Question

In reference to chapter 4, which talks about human and animal research and randomized trial for HIV. Such experimental methods are intended to reduce error and bias and can therefore reduce the uncertainty of the result. Randomized trials often place physicians in the ethically intolerable positions of choosing between the good of the patient and society. Describe and explain any ethical problems this may create for a patient or the society?

Answer 1

WHAT IS RANDOMISATION?

Randomization is a sampling method used in scientific experiments. It is commonly used in randomized controlled trials in experimental research.

Randomisation or (random allocation)

Assigning people in a research study to different groups without taking any similarities or differences between them into account.

For example, it could involve using a random numbers table or a computer-generated random sequence. It means that each individual (or each group in the case of cluster randomisation) has the same chance of having each intervention.

WHAT IS RANDOMIZED TRIAL ?

Randomised controlled trial

A study in which a number of similar people are randomly assigned to 2 (or more) groups to test a specific drug, treatment or other intervention. One group (the experimental group) has the intervention being tested, the other (the comparison or control group) has an alternative intervention, a dummy intervention (placebo) or no intervention at all.

The groups are followed up to see how effective the experimental intervention was. Outcomes are measured at specific times and any difference in response between the groups is assessed statistically. This method is also used to reduce bias.

In randomized controlled trials, the research participants are assigned by chance, rather than by choice, to either the experimental group or the control group.

Randomization reduces bias as much as possible. Randomization is designed to "control" (reduce or eliminate if possible) bias by all means.

The fundamental goal of randomization is to certain that each treatment is equally likely to be assigned to any given experimental unit.

Bias is the most unwanted element in randomized controlled trials and randomization give researchers an excellent tool to reduce or eliminate bias to maximum. Absence of bias means more reliable the results of study are and gives legitimacy to both research and researchers as well.

WHAT ARE THE ETHICAL PROBLEMS ARISING FROM THIS SAMPLING DESIGN?

The ethics of randomised controlled trials from the perspectives of patients and healthcare professionals

Since the introduction of randomised controlled trials, professionals and lay people alike have worried over whether doing this sort of experiment in humans is ethical. It has been argued that participants may be called to sacrifice their own best interests for the benefit of future patients.

The scientific rationale for conducting a trial rests in collective equipoise, which means that the medical community as a whole is genuinely uncertain over which treatment is best. The key point, however, is that future patients benefit at no cost to participants, provided that participants are in personal equipoise and give informed consent on this basis. In these circumstances, the trial arms are an equally good bet prospectively.

Summary points

Doctors do not seem to take informed consent from competent patients as seriously as they should; ways in which practice might be improved need to be tested empirically

Most doctors expressed willingness to enter their patients in trials even when the treatments offered were widely available but were not an equal bet prospectively; the fact that members of the public suspect this might undermine their confidence in trials

Willingness to undergo randomisation drops as prospective participants are given more preliminary data and as they are made aware of any accumulating evidence of effectiveness

A large number of participants, even in phase III trials, emerge from consultations expecting to benefit personally; self interest, rather than altruism, seems to be their motive for participating.

Informed consent

The concept that informed consent should always be obtained from competent patients was widely, though not universally, accepted.Two of these studies found that up to one in five doctors regularly entered competent patients in trials without even obtaining informed consent.

Despite this, patients generally seemed content with the information they received. The experiences of patients who had actually taken part in clinical trials were audited in four studies, which reported that at least 80% of responding participants were satisfied that they had made an autonomous decision to take part.

Of course, there is no way of knowing whether they really had received or understood all that they would have wished.

Expectations with respect to informed consent varied according to the type of experiment in question. Some responding doctors believed that informed consent was obtained more rigorously in phase I trials than in phases II or III studies, and in trials of supportive care, than in trials testing curative or palliative therapies.

Conclusion

The finding that so many people participate out of self interest needs exploring. Although the studies were of poor quality, especially regarding what exactly the respondents understood of the questions and hence what they meant by their answers, it is important to find out what well informed members of the public really think about trials and why they expect to benefit, if indeed they do.

The finding that self interest features so strongly, even in phase III trials, is consistent with our other findings that patients do not always understand that they have been randomised to a control group, which was just what the doctors had anticipated.

Given equipoise and freely available treatments, gain is not a realistic aim prospectively in late phase trials. Even if a trial effect is real, this can hardly be used as an inducement to participate because to do so would violate the Declaration of Helsinki.

Because patients are required to make informed choices, it is important that they both understand and accept that they stand neither to lose nor to gain in such cases.

Rationally, the reason for such participation must be an altruistic one or else a way of resolving an otherwise difficult (or finely balanced) decision—this latter reason was picked up by respondents in Snowdon et al’s study.

If patients expect to be personally worse off by being in a trial but nevertheless give their consent, they would be altruistic in a strong sense, meaning that they expect to sacrifice clinical benefit for the psychological satisfaction of helping others.

The other main theme is that a surprising number of doctors “owned up” to entering their patients when the treatments in the trial were probably otherwise freely available but when patients harboured a personal preference for one of the treatments. Worse, doctors seemed to have been aware that patients may not have fully understood what was going on.

For many, informed consent seemed little more than a ritual. More research needs to be carried out to see precisely what factors motivate doctors to offer randomised controlled trials as an option in health care. It is interesting to speculate, though.

Doctors may feel torn by their obligations to individual patients and to society at large, and they may even have got the impression, perhaps hyped up by advocates of evidence based medicine, that they are obliged to participate in research for the common good, even when they have a slight or moderate treatment preference.

As a result, there may be a stark difference of opinion between ethicists and practitioners over what is ethically acceptable. This brings us back to the need for clear public discussion of ethics and the conduct of medical research.