Guest post by Louise Lubetkin
A while ago this sardonic little vignette, titled Medicine Through the Ages, was doing the rounds on the Internet:
2000 B.C. – Here, eat this root.
1000 A.D. – That root is pagan. Here, say this prayer.
1750 A.D. – That prayer is superstition. Here, drink this potion.
1900 A.D. – That potion is snake oil. Here, swallow this pill.
1985 A.D. – That pill is ineffective. Here, take this antibiotic.
2000 A.D. – That antibiotic is unnatural. Here, eat this root.
We seem to have come full circle. The idea of health as a personal goal, something that can be achieved by taking nutritional supplements such as herbal preparations, vitamins and minerals, is a fundamental tenet of alternative medicine. Consequently the rise of alternative medicine has been accompanied by a parallel rise in the use of dietary supplements.
Most people assume that dietary supplements, like pharmaceuticals, are thoroughly tested before being allowed onto the market, and that in any case because they are “natural” they are ipso facto safe.
Neither assumption is correct.
First of all, it is a great mistake to assume that all “natural” substances are harmless and therefore fit for consumption. (Fugu anyone? Perhaps with some sautéed Amanita mushrooms?) Secondly, unlike pharmaceuticals, which must undergo protracted pre-market testing for safety and efficacy, dietary supplements need not undergo even rudimentary testing before being sold over the counter to the public.
Supplement usage is at an all-time high. Currently, almost 50 percent of us regularly take supplements. The older you are, the more likely you are to take them: usage climbs to 70 percent amongst people 70 years and older. Similarly, the more formal education you have had, and the higher your income level, the more likely you are to be a regular consumer of dietary supplements.
Our collective enthusiasm for taking supplements has undoubtedly done considerably more for the health of the supplement industry than it has for that of the public. There is mounting research evidence to suggest that taking dietary supplements may neither be as safe nor beneficial to health as has previously been assumed (more on this in another post). Nevertheless, physicians seem to be just as vulnerable as the rest of us to the blandishments of the supplement industry. According to one study published in the Journal of Nutrition, 75 percent of dermatologists, 73 percent of orthopedists and 57 percent of cardiologists reported personally using dietary supplements. An earlier study by the same research group found that a staggering 79 percent of physicians and 82 percent of nurses reported recommending dietary supplements to their patients. Of course the fact that supplements come with a personal recommendation by a physician only serves to reinforce the public’s ill-founded presumption of safety.
The manufacture and sale of supplements is a hugely profitable business, generating more than $25 billion in annual sales and contributing an estimated $60 billion to the US economy. While most other industries have languished during the current economic downturn, the supplement industry has grown steadily: overall, between 2008 and 2012, sales of supplements rose by 31.7 percent.
(Ironically, the huge popularity of these so-called “natural” health products has not escaped the notice of agribusiness and pharmaceutical giants such as Kellogg’s, Pfizer, Monsanto and others, all of which have now begun manufacturing and marketing nutritional supplements of their own.)
None of this would have been possible had it not been for the 1994 enactment by the US Congress of the Dietary Supplement Health and Education Act (DSHEA), an extraordinarily ill-conceived piece of legislation that drastically weakened the FDA’s regulatory control over vitamins, minerals, herbal, botanical and other “traditional” medical products. Prior to DSHEA, these products were classified as drugs and were therefore subject to FDA regulation. By reclassifying them as foods rather than drugs DSHEA effectively removed dietary supplements from FDA regulatory oversight. As a result, supplement manufacturers became exempt from any obligation to perform pre-market testing for purity, safety or effectiveness, and it became infinitely harder for the FDA to detect unsafe products and quickly remove them from the market.
While the FDA does have the authority to insist that manufacturers refrain from making unsubstantiated health claims, it no longer has the power to mandate removal of unsafe products from the market without first clearing the almost insurmountable legal hurdle of proving significant risk. In other words, DSHEA inverts the responsibility for ensuring safety. Before the FDA can act, consumers must first be harmed sufficiently seriously, and in sufficient numbers, to trigger an investigation.
In one fell legislative swoop, DSHEA dished up a profit bonanza to the supplement industry while simultaneously robbing the public of any meaningful protection. Thus disencumbered of all but token regulation, the dietary supplement industry quickly burgeoned. In 1994, when DSHEA was enacted, there were just 4,000 dietary supplements on the market. Today there are more than 75,000.
The brave new world spawned by DSHEA is well exemplified by the ephedra case. Herbal weight loss supplements containing the plant alkaloids ephedra and ephedrine were linked to a string of over 150 deaths and countless other serious adverse events. Metabolife, the manufacturer of the supplement, received 15,000 complaints of adverse events – including deaths – related to the product, yet was under no obligation to alert the FDA, and (not surprisingly) chose not to do so.
