In general, values and preferences increase the strength of the recommendation when there is high concordance and decrease it when there is great variability. In a situation in which the balance of benefits and risks are uncertain, eliciting the values and preferences of patients and empowering them and their surrogates to make decisions consistent with their goals of care becomes even more important. A recommendation can be described as having similar values, some variation, or large variation in typical values and preferences between patients and the larger populations of interest. Some of the discussion questions that fall under the purview of values and preferences include: Are you confident about the typical values and preferences and are they similar across the target population? What are the patient s values and preferences? Are the assumed or identified relative values similar across the target population? Other implications consider the practicality of the recommendation, including resource use, equity, acceptability, feasibility and subgroup considerations. Resource use is related to the uncertainty around the cost-effectiveness of a therapeutic or preventive measure. For example, statin use in the frail elderly and others with multiple co-occurring conditions may not be effective and, depending on the societal benchmark for willingness to pay, may not be a good use of resources. Equity, acceptability, feasibility, and subgroup considerations require similar judgments around the practically of the recommendation. The framework below (Table A-4) was used by the Work Group to guide discussions on each domain. Table A-4. GRADE Evidence to Recommendation Framework Decision Domain Questions to Consider Judgment Balance of desirable and undesirable outcomes Given the best estimate of typical values and preferences, are you confident that the benefits outweigh the harms and burden or vice versa? Are the desirable anticipated effects large? Are the undesirable anticipated effects small? 