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  • Experts have called for the worldwide eradication of cervical cancer, but this is not likely to happen for a long time
  • Significant progress has been made to eliminate cervical cancer in developed countries
  • The overwhelming burden of cervical cancer falls disproportionately on women in low- to middle-income countries (LMIC)
  • LMIC have relatively low levels of awareness of cervical cancer, patchy prevent programs and limited treatment options
  • Over 80% of cervical cancer cases and deaths occur in LMIC
  • Cervical cancer is the fourth most common cancer in women worldwide
  • In 2018 there were an estimated 680,000 new cases and 311,000 deaths from the disease worldwide
  • Cervical cancer is caused by sexually acquired infection from high-risk strains of the human papilloma virus (HPV)
  • The majority of women will be infected with HPV at some point in their life
  • HPV also causes genital warts and cancers of the head and neck and is also linked to cancers of the anus, vulva, vagina, penis and oropharynx
  • HPV vaccines protect against 70% of cervical cancers and about 90% of genital warts
  • Regular screening is also recommended to reduce the incidence of cervical cancer
 
Challenges to eradicate cervical cancer globally

Cervical cancer is a killer disease, which only affects women. It affects women of all ages from schoolgirls to grandmothers, but it is significantly more prevalent between the ages of 30 and 45.
 
The cervix, also known as the neck of the womb, connects a woman's womb and her vagina.
 
Lancet study raises hope of eradicating cervical cancer
 
Research findings published in the June 2019 edition of The Lancet suggest that HPV vaccination, which has been available to adolescent girls in wealthy developed countries since 2007, has led to a dramatic reduction in the number of HPV infections, precancerous cervical lesions and anogenital warts and provides hope of eradicating cervical cancer. Marc Brisson, Professor in the Department of Social and Preventative Medicine, Laval UniversityCanada, who led the research - a meta-analysis of over 65 former studies covering 60m people - said: "We will see reductions [in cervical cancer] in women aged 20-30 within the next 10 years, and eradication  of the disease [defined as <4 cases per 100,000] might be possible if sufficiently high vaccination coverage can be achieved and maintained". Over the past two decades, the incidence rates of cervical cancer in developed countries have fallen significantly, and between 1955 and 1992, the incidence rate of the disease decreased 70% in the US. These falls are attributed to effective nationwide screening.
 
Epidemiology

Cervical cancer is the fourth most common cancer in women worldwide and second for women between 15 and 44. In 2018 there were an estimated 680,000 new cases and 311,000 deaths from the disease worldwide. The overwhelming majority of cases are caused by two specific strains of the human papilloma virus (HPV). HPV infection and early cervical cancer typically do not present noticeable symptoms, and cervical cancer may take 20 years or longer to develop after an HPV infection. The overwhelming global burden of the disease falls disproportionately on women in low- to middle income countries (LMIC). There is a significant and growing gap in the incidence and mortality rates of cervical cancer between developed nations and LMIC. Despite international efforts, it seems unlikely that this gap will be narrowed in the medium term.
 
In this Commentary
 
This Commentary describes the spread of HPV, the vaccines developed to prevent infection from specific high-risk strains of the virus and recommended vaccination regimens. We describe the nature and significance of complementary screening programs and present evidence to suggest that women who fail to get screened are more likely to contract cervical cancer in later life than women who are screened. HPV vaccination programs are more prevalent in developed economies and are associated with a significant reduction in the incidence rates of cervical cancer. This suggests that the battle to eliminate cervical cancer is being won in some wealthy developed nations. Australia is positioned to become the first country in the world to eliminate cervical cancer. Despite substantial global efforts to reduce the incidence rates of cervical cancer, the gap in preventing, diagnosing and treating the disease between wealthy nations and LMIC is significant and growing. We conclude by suggesting that to eradicate cervical cancer, screening and prevention programs must be linked to easily accessible and effective treatment.
 
The spread of HPV
 
Over 70% of cervical cancer is caused by two high-risk strains of HPV. Most women will contract HPV at some stage during their life, but this usually clears-up on its own without the need for any treatment. HPV is most commonly spread during vaginal, anal or oral sex. The virus can be passed even when an infected person has no signs or symptoms. If you are sexually active you can get HPV, even if you only have sex with one partner. Notwithstanding, the risk increases with the number of new sexual partners and their sexual histories. You also can develop symptoms years after you have sex with someone who is infected. This makes it hard to know when you first became infected.
  
HPV vaccines
 
The US Food and Drug Administration (FDA) has approved three vaccines, which prevent infection with disease-causing HPV types. These are Gardasil, Gardasil 9 and Cervarix. All three vaccines prevent infection with HPV types 16 and 18 in women who have not already been infected by these types. These are two high-risk HPV’s that cause about 70% of cervical cancers and an even higher percentage of some of the other HPV-caused cancers. Gardasil also prevents infection with HPV types 6 and 11, which cause 90% of genital warts. Gardasil 9 prevents infection with the same four HPV types, plus five additional cancer-causing types.
 
About 79m Americans are currently infected with HPV, with roughly 14m people becoming newly infected in the US each year. In the UK, HPV is present in one in three people and 90% of individuals will come into contact with some form of the virus in their lifetime. About 80% of sexually active people are infected with HPV at some point in their lives, but most people never know they have the virus. Whitfield Growdon, a surgical oncologist at the Massachusetts General Hospital and professor at the Harvard University Medical School describes the HPV vaccination as, “one of the most meaningful interventions for reducing cervical cancer”; see video below.

 
 
Who should get vaccinated?

All girls and boys aged between 11 and 12 should get the HPV vaccination. Every year in the US, over 13,000 males contract cancers caused by HPV. Catch-up HPV vaccines are recommended for girls and women through the age of 26, and for boys and men through the age of 21, if they did not get vaccinated when they were younger. HPV vaccination is also recommended for the following people, if they did not get vaccinated when they were younger: (i) young men who have sex with men through the age of 26, (ii) young adults who are transgender through the age of 26 and (iii) young adults with certain immunocompromising conditions (including HIV) through the age of 26.
 
Early cervical cancer is asymptomatic
 
Because early cervical cancer is asymptomatic, it is important for women to have regular Papanicolaou (Pap) smears - also called Pap tests - to detect any precancerous changes in the cervix that might lead to cancer. This is in addition to the HPV vaccination. In England women are invited to have Pap smears every three years between the ages of 25 and 49, when rates of cervical cancer are at their peak, and every five years between 50 and 65. Other international screening guidelines recommend that women aged 21 to 29 have a Pap smear every three years. Women aged 30 to 65 are advised to continue having a Pap test every three years, or every five years if they also combine it with an HPV DNA test. Women over 65 can stop testing if they have had three consecutive normal Pap tests, or two HPV DNA and Pap tests with no abnormal results.
 
The HPV DNA test determines the most likely cause of cervical cancer by looking for pieces of DNA in cervical cells and is recommended for women over 30 and not for women under 30. This is because women in their 20s tend to be more sexually active and therefore are more likely (than older women) to have an HPV infection that will go away on its own. Results of an HPV DNA test carried out on a woman in her 20s is not as significant as in and older woman and also may be confusing. The HPV DNA test can also be used in women who have slightly abnormal Pap test results to find out if they might need more testing or treatment.
 

The Pap smear/test
 
The Pap smear or Pap test is a method of cervical screening used to detect potentially precancerous and cancerous processes in your cervix. During the routine procedure, cells from your cervix are gently scraped away and then examined for abnormal growth. Abnormal findings are often followed-up by more sensitive diagnostic procedures and if warranted, by interventions that aim to prevent progression to cervical cancer. Detecting cervical cancer early with a Pap smear significantly increases the chances of a cure. A Pap smear can also detect changes in your cervical cells, which suggest you might develop cancer in the future. In the two videos below Growdon describes the Pap smear and other tests for diagnosing cervical cancer.
 

What is a Pap smear test?
 
 
Diagnostic tests for cervical cancer
 
 Women failing to have the Pap test are 6-times at greater risk of cervical cancer
 
There is evidence to suggest that women over 50 who fail to have a regular Pap smear have a much higher risk of developing cervical cancer compared with other women the same age who have a history of regular screening. Research carried out by Cancer Research UK and reported in 2014 investigated the utility of regular cervical cancer screening after 50, and whether 64 was an appropriate age to stop screening and concluded “yes” and “yes”. The study compared the screening history of 1,341 women between 65 and 83 in England and Wales who were diagnosed with cervical cancer over a five-year period, with 2,646 women of the same age without the disease. Findings suggest that women who did not attend screening tests were six times more likely to develop cervical cancer between 65 and 83 compared with women that did. 
 
Australian the first country to eradicate cervical cancer
 
Australia is well positioned to become the first country in the world to eradicate cervical cancer. This is largely due to national vaccination and screening programs, which could see the disease effectively eliminated as a public health issue within the next two decades. In 2007, Australia launched a national publicly-funded school immunisation program to reduce HPV, which complemented a national  cervical cancer screening program that was launched in the 1990s. These have been shown to reduce the incidence of cervical cancer and significantly increase early diagnosis when the disease is curable.
 
A research paper about the Australian initiative published in the January 2019 edition of The Lancet Public Health concludes that, “the annual incidence of cervical cancer in Australia is likely to decrease to fewer than six new cases per 100 000 women by 2020 (range 2018–22) and to fewer than four cases per 100 000 women by 2028 (2021–35). The annual incidence of cervical cancer could decrease to one new case per 100 000 by 2066 (2054–77) if the existing HPV-based screening program continues in cohorts who are offered the nonavalent vaccine”; [a nonavalent vaccine works by stimulating an immune response against nine different antigens, such as nine different viruses or other microorganisms]. According to Suzanne Garland, Professor and Clinical Director of Microbiology and Infectious Diseases at the Royal Women’s Hospital, Melbourne, Australia, who led the research, “within 40 years the number of new cases of cervical cancer [in Australia] is projected to drop to just a few”.
 
The two worlds of cervical cancer
 
Global efforts to reduce the incidence rates of cervical cancer have focused on HPV vaccination  and the Pap test. Although experts are optimistic about eliminating cervical cancer in developed nations, which have advanced healthcare systems and extensive HPV vaccination, screening and treatment programs, they are significantly less sanguine about eradicating the disease in LMIC where there are relatively low levels of awareness of cervical cancer, a dearth of  preventative strategies, limited expertise and a narrow band of treatment options. This results in the disease being identified late when it is at an advanced stage, which leads to higher rates of morbidity and death. Indeed, 85% of all cases and cervical cancer deaths occur in LMIC, where the death rate is 18 times higher than in wealthy nations.
 
Cervical cancer a challenge for LMIC
 
The gap in preventing, diagnosing and treating cervical cancer between wealthy nations and LMIC is  described in a paper published in the November 2017 edition of Gynecologic Oncology Reports and suggests that, “Developing countries continue to bear a disproportionate percentage of the global cervical cancer burden. Investigations into the growing gap in incidence and mortality between developed nations and LMIC have cited persistent financial, infrastructural and educational limitations as key drivers. Pervasive lack of access to both preventative and definitive care has left a substantial portion of cervical cancer patients with minimal options for disease management”.
 
WHO strategy to eliminate cervical cancer
 
Recognising this disparity, in 2018, the Director-General of the World Health Organization (WHO) announced a call to action for the eradication of cervical cancer as a public health problem. In January 2019, the Executive Board of the WHO requested the Director General to develop a draft strategy to accelerate cervical cancer elimination, with clear targets for the period 2020 - 2030.
 
Vaccination and screening must be linked to effective therapies
 
The expansion of screening programs for cervical cancer in LMIC is only part of the answer to closing the gap with developed nations and eradicating cervical cancer globally. It is imperative that screening is linked to increased access to effective treatment for women with cervical cancer, particularly in its early stages when it is still curable.  In LMIC there is often not only reduced access to preventive HPV vaccines and screening, but limited access to treatment and trained personnel. Notwithstanding, there is evidence to suggest that, in LMIC less-invasive and less–resource-intensive treatment options can be effective and are increasingly being made available.
 
Late presentation of cervical cancer in LMIC
 
Women from LMIC generally seek treatment for cervical cancer only after the presentation of symptoms when the disease is advanced and challenging to treat. Also, they often lack awareness of the disease and ways to prevent it. Further, in some regions of the world, cultural norms and myths about cervical cancer pose additional barriers to prevention. Despite such obstacles, the disease can be prevented at low cost by healthcare providers employing relatively simple techniques to screen women for precancerous conditions and treat abnormal tissue early. Among the most promising low cost and low-tech screening alternatives to the Pap smear, is visual screening, which only requires either simple vinegar or iodine solutions and the eye of a trained healthcare provider to spot abnormal tissue.
 
Screening linked to effective therapy
 
Increasingly, these simply tests are being linked with effective treatment. Increasingly, in LMIC relatively cheap and simple therapies are being used to either destroy or remove abnormal cervical tissue, depending on the severity, location and size of the affected area. Two such procedures include cryotherapy and loop electrosurgical excision procedure (LEEP). The former uses extremely low temperatures to destroy abnormal tissue and requires no electricity. The latter involves using a thin wire to remove lesions in the affected area. While this procedure requires more medical equipment than cryotherapy, it allows tissue to be removed for analysis, reducing the possibility that advanced cancer will go unnoticed. Although many LMIC have had cervical cancer prevention programs and simple treatment strategies in place for some time, some have failed to reduce death rates of the disease.
 
Radiotherapy and cervical cancer in LMIC
 
Research findings published in the May 2019 online edition of The Lancet Oncology suggest that the availability of radiotherapy in LMIC (where gross national income is <US$12,000 a year) would generate millions of productive life years and billions of dollars in economic benefits for the patients' families and communities. The study suggests that implementing a 20-year strategy for radiotherapy to treat cervical cancer in LMIC between 2015 and 2035, in parallel with an HPV vaccination program, would save the lives of some 9.4m women and provide a net benefit to economies of US$151.5bn as a direct result of women living longer and more productive lives.

According to Danielle Rodin, lead author and Radiation Oncologist at the Princess Margaret Cancer Centre, University of Toronto, Canada, "Vaccination is hugely important, but we can't neglect the millions of women who are contracting cervical cancer and dying in pain without access to treatment. These are women who have curable cancers: even advanced cervical cancer can be cured with radiotherapy. The possibility exists to make this treatment universally available". Radiation therapy makes small breaks in the DNA inside cells. This stops cancer cells from growing and dividing and causes them to die. Unlike cisplatin therapy, [an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy], which usually exposes the whole body to cancer-fighting drugs, radiation therapy is usually a local treatment.

 
According to the 2019 Lancet Oncology study, HPV vaccination would result in a 3.9% reduction in cervical cancer incidence over the 20-year study period; assuming a best-case scenario of vaccinating every 12-year-old girl in the world starting in 2014. By 2072, when the first vaccinated cohort reaches 70, there would be a 22.9% reduction in incidence, still leaving 41.6m in need for therapy over that time period.

We know that when administered together (chemoradiation) you can give lower doses of both and get a better kill-rate on the tumour. This is now the backbone of cervical cancer therapy”, says Growdon; see video below.

 
 
Abu Dhabi’s endeavours to reduce cervical cancer
 
For some years, experts have discussed religious and cultural barriers to cervical cancer screening and drew attention to the relatively low levels of cervical cancer awareness and screening for women in Middle Eastern Arab countries. Meta-analysis of cervical cancer studies conducted in Arab countries between January 2002 and January 2017 and published in the December 2017 edition of Nursing & Health Sciences, suggest that in Arab speaking countries there tends to be, “low knowledge of and perceptions about cervical screening among Arab women, the majority of whom are Muslim. Factors affecting the uptake of cervical cancer screening practices were the absence of organized, systematic programs, low screening knowledge among women, healthcare professionals' attitudes toward screening, pain and embarrassment, stigma, and sociocultural beliefs”.
 
