Assessing asthma symptoms in children: qualitative research supporting the development of the Pediatric Asthma Diary-Child (PAD-C) and Pediatric Asthma Diary-Observer (PAD-O).

Background: Pediatric asthma has been identified by regulators, clinicians, clinical trial sponsors, and caregivers as an area in need of novel fit-for-purpose clinical outcome assessments (COAs) developed in accordance with the U.S. Food and Drug Administration's (FDA's) regulatory guidance for evaluating clinical benefit in treatment trials.

Recommendations on the Selection, Development, and Modification of Performance Outcome Assessments: A Good Practices Report of an ISPOR Task Force.

In evaluating the clinical benefit of new therapeutic interventions, it is critical that the treatment outcomes assessed reflect aspects of health that are clinically important and meaningful to patients. Performance outcome (PerfO) assessments are measurements based on standardized tasks actively undertaken by a patient that reflect physical, cognitive, sensory, and other functional skills that bring meaning to people's lives. PerfO assessments can have substantial value as drug development tools when the concepts of interest being measured best suit task performance and in cases where patients may be limited in their capacity for self-report.

Updated Recommendations on Evidence Needed to Support Measurement Comparability Among Modes of Data Collection for Patient-Reported Outcome Measures: A Good Practices Report of an ISPOR Task Force.

The ISPOR Task Force on measurement comparability between modes of data collection for patient-reported outcome measures (PROMs) has updated the good practice recommendations from the 2009 ISPOR electronic patient-reported outcome and 2014 patient-reported outcome mixed modes Good Research Practices Task Force reports in light of accumulated evidence of measurement comparability among different modes of PROM data collection. Furthermore, with the increasing use of electronic formats of clinical outcome assessments in clinical trials and the US Food and Drug Administration's encouragement of electronic data collection, this new task force report provides stakeholders with best practice recommendations reflecting the current body of evidence and enables them to respond to future developments in research and technology. This task force recommends an evidence-based approach to determine whether new research is needed to evaluate measurement comparability for a given questionnaire or technology.

Approaches to the Assessment of Clinical Benefit of Treatments for Conditions That Have Heterogeneous Symptoms and Impacts: Potential Applications in Rare Disease.

Objectives: Evaluating the clinical benefit of interventions for conditions with heterogeneous symptom and impact presentations is challenging. The same condition can present differently across and within individuals over time. This occurs frequently in rare diseases.

Comparing patient global impression of severity and patient global impression of change to evaluate test-retest reliability of depression, non-small cell lung cancer, and asthma measures.

Purpose: Score reproducibility is an important measurement property of fit-for-purpose patient-reported outcome (PRO) measures. It is commonly assessed via test-retest reliability, and best evaluated with a stable participant sample, which can be challenging to identify in diseases with highly variable symptoms. To provide empirical evidence comparing the retrospective (patient global impression of change [PGIC]) and current state (patient global impression of severity [PGIS]) approaches to identifying a stable subgroup for test-retest analyses, 3 PRO Consortium working groups collected data using both items as anchor measures.

Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ): Measurement Properties and Estimated Clinically Meaningful Thresholds From a Phase 3 Study.

Introduction: The NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ) was developed to assess NSCLC symptom severity in accordance with Food and Drug Administration evidentiary expectations leading to Food and Drug Administration qualification in 2018. This study evaluated the NSCLC-SAQ's measurement properties within a clinical trial.

Methods: The KEYNOTE-598 phase 3 study of participants with stage IV metastatic NSCLC with programmed death-ligand 1 tumor proportion score greater than or equal to 50% was used to assess the NSCLC-SAQ's reliability, construct validity, responsiveness, and estimate clinically meaningful within-person change.

Asthma Daytime Symptom Diary (ADSD) and Asthma Nighttime Symptom Diary (ANSD): Measurement Properties of Novel Patient-Reported Symptom Measures.

Background: The Asthma Daytime Symptom Diary (ADSD) and the Asthma Nighttime Symptom Diary (ANSD) were developed to meet the need for standardized patient-reported measures of asthma symptoms to assess treatment trial outcomes in adults and adolescents.

Objective: To determine scoring and evaluate the measurement properties of the ADSD/ANSD.

Methods: Adolescents (12-17 years) and adults (18+ years) with asthma completed draft 8-item electronic versions of the ADSD/ANSD for 10 days alongside the Adult Asthma Symptom Daily Scales (AASDS) and a Patient Global Impression of Severity (PGIS).

