HRQL is typically measured using Clinical Outcome Assessment (COA) tools, i.e., instruments designed to measure concepts that include symptoms, overall mental state, or the effects of a disease or condition on how the patient functions and feels in their daily life [8]. The USA FDA has classified COA tools into four types: (1) clinician reported, (2) observer reported, (3) performance, and (4) patient reported [8]. PRO instruments are based on a report that comes from the patient about the status of his/her health condition without amendment or interpretation by a healthcare professional or anyone else [8]. The focus in this chapter is on PRO instruments developed for use with AYA cancer patients and survivors. We are particularly interested in self-report tools, as these are generally considered to be the preferred method for assessing a patient’s experience of a construct [11].

PRO instruments that measure HRQL can be generic or condition/disease specific. Generic instruments are those designed for use across many types of diseases, treatments, and populations [12]. Such broad-based tools can lack content validity for particular patient populations, e.g., fail to measure issues that matter [12]. Content validity is the measurement property that assesses whether items are comprehensive and adequately reflect the patient’s perspective for the concept of interest (COI) [13]. A range of generic instruments have been used with AYA cancer patients [14]. For example, in the younger cohort of AYA, our team conducted a systematic literature review valid through May 2011 and found that ten generic HRQL instruments had been used in 148 publications involving patients and survivors up to 25 years of age [14]. In the 148 publications, the most common measure used was the Pediatric Quality of Life Inventory (PedsQL) [15], which appeared in 58 publications [14]. The PedsQL is a 23-item PRO instrument that measures health problems within the following four domains: physical, emotional, social and school function [15]. The Health Utilities Index (HUI) [16, 17] (used in 26 publications) and the Child Health Questionnaire (CHQ) [18] (used in 25 publications) were the second and third most common generic HRQL instruments [14].

Another approach is the use of cancer-specific PRO instruments that were designed for use with various cancer subtypes. Since disease-specific PRO instruments address aspects specific to one disease (e.g., cancer), they may be more responsive to changes in health status [19]. The most common examples of such scales for cancer patients include the Functional Assessment of Cancer Therapy Scale (FACT-G) [20] and The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) [21]. Both of these instruments, which were designed for adults (age range 27–89), also include a suite of scales for particular cancer subtypes. The FACT-G measures a range of domains, including physical, social, emotional, and functional well-being and relationship with doctor [20]. There are separate versions for certain cancer types prevalent among AYA (e.g., lymphoma, leukemia, and central nervous system (CNS) tumors) [20]. The EORTC QLQ-C30 measures a range of constructs, including function (physical, role, cognitive, emotional, and social), symptoms (fatigue, pain, and nausea/vomiting), global health, and QOL [21].

To understand the impact of childhood cancer on HRQOL, a longitudinal frame of reference is often necessary [22]. HRQOL effects may change substantially throughout the course of the illness. Unfortunately, our systematic review primarily identified cross-sectional studies, which cannot detect the effects of illness that evolve with time. The QOL for AYA patients can change dramatically during their treatment course. For example, teenagers with Hodgkin disease had a significant improvement in their PedsQL of more than ten points when compared between the radiation and chemotherapy phase of treatment, which further improved off treatment [23]. In general, only short-term follow-up studies have been done in these patients, with long-term studies sorely needed. Future research should seek to incorporate longitudinal assessments of HRQOL in order to capture the evolving effects of childhood cancer for AYAs.

In order to include the voice of AYA in the assessment of treatment outcome, well-defined, valid, reliable and responsive PRO instruments that measure the concepts of importance to AYA are needed. The choice of which PRO instrument to use in clinical research or clinical practice is a crucial decision. If the wrong scale is used, it may appear that an effective treatment has little or no benefit. The use of a generic or even cancer-specific scale that was not designed specifically for the AYA population may not provide evidence that a treatment works or may not adequately assess HRQL. The right scale to use in a clinical trial is the one that has content validity for the context of use [8, 13, 24].

There have been recent calls for the development of AYA-specific tools. Nightingale and colleagues reviewed 16 qualitative studies of young adult survivors of childhood cancer and suggested that existing HRQL instruments do not comprehensively cover the concerns of AYA, which they found to include the following six domains: physical, social, psychological, spiritual, fertility/sexual, resilience, and body appearance [25]. Quinn et al. took a different approach by interviewing 30 young adult survivors of childhood cancer to identify content limitations in two adult-onset cancer survivor-specific HRQL instruments, i.e., Quality of Life in Adult Cancer Survivors (QLACS), Quality of Life – Cancer Survivors (QOL-CS), and a generic HRQL instrument (SF-36) [26]. The authors report three areas where content was lacking, including perceived sense of self, relationships, and parenthood [24]. Kuhlthau and colleagues [27] conducted focus groups with 19 AYA survivors of CNS tumors and identified the following seven key survivorship domains: physical health and well-being, mental health and well-being, cognitive functioning, social health and well-being, health behaviors, sexual and reproductive health, and support systems. These authors suggest that there are aspects of HRQL important to patients that are not covered by currently available HRQL tools [27]. The common theme across these three qualitative studies is that HRQL tools not developed specifically for AYA may lack content validity [25–27].

In order to conceptualize the most important health concerns of AYA patients with cancer and survivors, our team performed a content analysis of HRQL instruments used with AYA to date. Our specific aims were as follows: (1) to identify cancer-specific PRO instruments measuring the HRQL concerns of AYA and (2) to perform a content analysis that involved coding and categorizing the items of each identified PRO instrument. Our overall goal was to develop a preliminary conceptual framework of HRQL content deemed important to AYA by PRO instrument developers.

We aimed to identify self-report cancer-specific PRO instruments for AYA, which were available in English and have published evidence of a development and/or validation process. We used the findings from two previous systematic reviews [14, 28] and performed an additional literature search of our own. In the first review, Anthony et al. sought to identify generic and cancer-specific PRO instruments that measured HRQL in cancer patients and/or survivors aged up to 25 years. The methods and results are described in detail elsewhere [14]. In the second review, Clinton-McHarg et al. [28] sought to identify cancer-specific multidimensional PRO instruments that measure psychosocial outcomes, including HRQL, in AYA cancer survivors. Finally, to ensure all possible HRQL instruments were identified, we performed an updated search of Medline, PsycINFO, EMBASE, and CINAHL databases from January 2008 to December 2014 for English language articles, replicating the search strategy outlined by Clinton-McHarg et al. [28]. For all PRO instruments identified, we obtained a paper copy and transferred the content into an Excel spreadsheet for coding. We then used the content analysis method described by Anthony et al. [14], which classified content according to the broad structure of the Patient-Reported Outcomes Measurement Information Systems (PROMIS), a health framework consisting of domains, subdomains, and identifying concepts [14].

Our search identified a total of 12 instruments for use with AYA cancer patients and survivors. Table 30.1 outlines the characteristics of each instrument. The age range of participants for whom the scales were developed ranges from 8 to 39 years. The number of items included in each instrument varied ranging from 16 to 90, and the number of domains ranged between four and nine. Seven instruments were designed for use with cancer patients both on and off treatment, and five were designed for childhood cancer survivors.