Assessment of Immunotherapy-Related Adverse Events Among Patients with Cancer in Saudi Arabia: A Mixed Methods Study

Abstract

This thesis contributes significantly to cancer care by focusing on patients undergoing immunotherapy in Saudi Arabia. it is the first study to explore the challenges these patients face, offering valuable insight into their experience. the research translated and validated an immunotherapy assessment tool and assessed its real world use by evaluating its acceptability, feasibility, and clinical utility. this study deepens the understanding of immune related adverse events and provide critical perspectives for clinicians, patients, and researcher. Ultimately, it contributes to improving the management of adverse events in cancer immunotherapy.

Background: Cancer is a rapidly growing healthcare system challenge, with more than 19.3 million incidences recorded globally in 2020; this is projected to surpass 29.5 million by 2040. The emergence of immunotherapy has positively changed many advanced cancer outcomes and improved survival rates. Despite immunotherapy being an efficacious and reliable treatment option for cancer, its success is tempered by associated immune-related adverse events (irAEs). Limited understanding of proactive irAE assessment further complicates this issue. Patient Reported Outcome (PRO) measures are standardised tools used to systematically collect data from patients about their health status, symptoms, functioning, and well-being, and are increasingly advocated for use in routine clinical care. However, their use in clinical care, and more specifically to assess irAEs and symptoms, is an understudied area. Objectives: To investigate the feasibility, acceptability, and usefulness of systematic assessment of irAEs from the perspectives of patients with cancer living in Saudi Arabia. Methods: The doctorate project involved five inter-related studies, underpinned by the theory of Symptoms Experience in Time (SET), a conceptual framework aimed at understanding the temporal dynamics of symptom manifestation and progression. In Study 1, a systematic literature review was completed. A comprehensive search strategy was employed to identify relevant literature on symptom assessment and management strategies related to irAEs in cancer patients. The review identified a PRO tool developed specifically for irAEs to assess 20 symptom and six interference items. In Study 2, the PRO tool identified for irAEs assessment from the review underwent robust translation from English into Arabic using the Brislin translation method. This involved forward and backward translations, consensus committees with health experts and linguists, and iterative adjustments to ensure linguistic accuracy and cultural appropriateness. Study 3 was an observational study undertaken in Saudi Arabia to evaluate the psychometric properties of the tool among Saudi Arabian cancer patients undergoing immunotherapy. The assessment involved mixed methods, including cognitive interviewing to assess item clarity and relevance, content validity and test–retest reliability analysis, and a post-assessment feedback survey to assess acceptability. Study 4 was a prospective observational cohort study over four weeks that investigated the feasibility, acceptability, and usefulness of the translated tool to assess irAEs and symptom experiences of patients undergoing immunotherapy for cancer in Saudi Arabia. Finally, in Study 5, a subset of participants from Study 4 participated in in-depth semi-structured interviews, which were analysed using qualitative content analysis.

Results: Study 1: The systematic literature review identified a suitable PRO tool for assessing diverse irAEs among cancer patients undergoing immunotherapy. The review also identified gaps in evidence, including the unclear frequency of symptom assessment and the role of non-pharmacological approaches for managing mild irAEs. In Study 2, the PRO tool was translated, creating the Arabic version of the tool: the Arabic Immunotherapy Symptom Assessment Inventory (AISAI). Study 3 evaluated the psychometric properties of the AISAI, which demonstrated content validity, reliability, linguistic precision, and cultural relevance. The Cronbach’s alpha coefficients for the internal consistency were calculated as 0.90 for the 20 symptom items and 0.88 for the interference scale, indicating satisfactory reliability. The test–retest reliability, assessed through intraclass correlation coefficients (ICC), showed excellent agreement between Time 1 and Time 2, with ICC values above 0.90. In Study 4, a real-world, 4-week evaluation involving a cohort of 69 patients undergoing cancer immunotherapy treatment was completed. The feasibility and acceptability of administering the AISAI were high, with 97.1% affirming its acceptability and applicability. The five most prevalent and severe symptoms, based on mean scores, were: numbness or tingling; pain; rash or skin change; interference with general activity; and impaired walking. Over the 4- week immunotherapy period, there was a notable increase in the severity of symptoms, with statistically significant changes observed. The number of participants with moderate (score 4–6) and severe (score 6–10) symptoms increased, indicating a worsening pattern over time. In Study 5, a qualitative evaluation affirmed that the AISAI was perceived as a valuable tool for early recognition and assessment of irAEs, with a preference for routine usage. The evaluation also highlighted knowledge gaps, emphasising the need for educational interventions to enhance comprehension and management capabilities among patients. Conclusion: This thesis represents a novel contribution to the field, particularly in the context of cancer patients undergoing immunotherapy treatment in Saudi Arabia. It introduces an innovative approach by incorporating PROs in Saudi Arabia. This marks a significant advancement in the assessment practices related to irAEs. Notably, it is the first study to explore the experience of irAEs in Saudi Arabia using PRO, providing a comprehensive understanding of the challenges faced by these patients. Moreover, this research pioneers the investigation of the use of the AISAI in real-world settings for cancer patients undergoing immunotherapy. It assesses the tool’s acceptability, feasibility, and usefulness, shedding light on its practical implications in the clinical setting. The research contributes a valid and comprehensive tool, the AISAI, designed specifically for assessing irAEs in Arabic cancer patients. This research makes a valuable contribution to clinicians, patients, and researchers, enhancing the overall understanding and approach to assessment of adverse events in the context of cancer immunotherapy.