Page 174 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

Chapter 9a
6 weeks follow-up
- Adverse effects of imiquimod treatment: patient reported side effects and side effects noticed at clinical investigation
- Adverse effects of LLETZ treatment: patient reported side effects, using a standardized report form
10 weeks follow-up
- Treatment compliance: amount of applied doses of imiquimod, as documented by the study subject on a dose calendar
- Histological presence and grading of CIN for the experimental arm
- Adverse effects of imiquimod treatment: patients reported side effects and side effects
noticed at clinical investigation
14 weeks follow-up
- Adverse effects of imiquimod treatment: patients reported side effects and side effects noticed at clinical investigation
20 weeks follow-up
- Treatment compliance: amount of applied doses of imiquimod, as documented by the study subject on a dose calendar
- Histological presence and grading of CIN for the experimental arm
- Adverse effects of imiquimod treatment: patients reported side effects and side effects
noticed at clinical investigation
- Quality of life
6, 12, 24 months follow-up
- Cervical cytology outcomes for all patients, including HPV genotyping - Quality of life for all patients at 12 months follow-up
Statistical methods
Logistic regression analysis will be used to evaluate treatment efficacy of imiquimod treatment, compared to LLETZ treatment. Covariates in this analysis are age at diagnosis, CIN grade, smoking and HPV-subtype. Analysis will be based on intention-to-treat protocol. Biomarker prediction models for adequate response to imiquimod treatment will be developed by backward logistic regression analysis of biomarkers based on likelihood ration tests. The prevalence and severity of side effects of imiquimod and LLETZ treatment will be presented as proportions and means with 95% confidence intervals. Differences in the rates of overall side effects and severe side effects between the imiquimod and LLETZ arms will be tested with a chi-square test. Disease recurrence rates after 6, 12 and 24 months will be evaluated in successfully treated patients by use of multiple logistic regression analysis, after adjustment for age at diagnosis, CIN grade, smoking sexual behaviour and HPV subtype. Repeated-measures analysis of variance will be used to test for between-group differences over time in Quality of Life scores.
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