Epub: Wright S, Duncombe P, Altman DG Assessment of blinding to treatment allocation in studies of a cannabis-based medicine (Sativex(R)) in people with multiple sclerosis: a new approach..Trials. 2012;13(1):189.
BACKGROUND: Maintenance of the blind-to-treatment allocation is one of the most important means of avoiding bias in randomised controlled clinical trials. Commonly used methodologies to determine whether patients have become unblinded to treatment allocation are imperfect. This may be of particular concern in studies where outcomes are patient-reported, and with products which have a characteristic adverse event profile. We report the results of an evidence-based statistical approach to exploring the possible impact of unblinding to a cannabis-based medicine (Sativex(R)) in people with muscle spasticity due to multiple sclerosis.
METHODS: All 666 (the number of the beast :-) patients included in three Phase III placebo-controlled studies were included in this analysis. The relationship between factors that might permit patients to identify their treatment allocation and the effect of treatment on the self-reported primary outcome measure was investigated using a general linear model where the dependent variable was the change from baseline in patient self-reported spasticity severity, and the various possible explanatory factors were regarded as fixed factors in the model.
RESULTS: There was no significant relationship between the effect of sativex on spasticity and the prior use of cannabis or the incidence of 'typical' adverse events. Nor was there any significant relationship between the prior use of cannabis and the incidence of 'typical' adverse events, nor between prior use of cannabis and dose of Sativex.
CONCLUSIONS: There is no evidence to suggest that there was widespread unblinding to treatment allocation in these three studies. If any patients did become unblinded, then there is no evidence that this led to bias in the assessment of the treatment difference between Sativex and Placebo for efficacy, adverse events or study drug dosing. This methodology may be suitable for assessment of the integrity of the blind in other randomized clinical trials.
Blinding is an issue in trials, because without it it can introduce bias which may over estimate the effect of the drug. This study looked at sativex a cannabis spray and suggests that in trials where the aim was "not to get high" there was nomuch unblinding. The cynic says if you you do not know you are taking it are you taking enough for optimum benefit because the side effect ad effect are controlled by the same things in different parts of the CNS. However even if unblinded it did not make a difference.
Will being unblinded have an influence on the regulators, we shall see the Lemtrada trials were not blinded and so subject to bias, because you knew if you were getting an i.v dose or were injecting yourself (beta interferon). In some other trials the companies have gone to much greater lengths to get class I evidence and have given fake infusions and repeated injections with fake interferon. The people on these trials are doing a heroic job.
Labels: cannabis, sativex, trials