Tradition measures of recovery, such as patient-reported symptoms, objective measures such as balance, specific dimensions such as depression, fatigue, cognitive status, and exercise tolerance do not fully capture the impact of the concussion on performing individual activities and participating in life situations as experienced by the patient. No concussion-specific measure of functional status currently exists. Objectives The overarching purpose of this dissertation was to develop a concussion-specific measure of functional status. There were two specific objectives: 1. To examine the concept of functioning post-concussion; 2. To generate questionnaire items based on a conceptual model of functioning. Methods This dissertation follows the recommendations of the Association for Medical Education in Europe as a framework with which to meet the objectives. The first objective was addressed by (1) generating a list of concussion-specific concepts through a systematic review (Chapter 3), and (2) qualitative interviews with individuals with persistent post-concussion symptoms and clinicians with concussion expertise (Chapter 4). The relationships between the concepts that emerged from those studies are presented graphically in a conceptual model to meet the second objective. The concepts were then transformed into questionnaire items and pretested through cognitive interviews with individuals with PPCS and clinicians with concussion expertise. Finally, the questionnaire items were critically evaluated for proportion of shared content against existing measures used in concussion clinical trials by coding all items to the International Classification of Functioning, Disability and Health. Results Objective 1 Three main themes emerged from the qualitative findings: (1) functioning at the level of the individual and society; (2) environmental barriers and facilitators; and (3) capacity, defined as the length of time one could perform a task before the onset of symptoms, and the length of time it took to recovery from those symptoms. Objective 2 The final questionnaire is presented as the CORE-Q, which is comprised of 53 items over three complimentary subscales, namely the Post-Concussion Functional Scale, the Concussion Modifiers Scale, and the Global Functional Recovery Scale. Each subscale corresponds to one of the three main themes. No existing outcome measure contained more than 40% of the content within the CORE-Q, or 55% of any subscale. Conclusions The CORE-Q is a unique measure of functional status post-concussion that considers functioning from a biopsychosocial perspective. Further studies are needed to assess the psychometric properties of the CORE-Q before it is adopted into clinical practice and intervention trials.

CHAPTER 1: Introduction: The most common craniofacial congenital anomaly is the cleft lip and/or palate (CLP). The CLEFT-Q is the first condition-specific comprehensive patient reported outcome instrument (PROM) for patients with CLP. Other measures used in assessment of patients with CLP are Child Oral Health Impact Profile (COHIP) and Cleft Hearing, Appearance and Speech Questionnaire (CHASQ). The development and validation of the CLEFT-Q have been completed in three phases. In phase I, 138 patients with CLP from six countries were interviewed, and data were used to form 13 scales measuring appearance, facial function and health-related quality of life (HR-QOL). In phase II, scales were field-tested internationally with 2434 patients to examine reliability and validity as well as develop a common scoring algorithm for international use. Phase III, the focus of this thesis, aimed to examine further construct validity and responsiveness of the CLEFT-Q scales. CHAPTER 2: Methods: Patients were recruited at six cleft centres in Canada, USA and UK between January 2018 and October 2019. The sample included patients aged 8-29 seeking rhinoplasty, orthognathic, cleft lip scar revision and alveolar bone graft (ABG) operations. Before and six months after surgery, participants were asked to complete the CLEFT-Q scales relevant to their operation and two other PROMs frequently used in cleft research, i.e., COHIP and CHASQ. Cross-sectional construct validity was examined by testing prespecified hypotheses about expected relationships between CLEFT-Q, CHASQ and COHIP instruments. Internal responsiveness was examined using the distribution-based method. Data were analysed using paired sample t-tests and calculation of effect sizes (ESs) and minimally important differences (MIDs). CHAPTER 3: Results: Examination of cross-sectional construct validity of the CLEFT-Q scales using the COHIP and CHASQ subscale resulted in 39/53 (74%) hypotheses having been supported by the results. The required sample size to examine