Survival of patients with chronic acid sphingomyelinase deficiency (ASMD) in the United States: A retrospective chart review study.

Background: Acid sphingomyelinase deficiency (ASMD), historically known as Niemann-Pick disease type A, A/B, and B, is a rare lysosomal storage pathology with multisystemic clinical manifestations. The aims of this study were to estimate the survival probability in patients in the United States with chronic ASMD (ASMD types B and A/B), and to describe the disease characteristics of these patients. Methods: This observational retrospective study included medical chart records of patients with chronic ASMD with retrievable data abstracted by 69 participating physicians from 25 medical centers in the United States. Included patients had a date of ASMD diagnosis or first presentation to a physician for ASMD symptoms (whichever occurred first) between January 01, 1990, and February 28, 2021. Medical chart records were excluded if patients were diagnosed with ASMD type A. Eligible medical chart records were abstracted to collect demographic, medical and developmental history, and mortality data. Survival outcomes were analyzed using Kaplan-Meier survival analyses from birth until death. Results: The overall study population (N = 110) included 69 patients with ASMD type B, nine with type A/B, and 32 with ASMD "non-type A" (ASMD subtype was unknown, but patients were confirmed as not having ASMD type A). The majority of patients were male with a median age at diagnosis of 3.8 years. Thirty-eight patients died during the study observation period, at a median age of 6.8 years. The median (95% confidence interval) survival age from birth was 21.3 (10.2; 60.4) years. At diagnosis or first presentation, 42.7% patients had ≥1 ASMD-related complication; splenic (30.0%) and hepatobiliary (20.9%) being the most common, and 40.9% required ≥1 medical visit due to complications. Conclusion: Patients with chronic ASMD in the United States have poor survival and significant burden of illness.

Multi-national observational study to assess quality of life and treatment preferences in patients with Crohn's perianal fistulas.

BACKGROUND: Patients with Crohn's disease (CD) are at risk of developing complications such as perianal fistulas. Patients with Crohn's perianal fistulas (CPF) are affected by fecal incontinence (FI), bleeding, pain, swelling, and purulent perianal discharge, and generally face a higher treatment burden than patients with CD without CPF. AIM: To gain insights into the burden of illness/quality of life in patients with CPF and their treatment preferences and satisfaction. METHODS: This cross-sectional observational study was conducted in patients with CD aged 21-90 years via a web-enabled questionnaire in seven countries (April-August 2021). Patients were recruited into three cohorts: Cohort 1 included patients without perianal fistulas; cohort 2 included patients with perianal fistulas without fistula-related surgery; and cohort 3 included patients with perianal fistulas and fistula-related surgery. Validated patient-reported outcome measures were used to assess quality of life. Drivers of treatment preferences were measured using a discrete choice experiment (DCE). RESULTS: In total, 929 patients were recruited (cohort 1, n = 620; cohort 2, n = 174; cohort 3, n = 135). Short Inflammatory Bowel Disease Questionnaire scores were worse for patients with CPF (cohorts 2 and 3) than for those with CD without CPF (cohort 1): Mean score 3.8 and 3.7 vs 4.1, respectively, (P < 0.001). Similarly, mean Revised FI and FI Quality of Life scores were worse for patients with CPF than for those with CD without CPF. Quality of Life with Anal Fistula scores were similar in patients with CPF with or without CPF-related surgery (cohorts 2 and 3): Mean score 41 and 42, respectively. In the DCE, postoperative discomfort and fistula healing rate were the most important treatment attributes influencing treatment choice: Mean relative importance 35.7 and 24.7, respectively. CONCLUSION: The burden of illness in CD is significantly higher for patients with CPF and patients rate lower postoperative discomfort and higher healing rates as the most desirable treatment attributes.

Real-world treatment preferences among health care providers in the United States in selecting disease modifying therapies for patients with multiple sclerosis: a discrete choice experiment.

