Page 58 - Read Online

Page 6 of 14 Webster et al. J Cancer Metastasis Treat 2020;6:8 I http://dx.doi.org/10.20517/2394-4722.2019.38

Framework development
For framework guidance, we reviewed publications related to recently issued guidelines for the
identification and management of irAEs. We selected seminal publications, highlighted key thematic
information from each, and organized our framework accordingly. Collectively, this provided a conceptual
framing for PRO measurement in the context of a complex matrix of ICM-related adverse events.

Data summaries
From our literature review, we extracted all relevant information regarding ICM-induced inflammatory
reactions and immune conditions, as well as their associated toxicity profiles and symptomatology. Data
were summarized in Excel spreadsheets, which allowed for detailed descriptions of symptom experience.
We added expert-identified symptoms to the composite and highlighted these for Primary Symptom List
consideration. Symptoms identified for possible inclusion in the library were reviewed by a team of experts
with extensive experience in PRO measure development for relevance, redundancy, and appropriateness as
measured by self-report. Symptoms for the Primary Symptom List were iteratively reviewed by our expert
panel. Redundant or similar symptoms were collapsed, and symptoms that could not be measured via
patient-report were excluded.

Item mapping
Once a comprehensive list of symptomatology had been finalized, we organized immune conditions
(inflammatory responses and autoimmune syndromes) and symptom profiles according to our conceptual
framework. We then mapped symptoms onto existing items in the FACIT Measurement System via the
FACIT Item library (https://wizard.facit.org), filling gaps by modifying existing items when possible and
writing new items as necessary [28,36] . The FACIT Measurement System includes over 100 distinct self-report
questionnaires that assess a wide variety of disease- and treatment-related symptoms, functional abilities
(physical, mental, and social), general perceptions of health and well-being, and other aspects of health-
related quality of life. The FACIT item library is a collection of more than 700 unique health-related PRO
questions that appear in the FACIT Measurement System. Most FACIT items have demonstrated face and
content validity, and were created with direct input from patients and expert clinicians. Many items have
also been translated into up to 70 languages using a standardized, rigorous translation methodology [37,38]
and tested for comprehension by native speakers.

For the immunotherapy library, our team identified the most suitable item for symptom assessment, and
then included other items related to impact or bother as appropriate. For the Primary Symptom List, when
more than one FACIT item was available, our expert panel assisted in selecting the top 1-3 items targeted to
symptom assessment in the setting of ICM therapy.

RESULTS
Expert input
Our panel of experts was tasked with identifying a Primary Symptom List of ICM-related adverse events.
Experts were MDs (n = 7), PhDs (n = 4), and a PhD candidate (n = 1), with 2-8 years of experience treating
cancer patients with ICM therapies and/or researching the incidence, nature, and HRQOL impact of irAEs
in the context of collaborative clinical and translational trials.

Experts identified an initial list of 61 commonly seen or clinically relevant irAE symptoms for ICM
Primary Symptom List inclusion. We then mapped symptoms onto existing items in the FACIT item bank,
which included those that address symptom presence, symptom bother and/or emotional or functional
impairment associated with symptom experience (e.g., “I have stiffness or tightness in my joints” and
“Joint stiffness limits my usual activities”). Mapped irAE symptoms yielded 153 unique FACIT items.