BLOWS AGAINST THE EMPIRE….? By Lionel Milgrom 

3rd April 2012

Introduction

Evidence Based Medicine (EBM) and its ‘Grand Inquisitor’, the Randomised Controlled Trial (RCT) are some squeaky clean gold standard by which any therapeutic modality can be scientifically judged. Those who believe EBM and RCTs are fit for purpose, demonstrate little or no understanding of the shortcomings embedded in their empirical, rationalist approach to human relationships (particularly the therapeutic relationship). For buried at the heart of the RCT is a fundamental mathematical error: trying to represent with numbers the processes which make up the stages of an RCT.

Consequently, this article sets out to support those who reject EBM and the RCT as the sole arbiters of clinical ‘truth’, and to fire a shot across the bows of those in therapeutic communities who, while accepting EBM and the RCT, purport to lead them.

Implicit assumptions

So, the RCT is predicated on the following implicit assumptions:-1

A. The healing process is a purely additive linear combination (i.e., there are no complicating non-linear contextual interactions) of:

1. The natural course of the disease;

2. The non-specific contextual effect of the consultation (treated as linear);

3. The specific effect of the treatment.

B. As a placebo is supposed to have no specific effect, then effects seen in a placebo arm of a trial are due to the purely additive linear combination of:-

1. The natural course of the disease

2. The consultation.

Ergo, to get a ‘result’ from the numbers generated by these processes, one simply subtracts B from A, i.e., A – B = (1 + 2 + 3) – (1 + 2) = 3. By this ever-so-simple arithmetic process (preceded by reducing the processes of the RCT to numbers, it should be remembered, so they can be treated in a linear fashion), one arrives at the ‘answer’, which is the specific effect of the treatment, i.e., 3.

The point is, the RCT imposes an artificial linear isolation of treatment from context that in real life simply doesn’t exist. This is why drugs in trials never seem to perform as ‘well’ as they do (‘side-effects’ aside) in real life. The classic example is Prozac which RCTs show is no better than placebo, yet has managed to earn a global pharmaceutical giant over $4 billion in profits…..nice work if you can get it…..But there’s more…..

Numbers commute; processes don’t

You don’t have to be a mathematical genius to understand the fundamental difference between numbers and processes. Numbers can be added or multiplied together in any order you like, and you will end up with the same result. Thus 3 + 4 = 7, and so does 4 + 3 = 7. In mathematical language, numbers are said to commute.

Processes on the other hand cannot be added or multiplied together in any order. You only have to think about the operations involved in, say, cooking to realise that it very much does matter how and in what order the operations are performed; whether you end up with cordon bleu or an inedible mess. In other words, and using the language of maths again, processes do NOT commute.

Consequently, the fundamental (but implicit) assumption of the RCT, as shown above, is to treat the data derived from a series of processes as if they are commutable numbers. And the rational for doing this is the imposition of an artificial linear isolation of treatment from the context in which that treatment is performed. Without that assumption, the RCT is seen for what it is – a vast over-simplification that now even the drug companies are not averse to fiddling in order to convince mainly their shareholders but Joe Public as well, that their drugs are somehow pukka.

Knocking EBM and the RCT off their perch

Now, this empirical approach (aka the scientific method) works fine when one is dealing with things mechanical, like washing machines, rockets, ballistics, even to some extent sub-atomic particles, etc, but when it comes to the awfully fuzzy (if you’re an empirical scientist) interactions between human beings it breaks down.

And you don’t have to be a homeopath or a CAM practitioner to realize that. Even those in the field of conventional medicine have noticed something odd. Indeed, the main objections to willy-nilly imposition of the RCT methodology (now the centre-piece of Evidence-Based Medicine – aka EBM) has come from lone but significant voices within the orthodox medical community – Sir Michael Rawlins of NICE, for example, “Their (RCTs) appearance at the top of hierarchies of evidence is inappropriate, and hierarchies are illusory tools for assessing evidence. They should be replaced by a diversity of approaches that involve analysing the totality of the evidence base.”2 He goes on to suggest observational studies might be a good approach, something homeopaths have already pioneered (the large Bristol study in the UK, for example).3

Then there’s the ridicule heaped on RCTs and EBM by philosophers (unfortunately, not from the UK) for its ‘fascistic’ intolerance of pluralism in healthcare systems;4 this from Devisch in Holland, for example, “EBM’s strict distinction between admissible (based on RCTs) and other supposedly inadmissible evidence is not itself based on evidence, but rather on intuition…..Ultimately, to uphold this fundamental distinction, EBM must seek recourse in (bio)political ideology and an epistemology akin to faith.” 5

