Can Medicine Be Cured Read online

  A few months ago, I saw one of the haematology consultants sitting at a desk by the front entrance of my hospital; next to the desk was a poster announcing that today (13 October) was World Thrombosis Day. Some patients admitted to hospital develop a clot in the veins in their calf, called a deep vein thrombosis (DVT); in some cases, these clots dislodge and travel to the lungs, causing a pulmonary embolus (PE), which can be fatal. DVTs and PEs are collectively known as venous thromboembolism (VTE), and the highest risk is in patients undergoing surgery, particularly orthopaedic procedures such as hip replacement. These patients are routinely given an injection with an anticoagulant (blood-thinning) drug called heparin, which significantly reduces the risk of developing such clots. There is consensus that these high-risk patients should be given heparin, but now all patients admitted to UK and Irish hospitals must undergo a tick-box assessment of their risk of clotting. Any patient over the age of sixty is regarded as being at risk. As most hospital patients are over sixty, the overwhelming majority of patients admitted acutely are now given heparin. One of the largest meta-analyses of this practice found that heparin decreased the risk of pulmonary embolus, but not DVT, and that there was no reduction in mortality. More worryingly, for every clot prevented, two major bleeds were caused. You need to give heparin to about 400 patients to prevent an embolus in one. This is not exactly persuasive data, yet the great majority of patients admitted to my hospital are given heparin, because a protocol forces the junior admitting doctor to do so. A poster advertising World Thrombosis Day is prominently displayed on my ward; the poster proclaims: ‘Everyone has a RIGHT to know if they are at risk of developing VTE.’

  Guidelines are just that: they guide. Protocols, however, are mandatory. Protocols such as those for suspected sepsis assume that doctors are incapable of recognizing sick patients and treating them in a timely and sensible manner. A sepsis protocol might have saved Rory Staunton; we shall never know. Sepsis protocols have come with a huge cost in terms of over-diagnosis and inappropriate treatment. The medical profession has blandly and bovinely accepted this. Sepsis protocols are driven by intensive care specialists who have a very narrow telescopic view. They see the teenage patient with septicaemia, but they don’t have to make a judgement on the eighty-five-year-old lady on the general medical ward who, because she is slightly confused and has a pulse rate greater than 90, has triggered the Sepsis Six, even though she probably doesn’t have sepsis. Similarly, haematologists drive the VTE prophylaxis protocols because they see the patients with PEs; they never see the patients who develop a major bleed from the heparin. These various specialists see only their own tiny quarter of the medical swamp. The rest of us are obliged to deal with the messiness and uncertainty.

  Pharma’s single greatest idea was to move its focus from the sick to the well, thus creating vast new markets of ‘patients’ requiring a lifetime of treatment with drugs like statins. Ivan Illich predicted this: ‘A culture can become the prey of a pharmaceutical invasion. Each culture has its poisons, its remedies, its placebos, and its ritual settings for their administration. Most of these are destined for the healthy rather than the sick.’ The medical establishment dismissed Illich as a crank and a ‘Jeremiah’, yet forty years on, much of what he warned against has come to pass. Illich’s prophesy that the pharmaceutical invasion would be aimed at the healthy rather than the sick has indeed come true, with the advent of ‘disease mongering’: the creation of new markets for drugs by redefining large populations of healthy people as being in need of whatever drug is being marketed. This is where awareness campaigns really come into their own. Having been encouraged by patient groups and doctors to get tested or screened, large numbers of people who hitherto thought of themselves as healthy, find that they are at risk of developing some disease in the future because of their blood pressure or cholesterol levels. They are told that a particular medication will lower that risk, and that they will need to take this medication for the rest of their lives. Disease mongering, wrote Iona Heath, has ‘meant a shift of attention from the sick to the well and from the poor to the rich’.