The success of HPV vaccination in Abu Dhabi and the UAE
 
Notwithstanding, there are signs that this is changing. Leading such changes is Abu Dhabi of the United Arab Emirates (UAE). Over a decade ago, a mandatory free HPV vaccination program for school girls was introduced by Abu Dhabi’s Ministry of Health and Prevention and extended in 2013 to include women between 18 and 26. Also, the Ministry recommends that woman aged 25 to 65 years get a Pap smear every three to five years. Since 2018, HPV vaccinations have been provided free and compulsory for all school girls in Dubai and the Northern Emirates following a campaign to raise awareness.
 
Although the UAE is among the few countries to have relatively low incidence rates of cervical cancer, the disease still ranks as the third most frequent cancer among women in the UAE and the third most frequent cancer among women between 15 and 44. Estimates suggest that every year, 93 women are diagnosed with cervical cancer and 28 die from the disease in the UAE. Although Abu Dhabi is successfully leading the fight against cervical cancer and provides a roadmap for others to follow, the incidence of cervical cancer in the Middle East generally is expected to more than double by 2035 (>33,000 cases) and be responsible for more than 18,000 deaths. In some countries including Morocco and Saudi Arabia, low societal awareness and relatively low levels of screening results in about one in four women with HPV.
 
 Takeaways
 
As cervical cancer screening and prevention programs have been growing and extending their reach, so increases the need to provide access to effective treatment. Despite growing awareness of the disease and global efforts to increase availability of appropriate resources, cervical cancer remains prevalent particularly in LMIC where effective treatment has not become widespread. In many LMIC, the default option is often to do nothing, which results in certain death. Researchers and policy makers should consider focusing their activities on how to best to reconcile the use of existing resources with the expected impact on the quantity and quality of life. Although gaps in oncological resources and barriers to treatment still exist, the good news is that there is increased political will and international attention to improve access to safe and effective treatment of cervical cancer. Notwithstanding, eradicating the disease globally appears to be more of a theoretical possibility than a medium term reality.
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  • AstraZeneca has turned traditional biopharma R&D on its head and is targeting early stage cancer
  • This strategy benefits from  some of AstraZeneca’s R&D endeavours
  • But the strategy faces strong headwinds, which include significant technological and market challenges and substantial Competition from at least two unicorns
  
AstraZeneca’s strategy to target early cancer

 
Will José Baselga’s gamble pay off?
 
Baselga is AstraZeneca's new cancer research chief who has turned traditional biopharmaceutical drug development on its head by announcing AstraZeneca’s intention to target early- rather than late-stage cancer. “We need to spend our resources on those places where we can cure more people and that’s in early disease”, says Baselga, who knows that early detection can significantly improve patient survival rates and quality of life, as well as substantially reducing the cost and complexity of cancer treatment. Baselga also must know his strategy is high risk. Will it work?
 
In this Commentary
 
In this Commentary we discuss the drivers and headwinds of AstraZeneca’s strategy to increase its R&D focus on early stage cancer. But first we briefly describe cancer, the UK’s situation with regard to the disease and explain why big pharma targets advanced cancers. Also, we provide a brief description of AstraZeneca’s recent history.  
 
What is cancer?

Cancer occurs when a normal cell’s DNA changes and multiplies to form a mass of abnormal cells, which we refer to as a tumour. If not controlled and managed appropriately the tumour can spread and invade other tissues and organs. In the video below Whitfield Growdon, a surgical oncologist at the Massachusetts General Hospital in Boston US, and a Professor at the Harvard University Medical School explains.
 
 
The UK’s record of cancer treatment
 
In the UK cancer survival rates vary between types of the disease, ranging from 98% for testicular cancer to just 1% for pancreatic cancer. Although the UK’s cancer survival rates lag those of other European countries, the nation’s overall cancer survival rate is improving. Several cancers are showing significant increases in five-year survival, including breast (80% to 86%), prostate (82% to 89%), rectum (55% to 63%) and colon (52% to 60%). Many of the most commonly diagnosed cancers in the UK have ten-year survival of 50% or more. With regard to cancer spending, compared with most Western European countries, including France, Denmark, Austria and Ireland, the UK spends less on cancer per person, with Germany spending almost twice as much per head.
 
Why big pharma targets advanced cancers?
 
Most cancers are detected late when symptoms have manifested themselves, which renders treatment less effective and more costly. When cancer is caught early, as in some cases of breast and prostate cancer, tumours tend to be removed surgically or killed by chemoradiation therapy (CRT) and this, for many people, provides a “cure”, although in some cases the cancer returns.
 
Studies in developed economies suggest that treatment costs for early-diagnosed cancer patients are two to four times less expensive than treating those diagnosed with advanced-stage cancer. Notwithstanding, there are physical, psychological, socio-economic and technical challenges to accessing early cancer diagnosis and these conspire to delay cancer detection. Thus, big pharma companies have traditionally aimed their new cancer drugs at patients with advanced forms of the disease. This provides pharma companies access to patients who are willing to try unproven therapies, which significantly helps in their clinical studies. And further, big pharma is advantaged because regulators tend to support medicines that slow tumour growth and prolong life, albeit by a few months.
 
Imfinzi: the only immunotherapy to demonstrate survival at three years
 
A good example of this is AstraZeneca’s immunotherapy drug called Imfinzi (durvalumab) used in unresectable stage-III non-small cell lung cancer (NSCLC), which has not spread outside the chest and has responded to initial chemoradiation therapy. Imfinzi works by binding to and blocking a protein called PD-L1, which acts to disguise cancer cells from your immune system. Imfinzi removes the disguise so that your immune system is better able to find and attack your cancer cells.
 
Findings presented at the June 2019 meeting of the American Society of Clinical Oncology (ASCO), build on a clinical study of Imfinzi reported  in the September 2018 edition of The New England Journal of Medicineand suggest that Imfinzi is the only immunotherapy to demonstrate survival at three years in unresectable stage-III NSCLC. AstraZeneca has begun a phase-3 clinical study of the PD-L1 inhibitor protein in stage II NSCLC patients.
 

 

Some information about AstraZeneca
 
AstraZeneca is a British-Swedish multinational biopharmaceutical company with a market cap of US$107bn and annual revenues of US$22bn. The company operates in over 100 countries, employs more than 61,000, has its headquarters in Cambridge, UK, and is recovering after patents expired on some of its best-selling drugs and a failed takeover bid in 2014 by Pfizer.
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A paradigm shift in cancer diagnosis
Patents, legacy drugs and new biologics
 
When pharma companies develop a new drug, they can apply for a patent that stops other companies from making the same thing. A patent lasts for 20 years, after which point other producers can replicate the drug and its selling price plummets. This happened to AstraZeneca’s when the patents expired on two of its best-selling drugs: Crestor (rosuvastatin), and Nexium (esomeprazole). The former is a statin  that slows the production of cholesterol by your body, lowers cholesterol and fats in your blood and is used to reduce your chances of heart disease and strokes. The latter is a drug used to treat symptoms of gastroesophageal reflux disease (GERD) and other conditions involving excessive stomach acid. Unlike some of its rivals, these were oral medicines based on small molecules that are easy for generic manufacturers to copy, which made AstraZeneca vulnerable to cut-price competition immediately after the legal protection of the drugs had expired. Notwithstanding, AstraZeneca’s new generation of biologic medicines, which it launched in the first decade of this century, are protected to some degree by the fact that they are difficult to copy as they are manufactured using cells, instead of big chemistry sets used to make conventional drugs.
 
AstraZeneca’s history with early stage cancer therapies
 
Baselga’s gamble benefits from the fact that AstraZeneca developed an interest in the detection of early stage cancer before his appointment. Today, AstraZeneca is active in clinical studies with other biopharma companies and leading academic institutions targeting earlier-stage therapies.

Working with collaborators over the past two decades, AstraZeneca has tested a number of drugs including Iressa (Gefitinib) and Tagrisso (Osimertinib) in cancers from stage-I onward, in some cases to try to shrink tumours before they are removed surgically. Tagrisso is a potential star-drug for AstraZeneca. It  was originally developed to treat a group of lung cancer patients whose cancer had become resistant to established tyrosine kinase inhibitor therapies such as Iressa  and Roche’s Tarceva (erlotinib). Tagrisso surprised AstraZeneca as it turned out to be better than Iressa and Tarceva when used in untreated patients with epithelial growth factor receptor (EGFR) mutations. EGFR is a protein present on the surface of both normal cells and cancer cells, and are most common in people with lung adenocarcinoma (a form of NSCLC), more common with lung-cancer in  non-smokers, and are more common in women.

 
Epithelial growth factor receptor (EGFR)
 
Think of EGFR as a light switch. When growth factors (in this case tyrosine kinases) attach to EGFR on the outside of the cell, it results in a signal being sent to the nucleus of the cell telling it to grow and divide. In some cancer cells, this protein is overexpressed. The result is analogous to a light switch being left in the "on" position, telling a cell to continue to grow and divide even when it should otherwise stop. In this way, an EGFR mutation is sometimes referred to as an "activating mutation". Tagrisso "targets" this protein and blocks the signals that travel to the inside of the cell and growth of the cell stops. In 2003, when AstraZeneca received regulatory approval of Iressa we had little understanding about EGFR. Today however about 50% of drugs approved for the treatment of lung cancer address this particular molecular profile.

Technological challenges
 
Baselga’s gamble is assisted by advances in  liquid biopsies, which work by detecting fragments of malignant tumour DNA in the bloodstream to identify oncogenic drivers, which help treatment selection. The challenge of this approach is that tumours shed meniscal amounts of circulating tumour DNA (ctDNA), which significantly raises the difficulty of detecting the genetic signals that oncologists need to identify specific cancers and select treatments. ctDNA should not be confused with circulating free DNA (cfDNA), which is a broader term that describes DNA that is freely circulating in the bloodstream but is not necessarily of tumour origin.
 
The good news for Baselga is that in recent years looking for ctDNA has become a viable proposition because of improvements in DNA sequencing technologies, (see below) which make it possible to scan fragments and find those few with alterations that may indicate cancer. While other blood-based biomarkers are being investigated, the advantage of ctDNA is that it has a direct link to a tumour and can be very specific at identifying cancer.  ctDNA also provides a means to profile and monitor advanced stage cancers to inform treatments.
 
Notwithstanding, a paper published in the June 2018 edition of the Journal of Clinical Oncology  suggests that, “there is insufficient evidence of clinical validity and utility for the majority of ctDNA assays in advanced cancer”, and therefore it is still early to adopt cfDNA analysis for routine clinical use.
 

Next generation genome sequencing
 
DNA sequencing is the process of determining the sequence of nucleotides in a section of DNA. The first commercialised method was “Sanger Sequencing”, which was developed in 1977 by Frederick Sanger, a British biochemist and double Nobel Laureate for Chemistry. Sanger sequencing was first commercialized by Applied Biosystems, and became the most widely used sequencing method for approximately 40 years. More recently, higher volume Sanger sequencing has been replaced by next-generation sequencing (NGS) methods, which cater for large-scale, automated genome analyses. NGS, also known as high-throughput sequencing, is a general term used to describe a number of different state-of-the-art sequencing technologies such as Illumina’s Solexa sequencing. These allow for sequencing of DNA and RNA significantly more quickly and cheaply than the previously used Sanger sequencing and has revolutionised the study of genomics and molecular biology.
 
Can AstraZeneca acquire success?
 
Baselgo’s gamble is not helped by the relative dearth of biotech companies engaged in clinical studies of early stage cancers. This significantly narrows AstraZeneca’s options if it wants to buy-in clinical-phase assets to fit with Baselga’s strategy.
 
Notwithstanding, there are at least two biotech companies of potential interest to AstraZeneca. One is Klus Pharma, founded in 2014, based in Monmouth Junction, New Jersey, US, and acquired for US$13m in October 2016 by the Sichuan Kelun Parmaceutical Co., a Chinese group based in Chengdu. Another is Dendreon, a biotech company based in Seal Beach, California, US. In 2014 Dendreon filed for chapter 11 bankruptcy. In 2015 its assets were acquired by Valeant Pharmaceuticals. In 2017, the Sanpower Group, a Chinese conglomerate, acquired Dendreon from Valeant for US$820m.  
 
Klus is recruiting patients with stage-I rectal cancer for a phase 1/2 clinical study of its anti-HER2 antibody drug, and is also working to extend its flagship product, Provenge (sipuleucel-T) as an option for patients with low-risk prostate cancer. Provenge is an autologous cellular immunotherapy. It was the first FDA-approved immunotherapy made from a patient’s own immune cells. Since its approval in 2010, nearly 30,000 men with advanced prostate cancer have been prescribed the therapy.  
 
Unicorns threaten AstraZeneca’s strategy for early cancer
 
Perhaps the biggest threat to Baselga’s gamble is competition from unicorns, which include  Grail, and Guardant Health.  
 
Grail
Grail was spun-out of the gene sequencing giant Illumina in 2016 and backed by more than US$1.5bn in funding, including money from Microsoft cofounder Bill Gates and Amazon founder Jeff Bezos. Grail is on a quest to detect multiple types of cancer before symptoms manifest themselves by way of a single, simple and cheap blood test to find fragments of ctDNA. Grail has made significant progress in its quest to develop highly sensitive blood tests for the early detection of many types of cancer, but it still has to engage in further large-scale clinical studies. At the 2018 ASCO conference, the company presented data from its Circulating Cell-free Genome Atlas (CCGA) project, which showed detection rates ranging from 59% to 92% in patients with adenocarcinoma, squamous cell and small cell lung cancers. The rate of false positives - a major concern for the oncology community - was under 2%.
 
In an effort to improve its technology and its outcomes, Grail has been working with researchers from the Memorial Sloan Kettering Cancer CenterMD Anderson Cancer Center and the Dana-Farber Cancer Institute, to develop a new assay. According to results published in the March 2019 edition of the journal Annals of Oncology, this joint venture has successfully come up with a method, which can detect mutations in NSCLC patients’ blood with high sensitivity. In some cases, the technology was useful when tissue biopsies were inadequate for analysis. The new tool uses Illumina’sultradeep next-generation sequencing", which involves reading a region of DNA 50,000 times, on average, to detect low-frequency variants. White blood cells were also sequenced to filter out "clonal hematopoiesis", which are noncancerous signals that can come from bone marrow. The sequencing information was then fed to a machine learning algorithm developed by Grail to determine mutation readouts.
 
Guardant Health
The other unicorn for AstraZeneca to watch is liquid biopsy developer Guardant Health. Founded in 2013, it is now an US$8bn precision oncology company based in Redwood City, California US. In April 2019 Guardant presented data of its oncology platform at the American Association of Cancer Research (AACR) in Atlanta, US. The platform leverages Guardant’scapabilities in technology, clinical development, regulatory and reimbursement to drive commercial adoption, improve patient clinical outcomes and lower healthcare costs.  In pursuit of its goal to manage cancer across all stages of the disease, Guardant has launched two next-generation sequencing liquid biopsy-based Guardant360 and GuardantOMNI tests for advanced stage cancer patients, for minimal residual disease/recurrence monitoring and for early detection screening, respectively.
 
The Guardant360 test is used to track patients’ responses to drugs and select most effective future therapies. It can identify alterations in 73 genes from cfDNA and has been used by more than 6,000 oncologists, over 50 biopharmaceutical companies and all 28 of the National Comprehensive Cancer Network Centers. 
 
Further, Guardant has launched a new liquid biopsy called Lunar.  At the April 2019 AACR meeting the company presented data of Lunar’s use as a screen for early-stage colorectal cancer. The assay was used to test plasma samples taken from 105 patients with colorectal cancer and 124 age-matched cancer-free controls. It is the test’s utility as a screen for early-stage disease that should interest AstraZeneca most. Guardant expects to position Lunar as something approaching a true diagnostic: a screening test to identify solid tumours in the healthy population. Wider clinical studies of Lunar are expected to start soon and Guardant believes that Lunar’s market opportunity as a cancer screen is some US$18bn and sees a US$15bn market opportunity in recurrence monitoring.
 
