The updated ICH E$6($R$2)$ 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.

Use of the PDA cycle $($Plan$,$ Do$,$ Act$)$ during the annual continuing review.

Mandatory use of ICH E$6$ template Case Report Forms for all drug studies to be submitted to regulatory authorities.

Identification of study risks to determine which may safely be omitted from continual monitoring.