It took a full 10 years of intense legal fighting for the FDA to succeed in getting ephedra-containing supplements removed from the market. Undeterred, powerful industry lobbying groups and vociferous opponents of regulation mounted a successful appeal challenging the legality of the FDA ban, and ephedra supplements once again went on sale in several states. The ruling against FDA was eventually overturned on appeal and the ephedra ban was upheld, but the cost, difficulty and duration of the legal process of restricting access to this dangerous “natural” supplement was staggering. Yet even now, despite the FDA’s hard-won ban on ephedra, it is perfectly legal to buy ephedrine hydrochloride – an extract of ephedra – over the counter in the US, where it is marketed for sale without prescription as a bronchodilator and nasal decongestant. The only restriction on its sale is that it must be presented in pill form with dosage not exceeding 8mg, and the label cannot promote it as a weight loss aid – a restriction which can be sidestepped with the greatest of ease, as this website, with the in-your-face domain name ephedrinediet.org, vividly demonstrates.
Perhaps not surprisingly, the ephedra case is the only time the FDA has attempted to force the removal of a dangerous supplement from the market. Hamstrung by DSHEA, the FDA can do little more than exert its limited authority over the wording on supplement labels to ensure that manufacturers make no explicit claims that their products may be used prevent, cure or treat a specific disease. However, the lack of seriousness with which an increasingly confident supplement industry takes the FDA and its semantic policing powers is well illustrated by the following statement which appears in a recent report published by the Natural Products Foundation, an industry umbrella and lobbying group:
Healthy consumers use supplements to decrease their risk of heart disease, boost their immune systems, prevent vision loss, build strong bones, or prevent birth defects. Less healthy or ill consumers turn to supplements as an alternative to traditional medical treatments, to either complement prescription drugs they may be taking or substitute supplements for prescription drugs they either cannot afford or do not trust.
There are encouraging signs that concern about the dangers posed by an largely unregulated supplement industry may at last be growing, although industry and grass-roots opposition to attempts to repeal DSHEA have been well organized, well funded and vociferous. Even so, in 2007, largely as a result of public unease over the FDA’s protracted struggle to ban ephedra, DSHEA was amended to make reporting of serious adverse events such as death, life-threatening emergencies, inpatient hospitalizations or significant, persistent incapacities, mandatory. As a result of this amendment, in the first 9 months of 2008 alone, the FDA received almost 600 reports of serious adverse events arising from the use of dietary supplements. Moreover, the FDA believes that adverse events are being seriously under-reported, and that the annual number of supplement-related adverse events in the US is close to 50,000.
Perhaps it will take another ephedra disaster to make us rethink DSHEA, take the handcuffs off the FDA and begin looking more critically at the notion that dietary supplements are intrinsically beneficial and harmless.
In the meantime, here’s the 2013 addendum to Medicine Through the Ages:
2000 A.D. – That antibiotic is unnatural. Here, eat this root.
2013 A.D. – Has that root been assayed for adulterants, standardized for potency and purity? Has that root been approved by the FDA following clinical trials to establish dosage, efficacy and safety? Is the use of that root use evidence-based? Is it safe to take that root concurrently with other roots? Are there any contraindications? My diet already contains roots; will taking more be too much?
There are few subjects in the area of alternative medicine which are more deceptive than the now fashionable topic of “integrated medicine” (or integrative medicine, healthcare etc.). According to its proponents, integrated medicine (IM) is based mainly on two concepts. The first is that of “whole person care”, and the second is often called “the best of both worlds”. Attractive concepts, one might think – why then do I find IM superfluous, deeply misguided and plainly wrong?
Whole patient care or holism
Integrated healthcare practitioners, we are being told, do not just treat the physical complaints of a patient but look after the whole individual: body, mind and soul. On the surface, this approach seems most laudable. Yet a closer look reveals major problems.
The truth is that all good medicine is, was, and always will be holistic: today’s GPs, for instance, should care for their patients as whole individuals dealing the best they can with physical problems as well as social and spiritual issues. I said “should” because many doctors seem to neglect the holistic aspect of care. If that is so, they are, by definition, not good doctors. And, if the deficit is wide-spread, we should reform conventional healthcare. But delegating holism to IM-practitioners would be tantamount to abandoning an essential element of good healthcare; it would be a serious disservice to today’s patients and a detriment to the healthcare of tomorrow.
It follows that the promotion of IM under the banner of holism is utter nonsense. Either it is superfluous because it misleads patients into believing holism is an exclusive feature of IM, while, in fact, it is a hallmark of any good healthcare. Or, if holism is neglected or absent in a particular branch of conventional medicine, it detracts us from the important task to remedy this deficit. We simply must not allow a core value of medicine to be highjacked.
The best of both worlds
The second concept of IM is often described as “the best of both worlds”. Proponents of IM claim to use the “best” of the world of alternative medicine and combine it with the “best” of conventional healthcare. Again, this concept looks commendable at first glance but, at closer inspection, serious doubts emerge.
They hinge, in my view, on the use of the term “best”. We have to ask, what does “best” stand for in the context of healthcare? Surely it cannot mean the most popular or fashionable – and certainly “best” is not by decree of HRH Prince Charles. Best can only signify “the most effective” or more precisely “being associated with the most convincingly positive risk/benefit balance”.