Also, in April 2019 Guardant acquired Bellwether Bio,  a privately held company founded in 2015, for an undisclosed sum. Bellwether is focused on improving oncology patient care through its pioneering research into the epigenomic content of cfDNA. This could aid  Guardant in its efforts to develop a cancer screen and further advance its research into cancer detection at earlier stages of the disease.
 
Guardant is well positioned to develop individual early indications of cancer. Grail, on the other hand,  is well positioned to develop a pan-cancer test. Notwithstanding, both companies need to engage in further lengthy, large-scale clinical studies before it will become clear which of these strategies will be more successful. However, both unicorns and other start-ups are potential competitors to AstraZeneca’s endeavours to target early cancer.
 
Takeaways

AstraZeneca’sproposed bold and risky shift in its R&D strategy is to be welcomed since the early detection and treatment of cancer should significantly enhance the chances of a cure, which would radically improve the quality of life for millions and substantially reduce the vast and escalating costs associated with the disease. AstraZeneca has some advantages since over the past two decade it has significantly enhanced its technology and been developing a platform of therapies for early stage cancer. Notwithstanding, for its strategy to target early stage cancer to be successful the company will have to overcome intense, fast growing, well-resourced competition and substantial technical and markets challenges.  
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  • People are living longer, the prevalence of age-related degenerative disc disease is increasing and sufferers are more and more turning to spinal implant surgery as a solution
  • As this significantly raises the burden on over-stretched healthcare systems, so is spine surgery increasingly becoming a key target for cost reduction within healthcare systems
  • This intensifies the pressure on manufacturers to innovate and make spinal implants more cost effective

Can 3D printing and the use of new alloys reduce the high costs of producing and marketing spinal implants?
 
On January 8th 2019 surgeons at Joseph Spinea specialist surgery centre based in Tampa Bay Florida, were the first in the US to implant a 3D printed interbody fusion device, which was produced  by Osseus Fusion SystemsThe company uses its proprietary 3D printing technology, also known as additive manufacturing,  to build spinal implants from titanium material that is optimized for bone fusion and biological fixation. In August 2018, a suite of Osseus’s devices received clearance from the US Food and Drug Administration (FDA) for a  range of heights and lordotic (inward spinal curvature) angles, which make them adaptable for a variety of patient anatomies. The interbody fusion devices work by being packed with biomaterials and bone grafts and inserted in between two vertebrae, where they fuse with the spine and work to prevent back pain.
 
In this Commentary
 
This Commentary explores whether 3D printing and the use of new alloys could be an appropriate strategy to help spine companies reduce  their production and sales costs and enhance their market positions. Our suggestions here complement a strategy, described in a previous Commentary, for MedTech companies to develop and implement digital strategies to enhance their go-to-market activities, strengthen the value propositions of products and services and streamline internal processes. The reasons spine companies might consider both strategies are because spinal implant markets, which are segmented  by type of surgery, product and geography, are experiencing significant competitive, regulatory, pricing and technological challenges as well as mounting consumer pressure for improved outcomes; and the business model, which served as an accelerator of their financial success over the past decade is unlikely to be effective over the next decade.
 
3D printing
3D printing is a process, which creates a three-dimensional (3D) object by building successive layers of raw material. Each new layer is attached to the previous one until the object is complete. In the healthcare industry, 3D printing is used in a wide range of applications, such as producing dental crowns and bridges; developing prototypes; and manufacturing surgical guides and hearing aid devices. Increasingly, 3D printing is being used for the production of spinal implants.

 
Spine surgery increasing significantly
 
An estimated US$90bn is spent each year in the US on the diagnosis and management of low back pain (LBP). LBP, caused by age related degenerative disc disease, is one of the most common and widespread public health challenges facing the industrialized world. It is estimated that the condition affects over 80% of the global population and inflicts a heavy and escalating burden on healthcare systems. Also, LBP affects  economies more generally in terms of lost production due to absenteeism, early retirement and the psychosocial impact caused by the withdrawal of otherwise active people from their daily activities. According to the American Association of Neurological Surgeons, more than 65m Americans suffer from LBP annually and the Chicago Institute of Neurosurgery and Neuroresearch suggests that by the age of fifty, 85% of the US population is likely to show evidence of disc degeneration. It is estimated that 10% of all cases of LBP will develop chronic back pain, which is one of the main reasons for people to seek surgical solutions and this significantly raises the burden on over-stretched healthcare systems.
 
Findings of a study published in the March 2019 edition of Spine, entitled, “Trends in Lumbar Fusion Procedure Rates and Associated Hospital Costs for Degenerative Spinal Diseases in the United States 2004 to 2015”, report that the rate of elective lumbar fusion surgeries in the US has increased substantially over the past decade. Such trends are indicative of most advanced industrial societies, which  are changing and ageing, primarily driven by improvements in life expectancy and by a decrease in fertility. This results in people living longer, reaching older ages and having fewer children later in life. Over the next decade, these market drivers are expected to make spine surgery a key target for cost reduction within healthcare systems and this, in turn, is likely to increase pressure on manufacturers of spinal implants to make spine surgery more cost effective.

 

The first surgery using a 3D printed spinal implant
 
The first surgery to implant a 3D printed interbody fusion device was carried out in China in August 2014, when surgeon Liu Zhongjun from Peking University Hospital successfully implanted an artificial 3D printed vertebra into a 12-year-old bone cancer patient to help him walk again. Liu first removed a tumour located in the second vertebra of the boy's neck before replacing it with the 3D printed implant between the first and third vertebrae to allow him to lift his head. “The customized 3D printed technology made the disc replacement stronger and more convenient than normal procedures”, said Liu.

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Age of the aged and low back pain
 
In July 2017, a team of doctors, led by Xiao Jianru, Professor of Orthopaedic Surgery at Shanghai Changzheng Hospital, China, treated a 28-year-old woman with a massive, rare neck tumour, by giving her a 3D printed spine. The patient had to have six consecutive cervical vertebrae replaced because they had been affected by the cancer, which was challenging to treat with chemotherapy. Cervical vertebrae, seven in total, which form your spine column in the neck are the most delicate bones in your body. The patient was discharged from the hospital after the operation. Reports suggest that she was able to walk, but had some difficulties turning her head.
 
First US company to receive FDA approval for 3D printed spinal implants
 
The first US  company to receive a 510(k) FDA approval for a 3D printed spinal implant was 4WEB Medical, in 2012. The company was founded in 2008 and since then has become a leader in 3D printed implant technology. Following FDA clearance, the company launched its proprietary and patented Truss Implant platform, which features a unique open architecture that allows for up to 75% of the implant to be filled with graft material and includes an anterior spine Truss System, a cervical spine Truss System, an osteotomy Truss System and a posterior spine Truss System. In April 2018,  at the annual meeting of the International Society for the Advancement of Spine Surgery (ISASS) 4Web announced that it has surpassed 30,000 implants worldwide of its proprietary Truss Implant Technology.
 
There is a plethora of established MedTech companies entering the 3D printing spinal implant market, which include Stryker, K2M, DePuy Synthes, Camber Spine, CoreLink, Medicrea, Renovis, NuVasive and Zimmer Biomet. With Stryker’s acquisition of K2M and DePuy Synthes’ acquisition of Emerging Implant Technologies GmbH (EIT), both in September 2018, the market for 3D printed spinal implants is positioned to grow rapidly over the next few years.
 
Increasing FDA approvals for 3D printed spinal implants
 
Significantly, spinal implants have become one of the most common cases of the FDA-cleared 3D printed medical devices. For instance, in 2018 Zimmer Biomet received FDA clearance for the company’s first 3D printed titanium spinal implantEIT received FDA approval in 2018 for its 3D printed multilevel cervical cage, which can treat multiple injuries in both the middle and top parts of the spine. Centinel Spine Inc, a US company based in Pennsylvania, which develops, manufactures and markets spinal devices used to treat degenerative disc disease, also received FDA clearance in 2018 for its 3D printed spinal implants called FLX devices, which are titanium fusion implants that work to stabilize vertebrae from the front of the spine in order to increase the healing process for patients.

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MedTech must digitize to remain relevant

 
3D printing medical devices market
 
The 3D printing medical devices market is projected to grow at a CAGR of 17.5% and reach US$2bn by 2022. Currently, the market is dominated by North America, followed by Europe, Asia Pacific and the rest of the world. Over the next decade, the Asia Pacific 3D printing medical devices market is expected to grow at the highest CAGR. Emerging markets are attractive for spine companies as they have large patient populations, which are growing fast, rising government healthcare expenditure, vast and rapidly increasing middle classes, rising income levels and rising obesity cases.
One example is India, with a middle class about twice the size of the US population, an economy growing at a rate of 7% year-on-year and a pro-business Prime Minister who has established himself as the country’s most formidable politician in decades and is committed to increasing healthcare spending. According to the World Bank’s March 2018 India Development Update the GDP of India had surpassed that of France and was on track to overtake the UK economy to make India the 5th largest economy in the world. Significantly, India’s GDP per capita has reached US$2,000, which is generally recognised by economists as a “tipping point”: when a country’s economic prospects improve, peoples’ confidence increases, and investment momentum remains at a desirable level for a long period. For instance, when the GDP per capita of China and South Korea reached US$2,000 their respective economies witnessed more than a decade of high growth with an average growth rate of about 10%. India appears to be on the cusp of something similar.
 
3D printing's competitive advantages
 
3D printing, although in its infancy, has the capacity to manufacture products of any complexity anywhere, at any time, which gives it a significant competitive-advantage over traditional manufacturing. Further, 3D printing is cheaper and quicker than traditional production methods because there is less machine, material, labour and inventory costs and less materials' waste. Complex designs can be created as a computer added design (CAD) model and then transformed into a reality in just a few hours. By contrast, traditional manufacturing methods can take weeks or even months to go from the design stage to a prototype and then onto the production process. Also, 3D printing is cost-effective in low production quantities and more environmentally friendly as the place of manufacture can be the same as the place of the product’s application.

The benefits of 3D printing specifically for spinal surgery include; (i) implants can be shaped to custom-fit patients, (ii) porosity and pore size can be personalized to a specific patient’s bone quality, which may improve integration. But perhaps the most significant potential advantage is bioprinting, where cells, growth factors and biomaterials are used to create living tissue.

 
Thinking beyond traditional metals used for spinal implants
 
Some spine companies are complementing their 3D printing endeavours by experimenting with new and stronger alloys. For the past two decades metals used for spinal implants have been mostly composed of cobalt chrome, titanium and stainless steel. The physical properties of these have prevented producers to reduce the size of spinal implants. But this is changing with the introduction of new alloys such as molybdenum-rhenium (MoRe), which is stronger than the traditional metals used for spine implants and has the potential to use less metal to achieve stronger, more durable constructs, while allowing for smaller sized products.

Already, MoRe is used for stents in cardiology and findings of a small animal study presented at the 2018 North American Spine Society meeting in Los Angeles suggested that MoRe is significantly more hydrophilic (having strong affinity to water) and therefore friendlier to bone when compared with cobalt chrome, titanium and stainless steel. This suggests MoRe might provide smaller rods with smaller pedicle screw heads, which decrease the prevalence of protruding, painful hardware in patients with wasting of the body due to severe chronic illness. Further, smaller spinal implants would be beneficial in minimally invasive spine surgery.

Another added benefit of MoRe is that it potentially decreases biofilm formations, which are typically caused by chronic medical device-related infections and allergenicity when compared to the traditional metals used in spine surgery. Bacteria are tougher to kill when they attach to the surface of a spinal implant, even before they form a biofilm. Research findings published in the December 2018 edition of Heliyon draws attention to the prevalence of the  antibiotic-resistant nature of bacterial biofilm infections on implantable medical devices and describes current state-of-the-art therapeutic approaches for preventing and treating biofilms. As the range of materials for spinal implants with improved biocompatibility, biodegradability and load bearing properties increase, so are biofilm infections expected to decrease.

 
Takeaways
 
Spine surgery is positioned to become a key target for cost reduction within healthcare systems over the next decade. This is because low back pain, caused by age related degenerative disc disease, is a common condition affecting most individuals at some point in their lives and increasingly people are turning to surgical solutions. As a consequence, we can expect increased pressure on stakeholders, including spinal implant manufacturers, to innovate to make spine surgery more cost effective. 3D printing and the use of new alloys, while in their infancy, are possible strategies to reduce the costs of producing spinal implants while improving patient outcomes.
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  • Two Boston Consulting Group studies say MedTech innovation productivity is in decline
  • A history of strong growth and healthy margins render MedTechs slow to change their outdated business model
  • The MedTech sector is rapidly shifting from production to solutions
  • The dynamics of MedTechs' customer supply chain is changing significantly and MedTech manufacturers are no longer in control
  • Consolidation among buyers - hospitals and group purchasing organisations (GPO) - adds downward pressure on prices
  • Independent distributors have assumed marketing, customer support and education roles
  • GPOs have raised their fees and are struggling to change their model based on aggregate volume
  • Digitally savvy new entrants are reinventing how healthcare providers and suppliers work together
  • Amazon’s B2B Health Services is positioned to disrupt MedTechs, GPOs and distributors 
  • MedTech manufacturers need to enhance their digitization strategies to remain relevant
 
MedTech must digitize to remain relevant
 
MedTech companies need to accelerate their digital strategies and integrate digital solutions into their principal business plans if they are to maintain and enhance their position in an increasingly solution orientated healthcare ecosystem. With growing focus on healthcare value and outcomes and continued cost pressures, MedTechs need to get the most from their current portfolios to drive profitability. An area where significant improvements might be made in the short term is in MedTechs' customer facing supply chains. To achieve this, manufacturing companies need to make digitization and advanced analytics a central plank of their strategies.
 
In this Commentary
 
This Commentary describes the necessity for MedTechs to enhance their digitization strategies, which are increasingly relevant, as MedTech companies shift from production to solution orientated entities. In a previous Commentary we argued that MedTechs history of strong growth and healthy margins make them slow to change and implement digital strategies. Here we suggest that the business model, which served to accelerate MedTechs' financial success over the past decade is becoming less effective and device manufacturers need not only to generate value from the sale of their product offerings, but also from data their devices produce so they can create high quality affordable healthcare solutions. This we argue will require MedTechs developing  innovative strategies associated with significantly increasing their use of digital technology to enhance go-to-market activities, strengthen value propositions of products and services and streamline internal processes.
 
MedTechs operate with an outdated commercial model
 
Our discussion of digitization draws on two international benchmarking studies undertaken by the Boston Consulting Group (BCG). The first,  published in July 2013 and entitled, “Fixing the MedTech Commercial  Model: Still Deploying ‘Milkmen’ in a Megastore World” suggests that the high gross margins that MedTech companies enjoy, particularly in the US, hide unsustainable high costs and underdeveloped commercial skills. According to BCG the average MedTech company’s selling, general and administrative (SG&A) expenses - measured as a percentage of the cost of goods sold -  is 3.5 times higher than the average comparable technology company. The study concludes that MedTechs' outdated business model, dubbed the “milkman”, will have to change for companies to survive. 
 
BCG’s follow-up 2017 study
 
In 2017 BCG published a follow-up study entitled, “Moving Beyond the ‘Milkman’ Model in MedTech”, which surveyed some 6,000 employees and benchmarked financial and organizational data from 100 MedTech companies worldwide, including nine of the 10 largest companies in the sector. The study suggested that although there continued to be downward pressure on device prices, changes in buying processes and shrinking gross margins, few MedTech companies “have taken the bold moves required to create a leaner commercial model”.
 