The sad truth is that the original founders of EBM never meant for it to become a reductionist ‘hammer’ to beat clinicians of any therapeutic persuasion over the head,6 but that is what it has become.7

So, for those practicing any therapeutic modality, even conventional medicine, to mindlessly bend the knee to EBM and RCTs as currently practiced is to be not just massively behind the curve as far as understanding their real significance is concerned, it is also by default, a dereliction of duty to their healing art. Ignorance no longer serves as an excuse. If therapeutic communities anywhere in the world (particularly in the UK) are being led by people such as these, then in my opinion, they are seriously undermining the future of their therapeutic modalities. Lions led by donkeys; lambs to the slaughter….

Down the rabbit hole….

But we have yet to scratch the surface of this problem….we are now going to descend into the rabbit (w)hole and see where it leads. You see, this isn’t just about homeopathy, CAM, conventional medicine, Edzard Ernst, Michael Baum, and David Colquhoun in the UK, James Randi in the US, or all the other trolls and pseudo-sceptics around the world who try to run homeopathy and CAM into the ground. This goes right to the very heart of what science is all about…..and to understand that, we need to consider one of the most fundamental central themes running through of all subjects, quantum theory: it’s called complementarity.

“Opposites are complementary”

Quantum theory and homeopathy or any therapeutic modality might seem strange bed fellows. Certainly, if you want to turn any sceptic or pseudo-sceptic into a seething mass of protoplasm, then simply mention quantum theory and homeopathy in the same breath! But the key to this connection is quantum theory’s notion of complementarity.

This principle was first enunciated by the Danish physicist Niels Bohr in 1928, and it goes something like this:-

• Depending on the experimental circumstances, the behavior of such phenomena as light and subatomic particles like electrons is sometimes wavelike and sometimes particle-like (i.e., light, subatomic particles, even atoms and whole molecules express wave-particle duality).8

• However, it is impossible to observe both the seemingly contradictory wave and particle aspects of such phenomena simultaneously….

• ….But together, they represent a fuller description of phenomena than either of the two taken alone: something Niels Bohr acknowledged by adopting the ying-yang symbol on his self-designed coat of arms, bearing the Latin inscription ‘‘Contraria sunt complementa’’ (opposites are complementary).9

Crucially, what this also means is that what we observe (be it particle or wave) is intimately dependent on the kind of experiment we do. In other words, the answer we get depends on how we ask the (experimental) question; and here’s the real nub of complementarity and quantum theory: Observer and observed are fundamentally and irrevocably connected—entangled if you like. There cannot be observation without an observer.

This is why one cannot even say the act of observation changes that which is observed: without an observer there is no observation in the first place. And it leads to one of the most startling conclusions to come out of quantum theory that leading quantum physicists from Max Planck onward (e.g., Henry Stapp)10 have proposed: Via consciousness, observation in part creates the universe. This is what Planck said, ”I regard consciousness as fundamental. I regard matter as derivative. We cannot get behind consciousness. Everything that we talk about, everything that we regard as existing, postulates consciousness.’’

Humpty-Dumpty sat on a wall….

Now, about eight years ago, Weatherley-Jones et al.11 suggested a similar complementary relationship might exist in the therapeutic process, between the specific and nonspecific effects of a treatment being non-additive (in other words, the whole is greater than the sum of the parts); this is something which I have tried to make more explicit elsewhere.12

You see, the thing is that most trials concentrate on the medicine and have only a vague idea about the consultation. Recently, however, in the UK Brien et al did a trial of homeopathy where they concentrated on the consultation.13 And do you know what happened? They lost sight of the remedy…..!

We’ve a long way to go yet before this can be enunciated as a general principle, but it could just be that Weatherley-Jones, myself,14 Harald Walach15 and others are right: the complementarity between sets of observables that Bohr first discovered via the quantum theory of physical particles, could also be operating when one tries taking the scientific ‘spanner’ to the therapeutic process. This is how it could work.

Thus, conventional RCTs with their concentration on the effect of the medicine/drug must necessarily lose sight of the consultation. What the Brien et al. trial could be suggesting is that RCTs that attempt to isolate the effect of the consultation must necessarily lose sight of the medicine: yet another reason perhaps why the RCT can no longer be regarded as a ‘‘gold standard.’’16 This would mean that just as in orthodox quantum theory, we can know fully about the medicine or the consultation as parts of a complementary pair of phenomena making up a whole, but we cannot know both with equal certainty at the same time: a kind of Heisenberg’s Uncertainty Principle for the therapeutic process. And this arises precisely because of the very nature of the process of observation in science.