AIMS: Health care providers (HCPs) treating multiple sclerosis (MS) in clinical practice have numerous disease-modifying therapies (DMTs) to consider when evaluating treatment options. This study assessed the treatment preferences of HCPs in the United States, both direct (explicit) and derived (explicit and implicit), when selecting MS DMTs based on clinical and logistical treatment attributes. MATERIALS AND METHODS: A 45-minute web-enabled questionnaire was administered to HCPs who manage patients with MS to assess the importance of treatment attributes. HCPs were recruited through an online panel. This study examined treatment attributes relevant to treatment decisions in MS, with a focus on the burden to HCPs and their staff, as well as HCP attitudes toward various aspects of MS care such as diagnosis, treatment prioritization, and ease of initiating or switching DMTs. The study also employed a discrete choice experiment (DCE) to assess direct and derived treatment preferences. RESULTS: The study recruited 145 HCPs. Direct assessments (a score of greater than 7.0 was considered important) suggested that safety (mean importance rating = 7.8/9) and relative risk reduction in relapses (7.6/9) and disability progression (7.5/9) were most important when selecting DMTs. In contrast, derived importance from the DCE (higher points corresponding to greater importance) suggested that logistical attributes such as dose frequency (mean relative attribute importance = 17.5%), dose titration (10.3%), formulation (9.4%), and volume of calls (9.1%) were important considerations, along with efficacy (16.5%), safety (9.8%), and gastrointestinal tolerability (9.4%). LIMITATIONS: This study may have been subject to selection bias due to the application of eligibility criteria, the convenient sampling recruitment methodology, and recruitment of HCPs with internet access. CONCLUSION: In the direct assessment, clinical attributes were chosen as the most important treatment attributes by HCPs. However, in the DCE, derived treatment decisions rated logistical attributes as also being as important in treatment choice.

In this study, researchers aimed to understand what multiple sclerosis (MS) neurologists, nurse practitioners, and physician assistants think is most important when choosing medicines for their patients. They surveyed 145 health care providers (HCPs) in the United States for this study. The HCPs reported that safety and reducing the risk of relapses and disability were most important when selecting medicines. Additionally, the researchers used a method called a discrete choice experiment to determine the relative importance of medication characteristics to HCPs. They found that additional factors, such as how often the medicine needs to be taken, how it is given, and how easy it is to use, were also very important. The study may not represent the opinions of all HCPs due to the number of participants and participation criteria.

Clinician Preferences for Oxybate Treatment for Narcolepsy: Survey and Discrete Choice Experiment.

INTRODUCTION: Immediate-release sodium oxybate (SXB) has been Food and Drug Administration (FDA)-approved to treat narcolepsy since 2002; in 2020, a mixed-salt oxybates formulation was also approved. Both are taken at bedtime with a second dose taken 2.5-4 h later. A third oxybate option, an investigational extended-release SXB, may soon be available. This study was undertaken to understand clinicians' preferences between these 3 different oxybate treatments. METHODS: Clinicians in active clinical practice for 3-35 years and experience treating patients with narcolepsy were recruited. A 30-min web-based survey quantified narcolepsy disease-state attitudes, treatment perceptions, and satisfaction with oxybates on 9-point scales. A discrete choice experiment (DCE) of 12 choice sets, with 2 hypothetical treatment profiles in each, was used to capture clinician preferences about overall oxybate therapy preference, impact on patient quality of life (QoL), and patient anxiety/stress. Attributes associated with current therapies and those expected to be available in the near future were included in the design. RESULTS: The clinicians surveyed (n = 100) indicated that narcolepsy has a negative impact on patient QoL (mean rating, 7.7) and rated impact on QoL and treatment efficacy as the most important aspects of a narcolepsy treatment (mean rating, 7.3-7.7). Clinicians with experience prescribing oxybates had moderately high satisfaction with SXB and mixed-salt oxybates efficacy (mean ratings, 6.5-6.9) and safety (mean ratings, 6.1-6.7) and lower satisfaction with nightly dosing frequency (mean rating, 5.9 and 6.3, respectively). In the DCE, dosing frequency was the most important attribute driving overall product choice, patient QoL, and reducing patient anxiety/stress (relative attribute importance, 46.1, 41.7, and 44.0, respectively), with once nightly preferred over twice nightly. CONCLUSION: Clinicians indicated a significantly higher preference for the once-at-bedtime dosing schedule versus twice nightly in selecting oxybate therapies overall and when aiming to improve patient QoL or reduce patient anxiety.

Current medications for narcolepsy include immediate-release sodium oxybate and mixed-salt oxybates. People taking these oxybates for narcolepsy take 1 dose at bedtime and must wake up 2.5­4 h later for the second dose. An investigational sodium oxybate, designed as a single bedtime dose, has been tentatively approved by the US Food and Drug Administration. This study used a 30-min web-based survey to learn what clinicians think about narcolepsy and narcolepsy medicines. A discrete choice experiment was used to identify which properties of current/future oxybate medicines are most important in a narcolepsy treatment. In this exercise, relevant properties of current/future oxybate medicines were mixed and matched to create hypothetical medicine profiles. Clinicians selected from these profiles which medication they preferred overall, which would improve patient quality of life, and which would reduce patient anxiety when thinking about taking the treatment. Clinicians were moderately satisfied with the effectiveness and safety of current narcolepsy medications. They strongly preferred oxybate treatments with fewer nightly doses and agreed that waking up for the second oxybate dose causes stress for patients. In the discrete choice experiment, the number of doses each night was the product characteristic that had the biggest impact on clinicians picking a medicine for narcolepsy. This was true for overall medicine choice, choosing a medicine that would improve patient quality of life, and choosing one that would reduce patient anxiety/stress. If granted marketing approval, extended-release sodium oxybate will be a once-at-bedtime option that may overcome challenges with current oxybate therapies.