According to the BCG’s 2017 study, “Overall, innovation productivity [in the MedTech sector] is in decline. In some product categories, low-cost competitors - including those from emerging markets - have grown rapidly and taken market share from established competitors. At the same time, purchasers are becoming more insistent on real-world evidence that premium medical devices create value by improving patient outcomes and reducing the total costs of care”. The growth and spread of value-based healthcare has shifted the basis of competition beyond products, “toward more comprehensive value propositions and solutions that address the entire patient pathway”. In this environment, MedTechs have no choice but to use data to deliver improved outcomes and a better customer experience for patients, healthcare providers and payers.
 
MedTech distributors increasing their market power and influence
 
Although supply chain costs tend to be MedTechs' second-highest expense after labour, companies  have been reluctant to employ digital strategies to reduce expenses and increase efficiencies. As a consequence, their customer supply chains tend to be labour intensive relationship driven with little effective sharing of data between different territories and sales teams. Customer relations are disaggregated with only modest attention paid to patients and payors and insufficient emphasis on systematically collecting, storing and analysing  data to support value outcomes.   
As MedTech manufacturers have been slow to develop strong and effective data strategies, so MedTech distributors have increased their bargaining power through M&As and internationalisation. Some distributors have even assumed marketing, customer support and education roles, while others have launched their own brands. MedTechs' response to these changes has been to increase their direct sales representatives. However, consolidation among buyers - hospitals and GPOs -  and the extra downward pressure this puts on prices, is likely to make it increasingly costly for MedTechs to sustain large permanent sales forces. 

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Who should lead MedTech?

 
Advantages of distributors but no way to accurately measure sales performance

Notwithstanding, the distributor model is still common with MedTechs and has been successful in many markets for a long time. Independent distributors are often used when producers have small product portfolios. In smaller markets, distributors are employed primarily to gain economies of scale as they can combine portfolios of multiple companies to create a critical mass opportunity and  obtain better and faster access to markets.
 
MedTechs have a history of investing in sales force effectiveness (SFE) typically to increase the productivity of sales representatives. Sales leaders have some indication that this pays-off through incremental revenue growth and profits, but they struggle to assess the true performance of such investments not least because SFE includes a broad range of activities and also it is almost impossible to obtain comparative competitor data.
 
Changing nature of GPOs
 
GPOs also have changed. Originally, they were designed in the early 20th century to bring value to hospitals and healthcare systems by aggregating demand and negotiating lower prices among suppliers. Recently however they have raised their fees, invested in data repositories and analytics and have been driving their models and market position beyond contracting to more holistic management of the supply chain dynamics. Notwithstanding, many GPOs are struggling to change their model based on aggregate volume and are losing purchasing volume amid increasing competition and shifting preferences.
 
New entrants
The changing nature of MedTechs' customer supply chain and purchasers increasingly becoming concerned about inflated GPOs' prices have provided an opportunity for data savvy new entrants such as OpenMarketsThe companyprovides healthcare supply chain software that stabilizes the equipment valuation and cost reduction and aims to reinvent how healthcare providers and suppliers work together to improve the way healthcare equipment is bought and sold. OpenMarkets’ enhanced data management systems allow providers to better understand what they need to buy and when. The company represents over 4,000 healthcare facilities and more that 125 equipment suppliers; and provides a platform for over 32,000 products, which on average sell for about 12% less than comparable offerings. In addition, OpenMarkets promotes cost efficiency and price transparency as well as stronger collaboration between providers and suppliers.
 
Amazon’s B2B Health Services
 
But potentially the biggest threat to MedTech manufacturers, GPOs and distributors  is Amazon’s B2B Health Services, which is putting even more pressure on MedTechs to rethink their traditional business models and to work differently with healthcare providers and consumers. With a supply chain in place, a history of disrupting established sectors from publishing to food and a US$966bn market cap, Amazon is well positioned to disrupt healthcare supply chain practices, including contracting. In its first year Amazon’s B2B purchasing venture generated more than US$1bn and introduced three business verticals: healthcare, education and government. Already, hundreds of thousands of medical products are available on Amazon Business, from hand sanitizers to biopsy forceps. According to Chris Holt, Amazon’s B2B Health Services program leader, “there is a needed shift from an old, inefficient supply chain model that runs on physical contracts with distributors and manufacturers to Amazon's marketplace model”.

If you look at the way a hospital system or a medical device company cuts purchase orders, identifies suppliers, shops for products, or negotiates terms and conditions, much of that has been constrained by what their information systems can do. I think that has really boxed in the way that companies’ function. Modern business and the millennials coming into the workplace, can’t operate in the old way,” says Holt.

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Is the digital transformation of MedTech companies a choice or a necessity?


Millennials are used to going to Amazon and quickly finding anything they need; even the most obscure items. According to Holt, “A real example is somebody who wants to find peanut butter that is gluten-free, non-GMO, organic, crunchy and in a certain size. And they want to find it in three to five clicks. That’s the mentality of millennial buyers at home, and they want to be able to do the same things at work. . . . The shift from offline traditional methods to online purchasing is very significant. It is our belief that the online channel is going to be the primary marketplace for even the most premium of medical devices in the future. That trend is already proven by data. So, we’ve created a dedicated team within Amazon Business to enable medical product suppliers to be visible and participate in that channel.
MedTechs fight back
 
According to the two BCG reports, MedTech companies can fight back by using digital technologies to strengthen and improve their go-to-market activities. This, according to BCG, would enhance MedTechs' connectivity with their customers and help them to learn more about their needs. Indeed, employing digitization to improve customer-facing activities could help standardise order, payment and after-sales service behaviour by defining and standardizing terms and conditions. This could provide the basis to help MedTechs increase their access to a range of customers - clinicians, institutions, insurers and patients - and assist them to tailor their engagements to the personal preferences of providers and purchasers. This could provide customers with access to product and service information at anytime, anywhere and could form the basis to implement broader digitalized distribution management improvements, which focus on value-based affordable healthcare in the face of escalating healthcare costs and variable patient outcomes.
 
Predictive models
 
Many companies use predictive-modelling tools to forecast demand and geo-analytics to speed delivery and reduce inventories. Online platforms provide customers with an easy way to order products and services, transparently follow their shipping status and return products when necessary. Barcodes and radio-frequency identification (RFID) chips, which use electromagnetic fields to automatically identify and track tags that contain electronically stored information attached to products, help customers track orders, request replenishments and manage consignment stock.
 
Back-office improvements
 
Further, the 2017 BCG study suggests that MedTechs only have made limited progress in improving their back-office operations. Many manufacturers  have more employees in their back offices than they do in their customer-facing functions and fail to leverage economies of scale. There is a significant opportunity for MedTechs to employ digital strategies to enhance the management of their back-office functions, including centralizing certain activities that are currently conducted in multiple individual countries.
 
Takeaway
 
For the past decade MedTech manufactures have been slow to transform their strategies and business models and still have been commercially successful. Some MedTech companies are incorporating digital capabilities into their products by connecting them to the Internet of Things (IoT), which potentially facilitate continuous disease monitoring and management. Notwithstanding, such efforts tend to be isolated endeavours - “one-offs” - and are not fully integrated into companies’ main strategies. This could run the risk of MedTech executives kidding themselves that they are embracing digitization while underinvesting in digital technologies. The two BCG studies represent a significant warning since digitization is positioned to bring a step-change to the MedTech sector, which potentially could wound successful manufacturers if they do not change.
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  • Each year unhealthy diets are linked to 11m deaths worldwide a global study concludes
  • Red and processed meat not only cause disease and premature death from chronic non-communicable diseases (NCD) but also put the planet at unnecessary risk
  • Evidence suggests that the health benefits of a Mediterranean diet reduces the risk of NCDs and is better for the Planet

Eat like Greeks, live healthier lives and save our planet

 
Findings of an international research project about the relationship between diet and chronic diseases are reported in a paper entitled, “Health effects of dietary risks in 195 countries 1990-2017. A systematic analysis for the Global Burden of Disease Study 2017”, which is published in the April 2019 edition of The Lancet. The paper suggests that millions of people throughout the world consume an unhealthy diet comprised of  too much processed meat, sodium and sugar and too little plant-based foods, such as fruits and vegetables, whole grains and nuts. This results in a significant increase in the prevalence of chronic non-communicable diseases (NCD) such as coronary heart disease, cancer and diabetes and  each year causes some 11m avoidable deaths worldwide - 22% of all adult deaths: 10m from cardiovascular disease, 913,000 from cancer and some 339,000 from type-2 diabetes. According to the paper’s authors, “A suboptimal diet is responsible for more deaths than any other risks globally, including tobacco smoking, highlighting the urgent need for improving human diet across nations”.
 
In this Commentary
 
This Commentary reviews evidence of recent large-scale epidemiology studies, which suggest that “you are what you eat”.  Not only do unhealthy diets cause ill health and premature death for millions, they also harm the environment and push the Earth beyond its planetary boundaries. All the studies we describe conclude that we know the answer to this vast and escalating health problem: eat like Greeks or indeed the Japanese. Notwithstanding, changing the way populations collectively eat is a massive challenge facing governments, healthcare systems and individuals.
 
The Global Burden of Disease project
 
The Lancet paper’s findings described above are based on the Global Burden of Disease (GBD) enterprise, which is one of the world’s largest scientific collaborative research projects, which was started in the early 1990s by the World Bank to measure the impact of disability and death from hundreds of diseases worldwide. Over the past two decades its work has grown, and the endeavour has become institutionalized at the World Health Organization (WHO). Today, the GBD project is an international consortium of more than 3,600 researchers, its findings are updated annually and they influence health policy throughout the world.
 
Red meat and bowel cancer
 
Findings of a more narrowly focussed but nonetheless significant study, published in the April 2019 edition of the International Journal of Epidemiology warn that red-processed meat consumption is linked with bowel cancer.  According to Tim Key, the study’s co-author, Professor of Epidemiology and Deputy Director at Oxford University's Cancer Epidemiology Unit, “Results strongly suggest that people who eat red and processed meat four or five times a week have a higher risk of developing bowel cancer than those who eat red and processed meat less than twice a week . . . . There’s substantial evidence that red and processed meat are linked to bowel cancer and the World Health Organization classifies processed meat as ‘carcinogenic’ and red meat as ‘probably carcinogenic’”. Notwithstanding, Key warns that, “Diet studies are problematic because those who take part often either forget what they have eaten or fail to tell the truth”. Key also suggests that, “Most previous research [on diet and cancer] looked at people in the 1990s or earlier and diets have changed significantly since then”.
 
Chronic non-communicable diseases
 
Chronic non-communicable diseases (NCD) are largely caused by humans and are therefore preventable. Notwithstanding, they account for more than 70% of all deaths globally and emergent NCDs pose significant systemic challenges for both nation states and individuals. Forty percent of all adults in the world are overweight and 1.4bn suffer from hypertension: both critical risk factors of NCDs. In 2016, 18m people died from cardiovascular disease (CVD), representing 31% of all global deaths. In the US an estimated 92m adults are living with CVD. By 2030, 44% of the US adult population is projected to have some form of CVD. There are around 7m people living with heart and circulatory disease in the UK. Worldwide some 0.5bn people have diabetes and in 2018 there were 17m new cases of cancer worldwide. Although there are some encouraging signs associated with the slowing of the prevalence rates of NCDs globally, prevalence of NCDs is expected to rise because of population growth and aging, misaligned healthcare policies and institutional inertia.
 
The paradox of food insecurity and obesity
 
Paradoxically, food scarcity and obesity are both forms of malnutrition and represent a vast and escalating burden on the worlds limited and diminishing resources. This is because food insecurity can contribute to people being overweight and obese. Nutritious fresh foods often tend to be expensive, so when household resources for food become scarce, people choose less expensive foods that are often high in calories and low in nutrients. As a result, adult obesity rates continue to rise each year, from 11.7% in 2012 to 13.2% in 2016. In 2017 the World Health Organization estimated that more than one in eight adults, or more than 672m people in the world, were obese and 2bn were classified as overweight. A report from the Center for Strategic and International Studies, a think-tank based in Washington DC, US, suggests that worldwide each year, "Malnutrition costs US$3.5trn, with overweight- and obesity-related NCDs, such as cardiovascular disease and type 2 diabetes, adding US$2trn”.
 
The EAT-Lancet Commission on Food, Planet and Health
 
Not only do unhealthy diets result in NCDs and premature death, but they also harm the environment. The dual aspects of unhealthy diets causing disease and harming the planet are described in research conducted by the EAT-Lancet Commission on Food, Planet and Healthand reported in the January 2019 edition of  The Lancet.
EAT is an independent non-profit organisation based in Oslo, Norway, dedicated to food-system reform, which collaborated with The Lancet. The report took 3-years to complete and brought together 37 world-renowned scientists from 16 countries with expertise in health, nutrition, environmental sustainability, food systems, economics and political governance; and tasked them with reaching a consensus that defines a sustainable “healthy planetary diet”, which the authors suggest approximates a Mediterranean diet, see below.

The EAT-Lancet research, financed by the Wellcome Trust,analysed the diets of people in 195 countries using survey data, as well as sales data and household expenditure data to estimate the impact of unhealthy diets on the risk of death and morbidity from NCDs. The Commission’s authors provide a comprehensive picture of the consumption of 15 dietary factors across nations and quantify the potential impact of suboptimal intake of each dietary component on NCD mortality and morbidity among 195 countries. Also, researchers calculate mortality related to other risk factors,such as smoking and drug use, at the global level.

 

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Obesity: is processed food the new tobacco?
 

Criticism of the EAT-Lancet Commission
 
The EAT-Lancet Commission’s report has its critics. One is the UK’s National Farmers’ Union whose Vice President Stuart Roberts said, “Scientific communities agree that red meat plays a vital role in a healthy, balanced diet as a rich source of essential nutrients, minerals, amino acids and protein. It is overly simplistic to target one food group for a significant reduction in consumption, and it ignores its medically accepted role as a key part of a healthy, balanced diet   . . . It is clear that climate change is one of the greatest challenges of our time and British farmers are continuing to take action. A combination of policies and practises will be needed to enable farmers to meet their ambitions, but we must not forget the impact of a changing climate on food production”.
 
Benefits of red meat
 
Roberts is right to point out that red meat has health benefits. Heme iron, which is found in red meat (also in poultry, seafood and fish) is easily absorbed by your body and is a significant source of your dietary iron. Red meat also supplies you with vitamin B12 and zinc. The former is required for red blood cell formation, neurological function and DNA synthesis, and the latter helps stimulate the activity of at least 100 different enzymes and helps to keep your immune system working effectively. Further, red meat provides protein, which helps to build your bones and muscles. People have been eating meat for millennia and have developed digestive systems well equipped to handle it.

Notwithstanding, the overwhelming majority of red meat consumed in the developed world today is processed: raised in a factory environment, fed grain-based feed and given growth-promoting hormones and antibiotics and some animals, after being slaughtered, are further treated with nitrates, preservatives and various chemicals. The findings of all three studies described above demonstrate the harm of eating too much red and processed meat and stress the health and environmental benefits of a Mediterranean diet.

 
An urgent challenge
 
According to the EAT-Lancet Commission’s authors, “Providing healthy diets from sustainable food systems is an urgent and pressing challenge”. As the global population continues to grow - projected to reach 10bn by 2050 - and become wealthier, there is expected to be a concomitant increase in unhealthy diets comprised of red meat, processed food and sugar. To address this vast and escalating challenge, populations will need to combine significant dietary changes with enhanced food production and reduced food waste.
 
The impact of food waste
 
Before broaching some of the challenges associated with changing the way we eat collectively let us briefly describe the magnitude and effect of food wastage. According to the United Nation’s (UN) 1.3bn tonnes of food are wasted every year, which is about 33% of the total produced. The cost of global food losses and waste amounts to roughly US$990bn and yet some 800m people worldwide do not get enough to eat and 2bn people are overweight.
 
