THE SIX PILLARS OF CLINICAL MEDICINE- PART TWO
Research and treatment are the other two pillars of clinical medicine which need a rigorous cross examination and reformation.
The importance of research to medicine, and indeed any specialty, cannot be overestimated. As Robert A. McCance put it, “the medical profession has a responsibility not only for the cure of the sick and for the prevention of disease, but for the advancement of knowledge upon which both depend. This third responsibility can only be met by investigation and treatment”.
The importance of research is so deeply emphasized by the different specialties that one cannot become a consultant in many of them here in the United Kingdom without having completed some research. The more research one does, the more audits, the more likely your chances are of impressing interviewers and securing a good job.
Unfortunately, the great downside of that is that, with an emphasis on quantity rather than quality, the quality of research has gone downhill. With that kind of emphasis, one cannot help getting the impression that being involved in research and especially audits is a measure of determination, stamina and ability to resist boredom, rather than a true measure of scientific rigour and creativity. Having done a few audits and research projects (particularly as a neuroscience student) I know how painful they can be, how tiring they are, and how frustrating it is when something goes wrong, data is lost, analyzers stop working. When the medical interviewer asks the prospective employee, “Tell me about a time when you were involved in clinical audit” he or she is not expressing a concern about your contribution to the medical world, since he or she knows that we are living in a time of low quality research. It is a measure of determination to do all that it takes to get the new job.
This is because clinical audit is not a creative activity. It is about looking at and analyzing existing knowledge; it never creates new knowledge, about new medicines, about new methods of investigation, and what is best; clinical audit simply tells if one is following ‘best practice’. Whereas research is based on a hypothesis, theories, tests, and analysis; clinical audit measures against standards. Research may involve a degree of experimentation on patients, to prove or disprove the proposed theory; clinical audit “never involves anything happening to the patient which is different to their normal treatment” and may involve sample sizes that are not scientifically valid. Research involves detailed statistical analysis of collected data, whereas clinical audit usually requires only basic statistic analyses. Research results ought to be generalisable and far reaching; clinical audit results are usually applicable within local settings only, and have a local influence on clinical practice (As I explain in the essay on women in medicine, because it involves determination rather than any creative act that is the reason why audit appeals to women much more than men, or at least men with masculine traits. I think that it cannot be denied that creativity is a far more prominent characteristic in men than women).
It cannot be denied too that we are living in an age of poor quality research. Part of the problem lies in, I think, in the emphasis on trivial projects. This is partly driven by a failure at serious progress in major ailments like cancer. There is a general pessimism with regards to these problems. As Professor Colin Dollery, who worked in one of the best research institutes in the world in the past put it:
“Problems seem larger, and solutions to them more elusive…the morality and cost-effectiveness of scientific medicine has been challenged…many people, including some of the most senior of the medical research hierarchy, are pessimistic about the claims of future advance. The age of optimism has ended.”
As a result, focus has shifted to lesser topics. James Le Fanu explains:
“Frustrated at the failure to find cures for serious diseases like cancer and dementia, the pharmaceutical industry has been forced to look elsewhere for profitable markets for its products. This explains the rise of the so-called ‘lifestyle’ drugs whose prime purpose is to restore those social faculties or attributes that tend to diminish with age: Regaine for the treatment of baldness, Viagra for male impotence, Xenical for obesity and Prozac for depression.”
Poor research is also driven by a growth of specialties that are not worth the research attention paid to them, because they are conceptually flawed. I think research on much alternative medicine, including homeopathy, belongs to this category, and to a great extent much research in ‘psychiatry’. In order to survive, in the absence of serious therapeutic revolutions, the pharmaceutical industry may invent illness, and do research on it, a task probably easiest in the field of psychiatry, whose disorders are diagnosed not in the same scientific, objective, quantitative fashion as other specialties, but is based totally on the patient’s ‘history’ and the observation of his or her behaviour and other aspects. Its diagnoses lack the objectivity of other specialties. Hence it is not uncommon to see five different diagnoses given for the same patient by five different psychiatrists. As explained by Richard Hunter in the ‘Proceedings of the Royal Society of Medicine’ in 1972:
“Psychiatrists do not diagnose their patients like other doctors do. They discard four of their senses and literally play by ear. It is the no-touch technique adapted to new purpose….Presenting symptoms are elevated to the status of disease like varieties of fever were in the eighteenth century. The pharmaceutical industry provides corresponding antidotes and reinforces the illusion.”
There are other reasons for the decline in research, but I would just like to focus on one more reason that I think is of paramount importance. The ascent of women in medicine; women, being the less creative (this is by no means a criticism, since they compensate for it by great determination, which many men lack) prefer audit to research, and when they accomplish research, it is likely to bring about no great insights. Women are not born researchers.