Rest assured however; in the UK, sceptical scientists like Edzard Ernst, Michael Baum, David Colquhoun, and campaigning journalists such as Simon Singh, Ben Goldacre, and their whole ‘troll’ choir invisible are never likely get this because it strikes at the very heart of what they think being a ‘real’ scientist is. They will no doubt accuse us of hiding behind badly-understood quantum theory as a fig-leaf for our own ‘quackery’…..but I think it is vital that WE get this. The scientific method can only go so far before it crumbles to dust in our hands….and all the Kings horses and all the kings men, can’t put Humpty Dumpty together again. To see how, we need to take a closer look at the RCT.

Deconstructing the RCT

There are different types of RCT, e.g., placebo-controlled and pragmatic trials, and certain drugs like antibiotics and anti-inflammatories seem to do well in RCTs. So to fully appreciate the problem with the RCT, it is probably a good idea to have a look at some figures.

Thus, by end of 2010, 156 RCTs of homeopathy (on 75 different medical conditions) had been published in peer-reviewed journals of which :

• 41% had a balance of positive evidence:

• 7% had a balance of negative evidence:

• 52% were not conclusively positive or negative.17

A cursory glance at these statistics might cause one to think the ratio of positive to negative trials was clearly in homeopathy’s favour…. except when one takes into account the number of trials for which no conclusions either way can be drawn, i.e., >50%. When one then looks at similar stats for RCTs of conventional medicine, something odd appears.

So data obtained from an analysis of 1016 systematic reviews of RCTs of conventional medicine indicate that:

• 44% of the reviews concluded that the interventions studied were likely to be beneficial (positive),

• 7% concluded that the interventions were likely to be harmful (negative), and

• 49% reported that the evidence did not support either benefit or harm (non-conclusive).18

That a similar spread of statistics was obtained regardless of the therapeutic modality would suggest:-

a) Homeopathy fairs no better or worse in RCTs than conventional medicine: therefore rejecting homeopathy on the basis of RCT data is false and biased as many conventional drugs/procedures should similarly be rejected but aren’t;

b) There is something fundamentally wrong with the RCT (and those who claim it to be a ‘gold standard’), when around 50% of RCTs fail to deliver a clear result.

This has been highlighted by Dr Amy Abernathy from the Duke Centre for Evidence-based Practice in the US, who reviewed thousands of RCTs and concluded, “Because of the paucity of high quality evidence, the data available – though voluminous– may have little meaning or value for informing clinical practice.”19

On a more cynical note, in 2003 two UK clinicians Smith and Pell published in the BMJ a critique of RCTs and EBM entitled, “Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of RCTs.” Their conclusions, though somewhat tongue-in-cheek, are still damning. “As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation using RCTs. Advocates of EBM have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of EBM organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.”20 In other words, they should go take a run and jump….!

….And then there’s the cheating….

The ‘value’ of the RCT is further compromised when it is realised that large-scale cheating goes on in drug trials, especially when Big Pharma funds academic research. Thus a report in the influential science journal Nature concluded, “In the US around 1000 incidents of suspected fabrication, falsification, and plagiarism go unreported every year.” 21 In addition, the Committee on Publication Ethics in the UK estimates there are about 50 cases per year of serious fraud in biomedical research, and that academia has been trying to cover up this abuse of science. The magazine Prospect recently reported on the systemic abuse of science in medical and pharmacological research22 concluding, “We may have to wait for fresh scandals before anyone acts. Until then, patients will remain in real danger of taking expensive drugs whose risk of harm or inability to cure, have been fraudulently suppressed.”23 And finally, when interviewed the ex-editor of the New England Journal of Medicine, Marcia Angell pointed out, “It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgement of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as editor of The New England Journal of Medicine.” 24

Conclusions: the real danger

This is all very well and most certainly we should be pressing home these points about EBM and RCTs and making them count. But regardless of how impossible it is to put Humpty-Dumpty back together again, the real danger to homeopathy/CAM is the persistent (and sadly not robustly defended) attacks of the pseudo-sceptics. Their repeated effect over time could be to make people believe that homeopathy doesn’t work, even as we have seen, by those who were once users of homeopathy. In their slightly less inflammatory moments, sceptics and pseudo-sceptics portray us at best, as purveyors of the placebo effect. They are wielding something perhaps as equally powerful: the opposite nocebo effect.

We can bang on all we like about how amazing homeopathy is and how dastardly are the trolls, pseudo-sceptics, and the organisations that openly and secretly support them, but if the message doesn’t get through and is constantly drowned out by their nocebo negativity, then we lose the hearts and minds of the people who really matter: our patients; past, present, and future.

