frontlinehealthcareworkers #keyworkers #healthcare

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  • The coronavirus CoVID-19 has created the greatest health-cum-economic-cum-societal crisis in history and put unprecedented pressure on overstretched and unprepared healthcare systems
  • Before the coronavirus outbreak, primary care in England already was in crisis, fuelled by an aging population, a large and increasing demand for its services and a shrinking supply of health professionals
  • In 2019, before the outbreak, 75% of primary care doctors (GPs) across 540 clinics in England were over the age of 55 and nearing retirement and a large percentage of newly trained GPs were seeking employment abroad
  • Patients who could not get GP appointments used A&E departments as convenient drop-in clinics for minor ailments, which significantly increased healthcare costs and burden
  • For decades successive UK governments have tried in vain to transform the nation’s primary care services predicated upon face-to-face patient-doctor consultations
  • Several well-funded long-term national plans advocated increased digitization of some routine primary care services
  • But before the coronavirus outbreak only 1% of all primary care consultations were online
  • What these national plans could not achieve in decades appears to have been achieved in days by the UK’s NHS’s response to the coronavirus outbreak
  • Today, millions of patients in England are having face-to-face appointments with their GPs replaced by telephone or video consultations
  • Could CoVID-19 transform the UK’s traditional primary care model?

 

Introduction
 
The UK’s National Health Service’s (NHS) response to the coronavirus CoVID-19 outbreak might improve the nation’s crisis ridden primary care service. This became evident in March 2020, when the UK government ordered all citizens except key workers to stay at home. At the same time, NHS England announced its ‘battle plan’ for CoVID-19, which recommended that England’s 7,000 primary care clinics start conducting as many remote consultations as soon as possible.  In a matter of days, millions of patients had face-to-face appointments with their GP replaced by telephone or video consultations. If this shift to online consultations becomes permanent then the NHS’s response to the coronavirus would have achieved in days what well-funded national healthcare plans, such as the NHS Digital First Primary Care drive, could not achieve in decades.
 
Future healthcare is digital
 
For years, the benefits of online doctor-patient consultations have been advocated by  Devi Shetty, a world-renowned heart surgeon and  founder and chairman of Narayana Health, one India’s largest hospital groups.  According to Shetty, “The next biggest thing in healthcare is not going to be a ‘magic’ pill, a faster scanner or a new operation but information technology (IT). IT will dramatically change the way a health professional will interact with a patient. Every step of patient care will be informed by a protocol embedded in a smartphone. This will make healthcare safer for the patient and remove a lot of traditional dace-to-face healthcare activities and shift healthcare away from the clinic and into the home. Doctors and patients don't need to be together; they could be in their respective homes and effective consultations could take place online.” (see video below)
 
The next ‘big thing’ in healthcare
 
The coronavirus CoVID-19
 
In December 2019, initial reports of a new coronavirus - CoVID-19 - emerged  when patients from Wuhan, the sprawling capital city of China’s Hubei province, which has a population of some 11m, presented with pneumonia of unknown origin. By December 2019 the virus had spread to other countries and on 11th March 2020, the World Health Organization characterised the outbreak as a pandemic. CoVID-19 is an illness caused by a member of the coronavirus family that has never been encountered before but is believed to come from animals.There have been other coronaviruses. For example, severe acute respiratory syndrome (Sars) and Middle Eastern respiratory syndrome (Mers) are both caused by coronaviruses that came from animals. In 2002, Sars spread virtually unchecked to 37 countries, causing global panic, infecting more than 8,000 people and killing about 800, but it soon ran itself out. Mers first emerged in 2012, cases of which have been occurring sporadically since. Mers appears to be less easily passed from human to human, but has greater lethality, killing 35% of about 2,500 people who were infected. CoVID-19 is different to Sars and Mers in that the spectrum of disease is broader, with around 80% of cases leading to a mild infection. There may also be many people carrying the disease and displaying no symptoms, making it even harder to control. CoVID-19 affects your lungs and airways and can cause pneumonia. So, people with an  inflammatory lung disease that causes obstructed airflow from the lungs, such as asthma and chronic obstructive pulmonary disease (COPD), are particularly vulnerable; as are people with weak immune systems, which make them susceptible to infections that might be more severe or harder to treat. In January 2020, China’s national health commission confirmed human-to-human transmission of CoVID-19, and there have been such transmissions in countries throughout the world. Those who have fallen ill are reported to suffer a general feeling of being unwell, fever, dry cough, tiredness, breathing difficulties and a loss of taste and smell. In roughly 14% of cases the virus causes severe disease, including pneumonia and shortness of breath. In about 5% of patients it is critical, leading to respiratory failure, septic shock and multiple organ failure. As this is viral pneumonia, antibiotics are of no use. The antiviral drugs we have against flu will not work. Recovery depends on the strength of your immune system. Many of those who have died were already in poor health. Initially, scientists were challenged to accurately assess how dangerous CoVID-19 was because there were inadequate data. A challenge  to  collecting data was because of a shortage of tests and also because people who had contracted the coronavirus were emitting, or “shedding,” infectious viruses early in the progression of the illness; sometimes before they develop symptoms.

The 1918 Spanish Influenza 
remains the most devastating virus in modern history. The disease swept around the globe and is estimated to have caused between 50m and 100m deaths. A cousin of the same virus was also behind the 2009 swine flu outbreak, thought to have killed as many as 0.58m. Other major viral outbreaks include the Asian flu in 1957, which led to roughly 2m deaths and the Hong Kong flu, which killed 1m people 11 years later. 

 
In this Commentary
 
This Commentary is produced by HealthPad, which is an online health solutions company. (see below). We begin the Commentary by briefly describing the underlying reasons for the UK’s primary care crisis, which include: (i)  the changing and aging population and the consequent increased demand for healthcare, (ii) the shrinking supply of health professionals, and (iii) failing national initiatives to improve the provision of primary care. We then draw attention to some well funded national plans, whose intentions have been to harness the power of information and digital strategies to reform and improve primary care services in England. We also cite research, which suggests that these plans have failed. The Commentary briefly describes a number of innovative online healthcare solution companies, (HealthPad is one).  The majority of these are private initiatives, which have taken advantage of the UK’s high smartphone penetration rates and advanced wireless networks to enter the UK’s healthcare market with an intention to transform the sector. Notwithstanding, to-date the overall impact of these companies has been marginal, due in part, to the general resistance of private enterprises playing a significant role in England’s public NHS, which offers free healthcare to all citizens at the point of care. However, they represent a nascent UK online healthcare solutions market, which is well positioned to benefit from the nation’s response to the coronavirus outbreak, which has forced more primary care services to be delivered online. To increase their footprint these companies, which are largely driven by technology, will need to become more strategic and consolidate. And this will take time. We conclude the Commentary by looking to China and WeDoctor to understand the potential that online services can make to the delivery of healthcare in England. WeDoctor is a Chinese mobile app launched in 2010 to help patients book doctor appointments. Over the past decade it has added more functions to help unclog China’s fragmented and bureaucratic healthcare system and has become a US$5.5bn healthcare company, which connects some 210m registered users with 360,000 doctors.
 
