It has been classically acknowledged (Hill Br Med J
1963 ii 1043-1049) that it is only appropriate to use the randomized
trial in medical research when it is uncertain which of two treatments
being compared is the more efficacious, when there is a genuine 50-50
chance that either is as effective as the other. There are two issues
here. Firstly, how often is this condition met within orthodox medical
research? Secondly, is it a condition that can be met when you are
wanting to compare not simply two treatments within the same overall
medical paradigm, but two treatments each of which belongs to a
different medical paradigm? A positive answer to the second question at
least requires that the two different medical paradigms, for example
allopathy and homoeopathy, share the same criteria of effective
outcomes. But there are deeper moral problems.
The randomized trial is easiest to implement, and most
valid methodologically, when patient consent to enter the trial is not
sought. For then there is no loss of accrual to the trial by patient
dissent, no problem in recruiting sufficient doctors to participate, no
issue about disturbing patient confidence in the doctor-patient
relationship, and no interfering test variable arising from the
information-giving activities involved in seeking consent. Hence patient
consent in this country is often not sought, or is at best thought to be
"desirable but not obligatory" (Cancer Research Campaign Working Party
Br Med J 1983 286 1117-1121).
We consider that
patient consent is obligatory before entry into a randomized trial.
Respect for personal autonomy has priority over the claims of
statistical argument. And respect for patient autonomy entails that
practitioners honour the right of each patient to fully informed
self-determination in the selection of available treatments. Hence
prospective entrants to a trial should be told that participants in the
trial will have their treatments selected by a randomizing process, and
told what the alternative treatments involved in the trial are. The
patient can then either agree to randomized selection, or decide not to
enter the trial and request one of the treatments involved in it.
It is sometimes
argued that since doctors do not know which is the better of two or more
treatments in the trial, nothing material is withheld if patients
entering the trial are not told about the random selection of
treatments. But this rather shockingly assumes that it is only the
medical view about the status of the treatments in the trial that
counts. We consider that patients have an important right to exercise
their reasoning, hunches, preferences in relation to the treatments
being tested, even if this leads to the loss of accrual to the trial and
to the exercise of irrational preference (Cf Schafer N Eng J Med
1982 307 719-724). Often patients are not told about randomization
precisely because it is feared that they may opt for self-determination
in the selection of treatment; but such a practice of not telling makes
the researchers morally subversive of patient autonomy.
If you use
randomized trials to compare conventional with complementary therapies,
you are asking entrants to the trial to forgo the exercise of their
intelligent self-determination in the selection of available treatment
to a rather extreme degree. For you are not simply asking them to agree
to be randomly allocated to different treatments within the same medical
paradigm or overall medical philosophy; you are asking them to agree to
be randomly allocated to treatments within quite different medical
paradigms. It would seem educationally and medically immoral not to
explain fully to prospective entrants to the trial the difference
between the two paradigms; but the result of such explanation might be
massively to disrupt and skew accrual to the trial.
We acknowledge
that if patient consent to entry into a randomized trial is sought on
the basis of full information about the treatments to be tested and the
randomized selection of them, then this tends to be subversive of the
trial. If many prospective trial patients opt out, then accrual to the
trial is undermined and accrual can no longer claim to be random but is
biased in favour of those who opt in. Prospective participating doctors
may drop out at the thought of all the consent-seeking activities
involved and their possible effects on doctor-patient relationships.
Furthermore, all the information-giving and consent-seeking may
constitute a treatment and test variable that itself clouds the
experimental treatment effect. We think these subversive tendencies
should be accepted: the moral principle of patient autonomy has
precedence over the statistical rationale for the randomized trial. If
morality and methodology conflict, it seems to us that the onus is upon
us to develop methodologies that harmonies with our morality, rather
than compromise with morality on the probably false assumption that we
are dealing with an immaculate methodology.
We consider that
the randomized trial does have further limitations. Firstly,
randomization generates statistical information by trying to make
patients as homogeneous as possible, and this by controlling for all
sorts of "irrelevant" variables other than the one primary variable
being studied. But patients, of course, are highly heterogeneous: some
patients with certain personal characteristics may benefit from one kind
of treatment, and other patients with other sorts of characteristics may
benefit from another kind of treatment. But a randomized study of these
two treatments might show no statistically significant difference in
their efficacy. Thus randomization tends to "obscure, rather than
illuminate, interactive effects between treatments and personal
characteristics" (Weinstein N Eng J Med 1974 291 1278-1285). Now
the practical question is often what is the treatment of choice for this
individual and idiosyncratic patient. But the data derived from
randomized clinical trials cannot help with this question, since
randomization is designed to eliminate any effect from idiosyncratic
variables.
