Bioequivalence and Bioavailability Forum

Dear ElMaestro,

❝ In BE the tradition is to have analysts blinded wrt treatment, so they know subject and period and time point but not randomisation and therefore they can't say if subject 3 in period 1 got treatment T or R. They will not be able to tell the T/R for any subject. And therefore they cannot easily manipulate it.

Yes they won't be able to tell the T/R ratio. But don't you think blinding wrt treatment will not change the bias of ensuring that the results of Period 1 and Period 2 are similar irrespective of whether it's T before R or vice versa?

For instance, if response for time point 2.0hr at Period 1 is 6.3 and response for same time point at Period 2 is 2.3, the bioanalyst might want to review the chromatogram once more (or the analysis methodology proper) to find out why the discrepancy....and he just might see something to justify a reanalysis .

But then again I think the statistical analysis for the Period and Sequence effect might further reveal some anomaly. So you are right.

❝ You mean they could use that info to create smooth profiles that more or less correspond to the expectation in terms of e.g. t half etc?

Yes. They have an idea of the expected absorption and elimination phase of the curve. So they already have an idea of the expected response of the respective timepoints.

❝ History has shown that if you really keep the randomisation code under lock and key then the chance to manipulate a trial is lower than if you don't.

I agree. I'm just saying if one could go beyond that and further blind the time points as well. But perhaps it's something that is not reasonable logistic wise.

❝ Conversely the PI in a BE trial needs not be blinded because she/he cannot easily manipulate the trial result. If the PI were scoring e.g. wound healing visually in a PD trial then she/he would often need to be blinded.

I totally understand the irrelevance of blinding the subjects or the PI since this is a BE study and the efficacy is measured purely via bioanalysis and not via a physician or a subject's assessment. I'm simply making a case for further blinding the bioanalyst from the sampling timepoints. But perhaps it's just me being overly paranoid over the likelihood of bias. Perhaps it's not likely that bias might result but it's the likelihood of reanalysis due to pharmacokinetic reasons which the guidelines have spoken against.