Psychometric validation of the Pyruvate Kinase Deficiency Diary and Pyruvate Kinase Deficiency Impact Assessment in adults in the phase 3 ACTIVATE trial.

Background: Pyruvate kinase (PK) deficiency is a rare hereditary disorder characterized by chronic hemolytic anemia and serious sequalae which negatively affect patient quality of life. This study aimed to psychometrically validate the first disease-specific patient-reported outcome (PRO) instruments: the 7-item PK Deficiency Diary (PKDD) and 12-item PK Deficiency Impact Assessment (PKDIA), designed to assess signs, symptoms, and impacts of PK deficiency in patients enrolled in the ACTIVATE global phase 3 study of mitapivat versus placebo (NCT03548220).

Methods: All validation analyses for the PKDD and PKDIA were performed on blinded data, with analyses on item integrity, scoring, reliability, and validity conducted on data from screening and baseline.

Comparison of raw and regression approaches to capturing change on patient-reported outcome measures.

Purpose: Patient-reported outcome (PRO) analyses often involve calculating raw change scores, but limitations of this approach are well documented. Regression estimators can incorporate information about measurement error and potential covariates, potentially improving change estimates. Yet, adoption of these regression-based change estimators is rare in clinical PRO research.

The Measurement Performance of the Parkinson's Disease Activities of Daily Living, Interference, and Dependence Instrument.

Parkinson's disease is a neurodegenerative disease that can be associated with motor fluctuations that result in substantial negative impact to an individual's activities of daily living. Understanding the patient's perspective about the impact of Parkinson's disease therapies is an important part of drug development and shared treatment decision-making. The objective of this research was to examine the structure, scoring, internal consistency, test-retest reliability, and concurrent and known groups validity of the Parkinson's Disease Activities of Daily Living, Interference and Dependence (PD-AID) instrument, a new, patient-reported outcomes instrument, developed to assess the clinical benefit of Parkinson's disease treatment from the patient's perspective.

Memory-Assisted Global Impression of Change (MAGIC).

Background: The United States Food and Drug Administration is developing a series of patient-focused drug development guidance documents regarding the collection of patient experience data, including methods for understanding treatment benefit from the patient perspective. The goal of this research was to investigate the concern that the global impression of change scale is subject to recall error and thus not optimal for use as an anchor for estimating meaningful within-person change thresholds. We explored whether memory assistance for recalling baseline status would make a difference in how study participants diagnosed with Parkinson's disease (PD) responded to a patient global impression of change (PGIC) and patient global impression static (PGIS) item.

Development of the Near Vision Presbyopia Task-based Questionnaire for use in evaluating the impact of presbyopia.

Background: Presbyopia is a progressive condition that reduces the eye's ability to focus on near objects with increasing age. After a systematic literature review identified no existing presbyopia-specific patient-reported outcome (PRO) instruments meeting regulatory guidance, a new PRO instrument, the Near Vision Presbyopia Task-based Questionnaire (NVPTQ), was developed.

Results: To explore the patient experience with presbyopia, concept elicitation interviews were conducted with 20 presbyopic participants.

Development of the Presbyopia Impact and Coping Questionnaire.

Introduction: Presbyopia is a progressive, age-related visual condition that is characterized by reduced ability to focus on near/close objects, causing impacts on individuals' daily function and health-related quality of life. The Presbyopia Impact and Coping Questionnaire (PICQ) is a new patient-reported outcome (PRO) instrument that assesses presbyopia impact and use of coping behaviors among presbyopic individuals.

Methods: To document the impacts of presbyopia and associated coping behaviors, concept elicitation (CE) interviews were conducted with 20 presbyopic participants.

Validation of the Overactive Bladder-Bladder Assessment Tool (OAB-BAT): A Potential Alternative to the Standard Bladder Diary for Monitoring OAB Outcomes.

Background: An advisory board concluded that a new, comprehensive overactive bladder (OAB) patient-reported outcome (PRO) measure should be developed in accordance with regulatory guidelines. The OAB-Bladder Assessment Tool (OAB-BAT) was developed with qualitative input from OAB patients and experts to measure symptoms, bother, impacts, and satisfaction with treatment.

Objective: Psychometric evaluation of the OAB-BAT assessing PRO OAB symptoms, bother, and impacts during a 7-d recall period.

Development and Initial Validation Analyses of the Living with Idiopathic Pulmonary Fibrosis Questionnaire.

Several new drugs for idiopathic pulmonary fibrosis (IPF) are in development. Tools are needed to assess whether these drugs benefit patients on outcomes that matter most to them. Health-related quality of life (HRQL) is one such outcome.

Effects of treatment with eluxadoline on abdominal pain in patients with IBS-D: Additional post hoc analyses of Phase 3 trials.