Worse, some therapeutic communities (e.g., homeopaths) seem more interested in scoring points off each other, than defending what they know to be true, right and just. If it continues like this, not by legislation but by negativity, homeopathy will surely die out in the UK, and the sceptics and pseudo-sceptics would have won.

“In the province of the mind, what one believes to be true either is true or becomes true within certain limits, to be found experientially and experimentally. These limits are beliefs to be transcended. In the province of the mind, there are no limits….” (John C Lilly, ‘The Centre of the Cyclone’)

“If I am not for myself, who will be for me? And when I am for myself, what am ‘I’?” And If not now, when?” (Hillel the Elder)

 

References

1. Weatherley-Jones E, et al. The placebo-controlled trial as a test of complementary and alternative medicine: Observations from research experience and individualised homeopathic treatment. Homeopathy 2004;93:186–189.

2. Rawlins M. De Testimonio: On the evidence for decisions about the use of therapeutic interventions. The Harveian Oration. Delivered to the Royal College of Physicians, London, October 16, 2008. Online document at: www.rcplondon.ac.uk-news-news.asp?PR_id¼422.

3. Spence DS, Thompson EA, Barron SJ, ‘Homeopathic Treatment for Chronic Disease: A 6-Year, University-Hospital Outpatient Observational Study’, Journal of Alternative and Complementary Medicine, 2005;11:793-798, p. 795.

4. Holmes D et al. Deconstructing the evidence-based discourse in health sciences: truth, power and fascism. Int J Evid Based Healthc 2006;4:180-186.

5. Devisch I, Murray SJ. ‘We hold these truths to be self-evident’: deconstructing ‘evidence-based’ medical practice. J Eval Clin Pract 2009;16:950-954.

6. Sackett, D.L. et al. (1996) Evidence based medicine: what it is and what it isn’t. British Medical Journal 312 (7023), 13 January, 71-72.

7. Leggett JR Medical scientism: good practice or fatal error. J R Soc Med 1997;90:97-101.

8. Rosenfeld L. Niels Bohr’s contribution to epistemology. Physics Today 1963;16:47–54.

9. Greiner W. Quantum Mechanics: An Introduction. New York: Springer, 2001.

10. Stapp H. Mindful Universe: Quantum Mechanics and the Participating Observer. The Frontiers Collection. Berlin, Heidelberg: Springer-Verlag, 2007.

11. Weatherley-Jones E, et al. The placebo-controlled trial as a test of complementary and alternative medicine: Observations from research experience of individualized homeopathic treatment. Homeopathy 2004;93:186–189.

12. Milgrom LR. Gold standards, golden calves, and random reproducibility: Why

homeopaths at last have something to smile about. J Altern Complement Med

2009;15:205–207.

13. Brien S, et al. Homeopathy has clinical benefits in rheumatoid arthritis patients

that are attributable to the consultation process but not the homeopathic remedy: A randomized controlled clinical trial. Rheumatology (Oxford) 2011;50:1070–1082.

14. Milgrom LR and Chatfield K. “It’s the Consultation, Stupid…” Isn’t It? J Altern

Complement Med. 2011;17(7):1-3.

15. Walach H. Generalised entanglement: A new theoretical model for understanding the effects of complementary and alternative medicine. J Altern Complement Med 2005;11:549–559.

16. Milgrom LR. Journeys in the country of the blind: Entanglement theory and the effects of blinding on trials of homeopathy and homeopathic provings. eCAM 2007;4:7.

17. The evidence for homeopathy, accessed from the website of the British Homeopathic Association, www.britishhomeopathic.org.

18. See reference 1 and El Dib RP, Atallah AN, Andriolo RB (2007). Mapping the Cochrane evidence for decision making in health care. Journal of Evaluation in Clinical Practice; 13:689–692.

19. Abernathy A. Draft systematic review of off-label use of oncology drugs. Duke EPC 07/11/2009.

20. Smith GCS and Pell JP. Hazardous Journey. Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of RCTs. BMJ 2003;327:1459-1451.

21. Titus SL et al., Nature 453, 980–982 (19 June 2008).

22. Fanelli D. How Many Scientists Fabricate and Falsify Research? A Systematic Review and Meta- Analysis of Survey Data. PLoS ONE 2009; 4(5): e5738.

23. Naish J. Faking it. Prospect August 2009, p63.

24. M. Angell. The New York Review of Books, Volume LV1, Number 1 January 15th 2009.