Search

In the phase 3 ANDROMEDA trial, patients treated with daratumumab, bortezomib, cyclophosphamide, and dexamethasone (D-VCd) had significantly higher rates of organ and hematologic response compared with patients who received VCd alone. Here, we present patient-reported outcomes (PROs) from the ANDROMEDA trial. PROs were assessed through cycle 6 using three standardized questionnaires. Treatment effect through cycle 6 was measured by a repeated-measures, mixed-effects model. The magnitude of changes in PROs versus baseline was generally low, but between-group differences favored the D-VCd group. Results were generally consistent irrespective of hematologic, cardiac, or renal responses. More patients in the D-VCd group experienced meaningful improvements in PROs; median time to improvement was more rapid in the D-VCd group versus the VCd group. After cycle 6, patients in the D-VCd group received daratumumab monotherapy and their PRO assessments continued, with improvements in health-related quality of life (HRQoL) reported through cycle 19. PROs of subgroups with renal and cardiac involvement were consistent with those of the intent-to-treat population. These results demonstrate that the previously reported clinical benefits of D-VCd were achieved without decrement to patients' HRQoL and provide support of D-VCd in patients with AL amyloidosis.

**Background:** Hepatitis C virus (HCV) infection and its treatments are associated with significant symptoms, side effects and impact on patients functioning. The Hepatitis C Symptom and Impact Questionnaire version 4 (HCV-SIQv4) was developed according to FDA Patient Reported Outcomes (PRO) Guidance, for evaluating chronic HCV infection and its treatment. **Objectives:** This study evaluated the psychometric properties and clinically important change (CIC) thresholds of the measure. **Methods:** PRO data were pooled from three Phase IIb and III trials evaluating interferon-free simeprevircontaining regimens for treatment of chronic HCV infection. Scale range adequacy, reliability, validity, responsiveness and CIC thresholds were assessed incorporating knowledge of the appropriate measurement model. **Results:** Data from 437 patients were analyzed. Stage of liver disease was associated with symptom severity and functioning at baseline. Reliability was acceptable (test-retest ICC ≥0.7) for most scores except the Gastrointestinal and Integumentary domains. Convergent validity was observed between HCV-SIQv4 scores and concurrent measures of conceptual similarity. Greater symptom severity and worse impact scores were associated with liver cirrhosis, depression, severe fatigue and health limitations. Patients who achieved SVR12 had better outcomes than those failing to. HCV-SIQv4 symptom and domain scores were responsive to changes in health state (effect sizes ≥0.5). Exploratory thresholds for change in scores indicating a clinically important improvement and worsening were HCV-SIQv4 Overall Body System Score (BSS), 8 and 8; Constitutional BSS, 10 and 10; Gastrointestinal BSS, 5 and 5; Psychiatric BSS, 8 and 8; Neurocognitive BSS, 8 and 8; and Integumentary BSS, 5 and 5. **Conclusions:** The HCV-SIQv4 offers reliable, responsive assessments within HCV clinical development. CIC thresholds are now available to aid score interpretation.

PURPOSE To evaluate the effects of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) on patient-reported outcomes (PROs) in the phase III MAIA study. PATIENTS AND METHODS PROs were assessed on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item and the EuroQol 5-dimensional descriptive system at baseline and every 3 months during treatment. By mixed-effects model, changes from baseline are presented as least squares means with 95% CIs. RESULTS A total of 737 transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma were randomly assigned to D-Rd (n = 368) or Rd (n = 369). Compliance with PRO assessments was high at baseline (> 90%) through month 12 (> 78%) for both groups. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item global health status scores improved from baseline in both groups and were consistently greater with D-Rd at all time points. A global health status benefit was achieved with D-Rd, regardless of age (< 75 and ≥ 75 years), baseline Eastern Cooperative Oncology Group (ECOG) performance status score, or depth of response. D-Rd treatment resulted in significantly greater reduction in pain scores as early as cycle 3 ( P = .0007 v Rd); the magnitude of change was sustained through cycle 12. Reductions in pain with D-Rd were clinically meaningful in patients regardless of age, ECOG status, or depth of response. Similarly, PRO improvements were observed with D-Rd and Rd on the EuroQol 5-dimensional descriptive system visual analog scale score. CONCLUSION D-Rd compared with Rd was associated with faster and sustained clinically meaningful improvements in PROs, including pain, in transplant-ineligible patients with newly diagnosed multiple myeloma regardless of age, baseline ECOG status, or depth of treatment response.