  To achieve this vast expansion, pharma needed the co-operation of the medical profession, particularly medical academics, who are known in the trade as ‘key opinion leaders’. The company typically sets up an advisory board stuffed with such handsomely paid ‘leaders’. This board advises the company on how best to shape professional opinion, usually though pseudo-educational meetings, sponsored supplements given out with medical journals and the establishment of new guidelines. The patient-support groups are wooed with money and educational material. Although pharmaceutical companies are banned in Ireland from advertising directly to the public, they get around this by sponsoring awareness campaigns on radio, newspapers, television and social media. Some of these campaigns are so well disguised that they are almost undetectable. I came across an article recently in the Irish Times with the emotive title ‘Patient organisations shouldn’t have to march on the streets to get access to medicines’. The author Sylvia Thompson wrote: ‘The Irish Platform for Patient Organizations, Science and Industry (IPPOSI) has expressed concern that new, innovative and improved drugs will not be available or will be significantly delayed to patients in Ireland.’ IPPOSI, according to its website, ‘is a patient-led organization that works with patients, government, industry, science and academia to put patients at the heart of health innovation’. The eighteen board members are a mixture of medical academics, pharmaceutical corporation executives and representatives of disease advocacy groups. It is not clear how this body is funded, but the Irish Times article was accompanied by the statement ‘Brought to you by the Irish Times Content Studio’, which according to the paper’s website ‘has been developed to drive brand stories, engage audiences with commercial content and to enhance the working relationship with our many commercial partners’.

  Drug companies argue that they meet a demand, that they operate in a market, just like any other commercial enterprise. This is not really true, because the market is gamed; demand is artificially created and then inflated. Medical academics are suborned, or even bribed, to talk up the new product. These inducements typically include lucrative invitations to speak at ‘satellite’ sessions at medical conferences. Conference delegates are attracted to these symposia with free food and drink. These events were traditionally regarded as separate from the conference, but over the last several years, they have begun to appear in the main programme. I attended one such industry-sponsored event at the British Society of Gastroenterology some years ago; the company concerned wanted to raise awareness of its very expensive drug for colitis and Crohn’s disease. The symposium was chaired by a famous television newsreader, not a recognized medical leader in the field of inflammatory bowel disease. He bore an expression of perplexity throughout the proceedings, as if he had wandered into the wrong room, and struggled both with the scientific terminology and the names of the panel members.

  The drug companies commonly fund patient-support groups; these support groups are bombarded with boosterist information about new drugs, which they then lobby for, as is commonly the case with cancer drugs. The relevant medical academics often give lectures to the support groups extolling the new drug, which in turn boosts the demand. The ease with which the medical profession has been recruited for these campaigns is remarkable. Academic doctors sometimes plead financial need; membership of an advisory board often covers the school fees. ‘It’s very rewarding’, one professor archly informed me. And lest I be accused of pompous and self-righteous grandstanding, I can confess that I have accepted my share of pharma’s bounty. I justified this to myself with the usual lame excuse that everybody else was doing it; it took me a long time to locate my conscience. In the late 1990s, I attended a session at a conference where two speakers debated whether a new biological drug was a ‘magic bullet’ for a particular intestinal disease. At the end of the debate, a show of hands was taken of the audience, who, by a large majority, vot
ed that this drug was most definitely not a magic bullet. I was surprised, therefore, when some months later, I received a glossy newsletter, purporting to be an educational supplement, which carried an article on the conference debate I had attended. The author reported that a large majority of the attendees had agreed that this drug truly was a magic bullet. I had few illusions about how pharma worked, but this was astonishing. I wrote a formal letter of complaint to the Association of the British Pharmaceutical Industry. They upheld my complaint, and issued the company concerned with a small fine. Shortly after, one of the company’s managers approached me at a conference, wondering if my wife and I would like to attend an educational meeting in Florida. I declined – the first step on my road to conversion to No Free Lunch Fundamentalism.

  The creation of these vast new markets has enriched pharma so much that global revenues in 2014 were more than $1 trillion. Meanwhile, the sick languish. The population are subjected to more and more screening programmes (for breast cancer, cervical cancer, colon cancer, high blood pressure, cholesterol levels, etc., etc.), but if they become acutely ill and need to go to hospital, it is likely that they will spend hours on a trolley in an emergency department. When they are finally admitted to a ward, it is often chaotic, squalid and understaffed. Hospices have to rely on charity just to keep going, and have so few beds that ten times as many people die in general hospitals than hospices.

