Methods for conducting international Delphi surveys to optimise global participation in core outcome set development: a case study in gastric cancer informed by a comprehensive literature review

Copyright © 2021, The Author(s) Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background: Core outcome sets (COS) should be relevant to key stakeholders and widely applicable and usable. Ideally, they are developed for international use to allow optimal data synthesis from trials. Electronic Delphi surveys are commonly used to facilitate global participation; however, this has limitations. It is common for these surveys to be conducted in a single language potentially excluding those not fluent in that tongue. The aim of this study is to summarise current approaches for optimising international participation in Delphi studies and make recommendations for future practice. Methods: A comprehensive literature review of current approaches to translating Delphi surveys for COS development was undertaken. A standardised methodology adapted from international guidance derived from 12 major sets of translation guidelines in the field of outcome reporting was developed. As a case study, this was applied to a COS project for surgical trials in gastric cancer to translate a Delphi survey into 7 target languages from regions active in gastric cancer research. Results: Three hundred thirty-two abstracts were screened and four studies addressing COS development in rheumatoid and osteoarthritis, vascular malformations and polypharmacy were eligible for inclusion. There was wide variation in methodological approaches to translation, including the number of forward translations, the inclusion of back translation, the employment of cognitive debriefing and how discrepancies and disagreements were handled. Important considerations were identified during the development of the gastric cancer survey including establishing translation groups, timelines, understanding financial implications, strategies to maximise recruitment and regulatory approvals. The methodological approach to translating the Delphi surveys was easily reproducible by local collaborators and resulted in an additional 637 participants to the 315 recruited to complete the source language survey. Ninety-nine per cent of patients and 97% of healthcare professionals from non-English-speaking regions used translated surveys. Conclusion: Consideration of the issues described will improve planning by other COS developers and can be used to widen international participation from both patients and healthcare professionals.This study is funded by the National Institute for Health Research (NIHR) Doctoral Research Fellowship Grant (DRF-2015-08-023). JMB is partially funded by the NIHR Bristol Biomedical Research Centre and the MRC ConDUCT-II Hub for Trials Methodology Research. PRW was funded by the MRC North West Hub for Trials Methodology Research (Grant ref: MR/K025635/01).info:eu-repo/semantics/publishedVersio

Current management of the gastrointestinal complications of systemic sclerosis.

Systemic sclerosis is a multisystem autoimmune disorder that involves the gastrointestinal tract in more than 90% of patients. This involvement can extend from the mouth to the anus, with the oesophagus and anorectum most frequently affected. Gut complications result in a plethora of presentations that impair oral intake and faecal continence and, consequently, have an adverse effect on patient quality of life, resulting in referral to gastroenterologists. The cornerstones of gastrointestinal symptom management are to optimize symptom relief and monitor for complications, in particular anaemia and malabsorption. Early intervention in patients who develop these complications is critical to minimize disease progression and improve prognosis. In the future, enhanced therapeutic strategies should be developed, based on an ever-improving understanding of the intestinal pathophysiology of systemic sclerosis. This Review describes the most commonly occurring clinical scenarios of gastrointestinal involvement in patients with systemic sclerosis as they present to the gastroenterologist, with recommendations for the suggested assessment protocol and therapy in each situation

OMERACT 2018 Modified Patient-reported outcome domain core set in the life impact area for adult idiopathic inflammatory myopathies

Objective. To present and vote on a myositis modified patient-reported outcome core domain set in the life impact area at the Outcome Measures in Rheumatology (OMERACT) 2018. Methods. Based on results from international focus groups and Delphi surveys, a draft core set was developed. Results. Domains muscle symptoms, fatigue, level of physical activity, and pain reached ≥ 70% consensus and were mandatory to assess in all trials. Domains lung, joint, and skin symptoms were mandatory in specific circumstances. This core set was endorsed by > 85% at OMERACT 2018. Conclusion. We propose a life impact core set for patients with idiopathic inflammatory myopathies and will proceed with instrument selections

Improved lung cancer clinical outcomes in patients with autoimmune rheumatic diseases

Purpose Concomitant autoimmune rheumatic diseases (ARD) can add morbidity and complicate treatment decisions for patients with lung cancer. We evaluated the tumour characteristics at diagnosis and clinical outcomes in lung cancer patients with or without ARD.Methods This retrospective cohort study included 10 963 patients with lung cancer, treated at Johns Hopkins. Clinical data including tumour characteristics and outcomes were extracted from the cancer registry. Data on patients’ history of 20 ARD were extracted from the electronic medical record. Logistic regression was used to compare tumour characteristics between those with and without ARD; Kaplan-Meier curves and Cox proportional hazards models were performed to compare survival outcomes.Results ARD was present in 3.6% of patients (n=454). The mean age at diagnosis was 69 (SD 10) and 68 (SD 12) in patients with and without ARD (p=0.02). Female sex and smoking history were significantly associated with a history of ARD (OR: 1.75, OR: 1.46, p<0.05). Patients with ARD were more likely to be diagnosed with stage 1 lung cancer (36.8% vs 26.9%, p<0.001) and with smaller tumour size (OR: 0.76, p=0.01), controlling for sex, race and histology. Notably, lung cancer patients with ARD had a significantly prolonged median overall survival (OS) (7.11 years vs 1.7 years, p<0.001), independent of stage.Conclusion Patients with ARD and lung cancer had better OS compared with their counterparts, independent of cancer stage and treatments and were less likely to have advanced stage lung cancer at diagnosis. Additional studies are needed to investigate the differential immunological anti-tumour immune activity and genomic variations in patients with and without ARD