Background: This study explored the degree of views towards supportive workplace policies among employees during coronavirus disease 2019 (COVID-19) pandemic and its association with health-related quality of life (HRQoL) in Hong Kong. Methods: A cross-sectional study was conducted in 1049 employees using online self-administered questionnaire. Views on workplace policies were measured in term of agreement on its comprehensiveness, timeliness and transparency whereas HRQoL was measured using EQ-5D-5L Hong Kong version. Univariate estimates on the impact of HRQoL from views of measures in workplace was done. Qualitative comments on the suggestions to strengthen workplace measures were collected and presented descriptively. Results: Of 1048 respondents, 16% reported that no workplace measures nor guidelines were existed in their company related to the COVID-19 pandemics. Those who reported having workplace policy were not satisfied with the arrangement in term of comprehensiveness (36%), timeliness (38%), and transparency (63%). Regarding to the policy measure, only 68% respondents reported that their workplace supplied face masks to them. The health index was 0897, which was lower than the norm of 0.924. 64% of respondents reported having a health problem in at least 1 of 5 dimension of EQ-5D-5L with the highest proportion of having problem in anxiety/depression (55%). In addition, the workplace policy and measure had a direct effect of 0.131 on health outcome. Perception of infection risk had a direct effect of 0.218 on health outcome and partly mediated the relationship between workplace policy and measure and health outcome (0.066). Conclusion: The study highlighted the workplace policy and measure is an important mean to minimize infection risk at workplace so as to reduce tremendous stress and health outcome caused by a COVID-19 pandemic. Workplace measures related to COVID-19 pandemic should be further strengthen to mitigate the risk of infection and protect employee’s health.

There is a need for measures to track symptom change in autism spectrum disorder (ASD). We conducted a validation study on a revised version of the Autism Behavior Inventory (ABI), and a short form (ABI-S). Caregivers of individuals (6–54 years) with confirmed diagnoses of ASD (N = 144) completed the ABI and other rating scales at 4 time points. Scale consistency for each domain, 3–5 day test–retest reliability, and construct validity, determined by comparison to pre-specified scales, were all good. Change in the ABI was congruent with changes in other instruments. Collectively, results suggest incipient suitability of the ABI as a measure of changes in core and associated symptoms of ASD. Trial Registration NCT02299700. Electronic supplementary material The online version of this article (10.1007/s10803-019-03965-7) contains supplementary material, which is available to authorized users.

Patient-reported outcomes (PROs) are used to assess benefit-risk in drug development. The relationship between PROs and clinical outcomes is not well understood. We aim to elucidate the relationships between changes in PRO measures and clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC).We investigated relationships between changes in self-reported fatigue, pain, functional well-being (FWB), physical well-being (PWB) and prostate cancer-specific symptoms with overall survival (OS) and radiographic progression-free survival (rPFS) after 6 and 12 months of treatment in COU-AA-301 (N = 1195) or COU-AA-302 (N = 1088). Eligible COU-AA-301 patients had progressed after docetaxel and had Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2. Eligible COU-AA-302 patients had no prior chemotherapy and ECOG PS 0 or 1. Patients were treated with abiraterone acetate (1000 mg/day) plus prednisone (10 mg/day) or prednisone alone daily. Association between self-reported fatigue, pain and functional status, and OS and/or rPFS, using pooled data regardless of treatment, was assessed. Cox proportional hazard regression modeled time to death or radiographic progression.In COU-AA-301 patients, PRO improvements were associated with longer OS and longer time to radiographic progression versus worsening or stable PROs (P 0.0001). In multivariate models, all except pain intensity remained associated with OS. Pain intensity, PWB and FWB improvements remained associated with rPFS. In COU-AA-302 patients, worsening PROs were associated with higher likelihood of radiographic progression (P ≤ 0.025) compared with improved or stable PROs. In multivariate models, worsening PWB remained associated with worse rPFS. The 12-month analysis confirmed the 6-month results.PROs are significantly associated with clinically relevant time-to-event efficacy outcomes in clinical trials and may complement and help predict traditional clinical practice methods for monitoring patients for disease progression.