If we understand “the best of both worlds” in this way, the concept becomes synonymous with the concept of evidence-based medicine (EBM) which represents the currently accepted thinking in healthcare. According to the principles of EBM, treatments must be shown to be safe as well as effective. When treating their patients, doctors should, according to EBM-principles, combine the best external evidence with their own experience as well as with the preferences of their patients.
If “the best of both worlds” is synonymous with EBM, we clearly don’t need this confusing duplicity of concepts in the first place; it would only distract from the auspicious efforts of EBM to continuously improve healthcare. In other words, the second axiom of IM is as nonsensical as the first.
The practice of integrated medicine
So, on the basis of these somewhat theoretical considerations, IM is a superfluous, misleading and counterproductive distraction. But the most powerful argument against IM is really an entirely practical one: namely the nonsensical, bogus and dangerous things that are happening every day in its name and under its banner.
If we look around us, go on the internet, read the relevant literature, or walk into an IM clinic in our neighbourhood, we are sure to find that behind all these politically correct slogans of holism and” best of all worlds” there is the coal face of pure quackery.Perhaps you don’t believe me, so go and look for yourself. I promise you will discover any unproven and disproven therapy that you can think of, anything from crystal healing to Reiki, and from homeopathy to urine-therapy.
What follows is depressingly simple: IM is a front of half-baked concepts behind which boundless quackery and bogus treatments are being promoted to unsuspecting consumers.
“Don’t take this therapy lightly. Multiple sclerosis, colitis, lupus, rheumatoid arthritis, cancer, hepatitis, hyperactivity, pancreatic insufficiency, psoriasis, eczema, diabetes, herpes, mononucleosis, adrenal failure, allergies and so many other ailments have been relieved through use of this therapy. After you overcome your initial gag response (I know I had one), you will realize that something big is going on, and if you are searching for health, this is an area to investigate. There are numerous reports and double blind studies which go back to the turn of the century supporting the efficacy of using urine for health”. This quote refers to a treatment that I, and probably most readers of this blog, find truly amazing – even in the realm of alternative medicine, we do not often come across a therapy as bizarre as this one: urine therapy.
Urine therapy enthusiasts claim that your own urine administered either externally, internally or both, has a long history of use, that most medical cultures have usefully employed it, that many VIPs swear by it, that it can cure almost all diseases and that it can save lives. What was new to me is the claim that it is supported by numerous double-blind studies.
Such trials would, of course, be entirely feasible; all you need to do is to give one group of patients the experimental treatment, while the other takes a placebo. Recruitment might be a bit of a problem, and the ethics committee might raise one or two eyebrows but, in theory, it certainly seems doable. So where are the “numerous” studies?
A quick, rough and ready Medline-Search found several unfortunate authors with the last name of “URINE”, yet no clinical trials of urine therapy emerged. A little more time-consuming search through my books on alternative medicine revealed nothing that remotely resembled evidence. At this point, I arrived at the conclusion that the clinical trials are either non-existent or extremely well hidden. Further searches of the proponents’ literature, websites etc made me settle for the former explanation.
All this could be entirely irrelevant, perhaps slightly amusing, would it not reveal a pattern which is so painfully common in alternative medicine: anyone can claim anything without fear of any type of retribution, gullible consumers are attracted through the exotic flair, VIP-promotion, long history of use etc. and follow in droves [yes, amazingly, urine therapy seems to have plenty of followers]; consequently, lives are put at risk whenever someone starts truly believing the bogus, irresponsible claims that are being made.
I do apologise for the rudeness of my words but I really do think THEY ARE TAKING THE PISS!
In my last post, we discussed the “A+B versus B” trial design as a tool to produce false positive results. This method is currently very popular in alternative medicine, yet it is by no means the only approach that can mislead us. Today, let’s look at other popular options with a view of protecting us against trialists who naively or willfully might fool us.
The crucial flaw of the “A+B versus B” design is that it fails to account for non-specific effects. If the patients in the experimental group experience better outcomes than the control group, this difference could well be due to effects that are unrelated to the experimental treatment. There are, of course, several further ways to ignore non-specific effects in clinical research. The simplest option is to include no control group at all. Homeopaths, for instance, are very proud of studies which show that ~70% of their patients experience benefit after taking their remedies. This type of result tends to impress journalists, politicians and other people who fail to realise that such a result might be due to a host of factors, e.g. the placebo-effect, the natural history of the disease, regression towards the mean or treatments which patients self-administered while taking the homeopathic remedies. It is therefore misleading to make causal inferences from such data.
Another easy method to generate false positive results is to omit blinding. The purpose of blinding the patient, the therapist and the evaluator of the outcomes in clinical trials is to make sure that expectation is not the cause of or contributor to the outcome. They say that expectation can move mountains; this might be an exaggeration, but it can certainly influence the result of a clinical trial. Patients who hope for a cure regularly do get better even if the therapy they receive is useless, and therapists as well as evaluators of the outcomes tend to view the results through rose-tinted spectacles, if they have preconceived ideas about the experimental treatment. Similarly, the parents of a child or the owners of an animal can transfer their expectations, and this is one of several reasons why it is incorrect to claim that children and animals are immune to placebo-effects.