As a result of this poor research, as James Le Fanu, one of the brilliant medical writers of our time emphasizes in his best-selling book, ‘The Rise and Fall of Modern Medicine’, the number of medical researchers has declined immensely over the years, with the consequence that “genuinely new drugs, had dropped off sharply from over seventy a year in the 1960s to less than twenty in the 1970s”, and “only a third… seemed to offer even moderate therapeutic gain.”
Le Fanu elaborates on this further in another chapter:
“It would be wrong to suggest the scientific road to discovery from the mid-1970s onwards has not produced some genuinely useful drugs. Its successes include, most recently, a vaccine against the chronic liver infection hepatitis B and ‘triple therapy’ for the treatment of AIDS. But the current list of the top ten big ‘blockbuster’ drugs – the ones that generate the billions of dollars of revenue that sustain the industry’s profitability – features, for the most part, new or more expensive variants of the antibiotics, anti-inflammatories and antidepressants that were originally introduced twenty or more years ago. They might well be more effective, have fewer side effects or be easier to take, but with the occasional exception none can be described as making a significant inroad into previously uncharted therapeutic areas in the way the discovery of chlorpromazine, for example transformed the treatment of schizophrenia.
The most striking feature of many of the most recently introduced drugs is that there is considerable doubt about whether they do any good at all. Thus, there was much hope that the drug finasteride, ‘scientifically designed’ to block the metabolism of testosterone and thus shrink the size of the prostate, would reduce the need for an operation in those in whom the gland is enlarged. This would indeed have been a significant breakthrough but, as an editorial in the New England Journal of Medicine observed, “The magnitude of the change in symptoms (of patients) is not impressive”. Similarly, a new generation of drugs for the treatment of epilepsy based on interfering with the neurotransmitter GABA were dismissed by an editorial in the British Medical Journal As having been ‘poorly-assessed’ with no evidence that were any better than the anti-epileptic drugs currently in use. New treatments for multiple sclerosis and Alzheimer’s disease appear to offer such marginal benefits that their “clinical cost-effectiveness falls at the first hurdle”
The solution to the problem of research lies partly with the medical interviewers, who ought not ‘bully’ their candidates into research; instead they ought to leave them to do the research based on the candidates creative desire. ‘Demanding’ creativity (which is what research is) from people never works, and the damage it has done to the arts, for instance, cannot be overemphasized. Artists, singers, musicians and what have deteriorated significantly since they were purchased by business companies that demand them to produce 5 albums a year for example. This is partly because creativity is based on love, and love cannot be forced.
It also lies in those researchers themselves, who ought to learn something from what the great immunologist Peter Medawar said:
“Any scientist of any age who wants to make important discoveries must study important problems. Dull or piffling problems yield dull or piffling answers…the problem must be such that it matters what the answer is”.
The researcher who is comparing the efficacy of lansoprazole with that of esomeprazole is wasting his time, and all the research that has gone into it is a waste of money, because logic entails there will be little or even no difference between the two isomers. And indeed this has been shown to be the case. Research into the neuropathology of schizophrenia and many ‘psychiatric illnesses’ is useless, because all sorts of abnormalities have been noted, and findings are so inconsistent. So is research into homeopathy – logic entails that giving patients with malaria a millionth of a milligram of malaria pathogens will not cure them, if not harm them. All of these things are conceptually flawed, and until those flaws are removed, research into them will be pointless. Also, needless to say, many researchers have conflicts of interest, which should always be paid attention to.
Finally, improvement in medical research may also be achieved by making more men interested in it. By brightening up the world of medicine to them, by making them see its beauty and joys, their minds may sparkle with interest in it, and then they may apply their creative minds to it. A reduction in the proportion of women in medicine may therefore help.
The world of treatment has been inflicted by many problems too. One of which I think is the desire to please the patient. A patient somehow feels that the consultation with the doctor is incomplete unless a prescription has been issued. In order to avoid the patients displeasure, and as complaint prophylaxis, the doctor issues many unnecessary treatments that are no better than placebo, whose prescription brings great pleasure to the manufacturing pharmaceutical company, and the relief of the patient. How many times have we seen general practitioners for example, issue antibiotics for colds and sore throats, when it is so obviously unnecessary? This has led to an antibiotic resistance problem, and the proliferation of diseases such as pseudomembranous colitis and MRSA infection. They have forgotten that, “one of the first duties of the physician is to educate the masses not to take medicine”, as the great William Osler put it. Over 120 years ago, Oliver Wendell Holmes, the great American physician condemned this practice in the following words:
“The habit of the English "general practitioner" of making his profit out of the pills and potions he administered was ruinous to professional advancement and the dignity of the physician. When a half-starving medical man felt that he must give his patient draught and boluses for which he could charge him, he was in a pitiable position and too likely to persuade himself that his drugs were useful to his patient because they were profitable to him. This practice has prevailed a good deal in America, and was doubtless the source in some measure of the errors I combated.”