Assessing the Burden of Illness Associated with Acquired Generalized Hypoactive Sexual Desire Disorder.

Background: Hypoactive sexual desire disorder (HSDD), which affects ∼10% of women in the United States, is defined as the persistent or recurrent deficiency/absence of sexual desire accompanied by personal distress. Although HSDD impacts patient quality of life and interpersonal relationships, the disorder often goes unaddressed or untreated. Recent studies of the burden of illness in women with HSDD, especially premenopausal women, are limited. Materials and Methods: A 45-minute web-based survey was designed to investigate the experience of women seeking treatment for HSDD and the impact of this disorder on several psychosocial aspects of women's lives. Women were recruited from an online panel of patients who participated in research studies for compensation. Validated questionnaires assessed sexual function (Female Sexual Function Index) and health-related quality of life (12-Item Short Form Survey [SF-12]), including mental and physical component scores. Results: A total of 530 women, aged ≥18 years, diagnosed with acquired generalized HSDD were included in the study. Premenopausal women indicated greater overall HSDD symptom burden compared with postmenopausal women. Patients with HSDD reported lower SF-12 scores compared with the general population. A multivariable regression analysis demonstrated that psychosocial factors influencing the burden of HSDD, including interference with their relationship with their partner (ß = -0.18; p < 0.005), mental and emotional well-being (ß = -0.23; p < 0.005), and household and personal activities (ß = -0.23; p = 0.02), negatively affected SF-12 mental component scores. Conclusions: HSDD symptom burden was found to be negatively and statistically significantly associated with patients' mental health; the impact was greater among premenopausal women compared with postmenopausal women.

Preferences for Attributes of Sodium Oxybate Treatment: A Discrete Choice Experiment in Patients with Narcolepsy.

Purpose: Current US FDA-approved treatments for narcolepsy include sodium oxybate (SXB) and calcium, magnesium, potassium, and sodium oxybates (mixed-salt oxybates), which require 2 nightly doses, 1 at bedtime and another 2.5 to 4 hours later. Once-nightly SXB (ON-SXB; FT218) is under FDA review to treat adults with narcolepsy. This study quantitatively characterized attributes of SXB treatment preferred by individuals with narcolepsy via a discrete choice experiment (DCE) and evaluated preferences for the product profiles of once-nightly vs twice-nightly SXB treatment. Patients and Methods: Adults with self-reported physician-diagnosed narcolepsy for ≥1 year and current or prior twice-nightly SXB treatment were eligible for this 30-minute, web-based study capturing patient experiences and a DCE. Participants responded to a survey instrument using 9-point scales; higher scores indicated greater severity/preference/satisfaction. In the DCE, hundreds of profiles were generated, each combining attributes of twice-nightly SXB and ON-SXB based on clinical trial data. The DCE was analyzed using a hierarchical Bayesian model. Results: Seventy-five participants were surveyed (50 current and 25 past twice-nightly SXB users). Dosing frequency was the most important attribute of SXB treatment; once nightly was significantly preferred vs twice nightly. The most common reasons for overall product preference were lack of need to wake up in the middle of the night for a second dose (48%), fewer side effects (46%), and ease of administration (32%). Number of nightly doses was the most important driver of taking the medication exactly as directed and reduced anxiety/stress. Participants were significantly more likely to prefer the blinded product profile of once-nightly SXB over twice-nightly SXB (mean rating, 7.5 vs 4.3; P<0.05). Conclusion: Among the choices presented, dosing frequency was the most important attribute for overall product choice, likelihood to take medication exactly as directed, and reducing anxiety/stress. The ON-SXB blinded profile was significantly preferred over twice-nightly SXB.

Development of the medication adherence estimation and differentiation scale (MEDS).