Introduction: In oncology clinical trials, overall survival (OS) is considered the gold standard efficacy endpoint. However, in multiple myeloma, the prolonged survival times and availability of multiple salvage therapies render it difficult to rely on OS as a primary endpoint. Instead, progression-free survival (PFS) or clinical response can be a relevant biomarker. At the same time, some health technology assessment bodies will only consider evidence based on patient-relevant endpoints, such as morbidity, mortality, and health-related quality of life (HRQoL), within their benefit assessments. Patient-reported outcomes (PROs) provide insights into how a treatment affects HRQoL, including symptoms and functioning. In the phase 3 MAIA trial, daratumumab, lenalidomide, and dexamethasone (D-Rd) demonstrated a significantly prolonged PFS and rapid and sustained improvements in PROs compared with lenalidomide and dexamethasone (Rd) alone at a median follow-up of 28 months. Updated results with longer follow-up confirmed a continued PFS benefit, deepening best clinical responses, and a significant OS benefit with D-Rd. Here, we report the results of analyses exploring the relationship between clinical efficacy endpoints and PROs in the MAIA trial. Methods: In MAIA (NCT02252172), TIE patients with NDMM were randomized to D-Rd or Rd until disease progression (PD) or unacceptable side effects. Clinical response and PD were defined per the International Myeloma Working Group uniform response criteria. PROs were assessed at baseline, on day 1 of cycles 3, 6, 9, and 12 for year 1, every 6 months thereafter until PD, or at end of treatment and at 8 and 16 weeks post-progression using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30). The current analyses were conducted on patients with a baseline PRO assessment and ≥1 post-baseline PRO assessment using a clinical cutoff date of February 19, 2021. Patients from both treatment groups were pooled and stratified by best clinical response. For PROs, the threshold for clinically meaningful change from baseline was defined a priori as ≥10 points based on published literature. Analyses were conducted for the global health status (GHS), fatigue, and pain scales of the EORTC QLQ-C30. The proportions of patients with clinically meaningful improvement in these PROs from baseline at any time while on treatment were calculated for and compared across best clinical response subgroups. For this analysis, patients were censored at the time of PD or discontinuation of therapy. Results were summarized with odds ratios and 95% confidence intervals. Additionally, the proportions of patients with clinically meaningful worsening in PROs from baseline at the time of and post-progression were also calculated for those who had PD. No adjustments were made for multiplicity. Nominal P-values are presented. Results: Best clinical response at a median follow-up of 56.2 months for the 710 patients included in this analysis is shown in the Table. For GHS, fatigue, and pain, the proportion of patients who reported clinically meaningful improvement from baseline increased with increasing depth of best clinical response. Odds ratios comparing best clinical response vs stable disease reflect this relationship and are shown in the Figure. Of the 264 patients who experienced PD and had PRO data at the time of or post-progression, 38.6%, 54.9%, and 39.4% reported meaningful worsening of GHS, pain, and fatigue, respectively, at the time of or post-progression. Conclusions: Patients with deeper best clinical response were more likely to report meaningful improvements in PROs. Patients who experienced PD reported worsening of GHS and symptoms at the time of or following progression. These analyses provide evidence of the association between key clinical efficacy endpoints and PROs and demonstrate the patient relevance of these clinical endpoints. Figure 1 Figure 1. Disclosures Perrot: Abbvie: Honoraria; BMS Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kumar: Amgen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Genentech: Consultancy, Research Funding; Bluebird Bio: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; Antengene: Consultancy, Honoraria; Oncopeptides: Consultancy; Beigene: Consultancy; Tenebio: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Plesner: