The journalist and broadcaster John Diamond was the unanimous choice for this year's HealthWatch award. Diamond wrote the acclaimed book "C: Because Cowards Get Cancer Too", which records his experiences since developing cancer of the tongue. He was present to receive the award at the HealthWatch Annual General Meeting on 24th October this year and HealthWatch Committee member Geoff Watts read out John Diamond's presentation to a packed audience. This is reproduced below in full.
The other week I wrote a piece in one of the papers I write for, about alternative medicine. If any of you have read more than four newspaper pieces with my name attached to them then the chances are that one of them was about the intellectual folly which is alternative medicine. I must have written that piece a hundred times now in various forms and the routine has become pretty standard: the true nature of scientific endeavour, the infallibility of the properly designed controlled experiment, the futility of purely anecdotal evidence-well, you all know how it goes.
This time among the outraged correspondence that these pieces invariably attract was a letter from a man in Liverpool. He'd read my piece and it had upset him. For he was a practitioner in alternative medicine and knew it worked. And what's more, he said, he also knew that orthodox medicine simply didn't work. He didn't say it didn't work as well as doctors thought it did, or as well as patients were suckered into believing it would by the grasping medical establishment. No: he was quite certain. Orthodox medicine is a complete sham. It just doesn't work.
He'd included an e-mail address on the letter and-what can I tell you? I was in front of my computer screen, I was bored with whatever it was I was writing-probably yet another piece on the intellectual folly that is alternative medicine-and I e-mailed him. Getting into e-mail arguments about alternative medicine on the internet is as foolish a waste of time as-well, getting into arguments on the internet about gun control or who killed JFK or any of the other cul de sacs up which internet users regularly disappear. But nonetheless I wrote the message and, fool that I am, pressed the 'send' button.
"If orthodox medicine doesn't work," I wrote, "how come life expectancy since, say, the turn of the century has almost doubled?" In fact I wasn't quite sure of the precise figure, but if my previous arguments with alternative medicine supporters are anything to go by, nor was he. He wrote back what they always write back: the reason life expectancy has increased is because infant mortality has decreased. Take out of the equation all those babies dying before they get to their first birthday, and your average Victorian, with his homoeopathy and naturopathy and Little Liver Pills and Tiger Balm, lived just as long as your 21st century pill-popper.
Up to a point he's right, of course. One of the reasons infant mortality has decreased is because of orthodox medicine. But that's not what I wrote to him. Instead I wrote something like this: yes, infant mortality is down. But life expectancy at 20 is up too. And at 30, 40, 50 and 90. A 50-year old with access to a reasonably sober GP and a branch of Boots has a greater chance of living to 80 or 90 than his father or grandfather did. And these aren't statistics worked out by evil doctors with their axes to grind, but by actuaries who work for life insurance companies and who have to get the figures right or the insurance companies will go bust.
I'll give the man his due. He was, by his lights at least, honest with me, for his next message said "Oh. I didn't know that. Look, let me get back to you." Yes, I thought. A result! For the first time in years of arguing the toss with these people, I've made a conversion.
His next message arrived the next day. He was grudging. He didn't know where I'd got my figures from, but he supposed I must be right. Nonetheless, he was sticking by his original statement: orthodox medicine doesn't work and alternative medicine does.
I, he said, was a case in point. I had cancer. The doctors had tried to cure me and had failed. On the other hand his mother had been diagnosed with cancer a couple of years earlier. She, like me, had been a scoffer, a cynic, an unbeliever and had put her faith in the wretched medical con-artists. But after a while he had persuaded her to take Essiac.
Essiac, some of you will know, is an ancient herbal remedy used by Native Americans in Canada to cure cancer, and was rediscovered by a Canadian nurse some time in the 30s. There's no evidence that cancerous Native Americans lived longer in Canada than anywhere else, but Canadian alternativists rather like having their very own national alternative remedy, and the stuff is now touted all over the place as a miracle cure. I don't have to tell you that it isn't, of course; or that every properly controlled study of Essiac has shown that patients might as well drink Tizer for all the good it does.
But this man had fed his mother Essiac and she had-well, since you ask, she'd died ten months later. And this proved Essiac worked? Yes, he said. Because the doctors had only given his mother two months to live. Now as it happens this is one of the things that alternativists are always telling me about in their success stories: "The doctors said the patient would be dead in two months, or a year or two years," they say, "but he took-insert name of alternative remedy-and lived twice as long". In fact doctors very rarely give a precise sell-by date for cancer. Until the very end is nigh, they can usually only ever give a ball park figure. But when doctors say "I'm sorry, we can't be precise. It might be a year, it might be as soon as a couple of months", what people hear, understandably enough, is "You'll be dead in two months." Believe me, I know. Before I had my last bout of chemotherapy I was forever telling people I had three months to live, because that was the worst-case scenario. That was over a year ago, and here I am talking to you tonight. Well, not talking to you exactly, but you know what I mean.
Anyway, the reason his mother had died wasn't because Essiac didn't work but because she'd taken it the wrong way. She had swigged it and she should have sipped it.
I know: the man sounds mad. But I promise you, I've had this conversation, or one like it, with dozens of people like him who make their livings passing on information like this to anyone who pays them: from people with vague symptoms their GPs have got bored trying to treat, to terminal cancer patients desperate for something, anything, to give them some hope.
And the thing about these people is they tell lies. They may not think they're telling lies, but that's what it comes down to. Those of us who doubt the efficacy of alternative medicine tend not to point this out; after all alternative practitioners are usually kind and gentle people who like to think they have their patients' best interests at heart. Saying a homoeopath tells lies is rather like saying that the tooth fairy sniffs glue. But they do. I keep on getting messages, for instance, from men and women who want me to try one or other of their cures, and who tell me a story which goes like this: "I had a patient/friend/client who had been given two months to live and sent home to die because the doctors said there was nothing they could do about the tumour on her liver/lung/brain. Together, though, we worked out a regime of coffee enemas/organic grape juice/zinc-and-aspirin (and I promise you, all of those cures come straight from my e-mail in-box) and what do you know? The next scan showed the tumour had shrunk by half." Which does, indeed, sound miraculous. But then you say to yourself, hang on: what are the doctors doing scanning the patient if she's been sent home to die? Even the best-equipped hospitals tend not to give expensive scans to patients whose time is up. And so after a bit of gentle prodding it turns out that actually the patient has been sent home, but comes in every day for some radiotherapy. Or is on chemotherapy. And, OK, the doctors didn't actually say that the patient was terminal, but ...
If orthodox doctors tried to get away with that sort of nonsense they'd be kicked out of the business in five minutes flat. But the alternativists do it all the time.
But then it occurred to me. Although my Liverpool correspondent was a resolute and unabashed alternativist and I'm a steely-hearted and over-rational supporter of the orthodoxy, we do share a single belief which is this: we both agree that it's possible, under certain circumstances, to alter the outcome of some illnesses by introducing some sort of specific preparation into the sufferer's system.
That basic agreement established, there are two differences between us. I think that the best way of determining what works and what doesn't is to try it out under controlled conditions. If you give Essiac to 100 patients with the same sort of cancer and they die as quickly as 100 patients not fed Essiac, then you can be pretty certain that Essiac doesn't work. Simple. But he doesn't believe that. His is an act of faith-a faith based on rumour, speculation, misheard anecdotage and all the rest of it.