Another major problem with treatment is the proliferation of alternative medicine; this is a subject I turn to in another section altogether.
But perhaps the most important problem with our treatment is related not to the treatments per se, but related to our concept of illness and health. Because of the medicalisation of many aspects of life, we have become obsessed with our ‘medical’ health; this is evidenced by the flourishment of ‘healthy eating’, gymnasiums and other things. As Roy Porter explains:
“The irony is that the healthier Western society becomes, the more medicine it craves…Immense pressures are created – by the medical profession, by the media, by the high pressure advertising of pharmaceutical companies – to expand the diagnosis of treatable illnesses. Scares are created, people are bamboozled into lab tests, often of dubious reliability. Thanks to diagnostic creep or leap, ever more disorders are revealed, extensive and expensive treatments are then urged…This is endemic to a system in which an expanding medical establishment, faced with a healthier population, is driven to medicalising normal events, converting risks into diseases and treating trivial complaints with fancy procedures…The law of diminishing returns necessarily applies. Extending life becomes feasible, but it may be a life exposed to degrading neglect as resources grow overstretched. What an ignominious destiny if the future of medicine turns into bestowing meager increments of unenjoyed life!”
James Le Fanu devotes a big chunk of his book on the analysis of this phenomenon of the ‘worried well’:
“This is not the only sign that medicine is in trouble. Surveys reveal that the proportion of the population claiming to be "concerned about their health" has increased from one in ten in 1968, to one in two last year. And the most curious aspect of this new phenomenon of the "worried well" is that it is medically inspired. The well are worried because repeatedly and systematically they have been told by experts that their health is threatened by hidden hazards. The commonsense advice of the past-"don't smoke and eat sensibly"-has metamorphosed into an all-embracing condemnation of every sensuous pleasure: food, alcohol, sunbathing and sex. And every week brings yet another danger. Who would have thought until a few weeks ago that night lights which have reassured generations of children should be damaging to their eyesight?
The paradox of modern medicine that requires explanation is why its spectacular success over the past 50 years has had such perverse consequences-leaving doctors less fulfilled and the public more neurotic about their health. These are, of course, complex matters with any number of explanations. But consider a list of significant medical advances in the past 60 years-starting in 1937 with blood transfusion, and moving through penicillin, kidney dialysis, radiotherapy, cortisone, polio vaccination, the oral contraceptive pill, hip replacement operations, kidney transplants, coronary bypass, the cure of childhood cancer, CAT scanners, test-tube babies and concluding with Viagra. Several themes are easy to identify: the assault on infectious disease (penicillin and childhood immunisation); major developments in the treatment of mental illness, cancer and heart disease; the widening scope of surgery (hip replacements and transplantation); and improvements in diagnostic techniques (the CAT scanner). But what is most noticeable about the list is the concentration of the important breakthroughs in a 30-year period from the mid-1940s to the mid-1970s. Since then, there has been a marked decline in the rate of therapeutic innovation. This "rise and fall" runs counter to the common view of an upward and onward march of medical progress-but it provides the key to understanding current medical discontents.”
The result of this overmedicalisation and disease manufacture is what we have now – the culture of the worried well. The consequences of this are phenomenal. The following is an extreme example, given by none other than Anton Chekhov, the Russian novelist and physician:
“Z. goes to a doctor, who examines him and finds that he is suffering from heart disease. Z. abruptly changes his way of life, takes medicine, can only talk about his disease; the whole town knows that he has heart disease and all the doctors, whom he regularly consults, say that he has got heart disease. He does not marry, gives up amateur theatricals, does not drink, and when he walks does so slowly and hardly breathes. Eleven years later he has to go to Moscow and there he consults a specialist. The latter finds that his heart is perfectly sound. Z. is overjoyed, but he can no longer return to a normal life, for he has got accustomed to going to bed early and to walking slowly, and he is bored if he cannot speak of his disease. The only result is that he gets to hate doctors--that is all”.
The culture of the worried well has been the most important impetus to the pharmaceutical industry. It has converted medicine, almost entirely, from a caring profession, into a trade.
