EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups: a methodology report.

Objective: To describe the methodology used to develop new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIMs) and their major subgroups.

Methods: An international, multidisciplinary group of myositis experts produced a set of 93 potentially relevant variables to be tested for inclusion in the criteria. Rheumatology, dermatology, neurology and paediatric clinics worldwide collected data on 976 IIM cases (74% adults, 26% children) and 624 non-IIM comparator cases with mimicking conditions (82% adults, 18% children).

2017 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies and Their Major Subgroups.

Objective: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups.

Methods: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology, and pediatric clinics worldwide.

2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups.

Objective: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups.

Methods: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide.

2016 ACR-EULAR adult dermatomyositis and polymyositis and juvenile dermatomyositis response criteria-methodological aspects.

Objective: The objective was to describe the methodology used to develop new response criteria for adult DM/PM and JDM.

Methods: Patient profiles from prospective natural history data and clinical trials were rated by myositis specialists to develop consensus gold-standard ratings of minimal, moderate and major improvement. Experts completed a survey regarding clinically meaningful improvement in the core set measures (CSM) and a conjoint-analysis survey (using 1000Minds software) to derive relative weights of CSM and candidate definitions.

2016 American College of Rheumatology/European League Against Rheumatism criteria for minimal, moderate, and major clinical response in adult dermatomyositis and polymyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.

To develop response criteria for adult dermatomyositis (DM) and polymyositis (PM). Expert surveys, logistic regression, and conjoint analysis were used to develop 287 definitions using core set measures. Myositis experts rated greater improvement among multiple pairwise scenarios in conjoint analysis surveys, where different levels of improvement in 2 core set measures were presented.

2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Adult Dermatomyositis and Polymyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.

Objective: To develop response criteria for adult dermatomyositis (DM) and polymyositis (PM).

Methods: Expert surveys, logistic regression, and conjoint analysis were used to develop 287 definitions using core set measures. Myositis experts rated greater improvement among multiple pairwise scenarios in conjoint analysis surveys, where different levels of improvement in 2 core set measures were presented.

2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Juvenile Dermatomyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.

Objective: To develop response criteria for juvenile dermatomyositis (DM).

Methods: We analyzed the performance of 312 definitions that used core set measures from either the International Myositis Assessment and Clinical Studies Group (IMACS) or the Paediatric Rheumatology International Trials Organisation (PRINTO) and were derived from natural history data and a conjoint analysis survey. They were further validated using data from the PRINTO trial of prednisone alone compared to prednisone with methotrexate or cyclosporine and the Rituximab in Myositis (RIM) trial.

Relative contributions of interface pressure, shear stress, and temperature on ischemic-induced, skin-reactive hyperemia in healthy volunteers: a repeated measures laboratory study.

Although the primary risk factors for pressure ulcer development - pressure, shear, skin temperature, moisture, and friction - have been identified for decades, the relative contribution of each to this risk remains unclear. To confirm the results of and expand upon earlier research into the relative contributions of interface pressures, shear stress, and skin temperature among 4 healthy volunteers, a study involving 6 additional healthy 40- to 75-year-old volunteers was conducted and results of the 2 studies were pooled. All 3 variables (interface pressures, shear stress, and skin temperature) were systematically and randomly varied.

Scientific factors and current issues in biosimilar studies.

Biological drugs are much more complicated than chemically synthesized, small-molecule drugs; for instance, their size is much larger, their structure is more complicated, they can be sensitive to environmental conditions such as temperature or pressure, and they may expose patients to immunogen reactions. Consequently, the assessment of biosimilarity calls for greater circumspection than the evaluation of bioequivalence. The present communication discusses scientific factors and some current issues related to biosimilarity and the interchangeability of drug products.

Early illness features associated with mortality in the juvenile idiopathic inflammatory myopathies.

Objective: Because juvenile idiopathic inflammatory myopathies (IIMs) are potentially life-threatening systemic autoimmune diseases, we examined risk factors for juvenile IIM mortality.

Methods: Mortality status was available for 405 patients (329 with juvenile dermatomyositis [DM], 30 with juvenile polymyositis [PM], and 46 with juvenile connective tissue disease-associated myositis [CTM]) enrolled in nationwide protocols. Standardized mortality ratios (SMRs) were calculated using US population statistics.

The relative contributions of interface pressure, shear stress, and temperature on tissue ischemia: a cross-sectional pilot study.