UK’s primary care crisis
 
There are three drivers to the UK’s primary care crisis: (i) the changing and aging population, which increases the demand for healthcare, (ii)  the shrinking supply of healthcare professionals to a point where GP workloads are becoming unsafe, and (iii) failing national initiatives to improve the provision of primary care. Let us briefly describe these.
 
Changing and aging population
 
The UK’s population is changing and aging, which is fuelled by improvements in life expectancy and a decrease in fertility. According to the UK’s Office of National Statistics, in 2016, there were 12m UK residents aged 65 years and over, representing 18% of the total population. 25 years before, in 1991, there were 9m, accounting for 16% of the population. By 2040, it is projected that there will be an additional 8m people aged 65 years and over in the UK: a population roughly the size of present-day London, which will account for 25% of the total population.
 
A report by Deloitte,  a consultancy, suggests that as people age so their propensity for illness increases and more than a quarter of the UK’s population of some 66m have long-term chronic illnesses. This places a significant extra burden on the nation’s overstretched primary care services by utilizing about half of all GP appointments. Deloitte’s analysis is supported by a British Medical Association’s 2019 GP Patient Survey, which found that GP clinics are now caring for 0.72m more patients than they were in 2018. Findings of a 2016 report by the UK’s Royal College of General Practitioners (RGCP), suggest that GPs see 1.3m patients a day and do more than 370m consultations annually: 60m more than in 2010. A research study on GP productivity carried out by the King’s Fund and also published in 2016, suggested that between 2010 and 2015 the total number of telephone consultations increased by 15%, but still only accounted for 1% of all patient-doctor consultations.
 
Shrinking supply of GPs
 
As the UK’s population has grown and aged and the consequent demand for healthcare has increased, so there has been a sustained fall in the number of GPs. This  dynamic is described in a Nuffield Trust report published in May 2019, which confirms the findings of a joint report from the Institute of Fiscal Studies and the Health Foundation for the NHS Confederation, which concluded that, “The fall in GPs per person reflects insufficient numbers previously being trained and going on to join NHS England, failure to recruit enough from abroad and more GPs leaving for early retirement”. As to the future, a  2019 report by three leading think tanks - the Nuffield Trust, the Health Foundation and the King's Fund - predicts that GP shortages in England will almost triple to 7,000 by 2024. According to NHS Statistics, Facts and Figures, currently there are just over 42,000 GPs working in England, down by nearly 1,500 since 2016.
 
Failure to stop or slow these trends means today, primary care services in England struggle with staff shortages and a rising demand for care. A 2019 Pulse Magazine survey found that  GPs in England are seeing more patients than is safe. A probe undertaken by The Times in 2019 suggested that the  national shortage of GPs has left some surgeries with one permanent doctor caring for as many as 11,000 patients and one in 10 GPs are seeing up to 60 patients a day, double the number considered safe.
 
GPs across the UK work an average 11-hour day. In that time, they typically see patients for 8 hours and spend the other 3 on administrative tasks such as checking test results and reading letters sent by hospitals.  A 2019 British Medical Association survey found that more than 80% of GPs said the pressure to attend to multiple tasks at once meant they were unable to guarantee safe care, while 91% said excessive workload was the main reason the NHS was struggling to recruit enough staff. The situation has resulted in patients having to wait longer - up to three weeks - for a GP consultation. It seems reasonable to suggest that GPs with too many patients and using traditional face-to-face delivery methods will fail in their duty of care, which obliges them to inform patients about their health and reach shared clinical decisions about treatments. This requires that patients understand their condition/s and are well informed. In many cases, a 10-minute  face-to-face GP consultation might not be the best way to achieve this.
 
Failing national initiatives to improve primary care
 
Subsequent UK governments have struggled to reduce the primary care crisis with well funded national plans. In 2019, the British Medical Journal published findings of a survey to report UK GPs’ views and experience of national healthcare initiatives introduced in England to address the workforce crisis in general practice. The survey was conducted in the same region as a similar survey undertaken in 2014. This allows for a comparative analysis to see how GPs’ views have changed over time. Findings confirm that primary care in England remains in crisis and suggest that numerous national initiatives to improve general practice are perceived by GPs as, “reactive in approach”. To reduce the primary care crisis, respondents suggested, “more GPs and better education of the public". 
 
The UK’s NHS
 
Healthcare in the UK is mainly provided by the National Health Service (NHS), which is a vast public institution funded largely from general taxation to the tune of some £134bn (US$161bn) a year. Created in 1948, the NHS  provides free health services at the point of care for everyone living in the UK and has become the largest single payer health system in the world, and the biggest employer in the UK with 1.2m full time equivalent (FTE) workers, which is the fifth-largest workforce in the world. NHS England is a vast bureaucratic and fragmented organisation, which has proven difficult to change. Private provision of NHS services has always been controversial, even though some services, such as dentistry, optical care and pharmacy, have been provided by the private sector to the NHS for decades and most GP practices are private partnerships. It is challenging to determine how much the NHS spends each year on the private sector because central bodies do not hold detailed information on individual contracts with service providers, especially where these contracts may cover relatively small amounts of activity and spending. Notwithstanding, estimates suggest the share of the NHS’s total revenue budget that is spent on private providers is about 7.3%. 

National plans to improve the NHS
 
The planning and authorising of NHS services is the responsibility of regional Clinical Commissioning Groups (CCGs). Although CCGs are constantly changing because of mergers, as of 2019, there were 191 CCGs in England supporting about 7,000 primary care clinics, some 42,000 GPs and about 15,800 FTE nurses who work in GP clinics, and 1,257 hospitals, which include NHS Trust-managed hospitals and private hospitals that provide services to the NHS. In total, the NHS employs around 150,000 doctors  and over 320,000 nurses and midwives.
 
Successive UK governments have been aware of the impact of technological advances, changing healthcare needs and societal developments on healthcare and have introduced a succession of well-funded national plans to change and improve the NHS. For example, in June 2018, the UK’s Prime Minister announced a new five-year funding settlement for the NHS that amounted to an extra £20.5bn (US$25.2bn) between 2019 and 2024, which represents a 3.4% real average annual increase.
 