The other difference is probably more telling. If you were to ask most alternativists they'd probably tell you that one of the big differences between their art and our science is that the medical establishment is so very sure of itself. It's closed minded. It knows it's right. But in fact that's the very opposite of the truth. Although we patients demand certainty of our doctors because we prefer certainty in our lives, medical science is as much about not knowing as it is about knowing. An experiment, by definition, is about what you don't know, about what you want to find out. It's the alternativists who are so certain of their beliefs that so many of them don't think it's necessary to submit them to proper scrutiny. Not that they dismiss experiment out of hand. Look through the alternativist's web sites and they have one thing in common: the slightest hint of experimental success is enough to support a vast body of alternative belief; the slightest hint of experimental failure is enough to demolish an equally vast body of established orthodox belief. To be more specific: I've been told scores of times that the Thalidomide case demonstrates how much nonsense orthodox medicine is (and it's interesting that 30 years after the discovery of Thalidomide's dangers, the alternativists still use it as their prime example of orthodox failure). Because Thalidomide was bad medicine it follows that all orthodox medicine is bad. You then go on to challenge them about homoeopathy and they'll tell you that the meta-research published by the EU last year showed that there are statistically significant results showing that homoeopathy has a benefit for hay fever sufferers and people with sore limbs. And on that tiny shred of evidence they start telling me about the wonders homeopathy can work in cases of cancer and heart disease.
It's nonsense. And much of it is offensive and dangerous nonsense too. And for as long as I can, and as long as I can sweet-talk indulgent editors, I hope I'll get the chance to say so again and again.
All of which is an unforgivably long way round of telling you how very honoured I am by this award, above any of them. Yes, I was grateful and usually pretty surprised to win prizes for my journalism and for the book. But to be told that I've done something to help people-too confused by the welter of nonsense about medicine they read in the papers to approach their illnesses rationally-to help them think twice about the claims made for the untested and the impossible...well as far as I'm concerned, that's something worth doing. Thank you.
John Diamond died on March 2nd 2001
Claire Rayner, who honored us by accepting the 2001 HealthWatch Award at the 1st November AGM, has picked up a few ideas in some fifty plus years of working in and around the NHS. It occurs to her that a question rarely asked is 'What are patients for?' In her presentation she entertained those present with her own answers to this question.
From whose point of view are we to look for the answer? That of the patient? Or that of the doctor? Or, since we have a highly politicised NHS, that of the politician? Clearly, it will have to be from all three. And I shall begin with that of the patient.
The most pressing is of course:
Curing: Above all else we seek relief from our symptoms and the banishment of fear of future symptoms. There are some unfortunate people, however, who have a desperate need for the attention of doctors and who are happiest when they have a few (preferably not too disagreeable) symptoms of sufficient medical interest to keep doctors hovering at their sides. These are the ones who want most of all:
Looking after while being cured: Regression into a state of juvenile dependency is a common part of being ill, be it physically or mentally. So, we need to have someone who makes us feel safe and cared for well within reach all through the illness stage and afterwards too if we can get it. Meeting your doctor in the supermarket and having him say, "And how's the old trouble then?" makes you feel important and valued, unless of course the old trouble is something mildly embarrassing like an addiction to masturbating while wearing scarlet panties.
One reason for wanting the doctor there during illness is to be:
Listened to at a time of stress: human beings have a deep need to talk about it, to anyone and indeed everyone who will listen, as anyone who has ever worked in an A & E department knows well. But it is not only after trauma that this need exists. Those who live in constant pain or discomfort need others to know how much they suffer. They may in consequence be shunned by their nearest and dearest, which means that finding someone else to listen to necessary outpourings of distress becomes very important indeed.
A caveat must be entered for some patients: the inarticulate, those who are overawed by doctors and those who simply don't have the language with which to express their needs for a listener. They are the patients who reckon their medical attendants are for:
Being psychic: some patients don't give you vital information about themselves and their condition, but instead look at you trustingly, sure that you will understand anyway and know exactly what they mean when they respond to your question about their pain by telling you it started in the middle of Mary's wedding reception.
And as if listening to patients wasn't enough for a busy practitioner, patients also believe that they are for:
Explaining to: how some clinicians must yearn for those fabled days when a doctor could pat a patient's shoulder or head and say; "Don't you worry your head about any of this, we're here to do the worrying and the thinking, you're here to hrrmph...get better." Well, those days are indeed long gone and not a moment too soon from a patient's point of view. We want to know, in every detail, what our symptoms mean, what signs you have observed in examining us and what they mean, what the latest treatment is for our condition, its safety rate, its failure rate and all other available evidence for its efficacy. And even those of us who are totally unable to comprehend such things as risk /benefit ratios (after all many of us buy a lottery ticket at fourteen million to one odds every week) we still want to be told. And told over and over again in order to take it in properly.
For being encouraged: being ill and getting over it does take a certain amount of patient as well as medical effort. They want - indeed, need - their doctors and other attendants to tell them at frequent intervals how well they are doing, how brave they are being, how hard they are trying, how patient and sensible they are, with always the underlying implication that this patient is and always will be the doctor's all time favourite. There is a particular group which needs this encouragement badly, wanting:
To be cared for however unlovable: as a young nurse the hardest lesson I had to learn was how to show all patients equal concern and interest, even the ones who stank, who coughed and spat revoltingly, who were triply incontinent (triply inasmuch as they always seemed to produce their most malodorous releases of flatus when I was tending to them) and who had eyes that were full of greenish exudates. I also had to learn how not to retch when they vomited or when they coughed and spat. Only those of us who have had need of this medical/nursing ability to dissemble can know how important it is. And now, to go from the truly sublime to the very irritating indeed, patients are for:
Requiring signatures on passport applications and similar extremely annoying trivia: There are GPs I have heard of who demand sizeable fees for appending their scribbles to the backs of ghastly passport photos and suchlike and I can't blame them. But I beg you not to blame the patients who make the requests. Attack instead the bureaucracy that demands it.
There is another thing that patients believe that they are for, and it is one that exercises greatly the minds of many of us. We are for:
Escorting through death: I, like a great many other patients, would like to be sure that all medical staff at all levels would, when the time comes for the inevitable ending of a life, make every effort to provide supportive, dignity-protecting and genuine care. Sadly, all too often hospital-based medics step back, leaving it to the family to cope with what time a GP has to spare them and, if they are lucky, the care of a specialist nurse. Old people tend to be the most neglected in this way, in my experience. Though I have at this point to express a deep and undying gratitude to a geriatrician who recently treated an elderly relative. He saw him at home at frequent intervals as well as in hospital, and continued to care for him, even though there was no doubt that that his death was inevitable. There is a great deal that can be done for a patient even after a disease process has triumphed and is galloping full tilt for the finish, and he did it. Of course, this geriatrician did what all patients want all of their carers to do at all times because patients are for:
Being kind to: There is not the least doubt in my mind that a doctor or other health worker could get away with literally murder, as long as he or she did it with kindness, warmth and an air of sympathy. Dr Shipman had many patients who even after he was found out commented on what a nice kind chap he had always been. And many are the so-called alternative practitioners who offer nonsensical nostra and pseudo-scientific chatter and then pocket comfortable sums and get away with it on account of being "ever so kind". Patients given even the most skimmed a portion of the milk of human kindness will forgive almost anything.
There, then, are the ten things patients think they are for. We must now turn the mirror the other way and look to see what doctors think patients are for.