OBJECTIVES: To develop a self-reported measure for medication adherence and compare its ability to predict the proportion of days covered (PDC) with contemporary scales. METHODS: Retrospective prescription fill data from three community pharmacies in the Southeastern US were assessed to identify patients that were 18 years of age or older, and had received at least one medication for diabetes, hypertension, or dyslipidemia. A cross-sectional survey containing the Medication adherence Estimation and Differentiation Scale (MEDS) was administered among these pharmacy patrons. The MEDS assessed the extent and reasons for non-adherence. Survey responses were anonymously linked with retrospective prescription fill data. A total of 685 patients were sampled. The proportion of days covered (PDC) was used as the criterion measure. The Morisky, Green, and Levine Adherence Scale (1986 Morisky scale) and the Medication Adherence Reasons Scale (MAR-Scale) were used as comparators. RESULTS: The MEDS presented a five-factor solution-worries about side-effects, worries about addiction, worries about cost, lack of perceived need, and unintentional non-adherence (CFI = 0.97; RMSEA = 0.06; SRMR = 0.03; standardized factor loadings greater than 0.5, and statistically significant). The relationship between MEDS scores and PDC was statistically significant (unstandardized regression coefficient = -0.50, p < .01). The MEDS performed better than the 1986 Morisky scale (R2 = 0.02 vs 0.05, standardized regression coefficient = -0.13 vs -0.21) and the MAR-Scale (R2 = 0.02 vs 0.05, standardized regression coefficient = -0.12 vs -0.21) in predicting PDC. CONCLUSIONS: The MEDS demonstrated good psychometric properties and performed better than the comparator scales in the prediction of PDC.

A patient-reported, non-interventional, cross-sectional discrete choice experiment to determine treatment attribute preferences in treatment-naïve overactive bladder patients in the US.

PURPOSE: Many pharmacotherapeutic treatment options are available for the symptoms of overactive bladder (OAB), each offering varying efficacy, safety, and tolerability profiles that must be carefully considered when selecting treatment. The objective of the present study was to characterize pharmacotherapy treatment preferences of individuals with symptoms of OAB and to examine how preferences differ by both patient characteristics and disease burden metrics. PATIENTS AND METHODS: Patient preferences for OAB treatment attributes were examined using a discrete choice experiment (DCE). Attributes were identified through literature review, clinical relevance, and input from patients. Eligible respondents were required to be ≥18 years of age, have a self-reported physician OAB diagnosis or have self-reported symptoms of OAB, and be naïve to pharmacotherapy or invasive OAB treatments. A hierarchical Bayesian random-effects-only model was used to estimate the mean relative preference weights and mean relative importance scores of treatment attributes. Multivariable linear regression models with backward selection were used to analyze the differences in relative importance scores by demographic characteristics and disease burden-related metrics. RESULTS: In total, 514 individuals participated in the study. Most respondents were <65 years of age (66.0%), female (68.5%), and reported moderate/severe OAB symptoms (64.2%). Overall, respondents placed the greatest importance on drug delivery method, with a preference for oral and patches over injectables, followed by efficacy defined as reduced daytime micturition and out-of-pocket cost. Multivariable linear regression analyses revealed that females were less likely to select injectables, that symptom control of incontinence was the most important to respondents who reported greater work productivity loss, and that out-of-pocket cost was the most important to respondents with moderate/severe OAB. CONCLUSION: OAB treatment preferences vary depending on individual patient characteristics and disease severity. Overall, drug delivery method, reduced daytime micturition, and out-of-pocket costs were the most important treatment attributes among treatment-naïve individuals with symptoms of OAB. Preferences for OAB treatment were also found to vary depending on patient demographics and disease comorbidities, which has previously not been examined.

Preliminary development of the Medication Nonpersistence Scale.

OBJECTIVES: To develop the Medication Nonpersistence Scale (MNPS)-a multi-item self-reported scale to measure medication persistence. SETTING: Six hundred seventy-five patients patronizing 3 separate independent community pharmacies in the southeastern United States participated in this research. PRACTICE INNOVATION: The MNPS, a self-reported measure, developed to provide an estimate of, and reasons for, medication nonpersistence. EVALUATION: Cross-sectional survey data were linked with retrospective prescription fill data obtained from 3 independent community pharmacies in the southeastern United States. The MNPS factor structure was studied by means of confirmatory factor analysis (CFA), and its scale reliability and convergent validity were evaluated with the use of the results of this analysis. Its concurrent validity was tested against a standardized days-to-discontinuation measure calculated over the past 12 months, and an attempt was made to arrive at an optimum cutoff point to identify patients who have been nonpersistent with their medications. RESULTS: The survey yielded 675 usable patients. The CFA confirmed a single-factor solution with good model fit (root mean square error of approximation = 0.06 [90% CI 0.05-0.07]; comparative fit index = 0.96). Moderate to strong evidence of scale reliability (Cronbach alpha = 0.75; construct reliability = 0.94; index of composite reliability developed for binary items = 0.91), convergent validity (standardized factor loadings >0.5 and statistically significant), and concurrent validity (unstandardized regression coefficient = -3.97; P = 0.03) was observed. Individuals who score 1 or higher on the MNPS were considered to be nonpersistent. CONCLUSION: The MNPS demonstrated good psychometric properties and offers a useful first step toward the self-reported measurement of medication persistence in clinical practice and research.