NHS long term plan to transform primary care
 
To unlock the funding, national bodies were asked to develop a long-term plan to help the NHS cut costs and improve services. The suggested plan articulated the need to integrate care in order to meet the needs of a changing population and was in line with the Forward View, a planning document published in 2014 and the General practice forward view,which was first published in 2016 and updated in subsequent years. The long-term plan committed the government to an extra £2.4bn (US$3bn) a year to speed up the transformation of primary care and suggested GP clinics join together to form networks typically covering 30,000 to 50,000 patients and provide them with multidisciplinary integrated care. The plan also suggested ‘significant changes’ in the existing performance management and payment of NHS GPs [the Quality and Outcomes Framework (QOF)] in order to encourage more personalised care.
 
NHS long term plans and private online healthcare solution companies have delivered little change
 
Three of five principal objectives of the latest NHS long term plan are to: (i) “give people more control over their own health and the care they receive”;  (ii) “increase the contribution to tackling some of the most significant causes of ill health, including new action to help people stop smoking, overcome drinking problems and avoid Type 2 diabetes”, and (iii) “provide more convenient access to services and health information for patients”.

The plan emphasises the importance of developing digital services, and recommends that within five years, all patients should be able to access GP consultations via a telephone or online. This goal is supported by NHS Digital, which is the national information and technology partner to the UK’s health and social care system. Its mission is to harness the power of information and technology to improve healthcare. Over the past decade there has been an increasing number of innovative online private  healthcare solutions companies entering the market. (see below). Notwithstanding, these and the NHS’s well-funded national plans, have failed to dent the primary care crisis by slowing the vast and escalating demand for healthcare and reversing the shrinking supply of healthcare professionals. So, for the past two decades at least, the NHS has tended to operate on the cusp of a crisis.
 
The death of distance
 
According to Deloitte, the UK has more than 90% smartphone penetration. The main driver of high smartphone adoption rates is the take-up among older age groups. By 2023 smartphone ownership among 55-to-75-year-olds will reach 85% in the UK, and the difference in smartphone penetration by age will disappear. Further, the UK’s smartphone market has seen a greater variety of choice of models and the introduction of faster and more reliable wireless networks. This has benefited the online private healthcare solution companies, which have entered the UK market to provide varying degrees of qualified online healthcare information, consultations, networking opportunities, triage and Q&A. According to Shetty, “A doctor only needs to touch a patient if s/he is going to operate on that patient. If a doctor doesn’t need to operate, a doctor-patient consultation can take place remotely. For a patient-doctor communication distance doesn’t matter.” (see video below)
 

 A doctor only needs to touch a patient if s/he is going to operate on that patient
 
Innovative online healthcare solution enterprises
 
The new online healthcare solution enterprises are a combination of private, public and charitable initiatives, which are well positioned to contribute to the transformation of the UK’s traditional primary care model and include: Babylon Health, which provides remote consultations with doctors and healthcare professionals via text and video; BioBeatsa workplace wellbeing platform designed to empower and improve mental health; Docly, a digital messaging healthcare service, which is a spin-off of Min Doktor; Doctorlink, which partners with payers, healthcare professionals and pharmacists to provide a 24-7 platform for NHS patients to assess symptoms; DrDoctor, a patient engagement platform, which enables patients to book, change and cancel their appointments; EggPlant, a software testing and monitoring company, which helps to streamline patient activities; Dr Fox, an online primary care clinic and pharmacy service; Gogodoc, an online GP video consultation service with possible follow-up home visits; Healthcare Communications UK, which provides appointment management software and patient experience surveys; HealthPad, an online platform that manages and distributes healthcare video information between health providers and patients in order to improve outcomes and cut costs, and has accrued a proprietary content library of over 6,000 short videos contributed by leading clinicians that address peoples FAQs across some 30 therapeutic pathways, (HealthPad is the publisher of this Commentary).  HealthTalksOnline, an events and community portal for health; HealthUnlocked, a social networking service that offers peer support to help people manage their health; Healum provides healthcare professionals with a software, which enables them to support and motivate their patients to better manage their conditions; LIVI, provides GP video consultations; Medshra platform for medical professionals to discover, discuss and share clinical cases and medical images; Microtest Health, a health informatics company that provides practice management systems for NHS GP surgeries. MSKnote Limited creates clinical applications for healthcare professionals and patients with a focus on musculoskeletal conditions; MyWay Digital Health provides advice and solutions to help patients better manage diabetes; NHS.uk/conditions provides online text-based information and advice about medical conditions; NHS 111, a free-to-call medical helpline; the Now Healthcare Group, a GP video consultation platform and tele-pharmacy; Patient Access, which started by enabling patients to book GP appointments online and order repeat prescriptions and has evolved to allow patients to connect with their GPs remotely and access their medical records online; Patientinfo provides patients and health professionals with online health information. PatientAccess and Patientinfo are subsidiaries of EMIS Health, a leading supplier of  software used by NHS England; Patients Know Best, a social enterprise, which provides patients with access to their medical records and information about treatments; PatientsLikeMe, an online service that helps patients find people with similar health conditions in order to take actions that are expected to improve outcomes; Push Doctor, an online video consultation service; SaySo Medical is a digital communications agency, which connects people in order to improve their health; SystmOne, a centrally hosted computer system that provides primary care professionals with electronic patient health records in real time at the point of care; uMotif, a platform that captures electronic patient-reported outcomes data across a range of conditions and works with pharmaceutical companies to measure patient’s health, outcomes and experience; Unminda workplace mental health platform designed to  empower organisations and employees to improve their mental wellbeing; Visiba Care, a digital solutions company, which provides communication and administration software for healthcare practices; VisionHealth provides NHS primary care professionals with software solutions; VisualDX provides clinical decision support systems to enhance diagnoses and therapeutic decisions in order to improve patient safety; WebMD, an online publisher of healthcare news and information, and Zava, an online GP and pharmacy service.
 
 Technologically heavy and strategically light
 
Despite a significant number of online healthcare solution enterprises entering the market and the fact that some provide services to millions of people in the UK, this market segment is in its infancy and fragmented. All the initiatives mentioned above have been advantaged by the NHS’s response to the coronavirus outbreak. Notwithstanding, to permanently increase their footprint and significantly influence primary care in England, barriers to private enterprises and to online services will need to be reduced; and private companies in this segment will need to act more strategically and consolidate.
 
