Assessing side-effect bother, burden, and tolerability: A qualitative study exploring the content validity of the...

Patient-reported measures of overall side effect burden such as the Functional Assessment of Cancer Therapy - item GP5 (GP5) can be used to assess the tolerability of cancer treatments. The single-item GP5, which reads "I am bothered by side effects of treatment," has served as an endpoint in clinical trials. The objectives of this qualitative study were to explore how participants with medullary thyroid cancer (MTC) conceptualize side effect bother, burden, and tolerability and to generate evidence to support the GP5 as a fit-for-purpose measure of patient-reported tolerability in the treatment of MTC and to establish which response options constitute "high side effect burden."

A purposive sample of 40 participants with MTC enrolled in the LIBRETTO-531 trial (NCT04211337) were recruited via clinical trial sites. Semi-structured interviews were conducted in the participant's preferred language to examine the concept of tolerability, demonstrate understanding of the GP5 content, and establish which response options constitute "high side effect burden." Interview transcripts were thematically analyzed with a mix of inductive and deductive coding methods.

In concept elicitation interviews, patients reported side effect bother as a highly relevant concept that was among the most proximal concepts to tolerability. The experience of side effects that are symptomatic and bothersome or burdensome are key contributors to how patients perceive the tolerability of a treatment. Cognitive interviewing showed the GP5 item was clear and understandable to all participants. Participants reported clear and concrete meaningful differences between each response option. Importantly, the qualitative data provide evidence that "high side effect burden" aligns with the response options of "Quite a bit" and "Very much" (score of 3 and 4, respectively) for most (60 %, n = 24) interview participants.

Participants described the concepts of side effect bother, side effect burden, and tolerability as highly relevant and related. The GP5 assesses a concept important to individuals undergoing treatment for MTC in a way that is understandable and relevant. The definition of "high side effect burden" is appropriately reflected by scores of 3 or 4. This qualitative evidence is supportive of the GP5 as a fit-for-purpose measure of comparative tolerability in MTC.