Failure to randomise is another source of bias which can make an ineffective therapy look like an effective one when tested in a clinical trial. If we allow patients or trialists to select or choose which patients receive the experimental and which get the control-treatment, it is likely that the two groups differ in a number of variables. Some of these variables might, in turn, impact on the outcome. If, for instance, doctors allocate their patients to the experimental and control groups, they might select those who will respond to the former and those who don’t to the latter. This may not happen with malicious intent but through intuition or instinct: responsible health care professionals want those patients who, in their experience, have the best chances to benefit from a given treatment to receive that treatment. Only randomisation can, when done properly, make sure we are comparing comparable groups of patients, and non-randomisation is likely to produce misleading findings.
While these options for producing false positives are all too obvious, the next possibility is slightly more intriguing. It refers to studies which do not test whether an experimental treatment is superior to another one (often called superiority trials), but to investigations attempting to assess whether it is equivalent to a therapy that is generally accepted to be effective. The idea is that, if both treatments produce the same or similarly positive results, both must be effective. For instance, such a study might compare the effects of acupuncture to a common pain-killer. Such trials are aptly called non-superiority or equivalence trials, and they offer a wide range of possibilities for misleading us. If, for example, such a trial has not enough patients, it might show no difference where, in fact, there is one. Let’s consider a deliberately silly example: someone comes up with the idea to compare antibiotics to acupuncture as treatments of bacterial pneumonia in elderly patients. The researchers recruit 10 patients for each group, and the results reveal that, in one group, 2 patients died, while, in the other, the number was 3. The statistical tests show that the difference of just one patient is not statistically significant, and the authors therefore conclude that acupuncture is just as good for bacterial infections as antibiotics.
Even trickier is the option to under-dose the treatment given to the control group in an equivalence trial. In our hypothetical example, the investigators might subsequently recruit hundreds of patients in an attempt to overcome the criticism of their first study; they then decide to administer a sub-therapeutic dose of the antibiotic in the control group. The results would then apparently confirm the researchers’ initial finding, namely that acupuncture is as good as the antibiotic for pneumonia. Acupuncturists might then claim that their treatment has been proven in a very large randomised clinical trial to be effective for treating this condition, and people who do not happen to know the correct dose of the antibiotic could easily be fooled into believing them.
Obviously, the results would be more impressive, if the control group in an equivalence trial received a therapy which is not just ineffective but actually harmful. In such a scenario, the most useless or even slightly detrimental treatment would appear to be effective simply because it is equivalent to or less harmful than the comparator.
A variation of this theme is the plethora of controlled clinical trials which compare one unproven therapy to another unproven treatment. Perdicatbly, the results indicate that there is no difference in the clinical outcome experienced by the patients in the two groups. Enthusiastic researchers then tend to conclude that this proves both treatments to be equally effective.
Another option for creating misleadingly positive findings is to cherry-pick the results. Most trails have many outcome measures; for instance, a study of acupuncture for pain-control might quantify pain in half a dozen different ways, it might also measure the length of the treatment until pain has subsided, the amount of medication the patients took in addition to receiving acupuncture, the days off work because of pain, the partner’s impression of the patient’s health status, the quality of life of the patient, the frequency of sleep being disrupted by pain etc. If the researchers then evaluate all the results, they are likely to find that one or two of them have changed in the direction they wanted. This can well be a chance finding: with the typical statistical tests, one in 20 outcome measures would produce a significant result purely by chance. In order to mislead us, the researchers only need to “forget” about all the negative results and focus their publication on the ones which by chance have come out as they had hoped.
One fail-proof method for misleading the public is to draw conclusions which are not supported by the data. Imagine you have generated squarely negative data with a trial of homeopathy. As an enthusiast of homeopathy, you are far from happy with your own findings; in addition you might have a sponsor who puts pressure on you. What can you do? The solution is simple: you only need to highlight at least one positive message in the published article. In the case of homeopathy, you could, for instance, make a major issue about the fact that the treatment was remarkably safe and cheap: not a single patient died, most were very pleased with the treatment which was not even very expensive.
And finally, there is always the possibility of overt cheating. Researchers are only human and are thus not immune to temptation. They may have conflicts of interest or may know that positive results are much easier to publish than negative ones. Certainly they want to publish their work – “publish or perish”! So, faced with disappointing results of a study, they might decide to prettify them or even invent new ones which are more pleasing to them, their peers, or their sponsors.
Am I claiming that this sort of thing only happens in alternative medicine? No! Obviously, the way to minimise the risk of such misconduct is to train researchers properly and make sure they are able to think critically. Am I suggesting that investigators of alternative medicine are often not well-trained and almost always uncritical? Yes.
How do you fancy playing a little game? Close your eyes, relax, take a minute or two and imagine the newspaper headlines which new medical discoveries might make within the next 100 years or so. I know, this is a slightly silly and far from serious game but, I promise, it’s quite good fun.