  Medicine should surely prioritize the sick, the dying and the vulnerable. Decisions on how money is spent on health care should be based on need not on sentimentality, and certainly not on the basis of lobbying by special-interest, disease-specific patient groups. So put your ice bucket away. Cancel the photo shoot. Disband your patient-support group. Stop pestering the healthy with awareness campaigns. Lobby, if you must, for humane treatment of frail, old people in emergency departments, but let’s not raise awareness.

  8

  The Never-Ending War on Cancer

  In the hierarchy of awareness raising, cancer is king. In 1971, Richard Nixon signed the National Cancer Act, promising to make ‘the conquest of cancer a crusade’. Nixon had a keen sense for what exercised his fellow Americans, and surmised that cancer had replaced nuclear annihilation as their greatest fear. He never used the phrase ‘War on Cancer’, but it is as indelibly linked to his name as the word ‘Watergate’. Nixon predicted that the National Cancer Act would prove to be the most significant achievement of his administration. The most bellicose of the new crusaders predicted that cancer would be ‘licked’ in time for the bicentennial celebrations in 1976. This optimism, in some ways, was not unreasonable. Hadn’t America put a man on the moon only two years before? The decades since the Second World War had seen remarkable progress in medicine: infectious disease had been largely conquered – why not cancer? But Nixon didn’t defeat cancer, which is now overtaking heart disease as the number one killer of Americans. In the forty-odd years from 1971 to 2012, $500 billion was spent on cancer research − $20,000 for every American who has died of cancer. There have been many modest – and a few spectacular – advances in cancer treatment since 1971, but for many of the common cancers, such as lung and pancreas, there has been little or no improvement in survival since Nixon signed the Cancer Act. The billions invested in elucidating the cell biology and genetic mutations has resulted in precious little of practical use. The monolithic and narrow scope of Big Science is to blame, as it devotes most of its efforts towards mechanistic ‘explication’ – documenting the biology of cancer cells – and little to ‘intervention’ or actual treatment. The cancer researcher David Pye put it succinctly: ‘How can we know so much about the causes and progression of disease, yet do so little to prevent death and incapacity?’ Cancer is a disease (or group of diseases) mainly of old age: if we lived long enough, we would all eventually get it. As the number of old people is steadily increasing, cancer keeps outrunning us.

  Cancer research is big business and has many stakeholders and beneficiaries. Barack Obama and Joe Biden launched their ‘Cancer Moonshot’ in 2016. Biden said: ‘I’m going to devote the rest of my life to working on this, and I think we’re perilously close to making some gigantic progress.’ Obama went even further: ‘Let’s make America the country that cures cancer once and for all.’ Even the vocabulary around cancer (‘moonshot’) is infected with a sort of hubristic oedema, a malignant hypertrophy. We live in a culture that focuses almost exclusively on benefit, and rarely considers cost. Progress in curing cancer is now reminiscent of the trench combat of the First World War, where a few hundred yards of territory might be gained at the expense of thousands of dead. Each new meagre, incremental advance is hailed as a ‘breakthrough’ or a ‘game changer’.

  The pharmaceutical companies who produce new cancer drugs, and the oncologists who carry out clinical trials on them, routinely use meaningless surrogate endpoints in these trials, such as ‘disease-free remission’ and ‘reduction in tumour size’, instead of traditional hard outcomes, such as survival. Two Canadian oncologists, Christopher Booth and Elizabeth Eisenhauer of the National Cancer Institute of Canada Clinical Trials Group at Queen’s University, Ontario, attacked such bogus statistics in a paper published in the Journal of Clinical Oncology in 2012 entitled ‘Progression-free survival: meaningful or simply measurable?’ Progression-free survival is defined as ‘the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse’. In the case of cancer, this means that the tumour is still present, but not increasing in size. The authors describe the increase in the number of randomized controlled trials of new drugs for metastatic cancers using this metric as the primary endpoint:

  Some trials showing improvement in progression-free survival, without a corresponding increase in overall survival, have led to approval of new drugs and/or changes in standard of care. This suggests a growing belief in the oncology community that delaying progression in metastatic disease is a worthy goal, even if overall survival is not improved. But is a new treatment that improves progression-free survival really an advance for patients? Or is it only lowering the bar to declare active some of our much-heralded new molecular targeted therapies? We believe that as a community, this trend requires discussion and debate.