Further, food wastage is estimated to release the equivalent of 3.3bn tonnes of CO2 into the atmosphere each year. The total volume of water used annually to produce food that is lost or wasted (250km³) is equivalent to three times the volume of Lake Geneva. Similarly, 1.4bn hectares of land - 28% of the world's agricultural area - is used to produce food that is lost or wasted. And agriculture is responsible for a majority of threats to at-risk plant and animal species tracked by the International Union for Conservation of Nature. 
 
Changing what we eat and how we produce food will save lives and the planet
 
According to Alan Dangour, Professor in Food and Nutrition for Global Health at the London School of Hygiene & Tropical Medicine (LSHTM), “The EAT-Lancet Commission’s analysis demonstrates that shifts in our diets can have enormous beneficial effects on health and also substantially reduce our impacts on the environment.  This significant ‘win-win’ for health and the environment is not a new finding, but this analysis, which for the first time defines environmental boundaries for the food system, is the most advanced ever conducted”.
 
In a similar vein, Tara Garnett, a contributor to the EAT-Lancet Commission and a principal investigator of another research project on the future of food, also suggests that there’s nothing new in the Commission’s report but its fundamental message is that, “We’re not going to address our environmental problems unless we address the problems caused by the food system and we’re not going to address the problems caused by the food system unless we shift the way we eat collectively and globally”.

 
Rebalancing unhealthy diets is a significant challenge
 
Changing how we eat collectively, which Garnett and others suggest is necessary to reduce NCDs and enhance our environment, is not going to be easy. This is because it would involve cutting by half our consumption of red meat, processed food and sugar, and doubling our consumption of vegetables, fruit, pulses and nuts. For people living in the US and UK it would be even more challenging because the EAT-Lancet Commission ranks the US 43rd and the UK 23rd for their respective unhealthy diets out of the 195 nations in its study. It is suggested that in order to adopt a healthy diet Americans would need to eat 84% less red meat and six times more beans and lentils, and British people would have to eat 77% less red meat and 15 times more nuts and seeds.

Countries with the lowest rates of diet-related deaths are Israel, France, Spain and Japan. The highest rates are reported to be found in Uzbekistan, Afghanistan and the Marshall Islands. According to the Commission’s authors a Mediterranean-type-diet, “is what we should all be eating if we are concerned about our health and that of the planet”: it lowers the incidences of heart disease, diabetes and cancer, enables more environmentally helpful use of land and reduces carbon emissions.

 
The Mediterranean diet
 
The Mediterranean diet has been around for millennia and tends to be more of a lifestyle than a diet. It entails significantly lower amounts of beef, dairy products, sugar, soft drinks, pastries and processed foods; higher amounts of fish, fruit, nuts and salads, and no pasta, French fries and pastries. Unlike fashionable commercial diets associated with the weight management market, the Mediterranean diet does not have a set of specific rules that focus on losing weight, but instead emphasises eating fresh food over a lifetime. Also, the Mediterranean diet has been well studied. Research suggests that it is associated with a reduced risk of heart disease and cardiovascular mortality because of its significantly lower amounts of oxidized low-density lipoprotein (LDL) cholesterol, (the "bad" cholesterol) which is more likely to build up deposits in your arteries. Other benefits include reduced incidence of cancer, Parkinson's and Alzheimer's diseases. Further, women who follow a Mediterranean diet have a reduced risk of breast cancer.
 
The PREDIMED study
 
Findings of a landmark clinical trial, entitled “Primary Prevention of Cardiovascular Disease with a Mediterranean Diet”, was published in the June 2013 edition of the New England Journal of Medicine (NEJM). Popularly known as the PREDIMED study (Prevencion con Dieta Mediterranea), it tested the impact of two Mediterranean diets on cardiovascular risk. The first included a Mediterranean diet plus 30 grams of mixed nuts per day and the second was a Mediterranean diet plus at least four tablespoons a day of extra-virgin olive oil. The two diets were then compared to a low-fat diet, which is popularly advocated and pursued in the US and UK and among other developed nations and discourages the consumption of any high-fat items such as butter, cheese, oil, meats and pastries.
 
The low-fat diet
 
In the 1960s low-fat diets as opposed to high-fat, high-cholesterol diets were considered to promote heart health. By the late 1980s and early 1990s the low-fat diet was advocated by doctors, policy makers, the food industry and the media although there was no hard evidence to demonstrate it prevented heart disease and promoted weight loss. Notwithstanding, the low-fat-diet became an important part of the large and rapidly growing global weight management market, which is valued at some US$169bn and projected to grow at a CAGR of 2.4% and reach a value US$279bn by 2023. Interestingly, in the 80s and 90s, as the low-fat diet became an institution in the US and UK so the prevalence of overweight and obesity increased. Only recently has the low-fat diet been challenged as scientific evidence about fats increased.
 
A significant study with some methodological challenges
 
The PREDIMED study involved 7,447 people between 55 and 80 who were free from heart disease, came from 11 study centres across Spain and were randomly assigned to one of the three diets for five years. Findings suggested that the Mediterranean diet significantly reduced the risk of heart attack, stroke and cardio-vascular mortality compared to the low-fat diet. However, researchers discovered flaws with the study’s methodology and withdraw their findings. Most significantly, not all participants were randomly assigned to their diet and this could have influenced their findings.
 
Revised study of the Mediterranean diet
 
Researchers adjusted their methodology for its "irregularities in the randomization procedures" and published “new” findings in the June 2018 edition of the New England Journal of Medicine (NEJM), which confirmed the health benefits of a Mediterranean diet for adults at high risk for heart disease and found that the Mediterranean diet, plus olive oil or nuts, reduced risk for heart events by 30% compared to a low-fat diet. Lead author Miguel Ángel Martínez-González suggested that only about 10% of participants were affected in their earlier study reported in 2013, and their 2018 analysis made researchers, "More convinced than ever of the robustness of the protection by the Mediterranean diet against cardiovascular disease”. According to Jeffrey Drazen, editor-in-chief of the NEJM, "Medical professionals and their patients can use the republished information with confidence". While reaction to the study’s initial findings was disappointing, experts are encouraged by the adjusted findings, which confirm the heart-health benefits of a Mediterranean diet, particularly in adults at high risk for heart disease. Notwithstanding, experts emphasise the significance of sustaining a healthy diet over time.
  
The health benefits of the Japanese diet
 
The Mediterranean diet is not the only diet, which has proven to have significant health benefits. The Japanese diet, which is low in calories and saturated fat and high in nutrients, especially phytonutrients such as antioxidants and flavonoids, found in different coloured vegetables, also has considerable health benefits. Findings of two studies; one published in the April 2017 edition of PLOS.ONE, and another published in the March 2016 edition of the British Medical Journal demonstrate that, closer adherence to a Japanese diet resulted in a significantly lower risk of death from NCDs and in particular from cardiovascular disease or stroke. Japan has the highest life expectancy of any country: 90 years for women and 84 for men. Okinawa, in southernmost Japan, has the highest number of centenarians in the world as well as the lowest risk of age-related diseases such as cancer and heart disease. There are nearly 800 centenarians in Okinawa, which has a population of 1,368,000. The diet of the Okinawan people has been little influenced by the dietary changes influenced by western culture, which also have been seen in more urban Japan.
 
Takeaways
 
All the research findings we describe in this Commentary confirm the adage that, “You are what you eat”. Nutrients from the food you eat provide support for all the cells in your body, which have different “shelf lives”. For example, your skin cells live for about a month and your red blood cells for about four months. So, your body is constantly regenerating new cells to replace those that have “expired”. The health of your new cells is partly determined by how well you have been eating. A diet high on processed red meat and low on nutrients does not help in this regeneration process. But a nutrient rich, whole food diet can help to build your cells so that they work better to help you recover from common illnesses and the wear-and-tear of everyday life and make you less susceptible to disease.
 
Although our concern about healthy eating has intensified in recent years, the phrase, “you are what you eat” is not new. In 1826 Anthelme Brillat-Savarin wrote in Physiologie du Gout, ou Meditations de Gastronomie Transcendante, "Dis-moi ce que tu manges, je te dirai ce que tu es[Tell me what you eat, and I will tell you what you are]. However, the phrase did not emerge in English until the 1920s when nutritionist Victor Lindlahr, who believed that food controls health, developed the Catabolic Diet. According to Lindlahr, "Ninety per cent of the diseases known to man are caused by cheap foodstuffs. You are what you eat". And in 1942, he published a book entitled, “You Are What You Eat: how to win and keep health with diet”. Eat like the Greeks, live healthier lives and save our planet.
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Devi Shetty’s model for affordable healthcare


On the 26th March 2019 Bloomberg Businessweek published an article entitled, "The World’s Cheapest Hospital has to Get Even Cheaper”, which describes one of India’s largest private hospital chain's - Narayana Health - response to Modicare, a signature initiative by Prime Minister Narendra Modi to provide basic healthcare for 500m of India’s poorest.
 
Devi Shetty, a world-renowned cardiac surgeon and chairman of Narayana Health, is up for the task. Since Shetty founded Narayana in 2000 it has grown to become a large multi-speciality hospital chain, comprising 31 state-of-the-art tertiary hospitals across 19 cities, employing 16,000 and each year treating over 2.5m patients across more than 30 medical specialities. Shetty’s mission is to provide high quality, affordable healthcare services to the broader population in India and he is convinced that quality and low-cost healthcare are not mutually exclusive. In conjunction with the state of Karnataka, Shetty has created a health insurance plan, which has enrolled some 3m poor people at an annual premium of about US$2.6. More than half of Narayana’s cardiac operations are performed on patients too poor to afford the full cost. In addition to the insurance scheme free or subsidized inpatient care is achieved through philanthropy and a cross-subsidy model, in which higher-income patients pay more for nonclinical amenities, such as private recovery rooms. Since the total charges are still far below the cost of comparable services at other private Indian hospitals, Narayana Health remains an attractive option for such consumers. Narayana Health’s business model is sustainable because of its ability to attract so many patients who can pay full price.  The Wall Street Journal has dubbed Shetty, The Henry Ford of Heart Surgery because he applies assembly line concepts to surgery in order to optimize productivity, minimize costs and leverage economies of scale. Because of these innovations the average cost of open-heart surgery, as reported by Narayana Health, is less than US$2,000. The same procedure at a US research hospital typically costs more than US$100,000.
 
Since 2012 HealthPad has worked closely with Devi Shetty. We published our first Commentary about Narayana Health and Devi Shetty’s model for affordable quality healthcare in 2013 and in subsequent years published two more. Shetty and his fellow senior surgeons have contributed over 700 videos to HealthPad’s  content library, which address FAQs across 11 clinical pathways. Further, Narayana’s clinicians have featured in HealthPad Commentaries on Chronic obstructive pulmonary disease (COPD),  Diabetes and Kidney Disease and Cardiovascular Disease.  Because of the large and growing international interest in Shetty’s alternative model for affordable healthcare we re-publish lightly edited versions of HealthPad’s three Commentaries about Narayana Health.

 



Will Devi Shetty have a major influence on global healthcare?
February 3rd, 2016


Devi Shetty’s hospital of the future
October 1st, 2014


The UK’s NHS loss is global healthcare’s gain
August 14th, 2013
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First published on 14th August 2013
 

The UK’s NHS loss is global healthcare’s gain

 
In 2011 Devi Shetty, an Indian doctor, received the coveted business process innovation award in London from The Economist for his contribution to global healthcare. Trained as a cardiac surgeon in the UK, Shetty returned to India and started a hospital in Bengaluru in 2000. Today, Shetty is on the cusp of changing healthcare in the 21st century.
 
Shetty’s no-frills hospital chain
 
In 2012 Shetty launched the first in a chain of no-frills hospitals: a 200-bed single-storey clinic in Mysore, India. Built in 10 months for US$7m, it charges only US$800 for open heart surgery. Shetty rejected the multi-storey hospital model, because it requires costly foundations, steel reinforcements, lifts and complex fire and safety equipment. Much of the Mysore building was pre-fabricated. Its five operating theatres and intensive care units are the only air-conditioned places and families are encouraged to provide supplementary care for patients.
 
Shetty’s no-frills hospital chain owes its existence to his pioneering hospital in Bengaluru.
 
Shetty’s medical city in Bengaluru
 
In 2000 Shetty started Narayana Hrudayalaya, a specialist hospital for cardiac surgery, which today performs the highest number of heart surgeries in the world for any one hospital: 7,000 annually and does not compromise on quality. “We are only technicians,”  says Shetty. ”We realised that as you do more surgical procedures, your results get better, and your costs go downIn the US the average cardiac surgeon does about 2,000 surgeries in his or her professional lifetime. We have surgeons who have done more than 3,000 surgeries and they’re only in their 30s . . . imagine the expertise that they have, at that young age.
 
Medicines and associated hospital costs in India are significantly lower than in the West, but Narayana offers Indian patients value for money. The average price for open heart surgery in Narayana is around US$2,000, compared to US$5,000 in the average private Indian hospital and $20,000 to $100,000 in a US hospital.
 
Shortly after starting his Bengaluru cardiac centre, Shetty acquired a 35-acre site next door and built a 1,400-bed cancer hospital and a 300-bed eye hospital and created Narayana Hrudayalaya Medical City, which has 3,000 beds in Bengaluru and is run at near to full capacity. In total Narayana has some 7,000 beds in a number of clinics and hospitals throughout India, and plans to expand to 50,000 beds in the next five years.
 
Tele-medicine
 
In association with India’s Space Research Organization, Sherry's Bengaluru hospital runs one of the world’s largest tele-cardiology programs, which reaches 100 facilities throughout India, over 50 across Africa and Narayana’s doctors have treated some 70,000 patients remotely. Narayana Health also disperses 5,000 kidney dialysis machines, which makes the company India’s largest kidney-care provider.
 
Health insurance
 
With the state of Karnataka, Shetty has created a health insurance plan, which has enrolled some 3m poor people at an annual premium of about US$2.6. Last year, about 60% of Narayana Hrudayalaya cardiac operations were performed on patients too poor to afford the full cost.
 
Shetty however is not a charity. His hospitals treat a cross section of patients at variable rates but refuse to turn away anyone who cannot pay. “Charity,”  he says, “is not scalable. Good healthcare depends on good business.”  Shetty’s hospital group earns an after-tax profit of 8%, slightly above the 6.9% average for a US hospital.
 
 
Health City Cayman Islands
 
Shetty has now turned his attention outside of India and is engaged in a joint venture with the government of the Cayman Islands and a group of American institutional investors, to construct and operate a hospital in Grand Cayman to capture share from the North and South American healthcare markets.
 
The first phase, a 140-bed tertiary care facility for cardiac surgery, cardiology and orthopaedics, was opened in 2014 and benefits from the cost-effective healthcare procedures honed by Shetty over the past decade. By 2020, the Cayman enterprise, which also will have a medical university and an assisted-care living community, is projected to expand into a 2,000-bed Joint Commission International-accredited Health City providing care in all major specialties.
 
Super-size hospitals
 
At a time when the global healthcare debate is emphasising community based preventative strategies, Shetty’s vision is, “affordable healthcare for everyone in super-size hospitalsToday healthcare has got phenomenal services to offer,” he says. Almost every disease can be cured and if you can't cure patients, you can give them meaningful lives.” Shetty is driven by the fact that a century after heart surgery was developed only 10% of the world’s population can afford it. Each year, India alone needs 2.5m heart operations and yet there are only 90,000 performed.
 
"Current regulatory structures, policies and business strategies [for healthcare] are wrong,” says Shetty, If they were right, we should have reached 90% of the world's population." Recently, he shocked a UK audience of health providers by suggesting that it would be better if England only had three centres for cardiac surgery rather than 22. 
 