responsiveness using the anchor-based approach was not reached. Assessment of internal responsiveness using the distribution-based approach demonstrated that the appearance scales were highly responsive to change following cleft-specific surgeries, with statistically significant results and ESs ranging from 0.4 (small) to 1.8 (large). Change on the CLEFT-Q HR-QOL scales was not statistically significant. As predicted, the ESs on scales measuring facial aspects most affected by rhinoplasty and orthognathic surgeries were larger than the ESs on scales measuring facial aspects least affected by these surgeries. MIDs for each scale in each operation were determined. CHAPTER 4: Discussion: Assessment of cross-sectional construct validity demonstrated that CLEFT-Q performs as it was intended when compared with other similar measures (i.e., CHASQ and COHIP). The CLEFT-Q appearance scales were responsive to change following rhinoplasty, orthognathic and cleft lip scar revision operations. As predicted, the CLEFT-Q appearance scales did not detect change following the ABG operation as this operation does not result in visible difference. As hypothesized, the CLEFT-Q HR-QOL scales were less responsive to change than appearance scales as HR-QOL is a more distal construct than appearance in relation to the cleft-related surgeries performed. The preliminary MIDs estimated by the distribution-based approach should be confirmed in studies with diverse CLP populations and larger sample sizes using the anchor-based approach. The findings of this phase III study build on the results of another CLEFT-Q validation study, which demonstrated the ability of the CLEFT-Q scales to detect differences between groups with varying surgical status, i.e., need surgery, have had surgery and never needed surgery. CHAPTER 5: Conclusion: Cross-sectional construct validity of the CLEFT-Q scales was supported by most prespecified hypotheses. The CLEFT-Q scales were found to be responsive to change. MIDs were determined. The results of this phase III study should be confirmed in a larger and more culturally diverse patient population. Future studies to examine reproducibility and measurement error as well as external responsiveness of the CLEFT-Q scales may be beneficial to add to the psychometric evaluation process. / Thesis / Master of Science (MSc)

No description available.

Throughout the last decades, evolving treatment-opportunities provide a better chance of cure and thereby a higher percentage of patients is being treated for chronic disease (Robert Koch Institut, 2016). As treatment-toxicity, side effects and disease-derived symptoms remain high, it has become crucial to assesses parameters reflecting patients’ perspective, instead of solely focusing on illness-centered outcomes such as survival or treatment response. During the last decades, Patient-reported outcomes (PROs) are on the rise throughout research and cancer care as a key component to capture a patient’s perspective. This work illustrates the broad framework that PROs can be conducted in. We gathered experience and pioneered a systematic PRO-assessment in routine outpatient care, which continues to be updated. We identified a suitable PRO-based geriatric screening tool to avoid a time and resource consuming comprehensive geriatric assessment. Furthermore, we explored the beneficial effects of a PRO-based tailored intervention on HRQoL and provided effect-size estimations. Assessing PROs yields many benefits throughout the care pathway (Andreassen et al., 2006; Basch et al., 2016; Kofoed et al., 2012; Velikova et al., 2004; Yang et al., 2018) and was shown to be feasible in different entities and treatment setting (Bennett et al., 2016; M. K. Schuler et al., 2016; Strasser et al., 2016; Warrington et al., 2019). As a strikingly large discordance between patients’ and clinicians’ perception of symptoms exists (Atkinson et al., 2016), PROs can increase the accuracy of detection of adverse events and even predict survival (Efficace et al., 2021). Based on these advantages, the EMA and the FDA advocate the use of PROs as endpoints in cancer research (European Medicines Agency, 2016; U.S. Department of Health and Human Services FDA Center for Drug Evaluation and Research et al., 2006). Throughout previous years, methodological progress has been made resulting in elaborated measurement technics such as computerized adaptive testing being applied to PRO-instruments (Petersen et al., 2018, 2020). Clinical usability was increased with development of summary scores, cut-off values and emerging normative data (Giesinger et al., 2016, 2020). Interventions based on PROs are promising (Ishaque et al., 2019; Kotronoulas et al., 2014). Despite this ever increasing body of literature on PRO, a significant number