So, as far as doctors are concerned, patients are for:
Curing the patients' reasons for wanting this are obvious. What are clinicians'?
Well, one has to assume that it was what he or she came into the profession to do. It must come as a shock to those eager students when they are told by their teachers at the start of their careers that cure is a word to be used very sparingly. Speak of giving relief, speak of amelioration, speak of repairs, but be very, very careful about discussing cures - they are few and far between and if you offer one and can't deliver patients will never forgive you. And the next one?
Being grateful: Having someone look at you with swimming eyes filled with something akin to worship because you've done a competent job, as you were trained to do, can be embarrassing at one level, but deeply, gloriously satisfying on another.
Nurses get a very large dollop of gratitude if they do their job even half well. I had a letter only last week from a middle aged woman I had nursed when she was a child back in the fifties. I confess to having no memory of her at all but she listed all sorts of things about her memories of me that made my day. Indeed, I think perhaps it's made my year.
Those are the lofty uses for patients, now its time for the mundane. They are for:
Making a living: This one is not as high on the list in the UK as it is elsewhere, notably in the USA. I have met a great many US doctors and they have all been, without exception, extremely comfortably off merging into downright rich. Swimming pools to die for. On both sides of the Atlantic, this use of patients moves on to another level when it is time to use them for:
Building a career. A modest living can be made in the UK with the most basic of medical qualifications and top-up education of the sort now demanded, but if you really want to Get On, papers are required. Published Papers.
Often, of course, patients are for:
Providing teaching material: Medicine is an art and craft as much as a science, because the objects of the practice of medicine are sentient human beings; all of them different, all with assortments of symptoms instead of nice tidy syndromes, all with their own special complications of gender, age, race, social class, degree of poverty and all the other imponderables that go to make us all so fascinating. The only way a doctor or a nurse or a physio or any other therapist can learn their job is by putting their hands on people and using their own eyes to look at them, their own ears to hear them and, a sometimes neglected but in my experience very important aid, their own noses to smell them. This use of the honest-to-goodness ailing person leads on to another. Patients are for:
Being research animals: A rather odd looking doctor used to come sometimes to the men's medical ward at the Royal Northern Hospital where I trained as a nurse in the fifties and ponder over those of our patients who had carcinomatosis and were there waiting to die, and to some of them he would administer some muddy brown liquid from a bottle he carried in his hip pocket.
He had this crazy notion, sister told us with a sniff, that it might be possible to treat cancer with drugs. We thought he was barmy. I stopped him one day and asked him what he was doing.
"Experimenting on 'em." he said, with commendable directness. "Is that right when they're so ill?" I asked. He clearly thought I was the one who was barmy. "What possible use are they to anyone else but me in that state?" he said and left me gaping. Next day I was transferred to theatres, I remember, and glad to get there.
I do not suggest that researchers are quite so cavalier these days. But I do know that medicine and its practitioners still need to use human beings for research as they set about their vital business of pushing forward the frontiers of medicine. One problem with research is of course that it is even more likely, if badly organised, than other forms of medical practice to lead to one of the most unpleasant uses of patients:
For being sued by on the whole, British patients are not particularly litigious, usually wanting simply an explanation, an assurance it won't happen again to any other patient and an apology when things go wrong. Evidence shows, however, that some of us are looking more sharply across the Atlantic than usual, especially now the legal concept of fighting a case on a "no-win, no-fee" basis has arrived here.
In case you feel I am being too cynical, do let me agree that one of the most important uses of a patient from the point of view of good, caring, well-balanced and well-disposed clinicians is as an:
Object of altruism. To this day many people - and I here include patients as well as doctors and all other health workers - feel a deep and genuine drive to take care of others, to minister to their needs to relieve pain and misery of all possible kinds, to do what Florence Nightingale, now slowly toppling off her pedestal, once described as the core of nursing. To comfort always. I have to admit, however, that altruism may come mixed with other motives. One of them may be the need to find a way of:
Escaping from real life Hospitals, surgeries, operating theatres and clinics are intensely exciting and romantic and diverting places when they're not being exhausting, disgusting, dangerous, frightening and sickening, that is. For people who lack the social skills needed to build satisfying personal relationships, being with colleagues and, above all, patients can be very comforting. Patients ask a lot of you, of course, but not as much as a lover or a child of your own might demand. I have to say I have met many nurses and doctors and others during my many years hanging around hospitals who fit into that category all too neatly.
There remains one final use of patients by doctors in particular and it is one that was expressed most neatly by a surgeon I knew well, for whose theatre cases I regularly acted as scrub nurse. He was MacNeill Love and he would tell each new houseman the same thing on his first day.
"Young man, a surgeon's career is in three stages. The first is to get on. The second is to get honour. And the third is to get honest."
I end by offering you, as I promised I would, the Politician's answer to the question "What Are Patients For?" I will list them while making no attempt to qualify them in any way. I rather doubt I need to. You will know the detail perfectly well:
For winning votes
For losing votes
For lying to (about waiting lists, quality control - "of course we don't allow post code prescribing" - and practically everything else
For appearing to spend money on while doing nothing of the sort
For counting and recounting in order to obfuscate true facts (see "for lying to" above)
For whipping the opposition at all times
For blaming ("you dare to ask doctors for antibiotics, you miss your appointments, you use the Internet!") and being the cause of all NHS problems in general
For sucking up to come election time
Screening for Breast Cancer: A cruel deception
"For every complex problem there's a simple solution; and it's wrong"
Why do I have a problem with screening and why do I appear to be out of step with the agents of the State? This question really bothers me. I have devoted my professional life to women's health, I come from a family with a bad history of breast cancer, I've studied the disease for the best part of 30 years and still I don't get it! Perhaps it's because I have an unusual perspective on the subject?
For example unlike those who deliver the screening programme I am at the sharp end, picking up the pieces after a screen detected abnormality drives an innocent woman crazy with fear. I'm also fairly numerate having been the principal investigator of many multi-centre randomized trials of the treatment of breast cancer. Finally I was responsible for setting up one of the first screening centres in the UK following the Forrest Report in 1987. This centre at Butterfly Walk, Camberwell, South East London not only serves the local population but acted as the training centre for the whole of the SE of England. I know a bit about screening, so why my problem?
Public perception of risk
Each year we enjoy breast cancer awareness month or what I choose to call "Black October". Each October women are advised to practice breast self examination (a thoroughly discredited practice ) and are reminded that their risk of developing the disease is 1 in 11. This number is true only if a woman outlives all competing risks to reach the age of 85 with 25 out of 26 women dying of other causes. It is essential therefore that both doctors and the lay public understand the risk of developing breast cancer in the age groups invited for screening and understand the expectation of life after the diagnosis of breast cancer in the absence of screening in order to appreciate the absolute value of submitting themselves to screening.
However before we get into that I wish to describe some of the biases inherent in mammographic screening which support my somewhat counter-intuitive view that screening ain't all that it's cracked up to be.
Biases in Screening
Lead Time Bias: Say you get on a train to Edinburgh that crashes at Newcastle, then the duration of your fatal journey depends on your departure point. If you leave from Milton Keynes the journey lasts two and a half hours whereas if you leave from Kings Cross it is three hours... but you still die at the same time. In other words merely shifting the period of observation of breast cancer to the left might extend survival from the point of diagnosis without necessarily extending the duration of your life.