Most of these online healthcare service providers are technologically heavy and strategically light. For private companies in this market to grow and increase their influence on the NHS they will need to increase their focus on profitability and scale, which will require them to become more strategic and develop merger-integration skills. To become a dominant player, a company will have to successfully consolidate. Speed and merger competence are paramount. Companies that capture critical ground early and move up the consolidation curve the fastest will be successful. Enterprises that are slow to consolidate will become acquisition targets and disappear. Companies that stay out of the consolidation contest altogether will not survive.

A Chinese example
 
History has shown that many short-term emergency measures have a tendency to  become permanent fixtures. Thus, the UK’s response to the coronavirus CoVID-19 outbreak might permanently reduce the barriers to moving routine primary care tasks to innovative private online enterprises.
 
In an attempt to fully appreciate the potential of increasing online primary healthcare services in England, consider WeDoctor, a Chinese mobile app launched in 2010 by artificial intelligence expert Jerry Liao. Originally called Guahao (Mandarin for “booking”), WeDoctor started as a simple booking platform that made it easier for patients to make appointments with doctors. From these humble beginnings WeDoctor grew by adding extra functions such as reminders for regular medical checks, screening, prescriptions and online diagnoses and consultations. This helped to unclog China’s fragmented and bureaucratic healthcare system and made quality healthcare more accessible to the average person.
 
WeDoctor secured backing from Tencent Holdings, a Chinese multinational conglomerate, Sequoia Capital, the Goldman Sachs Group and the insurer AIA Group. In 2018, the company raised US$0.5bn in a private financing round at a valuation of US$5.5bn. Today, WeDoctor has more than 210m registered users mainly in China for its online appointment booking, prescription and diagnosis services and is linked to about 3,200 hospitals and 360,000 doctors. In March 2020, at the height of the CoVID-19 pandemic, it was reported that, in the latter half of 2020, WeDoctor intends to raise HK$1bn in an IPO on the Hong Kong Stock Exchange at a valuation of HK$10bn.
 
Although NHS England is much smaller than China’s healthcare provision, it is similarly fragmented and bureaucratic. The UK online solutions enterprises described in this Commentary have significant potential simply by helping to reduce GPs large and increasing burden of administration while increasing the connectivity between patients and GPs. This will help GPs to concentrate on what they have been trained to do and improve healthcare for people in most need.
 
Takeaways
 
Over the past two decades, legacy primary care systems and attitudes in the UK have slowed the uptake of online healthcare solutions. Notwithstanding, the NHS’s response to the coronavirus CoVID-19 outbreak might prove to have helped to transform the UK’s traditional face-to-face primary care model by making GPs deliver some of their services online. In a recent interview with the New York Times, Dr Bruce Aylward, Assistant Director-General of the World Health Organization, stressed how the Chinese had responded to the coronavirus outbreak by significantly increasing the amount of medical care the nation provides online.  In light of the discussion in this Commentary, be minded that in Mandarin the word “crisis” is denoted by two characters: 危机, one means ‘disaster’ and the other means ‘opportunity’.
 
 
#coronavirus #coVID-19 #NHSEngland #NHS #pandemic #primarycarecrisis #ChinaWeDoctor #WeDoctor #DigitalHealthcare 
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  • The burden of breast cancer throughout the world is significant and increasing
  • Research has shown that a cheap pill (anastrozole) halves postmenopausal women’s risk of breast cancer and continues to be effective seven years after women stop taking the drug
  • Anastrozole has fewer side-effects and is more effective than comparable treatments
  • Government watchdogs both in the UK and US recommend anastrozole
  • But the uptake of the drug in the UK is relatively low
  • Doctors are not prescribing anastrozole and women are not availing themselves of the drug
  • The UK’s NHS should employ new behavioural techniques to influence and change doctors’ and patients’ decisions and increase the uptake of anastrozole to reduce the burden of breast cancer

Will behavioural techniques improve breast cancer outcomes?
 
Being a woman and growing older are two unavoidable risk factors for breast cancer. Indeed, most breast cancers are found in women who are 50 years or older. Despite significant advances in diagnoses and treatments, breast cancer is one of the rapidly increasing cancers among women and a significant cause of cancer-related morbidity and mortality worldwide.  Breast cancer alone accounts for 30% of all new cancer diagnoses among females and has become a major 21st century health challenge.
 
Study shows long term benefits of a cheap breast cancer pill

Research findings reported in the December 2019 edition of The Lancet and also presented at the  December 2019 San Antonio Breast Cancer Symposium in Texas, show that a cheap pill, anastrozole,  if taken once a day for 5 years, not only halves postmenopausal women’s risk of breast cancer, but continues to be effective seven years after stopping treatment, which for the first time, suggests a long-term benefit.
 
Relatively low uptake
 
The UK’s NHS watchdog, the National Institute for Health and Care Excellence (NICE), suggests that hundreds of thousands of healthy older women should take anastrozole to cut their risk of breast cancer and recommends that the drug is offered to postmenopausal women at moderate to high risk of breast cancer unless they have severe osteoporosis. However, evidence suggests that some doctors in the UK are not prescribing anastrozole and some women are not availing themselves of the drug despite its demonstrated clinical benefits and the fact that anastrozole is supported by NICE.
 
Jack Cuzick, the lead author of The Lancet 2019 paper, who is Professor of Epidemiology and the Director of the Wolfson Institute of Preventive Medicine at Queen Mary UniversityLondon, is concerned because although anastrozole is, “An agent that looks really effective with minimal side-effects and is available on the NHS in the UK; its uptake has been quite low with only a tenth of eligible women receiving it”. Cuzick’s concerns are echoed by Delyth Jane Morgan, Chief Executive of the charity Breast Cancer Now, who said: "It is worrying to hear that anastrozole may not be being offered to all that could benefit. We need to understand the extent of this potential issue. It's essential that we raise awareness of this option among doctors and patients".
 
 In this Commentary
 
Part 1 of this Commentary explores some of the reasons for the relatively low uptake of anastrozole. Part 2 describes new behavioural techniques, which could be cheaply and easily employed by health systems to increase the uptake of anastrozole and dent the burden of breast cancer. Also the Commentary: (i) describes breast cancer, (ii) provides some epidemiological facts of the disease, (iii) estimates the cost to treat breast cancer in the UK, (iv) describes hormone receptor positive breast cancer, (v) explains how anastrozole works and (vi) reports the findings of The Lancet 2019 study.

 
Part 1
 
 
Breast cancer
 
Cancer is a group of diseases that cause cells in your body to change and spread out of control. Most types of cancer cells eventually form a lump or mass called a tumour and are named after the part of your body where the tumour originates.

