Of the 157 patients who were randomized, 18 patients (11.5%) had discontinued treatment by week 24, with 3 patients stopping for adverse events, 3 for protocol deviation
or noncompliance, and 10 withdrawals.
One significant adverse event was a protocol deviation
in which 1 patient received an incorrect dose of IV sodium fluorescein (500 mg) instead of the recommended 25-mg dose.
Eighty-five patients (including the six patients excluded from the ITT population) presented at least one major protocol deviation
and were thus excluded from the PP population.
In total 164 patients were enrolled and randomly allocated to receive berberine or placebo, of which 12 subjects in the berberine arm and 20 from the placebo arm were subsequently excluded because of voluntary withdrawal or protocol deviation
. Thus 70 patients in the berberine and 62 in the placebo group completed the study with available data for analysis.
to treatment compliance was reported in majority of patients.
If the use of electrocautery was required in patients allocated to the nonintervention group, this protocol deviation
was to be annotated; however, no such situation occurred during the study period.
In fact, protocol deviation
was so significant that it invalidated the primary outcome of the study and the results looked too good to be true--they were.
This protocol deviation
did not affect the laboratories' abilities to detect weight increases in response to TP but was a source of a significant laboratory-to-laboratory variability when all laboratories were pooled ([R.sup.2] = 36%).
Reasons for attrition included withdrawal of consent, protocol deviation
, unavailability, and adverse experiences.
The entire team met for an hour each week to review each instance where a clinician deviated from protocol to (1) change the protocol (2) agree that the protocol was correct, or (3) decide that the protocol deviation
was justified but represented a rare event.
Other reasons for discontinuation were pregnancy, protocol deviation
, and physician or patient decision.