The Henry Ford of heart surgery
 
Sir Bruce Keogh, the UK’s former National Medical Director of the NHS Commissioning Board, once suggested that healthcare in England should become more like retail. Shetty thinks like a retailer, views patients as “customers” and has employed mass production techniques used in the early 20th century to automate the American car industry. Known as, “the Henry Ford of heart surgery”, Shetty has demonstrated that high volume complex surgeries mean better outcomes and lower costs. Similar to what Henry Ford did for the auto industry, Shetty has disaggregated clinical procedures into a number of discrete, standardized, unambiguous units, which can be learnt, practiced and repeated. His methods have successfully reduced hospital costs, increased efficiency, enhanced the quality of care and eliminated clinical mistakes. According to Shetty, “Healthcare has huge variation in procedures, outcomes and costs . . . It is the lack of standardization that contributes to hospital mistakes, high costs and low quality of care”.
 
Change is inevitable
 
Shetty is convinced that the dearth of health workers worldwide will force change and increase the use of emerging healthcare technologies. An advocate for open technological systems, he says, “In five years a computer will make more accurate diagnoses than doctors. In 10-years it will be mandatory for a doctor to get a second opinion from a computer before starting treatment.
 
Takeaways
 
Not only will Shetty’s Health City Cayman Islands be a lower cost alternative for North and South American patients, it will demonstrate how over-priced and inefficient hospitals in the West are. However, it is not altogether clear whether Shetty’s formula for low-cost high-quality surgical procedures will be effective outside of India. This is mainly because high quality ancillary services associated with complex surgeries, which are relatively inexpensive in India, tend to be patchy and significantly more costly outside of India. Notwithstanding, Shetty is determined to provide the world with a model of affordable healthcare.

 

 

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  • Diabulimia is when people with type-1 diabetes (T1DM) ration their insulin to lose weight
  • People with T1DM who reduce their insulin lose weight but increase their likelihood of serious complications and death
  • Diabulimia is neither an official medical nor psychiatric disease state but its prevalence is relatively high and increasing
  • Diabulimia is challenging to diagnose partly because it is a portmanteau of 2 separate conditions and people with the condition often keep the bulimic aspect secret
  • Recently research into the condition and a clinic dedicated to diabetes and eating disorders have been launched in London
  • These initiatives are expected to increase our understanding of diabulimia, improve screening and treatment options and provide integrated medical and psychiatric support for people with the condition

Diabulimia - the world's most dangerous eating disorder

In January 2019 the UK’s National Institute for Health Research (NIHR) awarded clinician scientist Marietta Stadler, from King's College Hospital, London, £1.2m to fund research into diabulimia, an eating disorder in which people living with T1DM deliberately and regularly restrict their prescribed insulin dosage for the purpose of weight loss.

Diabulimia is a media-coined term and only recently has it been considered as a separate disease state although it is still not formally recognised as such. We start this Commentary by briefly describing some aspects of the history of the condition.
  • On 27th September 2011 Sian, the 24-year-old daughter of UK parliamentarian George Howarth, died from complications related to T1DM. As a teenager Sian had not kept up with her medication, she had missed appointments with doctors and dieticians, and was suffering from depression as a result of the condition. Sian had also developed neuropathy, which is damage to the nerves caused by T1DM. Since his daughter’s death Howarth has campaigned to raise awareness of diabulimia.
  • In 2012 Maryjeanne Hunt published a book entitled Eating to Lose: Healing from a Life of Diabulimia, in which she describes her struggle with the condition.
  • On 13th February 2013 the UK’s South London and Maudsley NHS Trust (SLaM) published an   article entitled, The Growing Problem of Diabulimia. According to Janet Treasure, Professor of Psychiatry and Director of Eating Disorder Services at SLaM, “it is estimated that 40% of T1DM females aged between 15-30 regularly omit insulin for weight control”.
  • In the July 2014 edition of Clinical Nursing Studies, a review paper concluded that diabulimia, “is not often recognized by primary healthcare providers or members of the individual’s family. If diabulimia is detected early, interventions can be implemented to minimize the risk of early morbidity and mortality”.
  • In January 2017 the UK's first diabetes and eating disorder out-patient service began working with young women living with diabulimia. Until then people in the UK with diabetes and eating disorders have been able to seek help for one or the other of the conditions, but never together. At the time of the clinic’s launch, Jonathan Valabhji, NHS England’s national clinical director for diabetes and obesity, said: “As a diabetes clinician I’ve seen first-hand the devastating impact that this condition can have on people and their families, and so these services are an important step forward in the recognition of diabulimia”.
  • In early 2017 the UK’s National Institute of Health and Care Excellence (NICE) upgraded its guidelines and quality standards for T1DM to feature psychological support related to the increased prevalence of eating disorders and the potential for insulin omission in people with T1DM.
  • On 4 August 2017, 27-year-old teacher Megan Davison, who had diabulimia, committed suicide. "In the absence of the help she needed, she couldn't see any way of carrying on," said her mother.
  • In September 2017, BBC Three aired a documentary entitled Diabulimia: The World's Most Dangerous Eating Disorder.
  • On 2nd November 2017, the Scottish Parliament debated a motion on raising public awareness of diabulimia.
 
Diabulimia 
 
Diabulimia merges the words ‘diabetes’ and ‘bulimia’. Diabetes is a disease in which your body’s ability to produce or respond to the hormone insulin is impaired, resulting in abnormal metabolism of carbohydrates and elevated levels of glucose in your blood. Bulimia is an eating disorder where you binge on food and then purge it by vomiting, laxatives, diuretics, exercise or other purging behaviours to prevent weight gain. Diabulimia is a term coined by the media and used by the general public. Although not well-known, diabulimia is a dangerous eating disorder among people with T1DM and describes the deliberate and regular administration of insufficient insulin to maintain glycaemic control for the purpose of causing weight loss by ‘purging’ calories via excess glucose in the urine. While not formally recognised either as a medical term or as a mental health condition in its own right, the Diagnostic Statistical Manual of Mental Disorders(DSM-5),   considers that insulin omission in order to lose weight is a clinical feature of anorexia nervosa and bulimia. Diabulimia has also been recognised in the 2017 UK’s National Institute of Health and Care Excellence (NICE) guidance for eating disorders.
  
Insulin restriction and T1DM

To understand why insulin reduction causes weight loss, it helps to understand T1DM, which is a heterogeneous chronic lifetime disorder for which there is no known cure. T1DM is characterized by the destruction of pancreatic beta cells, culminating in absolute insulin deficiency and accounts for between five and 10% of the total cases of diabetes worldwide. In 2014 there were an estimated 422m people diagnosed with diabetes worldwide. The global prevalence of diabetes among adults over 18 has risen from 4.7% in 1980 to 8.5% in 2014.
Typically, T1DM has an early onset, but can occur at any age. It requires regular daily attention, which for children or adolescents can be daunting. The nutritional anomalies associated with the condition have important consequences (see below) and can be a physical and emotional struggle. To be diagnosed with T1DM represents a hard experience that requires subsequent psychological adaptation. Unfortunately, this often does not occur and can be followed by frustration and the non-acceptance of the disease.

T1DM occurs when your immune system attacks cells in your pancreas that make insulin and renders the pancreas unable to produce the hormone, which is needed to allow glucose (a sugar that circulates in your blood) to enter your cells to produce energy. When you consume food, your body converts it into glucose, which enters your bloodstream. Insulin helps to turn glucose into energy. Without a properly functioning insulin system, your body cannot break down glucose so it stays in your bloodstream and can be dangerous.

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If you are a person living with T1DM you must regularly check your blood glucose levels. Based on these levels and what you plan to eat, you must give yourself insulin. If you either fail to do so, or under-dose, your body cannot absorb glucose and it accumulates in your blood, a condition known as ‘hyperglycaemia’, in which case, your body attempts to compensate for the excess glucose, goes into starvation mode and starts to break down muscle and fat, releasing acids called ketones. The ketones build up, leading to diabetic ketoacidosis (DKA), which can be fatal.
 
Epidemiology

Data from large global epidemiological studies of T1DM reported in a paper published in the February 2014 edition of Diabetes Research and Clinical Practice, suggest that there are 0.5m children aged
It is estimated that as many as 11% of adolescent women with T1DM meet the criteria for a full-syndrome eating disorder. This is significant when compared to the incidence of eating disorders among women in general. It is estimated that between 0.5% and 3.7% of women suffer from anorexia nervosa, and an estimated 1.1% to 4.2% of women have bulimia in their lifetime. A paper in the June 2000 edition of the British Medical Journal, suggests that adolescent females with T1DM are 2.4 times more likely to develop eating disorders than peers of the same age without diabetes, and 1.9 times more likely to display symptoms of an eating disorder that does not meet the full diagnostic criteria. Other studies show that about 35% of females with T1DM have diabulimia.

 
Signs and symptoms

Diabulimia is challenging to diagnose and many primary care doctors and endocrinologists who treat people with T1DM may not recognize diabulimia among their patient population. This is partly because diabulimia is not an officially recognised disease state, partly because eating disorders and diabetes tend to be treated separately by different specialists, and partly because people with diabulimia may be ashamed and reluctant to seek help.

The most obvious sign of diabulimia is weight loss. Another common sign is poor blood-glucose control, as measured by elevated A1c levels, particularly if the person has a prior history of good control. Health professionals may wish to attune themselves to the classic signs of diabetes and the common symptoms of eating disorders. The former includes excessive urination, extreme thirst, constant hunger and fatigue. The latter includes dietary restrictions and heightened concerns about weight and body image.

 
Manipulating insulin to control weight
 
At the time of diagnosis with T1DM people have often lost a significant amount of weight. Regular doses of insulin are essential for controlling blood sugar levels and successfully managing the condition. However, a common side effect of such treatment is weight gain, and this can lead to a vicious circle. Insulin therapy can lead to weight gain; increasing weight may require increasing dosages of insulin to control blood glucose, which can lead to increased hunger and dietary intake, which can increase weight and enhanced concerns about body image.

Deliberately not taking or misusing insulin to cause weight loss is a purging behaviour that is uniquely available to individuals with T1DM. Weight loss can be achieved by decreasing the prescribed dose of insulin, omitting insulin entirely, delaying the appropriate dose, or manipulating the insulin itself to render it inactive. But when you have T1DM, you need insulin to live. Without it, you may lose weight, but more significantly you can lose your sight, harm your kidneys, damage the nerves in your feet and threaten your life.

 
Diets, social media and the thin ideal
 
The management of T1DM is further complicated because it also entails the careful selection of food, eating precise portions and the constant monitoring of carbohydrates. Because of the early onset of T1DM and the ubiquitous use of social media among children and adolescents, which often propagate the “thin ideal”; it seems reasonable to suggest that children and adolescents with T1DM are inherently more prone to issues revolving around food. Thus, in addition to manipulating insulin many people with T1DM commonly restrict their food intake, engage in bingeing and purging, misuse laxatives and adhere to overly strict exercise regimens to overcome body dissatisfaction.   
 
In the US the cost of insulin results in rationing dosages
 
It seems worth mentioning that a significant proportion of people with T1DM in the US appear to be forced into a similar state of diabulimia because of the high cost of insulin, lack of medical insurance cover (about 10% of the US population [33m] do not have healthcare insurance), and relatively high levels of co-payments for medical insurance. These aspects of the American healthcare ecosystem tend to drive a percentage of people with T1DM to reduce or ration their prescribed dosage of insulin, and their disease state then assumes similar manifestations to diabulimia.

According to research findings published in the June 2018 edition of Diabetes Care, about 27% of the 1.25m people in the US with T1DM say that affording insulin has impacted their daily life. For people with T1DM, “access to insulin is literally a matter of life and death. The average list price of insulin has skyrocketed in recent years, nearly tripling between 2002 and 2013 . . . . [and]  . . . individuals with diabetes are often forced to choose between purchasing their medications or paying for other necessities, exposing them to serious short- and long-term health consequences,” say the authors.

According to T1International, a charity which advocates affordable and accessible diabetes care, "People (in the US) spend most of their life in fear of losing their insurance, of running out of insulin and the cost going up, or of having to stay in terrible jobs or relationships to ensure they keep their health insurance coverage. . . . In the  worst case, folks are rationing insulin which has led to many reported deaths and excruciating complications."
 
Research aimed at improve treatment
 
Given the extent of diabulimia and the significant medical risks associated with the condition, more clinical and technological research aimed to improve its treatment is critical to the future health of this at-risk population. Stadler’s research referred in the opening paragraph of this Commentary is significant. Interestingly, the National Institute for Health Research only supports projects which potentially have a, "clear benefit to patients and the public". Stadler’s research is expected to take five years, aims to provide a better understanding of diabulimia and devise a 12-module treatment plan for people with the condition.
 
Clinic for people with diabulimia
 
People with diabulimia could only seek professional help for their eating disorder and T1DM separately, but never together: that was until January 2017 when an out-patients’ clinic opened in London specifically for people with T1DM and eating disorders. The clinic is led by Khalida Ismail, Professor of Psychiatry and Medicine at King's College, London and the lead psychiatrist for diabetes at King's Health Partners, London, which is comprised of King's College London, Guy's and St Thomas' NHS Foundation Trust, King's College Hospital NHS Foundation Trust and South London and Maudsley NHS Foundation Trust. Ismail wants to unite psychiatrists and diabetes experts. "They never meet patients together and it's an inefficient use of current resources . . . . we'd actually be saving money by joining up services," she says.
 
Takeaways
 
Diabulimia represents one of the most complex patient problems to be treated both medically and psychologically. Standard treatments for eating disorders are not usually appropriate for cases of diabulimia. Treatment for eating disorders tend to involve removing the focus on food, which is contrary to best practice for the management of T1DM. It is important for clinicians and researchers to better understand risk factors, screening tools and treatment options for diabulimia. Also, there needs to be better access to diabetes specialist psychological services that can provide the integrated support that people with diabulimia need. The London clinic for diabetes and  eating disorders and Stadler’s research are a good start.
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  • UK parliamentarians are proposing to raise the smoking age to 21
  • Tobacco smoking is the biggest preventable cause of  disease disability and death
  • People that start smoking in their teens are most likely to continue the habit into adulthood
  • Quitting smoking is more difficult than quitting addiction to opiates
  • Smoking harms every organ in your body and causes 90% of deaths from lung cancer
  • Smoking related illnesses cost healthcare systems billions
  • Some UK policy makers are denying smokers healthcare treatment
  • UK smokers may cover the medical cost of their habit in taxes
  • How should we and how do we treat smokers?

Stop teenagers smoking to reduce disease morbidity and mortality and save billions

An influential cross-party group of UK parliamentarians backed by the charity Action on Smoking and Health, (ASH) and 16 other health and welfare organisations, including the British Medical Association, Cancer Research UK, the Royal College of Physicians and the British Heart Foundation, has proposed raising the minimum smoking age to 21 and introducing a levy on big tobacco companies to fund measures to encourage people to quit smoking and to prevent youngsters taking up the habit.

Although the prevalence of smoking has declined dramatically in the UK over the past five decades, the decline has stalled, and policy makers are keen to stop teenagers from starting to smoke. This is because if you begin smoking in your teens you are more likely to continue the habit into adulthood when it becomes difficult to quit, and smoking related illnesses cause morbidity and mortality for millions and cost healthcare systems billions.
 
Further, it is becoming increasingly common among some policy makers to suggest that smokers should be denied healthcare because they represent an unnecessary and self-inflicted higher burden on healthcare systems due to the illnesses that they pick up as a result of their smoking habit. According to ASH, smoking costs NHS England approximately £2.7bn a year for treating smoking related diseases. Although high, it seems likely that smokers cover the cost of treating their “self-inflicted” illnesses by taxes.

