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Background: Despite the rise in gender-affirming care, our understanding of prostate cancer (PCa) in transgender women (TGW) remains in its infancy. Health disparities and lack of PCa awareness and screening are possible barriers to providing quality care for this population. In addition, the implication of hormonal manipulation for the aggressiveness of PCa in TGW is yet to be determined. Here, this study sought to compare oncological characteristics and survival outcomes between transgender and cisgender (CG) patients with PCa via two national data sets., Methods: The Veterans Affairs Informatics and Computing Infrastructure database (1999-2020) and the Surveillance, Epidemiology, and End Results-Medicare database (2010-2017) were reviewed. Demographic and clinical details were analyzed. Logistic regression analysis was performed on propensity score-matched groups to identify predictors of high-risk disease and metastasis in patients with PCa. Groups were matched 5:1 (CG:TGW) on the basis of age, race, year of diagnosis, and Charlson Comorbidity Index score. Primary outcomes included metastatic presentation, high-risk localized disease, overall survival (OS), and prostate cancer-specific mortality (PCSM)., Results: A total of 1194 patients were included (199 TGW; 995 CG). Associations between transgender identity and metastatic presentation (odds ratio [OR], 0.38; p = .2), high-risk localized disease (OR, 1.19; p = .50), or PCSM (hazard ratio [HR], 0.65; p = .3) were not detected. Transgender identity was associated with improved OS (HR, 0.67; p = .014)., Conclusions: PCa-specific outcomes seem comparable between TGW and CG men, although the study was underpowered to detect modest differences. Further investigation into the incidence and outcomes of PCa in TGW is warranted., (© 2024 American Cancer Society.)

The Patient-Focused Drug Development initiative of the U.S. Food and Drug Administration (FDA) aims to ensure that the patient experience of disease and treatment is an integral component of the drug development process. The 21st Century Cures Act and Prescription Drug User Fee Act (PDUFA) VI require the FDA to publicly report the type of patient-experience data reviewed in a new drug application (NDA) to inform regulatory decision-making. This report describes a recent approach adopted at Janssen of integrating patient-experience data into the NDA for esketamine (SPRAVATO®) nasal spray with a newly initiated oral antidepressant (esketamine + AD) for treatment-resistant depression. During the development of esketamine + AD, patient-experience data were collected using several patient-reported outcomes, including the Sheehan Disability Scale and 9-item Patient Health Questionnaire (PHQ-9). Additionally, a patient-preference study assessed the relative importance of benefits and harms that patients allocated to different attributes of treatment. Preferences were collected from patients enrolled in phase 3 esketamine trials and from an online panel of primarily ketamine-naive patients. Patient-experience data were integrated into the esketamine NDA, the FDA advisory committee meeting briefing document, and the Sponsor's presentation. The FDA acknowledged reviewing the patient-experience data and determined that they supported esketamine + AD for treatment-resistant depression. This report highlights the importance of integrating patient-experience methods early in drug development, their impact on assessing patient-relevant benefits and risks, and how they can help improve clinical program design., (© 2021. The Author(s).)

