Determination of minimal important difference and patient acceptable symptom state of patient reported outcome measures in immunologically mediated oral mucosal diseases
Immunologically mediated oral mucosal diseases are a group of chronic conditions that give rise to varying degrees of painful oral symptoms, leading to impairment of normal functions of the mouth and quality of life (QoL) of affected individuals. Patient reported outcome measures (PROMs) provide standardized methods of capturing important outcomes directly from the patients, which have practical implications for monitoring the impact of the disease on patients as well as assessing the effectiveness of interventions in clinical trials of immunologically mediated oral mucosal diseases. However, little is known regarding the suitability of using PROMs as well as translation of PROM data into clinically meaningful terms in immunologically mediated oral mucosal diseases. The aims of the present thesis were therefore to provide comprehensive overview of the application and quality properties of PROMs used in immunologically mediated oral mucosal diseases, to investigate measurement properties of frequently used PROMs specific to this patient population, and to enhance practical utility of these PROMs by developing a brief version of PROM (if needed), and determining clinically relevant thresholds for PROM scores. Overall, the vast majority of existing PROMs have limited evidence supporting their measurement properties and no documentation of interpretability for use in immunologically mediated oral mucosal diseases. While the Chronic Oral Mucosal Disease Questionnaire (COMDQ) was the most psychometrically assessed PROM, the adoption of this instrument in clinical practice and research in immunologically mediated oral mucosal diseases appeared to be low. A prospective two-visit study was then conducted to investigate measurement properties and interpretability of a variety of frequently used PROMs as well as providing cross-sectional studies on psychological status and QoL in a relatively large cohort of patients with immunologically mediated oral mucosal diseases in a tertiary Oral Medicine clinic in the UK. Secondary analysis of data was performed to develop a short version of the COMDQ to improve clinical feasibility and utility of this instrument. For the assessment of psychological outcomes, the present results provided some evidence of validity and reliability of two psychological PROMs including the Hospital Anxiety and Depression Scale (HADS) and the 10-item Perceived Stress Scale (PSS-10) for use in patients with oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS). Regarding QoL-PROMs, a short version of the COMDQ (COMDQ-15) was successfully developed and rigorously validated, using data of 520 patients with immunologically mediated oral mucosal diseases. The present findings showed that COMDQ-15 performed better than the 14-item Oral Health Impact Profile (OHIP-14) at capturing patient’s QoL in patients with OLP and RAS as shown by its greater association with symptoms and disease activity in both patient groups. As for the interpretation of PROM outcomes, cut-off scores for meaningful improvement thresholds including minimal important change (MIC) and minimal important difference (MID) of common measures of pain and QoL were determined to facilitate meaningful interpretation of improvement in PROM scores. Apart from PROM change scores, thresholds for patient acceptable symptom state (PASS) were estimated to provide clinically relevant cut-points for PROM individual scores. Overall, the results of the present study provide some evidence supporting quality properties of commonly used PROMs for the application in immunologically mediated oral mucosal diseases. The established estimates of meaningful improvement thresholds and patient acceptable symptom state thresholds will allow researchers and clinicians to adopt these as standard for clinically meaningful interpretation of scores of pain and QoL outcomes in immunologically mediated oral mucosal diseases
