Widening the field of vision
Senn's and Sackett's responses seem to reflect a rather narrow point
of view. Both correctly note that there is likely to be a strong
relationship between an individual's improvement, real or perceived, and a
subsequent guess that they are receiving active treatment. That is why
assessing unblinding by simply examining the proportion of correct
'guesses' is not a particularly good choice. However, to argue that we
should therefore not attempt to assess whether blinding has been
maintained is an even poorer choice.
Our paper examines how trialists report on blinding, not only with
regard to outcome, but also with regard to process. To be charitable, one
might categorize the result as 'not very well'. Since the claim of assay
sensitivity for trials with a placebo arm rests on the assumption of
appropriate blinding, we do not have the luxury of continuing to avoid the
challenging measurement issues involved. It seems contrary to an evidence
based approach to avoid obtaining data because we have to struggle with
its interpretation. Asking individuals to provide not only their
'guesses', but the reasons for them may help the process. A variety of
additional approaches need to be explored.
We applaud the aim of CONSORT and understand Altman and colleagues
reticence to be prescriptive with regard to trial conduct. However, the
CONSORT statement does ask trialists to report not only the method used to
generate a random allocation sequence, but also the details of its
implementation and concealment. Similarly, we feel that there is room and
need for better attention and guidance with regard to the reporting of
Caveats regarding the evaluation of new therapies via non-inferiority
trials(1,2) are certainly appropriate. However, methodological caveats
with regard to placebo controls need similar attention, and it appears
that this is being ignored(2). As we note, and Double echoes, the more
subjective the outcome the greater the concern. We believe that licensure
of an ineffective agent (a new anti-depressant for example) based on
studies with poorly designed and executed placebo controls should be
considered as serious an error as licensure on the basis of poorly
designed and executed non-inferiority trials. Since details about
maintenance of blinding are not being routinely sought, that symmetry
appears to be lacking. We think this needs to change.
(1) D'Agostino RB Sr. Non-inferiority trials: advances in concepts
and methodology. Stat Med 2003;22:166-167.
(2) International Conference on Harmonization of Technical
Requirements for the Registration of Pharmaceuticals for Human Uses (ICH).
Choice of control group and related issues in clinical trials (E-10).
Competing interests: No competing interests