Background: Cleft lip and/or palate (CL/P) is the most common congenital craniofacial anomaly, which may negatively impact one’s appearance, health-related quality of life, and facial function. The course of treatment is intensive and multifaceted. Patients with CL/P can undergo numerous procedures, with the goal of improving their appearance or facial function. To assess the outcomes of treatment in patients, a well-developed, valid, and reliable patient-reported outcome instrument is required. The CLEFT-Q is a new patient-reported outcome instrument developed to evaluate outcomes of treatment in patients aged 8 to 29 years with cleft lip and/or palate. The purpose of this thesis was to establish content validity and transferability of the CLEFT-Q. Methods: Study 1 of this thesis presents findings from cognitive interviews with patients and expert feedback. Patients aged between 6 and 29 years were recruited from 6 plastic surgery clinics. Healthcare providers and experts from 8 countries participated in a focus group or provided individual feedback. Input was sought on all aspects of the CLEFT-Q development, including item wording, instructions, response options, and to identify missing content. Studies 2 and 3 present findings from the translation and cultural adaptation of the CLEFT-Q to evaluate its transferability. Guidelines set forth by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) were applied. Results: Study 1 involved 69 patients and 44 experts who reviewed the CLEFT-Q. The first draft of the CLEFT-Q consisted of 163 items measuring 12 constructs. Three rounds of interviews and expert feedback were needed to establish content validity. At the completion of the cognitive interviews and expert review, the CLEFT-Q comprised 171 items within 13 scales that measure appearance (of the face, nose, nostrils, teeth, lips, jaws, cleft lip scar), health-related quality of life (psychological, social, school, speech-related distress), and facial function (speech, eating/drinking). Studies 2 and 3 involved the translation and cultural adaptation of the CLEFT-Q from English to 6 different languages including Arabic, Catalan, Dutch, Hindi, Swedish, Turkish, and 3 Spanish language varieties (Colombian, Chilean, and Spain). A total of 18 (12%), 18 (12%), 7 (5%), and 4 (3%) items were difficult to translate during the forward translations for the Arabic, Swedish, Dutch, and Hindi versions respectively. Among the Spanish varieties (study 3) only 10 (7%) items were difficult to translate into Chilean. Comparison of the back translation to the source language version of the CLEFT-Q identified that the meaning of 40 (26%), 17 (11%), 9 (6%), and 5 (3%) items in the Turkish, Arabic, Hindi, and Swedish translations respectively had changed and required re-translation, and none were changed for the Dutch translation in study 2. Similarly, in study 3, back translations identified 23 (15%), 21 (13%), 12 (8%), and 10 (6%) items in the Colombian, Catalan, Chilean, and Spanish (Spain) versions respectively whose meanings were changed. Study 2 cognitive debriefing interview participants were mostly below 20 years of age (n= 36, 88%) with CL/P (n=30, 73%). Participants in study 3 were primarily male (n=14, 67%) diagnosed with CL/P (n=17, 81%). Overall, participants in the cognitive debriefing interviews described the CLEFT-Q as understandable and easy to complete. Conclusion: This thesis presents evidence of the CLEFT-Q’s content validity and transferability. After the completion of study 1, no changes were required to the original CLEFT-Q conceptual framework; however, cognitive interviews and expert review allowed us to identify items that required re-wording, re-conceptualizing, to removal, or addition. Finally, the process of translating and culturally adapting the CLEFT-Q in studies 2 and 3 was useful for finalizing the CLEFT-Q scales, and provided evidence of its transferability to other contexts. / Thesis / Doctor of Philosophy (PhD) / Background: Treatment of cleft lip and/or palate (CL/P) is intensive and involves multiple procedures to improve ones appearance or facial function. To assess outcomes of treatment in patients with CL/P, a well-developed, valid, and reliable patient-reported outcome instrument is required. The purpose of this thesis was to establish content validity and transferability of the CLEFT-Q. Methods: Cognitive interviews with patients and expert feedback were obtained in Study 1. Input was sought on the CLEFT-Q item wording, instructions, response options, and to identify missing content. Studies 2 and 3 involved the translation and cultural adaptation of the CLEFT-Q to evaluate its transferability. Results: Three rounds of cognitive interviews with patients and expert feedback were needed to establish content validity of the CLEFT-Q in study 1. Studies 2 and 3 involved the translation and cultural adaptation of the CLEFT-Q from English to 6 different languages including Arabic, Catalan, Dutch, Hindi, Swedish, Turkish, and 3 Spanish language varieties (Colombian, Chilean, and Spain). Translation and cultural adaptation processes provided evidence of the CLEFT-Qs transferability. Conclusion: This thesis presents evidence of the CLEFT-Q’s content validity and transferability.

Background: The management of cleft lip and/or palate (CL/P) includes multidisciplinary care beginning in infancy and continuing through to adulthood. Outcomes of cleft care have been difficult to measure because of the subjective nature of evaluating concepts such as appearance and speech. Including the patient perspective in outcome evaluation through the use of a patient-reported outcome (PRO) measure would provide a more accurate reflection of a patient’s status. The overall objective of this thesis is to show that through adherence to rigorous methods of development, a PRO measure can provide clinically meaningful outcome evaluation in cleft care. Methods: The first paper uses the qualitative method of interpretive description to define a conceptual framework to guide the development of a PRO measure for patients with CL/P, the CLEFT-Q. The second paper describes the protocol for the entire development of the CLEFT-Q. The third paper analyzes the results of the cross-sectional field-test of the CLEFT-Q scales to determine whether or not the CLEFT-Q is able to detect differences between specific cleft types. Results: The qualitative study included 138 patients with CL/P from six countries. The final conceptual framework contained thirteen concepts within the domains of appearance, facial function, and health-related quality of life. The second paper details the process of designing the CLEFT-Q scales. The field-test included 2,434 patients from thirty sites in twelve countries, and CLEFT-Q scores were found to vary with cleft type for all scales. Conclusions: PRO measures need to be rigorously designed in order to provide scientifically sound, clinically meaningful measurement. The CLEFT-Q is able to detect differences between patients with various cleft types, and will be a useful tool to provide the patient perspective in future outcome evaluation in cleft care. / Thesis / Doctor of Philosophy (PhD) / Measuring outcomes of treatment for cleft lip and/or palate (CL/P) should include the patient perspective. The objective of this thesis is to show that through rigorous methods of development, a patient-reported outcome (PRO) measure, the CLEFT-Q, can provide clinically meaningful evaluation of outcomes. First, 136 patients with CL/P from six countries were interviewed to learn what concepts related to having a cleft or its treatment are important to them. A conceptual framework was developed that informed the CLEFT-Q scales. Describing the methodology behind developing the CLEFT-Q then served to inform and engage members of the community. A field-test of the CLEFT-Q scales showed that in a sample of 2,434 patients with CL/P from twelve countries, CLEFT-Q outcomes varied in patients with different types of CL/P. The CLEFT-Q can be used to provide rigorous measurement of PROs in patients with CL/P in the future.