Length bias: If you were to trawl the sea for fish with a slow boat you'd catch the slow fish but miss those who can outswim your trawler. In other words if you trawl the female population for breast cancer at intervals you will catch the slow growing cancers that might be cured if allowed to grow to a clinically detectable stage whilst missing the rapidly growing cancers that appear in the intervals between screening and are probably the ones that will kill you in any case.
Class bias: Not all women invited for screening are "compliant" and graciously accept your invitation. The affluent upper classes who are health conscious tend to accept, whilst the poorer-educated lower classes may ignore your invitation or never get it in the first place because they maybe of no fixed abode. Futhermore we know that the outcome of treatment, stage for stage, is better amongst the better off so the apparent benefit of screening might just be a surrogate for class.
To get round these biases in order to truly assess the value of screening it is necessary to carry out randomized trials in whole populations with the outcome measure being breast cancer mortality. At the same time for all we know the intervention and its consequences might indirectly impact unfavourably on other causes of death. Ideally therefore the trials should be sufficiently well powered to look at all causes of death.
The trials of screening and relative risk reductions
There have been eight randomized or quasi-randomized trials of population mammographic screening for breast cancer and a number of observational studies which I will choose to ignore because of the biases described above. In addition there have been a number of attempts to conduct a meta-analysis of all these studies to improve the precision of the estimate. Finally there was the 2001 Cochrane review1, which attempted to weight the studies for quality before providing a summary statistic. Let us first dispose of the latter. This provoked the editor of the Lancet, Richard Horton to state, "At present there is no reliable evidence from large randomized trials to support mammography programmes". This then provoked the screening enthusiast to cry foul!
Whatever the merits or flaws in the Cochrane review there are a number of unassailable facts that emerge. The Canadian study, that produced a negative result, was the only one with individual randomization with informed consent. The HIP study New York, which produced the most favourable result, excluded 336 subjects in the control arm because of a past history of breast cancer compared with 853 in the screened population. The Edinburgh trial, which randomized according to postal district, ended up with huge imbalances in socio-economic factors favoring those invited for screening. Finally the largest effects were seen in the trials with the worst equipment and the longest screening intervals.
We therefore start off with the concern that screening has no proven effect.
Let's leave that for a moment and consider the more optimistic estimates produced by two overview analyses, Kerlikowske et al in 1995 and the US preventive services task force 2002. Neither could show a significant advantage for women under the age of 50 (in fact the latest result from the Canadian trial for the over 50 group actually showed a detriment for the first 10 years!) whereas their estimates for the under 50 age group varied between a hazard ratio of 0.76 (i.e. a relative risk reduction of 24%) and a hazard ratio of 0.84 (i.e. relative risk reduction of 16%) for breast cancer specific mortality. It is worth noting that most promotional material for screening includes a statement to the effect that screening will reduce the woman's risk of dying of breast cancer by 25%.
Let us now compute what that means in absolute terms so that an individual woman can work out her chances of benefit following a decade of mammographic screening. I can promise you that the numbers I describe are not in dispute but simply not offered up to the lay public.
The risk of a woman aged 50-60 for developing breast cancer is 2/1,000 a year or 2% over a decade(20 out of 1,000). The anticipated 10 year survival for clinically detected breast cancer in the absence of screening today is about 75%. Therefore we can expect 5 deaths per thousand women from breast cancer over this period (75% of 20). The relative risk reduction for screening applies to these 5 women. From the above overviews a realistic estimate would be the saving of 1 life (a relative risk reduction of between 16 and 24%). Therefore one in a thousand women stand to benefit from a decade of screening whilst 999 have to share the cost and by this I don't mean financial cost but the price in terms of "side effects".
This is what is meant by, "framing the result". Each year I play a little game with the senior postgraduate students at a course for specialists in breast cancer run by the Royal College of Surgeons of England. I tell them that there are two potentially effective screening tools for prostate cancer - one which will reduce their chances of dying from the disease by 20-30% whilst the other will save one life after 10,000 years of person screening. As a consumer or as a public health official which would you buy into? They all vote for the first and none vote for the second; yet if applied to breast cancer, they are the same. To continue marketing screening in terms of relative risk reduction in breast cancer mortality is disingenuous in the extreme.
The down side of screening
Of course if screening were as innocent an intervention as wearing seat belts or fluoridization of the water supply, then apart from opportunity costs, there wouldn't be a problem. However screening is by no means an innocent activity.
Like any other imperfect screening tool there has to be a balance between sensitivity and specificity. Sensitivity is a measure of the ability to detect those cancers present in the population whereas specificity is a measure of the accuracy of the screening tool. These two measures tend to pull in opposite directions. For 100% sensitivity i.e. not missing a single cancer, specificity will fall and many women with benign changes on mammography will be recalled for biopsy. There always has to be a delicate balance between these opposing needs, to catch all the cancers whilst protecting women without cancer from false alarms and unnecessary invasive procedures. Even at its best for every cancer detected another woman will have a false alarm. Whereas at its worst, fuelled by a fear of litigation, the cumulative risk of a false alarm over a decade of screening is around 40%.
All this unnecessary surgery has its morbidity but also tends to throw up pathology of borderline significance. The lay public can be forgiven in thinking that a pathologist can make a clear distinction between cancer and non-cancer, but sadly that is not the case. There is a whole spectrum of abnormalities ranging from epithelial hyperplasia with or without atypia, lobular carcinoma in situ, low grade duct carcinoma in situ (DCIS), high grade DCIS, micro invasive DCIS and tubular carcinoma of uncertain significance and unknown natural history. A conservative estimate would suggest that fewer than half of these would threaten a woman's life if left undetected and yet they account for 20% of "cancers" detected at screening. Furthermore many of these cases have field changes that affect the whole breast leading to a mastectomy for what might be a non-progressive condition. As a result the screening programme cannot claim that there is a net reduction of the mastectomy rate in the population, the opposite might be the truth.
Next there is the issue of "lead time". If the woman with the screen detected cancer is either doomed to die or at the other extreme diagnosed with a cancer that would have been curable even if left to develop to the point of clinical diagnosis, she will live as a "breast cancer patient" for one or two years longer than needs be.
Finally women invited for screening should be aware that the detection of DCIS with all the uncertainties described above might have an effect on the premiums for their health or life insurance. In fact I would go further and advise women intending to accept the summons for screening, at the same time they are buying a house, to postpone the event until after they've negotiated their mortgage.
Where do we go from here?
I believe that to carry on complacently now that we know the full costs and benefits of screening is NOT an option, so what should be done? In an ideal world I would recommend that we shut down the service and divert the resources (opportunity costs) to other issues to preserve the health of women. This might include improving the clinical care of women with symptomatic breast cancer as for example getting rid of the 12 week waiting list in some parts of our country for postoperative radiotherapy. We could also fund first class breast cancer research with the £50,000,000 a year so released. The promise of improved treatments holds more than improved screening which has nowhere to go.
Prevention of heart disease and osteoporosis would save more lives than the prevention of breast cancer yet the strategies could well be the same with the use of selective oestrogen response modifiers (SERMS).
However I see this as politically inexpedient so the best I could hope for here might be a shift in the screening window, to the 55-69 age group where sensitivity and specificity might be improved.
Finally if nothing else I believe there is an ethical imperative to offer women full informed consent with the risk and benefits spelled out in terms that don't patronize or deceive them. If after that the women vote with their feet - so be it.