 

Breast cancer is characterized by the presence of cancer cells in the tissue or ducts of your breast. Most breast cancers begin either in the breast tissue made up of glands for milk production, called lobules, or in the ducts that connect the lobules to the nipple. The remainder of the breast is made up of fatty, connective and lymphatic tissues. Advanced breast cancer refers to cancer that has spread outside of your breast to lymph nodes and/or distant locations in your body, often invading your vital organs.
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Epidemiology of breast cancer
 
Breast cancer is a common malignancy. Although more and more women are surviving the disease, each year in the UK there are over 55,000 new breast cancer cases: which equates to over 1,000 diagnosed each week. In the US, there are some 250,000 new breast cancer cases diagnosed each year: nearly 5,000 a week. Between 1993 and 2016 the incidence of breast cancer in the UK increased by 24%. Over a similar period, breast cancer incidence in the US declined, but an increasing trend of some 1.1% was observed among American Asians. In China, between 2000 to 2013, breast cancer increased at an annual rate of around 3.5%. Breast cancer rates in China are higher in urban areas than in rural areas: the higher the population density, the higher the rate. It is not altogether clear why breast cancer incidence is increasing. Experts suggest that breast cancer is a complicated disease with a variety of causes. Most cases of the disease are not linked to a family history. Around 5% of people diagnosed with breast cancer have inherited a faulty BRCA1 or BRCA2 gene. However, if you have a faulty gene, it does not mean that you will automatically develop breast cancer, but you are at higher risk. Out of every 100 women with a faulty gene, between 40 and 85 will develop breast cancer in their lifetime. Optimal therapy for breast cancer often requires several different treatment modalities including surgery, radiation, chemotherapy and hormone therapy (see below).
 
Cost of breast cancer treatment in the UK
 
The cost of treating breast cancer in the UK is significant and rising. Findings of research on the treatment costs of breast cancer published in the August 1999 edition of The Breast estimated that the average cost per case of breast cancer in the UK to be £7,247 (US$9,418).  Although the estimate is dated, it provides a guide. With 55,000 new cases of breast cancer diagnosed each year, the annual cost of treating the newly diagnosed alone, would be about £0.4bn (US$0.52bn). According to the UK charity Breast Cancer Now, an estimated 840,000  women  living in the UK have been diagnosed with breast cancer and the charity predicts that this figure will increase to 1.2m over the next decade. Thus, ceteris paribus, we can assume that the current annual cost  of treating breast cancer in the UK is significantly higher than £0.4bn and this figure is expected to increase substantially by 2030.
 
 
Hormones and hormone therapy
 
Hormones are chemical messengers secreted directly into your bloodstream, which carry them to organs and tissues of your body to exercise their functions.  Oestrogen and progesterone are steroid hormones produced by the ovaries in premenopausal women and by some other tissues, including fat and skin, in both premenopausal and postmenopausal women. These hormones play a critical role in regulating reproduction. Oestrogen promotes the development and maintenance of female sex characteristics and the growth of long bones. Progesterone plays a role in the menstrual cycle and pregnancy.
 
Similar hormones are produced artificially either for use in oral contraceptives or to treat menopausal and menstrual disorders. Oestrogen and progesterone also promote the growth of some breast cancers, which are called hormone-sensitive (or hormone-dependent) breast cancers. Hormone-sensitive breast cancer cells contain proteins called hormone receptors, which become activated when hormones bind to them. The activated receptors cause changes in the expression of specific genes that can stimulate cell growth.
 
Anastrozole is a hormone therapy (also called hormonal therapy and endocrine therapy), which slows or stops the growth of hormone-sensitive tumours by either blocking the body’s ability to produce hormones or by interfering with the effects of hormones on breast cancer cells. Anastrozole blocks a process called aromatisation, which changes sex hormones called androgens into oestrogen. This happens mainly in the fatty tissues, muscle and the skin and needs a particular enzyme called aromatase.
 
 Prescribing anastrozole
 
Anastrozole belongs to a group of drugs called aromatase inhibitors, which are specifically designed to treat postmenopausal women diagnosed with hormone-receptor-positive, early-stage breast cancer.  It is most often prescribed as an adjuvant therapy (after surgery) to decrease the risk of your cancer returning but can also be used in the neoadjuvant setting (prior to surgery) to decrease the size of your cancer in the breast. Hormone blocking therapy is also used to treat breast cancer that has recurred or spread. Most hormone blocking therapy drugs such as anastrozole are taken daily in pill form.
 
Anastrozole also may be given to reduce the risk of breast cancer in women who have not had breast cancer but have an increased risk of developing it because of their family history. Most experts suggest that your breast cancer risk should be higher than average for you to consider taking anastrozole as a preventative strategy. If your cancer is hormone receptor negative, then anastrozole will not be of any benefit, because these cancers do not need oestrogen to grow and usually such cancer cells do not stop growing when treated with hormones that block oestrogen from binding.
 
Reasons for the relatively low uptake of anastrozole
 
There are at least three probably reasons for the relatively low uptake of anastrozole. These include: (i) doctors becoming so used to prescribing the gold standard tamoxifen as an adjuvant hormone therapy, (ii) doctors wanting to be convinced about anastrozole’s long term benefits, and (iii) doctors wanting assurance about anastrozole’s minimal side effects.
  
Tamoxifen
 
Tamoxifen is the oldest and most-prescribed aromatase inhibitor and for the past three decades has become the standard of care as the adjuvant treatment of postmenopausal women with hormone-responsive early breast cancer. The drug reduces the risk of breast cancer returning by 40% to 50% in postmenopausal women and by 30% to 50% in premenopausal women. Notwithstanding, over the past two decades a new generation of aromatase inhibitors have been developed, and anastrozole is one of these. How does anastrozole compare with the gold standard tamoxifen?

Tamoxifen and anastrozole compared
 
Findings of two long-term comparative clinical studies undertaken in North America and Europe involving over 1,000 women with oestrogen receptor positive advanced breast cancer, showed that anastrozole is better than tamoxifen for: (i) increasing the time before the cancer returns in those who experience recurrence, (ii) reducing the risk of the cancer spreading to other parts of the body and (iii) reducing the risk of a new cancer developing in the other breast.

Significantly, studies have shown that anastrozole avoids two of tamoxifen's more serious side-effects: an increased risk of developing a blood-clotting disease and an increased risk of developing womb cancer.  Anastrozole can make bones weaker and so it is not recommended for women with osteoporosis and also it can cause stiff joints, hot flushes and vaginal dryness, which clinicians need to recognize and manage. But overall, the benefits of anastrozole over tamoxifen were maintained without a detrimental impact on quality of life. However, anastrozole is not a therapy for  premenopausal women because it blocks the hormone oestrogen and in effect creates a drug-induced menopause.


