# Delving into Causal Discovery in Health-Related Quality of Life Questionnaires
## 1 Introduction  
Health-related quality of life (HRQoL) questionnaires are standardized instruments designed to assess individuals' perceptions of their well-being and health status. HRQoL questionnaires cover various aspects of life, including physical, psychological, emotional, and social dimensions, and they are commonly used in clinical research and healthcare to measure the impact of health conditions and treatments on individuals' lives. The EuroQol questionnaire with five dimensions and five levels (EQ-5D-5L) is one of the most widely used HRQoL questionnaires [1]. It was designed to assess individuals' overall health across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression [1]. Each dimension has five response levels, providing a more informative evaluation compared to the original EQ-5D-3L that included three response levels [2, 3]. The MOS 36-Item Short-Form Health Survey (SF-36) assesses eight health domains, including physical functioning, role limitations due to physical health, body pain,general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health [4]. The World Health Organization Quality of Life--Brief Version (WHOQOL-BREF) was developed by the World Health Organization [5] and is an abbreviated version of the WHOQOL-100 quality of life assessment [6; 7; 8]. It produces scores for four dimensions: physical health, psychological health, social relationships, and environment. Health-related quality of life questionnaires specifically tailored for cancer patients aid healthcare professionals in better understanding the broader implications of cancer beyond traditional clinical measures and in tailoring supportive care strategies to enhance the overall well-being of cancer patients. Thus, they emerge as an integral tool in managing cancer patients. One of the most widely utilized HRQoL questionnaires in cancer research is the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) [9]. It assesses the HRQoL of cancer patients across physical, emotional, and social functioning domains, and symptoms such as fatigue and pain [9]. The EORTC QLQ-CLL17 is a module designed as an extension of EORTC QLQ-C30, specifically focusing on symptoms, treatment side effects, and disease-related issues unique to patients with chronic lymphocytic leukemia (CLL) [10]. By combining QLQ-C30 with QLQ-CLL17, a more enhanced understanding of the impact of CLL and its treatment on a patient's overall well-being can be obtained. Other HRQoL questionnaires that delve into disease-specific symptoms and treatment-related concerns, thus offering a more targeted approach for specific cancer types, are included in the Functional Assessment of Cancer Therapy (FACT) measurement system [11]. The FACT system comprises a widely used set of instruments that are designed for various cancer types, such as breast cancer (FACT-B) [12], lung cancer (FACT-L) [13], colorectal cancer (FACT-C) [14], leukemia (FACT-Leu) [15], and vulvar cancer (FACT-V) [16]. There are multiple examples in the literature where HRQoL questionnaires have been employed. For example, EQ-5D-5L has been employed by the authors of [17; 18; 19; 20], SF-36 by [21; 22; 23; 24], WHOQOL-BREF by [25; 26; 27], EORTC QLQ-C30 by [28; 29; 30; 31], QLQ-CLL17 by [31], and FACT-based questionnaires by [32; 33; 34; 35]. The analysis of HRQoL data is most frequently based on descriptive statistics, standard correlation analysis, and inferential statistics (see, e.g., [37]). For instance, the correlation ([PERSON], [PERSON]) between HRQoL scores and demographic, clinical, biological, and other parameters was assessed by the authors of [18; 23; 25; 26; 27; 29; 35; 36]. HRQoL scores were compared either among different subgroups of patients [17; 18; 21; 22; 24; 30; 32] or between the subgroups of patients and controls [20; 22; 23; 25; 27; 31].