of questions remain unanswered. Firstly, there was scarce knowledge about the benefits of a PRO-based intervention in sarcoma patients as there was limited PRO-data available in this entity. Sarcomas are rare diseases, still accounting for slightly less than 1% of all malignant neoplasia worldwide. The age adjusted incidence ranged from 7.4 per 100.000 men and 6.6 per women in Germany (Ressing et al., 2018). As sarcoma-treatment is improving, side-effects and toxicity remain to occur frequently (Gough et al., 2011; McDonough et al., 2019; Reichardt et al., 2012; Storey et al., 2019; Winnette et al., 2017). Until recently, there was quite limited knowledge about the patient-reported burden in terms of HRQoL, symptoms and psychological distress in patients with STS (Tang et al., 2012). PRO-based interventions yield beneficial effects in different cancer entities. Nevertheless, the effects of a PRO-based intervention in STS-patients was scarcely explored. The YonLife-Study (Publication B, Hentschel et al., 2020) contributes new evidence that a PRO-based intervention yields beneficial effects on HRQoL and suggests a positive, yet non-significant effect on survival. Concerning symptoms, the results of the YonLife-intervention remain far from being encouraging. As effects sizes are available now, RCTs which are powered to a confirmatory purpose could be performed in this population. Secondly, the importance of PROs are emphasized by authorities such as EMA or FDA that emphasize the need to incorporate PRO in scientific studies. Yet during the early 2010s, the actual incorporation of PROs in clinical routine was limited in Germany. We therefore designed and established a routine assessment of PROs (Publication C, (Trautmann, Hentschel et al., 2016) incorporating the automatized calculation, comparison with normative or threshold data and implemented it to our hospital information system. As until recently, feasibility data such for such an intervention is scarce, we collect measures of adherence, required time and barriers reported by staff. For the clinical benefit, the established PRO-assessment is being developed further and expanded to other departments and clinics of our institution. Thirdly, as numbers of geriatric cancer patients rise (Le Saux et al., 2019), older patients continue to be underrepresented in clinical trials (Singh et al., 2017), therefore an immense lack of knowledge on treatment-toxicities and side effects in this population exists. Treatment needs to be adapted to older patients frailty-level, which can be conducted applying a time- and resource consuming Comprehensive Geriatric Assessment (Le Saux et al., 2019). Still, there is no consensus on which domains to include and how to measure them (Hamaker, Jonker, et al., 2012). A geriatric screening can alleviate burden of conducting a whole CGA. Several screening instruments exists, yet there is inconsistent data (Kotzerke et al., 2019; Mohile et al., 2018; Soubeyran et al., 2014) which tool yields the best predictive performance. Our project aimed to compare three of the available screening tools (VES-13, G8, POT/CARG). Being far from having a perfect predictive performance, the POT/CARG occurs to be the screening instrument with a high sensitivity and sufficient negative predictive value. Furthermore, our research supports the increasing evidence that ultra-short-screeners such as ECOG state or age bear only insufficient predictive performance.:1. Introduction 1.1 What are Patient-reported outcomes (PROs)? 1.2 Assessment of PROs 1.2.1 Feasible in clinical routine, improving relevant outcomes 1.2.2 Improving diagnostic accuracy 1.2.3 Supporting drug development 1.2.4 Evolving measurement techniques and standardization 1.3 PRO-based feedback interventions 1.4 PRO-based geriatric screening 1.5 Research needs 1.5.1 Identifying a suitable geriatric screener 1.5.2 Limited PRO-data on Soft-Tissue Sarcoma (STS) patients 1.5.3 Feasibility-research in routine care 1.6 study aims 2. Methods 2.1 Design and Sample of Publication A 2.2 Design and Sample of Publication B 2.3 Design and Sample of Publication C 2.4 Instruments 2.5 Non-PRO-Outcomes 2.5.1 Predictive performance 2.5.2 Survival analysis 2.5.3 Feasibility analysis 2.6 Statistical Analysis 2.6.1 Sample Size Estimation 2.6.2 Non-participation and drop-out analysis 2.6.3 Regression Analyses 2.6.4 Statistical software 2.6.5 Statistical analysis plans 3. Outline of Publications Publication A Publication B Publication C 4. Discussion 4.1 Main findings, integration in existing research and research implications 4.1.1 Geriatric screening tools 4.1.2 PROs in soft tissue sarcoma (STS) 4.1.3 Implementation of PROs into routine care 4.2 Strengths and Limitations 4.2.1 Strengths 4.2.2 Limitations 5. Conclusions 6. Summary 7. References 8. Appendix 8.1 Darstellung des eigenen Beitrags 8.1.1 Darstellung des eigenen Beitrags zur Publikation A 8.1.2 Darstellung des eigenen Beitrags zur Publikation B 8.1.3 Darstellung des eigenen Beitrags zur Publikation C 8.2 Erklärung über die eigenständige Abfassung der Arbeit 8.3 Curriculum Vitae 8.4 Publikationsverzeichnis 8.5 Danksagung