Non-Small Cell Lung Cancer Symptom Assessment Questionnaire: Psychometric Performance and Regulatory Qualification of a Novel Patient-Reported Symptom Measure.

Background: The Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) was developed to incorporate the patient's perspective into evaluation of clinical benefit in advanced non-small cell lung cancer trials and meet regulatory expectations for doing so. Qualitative evidence supported 7 items covering 5 symptom concepts.

Objective: This study evaluated measurement properties of the NSCLC-SAQ's items, overall scale, and total score.

Comparison of Surgical Outcomes and Recurrence Rates of Cystic and Solid Vestibular Schwannomas.

 Cystic vestibular schwannomas (CVSs) are anecdotally believed to have worse clinical and tumor-control outcomes than solid vestibular schwannomas (SVSs); however, no data have been reported to support this belief. In this study, we characterize the clinical outcomes of patients with CVSs versus those with SVSs.  This is a retrospective review of prospectively collected data.

Agreement Among Paper and Electronic Modes of the EQ-5D-5L.

Introduction: While the EQ-5D-5L has been migrated to several electronic modes, evidence supporting the measurement equivalence of the original paper-based instrument to the electronic modes is limited.

Objectives: This study was designed to comprehensively examine the equivalence of the paper and electronic modes (i.e.

Why Reinvent the Wheel? Use or Modification of Existing Clinical Outcome Assessment Tools in Medical Product Development.

Assessment of clinical benefit in treatment trials can be made through report by a clinician, a patient, or a nonclinician observer (eg, caregiver) or through a performance-based assessment. The US Food and Drug Administration (FDA) published a final guidance for industry for one type of clinical outcome assessment (COA)-patient-reported outcome (PRO) measures-in 2009 that described how FDA reviews PRO measures for their adequacy to support medical product-labeling claims. Many of the principles described in the PRO Guidance could be applicable to the other types of COAs, including instruments completed by clinicians (ie, clinician-reported outcome assessments) and nonclinician observers (ie, observer-reported outcome assessments).

Symptoms of Major Depressive Disorder Scale: Performance of a Novel Patient-Reported Symptom Measure.

Background: The Symptoms of Major Depressive Disorder Scale (SMDDS) was expressly developed on the basis of qualitative data to directly incorporate patients' voices into evaluation of treatment benefit in major depressive disorder (MDD) clinical trials.

Objectives: To collect quantitative data necessary to refine/optimize the SMDDS and document its psychometric properties.

Methods: In this multicenter, observational study, participants with clinically diagnosed MDD completed questionnaires in 2 waves.

Assessing test-retest reliability of patient-reported outcome measures using intraclass correlation coefficients: recommendations for selecting and documenting the analytical formula.

Purpose: The US Food and Drug Administration (FDA) 2009 guidance for industry on patient-reported outcome (PRO) measures describes how the Agency evaluates the psychometric properties of measures intended to support medical product labeling claims. An important psychometric property is test-retest reliability. The guidance lists intraclass correlation coefficients (ICCs) and the assessment time period as key considerations for test-retest reliability evaluations.

Response scale selection in adult pain measures: results from a literature review.

Background: The purpose of this literature review was to examine the existing patient-reported outcome measurement literature to understand the empirical evidence supporting response scale selection in pain measurement for the adult population.

Methods: The search strategy involved a comprehensive, structured, literature review with multiple search objectives and search terms.

Results: The searched yielded 6918 abstracts which were reviewed against study criteria for eligibility across the adult pain objective.

Informing the Tolerability of Cancer Treatments Using Patient-Reported Outcome Measures: Summary of an FDA and Critical Path Institute Workshop.

The US Food and Drug Administration and the Critical Path Institute's Patient-Reported Outcome (PRO) Consortium convened a cosponsored workshop on the use of PRO measures to inform the assessment of safety and tolerability in cancer clinical trials. A broad array of international stakeholders involved in oncology drug development and PRO measurement science provided perspectives on the role of PRO measures to provide complementary clinical data on the symptomatic side effects of anticancer agents. Speakers and panelists explored the utility of information derived from existing and emerging PRO measures, focusing on the PRO version of the National Cancer Institute's Common Terminology Criteria for Adverse Events.

Selection of and Evidentiary Considerations for Wearable Devices and Their Measurements for Use in Regulatory Decision Making: Recommendations from the ePRO Consortium.

Background: Wearable devices offer huge potential to collect rich sources of data to provide insights into the effects of treatment interventions. Despite this, at the time of writing this report, limited regulatory guidance on the use of wearables in clinical trial programs has been published.

