Identification of tamoxifen-associated symptoms and analysis of dose dependency
Change in reported symptom severity from baseline to end of treatment was calculated by subtracting the baseline Likert-scale score (0–4) from the score reported at the end of study (6 months or date of discontinuation). A mean of the individual change was calculated for each of the 48 predefined symptoms. The rationale for this method was to take background conditions into consideration, for comparison of pre- and postmenopausal women, and to capture the magnitude of change. To recognise side effects associated with tamoxifen, the placebo group was contrasted to the 20 mg group and symptoms significantly related to tamoxifen were identified.In the dose-dependent analyses, we contrasted the mean change of the score for those symptoms significantly associated with tamoxifen. In a subsequent analysis, we contrasted low-dose tamoxifen, defined as 2.5 and 5 mg, to high-dose tamoxifen (10 and 20 mg). The reason not to include the 1 mg tamoxifen dose in the low-dose group was that no RCTs, including our own [