 
Teenage smoking
 
The UK's proposal to raise the smoking age is likely to be well received because the British government wants to reduce the prevalence of 15-year-olds who regularly smoke from 8% to 3% or less and reduce smoking among adults from 15.5% to 12% or less by the end of 2022. A 2009 report by the Public Health Research Consortium entitled A Review of Young People and Smoking in England, provides a comprehensive review of smoking and young people and suggests, “Most young people start experimenting with smoking in their early to mid-teens, but smoking prevalence and consumption increases until the mid-twenties”.
 
Teenage smoking increases DNA damage
 
Nearly 90% of adult cigarette smokers in the UK first tried cigarettes as teenagers. The continued prevalence of smoking by children and adolescents represents a significant public health challenge. Studies at the molecular and cellular levels suggest that early exposure to tobacco smoking enhances DNA damage and is associated with the induction of DNA alterations in specific chromosomal regions. Chemicals in cigarette smoke enter your blood stream and can then affect your entire body. Adolescence is recognised to be the period of greatest development for your lungs, and therefore it is reasonable to assume that adolescence constitute a "critical period" in which tobacco carcinogens can induce fields of genetic alterations that make the early smoker more susceptible to the damaging effects of continued smoking.

In addition to raising the smoking age, the UK policy proposal suggests that each tobacco manufacturer should pay an annual fee based on the volume of cigarettes it sells in the UK, potentially raising hundreds of millions for the government. Deborah Arnott, chief executive of ASH, said: “Legislation to strictly regulate smoking used to be considered controversial and extreme by all mainstream political parties but governments now have confidence that tough tobacco regulation both delivers results, and, crucially, has widespread cross-party and public support.” The tobacco industry has fought hard to resist successive British governments from introducing legislation that would reduce its profits.

 
Tobacco 21

The proposed British policy is not new. In March 2015 the US Institute of Medicine published a research report entitled, Health Implications of Raising the Minimum Age for Purchasing Tobacco Products, which suggests that raising the legal sale age from 18 to 21, known in the US as “Tobacco 21”, would significantly reduce youth tobacco use and prevent adolescents from starting to smoke. Notably, the report estimated that,  “there would be a 25% reduction in smoking initiation among 15-to-17-year-olds if the age to purchase tobacco were raised to 21”.
 
According to a paper by the US Centers for Disease Control and Prevention (CDC) published in the July 2015 edition of the  American Journal of Preventive Medicine, three out of four American adults, including seven in ten cigarette smokers, favour raising the minimum age of sale for all tobacco products to 21. Notwithstanding, 11% of adults strongly opposed making 21 the legal age of sale, while 14% somewhat opposed such measures. Today, five American states have raised their minimum tobacco sale age to 21 and more than 425 communities in 23 other states have adopted a Tobacco 21 policy.

 
Cigarette smoking harms every organ in your body

According to the 2014 US Surgeon General’s Report entitled, The Health Consequences of Smoking: 50 Years of Progressthe century-long epidemic of cigarette smoking has caused an enormous avoidable public health tragedy. Since the first Surgeon General’s report in 1964 more than 20m premature deaths in the US can be attributed to cigarette smoking”.
Although smokers today tend to smoke fewer cigarettes than in the past, this does not necessarily translate into reduced harm: biochemical indices of smoking intensity have not shown commensurate declines. Tobacco smoking harms nearly every organ of your body and is the biggest preventable cause of disease, disability and death. It causes so many different types of cancer including  cancers of the lung, oesophagus, larynx, mouth, throat, kidney, bladder, liver, pancreas, stomach, cervix, colon and rectum, anus, as well as acute myeloid leukaemia. Each year smoking is responsible for some 81,700 and 480,000 deaths in the UK and US respectively.

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In wealthy countries such as Britain and the US, smoking cigarettes kills more people than alcohol, car accidents, HIV, guns, and illegal drugs combined. An estimated 36% of all respiratory disease deaths, 30% of all cancer deaths and 14% of all circulatory disease deaths are attributable to smoking. This figure rises to 87% of deaths from chronic obstructive pulmonary disease (COPD) and 82% of deaths from lung, bronchus and trachea cancer.
 
Nicotine, carbon monoxide and tar

Some experts suggest that it may be harder to stop smoking than to stop using cocaine or opiates  such as heroin. About two out of three smokers say they want to quit and each year about half of all cigarette smokers in developed economies try to quit, but few succeed even with professional help. This is because smokers become physically addicted to nicotine.
 
Tobacco smoke contains a deadly mix of more than 7,000 chemicals; hundreds are harmful and about 70 can cause cancer. However, it is the chemical nicotine, which is the addictive agent, and smoking is an effective way to deliver nicotine to your brain. When you smoke cigarettes, nicotine is quickly absorbed through your lungs into your bloodstream, where it is carried directly to your heart and onto your brain. Because it takes only 6 to 10 seconds for each inhalation of cigarette smoke, nicotine does not get an opportunity to dissipate, so the high concentration of nicotine in your lungs remains in your blood until it reaches your brain. Whilst addictive, nicotine is relatively safe; it is the carbon monoxide and tar, which deposit in your lungs and airways that contain the harmful carcinogens.
 
According to the 2012 US Surgeon General’s Report: “Of every 3 young smokers, only 1 will quit, and 1 of those remaining smokers will die from tobacco-related causes. Most of these young people never considered the long-term health consequences associated with tobacco use when they started smoking; and nicotine, a highly addictive drug, causes many to continue smoking well into adulthood, often with deadly consequences.”
 
Large and rising revenues of giant tobacco companies
 
Although sales of cigarettes are slowing in wealthy countries as people move to vaping, (which is not safe) the annual revenues of the giant tobacco companies continue to rise and their annual marketing and advertising spend also continues to rise. In 2016 the world’s leading tobacco company, Imperial Tobacco Groupgenerated revenues of some US$39bn and the combined annual advertising and marketing spend of the leading tobacco companies in 2017 was nearly US$9bn.
 
Price hikes and demand

There is some evidence to suggest that price increases of cigarettes reduce their demand. For example, findings of a 2014 report published  by the US Centers for Disease Control (CDC), suggested that the smoking rate in the US fell by 15% between 2008 and 2012 when the price of cigarettes increased 40%. Today, it is generally accepted in developed nations that a 10% price hike will reduce demand for cigarettes by about 4%. In 2018, New York raised the cost of a pack of cigarettes from US$10.50 to US$13. Australia has started increasing the average price of a pack of cigarettes from AUS$20 and expects to raise it to AUS$45 by 2020. This represents annual 12.5% hikes in tobacco excise tax, which by 2020 is expected to be nearly 70%; the level recommended by the World Health Organization (WHO).

As an aside, it is interesting to note that the ‘one-size-fits-all’ global excise tax incidence target of 70% proposed by the WHO could be potentially destabilizing. This is because key economic drivers influencing the illicit tobacco trade, which is now a global phenomenon, are excessive tax levels, which result in a sharp decline in cigarette affordability and organised crime’s willingness to supply illicit cigarettes given the opportunity to gain large profits from tax avoidance. The policy challenge is to reconcile cigarette affordability, tax levels and revenues and consumption.

 
The effects of advertising restrictions and graphic labelling
 
The 2014 US Surgeon General’s report suggested that, “The tobacco epidemic was initiated and has been sustained by the aggressive strategies of the tobacco industry, which has deliberately misled the public on the risks of smoking cigarettes”.  Advertising restrictions of cigarettes have been in existence in the US since the late 1990s and many other countries have restricted tobacco advertising. For example, China, where about half of the adult male population smoke, has banned many forms of tobacco advertising. Further, several nations have added graphic warning labels to illustrate the dangers of tobacco smoking. Findings of a Canadian study on the effects of such graphic warnings reported in a 2014 edition of the British Medical Journal concluded that they could decrease the number of adult smokers in the US by 5m to 9m. Each year the tobacco industry continues to spend billions on marketing and advertising.
 
Marketing changes but the same messaging
 
Because direct tobacco advertising is banned in many developed countries, increasingly marketing strategies of tobacco companies have become more subtle and indirect and feature on video games and on all forms of social media, but the overall message remains the same: that  smoking is exciting, glamorous and safe. Research suggests that young people who are introduced to cigarette smoking via such media are more likely to start smoking. Also, tobacco companies give significant price discounts amounting to over US$7bn annually to retailers and wholesalers to reduce the price of cigarettes. They also pay retailers over US$200m to stock and display particular brands of cigarettes, and nearly US$400m is paid annually to retailers and wholesalers in volume rebates and as incentives to undertake their own promotions.
 
Rationing healthcare for smokers
 
Some policy makers argue that smokers are an unnecessary and self-inflicted higher burden on over-stretched healthcare systems due to the illnesses that they pick up as a result of their own decision. The annual direct costs of medical care in the UK resulting from smoking related illnesses amounts to £2.7bn. Rationing treatment based on patients who smoke is gaining momentum in the UK. In 2016 the UK’s Royal College of Surgeons (RCS) reported findings of a 2015 survey of Clinical Commissioning Group (CCG) leaders, which found that some NHS hospitals were either delaying or denying routine surgeries, such as hip and knee replacements, for patients who smoke. Findings suggested that 39% of CCG leaders were considering new limits on the eligibility of services for financial, value or efficiency reasons. Some reported that their CCG was considering introducing referral thresholds for joint surgery. A 2015 survey of clinicians reported that 75% had witnessed rationed care in their area, and 89% of these respondents said that rationing for smokers was occurring owing to financial reasons. In November 2016, two CCG’s in Yorkshire, UK, announced plans to delay surgeries for many cigarette smokers by either 6 or 12 months if they could not prove they have stopped smoking for two months. In one of the CCG’s almost 14% of adults are smokers.
 
Factors driving increased demand
 
Although wounds heal faster and recovery is quicker in non-smokers, there is no evidence to suggest that withholding surgery successfully reduces smoking.
 
A paper published in a 2018 edition of Medical Ethics, argues that where smoking has, “significant implications for elective surgical outcomes, bearing on effectiveness, the rationing of this surgery can be justified on prognostic grounds”. But warns that although rationing certain surgeries for prognostic reasons is sound, authorities, “should avoid explicit statements, which suggest that personal responsibility is the key justificatory basis of proposed rationing measures”.

It is not only smoking, which increases demand on NHS England’s over-stretched resources. Other drivers include the UK’s aging population, reduced social care budgets, which have led to “bed-blocking”, (where people with no medical need remain in hospital because they cannot be supported at home) and staff shortages. While hospital doctor and nurse numbers have risen in the UK over the last decade, they have not kept pace with the rise in demand for healthcare services.
 
Smokers may actually be paying for their habits
 
With regards to rationing treatment for smokers, successive UK governments are conflicted as they are beneficiaries of tobacco excise tax revenues, corporation tax and the taxes of the employees of tobacco firms. When the arithmetic is done, it is not altogether clear that smokers exert a significant extra burden on healthcare resources. Indeed, it is possible that smokers actually contribute more in taxes than is needed to cover the costs of their potential health issues.  Without going into a detailed cost benefit analysis, the headline figures suggest that smokers pay for their medical costs caused by their habit in taxes. Although the cost side of the equation is challenging to pin down, we estimate the overall annual smoking-related cost to the UK taxpayer to be some £14bn, which includes £2.7bn direct cost of medical care from smoking related illnesses. Offset £12bn annual cigarette taxes - £9.5bn in excise duty plus £2.5bn of VAT - which 8m UK smokers contribute each year and you arrive at the conclusion that smokers almost cover the cost of their habit.
 
Takeaways

A range of inter-related factors operating at the individual, family, social, community and societal levels influence whether a young person starts and continues to smoke. This raises a number of unresolved questions that impinge upon health equity, including: How should we treat smokers?  How do we treat smokers? Why do we treat smokers in the ways that we do?
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Will China become a world leader in health life sciences and usurp the US?
 
After World War II, the US captured the global lead from Europe in life sciences thanks to the large American domestic market, its strong network of university research laboratories, competent regulation, effective pricing regimens and generous federal R&D funding.
 
America’s leadership in life sciences is slipping
 
Over the past two decades, as China has systematically upgraded its economy from low-grade to high-grade production, it has come to realize the significance of the health life sciences and Beijing has become determined to win a larger share of the industry’s activity. During this time America’s leadership position in the life sciences industry has slipped.
 
  • Will China usurp the US and become a world leader in health life sciences?
  • What could the erosion of the life sciences industry mean for the US economy?
  • What can American life sciences corporations do to reduce or slow their market slippage?
 
Health life sciences
 
Health life sciences refers to the application of biology and technology to improve healthcare. It includes biopharmaceuticals, medical technology, genomics, diagnostics and digital health and is one of the future growth industries positioned to radically change the delivery of healthcare, substantially reduce the morbidity and mortality of a range of chronic and incurable diseases and save healthcare systems billions. The life sciences industry plays a key role in supporting the economies of the US and China as well as other nations and helps them to compete internationally. The sector requires a complex ecosystem, which integrates high-tech research, large, long-term investments of capital in the face of significant technological, market and regulatory risks, skilled labour, specific manufacturing skills, intellectual property (IP) protection and policy support. According to a 2019 Deloitte’s report on health life sciences the global market size of the industry is projected to grow from US$7.7trn in 2017 to US$10trn by 2022.
 
Reason’s for America’s slippage
 
America’s slippage in its life sciences industry is due to:
  • Increased fair competition from a number of nations, including the UK, and increased unfair competition from China who aggressively steals US IP to piggyback on American life-sciences innovations in order to benefit from enhanced therapies without having to pay their fair share for the costly R&D. China then uses its government’s monopsony power as a purchaser of life sciences offerings to limit the prices of US and other international firms
  • Recent US Administrations’ lukewarm support for the industry. Federal biomedical research funding has been cut in real terms. Reimbursement policies are changing to a value-based approach and pricing policies have tightened. Such policies create uncertainty regarding the government’s willingness to pay for future treatments and the research necessary to discover and bring them to market. The US is also falling behind in providing innovative tax incentives for the industry
  • American life sciences corporations’ reluctance and inability to adapt their strategies and business models to changing international markets.
 
Permanent economic damage
 
The Chinese competitive threat is real and significant. It is important for the US to maintain a competitive life-sciences sector since it generates high-skilled, high-paying jobs and its product offerings are sold throughout the world and the industry is a key component of the US traded economy. A weaker American competitive position in the life sciences could mean a lower value for the dollar, a larger trade deficit, plant closures and job losses. China and other nations, which are gaining global market share at the expense of the US, could cause significant damage to the American life-sciences industry.
 
Creating a health life sciences industry is challenging enough, recreating one after it has lost significant market share is even more challenging, if not impossible. We suggest that to reduce to possibility of this happening US life sciences corporations might consider changing the mindsets of their leaders and demonstrate a greater willingness to learn from and engage with Chinese start-ups, especially those in adjacent industries with AI and machine learning capabilities and experience. The cost of doing this will be to give up some IP, which might be worth doing given the potential financial benefits from such a strategy.

 
A “bullish” American perspective
 
The generally accepted Western perspective is that the US excels at visionary research and moon-shot projects and will always be the incubator for big ideas. The reasons for this include: (i) American education is open, encourages individuality and rewards curiosity and its universities have consistently produced vast numbers of innovative discoveries in the life sciences, (ii) American scientists have been awarded the majority of Nobel prizes in physiology/medicine, physics and chemistry, and (iii)  America is the richest nation in the world. This suggests that there are no apparent reasons why the US should not continue as a world leader in health life sciences.

By contrast, China has stolen and copied America’s intellectual property (IP) for years and is a smaller economy fraught with politico-economic challenges. Although China’s economic growth has lifted hundreds of millions of people out of poverty, China remains a developing country with significant numbers of people still living below the nation’s official poverty level. Beijing has challenges balancing population growth with the country’s natural resources, growing income inequality and a substantial rise in pollution throughout the country. Further, China’s educational system is conformists and not geared to producing scientists known for making breakthrough discoveries. This is borne-out by the fact that China only has been awarded two Nobel prizes for the sciences: one for physiology and medicine in 2015 and another for physics in 2009.