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23790号 / 医博第4836号 / 新制||医||1057(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 山本 洋介, 教授 佐藤 俊哉, 教授 柳田 素子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

In deciding whether to use a particular treatment for conditions such as depression, arthritis, or heart disease, clinicians and patients must balance the benefits against the side effects and burden. To make this trade-off, they must understand the likely degree of benefit in patients’ symptoms and perceived wellbeing, best undertaken using patient-reported outcomes (PROs). PROs are measures of any aspect of a patients’ health status that are obtained from direct patient inquiry without interpretation by a clinician or anyone else. PRO measures (PROMs) are increasingly used in clinical trials and systematic reviews to evaluate health care interventions, and information obtained from PROMs can guide clinical decisions and inform shared-decision making. The use of PROMs, however, involves challenges, the most important of which is deciding if a particular treatment effect is trivial, small but important, moderate or large. One way to make this judgment is to consider the minimal important difference (MID), the smallest change in a PROM score that is important enough that patients would consider a change in treatment to achieve that benefit. The number of published studies providing anchor-based MIDs for PROMs has grown rapidly over the last three decades, and researchers have proposed several anchor-based methods to derive MID estimates, each with its own merits and limitations. This thesis begins with the development of a framework to determine the extent to which the design and conduct of studies measuring anchor-based MIDs are likely to have protected against misleading estimates. Subsequently, this thesis presents a comprehensive inventory of empirically estimated anchor-based MIDs and their associated credibility for all PROMs published in the medical literature. Further, this thesis highlights critical issues that key stakeholders should consider, and demonstrates how the use of credible MIDs may inform the development of a clinical practice guideline in which PROs were identified as critically important. Finally, this thesis concludes with insights to improve the methodological quality and transparency for researchers in the PRO and MID field. / Thesis / Doctor of Philosophy (PhD)

Background: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons. Preference-based measures (PBMs) of health-related quality of life (HRQL) can be utilized for cost-effectiveness analyses of interventions in individuals with ALS. However, current measures are generic (GPBMs) and the psychometric properties of these measures have not yet been evaluated in ALS. Purpose: The purpose of this thesis was to evaluate the psychometric properties of GPBMs in ALS by 1) conducting a systematic review of the psychometric properties of GPBMs, and 2) assessing the content and convergent validity of GPBMs in ALS. Methods: Two studies were conducted. First, a systematic review was performed, and four databases were searched to identify studies that used and reported on the psychometric properties of GPBMs in ALS. Second, participants were recruited from three clinical sites across Canada and outcome measures were administered through an online or hardcopy survey. Areas of importance to the HRQL of individuals with ALS were identified using the Patient Generated Index (PGI), mapped against GPBMs to determine their coverage and scores were compared to determine convergent validity. Results: For the first study, the EQ-5D-3L was found to be the most commonly used GPBMs in ALS. It demonstrated convergent and known-groups validity however, significant floor effects were observed. For the second study, results indicated that the majority of GPBMs identified approximately half of the areas impacted by ALS. In addition, there were several domains not identified by GPBMs. Conclusion: This thesis highlights the importance of complete psychometric evaluation of measures in ALS. There is the need for the development of an ALS specific preference-based measures that reflects the health concerns of individuals with ALS; as GPBMs used in ALS were evaluated and deemed to be lacking in support for their usage in ALS. / Thesis / Master of Science Rehabilitation Science (MSc) / Amyotrophic Lateral