Defining Clinical Trial Estimands: A Practical Guide for Study Teams with Examples Based on a Psychiatric Disorder.

While the ICH E9(R1) Addendum on "Estimands and Sensitivity Analysis in Clinical Trials" was released in late 2019, the widespread implementation of defining and reporting estimands across clinical trials is still in progress and the engagement of non-statistical functions in this process is also in progress. Case studies are sought after, especially those with documented clinical and regulatory feedback. This paper describes an interdisciplinary process for implementing the estimand framework, devised by the Estimands and Missing Data Working Group (a group with clinical, statistical, and regulatory representation) of the International Society for CNS Clinical Trials and Methodology.

Identification, transformations and mobility of hazardous arsenic-based pigments on 19th century bookbindings in accessible library collections.

This study focused on the non-destructive characterization of potentially hazardous Victorian-era books found in the Northwestern University Libraries. XRF, Raman and FTIR were used to identify and isolate hazardous books containing As-based pigments. These techniques also permitted, on selected books, to characterize the pigment as being Emerald green.

Identifying a core outcome set for pulmonary sarcoidosis research - the Foundation for Sarcoidosis Research - Sarcoidosis Clinical OUtcomes Taskforce (SCOUT).

Background: Pulmonary sarcoidosis is a rare granulomatous disease of unknown aetiology. Heterogeneity in the outcomes measured in trials of treatment for pulmonary sarcoidosis has impacted on the ability to systematically compare findings, contributing to research inefficiency. The FSR-SCOUT study has aimed to address this heterogeneity by developing a core outcome set that represents a patient and health professional consensus on the most important outcomes to measure in future research for the treatment of pulmonary sarcoidosis.

Scout - sarcoidosis outcomes taskforce. A systematic review of outcomes to inform the development of a core outcome set for pulmonary sarcoidosis.

Background: Clinical trials evaluating different management strategies for pulmonary sarcoidosis may measure different outcomes. This heterogeneity in outcomes can lead to waste in research due to the inability to compare and combine data. Core outcome sets (COS) have the potential to address this issue and here we describe a systematic review of outcomes as the first step in the development of a COS for pulmonary sarcoidosis research.

Application of Uniform Manifold Approximation and Projection (UMAP) in spectral imaging of artworks.

This study assesses the potential of Uniform Manifold Approximation and Projection (UMAP) as an alternative tool to t-distributed Stochastic Neighbor Embedding (t-SNE) for the reduction and visualization of visible spectral images of works of art. We investigate the influence of UMAP parameters-such as, correlation distance, minimum embedding distance, as well as number of embedding neighbors- on the reduction and visualization of spectral images collected from Poèmes Barbares (1896), a major work by the French artist Paul Gauguin in the collection of the Harvard Art Museums. The use of a cosine distance metric and number of neighbors equal to 10 preserves both the local and global structure of the Gauguin dataset in a reduced two-dimensional embedding space thus yielding simple and clear groupings of the pigments used by the artist.

The adaptive designs CONSORT extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design.

Adaptive designs (ADs) allow pre-planned changes to an ongoing trial without compromising the validity of conclusions and it is essential to distinguish pre-planned from unplanned changes that may also occur. The reporting of ADs in randomised trials is inconsistent and needs improving. Incompletely reported AD randomised trials are difficult to reproduce and are hard to interpret and synthesise.

Hand-guided qualitative deflectometry with a mobile device.

We introduce a system that exploits the screen and front-facing camera of a mobile device to perform three-dimensional deflectometry-based surface measurements. In contrast to current mobile deflectometry systems, our method can capture surfaces with large normal variation and wide field of view (FoV). We achieve this by applying automated multi-view panoramic stitching algorithms to produce a large FoV normal map from a hand-guided capture process without the need for external tracking systems, like robot arms or fiducials.

Development process of a consensus-driven CONSORT extension for randomised trials using an adaptive design.

Background: Adequate reporting of adaptive designs (ADs) maximises their potential benefits in the conduct of clinical trials. Transparent reporting can help address some obstacles and concerns relating to the use of ADs. Currently, there are deficiencies in the reporting of AD trials.

Nonlinear Unmixing of Hyperspectral Datasets for the Study of Painted Works of Art.

Nonlinear unmixing of hyperspectral reflectance data is one of the key problems in quantitative imaging of painted works of art. The approach presented is to interrogate a hyperspectral image cube by first decomposing it into a set of reflectance curves representing pure basis pigments and second to estimate the scattering and absorption coefficients of each pigment in a given pixel to produce estimates of the component fractions. This two-step algorithm uses a deep neural network to qualitatively identify the constituent pigments in any unknown spectrum and, based on the pigment(s) present and Kubelka-Munk theory to estimate the pigment concentration on a per-pixel basis.

Use of Mobile Devices to Measure Outcomes in Clinical Research, 2010-2016: A Systematic Literature Review.

Background: The use of mobile devices in clinical research has advanced substantially in recent years due to the rapid pace of technology development. With an overall aim of informing the future use of mobile devices in interventional clinical research to measure primary outcomes, we conducted a systematic review of the use of and clinical outcomes measured by mobile devices (mobile outcomes) in observational and interventional clinical research.