Secondly, just
as the patient's right to self-determination in the selection of
available treatments is an embarrassment for the randomized trial, so
too is the patient's potential as a consciously self-healing agent.
Biofeedback, autogenic training and related approaches indicate that
persons can exercise conscious self-regulation of physiological
states in ways that promote well-being. If some patients in a randomized
trial are privately exercising such self-regulation, then its effect
will simply be eliminated by the randomized design since it will fall
within the general class of "nuisance" variables. But if you set up a
randomized trial to test the relative efficacy of conscious
self-regulation as against some other kind of treatment, then you are in
a quandary indeed. On the one hand it is psychologically odd for a
patient to be randomly allocated to the practice of conscious
self-regulation since this is surely an activity whose effectiveness
depends in part upon its being freely chosen. On the other hand, it is
morally dubious, if you practice the seeking of informed consent, to ask
patients to agree to the possibility of being randomly allocated to a
treatment in which they are not to practise conscious
self-regulation, and this when there is already evidence that in some
other fields such self-regulation is efficacious. Would, and should, any
intelligent ill person agree not to attempt intentional self-healing?
And should any ill person ever be asked not to attempt such
mental self-help?
Thirdly, for all
the above reasons, and as long as the randomized trial is practised as
the central paradigm of medical research, it will tend to sustain and
breed a culture of patient alienation, in which patients are
conditioned to see their diseased bodies as cut off from the
exercise of self-determination and of intentional self-healing, and from
the influence of idiosyncratic personal characteristics.
Special
difficulties arise when considering the use of randomized trials in the
field of complementary medicine, at any rate with respect to their use
on patients (non-patients are a different case, see below).
Suppose you want to use a randomized trial to compare the effects
of a conventional form of treatment or of no treatment with some
complementary form of treatment. In the case of osteopathy and
acupuncture, you cannot do the trial blind, and the results will not
enable you to differentiate between the effects of the physical
osteopathic or acupuncture technique used and the effects of the
osteopath or acupuncturist qua person. You may say this does not
matter, and that you simply want to know whether the complementary sort
of treatment is better or not, however its outcomes are achieved. Yet
this seems less than satisfactory.
In the case of
homoeopathy and herbalism, you can certainly do the trial double blind
and thus claim to be getting at an independent physical effect, but if
the trial is done likethat of an allopathic drug, all the patients in
the experimental group would get the same homoeopathic or herbal remedy.
It could then be argued that this is no test of either homoeopathy or
herbalism. Indeed it has already been argued (Ives Br Hom J 1983
72 224-228) that a study by Shipley et al (Lancet Jan 15 1983
97-98) comparing Rhus Tox 6x with phenoprofen and
placebo in the treatment of arthritis "only poorly approximated to
normal homoeopathic practice, in that it would be unusual to treat a
chronic condition with only a single remedy in low potency" (Ives op.cit.).
For in homoeopathy especially, and to a lesser extent with
herbalism, the prescription for a chronic condition is tailored to the
idiosyncratic patient as a whole: with regard to patients with the same
disease, each may receive a significantly different series of
prescriptions. You could deal with this by having all entrants to a
trial undergo thorough homoeopathic history taking, then
randomize some into a placebo group and some into a group whose
members receive idiosyncratic individually tailored remedies. If the
trial is administered double blind, and the experimental group show a
significantly better outcome, then it is reasonable to infer there is a
homoeopathic effect that is due neither to elaborate history taking nor
to placebo; although no one homoeopathic drug in only one potency is
being tested. However, "in certain acute conditions the choice of remedy
may be sufficiently narrow, or the criteria for selecting a
remedy sufficiently obvious, for a double blind trial along traditional
lines to be feasible"
(Ives op.cit.).
We consider it
would be entirely improper to argue that the randomized trial has no
place in research into complementary medicine using groups of patients.
But we do consider it is a method which tends to contradict much of the
legitimate ethos of complementary medicine - its emphasis on
self-determination, self-help and self-healing, on treatment tailored to
the patient as idiosyncratic whole person. And it is a method which
within any kind of medicine is morally and medically problematic.
We think
therefore there is a strong case for considering the claims for using
non-randomized controls in research on complementary medicine. Such
selected controls may be historical controls, chosen from the
literature, from preceding trials, or matched from a previous study. Or
they may be selected from matching patients being treated concurrently.
