Heterogeneity of reported outcomes in epidermolysis bullosa clinical research: a scoping review as a first step towards outcome harmonization.

BACKGROUND: Epidermolysis bullosa (EB) is a rare, genetically and clinically heterogeneous group of skin fragility disorders. No cure is currently available, but many novel and repurposed treatments are upcoming. For adequate evaluation and comparison of clinical studies in EB, well-defined and consistent consensus-endorsed outcomes and outcome measurement instruments are necessary. OBJECTIVES: To identify previously reported outcomes in EB clinical research, group these outcomes by outcome domains and areas and summarize respective outcome measurement instruments. METHODS: A systematic literature search was performed in the databases MEDLINE, Embase, Scopus, Cochrane CENTRAL, CINAHL, PsycINFO and trial registries covering the period between January 1991 and September 2021. Studies were included if they evaluated a treatment in a minimum of three patients with EB. Two reviewers independently performed the study selection and data extraction. All identified outcomes and their respective instruments were mapped onto overarching outcome domains. The outcome domains were stratified according to subgroups of EB type, age group, intervention, decade and phase of clinical trial. RESULTS: The included studies (n = 207) covered a range of study designs and geographical settings. A total of 1280 outcomes were extracted verbatim and inductively mapped onto 80 outcome domains and 14 outcome areas. We found a steady increase in the number of published clinical trials and outcomes reported over the past 30 years. The included studies mainly focused on recessive dystrophic EB (43%). Wound healing was reported most frequently across all studies and referred to as a primary outcome in 31% of trials. Great heterogeneity of reported outcomes was observed within all stratified subgroups. Moreover, a diverse range of outcome measurement instruments (n = 200) was identified. CONCLUSIONS: We show substantial heterogeneity in reported outcomes and outcome measurement instruments in EB clinical research over the past 30 years. This review is the first step towards harmonization of outcomes in EB, which is necessary to expedite the clinical translation of novel treatments for patients with EB.

Prognostic Value of Serial Risk Stratification in Adult and Pediatric Pulmonary Arterial Hypertension: A Systematic Review.

BACKGROUND: In pulmonary arterial hypertension, it is recommended to base therapeutic decisions on risk stratification. This systematic review aims to report the prognostic value of serial risk stratification in adult and pediatric pulmonary arterial hypertension and to explore the usability of serial risk stratification as treatment target. METHODS AND RESULTS: Electronic databases PubMed, Embase, and Web of Science were searched up to January 30, 2023, using terms associated with pulmonary arterial hypertension, pediatric pulmonary hypertension, and risk stratification. Observational studies and clinical trials describing risk stratification at both baseline and follow-up were included. Sixty five studies were eligible for inclusion, including only 2 studies in a pediatric population. C-statistic range at baseline was 0.31 to 0.77 and improved to 0.30 to 0.91 at follow-up. In 53% of patients, risk status changed (42% improved, 12% worsened) over 168 days (interquartile range, 137-327 days; n=22 studies). The average proportion of low-risk patients increased from 18% at baseline to 36% at a median follow-up of 244 days (interquartile range, 140-365 days; n=40 studies). In placebo-controlled drug studies, risk statuses of the intervention groups improved more and worsened less compared with the placebo groups. Furthermore, a low-risk status, but also an improved risk status, at follow-up was associated with a better outcome. Similar results were found in the 2 pediatric studies. CONCLUSIONS: Follow-up risk stratification has improved prognostic value compared with baseline risk stratification, and change in risk status between baseline and follow-up corresponded to a change in survival. These data support the use of serial risk stratification as treatment target in pulmonary arterial hypertension.

Evaluating the Cost-Utility of Continuous Glucose Monitoring in Individuals with Type 1 Diabetes: A Systematic Review of the Methods and Quality of Studies Using Decision Models or Empirical Data.