Objectives: To present recommendations from the Critical Path Institute's Electronic Patient-Reported Outcome Consortium regarding the selection and evaluation of wearable devices and their measurements for use in regulatory trials and to support labeling claims.

Developing and Implementing Performance Outcome Assessments: Evidentiary, Methodologic, and Operational Considerations.

The use of performance outcome (PerfO) assessments to measure cognitive or physical function in drug trials presents several challenges for both sponsors and regulators, owing in part to a relative lack of scientific guidance on their development, implementation, and interpretation. In December 2016, the Duke-Margolis Center for Health Policy convened a 2-day workshop to explore the evidentiary, methodologic, and operational challenges associated with PerfO measures, and to identify potential paths to addressing these challenges. This paper presents both a summary of the discussion as well as additional input from a working group of experts from FDA, industry, academia, and public-private consortia.

Immediate Label-Free Ex Vivo Evaluation of Human Brain Tumor Biopsies With Confocal Reflectance Microscopy.

Confocal microscopy utilizing fluorescent dyes is widely gaining use in the clinical setting as a diagnostic tool. Reflectance confocal microscopy is a method of visualizing tissue specimens without fluorescent dyes while relying on the natural refractile properties of cellular and subcellular structures. We prospectively evaluated 76 CNS lesions with confocal reflectance microscopy (CRM) to determine cellularity, architecture, and morphological characteristics.

Hypothalamic hamartoma: Neuropathology and epileptogenesis.

Hypothalamic hamartomas (HHs) are congenital malformations of the ventral hypothalamus resulting in treatment-resistant epilepsy and are intrinsically epileptogenic for the gelastic seizures that are the hallmark symptom of this disorder. This paper reviews the neuropathologic features of HHs associated with epilepsy, with an emphasis on characterizing neuron phenotypes and an ultimate goal of understanding the cellular model of ictogenesis occurring locally within this tissue. We also present previously unpublished findings on Golgi staining of HH.

An extent of resection threshold for seizure freedom in patients with low-grade gliomas.

OBJECTIVE Seizures are the most common presenting symptom of newly diagnosed WHO Grade II gliomas (low-grade glioma [LGG]) and significantly impair quality of life. Although gross-total resection of LGG is associated with better seizure control, it remains unclear whether an extent of resection (EOR) "threshold" exists for long-term seizure control. Specifically, what proportion of FLAIR-positive tissue in patients with newly diagnosed LGG must be removed to achieve Engel Class I seizure freedom? To clarify the EOR threshold for long-term seizure control, the authors analyzed data from a consecutive series of patients with newly diagnosed LGG who presented with seizures and subsequently underwent microsurgical resection.

Immediate ex-vivo diagnosis of pituitary adenomas using confocal reflectance microscopy: a proof-of-principle study.

OBJECTIVE The objective of this study was to evaluate the feasibility of using confocal reflectance microscopy (CRM) ex vivo to differentiate adenoma from normal pituitary gland in surgical biopsy specimens. CRM allows for rapid, label-free evaluation of biopsy specimens with cellular resolution while avoiding some limitations of frozen section analysis. METHODS Biopsy specimens from 11 patients with suspected pituitary adenomas were transported directly to the pathology department.

Development of a harmonized patient-reported outcome questionnaire to assess myelofibrosis symptoms in clinical trials.

Along with reducing spleen size, relieving symptom severity is a key objective of the treatment of myelofibrosis (MF). Several questionnaires have been developed for patient self-report of MF symptoms in clinical trials and each includes unique instructions, items, and/or response scales. This variability in questionnaire content increases uncertainty; it is unclear which questionnaire is the most appropriate for assessing MF symptoms and it makes comparisons across trials difficult.

Clinically Meaningful Outcomes in Early Alzheimer Disease: A Consortia-Driven Approach to Identifying What Matters to Patients.

Background: Numerous statistically derived composite measures have recently been proposed as clinical outcome assessments (COAs) for clinical trials in the early stages of Alzheimer disease. Critical Path Institute's Coalition Against Major Diseases (CAMD) advanced a proposed statistically derived composite measure to regulatory agencies with the goal of qualifying it as a COA for pre-dementia trials. In response to FDA's requirement to demonstrate that proposed COAs are meaningful to patients, this project aimed to identify the most important cognition-related concerns patients and informants report early in the disease and determine how this information maps to what is assessed by several statistically derived composite measures.