Perceptions of patients, caregivers, and healthcare providers of idiopathic inflammatory myopathies: An international OMERACT Study

Objective. Patient-reported outcome measures (PROM) that incorporate the patient perspective have not been well established in idiopathic inflammatory myopathies (IIM). As part of our goal to develop IIM-specific PROM, the Outcome Measures in Rheumatology (OMERACT) Myositis special interest group sought to determine which aspects of disease and its effects are important to patients and healthcare providers (HCP). Methods. Based on a prior qualitative content analysis of focus groups, an initial list of 24 candidate domains was constructed. We subsequently conducted an international survey to identify the importance of each of the 24 domains to be assessed in clinical research. Patients with IIM, their caregivers, and HCP treating IIM completed the survey. Results. In this survey, a total of 638 respondents completed the survey, consisting of 510 patients, 101 HCP, and 27 caregivers from 48 countries. Overall, patients were more likely to rank “fatigue,” “cognitive impact,” and “difficulty sleeping” higher compared with HCP, who ranked “joint symptoms,” “lung symptoms,” and “dysphagia” higher. Both patients and providers rated muscle symptoms as their top domain. In general, patients from different countries were in agreement on which domains were most important. One notable exception was that patients from Sweden and the Netherlands ranked lung symptoms significantly higher compared to other countries including the United States and Australia (mean weighted rankings of 2.86 and 2.04 vs 0.76 and 0.80, respectively; p < 0.0001). Conclusion. Substantial differences exist in how IIM is perceived by patients compared to HCP, with different domains prioritized. In contrast, patients’ ratings across the world were largely similar

A Draft Modified Core Domain Set for Patient-Reported Outcomes (PRO) in Patients with Idiopathic Inflammatory Myopathies (IIM): An Omeract Report

Background/Purpose: The OMERACT Myositis special interest group (SIG) represents clinicians, patients, and researchers from four continents. Focus groups were conducted including 61 patients on three countries resulting in a list of 26 domains (1). In collaboration with International Myositis Assessment Clinical Study Group (IMACS), our goal was to identify a set of core patient-reported outcomes (PRO) in regards to life impact important to assess in clinical trials and clinical practice in myositis. Methods: Patients with adult polymyositis, dermatomyositis, antisynthetase syndrome, or immune-mediated necrotizing myopathy (IMNM) in South Korea, Sweden and USA (N=638) responded to the first online modified Delphi in 2016. The second modified Delphi included patients (N=563), health care providers (HCP) (N=101), care givers (N=27) and regulatory agencies (n=xx) from multiple countries in 2017. A third modified Delphi was administered in 2018 including 410 patients, 109 HCP, 22 caregivers. Results: From this work, four domains were deemed mandatory to measure in all clinical trials for IIM: fatigue, pain, levels of physical activity, and muscle symptoms (Figure 1). Additional optional domains include skin symptoms, lung symptoms, and joint symptoms. Several other domains were deemed important to study with further research efforts including sleeping difficulty, cognitive distress, ability to work, and emotional distress. Conclusion: A draft set of core PRO has been developed through validated methods based on OMERACT guidelines. Fatigue, pain, levels of physical activity and muscle symptoms were included in the inner circle and should always be used in clinical trials in IIM. We next seek to develop corresponding instruments with each of these domains with future efforts

Assessing the content validity of patient-reported outcome measures in adult myositis: A report from the OMERACT myositis working group

Objective To investigate the content validity of several patient-reported outcome measures (PROMs) in patients with idiopathic inflammatory myopathies (IIM). Methods Seven individual PROM instruments were selected by the Outcome Measures in Rheumatology (OMERACT) Myositis Working Group relating to the following domains: pain, fatigue, physical function and physical activity. Twenty patients from the Johns Hopkins Myositis Center were selected for one-on-one face-to-face or phone interviews for cognitive interviewing of individual PROMs to assess comprehension and content validity. Additionally, patients were asked if they thought muscle symptoms, an area originally identified in qualitative studies, were encapsulated by the other four domains. Results The majority of patients (>70%) felt that each of the instruments was clear, easy to read and understand, and could be used for assessment of its domain. Two-thirds (66%) of patients felt that ‘muscle symptoms’ were captured by the other domains. Conclusions We provided evidence to support adequate content validity for several PROMs. Further research is needed to determine whether ‘muscle symptoms’ warrant a separate domain

Morphometric Differences in the Heschl's Gyrus of Hearing Impaired and Normal Hearing Infants

This study investigates the morphometry of Heschl's gyrus and its included primary auditory cortex (PAC) in hearing impaired (HI) and normal hearing (NH) infants. Fourty-two infants, age 8–19 months, with NH (n = 26) or hearing impairment (n = 16) were studied using high-resolution 3D magnetic resonance imaging. Gray matter (GM) and white matter (WM) volumes were obtained using software for automatic brain imaging segmentation to estimate the volume of each tissue within manually defined regions for the anterior portion of Heschl's gyrus (aHG) in each individual subject, transformed to an infant brain template space. Interactions among group (HI, NH), tissue type (GM, WM), and hemisphere (left, right) were examined using analysis of variance. Whole-brain voxel-based morphometry was utilized to explore volume differences between groups across the entire brain. The HI group showed increased GM and decreased WM in aHG compared with the NH group; likely effects of auditory deprivation. The HI group did not exhibit their typical L > R asymmetry pattern that the NH group showed. Increased GM in aHG in HI infants may represent abnormal cortical development in PAC as seen in animal models of sensory deprivation. Lower WM volume is consistent with studies with deaf adults