Professor Emeritus of Surgery at University College London
Olzen O, Gøtzsche PC. Cochrane review on screening for breast cancer with mammography. Lancet 2001; 358: 1340 - 2.
Obstacles to honesty in medical research
Dr Peter Wilmshurst, a consultant cardiologist, has spent the last two decades trying to expose research misconduct and has reported more than twenty doctors to the General Medical Council. In recognition of his dogged and selfless pursuit of the truth, Dr Wilmshurst was presented with the HealthWatch Award 2003.
I feel greatly honoured to receive the Health Watch Annual Award and I am grateful for the opportunity to speak to you about obstacles to honesty in medical research.
I have been interested in this subject for 20 years, since I first experienced research misconduct when I was a research registrar. I hope that a personal account of my experiences may explain why I believe this is a serious problem.
In 1986 I went to the Guardian Newspaper with the story after the medical and pharmaceutical regulators refused to take any action. I supplied the Guardian's lawyers with over 200 pages of documents and statements, which convinced them that they could successfully defend any legal action if sued. We were not.
My research was on heart failure. This is a common condition and it has a worse 5-year survival than many forms of cancer. Twenty years ago there were few treatment options to improve symptoms and none was proven to improve survival. I was offered the opportunity to do research on a promising new drug, named amrinone. It was patented by Sterling-Winthrop. Preliminary research looked promising. Research, mainly from the company, showed that the drug increased the strength of contraction of the heart in animals. But the most influential article and the one that persuaded me that the drug was worthy of research was on patients and was published in the New England Journal of Medicine in 1978.
The New England Journal is the most influential medical journal in the world. The article came from the Cardiology Department at Harvard and one of its five authors was the most well known cardiologist in the world and head of medicine at Harvard, Professor Eugene Braunwald. The paper was given extra prominence by being the first article in that issue of the Journal and it was accompanied by an editorial.
In a large series of experiments we showed that, although amrinone increased the strength of contraction of normal heart muscle, it did not affect contractility in patients with heart failure. We also found that amrinone frequently caused life threatening side effects.
With hindsight there were two things that should have raised my concerns when we started our research. The first were anomalies in the study from Braunwald's group. It was a small study, which made claims that were not substantiated by the observations reported.
Later I discovered that though the article stated that the 5 authors were employed in the Cardiology Department at Harvard Medical School, 2 were full-time employees of Sterling-Winthrop and had never worked at Harvard. Two of the three that worked at Harvard were paid consultants to the company. These conflicts of interest were not declared. In fact the New England Journal of Medicine had no policy on declaration of conflicts of interest at the time. The first statement on conflicts of interest was published in the New England Journal one month after I wrote to the Massachusetts Medical Society, which owns the Journal, complaining about the undeclared conflicts of interest in this case.[3,4]
The second thing that should have alerted me was a letter published in the New England Journal of Medicine from cardiologists in Los Angeles. The letter reported fatal side effects from amrinone. The first author, Dr Stanley Rubin, had a patient with severe heart failure. The patient's wife was a stock-broker. She saw the dramatic increase in the price of Sterling-Winthrop shares after the paper from Braunwald's group was published. She reasoned that this proved that amrinone was an important advance. She asked Dr Rubin to get amrinone for her husband. Rubin was able to persuade the company to let him have amrinone on a named-patient basis and the amrinone swiftly killed his patient. Rubin and colleagues sent the New England Journal the first report of side effects with amrinone. They did not tell Sterling-Winthrop that they had submitted the report. Within 48 hours Rubin was under pressure by the company to retract the report. The Journal admitted that it had sent Sterling-Winthrop a copy of Rubin's report. The Journal initially refused to publish the report but was forced to do so when Rubin said that if they did not he would go to the press.[3,6,7]
However the conflicts of interest involving the New England Journal, the Cardiologists at Harvard and Sterling-Winthrop did not end there. The company later produced a congener of amrinone, named milrinone. The initial human research on milrinone was also performed in Braunwald's department. Unusually it was agreed before the research had been completed that it would be published in the New England Journal. When the first 2 referees chosen by the journal to review the paper recommended rejection, the editor, Dr Arnold Relman sent the article to 2 more referees. They also recommended rejection, but the Journal published the paper on milrinone as previously agreed.[3,6,7] This says much about peer review in the World's most prestigious medical journal.
I discovered this much later. In the early days of our research my colleagues and I were more concerned that we could not confirm in our large number of experiments claims made in the small study from Braunwald's department.
We reported to Sterling-Winthrop that we were unable to find evidence that amrinone injections increased contractility in patients with heart failure and we reported our experience of serious adverse effects with the oral preparation of the drug. Company employees asked us to exclude some patients from the analysis. These were ones where there was a downward trend in contractility. The effect of excluding them would have been to produce an apparent but spurious increase in contractility in the remainder. We refused. My supervisor and I were then threatened with litigation. We published.
Our on-going research studies on amrinone ended when company employees removed the drug stocks from the pharmacy in the hospital and research institute. As a result, 2 of our publications contain statements pointing out that the studies were smaller than planned because Sterling-Winthrop had prematurely discontinued our trials without our agreement.[9,10]
A number of tactics were used to try to prevent my colleagues and I presenting our findings at meetings and to discredit us when we did present. One strange incident involved one of my colleagues, Alex Crowther, who was due to present some of our work on amrinone on the second day of a meeting in Luxembourg. He just managed to get on the last flight of the day that would permit him to attend the first session of the meeting. When he arrived he discovered that his talk had been rescheduled for the previous day. The organisers had received a forged letter that appeared to be from him asking for his talk to be brought forward a day. Those responsible were never identified.
When I presented our findings on side effects a company employee stood up and said that I had made up the findings. I had to point out that I was an independent investigator, but that my accuser was a company employee. I had nothing to gain by claiming that the drug was unsafe. I asked the chairman to appoint people to review our data. A few days after the meeting I received an apology from the company, but the hundreds who heard the allegations at the meeting would not be aware of the company's retraction.
At a number of other meetings at which I presented our findings, three eminent professors of cardiology, each of who was a paid consultant to Sterling-Winthrop, made public statements that they had tried to replicate our findings and failed. None of them acknowledged their affiliation to the company. Twenty years later none of those failures to replicate has been published. This tactic came to an end at a European Congress of Cardiology, in front of several hundred doctors. I pointed out that a professor who made these claims was a paid consultant to the company and that he had been making the claims for two years. I suggested that if he continued to make the claims without publishing his data people might think that he was lying. My findings were not challenged again.
At one point, my supervisor and I were asked to meet with the company and a different American professor of cardiology who is an opinion leader in the treatment of heart failure and who was a consultant to the company. The American professor told us that we were mistaken about the drug. He said that he was aware of finding by other investigators and that these entirely refuted ours. He advised us that we should not publish any more of our findings. He said that we would be found to be wrong and our reputations would be adversely affected. We went on to present 14 abstracts, and 15 publications.
One of the presentations was at the American Heart Association meeting in November 1982. I presented data, which showed that amrinone did not have the cardiac effects claimed. After my presentation, 3 professors of cardiology at separate American university hospitals told me that they had also obtained results similar to ours. They were unaware of each other's research or of our research. They informed Sterling-Winthrop. The company arranged meetings between each of them individually and the same professor of cardiology, who had told us that our findings were aberrant. He also told each of them the same thing. He persuaded two of them not to publish. The third did publish, after much soul searching because he was afraid that he would lose research contracts with Sterling-Winthrop and other pharmaceutical companies. After he published he received threats, including a threatening phone call at 2am.
