The European Medicines Agency (EMA) on Thursday released for consultation a revised ICH guideline on reproductive toxicology and an addendum to another guideline on statistical principles for clinical trials.
Draft ICH E9 (R1)
The 23-page addendum, which is open for comments through 28 February 2018, clarifies and extends ICH E9.
While noting that it “remains undisputed that randomisation is a cornerstone of controlled clinical trials and that analysis should aim at exploiting the advantages of randomisation to the greatest extent possible,” the addendum notes that “the question remains whether understanding the effect of a treatment policy always targets the treatment effect of greatest relevance to regulatory and clinical decision making.”
The addendum outlines a framework that can be used to discuss other treatment effects and some points to consider for the design and analysis of trials to give estimates of these treatment effects.
The addendum also “invites consideration of the important distinction between non-adherence with, or withdrawal from, randomised treatment and discontinuation from the trial; also between measurements that exist but have not been collected, and measurements that do not, or cannot, exist.”
In addition, the concept of analysis sets is considered in the proposed framework.
“Section 5.2 strongly recommends that analysis of superiority trials be based on the full analysis set, defined to be as close as possible to including all randomised subjects,” the addendum says.
The concept of robustness is also included in the addendum under the section on sensitivity analysis.
Draft ICH S5 (R3)
The 63-page revised guideline, which is also open for comments until 28 February 2018, seeks to provide key considerations for developing a strategy to identify hazards and characterize reproductive risks for pharmaceuticals.
“The guidance informs on the use of existing data and identifies potential study designs to supplement available data to identify, assess, and convey risk. General concepts and recommendations are provided that should be considered when interpreting study data and making an assessment of reproductive risk in support of clinical development and marketing approval,” the document says.
Draft ICH E9 (R1) addendum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials, step 2b - Revision 1
Draft ICH S5 (R3) guideline on reproductive toxicology: detection of toxicity to reproduction for human pharmaceuticals, step 2b - Revision 3