Takeda: Research Funding; Genentech: Other: Advisor, Research Funding; Oncopeptides: Other: Advisor, Research Funding; AbbVie: Other: Advisor, Research Funding; CSL Behring: Other: Advisor; Janssen: Other: Advisor, Research Funding; Celgene: Other: Advisor, Research Funding; Genmab: Research Funding. Orlowski: Asylia Therapeutics, Inc., BioTheryX, Inc., and Heidelberg Pharma, AG.: Other: Laboratory research funding; CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Other: Clinical research funding; Amgen, Inc., BioTheryX, Inc., Bristol-Myers Squibb, Celgene, EcoR1 Capital LLC, Genzyme, GSK Biologicals, Janssen Biotech, Karyopharm Therapeutics, Inc., Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, Inc., Sanofi-Aventis, and Takeda P: Consultancy, Honoraria; Asylia Therapeutics, Inc.: Current holder of individual stocks in a privately-held company, Patents & Royalties; Amgen, Inc., BioTheryX, Inc., Bristol-Myers Squibb, Celgene, Forma Therapeutics, Genzyme, GSK Biologicals, Janssen Biotech, Juno Therapeutics, Karyopharm Therapeutics, Inc., Kite Pharma, Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, I: Membership on an entity's Board of Directors or advisory committees. Moreau: Abbvie: Honoraria; Oncopeptides: Honoraria; Celgene BMS: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; Janssen: Honoraria. Bahlis: Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Genentech: Consultancy; GlaxoSmithKline: Consultancy, Honoraria. Nahi: XNK Therapeutics AB: Consultancy. Hulin: abbvie: Honoraria; Celgene/BMS: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Janssen: Honoraria. Quach: Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen/Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Goldschmidt: GSK: Honoraria; Incyte: Research Funding; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Adaptive Biotechnology: Consultancy; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Novartis: Honoraria, Research Funding; Dietmar-Hopp-Foundation: Other: Grant; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Takeda: Consultancy, Research Funding; Johns Hopkins University: Other: Grant; Mundipharma: Research Funding; MSD: Research Funding; Molecular Partners: Research Funding. O'Dwyer: Bristol Myers Squibb: Research Funding; ONK Therapeutics: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy. Venner: Amgen: Research Funding; Celgene: Research Funding; Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria; BMS: Honoraria; Sanofi: Honoraria; Pfizer: Honoraria. Weisel: Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. Raje: Celgene, Amgen, Bluebird Bio, Janssen, Caribou, and BMS: Other. Macro: Takeda: Honoraria, Other: Travel accomodation, Research Funding; Janssen: Honoraria, Other: Travel accomodation, Research Funding; GSK: Honoraria; Celgen/BMS: Honoraria; Sanofi: Honoraria. Leleu: Sanofi: Honoraria; Roche: Honoraria; Pierre Fabre: Honoraria; Oncopeptides: Honoraria; Novartis: Honoraria; Mundipharma: Honoraria; Merck: Honoraria; Karyopharm Therapeutics: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Carsgen Therapeutics Ltd: Honoraria; Celgene: Honoraria; Gilead Sciences: Honoraria; Janssen-Cilag: Honoraria; AbbVie: Honoraria; Takeda: Honoraria, Other: Non-financial support. Liu: Janssen: Current Employment, Current equity holder in publicly-traded company. Fastenau: Janssen: Current Employment, Current equity holder in publicly-traded company. Gries: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Ho: DRG Abacus: Consultancy; Emalex Biosciences: Consultancy; Janssen: Consultancy. Mistry: Janssen: Current Employment, Current equity holder in publicly-traded company. Tromp: Janssen: Current Employment, Current equity holder in publicly-traded company. Delioukina: Janssen: Current Employment. Vermeulen: Janssen: Current Employment, Current equity holder in publicly-traded company. Usmani: Amgen: Consultancy, Research Funding, Speakers Bureau; Abbvie: Consultancy; Array BioPharma: Consultancy, Research Funding; GSK: Consultancy, Research Funding; EdoPharma: Consultancy; SkylineDX: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Janssen: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy, Research Funding, Speakers Bureau; Janssen Oncology: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding.

