Log-transformation of "null" PK para­meters [General Sta­tis­tics]

posted by fno Homepage – Belgium, 2014-03-11 13:18 (3670 d 06:37 ago) – Posting: # 12592
Views: 10,625

Hello,

A multiplicative model is commonly admitted for PK parameters, which justifies that any statistical analysis is performed after log-transformation.

In one study (not a BE :wink:) we have to analyze, one patient has all concentrations < LLOQ after one treatment.
As this was not really expected, this case was specifically planned neither in the study protocol nor in the SAP. The SAP however specified that concentrations < LLOQ should be set to zero, which then resulted in Cmax and AUClast = 0.

Nothing weird has been noticed on the clinical or laboratory side, and other patients also show a very low concentrations profile (but with at least one or two concentrations > LLOQ).
It therefore makes sense trying to keep these Cmax and AUC = 0 in the outcome of the statistical analysis, but of course, this information is being lost by the log-transformation: log(0)= :confused:.

Different workarounds are possible:
  1. Analyzing the data in the original scale without log-transformation
  2. Imputing Cmax and AUClast by something positive. For Cmax, one can think using LLOQ or LLOQ/2, but what for AUClast? Moreover, the results of the statistical analysis then become quite dependent of the selected imputation rule.
  3. Applying a log(Param+d)- instead of a log(Param)-transformation, where d is a very small positive number. But again the statistical outcome is very dependent of the value chosen for d.
    :blahblah:
As it is the second time I face such a special case over the last few months, I would be very interested in having expert advices on the best (or less worse) practice to deal with it?

Many thanks in advance for sharing your thoughts!

Kind regards,
Fabrice

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