Table 2:

Recommendations

Number	Recommendation
1.	Patients with ECOG PS2 (or KPS 60–70) should be included unless there is a scientific and/or clinical rationale for exclusion justified by established safety considerations.  a. PS eligibility criteria should be based on the patient population in which the intervention is expected to be applied in clinical practice.  b. PS eligibility criteria should be continually re-evaluated and modified throughout the drug development process to reflect accumulated safety data of the investigational treatment. Decisions about PS eligibility criteria should be based on early clinical safety and efficacy data about the specific investigational agent or based on known data from other drugs in the same class with similar mechanism of action. Later phase trials (e.g. phase II/III) should generally mirror the intended use population and ECOG PS2 (or KPS 60–70) patients should be included, unless safety concerns have manifested in earlier phase trials. The rationale for exclusion should be justified and stated explicitly.  c. Incorporating the rationale for inclusion of a broader population into the protocol could help encourage investigators to enroll these patients.  d. Performance status data should still be collected for use as a stratification factor, regardless of how it is incorporated into eligibility criteria.
2.	Consider alternative trial designs, such as pre-specified cohorts with lower-functioning PS that are exempt from the primary analysis, to encourage inclusion of these patients. These cohorts would generally be small in size and exploratory in nature and could be enrolled in an incremental way to enable an early stopping rule based upon safety data. Consideration of the data analysis approach for the broader eligibility cohort and subgroup analysis should be determined during the study design phase and its implications for marketing and post-marketing requirements discussed with FDA when appropriate.
3.	Additional assessments of functional status should be considered to better characterize the functional status of ECOG PS2 patients and patients aged ≥65, such as Activities of Daily Living (ADLs) and Instrumental ADLs.