Research ethics and trials on unconscious patients

By Guest Author 19/05/2014

Prof Grant Gillett from the University of Otago’s Bioethics Centre explores the issue of informed consent in medical research in the wake of media coverage of a planned clinical trial involving unconscious patients.

Prof Grant Gillett

ICU research ethics and trials on unconscious patients

In intensive care there are standard practices which, as is the case throughout medicine, either outstrip the best evidence for their efficacy in the conditions they are used for or are being constantly improved to increase their safety and/or efficacy. ICU specialists are activists (and therefore, in one important respect, like surgeons) and experimentalists because they deal with a constantly evolving range of conditions that have been shifted from the category of fatal to the category of seriously life threatening or potentially rescue-able. ICU also requires rapid definitive intervention often under extreme time pressure and despite considerable uncertainties about the clinical situation or the best way to treat it. Therefore it is not surprising that many of our treatments, as in crisis medicine in general and in surgery, are based on current theories about the human body and its workings and things which have been found to work in some cases but not definitely proven as effective and safe interventions. In ICU we have near total control over what goes on in the body, we have drugs to manipulate bodily physiology, we regulate breathing patterns, we induce unconsciousness, and so on. We are working by guesswork as much as and no more than in any other complex area of science but the complexities of holistic human function can sometimes confound the “knowledge” that our theories endorse, (as we see in the case of alternative healing methods and things like the placebo effect).

Two examples help to make the point.

It is reasonable to believe that because blood carries oxygen and nutrients around the body and nature has designed the human blood system to work with a certain level of haemoglobin (Hb – the oxygen carrying protein) then maintaining a level close to that would provide optimal conditions for healing and recovery from major trauma or illness. Not so. An important study found that patients maintained at a haemoglobin level of 10-12 g/l (close to the normal values of 12-18 g/l) did worse than those who were only transfused when they dropped below 7g/l.

It is plausible that patients who have cardiac arrhythmias (irregularities in the heart beat) after heart attacks are at greater risk of death than others and therefore that anti-arrythmic drugs would be of benefit to such patients in terms of mitigating that risk. Indeed it seems almost unethical not to give such drugs to patients after heart attacks. However a PRCCT (Prospective Randomised Controlled Clinical Trial) of anti-arrythmics against placebos showed a totally unexpected increase death rate in the actively treated group.

In each of these cases we see that plausible theories about the human body and how it works can mislead us about whether this or that intervention is beneficial and that we need careful clinical trials to tell us whether our beliefs about the right way of treating certain serious conditions actually are correct. Thus there is a real need in ICU care (as there is in surgery) to do the trials that will show us what should be done in a given clinical situation but there is also a need to protect patients from unilateral decision-making that may put them at risk (as we saw in the Cartwright inquiry that led to a reformation in New Zealand medical ethics).

But this immediately provokes a set of questions about the need for informed consent to medical research. This need should be discussed in the light of the facts already mentioned which ground a number of substantial conclusions about research on those who cannot give consent. In fact, those conclusions are predictable from an informed discussion of advances in surgery, the need for clinical trials in modern medicine so that we all benefit from evolving and improved medical care, and the best interests of patients who cannot speak for themselves.

First, any person making choices about treatment should opt for the treatment that stands the best chance of returning him or her to health. There may, however, be specific reasons why some particular intervention is not acceptable to a person, for instance a Jehovah’s Witness patient may, on the strength of their interpretation of the Old Testament, refuse a blood transfusion.  We could also imagine a person with extreme racist views not wanting an organ transplant from someone of a different race – a decision which might be abandoned when the patient is in extremis.

Second, it is rational for any patient to accept the best available treatment according to the current state of knowledge at the time of their illness and contemporary clinical care particularly in academic hospitals, recognises this is the prevailing standard of treatment. But it is quite possible that an ideally informed clinician would be unable to decide between a currently accepted standard treatment and a suggested modification or innovation. In such a case the doctor does not know whether the treatment proposed for a given patient at a given time is the best thing to do or whether what is being trialled may be a whole lot better (given that safety assessments have been done). Therefore, looking at it from the patient’s point of view, the patient has no reason to opt for the standard treatment rather than any other of the possibilities on offer. In fact the patient, considering that he and others like him may require further treatment at a later date, has a definite interest in his doctors getting to know as much as possible about his condition, and making well-considered judgments about his management as he undergoes it. This is most likely to happen in the context of a well-designed scientific trial (where the patient is guaranteed to get treatment equal to the currently accepted standard of care).