Personally, I see the following headlines emerging in front of my eyes:
VACCINATION AGAINST AIDS READY FOR ROUTINE USE
IDENTIFICATION OF THE CAUSE OF DEMENTIA LEADS TO FIRST EFFECTIVE CURE
GENE-THERAPY BEGINS TO SAVE LIVES IN EVERY DAY PRACTICE
CANCER, A NON-FATAL DISEASE
HEALTHY AGEING BECOMES REALITY
Yes, I know this is nothing but naïve conjecture mixed with wishful thinking, and there is hardly anything truly surprising in my list.
But, hold on, is it not remarkable that I visualise considerable advances in conventional healthcare but no similarly spectacular headlines relating to alternative medicine? After all, alternative medicine is my area of expertise. Why do I not see the following announcements?
YET ANOTHER HOMEOPATH WINS THE NOBEL PRIZE
CHIROPRACTIC SUBLUXATION CONFIRMED AS THE SOLE CAUSE OF MANY DISEASES
CHRONICALLY ILL PATIENTS CAN RELY ON BACH FLOWER REMEDIES
CHINESE HERBS CURE PROSTATE CANCER
ACUPUNCTURE MAKES PAIN-KILLERS OBSOLETE
ROYAL DETOX-TINCTURE PROLONGS LIFE
CRANIOSACRAL THERAPY PROVEN EFFECTIVE FOR CEREBRAL PALSY
IRIDOLOGY, A VALID DIAGNOSTIC TEST
How can I be so confident that such headlines about alternative medicine will not, one day, become reality?
Simple: because I only need to study the past and realise which breakthroughs have occurred within the previous 100 years. Mainstream scientists and doctors have discovers insulin-therapy that turned diabetes from a death sentence into a chronic disease, they have developed antibiotics which saved millions of lives, they have manufactured vaccinations for deadly infections, they have invented diagnostic techniques that made early treatment of many life-threatening conditions possible etc, etc, etc.
None of the many landmarks in the history of medicine has ever been in the realm of alternative medicine.
What about herbal medicine? Some might ask. Aspirin, vincristine, taxol and other drugs originated from the plant kingdom, and I am sure there will be similar such success-stories in the future.
But were these truly developments driven by traditional herbalists? No! They were discoveries entirely based on systematic research and rigorous science.
Progress in healthcare will not come from clinging to a dogma, nor from adhering to yesterday’s implausibilites, nor from claiming that clinical experience is more important than scientific research.
I am not saying, of course, that all of alternative medicine is useless. I am saying, however, that it is time to get realistic about what alternative treatments can do and what it cannot achieve. They will not save many lives, for instance; an alternative cure for anything is a contradiction in terms. The strength of some alternative therapies lies in palliative and supportive care and not in changing the natural history of diseases.
Yet proponents of alternative medicine tend to ignore this all too obvious fact and go way beyond the line that divides responsible from irresponsible behaviour. The result is a plethora of bogus claims – and this is clearly not right. It raises false hopes which, in a nutshell, are always unethical and often cruel.
What is and what isn’t evidence, and why is the distinction important?
In the area of alternative medicine, we tend to engage in sheer endless discussions around the subject of evidence; the relatively few comments on this new blog already confirm this impression. Many practitioners claim that their very own clinical experience is at least as important and generalizable as scientific evidence. It is therefore relevant to analyse in a little more detail some of the issues related to evidence as they apply to the efficacy of alternative therapies.
To prevent the debate from instantly deteriorating into a dispute about the value of this or that specific treatment, I will abstain from mentioning any alternative therapy by name and urge all commentators to do the same. The discussion on this post should not be about the value of homeopathy or any other alternative treatment; it is about more fundamental issues which, in my view, often get confused in the usually heated arguments for or against a specific alternative treatment.
My aim here is to outline the issues more fully than would be possible in the comments section of this blog. Readers and commentators can subsequently be referred to this post whenever appropriate. My hope is that, in this way, we might avoid repeating the same arguments ad nauseam.
Clinical experience is notoriously unreliable
Clinicians often feel quite strongly that their daily experience holds important information about the efficacy of their interventions. In this assumption, alternative practitioners are usually entirely united with healthcare professionals working in conventional medicine.
When their patients get better, they assume this to be the result of their treatment, especially if the experience is repeated over and over again. As an ex-clinician, I do sympathise with this notion which might even prevent practitioners from losing faith in their own work. But is the assumption really correct?
The short answer is NO. Two events [the treatment and the improvement] that follow each other in time are not necessarily causally related; we all know that, of course. So, we ought to consider alternative explanations for a patient’s improvement after therapy.
Even the most superficial scan of the possibilities discloses several options: the natural history of the condition, regression towards the mean, the placebo-effect, concomitant treatments, social desirability to name but a few. These and other phenomena can contribute to or determine the clinical outcome such that inefficacious treatments appear to be efficacious.
What follows is simple, undeniable and plausible for scientists, yet intensely counter-intuitive for clinicians: the prescribed treatment is only one of many influences on the clinical outcome. Thus even the most impressive clinical experience of the perceived efficacy of a treatment can be totally misleading. In fact, experience might just reflect the fact that we repeat the same mistake over and over again. Put differently, the plural of anecdote is anecdotes, not evidence!