Background: Recurring abdominal pain is a characteristic and often unpredictable and debilitating symptom of irritable bowel syndrome with diarrhea (IBS-D). Measuring the effects of IBS-D treatments on abdominal pain remains a significant challenge in clinical trials. Here, we aimed to examine the effect of eluxadoline through various post hoc analyses.

Evaluation and Validation of the Modified Reflux Symptom Questionnaire-Electronic Diary in Patients With Persistent Gastroesophageal Reflux Disease.

Objectives: This study aimed to examine the validity of the modified Reflux Symptom Questionnaire-electronic Diary (mRESQ-eD) through patient input and psychometric testing of the questionnaire to support use in clinical trials in patients with persistent gastroesophageal reflux disease (GERD) and in accordance with Food and Drug Administration guidance on patient-reported outcome instruments.

Methods: Cognitive interviews were conducted with patients (n = 30) to evaluate the interpretability and content validity of draft mRESQ-eD items. Patient data from a phase 2b clinical study (ClinicalTrials.

Economic Burden of Irritable Bowel Syndrome with Diarrhea: Retrospective Analysis of a U.S. Commercially Insured Population.

Background: The economic burden associated with irritable bowel syndrome with diarrhea (IBS-D) is not well understood.

Objectives: To (a) evaluate total annual all-cause, gastrointestinal (GI)-related, and symptom-related (i.e.

Economic burden of inadequate symptom control among US commercially insured patients with irritable bowel syndrome with diarrhea.

Aims: To assess healthcare resource use and costs among irritable bowel syndrome (IBS) with diarrhea (IBS-D) patients with and without evidence of inadequate symptom control on current prescription therapies and estimate incremental all-cause costs associated with inadequate symptom control.

Methods: IBS-D patients aged ≥18 years with ≥1 medical claim for IBS (ICD-9-CM 564.1x) and either ≥2 claims for diarrhea (ICD-9-CM 787.

Eluxadoline for Irritable Bowel Syndrome with Diarrhea.

Background Effective and safe treatments are needed for patients who have irritable bowel syndrome (IBS) with diarrhea. We conducted two phase 3 trials to assess the efficacy and safety of eluxadoline, a new oral agent with mixed opioid effects (μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist), in patients with IBS with diarrhea. Methods We randomly assigned 2427 adults who had IBS with diarrhea to eluxadoline (at a dose of 75 mg or 100 mg) or placebo twice daily for 26 weeks (IBS-3002 trial) or 52 weeks (IBS-3001 trial).

Item-level assessment of the irritable bowel syndrome quality of life questionnaire in patients with diarrheal irritable bowel syndrome.

Background: In previous studies, the Irritable Bowel Syndrome Quality of Life (IBS-QOL) instrument has been determined to have good measurement properties for general irritable bowel syndrome (IBS) and the diarrheal IBS (IBS-d) subtype in clinical trials.

Objective: This article aims to extend the true-score analyses that have been previously conducted to evaluate the IBS-QOL in IBS-d patients.

Methods: Item response theory analysis was conducted by fitting models to responses from 753 patients with severe IBS-d from a recent clinical trial.

Evaluation of the Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire in diarrheal-predominant irritable bowel syndrome patients.

Background: Diarrhea-predominant irritable bowel syndrome (IBS-d) significantly diminishes the health-related quality of life (HRQOL) of patients. Psychological and social impacts are common with many IBS-d patients reporting comorbid depression, anxiety, decreased intimacy, and lost working days. The Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire is a 34-item instrument developed and validated for measurement of HRQOL in non-subtyped IBS patients.

Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study.

Background & Aims: Simultaneous agonism of the μ-opioid receptor and antagonism of the δ-opioid receptor can reduce abdominal pain and diarrhea in patients with irritable bowel syndrome with diarrhea (IBS-D) without constipating side effects. We evaluated the efficacy and safety of a minimally absorbed, μ-opioid receptor agonist and δ-opioid receptor antagonist (eluxadoline) in a phase 2 study in patients with IBS-D.

Methods: We randomly assigned 807 patients to groups that received oral placebo twice daily or 5, 25, 100, or 200 mg oral eluxadoline for 12 weeks.

Randomized, double-blind, phase II, multicenter study evaluating the safety/tolerability and efficacy of JNJ-Q2, a novel fluoroquinolone, compared with linezolid for treatment of acute bacterial skin and skin structure infection.

JNJ-Q2 is a fluoroquinolone with broad coverage including methicillin-resistant Staphylococcus aureus (MRSA). A double-blind, multicenter, phase II noninferiority study treated 161 patients for 7 to 14 days, testing the efficacy of JNJ-Q2 (250 mg, twice a day [BID]) versus linezolid (600 mg, BID) in patients with acute bacterial skin and skin structure infections (ABSSSI). The prespecified criterion for noninferiority was 15%.