Method: We conducted a PubMed search using a range of search terms to retrieve peer-reviewed articles on clinical research published between January 2010 and May 2016 in which mobile devices were used to measure study outcomes.

Optimizing the analysis strategy for the CANVAS Program: A prespecified plan for the integrated analyses of the CANVAS and CANVAS-R trials.

Two large cardiovascular outcome trials of canagliflozin, comprising the CANVAS Program, will complete in early 2017: the CANagliflozin cardioVascular Assessment Study (CANVAS) and the CANagliflozin cardioVascular Assessment Study-Renal (CANVAS-R). Accruing data for the sodium glucose co-transporter 2 (SGLT2) inhibitor class has identified questions and opportunities that were not apparent when the trials were designed. Accordingly, a series of modifications have been made to the planned analyses.

Clinician-Reported Outcome Assessments of Treatment Benefit: Report of the ISPOR Clinical Outcome Assessment Emerging Good Practices Task Force.

A clinician-reported outcome (ClinRO) assessment is a type of clinical outcome assessment (COA). ClinRO assessments, like all COAs (patient-reported, observer-reported, or performance outcome assessments), are used to 1) measure patients' health status and 2) define end points that can be interpreted as treatment benefits of medical interventions on how patients feel, function, or survive in clinical trials. Like other COAs, ClinRO assessments can be influenced by human choices, judgment, or motivation.

The Human Immune Response to Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infections, particularly in children. Much information regarding the immune response to RSV comes from animal models and studies. Here, we provide a comprehensive description of the human immune response to RSV infection, based on a systematic literature review of research on infected humans.

DIA's Adaptive Design Scientific Working Group (ADSWG): Best Practices Case Studies for "Less Well-understood" Adaptive Designs.

Adaptive design (AD) clinical trials use accumulating subject data to modify the parameters of the design of an ongoing study, without compromising the validity and integrity of the study. The 2010 US Food and Drug Administration (FDA) Draft Guidance on Adaptive Design Clinical Trials described a subset of 7 primary design types as "less well-understood." FDA defined these designs as those with limited regulatory experience.

Clinical Outcome Assessments: Conceptual Foundation-Report of the ISPOR Clinical Outcomes Assessment - Emerging Good Practices for Outcomes Research Task Force.

An outcome assessment, the patient assessment used in an endpoint, is the measuring instrument that provides a rating or score (categorical or continuous) that is intended to represent some aspect of the patient's health status. Outcome assessments are used to define efficacy endpoints when developing a therapy for a disease or condition. Most efficacy endpoints are based on specified clinical assessments of patients.

Challenges and opportunities in designing clinical trials for neuromyelitis optica.

Current management of neuromyelitis optica (NMO) is noncurative and only partially effective. Immunosuppressive or immunomodulatory agents are the mainstays of maintenance treatment. Safer, better-tolerated, and proven effective treatments are needed.

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. The 2014 Biomarker Working Group Report.

Biology-based markers to confirm or aid in the diagnosis or prognosis of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation or monitor its progression are critically needed to facilitate evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biological or pathogenic process, or of a pharmacologic response to a therapeutic intervention. Applications of biomarkers in chronic GVHD clinical trials or patient management include the following: (1) diagnosis and assessment of chronic GVHD disease activity, including distinguishing irreversible damage from continued disease activity; (2) prognostic risk to develop chronic GVHD; and (3) prediction of response to therapy.

Commonalities and challenges in the development of clinical trial measures in neurology.

As neurologists and neuroscientists, we are trained to evaluate disorders of the nervous system by thinking systematically. Clinically, we think in terms of cognition, behavior, motor function, sensation, balance and co-ordination, and autonomic system function. But when we assess symptoms of neurological disorders for the purpose of drug development, we tend to create disease-specific outcome measures, often using a variety of methods to assess the same types of dysfunction in overlapping, related disorders.

Evaluating cognitive outcome measures for MS clinical trials: what is a clinically meaningful change?

Brief cognitive assessments are increasingly emphasized in MS treatment studies and clinical care. While much is known about the reliability of several widely-used neuropsychological tests, interpretation of the changes in individual patients is inadequate. The FDA offers guidance on the issue, as related to patient-reported outcomes.

Qualifying biomarkers for use in drug development: a US Food and Drug Administration overview.

Despite huge investments, there are still difficulties in the development of novel therapies. This has led to a growing interest in the use of new tools, such as biomarkers, that can help overcome development hurdles while providing increased certainty about drug safety and efficacy. Until recently, no formal process has existed for qualifying biomarkers for regulatory decision making.

Translational biomarkers: from preclinical to clinical a report of 2009 AAPS/ACCP Biomarker Workshop.

There have been some successes in qualifying biomarkers and applying them to drug development and clinical treatment of various diseases. A recent success is illustrated by a collaborative effort among the US Food and Drug Administration, the European Medicines Agency, and the pharmaceutical industry to provide a set of seven preclinical kidney toxicity biomarkers for drug development. Other successes include, but are not limited to, clinical biomarkers for cancer treatment and clinical management of heart transplant patients.

Addressing and advancing the problem of missing data.

Missing data can pose substantial risk of reaching incorrect conclusions from clinical studies. Imputation for the missing values is common, but can supply only an approximate result desired to be "close enough" to the intended true result. Prevention optimally addresses the issue.