Clinicians tend to get quite miffed when anyone tries to explain to them how multifactorial the situation really is and how little their much-treasured experience tells us about therapeutic efficacy. Here are seven of the counter-arguments I hear most frequently:
1) The improvement was so direct and prompt that it was obviously caused by my treatment [this notion is not very convincing; placebo-effects can be just as prompt and direct].
2) I have seen it so many times that it cannot be a coincidence [some clinicians are very caring, charismatic, and empathetic; they will thus regularly generate powerful placebo-responses, even when using placebos].
3) A study with several thousand patients shows that 75% of them improved with my treatment [such response rates are not uncommon, even for ineffective treatments, if patient-expectation was high].
4) Surely chronic conditions don’t suddenly get better; my treatment therefore cannot be a placebo [this is incorrect, eventually many chronic conditions improve, if only temporarily].
5) I had a patient with a serious condition, e.g. cancer, who received my treatment and was cured [if one investigates such cases, one often finds that the patient also took a conventional treatment; or, in rare instances, even cancer-patients show spontaneous remissions].
6) I have tried the treatment myself and had a positive outcome [clinicians are not immune to the multifactorial nature of the perceived clinical response].
7) Even children and animals respond very well to my treatment, surely they are not prone to placebo-effects [animals can be conditioned to respond; and then there is, of course, the natural history of the disease].
Is all this to say that clinical experience is useless? Clearly not! I am merely pointing out that, when it comes to therapeutic efficacy, clinical experience is no replacement for evidence. It is invaluable for a lot of other things, but it can at best provide a hint and never a proof of efficacy.
What then is reliable evidence?
As the clinical outcomes after treatments always have many determinants, we need a different approach for verifying therapeutic efficacy. Essentially, we need to know what would have happened, if our patients had not received the treatment in question.
The multifactorial nature of any clinical response requires controlling for all the factors that might determine the outcome other than the treatment per se. Ideally, we would need to create a situation or an experiment where two groups of patients are exposed to the full range of factors, and the only difference is that one group does receive the treatment, while the other one does not. And this is precisely the model of a controlled clinical trial.
Such studies are designed to minimise all possible sources of bias and confounding. By definition, they have a control group which means that we can, at the end of the treatment period, compare the effects of the treatment in question with those of another intervention, a placebo or no treatment at all.
Many different variations of the controlled trial exist so that the exact design can be adapted to the requirements of the particular treatment and the specific research question at hand. The over-riding principle is, however, always the same: we want to make sure that we can reliably determine whether or not the treatment was the cause of the clinical outcome.
Causality is the key in all of this; and here lies the crucial difference between clinical experience and scientific evidence. What clinician witness in their routine practice can have a myriad of causes; what scientists observe in a well-designed efficacy trial is, in all likelihood, caused by the treatment. The latter is evidence, while the former is not.
Don’t get me wrong; clinical trials are not perfect. They can have many flaws and have rightly been criticised for a myriad of inherent limitations. But it is important to realise that, despite all their short-commings, they are far superior than any other method for determining the efficacy of medical interventions.
There are lots of reasons why a trial can generate an incorrect, i.e. a false positive or a false negative result. We therefore should avoid relying on the findings of a single study. Independent replications are usually required before we can be reasonably sure.
Unfortunately, the findings of these replications do not always confirm the results of the previous study. Whenever we are faced with conflicting results, it is tempting to cherry-pick those studies which seem to confirm our prior belief – tempting but very wrong. In order to arrive at the most reliable conclusion about the efficacy of any treatment, we need to consider the totality of the reliable evidence. This goal is best achieved by conducting a systematic review.
In a systematic review, we assess the quality and quantity of the available evidence, try to synthesise the findings and arrive at an overall verdict about the efficacy of the treatment in question. Technically speaking, this process minimises selection and random biases. Systematic reviews and meta-analyses [these are systematic reviews that pool the data of individual studies] therefore constitute, according to a consensus of most experts, the best available evidence for or against the efficacy of any treatment.
Why is evidence important?
In a way, this question has already been answered: only with reliable evidence can we tell with any degree of certainty that it was the treatment per se – and not any of the other factors mentioned above – that caused the clinical outcome we observe in routine practice. Only if we have such evidence can we be sure about cause and effect. And only then can we make sure that patients receive the best possible treatments currently available.
There are, of course, those who say that causality does not matter all that much. What is important, they claim, is to help the patient, and if it was a placebo-effect that did the trick, who cares? However, I know of many reasons why this attitude is deeply misguided. To mention just one: we probably all might agree that the placebo-effect can benefit many patients, yet it would be a fallacy to assume that we need a placebo treatment to generate a placebo-response.
If a clinician administers an efficacious therapy [one that generates benefit beyond placebo] with compassion, time, empathy and understanding, she will generate a placebo-response PLUS a response to the therapy administered. In this case, the patient benefits twice. It follows that, merely administering a placebo is less than optimal; in fact it usually means cheating the patient of the effect of an efficacious therapy.
The frequently voiced counter-argument is that there are many patients who are ill without an exact diagnosis and who therefore cannot receive a specific treatment. This may be true, but even those patients’ symptoms can usually be alleviated with efficacious symptomatic therapy, and I fail to see how the administration of an ineffective treatment might be preferable to using an effective symptomatic therapy.
