"You decide doctor". What do patient preference arms in clinical trials really mean?

I t is well established that random assignment between experimental treatment and control arms is the gold standard in clinical trials to minimise differences between the groups being compared and safeguard against bias. There is, however, a fear that such random allocation may not accord with patients’ preferences for the intervention or treatment, thereby compromising trial validity. It is possible that patients may resent not receiving their treatment of choice, and their negative attitude may lead to non-adherence to treatment or affect outcomes in some other way. Consequently, one option for trial designers is to include patient preference arms, whereby patients with no treatment preference are randomly allocated to experimental and control arms, while patients expressing a treatment preference are allocated to receive their preferred treatment. Most of the debate about preference arms has focused on issues concerning increases in the sample size required, the types and stages of randomised design, and how to compare the groups. Ethical issues also arise, leading to concerns about those with strong treatment preferences being included in studies in the first place, especially those in which randomisation takes place irrespective of patients’ elicited preferences (that is, to measure whether those who received their preferred treatment, or not, differed from the no preference groups). There is less information about how doctors’ preferences for treatment influence their patients’ preferences. A recent systematic review of the impact of patient and doctor preference for intervention in randomised trials, across a range of disorders, reported that elicitation of preferences led to a substantial proportion of potential participants (patients, including parents, and doctors) refusing randomisation. However, differences in outcome across the trials between randomised and preference groups were reported to be small, and where preference effects were noted these were generally inconsistent. The authors of this study concluded that there was little evidence that preference substantially interfered with the internal or external validity of trials. The review included studies according to methodological criteria and if they ‘‘measured or recorded patient or physician preference’’ (page 1090). However, the reviewed studies varied widely in their approach to eliciting preferences, and preferences often appeared to have been simply noted in the consent to randomise procedures used. The methods used in most research on preferences include single item questions asking patients to state the option they would choose, Likert scales of the strength of the stated preference, and utility measurements (for example, rating scales, time trade offs, standard gamble methods); less commonly, preferences have been explored using discrete choice analysis. The question arises: does it really matter if preferences are not rigorously assessed in trials?