 
Copiers rather than inventors
 
Over the past four decades Chinese scientists, with the tacit support of Beijing, have aggressively and unethically stolen Western technologies and scientific knowhow. According to findings of a 2017 research report from the US Intellectual Property (IP) Commission entitled The Theft of American Intellectual Propertythe magnitude of "Chinese theft of American IP currently costs between US$225bn and US$600bn annually."

America’s response to China’s IP theft has been to adopt the moral high-ground, dismiss China as an unscrupulous nation not worthy of investment and focus on commercialising its discoveries with “single bullet” product offerings and marketing them in wealthy regions of the world, predominantly North America, Europe and Japan. Over the past decade, this strategy has been supported by a US Bull market in equities, which started in 2009, outpaced economic growth in most developed nations and led to a significant degree of satisfaction among C-suites and boards of directors of US life sciences corporations, which did not perceive any need to adjust their strategies and business models despite some market slippage and changing market conditions.

 
Confucian values support conformism rather than discovery
 
Although China has benefitted economically from the theft of American IP, the American view tends to be that China is unlikely to become a world leader in the life sciences because the nation has not produced a cadre of innovative scientists and its education system is unlikely to do so in the near to medium term. Chinese education encourages students to follow rather than to question. Indeed, Confucian values remain a significant influence on Chinese education and play an important role in forming the Chinese character, behaviour and way of living. Confucianism aims to create harmony through adherence to three core values: (i) filial piety and respect for your parents and elders, (ii)  humaneness, the care and concern for other human beings, and (iii) respect for ritual. According to Confucian principles, “a good scholar will make an official”. Thus, some of China’s best scientists leave their laboratories for administrative positions.
 
Further, Chinese universities tend to bind students to their professors who expect unquestioning loyalty. Scepticism towards generally accepted scientific theories is discouraged, especially when they are held by senior academics. Also, China unlike the US, does not tolerate “failure”, and this incentivises Chinese scientists to conduct “safe” research that yields quick and “achievable” outcomes. All these factors conspire to discourage high risk creative scientific activity and encourages safer, “copycat” research endeavours.
 
The strength of the US$ and the US economy
 
America’s global leadership in the life sciences is supported by the fact that the US is the world’s richest and most powerful nation. In nominal terms (i.e., without adjustment for local purchasing power) the US and China have GDPs of US$19trn and US$12trn respectively and  populations of 326m and 1.4bn. Further, the US has an “unrivalled” global trading position: the US dollar is the strongest currency in the world and dominates the overwhelming percentage of all international trade settlements: 70% of all world trade transactions are in US$, 20% in €’s and the rest in Asian currencies, particularly the Japanese ¥ and increasingly the Chinese ¥. Also, US dollar holdings make up the largest share of foreign exchange reserves and the effect of this is to maintain the high value of the US$ compared with other currencies and provide US corporations with significant profits, US citizens with cheap imports and the US government with the ability to refinance its debts at low interest rates.
 
An Asian context
 
We suggest that it is increasingly important for American health life science professionals to get a better understanding of China and Asia. The Asian perspective described here is drawn from three recent books: The New Silk Roads: The Present and Future of the World by Peter Frankopan, The Future is Asian by Parag Khanna and AI Super-Powers: China, Silicon Valley and the New World Order published in late 2018 by Kai-Fu Lee.  

Crudely put: the 19th century was British, the 20th century American and the 21st century is expected to be Asian. The era of breakthrough scientific discoveries and stealing American IP is over, and we have entered an “age of implementation”, which favours tenacious market driven Chinese firms. “Asians will determine their own future; and as they collectively assert their interests around the world, they will determine ours as well”, says Khanna. This is starkly different to American prognosticators who assume that the world will be made in the American image, sharing American values and economics.
Asian view of the US$

Some observers suggest that there are chips appearing in the giant US edifice of international trade described above. The current US Administration’s policies have triggered and intensified discussions in Europe and Asia about America’s dominant global economic position and suggest that the US$ might be starting to weaken against a basket of currencies as China, Russia, Iran, Turkey and other nations, choose to use local currencies for some international trade transactions, which they then convert into gold. Further, central banks are tightening their monetary policies and adjusting their bond purchasing strategies. A common US view is that such trading activities are so small relative to global US$ transactions they will neither weaken the US$ nor dent America’s pre-eminent global trading position.
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Can Western companies engage with and benefit from China?
Notwithstanding, replacing the US$ with the Chinese ¥ seems to be part of Beijing’s long-term strategy, as Beijing encourages its trading partners to accept the ¥ as payment for Chinese exports. China’s recent trading agreements with Canada and Qatar for instance have been based upon local currencies rather than the US$. China, which is the biggest importer of oil, is preparing to launch a crude oil futures contract denominated in Chinese ¥ and convertible into gold. European, Asian and Middle Eastern countries have embarked on domestic programs to exclude the US$ from international trade transactions. Also, oil exporting countries are increasingly able to choose which currencies they wish to trade in. At the same time, oil-producing countries no longer seem so interested in turning their revenues into “petrodollars. For the past decade, President Putin of Russia has been calling for the international community to re-evaluate the US$ as the international reserve currency. All this and more suggests that increasingly, emerging economies may transition from their undivided dependence on the US$ for international trade settlement to a multipolar monetary arrangement. Whilst small relative to the full extent of global trade, it is instructive to view these changes within a broader Asian context.
 
The US has had little exposure to China and Asia
 
One outcome of America’s pre-eminent global economic position and the financial success of American life sciences companies is that corporate leaders and health professionals tend to have little or no in-depth exposure to Chinese and Asian culture and markets. For example, few Fortune 500 senior executives have worked in China; few American life sciences corporations have sought in-depth briefings of Asian markets and few US students and scientists have studied or carried out research in China. Instead, American life science corporate leaders tend to be US-centric; they condemn China for its IP theft and recommend not to invest in China because a condition of doing so is that you are obliged to part with some of your IP.
 
Asia a potential economic powerhouse
 
This distancing has resulted in life science professionals “misdiagnosing” China in a number of ways, which we will discuss. One misdiagnosis is to conflate China with Asia. Asia is comprised of 48 countries. East Asia includes China, Japan and North and South Korea. South Asia includes India, Pakistan and Bangladesh. South East Asia includes Indonesia, Malaysia, Philippines, Singapore and Thailand. These three sub-regions link 5bn people through trade, finance, infrastructure and diplomatic networks, which together represent 40% of the world’s GDP. China has taken a lead in building new infrastructure across Asia - the new Silk Roads - but will not necessarily lead this vast region alone. Rather, as Khanna reminds us, “Asia is rapidly returning to the centuries-old patterns of commercial and cultural exchanges, which thrived long before European colonialism and American dominance”.
 
The difference between IP theft and imitating ‘what works

Market driven Chinese start-ups, supported by the government, are expected to transform China into a world leader in health life sciences by 2030. The thing to understand about China is that it is not just a few start-ups that steal and copy American IP but thousands, which then aggressively compete. This entails cutting prices, improving and adapting their product offerings, developing leaner operations and aligning their strategies and business models to the demands of different markets. The vast scale of this activity has led to a unique cadre of über agile Chinese entrepreneurs, who imitate successful business models and then engage in value added culture-specific product development processes. This has led to Chinese companies becoming exemplary “market driven” implementors. By contrast American companies tend to be “mission driven” and operate a “single bullet” business model and are either slow or reluctant to adapt to the demands of different markets. This results in US discoveries being exploited in Asia by Chinese rather than American companies. We suggest that there are significant benefits to be derived from American life sciences companies developing joint ventures with market driven Chinese start-ups even if it means surrendering some IP.
 
As a postscript, it is worth pointing out that the first Chinese patent was only granted in 1985 and recently, after decades of widespread theft, IP protection in China has improved at lightning speed. As Chinese companies issue more patents, the keener they are to protect them. According to the World Intellectual Property Organization in 2017 China accounted for 44% of the world’s patent filings, twice as many as America.

 
US inventions exploited in Asia by Chinese start-ups
 
An illustration of a disruptive life science technology invented in the US but exploited faster and more extensively in China is CRISPR-Cas9 (an acronym for Clustered Regularly Interspaced Short Palindromic Repeats), which is generally considered to be the most important invention in the history of biology.  The initial discovery was made in 2012 by a collaboration between Jennifer Doudna, at the University of California, Berkeley, USA and French scientist Emmanuelle Charpentier. Applications of CRISPR technology are essentially as infinite as the forms of life itself. Since its discovery, modified versions of the technology by Chinese scientists have found a widespread use to engineer genomes and to activate or to repress the expression of genes and launch numerous clinical studies to test CRISPR-Cas9 in humans.
 
Virtuous circle
 
Notwithstanding, transforming CRISPR genomic editing technologies into medical therapies requires mountains of data and advanced AI capabilities. China has both. The more genomic data you have the more efficacious clinical outcomes are likely to be. The better your clinical outcomes the more data you can collect. The more data you collect the more talent you attract. The more talent you attract the better the clinical outcomes. China is better positioned than America to benefit from this virtuous circle. China’s less than stringent regulation with regards to privacy and storing personal data gives it a distinct competitive advantage over American and Western life sciences companies. China also has more efficient means than any Western nation for collecting and processing vast amounts of personal data.
 
Collecting personal data

Any casual visitor to China will tell you that one of the striking differences with Western nations is that the Chinese economy is cashless and card-less. Citizens pay for everything and indeed organise their entire lives with a mobile app called WeChat, a multi-purpose messaging, social media and mobile payment app developed by TencentWeChat was first released in 2011 and by 2018 it was one of the world's largest standalone mobile apps, with nearly 1bn daily users who every day send about 38bn messages. Not only is WeChat China's biggest social network it is also where people turn to book a taxi, hotel or a flight, order food, make a doctor’s appointment, file police reports, do their banking or find a date and has become an integral part of the daily life of every Chinese citizen. State-run media and government agencies also have official WeChat accounts, where they can directly communicate with users. Further, an initiative is underway to integrate WeChat with China’s electronic ID system. It may be hard for people outside of China to grasp just how influential WeChat has become. There is nothing in any other country that is comparable to WeChat, which captures an unprecedented amount of data on citizens that no other company elsewhere in the world can match. This represents a significant competitive advantage. Applying AI and machine learning technologies to such vast data sets provide better and deeper insights and patterns. These vast and escalating data sets, and advanced AI capabilities for manipulating  them, give China a significant competitive advantage in the high growth life sciences industry, which  increasingly has become digital.
 
 Processing personal data
 
AI is another example of  a technology invented in the West and implemented much faster in China. The “watershed” moment for China was in 2017, when AlphaGo became the first computer program to defeat a world champion at the ancient Chinese game of Go. Since then, China has been gripped by “AI fever”.

Until recently AI machines were not much better than trained professionals at spotting anomalies and mutations in assays and data. This changed in early-2,000 with the ubiquitous spread of mobile telephony and the confluence of vast data sets and the development of neural networks, which made the onerous task of “teaching” a computer rules redundant. Neural networks allow computers to approximate the activities of the human brain. So, instead of teaching a computer rules, you simply feed it with vast amounts of data and neural networking and deep learning technologies identify anomalies and mutations in seconds with exquisite accuracy.

The Beijing Genetics Institute

An illustration of the scale and seriousness of China’s intent to become a world-leader in life sciences and to eclipse similar initiatives by the US is the 2016 launch of a US$9bn-15-year national initiative to develop technologies for interpreting genomic and healthcare data. This national endeavour followed the launch in 1999 of the Beijing Genomics Institute (BGI), which today is a recognised global leader in next generation genetic sequencing. In 2010, BGI received US$1.5bn from the China Development Bank, recruited 4,000 scientists and established branches in the US and Europe. In 2016 BGI created the China National GeneBank (CNGB) on a 47,500sq.m site in Shenzhen, which benefits from BGI’s high-throughput sequencing and bio-informatics capacities. CNGB officially opened in July 2018 and is the largest gene bank of its kind in the world. Dozens of refrigerators can store samples at temperatures as low as minus 200 degrees Celsius, while researchers have access to 150 domestically developed desktop gene sequencing machines and a US$20m Revolocity machine, known as a “super­sequencer”. The Gene Bank enables the development of novel healthcare therapies that address large, fast growing and underserved global markets and to further our understanding of genomic mechanisms of life. Not only has CNGB amassed millions of bio-samples it has storage capacity for 20 petabytes (20m gigabytes) of data, which are expected to increase to 500 petabytes in the near future. The CNGB represents the new generation of a genetic resource repository, bioinformatics database, knowledge database and a tool library, “to systematically store, read, understand, write, and apply genetic data,” says Mei Yonghong, its Director.

US life sciences benefit by engaging with Chinese companies

Lee, in his book about AI, suggests that it is not so much Beijing’s policies that keep American firms out of the Chinese markets, but American corporate mindsets, which misdiagnose Chinese markets, do not adapt to local conditions and fail to understand the commercial potential of Chinese start-ups and consequently get squeezed out of the Chinese market.

This is what happened as Google failed to Baidu, Uber failed to DiDi, Twitter failed to Weibo, eBay failed to TaoBao, and Groupon failed to Meituan-Dianping. We briefly describe the demise of Groupon and point to lessons, which can be learned from it.
 
Lessons from Groupon’s failure in China

Groupon failed to adapt its core offering when group discounts in China faded in popularity and as a consequence it rapidly lost market share. Meituan, founded in 2010 as a Chinese copy of Groupon, quickly adapted to changing market conditions by extending its offerings to include cinema tickets, domestic tourism and more importantly, “online-to-offline” (O2O) services such as food and grocery delivery, which were growing rapidly.
 
In October 2015, Meituan merged with Dianping, another Chinese copy of Groupon, to become Meituan-Dianping the world's largest online and on-demand booking and delivery platform. The company has become what is known as a transactional super app, which amalgamates lifestyle services that connect hundreds of millions of customers to local businesses. It has over 180m monthly active users and 600m registered users and services up to 10m daily orders and deliveries. In the first half of 2018 Meituan-Dianping facilitated 27.7bn transactions (worth US$33.8bn) for more than 350m people in 2,800 cities. That is 1,783 enabled services every second of every day, with each customer using the company’s services an average of three times a week. Meituan-Dianping IPO’d in 2018 on the Hong Kong stock exchange and raised US$4.2bn with a market cap of US$43bn.
 
Efficiency also drives innovation. Meituan-Dianping’s Smart Dispatch System, introduced in 2015, schedules which of its 600,000 motorbike riders will deliver the millions of food orders it fulfils daily. It now calculates 2.9bn route plans every hour to optimize a rider’s ability to pick up and drop off up to 10 orders at once in the shortest time and distance. Since Smart Dispatch launched, it has reduced average delivery time by more than 30% and riders complete 30 orders a day, up from 20, increasing their income. In 2019, the American business magazine Fast Company ranked Meituan-Dianping as the most innovative company in the world.
 
Takeaways
 
Although Meituan-Dianping and other companies we mention may not be well known in the West and are not in the health life sciences industry, they are engaged in highly complex digital operations disguised as simple transactions, which enhance the real-world experiences of hundreds of millions of consumers and millions of merchants. To achieve this the companies have amassed vast amounts of data and have perfected AI and machine learning technologies, which make millions of exquisitely accurate  decisions every hour, 24-7, 365 days a year. Such AI competences are central to the advancement of health life sciences. American life science professionals might muse on the adage: “make your greatest enemy your best friend” and consider trading some of their IP to joint venture with fast growing agile Chinese data companies in a strategy to restore and enhance their market positions.
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