Sclerosis (ALS) is a fatal disease that causes individuals to lose their strength and eventually the ability to speak, eat, move and breathe. Questionnaires can be used to understand the health-related quality of life (HRQL) of individuals with ALS however these measures do not always reflect the experiences of these individuals. The goal of this dissertation was to identify whether measures truly capture areas important to individuals with ALS. In our studies, we found that there is little proof in the accuracy of measures used. In addition, the measures do not fully capture the areas of life important to individuals with ALS. This is important to help researchers and health care professionals understand the effects of ALS on HRQL. These results will help them determine which treatments are worthwhile and the best to use in practice and provide recommendations for future research.

Measurement Based Care (MBC) is considered to be an evidence-based practice. Despite its well-documented efficacy, it is underutilized in the clinical community for various reasons, including clinician and patient buy-in. A key component to the successful implementation of MBC is the routine administration of Patient Reported Outcome Measures (PROMs). There is a lack of research describing the utilization of MBC in a telehealth setting. As technological innovations continue, a greater number of clinics are offering telemental health services. Additionally, the COVID-19 pandemic caused a majority of underprepared clinics to begin implementing telehealth. The present study sought to evaluate patient compliance with PROMs in MBC after an abrupt shift to telehealth due to the COVID-19 pandemic. Participants were collected from a clinical population at a community based psychological training clinic. The participants were separated into groups: modality 1 (in-person services, n = 17), modality 2 (telehealth services, n = 17), and modality 3 (hybrid of modalities 1 and 2, n = 10), to assess the effect of modality on mean PROM compliance. The participants were separated into groups adult (≥18 years of age, n = 23) and child (<18 years of age, n = 17), to assess the effect of maturity on mean PROM compliance. Results showed that mean PROM compliance was significantly higher in the in-person modality than the telehealth modality. Results also showed that PROM compliance was significantly higher in adults than in children. There was not a significant interaction effect of modality and maturity on PROM compliance. Additionally, results showed that PROM compliance decreased significantly after the switch from in-person services to telehealth services in the hybrid modality. These findings show that clinics may face significant barriers to the implementation of MBC after a sudden shift to telehealth caused by an unforeseen stressful event. / M.S. / Measurement-Based Care (MBC) is an effective practice for the treatment of patients in psychological practices. It is a collaborative process that involves the clinician and patient tracking treatment progress and outcomes through the use of consistently administered measures known as Patient Reported Outcome Measures (PROMs). Although MBC has been shown to be effective, there is little literature regarding its use in a telehealth setting. As a greater number of clinics begin offering telehealth services, questions regarding patient adherence to interventions have arisen. Furthermore, the global COVID-19 pandemic forced a majority of underprepared clinics to offer telehealth services. The current study sought to better understand potential barriers to the implementation of MBC in a telehealth setting. Participants were collected from patients receiving therapy at a community based psychological training clinic. The participants were separated into the groups: in-person services (n = 17), telehealth services (n = 17), and hybrid of in-person and telehealth (n = 10), to assess the effect of modality on mean PROM compliance. The participants were separated into groups adult (≥18 years of age, n = 23) and child (<18 years of age, n = 17), to assess the effect of maturity on mean PROM compliance. Results showed that patients in the in-person therapy group were more likely to complete their measures than patients in the telehealth therapy group, regardless of their maturity. Additionally, adult patients were more likely to complete their measures than child patients, regardless of the modality. Results also showed that patients who experienced both in-person and telehealth services were more likely to complete their measures before the switch to telehealth. These findings show that clinics may face significant barriers to the implementation of MBC after a sudden shift to telehealth caused by an unforeseen stressful event.