Because of human greed, pharmaceutical companies, which may be regarded as the right arm of medicine, have turned into political and economic forces. For anyone interested in this exploitative aspect of medicine, there are many books and articles clarifying their many crimes. Far from being the idealistic research institutes that appear to be solely interested in the health and welfare of individuals, medicine as currently practised is dominated by the presence of these companies, which spend over twice as much of their income on marketing than on research, often on drugs of dubious effectiveness or value, or what are referred to as ‘me too drugs’. It is a world where marketing is mostly dressed up as science, where consultants and GPs, as well as more junior doctors fall often to the many temptations of the often artificially-friendly drug company representatives (‘drug reps’), which is often dressed up in an ‘educational meeting’ cloak. As explained by Marcia Angells, a prominent American physician and one of the foremost critics of the pharmaceutical industry, as well as a senior lecturer in Social Medicine at Harvard Medical School and former Editor in Chief of ‘The New England Journal of Medicine’, writing in the ‘New York Review of Books’ under the heading, “The Truth About the Drug Companies: How They Deceive Us and What to Do About It”:
“While the rhetoric is stirring, it has very little to do with reality. First, research and development (R&D) is a relatively small part of the budgets of the big drug companies—dwarfed by their vast expenditures on marketing and administration, and smaller even than profits. In fact, year after year, for over two decades, this industry has been far and away the most profitable in the United States. (In 2003, for the first time, the industry lost its first-place position, coming in third, behind "mining, crude oil production," and "commercial banks.") The prices drug companies charge have little relationship to the costs of making the drugs and could be cut dramatically without coming anywhere close to threatening R&D.
Second, the pharmaceutical industry is not especially innovative. As hard as it is to believe, only a handful of truly important drugs have been brought to market in recent years, and they were mostly based on taxpayer-funded research at academic institutions, small biotechnology companies, or the National Institutes of Health (NIH). The great majority of "new" drugs are not new at all but merely variations of older drugs already on the market. These are called "me-too" drugs. The idea is to grab a share of an established, lucrative market by producing something very similar to a top-selling drug. For instance, we now have six statins (Mevacor, Lipitor, Zocor, Pravachol, Lescol, and the newest, Crestor) on the market to lower cholesterol, all variants of the first. As Dr. Sharon Levine, associate executive director of the Kaiser Permanente Medical Group, put it,
If I'm a manufacturer and I can change one molecule and get another twenty years of patent rights, and convince physicians to prescribe and consumers to demand the next form of Prilosec, or weekly Prozac instead of daily Prozac, just as my patent expires, then why would I be spending money on a lot less certain endeavor, which is looking for brand-new drugs?
Third, the industry is hardly a model of American free enterprise. To be sure, it is free to decide which drugs to develop (me-too drugs instead of innovative ones, for instance), and it is free to price them as high as the traffic will bear, but it is utterly dependent on government-granted monopolies—in the form of patents and Food and Drug Administration (FDA)–approved exclusive marketing rights. If it is not particularly innovative in discovering new drugs, it is highly innovative—and aggressive—in dreaming up ways to extend its monopoly rights.”
Noam Chomsky wrote extensively too on this topic in many of his works, such as his book, ‘Year 501’, saying:
“While the US seeks to ensure monopoly control for the future, the drug companies it protects are cheerfully exploiting the accumulated knowledge of indigenous cultures for products that bring in some $100 billion profits annually, offering virtually nothing in return to the native people who lead researchers to the medicines, seeds, and other products they have developed and refined over thousands of years. "The annual world market value for medicines derived from medicinal plants discovered from indigenous peoples is US $43 billion," ethnobotanist Darrell Posey estimates. "Less than 0.001 percent of the profits from drugs that originated from traditional medicine have ever gone to the indigenous people who led researchers to them." Profits of at least the same scale derive from natural insecticides, insect repellents, and plant genetic materials, he believes. The international seed industry alone accounts for some $15 billion a year, based in large measure on genetic materials from crop varieties "selected, nurtured, improved and developed by innovative Third World farmers for hundreds, even thousands of years," Maria Elena Hurtado adds. Only the knowledge of the rich and powerful merits protection.”
Only by exposing their inhumane practices, by disclosing their intentions, by knowing that, to paraphrase Oliver Wendell Holmes that, if the majority (and not the whole) of “pharmacopoeia were thrown into the sea it would be the better for mankind and the worse for the fishes”, because, as Richard Gordon put it in ‘The Alarming History of Medicine’, “among the greatest of discoveries of medicine are the generally belated ones that some treatments are utterly useless”, and by applying rigorous, neutral scientific methods to their research – will pharmaceutics, the right arm of treatment progress.