This HomVEE Version 2.2 handbook adjusts the earlier version to incorporate public and expert consultants’ feedback. This update also describes a revised approach to prioritizing research for review (including changes to searching and screening), provides a clarified definition of subgroup, describes a new approach to limit findings eligible for review, highlights changes to the requirements for demonstrating face validity of outcome measures, and provides a new indeterminate quality rating (see Exhibit I.2). Finally, this update also includes editorial changes to improve clarity. (author abstract)