Development and Content Validity Testing of The Patient-Reported Outcomes of Fatigue In Cancer (Proof-C) Symptom Severity Assessment (Ssa)


      Cancer-related fatigue (CaF) is a common symptom of cancer and one that can be burdensome to patients. It is possibly under-reported due to its complex origins, inconsistent definitions and assessment methods. In recent years, no existing measures have been accepted by the US Food and Drug Administration (FDA) to support labeling claims in CaF. The Patient-Reported Outcomes of Fatigue in Cancer (PROOF-C) Consortium have developed the Symptom Severity Assessment (SSA), a patient-reported outcome (PRO) measure of CaF to be aligned with FDA expectations as part of the FDA’s Drug Development Tool (DDT) Qualification Program.


      In total 91 open-ended concept elicitation (CE) interviews were conducted among eight cancer types to spontaneously elicit the patient experience of CaF. Items were generated based on qualitative, thematic analysis of verbatim transcripts and with input from a clinical expert. Subsequently, 61 cognitive interviews (CIs) were conducted with patients in six cancer types, wherein a “think-aloud” process and targeted debriefing questions were used to assess concept relevance and patients’ understanding of the instructions, items, and response options.


      CE data supported the development of a draft, 13-item SSA, measuring eight symptoms of CaF, with a 24-hour recall period and an 11-point numeric rating scale. The results of the 61 CIs confirmed that the draft SSA was interpreted as intended by patients, and assesses concepts relevant to and experienced by patients across all examined cancer types. Minor revisions were made to nine items to improve clarity. One additional item was added to ensure comprehensiveness.


      The SSA demonstrates strong content validity, assessing relevant CaF concepts in a manner patients understand. Planned future development activities include additional CIs to confirm content validity of the revised, 14-item SSA in an electronic format, followed by an observational study for the development of scoring, item reduction, and psychometric validation.