Part 2

Increasing the uptake of anastrozole
 
For healthcare systems to function effectively and efficiently we expect doctors and patients to behave rationally and make effective and efficient decisions. Traditionally, the rational choice model, which is predicated upon the belief that all human beings (including doctors and patients) act rationally in their own self-interest, has been used to influence people to behave in desirable ways. However, evidence suggests that, despite the well-founded theory and sound evidence to support it, the rational choice approach does not appear to work that well in practice.



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Behavioral scientists not doctors will prevent CVD

 A newer theory to explain peoples’ choices and behaviours
 
A newer approach to influencing behaviour, which builds on decades of research by Nobel prize-winning psychologist Daniel Kahneman, and described in a book published in 2008 entitled Nudge, by Nobel Prize winning economist Richard Thaler and Harvard Law School professor Cass Sunstein, suggests that no choice is ever presented in a neutral way and people - including doctors and patients - are susceptible to biases that can lead them to make suboptimal decisions. The authors suggest that many decisions and consequent behaviours are made automatically rather than after a considered rational decision. And this applies to decisions about your health.
Policymakers have been quick to latch onto the possibilities of these new behavioural techniques. Following the publication of Thaler and Sunstein’s book in 2008, President Obama set up a “Nudge Unit” in the White House and the UK Government, under Prime Minister David Cameron, set up the Behavioural Insights Team, popularly known as the Nudge Unit, in 10 Downing Street, and other governments around the world have since followed suit.

Nudges
 
Nudges are particular types of interventions, which are used to change peoples’ behaviour and improve outcomes at lower cost than traditional tools across a range of policy areas. Nudge techniques have been used in healthcare to influence behaviour and decision making to improve patient outcomes. For instance, the behavioural analysis of the decision-making that leads to a patient taking one drug instead of another. A research paper published in 2015 by the UK’s Health Foundation entitled “Behavioural insights in healthcare” suggests that health messages are often inconsistent and confusing to patients and framing them using social comparison via descriptive social norms (pointing out what is commonly done) or using injunctive norms (pointing out what is approved of) has been demonstrated to change patients’ behaviour and thereby have the potential to improve patient outcomes.
 
Information design
 
Behavioural techniques suggest that more attention should be given to the design of health information because the design and the way information is presented can influence and change doctors' and patients’ behaviour. Clinical guidelines, patients’ checklists and decision aids can all be improved in terms of text and language (e.g. the use of “plain English” and behaviourally specific, concrete statements and presentation of risk) and appearance (e.g. colour, visual stimuli, images etc).
 
HealthPad advocates that health information can have significantly more influence on the choices that doctors and patients make and on their  behaviour simply by presenting critical information in a video format. Over the past few decades people have moved away from consuming information in written and audio formats to consuming information predominantly in a visual format.  
 
Shift to consuming information in video format
 
Consider the following as being indicative of this shift. 82% of Twitter’s 330m average monthly users consume information in video format. The video channel You Tube has over a billion users and more than 500m hours of video are watched on the channel each day. 72 hours of video are uploaded to You Tube every 60 seconds, and more video content is uploaded onto the channel in 30 days than the major US television networks have created in 30 years. To further put things into perspective, in 2017, 56 exabytes (equivalent to 1bn gigabytes) of internet video content was consumed on a monthly basis, and this figure is expected to more than quadruple to 240 exabytes per month by 2022.

Today, almost all industries,  with the exception of healthcare, use video formats to communicate and the overwhelming majority of people who have consumed information in video format say it has influenced their choices and changed their behaviour. With video becoming the most significant influence on consumer decisions, it seems reasonable to suggest that more health information needs to be communicated in a video format if it is to influence and change doctors’ and patients’ behaviours in order to improve medical outcomes, increase the quality of care and slow and prevent chronic lifetime diseases.
 
Prompts cues reminders and audits
 
Prompts, cues and reminders have been demonstrated to be generally effective “nudges” that can successfully change the behaviour of healthcare providers and consumers, as well as being relatively inexpensive and easy to administer. Audit and feedback “nudges” are also effective. A set of best practices derived from systematic review evidence suggests that various nudge-type interventions (notably information design and presentation) may offer new ways to enhance choices and change behaviour.
  
Takeaways
 
The burden of breast cancer is huge and increasing globally. Research has demonstrated that a cheap pill, anastrozole, halves postmenopausal women’s risk of the disease and continues to be effective seven years after women stop taking the drug. We suggest that healthcare systems should consider using new behavioural techniques to influence and change doctors' and patients’ decisions to increase the uptake of anastrozole to help reduce the burden of breast cancer. Evidence suggests that nudge-type interventions, if suitably applied, can influence and change the behaviour of doctors and patients and thereby contribute to the reduction of the burden of breast cancer. However, given the newness of these techniques the quality of evidence available about their impact is relatively thin and patchy. Notwithstanding, this suggests a need for more quality evaluation and synthesised evidence of nudge-type interventions, their behaviour change potential and their impact on reducing the burden of breast cancer and other chronic lifetime diseases.
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  • Bioengineers throughout the world are competing to achieve the Holy Grail: an affordable, point-of-care blood test - liquid biopsy - that detects cancer before any symptoms present
  • Success in achieving this will save millions of lives, substantially reduce healthcare costs and make investors, researchers and organisations billions
  • Despite significant advances no one has yet achieved the Holy Grail and there remains a substantial gap between researchers’ aspirations and reality
  • How close are we?

 
 

Finding the Holy Grail: early detection tests for cancer
 

 

“It’s too soon to even claim that the research is promising," commented Paul Pharoah, a professor at Cambridge University’s Centre for Cancer Genetic Epidemiology, on the research findings of  Daniyah Alfattani, a PhD student in the Centre of Excellence for Autoimmunity in Cancer (CEAC) at Nottingham University’s School of Medicine in the UK.
 
Alfattani was presenting research findings of a small study at the National Cancer Research Institute’s (NCRI) conference in Glasgow, Scotland, in November 2019, which is an international forum for showcasing cancer advances.
 
A September 2019 HealthPad Commentary described another early detection test for breast cancer called CanRisk, which has been developed by researchers from Cambridge University’s Centre for Cancer Genetic Epidemiology and  has the potential to identify women with different levels of risk of breast cancer.
 
