The new ICH E6(R2) integrated addendum requires sponsors to implement systems to manage quality throughout all stages of the trial process. The system should use a risk-based approach including which of the following? Complete on-site documentation audits every 3-6 months. Mandatory use of ICH E6 template Case Report Forms for all drug studies to be submitted to regulatory authorities Use of the PDA cycle (Plan, Do, Act) during the annual continuing review. Identification of study risks to determine which may safely be omitted from continual monitoring