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IN RESPONSE
Submit responseDr Heckerling argues that by offering vestibular rehabilitation (VR) to patients in the control group after three months we implied that VR is an effective treatment, thereby violating the important principle of ‘equipoise’. However, in a pragmatic[1] or ‘Phase III’ trial such as ours it is assumed that the treatment has already been shown to be beneficial under ideal conditions (normally, this will have been established in efficacy or ‘Phase II’ trials). Consequently, equipoise is maintained instead with regard to the research question: Is the treatment more effective than usual care in typical clinical practice? Moreover, it is accepted that clinician and patient attitudes to the treatment will affect outcomes. It was important for this reason (as well as to permit fully informed consent) that we explained to potential participants that there was some existing evidence of efficacy, but no previous demonstration of effectiveness, particularly when VR was delivered by practice nurses in a primary care setting. We therefore also drew attention in the paper to the likelihood that positive motivation and placebo effects may have contributed to outcomes, although the pattern of findings was indicative of specific effects on the balance system rather than simply a generalised improvement in subjective wellbeing. However, if control participants had stayed in the study simply because they were ‘coerced’ by our offer of a treatment of unknown effectiveness after three months, then substantial dropout might have been expected at follow-up in both control and intervention groups – yet dropout was as low at three months in the treatment as the control group, and remained similarly low in both groups at six months.
Regarding the subsidiary point made by Dr Heckerling, we concur that there was no compelling scientific rationale for presenting outcomes in the control group after they had received therapy. However, we had collected follow-up data in both groups in order to analyse predictors of adherence to treatment in the whole sample (manuscript in preparation), and we felt that if we failed to report these outcomes alongside the longitudinal follow-up of the intervention group readers might reasonably wonder whether this was because the intervention had inexplicably proved to be less successful in the control group.
[1] Roland M, Torgerson DJ. Understanding controlled trials: What are pragmatic trials? BMJ 1998; 316: 285.
Conflict of Interest:
None declared
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"Treating" Controls in Unblinded Trials
Submit responseTo the Editor:
In the study by Yardley et al (1) of vestibular rehabilitation for patients with chronic dizziness, it is not clear what scientific information was gained by crossing control subjects over to vestibular training at three months. Efficacy could not be measured, since the intervention group was not crossed over to the control condition (nor could it be, given an inability to wash out the initial vestibular training). Maintenance of effect at three months was already measurable in the intervention group, so a similar three-month period for controls would not add new information. And since vestibular training was not standard of care, a "staggered-start" trial to measure adverse effects during a three-month control window-period was not ethically mandated.
One non-scientific reason for offering controls vestibular training may have been to reduce the likelihood that they would drop out of the trial because of disappointment in not receiving the training. Because the trial was unblinded, controls would have been aware of their control status. These patients, who suffered from chronic dizziness, may have entered the trial in hope of receiving the vestibular training. Offering them such training after three months may have served as inducement to them to remain in the trial as controls.
There are, however, two concerns over offering control subjects delayed intervention in an unblinded trial, absent valid scientific reasons for doing so. First, such an offer might be considered potentially coercive. But more important, it portrays the study intervention as "treatment" rather than as something being investigated under equipoise concerning its efficacy (2,3). An honest null hypothesis at this trial's inception must have allowed for the possibility that vestibular training would have proven ineffective at three months, compared with the control condition. Given this possibility, what is the justification for providing this "treatment" to controls at three months, as part of the trial?
References
1. Yardley L, Donovan-Hall M, Smith HE, Walsh BM, Mullee M, Bronstein AM. Effectiveness of primary care-based vestibular rehabilitation for chronic dizziness. Ann Intern Med 2004; 141: 598-605
2. Freedman B. Equipoise and the ethics of clinical research. N Engl J Med 1987; 317: 141-145
3. Miller FG, Rosenstein DL. The therapeutic orientation to clinical trials. N Engl J Med 2003; 348: 1383-1386
Conflict of Interest:
None declared