We all agree that helping the patient is the most important task of a clinician. This task is best achieved by maximising the non-specific effects [e.g. placebo], while also making sure that the patient benefits from the specific effects of what medicine has to offer. If that is our goal in clinical practice, we need reliable evidence and experience. Therefore one cannot be a substitute for the other, and scientific evidence is an essential precondition for good medicine.
Guest Post by Louise Lubetkin
A study published last week in the New England Journal of Medicine (NEJM) has brought to light some stark differences in the way that physicians and their patients see the role of chemotherapy in the management of advanced (i.e., metastatic) cancer.
Physicians who treat patients with advanced cancer know only too well that while chemotherapy can sometimes be helpful in easing symptoms, and may temporarily slow tumor growth, it cannot reverse or permanently cure the disease. In other words, when chemotherapy is given to patients with advanced cancer it is always given with palliative rather than curative intent. However, this is a distinction that a sizeable majority of cancer patients apparently do not fully understand.
In the NEJM-study, which involved 1193 patients with advanced lung or colorectal cancer, only 20-30 percent of patients reported understanding that chemotherapy was not at all likely to cure their cancer. The remainder, a full 81 percent of patients with colorectal cancer and 69 percent of patients with lung cancer, continued to believe, even when told otherwise, that chemotherapy did indeed offer them a significant chance of cure.
The study raises important questions concerning possible lack of informed consent: would patients still accept chemotherapy if they knew that it stood no chance of curing them? The authors cite a study which revealed that patients – especially younger patients – would opt for chemotherapy if it offered even a 1 percent chance of cure, but would be considerably less willing to accept the same treatment if it offered only a significant increase in life expectancy. In the light of this, the authors write, “…an argument can be made that patients without a sustained understanding that chemotherapy cannot cure their cancer have not met the standard for true ongoing informed consent to their treatment.”
Because of the searching nature of the questions raised by the NEJM-study, and its potential ethical ramifications, it seems destined to be picked up by advocates of alternative medicine and used as a cudgel against standard medicine. To promoters of alt med, oncology represents a cynical institutionalized conspiracy to obstruct the use of purported “natural” cures, and chemotherapy is simply a license to poison patients in pursuit of profit. Take, for example this fevered headline and article from the Natural News website : “Chemo ‘benefits’ wildly over-hyped by oncologists; cancer patients actually believe they will be ‘cured’ by poison.”
“…chemotherapy is nothing but a sham “treatment” that puts cancer patients through needless pain and suffering while making the cancer industry rich,” continues the Natural News article.
“And perhaps the most disturbing part about this now-normalized form of medical quackery is that oncologists typically fail to disclose to their patients the fact that chemotherapy does not even cure cancer, which gives them false hope.”
(Which incidentally is pretty rich, coming from a website which carries, on the same page as this article, an ad which reads “How to CURE almost any cancer at home for $5.15 a day.”)
In fact, as more than one study has previously demonstrated, the majority of oncologists do indeed try their best to convey the incurable nature of metastatic cancer, and do mention the limited aims of chemotherapy in this setting. However, patients themselves are not always psychologically receptive, and are not always immediately able to confront the bleak truth. Neither, understandably, are physicians always eager to dwell on the negative aspects of the situation during “bad news” consultations. While two thirds of doctors tell patients at their initial visit that they have an incurable disease, only about a third explicitly state the prognosis. And even when prognosis is explained, more than one third of patients simply refuse to believe that treatment is unable to cure them (see Smith TJ, Dow LA, Virago EA, et al., here).
Moreover, patients’ initial reaction to the news that their cancer has recurred, or has metastasized, is typically “What can be done?” rather than “When will I die?” Similarly, physicians – who, contrary to the calumnies of alt med conspiracy-mongers, are just as human as the rest of us, and just as averse to being the bearer of awful news – are apt quickly to follow their patients’ lead away from the hopelessness and finality of the situation and towards a practical discussion of treatment options, a realm in which they feel far more at home.
Significantly, the NEJM-study found that the very physicians who most explicitly drummed home the message that chemotherapy would not cure advanced cancer were consistently given the lowest marks for empathy and communication skills by their patients. Conversely, those physicians who projected a more optimistic view of chemotherapy were perceived as better communicators.
“In an era of greater measurement and accountability in health care,” the study concludes, “we need to recognize that oncologists who communicate honestly with their patients, a marker of high quality of care, may be at risk for lower patient ratings.”
In an accompanying NEJM editorial titled “Talking with Patients about Dying” (unfortunately it’s behind a paywall but you can read a summary here), Thomas J. Smith, MD, and Dan L. Longo, MD, provide a trenchant commentary on this important subject.
“Chemotherapy near the end of life is still common, does not improve survival, and is one preventable reason why 25 percent of all Medicare funds are spent in the last year of life. Patients need truthful information in order to make good choices. If patients are offered truthful information – repeatedly – on what is going to happen to them, they can choose wisely. Most people want to live as long as they can, with a good quality of life, and then transition to a peaceful death outside the hospital. We have the tools to help patients make these difficult decisions. We just need the gumption and incentives to use them.”