Tissue ischemia is thought to play a major role in the development of pressure ulcers. Pressure, shear, and temperature are acknowledged contributors, but the relative magnitude of each factor is largely unknown. A cross-sectional pilot study was conducted on the sacrums of four healthy volunteers to estimate the relative contributions of each variable by systematically varying and assessing the resulting level of ischemia in the skin tissue.

Scientific considerations for assessing biosimilar products.

The problem for assessing biosimilarity and drug interchangeability of follow-on biologics (biosimilar products) is studied. Unlike the generic products, the development of biosimilar products is much more complicated because of fundamental differences in functional structures and manufacturing processes. As a result, the criteria and standard methods for the design and analysis of bioequivalence assessment of generic drug products may not be directly applicable to assessing biosimilarity of biosimilar products.

Comments on the FDA draft guidance on biosimilar products.

The Food and Drug Administration issued on February 9, 2012, drafts of three new guidance documents about the demonstration of biosimilarity. One of these deals with scientific considerations. It suggests, among others, that demonstration of biosimilarity be developed by a stepwise (step-by-step) approach and that it be assessed by considering the totality of the evidence.

Variable selection when missing values are present: a case study.

We consider variable selection when missing values are present in the predictor variables. We compare using complete cases with multiple imputation using backward selection (backwards stepping) and least angle regression. These are studied using a data set from a rheumatological disease (myositis).

Damage extent and predictors in adult and juvenile dermatomyositis and polymyositis as determined with the myositis damage index.

Objective: We undertook this study to validate the Myositis Damage Index (MDI) in juvenile and adult myositis, to describe the degree and types of damage and to develop predictors of damage.

Methods: Retrospective MDI evaluations and prospective assessment of disease activity and illness features were conducted. Patients with juvenile-onset disease (n = 143) were evaluated a median of 18 months after diagnosis; 135 patients were assessed 7-9 months later, and 121 were last assessed a median of 82 months after diagnosis.

On Determining the Effects of Therapy on Disease Damage in Non- randomized Studies with Multiple Treatments: A study of Juvenile Myositis.

This article discusses predicting damage in patients with juvenile myositis after treatment with various medications. These data were taken from medical records and not randomized. Investigators advocate using propensity scores for analysis of such non-randomized studies in order to reduce the effect of selection of treatment.

Alternative scoring of the Cutaneous Assessment Tool in juvenile dermatomyositis: results using abbreviated formats.

Objective: The Cutaneous Assessment Tool (CAT) is a comprehensive, semiquantitative tool for the assessment of skin disease in juvenile dermatomyositis (DM). The goal of this study was to determine whether alternative scoring methods would shorten the CAT without compromising its measurement characteristics.

Methods: A total of 113 children with juvenile DM were assessed at baseline; 94 were assessed again 7-9 months later.

Preliminary validation and clinical meaning of the Cutaneous Assessment Tool in juvenile dermatomyositis.

Objective: To provide preliminary validation of the Cutaneous Assessment Tool (CAT), a new tool to assess cutaneous manifestations of juvenile dermatomyositis (DM), and to explore the clinical meaning of CAT scores.

Methods: Children with juvenile DM (n = 113) were assessed at baseline and 7-9 months later (n = 94). Internal consistency, redundancy, construct validity, and responsiveness of the CAT were examined.

Developing international consensus on measures of improvement for patients with myositis.

We discuss methods of developing consensus in measuring improvement in myositis. We consider selecting candidate variables, reliability and validity, percentage improvement/worsening rules, rules based on CART and logistic regression. We discuss criteria for determining an acceptable rule that include both numerical measures and physician acceptance.

Quantification of hepatitis B virus genomes and infectivity in human serum samples.

Background: Hepatitis B virus (HBV) infections are still a major health issue, with approximately 350 million people chronically infected with HBV worldwide. Information about the minimum copy number of HBV genomes required for infection would be useful as a reference for drug and vaccine development; for monitoring HBV patients during treatment; for screening of blood, organ, and tissue donors; and for regulating nucleic acid amplification assays for HBV.

Study Design And Methods: Serum samples from chronic carriers (hepatitis B surface antigen-positive and antibody to HBV core antigen-positive) of the three most common subtypes of HBV were studied; their infectivity titers had been evaluated previously in chimpanzees.

Opening the adaptive toolbox.

This is a discussion of the following three papers appearing in this special issue on adaptive designs: 'A regulatory view on adaptive/flexible clinical trial design' by H. M. James Hung, Robert T.

Some aspects of the application of internal pilot studies.

This is a discussion of the paper' Sample size recalculation in internal pilot study designs' by Tim Friede and Meinhard Kieser, appearing in this special issue on adaptive designs.