The Netherlands Committee for the Evaluation of Medicines spotted our paper on the side effects of amrinone. There were major discrepancies when compared with the clinical record cards submitted by the company on our patients. We showed that the company had sent the Netherlands Committee forged clinical records for our patients with the information on adverse events deleted.
Because of this I contacted the UK Committee on Safety of Medicines and discovered that Sterling-Winthrop had also failed to notify the CSM of side effects in our patients. During discussions I discovered that contrary to statements made to us at the outset of our research, Sterling-Winthrop had not obtained a Clinical Trials Certificate for oral amrinone, though they had got a CTC for amrinone injection. This meant that the research with oral amrinone conducted by us as well as by doctors in the National Heart Hospital in London, in Newcastle-upon-Tyne and in Birmingham had been illegal.
When I raised this with the company, the senior vice president bragged that they were telling the government that if the company was prosecuted it would close down its large manufacturing plant near Newcastle upon Tyne. The company was not prosecuted for breaches of the Medicines Act.
I tried unsuccessfully to get sanctions against the company or its employees, but the Association of the British Pharmaceutical Industry, the Faculty of Pharmaceutical Medicine of the Royal College of Physicians and the General Medical Council were not interested. I spoke to editors of medical journals, including BMJ, Lancet and Nature. None disputed the facts but all were afraid to take on a multinational pharmaceutical company with unlimited financial and legal resources. One editor mentioned the loss of advertising revenue from the company.
The process of being rejected by all the official bodies that I believe should have dealt with the issues took nearly 5 years. While this was going on, in 1984, the company told a hearing of the Food and Drugs Administration in the USA that there had been over 1400 serious adverse events in 1200 patients given amrinone in trials and the company announced that they would cease trials and applications for product licences worldwide. Officially the drug was unsafe to take even on a doctor's prescription. Two years later, in 1986, I discovered that the company was still marketing amrinone in parts of Africa and Asia. In those countries it was being sold as an over the counter treatment for heart failure. I approached Oxfam, which had workers in the developing countries where this was happening. They collected evidence, which was presented at a meeting of the World Health Association in Geneva. Sterling-Winthrop was finally embarrassed into withdrawing the drug world wide in 1986.
It was my contact at Oxfam who put me in touch with James Erlichman, a Guardian reporter. He and the deputy editor, Peter Preston, were convinced by the evidence I had and so were the Guardian's lawyers. The paper covered the story on the front, back and the whole of an inside page of one issue and in follow-up stories in other issues.
I had seen how corporate greed and personal ambition had tended to distort scientific evidence. Sterling-Winthrop believed that my supervisor and I could be bribed or threatened into suppressing our data. Others, such a Drummond Rennie, Deputy Editor of the Journal of the American Medical Association, have documented this occurrence. Some professors preferred to suppress their findings rather than run the risk of losing prestige by appearing mistaken or losing lucrative contracts for future pharmaceutical research. Financial conflicts of interest caused some opinion leaders to behave dishonestly. Conflicts of interest, affected publication decisions at the New England Journal of Medicine. The institutions including government, which one might expect to help preserve research integrity, were not prepared to take on a multinational pharmaceutical company.
However these are not the only obstacles to honesty in medical research I have come across. In one case an eminent clinician, who was the president of his specialist society, and who had a large private practice doing a particular interventional procedure wished to publish a series of 400 cases. It was then the largest series in the United Kingdom. When the data was analysed it was found that his mortality rate for the procedure was unacceptably high compared with rates in other countries. If this became known it would have a disastrous impact on his private practice. So the mortality rate was falsified. However, they had already published an abstract at an obscure meeting at which amongst other things they reported the deaths in the first 254 patients. The number of deaths reported in the abstract was greater than in the 400 reported in the paper. This discrepancy became common knowledge in the specialty. I was present during a meal at which a junior doctor that was a co-author of the paper admitted that the falsification had occurred. He implied that he and other junior doctors had little option but to go along with their boss. Five other junior doctors heard the admission. I contacted the editor of the journal. It was part owned by the specialist society of which the senior author of the paper was the president. The editor knew of the rumours. He said that if I could get one of those who heard the incriminating admission to confirm it, he would act. I went back to those who had heard the admission. Now, years after those events, some have provided me with written statements confirming that they heard the admission, but at the time all said that they would not support my efforts to get the paper retracted. Some said that it would be bad for their careers. Some said that it would be bad for medicine or the specialty. One said that he thought that it was the sort of thing that any of us would do. Those 5 junior doctors went on to get consultant posts and one went on to be a president of the society himself.
My efforts to get the paper retracted were common knowledge in the specialty. I was asked to see the post-graduate dean who advised me to stop upsetting influential people. Until that point things had gone well in my career. As an undergraduate, I had obtained honours or distinction in 10 out of 11 subjects. I had been awarded an Honours degree overall, plus six undergraduate prizes and an Intercalated B.Sc. My house jobs were in my teaching hospital, and included the professorial medical job. Then I was senior house officer at the Hammersmith and in Oxford, medical registrar at Northwick Park, and cardiac registrar and senior registrar at St Thomas'. After these events, for the first time in my career, I had difficulty getting a job. I stopped counting the rejections after the 42nd. In many cases individuals with much less clinical and research experience were appointed. It was clear to me that loyalty, no matter how misplaced, was valued more highly in medicine than honesty.
I believe that obstacles to honesty in medical research generally fall into a few categories. One is personal ambition for promotion, advancement, money, kudos and power.
A second obstacle is that those who achieve success by becoming heads of departments or institutions can only maintain their position if their institution continues to succeed. Success is judged in many ways, but the most common measure of success is the balance sheet. Department heads are expected to pull in research grants. So money is another obstacle to honesty in research. This does not apply purely to pharmaceutical companies. I do not imagine that executives of Elsevier, which owns the Lancet, asks the editors much about the research published. I imagine that Elsevier asks how much was earned from drug advertising, how much was earned from sales to pharmaceutical companies of reprints of trials showing their drugs in a positive light and how the current citation rating will affect circulation profits. Of course academic institutions are the most mercenary of all.
However the greatest obstacle to honesty in medical research is the code of silence that pervades the medical profession and the research establishment. There is still considerable reluctance to shop another doctor, no matter how dishonest he is. In this setting of tolerance is there any wonder that ambitious young doctors, aware that to progress they need lots of publications with exciting findings, will embellish their findings and some will falsify the lot? Should we be surprised that a search for funding for their department and personal gain, from drug company consultancies, result in dishonest behaviour by senior academics and opinion leaders? Who will blow the whistle on them? Institutions seeking high rating in the research assessment exercise will try to suppress knowledge of dishonesty in their establishments, even to the extent of letting the guilty escape punishment. Those institutions demand success from their department heads and do not look too carefully at whether that success was achieved honourably or honestly. In this setting it is almost invariable that whistle blowers are damaged more than the guilty they expose. Academic institutions and journals do not want to be associated with dishonest research and treat harshly anybody that brings it to attention.