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. Wave 1 was designed to refine the SMDDS using Rasch measurement evaluations and item reduction analyses. On a subset of wave 1 subjects, 7 to 12 months later, wave 2 further examined item performance and measurement properties. Exploratory factor analyses and assessments of construct validity and reliability (internal consistency and reproducibility) were completed., Results: Using wave 1 data (N = 315; females = 71%, white = 81%, mean age = 44 years), the SMDDS was revised from 36 to 16 items. The Rasch item threshold map indicated that all but 1 item (suicidal ideation) were appropriately ordered. The 207 wave 2 participants were 74% females, 82% white, with a mean age of 45 years. The exploratory factor analyses resulted in a single component (all standardized factor loadings >0.46). Cronbach α was 0.93 and the 7-day test-retest intraclass correlation coefficient (n = 93) was 0.84 (95% confidence interval 0.77-0.89). SMDDS scores discriminated between MDD severity levels., Conclusions: The 16-item SMDDS generated highly reliable scores with substantial evidence of construct validity. On the basis of the evidence of appropriate content validity and sound psychometric performance, the Food and Drug Administration qualified the SMDDS as an outcome measure to support exploratory efficacy endpoints in MDD clinical trials., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Activation of the Hedgehog signalling pathway contributes to cancer progression and the development of myeloid leukaemia stem cell therapeutic resistance. We aimed to identify the maximum tolerated dose (MTD) and the recommended phase 2 dose of the selective Hedgehog antagonist PF-04449913 in myeloid malignancies., Methods: We undertook an open-label, dose-finding, standard 3+3 design phase 1 study of PF-04449913 in adult patients with acute myeloid leukaemia, chronic myeloid leukaemia, chronic myelomonocytic leukaemia, myelodysplastic syndrome, or myelofibrosis who were refractory, resistant, or intolerant to previous treatments, at three centres in the USA and one in Italy. Patients who had newly diagnosed, untreated disease were included if they were not eligible for standard treatment options or if standard treatments were not deemed appropriate. Patients received PF-04449913 once daily continuously until disease progression, unacceptable toxic effects, or patient withdrawal for up to 12 28-day cycles. Additional cycles were given if patients showed evidence of clinical benefit. The starting dose was 5 mg and was increased by 100% until the first dose-limiting toxic effect (DLT) and by 50% thereafter, in keeping with a 3+3 clinical trial statistical design. The primary endpoint was first-cycle DLTs. Secondary endpoints were safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity. This trial is registered with ClinicalTrials.gov, number NCT00953758., Findings: Between March 24, 2010, and Sept 7, 2012, 47 patients were enrolled and included in the study: 28 with acute myeloid leukaemia, six with myelodysplastic syndrome, five with chronic myeloid leukaemia (two with chronic-phase and three with blast-phase disease), one with chronic myelomonocytic leukaemia, and seven with myelofibrosis. Patients received PF-04449913 once daily at 5 mg (n=3), 10 mg (n=3), 20 mg (n=4), 40 mg (n=4), 80 mg (n=8), 120 mg (n=3), 180 mg (n=3), 270 mg (n=5), 400 mg (n=9), and 600 mg (n=5). Two patients experienced DLTs (one each in the 80 mg and 600 mg dose groups). The MTD for PF-04449913 was established to be 400 mg once daily. Of the 47 patients enrolled, 28 (60%) experienced treatment-related adverse events, three of which were grade 4 in severity. The most common treatment-related adverse events included dysgeusia (13 [28%] patients), decreased appetite (nine [19%]), and alopecia (seven [15%]). None of the 15 deaths reported were treatment related. Pharmacokinetics seemed to be dose proportional. The mean half-life was 23·9 h (SD 14·0) in the MTD group. Some suggestion of clinical activity was noted in 23 (49%) of 47 patients with haematological malignancies. Based on these results, the recommended phase 2 dose was 200 mg or lower once daily., Interpretation: Based on these findings, PF-04449913 is being tested in phase 2 studies in patients with myelodysplastic syndrome, acute myeloid leukaemia, and myelofibrosis., Funding: Pfizer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Faculty members' educational endeavors have generally not received adequate recognition. The Association for Surgical Education in 1993 established a task force to determine the magnitude of this problem and to create a model to address the challenges and opportunities identified. To obtain baseline information, the task force reviewed information from national sources and the literature on recognizing and rewarding faculty members for educational accomplishments. The group also developed and mailed to surgery departments at all U.S. and Canadian medical schools a questionnaire asking about the educational endeavors of the surgery faculty and their recognition for such activities. The response rate after two mailings was only 56%, but the responses reaffirmed the inadequacy of systems for rewarding and recognizing surgeon-teachers and surgeon-educators, and confirmed that the distinction between the roles of teacher and educator was rarely made. The task force created a four-tier hierarchical model based on the designations teacher, master teacher, educator, and master educator as a framework to offer appropriate recognition and rewards to the faculty, and endorsed a broad definition of educational scholarship. Criteria for various levels of achievement, ways to demonstrate and document educational contributions, appropriate support and recognition, and suggested faculty ranks were defined for these levels. The task force recommended that each surgery department have within its faculty ranks a cadre of trained teachers, a few master teachers, and at least one educator. Departments with a major commitment to education should consider supporting a master educator to serve as a resource not only for the department but also for the department's medical school and other medical schools. Although this model was created for surgery departments, it is generalizable to other disciplines.