As these uncompromisingly candid editorialists point out, chemotherapy is a crude and ineffective treatment for advanced cancer. But to claim, as do many proponents of alternative approaches to cancer, that palliative chemotherapy represents a highly lucrative business built on the deliberate deception of dying patients, is a clear-cut case of the pot calling the kettle black.
When advocates of alternative cancer therapies have subjected their own highly profitable nostrums to the same kind of scientific scrutiny and honest, unsparing self-criticism as the NEJM researchers and editorialists, and when they produce evidence that their remedies and regimens, their coffee enemas and latter-day reincarnations of laetrile offer greater efficacy, whether palliative or curative, than chemotherapy, then, and only then, will they will have earned the right to criticize rational medicine for its shortcomings.
Guest post by Louise Lubetkin
A few months ago The Economist ran one of its Where Do You Stand? polls asking readers whether alternative medicine should be taught in medical schools:
In Britain and Australia, horrified scientists are fighting hard against the teaching of alternative therapies in publicly funded universities and against their provision in mainstream medical care. They have had most success in Britain. Some universities have been shamed into ending alternative courses. The number of homeopathic hospitals in Britain is dwindling. In 2005 the Lancet, a leading medical journal, declared “the end of homeopathy”. In 2010 a parliamentary science committee advised that “the government should not endorse the use of placebo treatments including homeopathy.” So, should alternative medicine be treated on a par with the traditional sort and taught in medical schools?
It may surprise you to discover that more than two thirds of the almost 43,000 respondents were of the opinion that yes, it should.
Given that the use of alternative therapies is now so widespread, a plausible case can be made for giving medical students a comprehensive overview of the field as part of their training. But that’s not at all what the poll asked. Here again is how it was worded:
So, should alternative medicine be treated on a par with the traditional sort and taught in medical schools? (emphasis added)
That such a hefty majority of those who responded – and Economist readers are generally affluent and well-educated – came out firmly in favour not just of the teaching of alternative medicine but explicitly of parity between it and standard medicine, is both a reflection of the seemingly unstoppable popularity of alternative medicine and also, in a wider sense, of just how respectable it has become to be indifferent to, or even overtly hostile towards science.
It is ironic that since its very first issue in 1843 The Economist has proudly displayed on its contents page a mission statement declaring that the magazine is engaged in “a severe contest between intelligence, which presses forward, and an unworthy, timid ignorance obstructing our progress.”
It would seem that a significant sample of its poll-answering readership has a somewhat distorted vision of the struggle between intelligence and ignorance. In this postmodern worldview truth is relative: science is simply one version of reality; anti-science is another – and the two carry equal weight.
The very term “alternative medicine” – I use that expression with the greatest reluctance – is itself an outgrowth of this phenomenon, implying as it does that there are two valid, indeed interchangeable, choices in the sphere of medicine, a mainstream version and a parallel and equally effective alternative approach. That the term “alternative medicine” has now so seamlessly entered our language is a measure of how pervasive this form of relativism has become.
In fact, alternative medicine and mainstream medicine are absolutely not equivalent, nor are they by any means interchangeable, and to speak about them the way one might when debating whether to take the bus or the subway to work – both will get you there reliably – constitutes an assault on truth.
How did alternative medicine, so very little of which has ever been conclusively shown to be of even marginal benefit, achieve this astounding degree of acceptance?
Certainly the pervasive and deeply unhealthy influence of the pharmaceutical industry over the practice of medicine has done much to erode public confidence in the integrity of the medical profession. Alternative medicine has nimbly stepped into the breach, successfully casting itself as an Everyman’s egalitarian version of medicine with a gentle-sounding therapeutic philosophy based not on pharmaceuticals with their inevitable side effects, but on helping the body to heal itself with the assistance of “natural” and freely available remedies.
This image of alternative medicine as a humble David bravely facing down the medico-pharmaceutical establishment’s bullying Goliath does not, however, stand up well to scrutiny. Alternative medicine is without question a hugely lucrative enterprise. Moreover, unlike the pharmaceutical industry or mainstream medicine, it is almost entirely unregulated.
According to the US National Institutes of Health, in 2007 Americans spent almost $40 billion out of their own pockets (i.e., not reimbursed by health insurance) on alternative medicine, almost $12 billion of which was spent on an estimated 350 million visits to various practitioners (chiropractors, naturopaths, massage therapists, etc.) The remaining $28 billion was spent on non-vitamin “natural” products for self-care such as fish oils, plant extracts, glucosamine and chondroitin, etc. And that’s not all: on top of this, sales of vitamin and nutritional supplements have been estimated to constitute a further $30 billion annually.
And then, of course, there’s the awkward fact of its almost total lack of effectiveness.
Look at it this way: illness is the loneliest and most isolating of all journeys. In that bleak landscape, scientifically validated medicine is not just the best compass and the most reliable map; it’s also the truest friend any of us can have.
So, should alternative medicine be treated on a par with the traditional sort and taught in medical schools?
Not on your life.