I have, with difficulty, persuaded a few journals to publish a small number of articles describing research misconduct.[3,13,14] Each article has been reviewed sentence by sentence by lawyers wanting evidence to support individual statements. This was because the editors of the journals were concerned that they might by sued if individuals or institutions were libelled. In a libel case it is no defence to say I am only the publisher not the author. This is in stark contrast to scientific publications. I have submitted many scientific articles for publication and many had implications for survival of patients, but no journal has ever asked me to prove that I got the results claimed. This might suggest that medical journal editors are more concerned with the reputations of academics and their institutions than the lives of patients. The simple truth is that editors are most concerned with money. Journals are never sued for publishing false results no matter how many patients died. In scientific research they can have the best of both worlds. They are absolved from blame if a study is wrong and gain an improved impact rating if the research is an important advance. A higher impact rating increases revenue from sales and advertising. Editors know that research can bring major reward to individuals and organisations, which may act as a temptation for dishonesty, but journals accept submissions on trust without checking their accuracy. Journals almost never retract work shown to be false. When they do, they make it clear that publication of the false research was entirely the fault of the authors. I would like to see whether the policies at journals changed if some were sued by patients harmed by implementation of treatments based on their publications.
There are few objective medical scientists, because they all know that success in their career is dependent on the results they obtain. Every one has a conflict of interest, everyone is human and some are venal.
Do academic institutions or journals recognise the humanity and venality of their staff? They do in some areas of activity. When paying wages, do any of these organisations leave out a bag of money and trust their staff to take the wages to which they are entitled? Of course they don't, because they realise that for some the temptation for dishonesty would be too great. The gains from dishonesty in research can be greater but institutions and journals trust researchers not to fall prey to these. We need to put in place robust checks on research. I believe that there should be random checks of raw data of work in progress and of submitted work. We know that use of performance enhancing drugs is common in competitive sports because of enforced drug checks without warning at sporting events and between events. If we did not have these checks we might mistakenly conclude that doping was not common in sport. I believe that the checks reduce the dishonesty in sport. We need a similar approach to research. The raw data could be demanded at a routine check during a visit to the research institution or when the research is submitted for publication. Failure to produce the raw data should be considered the equivalent of failing the inspection and should result in a ban on future research for a specified period and a review of previous research published. A finding that a department in an institution had falsified research should be a negative factor when assigning ratings in the research assessment exercise. In this setting justified whistle-blowing would be welcomed by institutions. Publication of dishonest research by a journal should affect its impact rating. The failure of a journal to publish a retraction of dishonest research should have a multiplied negative effect on the journals rating.
However the most important thing is that we must change the culture in medicine in which research success is viewed as the passport to success in ones career. For most clinicians only a limited experience of research is required to enable you to understand what you read in research articles and to participate in multicentre trials, organised by career medical scientists.
However there is a more fundamental problem, which is the issue of honesty. Most medical students start with high ideals. Research, which I hope is honest, has shown that as medical students go through medical school a progressively greater proportion believe that cheating in exams is acceptable. The institutions tolerate it. Three years ago Richard Smith wrote in the BMJ about a medical school that permitted a student caught cheating in the final exams to pass. I know of examples where Universities have refused to withdraw higher research medical degrees that are known to contain falsified research. I know of an academic institution in London in which senior officers know that one of their professors lied about his qualifications when he was appointed to that institution. Specifically he claimed to have a MD that he had not been awarded. The institution does not think he should be sacked and the GMC does not feel that he should appear before it. In that and other institutions there is tolerance of dishonesty at all levels. Only a sea change in opinion will produce the required improvement. I fear that it must be imposed from without because our leaders in medicine and academe lack the appetite to produce the required changes.
1. Erlichman J. Drug firm "made threats". Company tested heart drug with DHSS clearance. The Guardian 3rd November 1986; 1 and 6.
2. Benotti JR, Grossman W, Braunwald E, Davolos DD, Alousi AA. Hemodynamic assessment of amrinone. N Engl J Med 1978; 299: 1373-7.
3. Wilmshurst P. The politics of disclosure. Lancet 1997; 349: 510.
4. Relman AS. Dealing with conflicts of interest. N Engl J Med 1984; 310: 1182-3.
5. Rubin SA, Lee A, O'Connor L, Hubenette A, Tober J, Swann HJC. Thrombocytopenia and fever in a patient taking amrinone (letter). N Engl J Med 1979; 310: 1185.
6. Relman AS. The politics of disclosure. Lancet 1997; 349: 885.
7. Wilmshurst P. The politics of disclosure. Lancet 1997; 349: 1558.
8. Baim DS, McDowell AV, Cherniles J et al. Evaluation of a new bipyridine agent - milrinone - in patients with severe heart failure. N Engl J Med 1983; 309: 748-56.
9. Wilmshurst PT, Walker JM, Fry CH, et al. Inotropic and vasodilator effects of amrinone on isolated human tissue. Cardiovasc Res 1984, 18: 302-9.
10. Wilmshurst PT, Thompson DS, Juul SM, Dittrich HC, Dawson JR, Walker JM, Jenkins BS, Coltart DJ, Webb-Peploe MM. Effects of intracoronary and intravenous amrinone infusion in patients with cardiac failure and patients with near normal cardiac function. Br Heart J 1985; 53: 493-506.
11. Wilmshurst PT, Webb-Peploe MM. Side-effects of amrinone therapy. Br Heart J 1983; 49: 447-51.
12. Rennie D. Thyroid storm. JAMA 1997; 277: 1238-43.
13. Wilmshurst P. The code of silence. Lancet 1997; 349: 567-9.
14. Wilmshurst P. Institutional corruption in medicine. BMJ 2002; 325: 1232-5.
15. Smith R. Cheating at medical school. BMJ 2000; 321: 398.
16. Wilmshurst P. Doctors seem not to be punished for dishonesty in their cv. BMJ 2001; 323: 1309.
Medical journals: an extension of the marketing arm of drug companies?
Everyone knows that medical journals and drug companies are economically interdependent. Drug companies need journals to publish the results of their clinical trials showing the efficacy and safety of new drugs in order to obtain product licences for these drugs. Journals obtain substantial income from drug advertisements, reprints and supplements. "So what?" you may say, "isn't this how it is with all products advertised through the print and broadcast media, so why make a fuss?"
After accepting the 2004 HealthWatch Award Dr Richard Smith, formerly editor of the British Medical Journal, explained to his audience why it is very necessary to make a fuss, reports John Garrow.
The relationship between medical journals and the pharmaceutical industry is far more intimate and sinister than that between advertisers and the general media. It is not only Smith that says so. He cited some important commentators in support of his case: Lancet editor Richard Horton (1) claims, "Journals have evolved into information laundering operations for the pharmaceutical industry". Marcia Angell, former editor of the New England Journal of Medicine, has commented (2), "[The pharmaceutical industry] has moved very far from its original high purpose of discovering and producing useful new drugs. Now primarily a new marketing machine to sell drugs of dubious benefit, this industry uses its wealth and power to co-opt every institution that might stand in its way, including the U.S. Congress, the Food and Drug Administration, academic medical centres, and the medical profession itself." The promotional blurb of a book by Jerry Kassirer (3), another previous editor of the NEJM, reads, "Dr Jerome Kassirer offers an unsettling look at the pervasive payoffs that physicians take from big drug companies and other medical suppliers, arguing that the billion-dollar onslaught of industry money has deflected many physicians' moral compasses and directly impacted the everyday care we receive from the doctors and institutions we trust most."