Introduction: Conversation treatment for individuals with aphasia (IwAs) aims to enhance language and communication skills within naturalistic settings. Group dynamics, including psychosocial support (PSS) and vicarious learning (VL), are important components of this treatment. However, the lack of established aphasia-friendly methods for quantifying group dynamics impedes understanding of its contribution to treatment efficacy. This study addresses three key research goals: (1) Can group dynamics be reliably quantified? (2) Do measures of group dynamics vary with group size or time? (3) Are group dynamics linked to changes in self-reported psychosocial health measures? Methods: IwAs were assigned to participate in either a large group or dyadic condition as part of a larger study. Participants completed multiple standardized assessments before and after receiving conversation treatment for one hour twice a week for ten weeks. A coding system was developed to track PSS and VL during sessions. Video recordings of sessions at the start (Session 2) and end (Session 19) of the treatment period were analyzed for five large groups and six dyads, with seven additional dyads coded for Session 19 after reliability was confirmed. Intrarater and interrater reliability were assessed by recoding 21% of the videos randomly. Results: To address the first research goal, group dynamics were defined and then a code was created to represent occurrences of PSS and VL. After establishing a reliable coding system, instances of PSS and VL were compared across size conditions to address the second research goal. The results suggested that PSS differed between conditions later in treatment, but VL did not. For research goal three, the data suggest that large groups experience larger gains in quality of life measures, possibly due to increased exposure to PSS. Conclusion: Findings indicate that group dynamics can be reliably tracked and used for quantitative analysis. PSS was more common in groups than dyads later in the 10 week treatment period, but VL did not vary across conditions or at the start or end of treatment. Further, there is some evidence that PSS in larger groups contributes to improvements in quality of life measures. / Communication Sciences

Yes / Purpose: To develop and validate the first patient-reported outcome measure (PROM) to quantify vision-related dizziness. Dizziness is a common, multifactorial syndrome that causes reductions in quality of life and is a major risk factor for falls, but the role of vision is not well understood. Methods: Potential domains and items were identified by literature review and discussions with experts and patients to form a pilot PROM, which was completed by 335 patients with dizziness. Rasch analysis was used to determine the items with good psychometric properties to include in a final PROM, to check undimensionality, differential item functioning, and to convert ordinal questionnaire data into continuous interval data. Validation of the final 25-item instrument was determined by its convergent validity, patient, and item-separation reliability and unidimensionality using data from 223 patients plus test–retest repeatability from 79 patients. results: 120 items were originally identified, then subsequently reduced to 46 to form a pilot PROM. Rasch analysis was used to reduce the number of items to 25 to produce the vision-related dizziness or VRD-25. Two subscales of VRD-12-frequency and VRD-13-severity were shown to be unidimensional, with good psychometric properties. Convergent validity was shown by moderately good correlations with the Dizziness Handicap Inventory (r = 0.75) and good test–retest repeatability with intra-class correlation coefficients of 0.88. conclusion: VRD-25 is the only PROM developed to date to assess vision-related dizziness. It has been developed using Rasch analysis and provides a PROM for this under-researched area and for clinical trials of interventions to reduce vision-related dizziness. / College of Optometrists (UK) research studentship.