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

World workshop on oral medicine VIII: development of a core outcome set for dry mouth: a systematic review of outcome domains for xerostomia

Objective The purpose of this study was to identify all outcome domains utilized in clinical studies of xerostomia, i.e. subjective sensation of dry mouth. This study is part of the extended project ‘World Workshop on Oral Medicine Outcomes Initiative for the Direction of Research (WONDER)’ to develop a core outcome set (COS) for dry mouth. Study design A systematic review was performed on MEDLINE, EMBASE, CINAHL and Cochrane Central Register of Controlled Trials databases. All clinical and observational studies that assessed xerostomia in human subjects from 2001 to 2021 were included. Information on outcome domains was extracted and mapped to the Core Outcome Measures in Effectiveness Trials (COMET) taxonomy. Corresponding outcome measures were summarized. Results From a total of 34,922 records retrieved, 688 articles involving 122,151 persons with xerostomia were included. There were 16 unique outcome domains and 166 outcome measures extracted. None of these domains or measures was consistently utilized across all the studies. Severity of xerostomia and physical functioning were the two most frequently assessed domains. Conclusion There is considerable heterogeneity in outcome domains and measures reported in clinical studies of xerostomia. This highlights the need for harmonization of dry mouth assessment in order to enhance comparability across studies and facilitate synthesis of robust evidence for the management of patients with xerostomia

World Workshop on Oral Medicine VIII: Development of a core outcome set for dry mouth: A Consensus Study

Objective To develop a consensus-based core outcome set (COS) to be used in clinical trials assessing dry mouth interventions. Study design Through two systematic reviews of the literature and interviews with dry mouth patients we identified relevant outcome domains for dry mouth assessment. A Delphi survey was presented to health care providers attending the American Academy of Oral Medicine annual meeting in Memphis, Tennessee, USA, May 2022 (n = 104) and ten dry mouth patients at Cork University Dental School and Hospital, Republic of Ireland. Outcome domains for which no consensus was reached were subsequently discussed in a second consensus process led by a virtual Special Interest Group (SIG) of 11 oral medicine experts from the World Workshop on Oral Medicine VIII dry mouth working group. Results After the two-step consensus process, consensus was reached for 12 dry mouth outcome domains (salivary gland flow, signs of hyposalivation, mucosal moisture/wetness, severity of xerostomia, duration of xerostomia, overall impact of xerostomia, impact on physical functioning, impact of hyposalivation on general health, impact on social activities, quality of life, economic impact of dry mouth, patient satisfaction) to be included in the final COS. Conclusion We propose a consensus-based COS to assess dry mouth interventions in clinical trials. This COS includes the minimum, but mandatory set of domains that all clinical trials evaluating dry mouth treatments should assess

World workshop on oral medicine VIII: Development of a core outcome set for dry mouth: A systematic review of outcome domains for salivary hypofunction

Objective To identify all outcome measures used to assess salivary gland hypofunction (i.e.: objective measures used to determine actual changes in saliva quantity or to assess response to treatment of salivary gland hypofunction) and to group these into domains. Study Design A systematic review including clinical trials, and prospective or retrospective observational studies involving human participants with dry mouth, with any type of intervention where objective assessment of salivary gland hypofunction was described. Results Five hundred fifty-three studies involving 31,507 participants were identified. The majority assessed both salivary gland hypofunction and xerostomia (68.7%), whilst 31.3% assessed salivary gland hypofunction alone. The majority of studies investigated ‘amount of saliva’ and the highest number of outcome measures was within the domain ‘clinical/objective signs of salivary gland hypofunction’. Conclusions Seven domains encompassing 30 outcome measures were identified, confirming the diversity in outcomes and outcome measures used in research regarding salivary gland hypofunction. Identified items will be used in conjunction with those identified regarding xerostomia to create a COS for dry mouth quantification for use in future clinical trials, with the overall goal of improving the standardization of reporting, leading to the establishment of more robust evidence for the management of dry mouth and improving patient care