These are eminent medical editors whose warnings we should heed. If, as Kassirer states, the enormous economic power and influence of drug companies has "deflected many physicians' moral compasses" to the extent that the public is now fed misleading information about the efficacy of drugs, this is something HealthWatch should mind about very much indeed. A few simple figures illustrate the great economic power and profitability of the drug industry. They are now producing relatively few new drugs, but concentrating their efforts more on marketing existing drugs. US companies spent $15.7 billion on drug promotion in the year 2000. That represents about $10,000 on each individual doctor. Since 1995 research staff numbers have been reduced by 2%, while marketing staff have increased by 59%. Researchers comprise just one in five of drug company staff - they are outnumbered two to one by marketing staff.
At present prescription drugs cannot be advertised in the general media (although this rule is being undermined by advertisements on the internet) so the industry needs to persuade doctors to promote and prescribe new drugs in place of older and less profitable ones. It has been shown that endorsement by doctors is more effective in altering prescribing practice than an equal expenditure on company representatives. Independent expert reviewers have found that about half of the advertisements for prescription drugs in medical journals are biased in favour of the drug, giving too great prominence to claims of efficacy, and too little to side effects, and that often the advertisement recommended the use of the drug in a patient group other than that in which it had been tested. It would be possible to peer review all advertisements in medical journals, but this would be very expensive and most editors would rather spend the money on maintaining as high a standard as possible in the research publications. It is not unknown for advertisers to strike a deal with editors, such as favourable editorial mention of a drug in return for placing an expensive advertisement. Some journals carry a section on "product news" which appears to be independent but is in fact "advertorials". And as we heard from the winner of the 2003 HealthWatch Award, Dr Peter Wilmshurst, it may be very difficult to publish reports of an adverse drug effect in major journals, because the makers of the drug will fight vigorously to suppress any such publication.
But perhaps the most important, and certainly the most subtle, way in which the drug industry can influence the opinion of doctors about the efficacy of a drug is by the publication of clinical trials in reputable journals. Systematic reviews of randomised controlled trial are the very best evidence on which Evidence Based Medicine is based. But the systematic reviews are only as reliable as the trials that the meta-analysts have analysed. Of course if trials are technically poor (bad randomisation, weak blinding, inappropriate statistical analysis, etc.) they are given little weight in good systematic reviews, but if the trial is technically perfect we must believe it, mustn't we?
It is unthinkable that reputable pharmaceutical companies and reputable medical journals would collude to publish fraudulent results about a drug trial, but we should bear in mind the pressures that operate when a major drug trial is submitted to a journal for publication. From the journal's viewpoint the financial benefits of publishing the trial are very large (see below). From the drug companies' viewpoint the stakes are even higher. They have already spent many £m in developing the drug, but if a major multicentre trial shows that the drug is relatively ineffective, or has serious side effects, that is a commercial disaster that must be avoided if that is at all possible. Initial drug trials are usually designed and funded by the manufacturer of the drug, the design of the trial is beyond reproach, and almost always the results are favourable to the sponsor. However, when independent researchers study the same drug the results are usually less favourable, and in some cases the drug is withdrawn because it is shown to be ineffective or unsafe. How can this occur?
Dr Smith led us through the methods that can enable companies to get the results they want without falsifying the data:
No need to falsify data: ways in which companies might use real trial results to get the results they want
The new drug can be compared with placebo, or too low a dose of a competitor drug, so the new drug is shown to be "effective", when really it is no better than an alternative treatment.
The new drug can be compared with too high a dose of a competitor drug, so it can be seen to have fewer side effects.
The new drug can be compared with a better (but more expensive) drug in a small trial so the results show "no significant difference" and the new drug appears good value for money.
The trial may have several different end-points, and the report cites those results in which the new drug performed well, but not those in which it performed badly.
The drug may be tested on a heterogeneous group of patients, some of whom did well and others badly. Select a group (eg. men over age 50) who did well and publish those results and forget the rest.
If there is no subgroup that does well do not publish that study at all.
If you have a good study, publish it more than once.
Sponsor multicentre trials, but publish only those centres that show favourable results.
Publish separately different outcome measures from the same trial.
Publish different follow-up periods, eg. results at 3 months, one year, two years...
Publish positive results in major journals and negative or neutral results in minor journals.
Combine results in ways that are favourable.
As an illustration he cited one particular drug about which there were publications describing 84 trials on 11,980 patients. In fact there were only 70 trials involving 8,645 patients, but 17% of the trials had been published more than once, though this was impossible to tell from the published studies. Smith used a Cochrane-type diagram to illustrate the way in which duplicated trials could increase apparent effectiveness. Initially 16 trials (group A) showed that the Number Needed to Treat (NNT) to obtain one favourable result was 9 patients (confidence interval 7-16). Three of the most favourable trials were duplicated (group B): now analysis showed only 4 NNT.
Next group B was duplicated again to give group C, so combining B+C gave 9 trials with 4 NNT, and finally combining all the trials and their selected duplicates there were (apparently) 25 trials giving 5 NNT (CI 4-6), which is a considerable improvement on the initial 9 (CI 7-16). Further examples were given of drugs that had apparently favourable clinical trial evidence (for example Cox-2 inhibitors vs NSAIDs, or HRT to protect against coronary heart disease) but scrutiny by independent experts showed the evidence was flawed. Setting the record straight about the efficacy of drugs is not a task for the faint-hearted: those with an interest in selling, say, Cox-2 inhibitors or HRT will fight fiercely to discredit any evidence that their value has been overstated.
At this stage of the address Dr Smith had convinced us that his title proposition was true: to a very great extent medical journals are an extension of the marketing arm of the drug companies, and someone should do something to correct the situation. But what about those pillars of society - physicians sworn to serve only the interests of their patients? Or the medical press - are they not part of the Fourth Estate, champions of the people, said by Edmund Burke to be more powerful than parliament itself? Why do they condone this scandalous abuse of public trust? As I looked around the audience, many of whom were, or had been (like myself) physicians and medical editors, there were no confident smiles to be seen. A lone representative of the pharmaceutical industry was not looking very happy. How had we got into this mess, and how could we get out?
The first question was easily answered. Reprints of important drug trials, or supplements sponsored by drug firms, are major sources of revenue for journals. Two-thirds of trials in major journals (Archives of Internal Medicine, JAMA, Lancet, New England Journal of Medicine) are funded by the drug industry - for the British Medical Journal it is only one third4. Editors of journals (or their publishers) cannot afford to reject everything that is commercially sponsored. In many fields of medical research (such as obesity, in which I have experience) industry is virtually the only source of funding to employ research registrars, or buy expensive equipment. Unless (like me) they are fortunate to have departments funded by a charity, the great majority of physicians depend upon industry for their research bread and butter, never mind the champagne and canapés that may also be on offer. Politicians call it "partnership with industry" but it is a partnership in which power lies with the commercial sponsor.
What is the solution? Dr Smith offered some answers: A register of trials, so unfavourable trials do not "disappear". Publication of online journals not beholden to commercial sponsorship, such as PLOS Medicine (http://medicine.plosjournals.org); critical review of trial protocols by independent experts; and of course much more public funding of clinically-important trials. Whether his call will be heeded remains to be seen, but it will be certainly receive support from members of HealthWatch.
At the end Dr Smith received a standing ovation, and coped with another 30 minutes of well-informed and pertinent questions. Truly he is a worthy recipient of the 2004 HealthWatch Award.
1. Horton R. New York Review of Books; March 11, 2004.
2. Angell, Marcia. The New York Review of Books; July 15, 2004; 51 (12).
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