  An improvement in progression-free survival for most cancer patients simply means that their cancer is no bigger on the CT scan, but they don’t live any longer. Booth and Eisenhauer concluded that progression-free survival was neither clinically significant for doctors, nor existentially meaningful for patients, and cited the use of such bogus metrics as an example of the McNamara, or quantitative, fallacy, which I will discuss later.

  Most of these new cancer drugs are very, very expensive. Patients stricken with cancer, not surprisingly, want to access the very latest treatment, regardless of the evidence of benefit – or lack of it. In Britain, new drugs are assessed by the government agency called the National Institute for Health and Care Excellence (NICE), which uses a number of criteria to determine whether these new agents offer benefit and value for money. (Archie Cochrane had argued for this kind of cost/benefit assessment in 1972.) Many such drugs are turned down by NICE, leading to a predictable public outcry. In response to this protest, the prime minister, David Cameron, set up a special fund to pay for cancer drugs that had either been rejected by NICE or were awaiting assessment. The fund paid out £1.27 billion between 2010 and 2016. In 2017, a group of health services researchers at the London School of Hygiene and Tropical Medicine published an analysis of this spending in the cancer journal Annals of Oncology. Of the 47 drugs funded, only 18 (38 per cent) improved survival, and then only by a meagre average of 3 months. The remaining 29 had no benefit, and caused significant side effects. The senior author, Professor Richard Sullivan from the Institute of Cancer Policy at King’s College London, told the Guardian that the Cancer Drugs Fund had been ‘a massive health error’. He went on: ‘In science, we demand levels of evidence, but pub
lic policy is opinion-based, not evidence-based. You can’t have that in health. Populism doesn’t work.’

  Populism doesn’t cure cancer, but it trumps justice, evidence and fairness every time. In 2016, hospices in Britain cost a total of £868 million. The money wasted on the Cancer Drugs Fund would have paid for every hospice in the UK for a year-and-a-half. The medical–industrial complex is a very devious bully, fantastically adept at recruiting the general public: who could possibly be against more spending on cancer? What kind of monster could possibly question giving a dying person a chance, no matter how small? How can you possibly put a price on a human life? Meanwhile, some oncologists stoke the demand: they casually mention a new ‘experimental’ treatment to the patient and their family. If you’re dying of cancer, you’ll try anything. Cancer patient-support groups – very often funded by drug companies – lobby for access to the new drugs. In the NHS, there is the phenomenon of ‘postcode prescribing’, where some health authorities will fund cancer drugs and others will not. Some cancer patients beg, borrow or crowdfund the cost of the last futile throw of the dice.

  One such patient was Anthony Wilson, broadcaster, nightclub owner and music impresario. He was diagnosed with kidney cancer in 2006. He underwent surgery, but the cancer had spread (metastasized). Standard chemotherapy failed, and his oncologist recommended Sunitinib (‘Sutent’), a new drug for metastatic kidney cancer. Wilson’s local health authority in Manchester refused to fund this drug, which then cost £3,500 a month. BBC news reported in July 2007 that a group of Wilson’s friends had set up a fund to pay for the drug. Wilson said: ‘This is my only real option. It is not a cure but can hold the cancer back, so I will probably be on it until I die… I’ve never paid for private healthcare because I’m a socialist. Now I find you can get tummy tucks and cosmetic surgery on the NHS but not the drugs I need to stay alive. It’s a scandal.’ One of the largest trials of Sunitinib was carried out by the Memorial Sloan Kettering Cancer Center in New York − one of the great cathedrals of modern oncology − and was published in the Journal of Clinical Oncology in 2009. They compared Sunitinib with the standard drug for metastatic kidney cancer, interferon alpha. Sunitinib increased survival by 4 months (26.4 v. 21.8 months), hardly a dramatic improvement. The study, predictably, also measured the usual meaningless surrogate endpoints, such as ‘progression-free survival’ and ‘objective response rate’. Wilson died in August 2007 at the Christie Cancer Hospital in Manchester; his oncologist claimed that his death was unrelated to his cancer.