The case for the use of selected, non-randomized controls in comparative
studies in cancer clinical trials in conventional medicine has already
been argued for (Gehan and Freireich N Eng J Med 1974 290
198-203). And other papers in the medical literature have pressed the
case (Weinstein N Eng J Med 1974 291 1278-1285; Dudley Br Med
J 1983 287 957-960). But where selected controls are patients being
treated concurrently, we do think their informed consent should be
sought. The most non-problematic use of non-randomized concurrent
controls from a moral point of view is where, for example, a
study compares treatment given to patients who are voluntarily attending
a conventional medical centre with treatment given to patients who are
voluntarily attending a complementary medical centre. We think that
researchers and statistician should work at legitimating such a study
rather than rule it out dogmatically on the grounds of
non-randomization.
The strength of
the randomized trial, especially if it is double blind, is that it is an
elegant way of demonstrating whether the treatment variable does have
a physical effect relatively independent of other variables
including psychosocial variables. And it is certainly reasonable to ask
whether homoeopathy and herbalism do have such an effect, however
important psychosocial variables in the treatment may also be. We think
there may well be a case for the use of randomized trials with
non-patients in order to test for relatively independent physical
effects of homoeopathic and herbal substances. The argument is as
follows.
The claim of
complementary therapies such as homoeopathy and herbalism, osteopathy
and acupuncture, is that they work on disease indirectly by means of a
catalytic effect on the body's self-regulatory functions, whereas
conventional treatments using drugs and surgery directly confront
diseased part or process seeking to eliminate it, restructure it, subdue
it, re-educate it or whatever. Hence homoeopathic and herbal remedies
may well show an effect on the physiological functions of non-patients,
and for some remedies that effect may be relatively independent of other
variables. Hence given suitable assessment techniques for regulatory
changes in physiological functions, with pre- and post- testing on a
randomized trial with non-patients, double-blind using a placebo control
group, such a relatively independent physical effect may be
demonstrated.
Such a trial is
ethically sound, since the participants are non-patients, provided their
consent is sought; and provided that it is reasonable to infer from all
available evidence that the remedies used in this context would have no
undesirable physical consequences or side-effects. If the trial were
successful it would certainly show that the remedies used in it had more
than a placebo effect on physiological functions in non-patients. It
would demonstrate a homoeopathic or herbal effect. But it would not
per se entail any practical consequences for treating
patients. And it would be false to assume that any general effect of a
given remedy on non-patients would detract from the importance of
particular, idiosyncratic prescribing for patients.
Randomized
trials on consenting non-patients can also be used to compare the
effects of attempts at conscious self-control on physiological processes
with the effects of doing nothing or doing something different. This
still suffers from the anomaly of randomly allocating a person to
practise conscious self-regulation - which is presumably most effective
when it is chosen out of a free commitment. On the other hand this
anomaly may be much less critical with a person who is well than with a
person who is ill.
An interesting
use of the double blind randomized trial is internal to the
belief-system of homoeopathy. It is in relation to the practice of
provings: non-patients take somewhat larger doses of a drug, note down
what disease elements it tends to produce in them, then the principle of
similia holds that patients who show similar disease elements will tend
to be cured by minute or potentised doses of the drug. In a trial on a
proving, some healthy persons would take moderate doses of a drug,
others would take a placebo, on a random double blind basis, in order to
see whether the "disease elements" produced by the drug are independent
of a placebo effect (see Clover et al Br Hom J 1980 69 134-149).
This inquiry is problematic: the sort of full explanation involved in
seeking informed consent for entry into the trial may well on its own
induce a placebo effect. Again those already committed to homoeopathy
are most likely to assent to enter the trial, and this prior commitment
may again induce a placebo effect by itself. If you push the dos of the
drug up high enough to transcend placebo effects demonstrated on earlier
trials with lower doses, then you start to need heroic and highly
committed entrants to the experiment who are willing to undergo
possibly very unpleasant physical and mental discomfort.
Finally,
randomized trials could be used with animal subjects in the laboratory
and in veterinary practice, to test for a homoeopathic, herbal or
acupuncture effect as against no treatment or conventional treatment.
The complementary therapies used will not, it is reasonable to suppose,
do any harm to the animals; there are no ethical problems to do with
self-determination and informed consent of the subjects (although the
consent of their owners is another matter). And while extrapolation from
animal studies to human beings remains problematic, at least a
determinate effect will or will not be demonstrated.