|
Abstract:
|
Considering a clinical development program as a whole, the Integrated Summary of Safety (ISS), essentially a meta-analysis of individual patient data, should be planned to address safety questions of interest. Planning should involve consideration of statistical power and precision, anticipated subgroup analyses, and how study design elements will complement each other across the program. Planned meta-analyses offer precision for subgroup analyses that won't be available within individual studies. With regard to design elements, the issue of confounding of study design elements should be explicitly addressed. For example, a low dose study in one subgroup (e.g., women) and a high dose study in another (e.g., men), completely confounds dose and sex, making it impossible to disaggregate the effects of either on study findings.
|
