Blinding in pharmacological trials: the devil is in the details

While the methodological principle of ‘blinding’ for minimising bias in randomised controlled trials (RCT) is widely debated and accepted, rarely is this depth of thinking applied to its correct handling with respect to design, reporting and analysis. Beyond the general comprehension of the definition of the word, the practical aspects of establishing blinding in investigator-initiated pharmacological trials are often grossly underestimated,1 and very much an afterthought. The resulting inadequacy can lead to trial delayed and increased costs,1 and can also potentially place the entire trial at risk. It is worth nothing that reporting of blinding methodology is often absent or of low quality in published articles of RCTs.2 ,3 Thus, in such context, when these fundamental details of trial design are inadequately reported,2 ,3 it becomes easier to see why it should be of no surprise that there are, equally, very few published commentaries addressing the challenges of blinding that those embarking on pharmacological trials face. So, it would seem that little is available, at least in biomedical literature, to guide investigators on this particular methodological aspect. A review of RCTs published over 15 years in this journal identified only 176 RCTs in children involving pharmaceutical interventions4; the authors suggested that difficulties in obtaining adequate placebos without the collaboration of pharmaceutical companies may have contributed to the low number.4 Our experience over the years has also highlighted, among investigators, a deficiency in the awareness of how pharmaceutical ramification can constrain trial design and its validity.5 ,6 There is no denying that the science underpinning blinding is very much pharmaceutical based, and may be technical at times, but part of this paucity of knowledge is undoubtedly due to a certain lack of recognition for the pharmaceutical properties of a medicine. This …