Table 1.

Considerations for the evaluation, analysis, and potential measurement issues of cancer symptom response (CSR) in oncology clinical trials.

Topic	Summary
Evaluation of CSR in oncology clinical trials	•  CSR assessments should include questionnaires developed and validated to address disease-specific symptoms. •  Optimal CSR assessment depends on numerous factors (e.g., the progressive nature of the disease, time from initial   diagnosis, number and type of comorbidities, age, gender). •  The goal of CSR assessment may vary across studies and populations. •  Patients must complete CSR assessments at least twice to assess progress over time. CSR is typically evaluated   frequently in clinical trials to minimize unobserved gaps in treatment effects. •  Timing of CSR assessments should be carefully considered and planned to best capture the information of interest   (e.g., pre- and post-chemotherapy administration).
Analysis of CSR in oncology clinical trials	•  There are multiple methods for assessing cancer treatment impact on CSR. •  Time to symptomatic progression (TTSP) assesses the length of time that transpires before symptom severity worsens. •  Change from baseline assesses change in symptom severity from baseline to a pre-specified time point, and is typically   compared between randomized treatment groups. •  Important difference is the point at which a meaningful difference or change in symptoms is noted, which is instrument   and context-specific. •  Responder analysis assesses the proportion of patients who achieve a pre-specified level of improvement in symptoms   over time with randomized treatment.
Potential measurement issues	•  Oncology clinical trials prefer analyzing CSR via TTSP analyses using an intent-to-treat (ITT) approach, which   includes all randomized patients regardless of trial withdrawal or drop-out. •  Informative censoring occurs when withdrawal rates differ between treatment groups. •  Informative censoring threatens the validity of ITT analysis and should be minimized with study design and analysis   techniques (e.g., mixed effects analyses, imputation of missing data). •  Responses to symptom-related questionnaires may be influenced by drug tolerability issues. •  If CSR is highly correlated with other measures of efficacy (e.g., survival, tumor response), this lends credibility to   CSR data as evidence of efficacy. •  If CSR only correlates with adverse event reporting, differences in CSR could be attributed to treatment safety.