Now, given that a treatment in ICU is only trialled if it is unclear whether a new treatment actually offers more benefit to patients than the existing ones, it follows that it is a matter of indifference, ethically speaking, which of the two arms of a clinical trial (the treatment arm – where something new is tried, or the control arm – where standard treatment is used) any given patient is assigned to. For this reason it is best, on the grounds of self-interest or care of the patient – for an ICU patient to be enrolled in a trial of treatment where a sensible question can be asked about how he ought to be treated.

Third, it would be in accordance with good care and the best interests of patients, more broadly conceived, for people to want to contribute to medical knowledge in conditions of uncertainty. This is almost self-evident because it is always good for a health care system to be extending and using knowledge about the patient and his problem and there are real benefits to a patient in being cared for by a medical system in which active clinical research is going on. Indeed, given that there is a certain amount of community feeling in all of us, we should all want the members of our community to benefit from lessons learnt when misfortune befalls any of us if we can be sure that gaining that knowledge will not increase the risks of clinical treatment. In retrospect, of course, it may turn out that patients enrolled in one or other arm of a study (sometimes the opposite one to that expected) have been disadvantaged by the clinical trial but that fact cannot be known at the time of enrolment and the dangers continue to exist until the relevant facts are discovered.

Therefore we should conclude that clinical research trials of treatment in ICU exposes no patient to any extra risk over and above those that exist for them in virtue of their eligibility for the trial and that the cessation of that research means that they and their fellow citizens will probably be exposed to unnecessary risks in the future.

Fourth, it is reasonable to assume that everybody has some altruism, however limited, and that it should be encouraged by ethicists  for the following reasons.

  1. Most people have a positive interest in the well-being of the fellow members of their community and in the best treatment being used in the care of the community.
  2. Where someone stands to gain by a community practice such as best ICU care and the research that supports we should support and participate in it.
  3. We all recognise that altruism is something to which, in our best moments, we aspire so it does no harm to assume that people should be treated in a way that reflects their values (unless that decision involves forgoing one’s own objective best interests). Therefore we should enrol each other in properly conducted trials of ICU research even without consent.

Fifth, relatives are often badly placed to make life and death decisions as has been objectively demonstrated and is easy to understand. All the uncertainties associated with life and death decisions cluster around every conversation between an ICU team and relatives. In addition to the informational turmoil there is an emotional cauldron – some feel shocked, others guilty, yet others protective. So a mortal decision must be made; the context is heavily overlaid by technology, the power of the medical establishment, and urgency; and  there are often conflicted feelings so that it is unrealistic to believe that anything like informed consent can prevail. In reality, we can only hope for a sensitive and supportive partnership between the clinical team and the patient’s whanau and a climate in which a duty of care is clearly thought through.

Sixth, clinical staff have a duty to make the best decisions for any given patient, to be suitably sensitive to the realistic interests, concerns, fears and expectations of ordinary folk (and not be influenced by distorting factors such as extreme right to life or euthanasia views, the fear of litigation, or financial gain). That implies that the best chance of getting soundly researched clinical care in an area of medicine where intuitions and theory based reasoning can both mislead even the best of well-intentioned clinicians is if we continue to enrol unconscious patients in clinical trials.

Therefore it is best for the clinical team looking after you to make a plan for your management if you are incompetent and your life is in danger. It is clear that in ethical terms, this should be the default position with disputed cases being arbitrated by some suitably impartial body such as an ethics committee and with the courts being used only when, here as elsewhere in medical care, things cannot be managed in a better way. In any event, we can commend, in ethical terms, the general practice of doing ICU research under the condition that the clinical team, acting in good conscience, can enter their patients into well designed trials, even where informed consent prior to entry into the trial cannot be obtained.