Alfattani and bioengineers from the universities of Nottingham and Cambridge are players in a vast and rapidly evolving international army of researchers engaged in an intensely competitive global race to develop an affordable, point-of-care, early detection test (EDT) for cancer based upon a liquid biopsy and next generation sequencing technologies. The Holy Grail is for such a test to detect cancer cells in an asymptomatic patient, locate the tissue of origin and give that person an early diagnosis when treatment is more likely to be successful; and to do all this with 100% accuracy. 

Although Alfattani’s research study is modest, her findings are potentially clinically relevant because they are on the Holy Grail therapeutic pathway, and her preliminary findings suggest that a simple, cheap and easy-to-use blood test - liquid biopsy - could detect breast cancer five years before any symptoms present. If demonstrated to be exquisitely accurate, safe and efficient by a larger study, which already is underway at Nottingham University’s CEAC, Alfattani’s research could be a key to saving thousands of lives and substantial amounts of money.

 


Gold standard breast cancer screening
 
Currently, mammography screening is the gold standard for preventing and controlling breast cancer, which is costly to administer and only has a sensitivity between 72% and 87%.  For every death from breast cancer that is prevented by mammography screening, it is estimated there are three false-positive cases detected and treated unnecessarily. Further, nearly half of all cancer sufferers are diagnosed late, when their tumours have already metastasized. It is estimated that 30% to 40% of cancer deaths could be prevented by early detection and treatment.
 
In this Commentary
 
This Commentary provides a partial update of some bioengineering initiatives described in a 2016 HealthPad Commentary, to speed up and improve liquid biopsies, which can simultaneously detect cancer early and identify its tissue of origin. Although there have been significant developments, the challenge for liquid biopsy assays still remains the level of their positive predictive values. This Commentary provides a brief and partial epidemiology of breast cancer, describes Alfattani’s research and its findings and briefly mentions some similar research that is underway. We describe categories of biomarkers employed by researchers and indicate some advances in EDTs made by some giant biopharma companies as well as briefly describing another innovative university-based development. We conclude by suggesting that: (i) despite significant and well supported research endeavours over the past decade to develop EDTs, there still remains a gap between scientific aspirations and reality; and (ii) there appears to be a gap opening between commercially available personalised cancer therapies, which are by-products of EDT research and standard oncological therapies.
 
Partial epidemiology of breast cancer
 
Despite significant advances in the awareness, diagnosis and treatment of breast cancer, it still remains the most common cancer in women worldwide, contributing 25.4% of the total number of new cases of cancer diagnosed in 2018. Each year, more than 0.5m women throughout the world die from the condition.  In the US each year, over 268,000 new cases of invasive breast cancer are diagnosed in women, and over 41,000 women die from breast cancer. Between 1989 and 2016, death rates from female breast cancer in the US dropped by 40%. Over the past decade, death rates from breast cancer in older women in the US continued to decrease but remained steady in women under 50. Such decreases are attributed to increased awareness of the condition, earlier detection through screening and improved treatments. In the UK, there are over 55,000 new breast cancer cases diagnosed each year. In contrast to the US, since the early 1990s, breast cancer incidence rates in the UK have increased by around 19%, but death rates have fallen because of greater awareness, earlier detection and enhanced therapies. Notwithstanding, each year more than 11,000 women in the UK die from breast cancer. Furthermore, each year in the US, there are over 1.7m new diagnoses of all cancers, while in the UK there are over 360,000 new cases. Although recent advances in EDTs have the potential to decrease cancer deaths, as yet there is not a simple and cheap liquid biopsy, which can be used routinely  in clinics to diagnose a range of cancers early. .
 
Alfattani’s research
 
The research pursued by Alfattani and her Nottingham colleagues is predicated upon the fact that cancer cells produce proteins called antigens, which trigger the body to make antibodies against them. These are called “autoantibodies”. Researchers discovered that these tumour-associated antigens (TAAs) are good indicators (biomarkers) of cancer. Alfattani and her colleagues developed panels of TAAs, which are known to be linked with breast cancer as a technique to detect whether or not there are autoantibodies against them in blood samples taken from patients.

The Nottingham researchers took blood samples from 90 breast cancer patients at the time they were diagnosed with the disease and matched them with samples taken from 90 patients without breast cancer (the control group). Researchers employed technology (protein microarray), which allowed them to screen the blood samples for the presence of autoantibodies against 40 TAAs associated with breast cancer and also 27 TAAs not known to be linked with the disease. The accuracy of the test improved in the panels that contained more TAAs.

Findings

A panel of five TAAs correctly detected breast cancer in 29% of the samples from the cancer patients and correctly identified 84% of the control group as being cancer-free. A panel of seven TAAs was able to detect disease in 35% of cases with breast cancer and rule out 79% of patients in the control group. The most successful technique was a panel of nine antigens, which correctly identified the disease in 37% of cancer samples and no cancer in 79% of the controls. “The results of our study showed that breast cancer does induce autoantibodies against panels of specific tumour-associated antigens. . . . . The results are encouraging and indicate that it is possible to detect a signal for early breast cancer. Once we have improved the accuracy of the test, then it opens the possibility of using a simple blood test to improve early detection of the disease”, said Alfattani.

David Crosby, head of early detection at the Cancer Research UK charitysaid, “Diagnosing cancer at the earliest stages before it grows or spreads gives patients the best chance that their treatment will be successful. So, the potential to detect markers in the blood before other signs appear is promising”.
 
Similar studies
 
Nottingham University’s CEAC is also working on similar tests to that used by Alfattani for pancreatic, colorectal and liver cancers. Solid tumours like these, as well as lung and breast cancer, represent around 70% of all cancers. Further, a similar test for lung cancer is currently being tested in a randomised controlled clinical study in Scotland, which is believed to be the largest trial of its kind in the world, involving 12,000 people at high risk of developing lung cancer because they smoke.
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Participants in the study have been randomly assigned to two groups: one is given an autoantibody blood test and the other (the control group ) is not. Participants who test positive for the autoantibodies are then followed up with a CT scan every two years in order to detect lung cancer in its early stages when it is easier to treat. Findings suggest that the test detects lung cancer four years or more before standard clinical diagnosis. In the UK about 85% of lung cancer patients are left undiagnosed until the disease has spread to other parts of the body.