INTRODUCTION: This review presents a critical appraisal of differences in the methodologies and quality of model-based and empirical data-based cost-utility studies on continuous glucose monitoring (CGM) in type 1 diabetes (T1D) populations. It identifies key limitations and challenges in health economic evaluations on CGM and opportunities for their improvement. METHODS: The review and its documentation adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews. Searches for articles published between January 2000 and January 2023 were conducted using the MEDLINE, Embase, Web of Science, Cochrane Library, and Econlit databases. Published studies using models and empirical data to evaluate the cost utility of all CGM devices used by T1D patients were included in the search. Two authors independently extracted data on interventions, populations, model settings (e.g., perspectives and time horizons), model types and structures, clinical outcomes used to populate the model, validation, and uncertainty analyses. They subsequently met to confirm consensus. Quality was assessed using the Philips checklist for model-based studies and the Consensus Health Economic Criteria (CHEC) checklist for empirical studies. Model validation was assessed using the Assessment of the Validation Status of Health-Economic decision models (AdViSHE) checklist. The extracted data were used to generate summary tables and figures. The study protocol is registered with PROSPERO (CRD42023391284). RESULTS: In total, 34 studies satisfied the selection criteria, two of which only used empirical data. The remaining 32 studies applied 10 different models, with a substantial majority adopting the CORE Diabetes Model. Model-based studies often lacked transparency, as their assumptions regarding the extrapolation of treatment effects beyond available evidence from clinical studies and the selection and processing of the input data were not explicitly stated. Initial scores for disagreements concerning checklists were relatively high, especially for the Philips checklist. Following their resolution, overall quality scores were moderate at 56%, whereas model validation scores were mixed. Strikingly, costing approaches differed widely across studies, resulting in little consistency in the elements included in intervention costs. DISCUSSION AND CONCLUSION: The overall quality of studies evaluating CGM was moderate. Potential areas of improvement include developing systematic approaches for data selection, improving uncertainty analyses, clearer reporting, and explaining choices for particular modeling approaches. Few studies provided the assurance that all relevant and feasible options had been compared, which is required by decision makers, especially for rapidly evolving technologies such as CGM and insulin administration. High scores for disagreements indicated that several checklists contained questions that were difficult to interpret consistently for quality assessment. Therefore, simpler but comprehensive quality checklists may be needed for model-based health economic evaluation studies.

Risk stratification in adult and pediatric pulmonary arterial hypertension: A systematic review.

Introduction: Currently, risk stratification is the cornerstone of determining treatment strategy for patients with pulmonary arterial hypertension (PAH). Since the 2015 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines for the diagnosis and treatment of pulmonary hypertension recommended risk assessment, the number of studies reporting risk stratification has considerably increased. This systematic review aims to report and compare the variables and prognostic value of the various risk stratification models for outcome prediction in adult and pediatric PAH. Methods: A systematic search with terms related to PAH, pediatric pulmonary hypertension, and risk stratification was performed through databases PubMed, EMBASE, and Web of Science up to June 8, 2022. Observational studies and clinical trials on risk stratification in adult and pediatric PAH were included, excluding case reports/series, guidelines, and reviews. Risk of bias was assessed using the Prediction model Risk Of Bias Assessment Tool. Data on the variables used in the models and the predictive strength of the models given by c-statistic were extracted from eligible studies. Results: A total of 74 studies were eligible for inclusion, with this review focusing on model development (n = 21), model validation (n = 13), and model enhancement (n = 9). The variables used most often in current risk stratification models were the non-invasive WHO functional class, 6-minute walk distance and BNP/NT-proBNP, and the invasive mean right atrial pressure, cardiac index and mixed venous oxygen saturation. C-statistics of current risk stratification models range from 0.56 to 0.83 in adults and from 0.69 to 0.78 in children (only two studies available). Risk stratification models focusing solely on echocardiographic parameters or biomarkers have also been reported. Conclusion: Studies reporting risk stratification in pediatric PAH are scarce. This systematic review provides an overview of current data on risk stratification models and its value for guiding treatment strategies in PAH. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022316885], identifier [CRD42022316885].

Benefits and drawbacks of videoconferencing for collaborating multidisciplinary teams in regional oncology networks: a scoping review.

INTRODUCTION: Various forms of videoconferenced collaborations exist in oncology care. In regional oncology networks, multidisciplinary teams (MDTs) are essential in coordinating care in their region. There is no recent overview of the benefits and drawbacks of videoconferenced collaborations in oncology care networks. This scoping review presents an overview of videoconferencing (VC) in oncology care and summarises its benefits and drawbacks regarding decision-making and care coordination. DESIGN: We searched MEDLINE, Embase, CINAHL (nursing and allied health) and the Cochrane Library from inception to October 2020 for studies that included VC use in discussing treatment plans and coordinating care in oncology networks between teams at different sites. Two reviewers performed data extraction and thematic analyses. RESULTS: Fifty studies were included. Six types of collaboration between teams using VC in oncology care were distinguished, ranging from MDTs collaborating with similar teams or with national or international experts to interactions between palliative care nurses and experts in that field. Patient benefits were less travel for diagnosis, better coordination of care, better access to scarce facilities and treatment in their own community. Benefits for healthcare professionals were optimised treatment plans through multidisciplinary discussion of complex cases, an ability to inform all healthcare professionals simultaneously, enhanced care coordination, less travel and continued medical education. VC added to the regular workload in preparing for discussions and increased administrative preparation. DISCUSSION: Benefits and drawbacks for collaborating teams were tied to general VC use. VC enabled better use of staff time and reduced the time spent travelling. VC equipment costs and lack of reimbursement were implementation barriers. CONCLUSION: VC is highly useful for various types of collaboration in oncology networks and improves decision-making over treatment plans and care coordination, with substantial benefits for patients and specialists. Drawbacks are additional time related to administrative preparation.