 


Liquid biopsies

 
Liquid biopsies require biomarkers, which are substances, structures, or processes in your body that can be analysed in order to explain the pathogenesis of cancer and other disease states, and thereby inform diagnosis, predict onset and suggest appropriate therapies. Notwithstanding, the multiple types of biomarkers have varying degrees of reliability. Initially, the principal focus of research into EDTs was largely focussed on circulating tumour cells (CTC) and DNA. More recently however, additional biomarkers have become an important focus for such research. Antibodies are just one type of molecular biomarker. Because antibodies function by binding specific antigens, attempts to identify antibody biomarkers have involved using antigens to capture antibodies that are overproduced in cancer. Identifying relevant antigens is critical for discovering antibody biomarkers. Array-based approaches employed by Alfattani and her colleagues depend on exposing serum samples from patients to an ordered array of putative antigens, capturing those antibodies that bind antigens on the arrays and measuring their levels. Antibodies that are present at significantly higher levels in the serum of patients with breast cancer, (compared to control serums from healthy patients) are candidate biomarkers. 
 
Because of the unreliability of such biomarkers, new liquid biopsy tests tend to be predicated upon the levels of cell-free DNA (cfDNA), circulating tumour DNA (ctDNA) and exosomes. These also pose challenges because of the varying physiological levels of the different biomarker fragments in your bloodstream.
cfDNA refers to DNA molecules that circulate in your blood after cell death. The amount of cfDNA varies significantly depending on the location, type and stage of your cancer. Concentrations of cfDNA can range from 1 to 100,000 fragments per ml of blood.

ctDNA refers to DNA that comes from cancerous cells and is present in your bloodstream. As a tumour grows, your cells die and are replaced by new cells. Your dead cells decompose and their contents, including DNA, are released into your bloodstream. So, ctDNA are small fragments of DNA, the quantity of which varies between individuals and the location, type and stage of your cancerous tumour. Detection of single mutations in ctDNA requires a large volume of blood. The principal challenge of research predicated upon ctDNA is their relatively low abundance in your bloodstream. As a consequence, scientists cannot rely solely on ctDNA, and are forced to search for other genetic and epigenetic mutations in your blood.
Exosomes is another class of biomarker. Cancer related exosomes are nano-size membrane vesicles that play important roles in tumour microenvironment. A 2007 paper in Nature Cell Biology 
suggested that exosomes can load unique cargoes, including proteins and nucleic acids that reflect the condition of a tumour. Since the 2007 Nature paper, research into exosomes has increased and they are now being used as diagnostic and prognostic biomarkers for various cancers. 

 
CancerSEEK

 
An innovative liquid biopsy called CancerSEEK, which has been developed by researchers from the Johns Hopkins Kimmel Cancer Center, in Baltimore, USA, is expected to make early cancer detection a part of routine medical care. Significantly, the test screens for eight common cancers, which account for more than 60% of all cancer deaths in the US. Currently, five of the cancers covered by the test have no screening test. CancerSEEK combines cutting-edge liquid biopsy technology with a machine learning engine, which is expected to improve the test’s accuracy with every person it screens. Findings of a retrospective study of multiple cancer types published in the February 2018 edition of the journal Science suggested that CancerSEEK has a sensitivity between 69% and 98% for ovarian, liver, stomach, pancreatic and oesophageal cancers, a specificity of 99%. Further, the study suggested that the test  has a false-positive rate of less than 1%. In 2019, CancerSEEK received Breakthrough Device designation from the US Food and Drug Administration (FDA) for the detection of genetic mutations and proteins associated with pancreatic and ovarian cancers, and also raised US$110m to launch a start-up company to develop the technology further.
 
FDA approval for a liquid biopsy developed by Roche
 
In June 2016, Roche, a global biopharma, became the first company to receive FDA approval of a liquid biopsy test to detect mutations associated with non-small cell lung cancers (NSCLC). Notwithstanding, the biopsy is not a universal test to detect the presence of NSCLC, but rather a test, which is being used in people with lung cancer to enhance personalised targeted therapies, and to monitor progression of the cancer. Some patients may benefit from the test's accompanying drug erlotinib (Tarceva), which treats NSCLC.
 
In September 2019, Genentech, a member of the Roche Group, announced positive results from the first prospective phase II/III clinical study to use a liquid biopsy and next generation sequencing to select treatment for people with NSCLC, without the need for a tissue biopsy. Next-generation sequencing facilitates the analysis of minute quantities of cfDNA circulating in the blood. In addition, Genentech is using machine learning algorithms on large data sets to characterize the molecular signatures of various cancer types.
 
Guardant and GRAIL
 
Previous HealthPad Commentaries have described research endeavours by Guardant Health  and GRAILwhich are “betting-on” liquid biopsies. Here briefly we update the developments of these two giant biopharma companies.

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In 2014 Guardant launched a next generation sequencing cfDNA assay called Guardant360 for treatment selection in a number of solid tumour cancers. In December 2018, the company launched an assay referred to as LUNAR to detect a range of early stage and recurrent cancers. LUNAR is based on data that Guardant collected from 80,000 advanced cancer patients using its 360 technology. In October 2019, the company launched ECLIPSE, a 10,000-patient clinical study to evaluate the performance of a second generation LUNAR blood test to detect colorectal cancer (CRC) in average-risk adults. The study is intended to improve CRC screening rates by offering a simpler liquid biopsy that overcomes challenges associated with current testing methods described above.
GRAIL has developed a prototype cfDNA sequencing assay to detect a range of cancers, many of which are not screened today and often present at late stages. Significantly, GRAIL has developed a prospective, observational, longitudinal clinical study called the Circulating Cell-free Genome Atlas (CCGA). The study has 15,000 participants across 142 sites in the US and Canada and has been designed to characterize the landscape of genomic cancer biomarkers of people with and without cancer. The company’s STRIVE study is fully enrolled with approximately 115,000 women and another study called SUMMIT also is fully enrolled with approximately 50,000 men and women aged 50 and older who do not have a cancer diagnosis at the time of enrolment.
 
Despite advancing technologies, FDA approvals, ongoing clinical studies and large and increasing investments in the development of liquid biopsies, (see a paper published in the June 2019 edition of Clinical and Translational Science entitled, “The Labyrinth of Product Development and Regulatory Approvals in Liquid Biopsy Diagnostics”) there remains a substantial gap between scientific aspirations and reality. Liquid biopsies still do not provide physicians with a reliable, point-of-care means to detect cancer early and become a reliable substitute for the more invasive and more expensive gold standard tissue biopsy.
 
Takeaways
 
Liquid biopsies represent a large and rapidly evolving area of bioengineering. There are hundreds of research papers published in peer reviewed medical journals, which describe findings of the latest research in this area. Oncologists involved in EDT research are familiar with genomics, the molecular properties of cancer tumours and commercially available innovative therapies, which are by-products of EDT research, but many oncologists are not. This difference of knowhow seems to be creating another gap  between certain personalised cancer therapies advocated by research oncologists and standard cancer management provided in many clinics. Closing these gaps is partly contingent upon continued and open EDT research and more effective education.
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