Introduction: Multiple myeloma (MM) is a chronic hematologic malignancy with a high symptom burden that can have a substantial negative impact on patients' (pts) health-related quality of life (HRQoL). The introduction of novel triplet regimens for newly diagnosed MM (NDMM) has extended progression-free survival (PFS) and overall survival (OS); however, adverse events and demanding administration and monitoring schedules have a further negative effect on HRQoL, especially among pts who are transplant ineligible (TIE) due to older age and/or frailty. Optimizing initial treatment is particularly important in older pts, many of whom receive only 1 line of therapy. The phase 3 MAIA trial compared daratumumab, lenalidomide, and dexamethasone (D-Rd) vs lenalidomide and dexamethasone (Rd) in TIE pts with NDMM. At a median follow-up of 28 months, D-Rd significantly prolonged PFS and was associated with faster and sustained clinically meaningful improvements in patient-reported outcomes (PROs) vs Rd. Results of an updated analysis with longer follow-up recently confirmed a significant benefit in OS with D-Rd vs Rd as well as a continued significant PFS benefit and higher rates of complete response or better and very good partial response or better. Here we present an update of the HRQoL analysis with additional follow-up. Methods: MAIA (NCT02252172) is a randomized, open-label, active controlled, multicenter, phase 3 study of TIE pts with NDMM who were randomly assigned 1:1 to receive D-Rd or Rd until disease progression (PD) or unacceptable toxicity. PROs were recorded using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and the EQ-5D-5L visual analog scale. EORTC QLQ-C30 has 30 items comprising 5 functional scales (physical, role, emotional, cognitive, and social functioning), 1 global health status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain) and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Questionnaires were completed at baseline, on day 1 of cycles 3, 6, 9, and 12 for year 1, and every 6 months thereafter until PD. Analyses were conducted on all pts with a baseline and ≥1 post-baseline PRO assessment. Pts were censored at PD or discontinuation of study treatment. Thresholds for meaningful improvement and worsening were defined a priori based on published literature (≥10-point change). Treatment effect was analyzed using a mixed-effects model for repeated measurements including baseline value, visit, treatment, visit by treatment interaction, and randomization stratification factors as fixed effects and individual subject as random effect. Results: At a median follow-up of 56.2 months, discontinuation rates were lower with D-Rd than Rd (56.8% vs 80.8%). For GHS, physical functioning, fatigue, pain, and dyspnea, PROs that are particularly relevant to pts with MM, a numerically greater proportion of pts achieved a meaningful improvement with D-Rd vs Rd (Table 1). Differences were significant for physical functioning, fatigue, and dyspnea. The proportion of pts achieving a meaningful worsening on therapy was similar in both treatment groups (Table 1). The median time to improvement was numerically shorter with D-Rd vs Rd for physical functioning and pain and with Rd vs D-Rd for GHS and fatigue; differences were not significant (Table 2). The median time to worsening of fatigue was similar between groups, numerically longer for D-Rd vs Rd for GHS, and significantly longer with D-Rd than Rd for physical functioning, pain, and dyspnea (Table 2). Median time to worsening of pain with D-Rd vs Rd was 39.43 vs 17.97 months, reflective of an additional ~21 months without worsening pain among pts treated with D-Rd. Between-group differences for least squares mean change from baseline for these 5 PROs favored D-Rd vs Rd at all assessment time points except cycle 3 for physical functioning and cycle 6 for fatigue; differences were significant at ≥1 timepoint for each scale. Conclusions: These updated PRO analyses from the MAIA study demonstrate sustained and clinically meaningful improvements in HRQoL with D-Rd vs Rd with almost 5 years of follow-up. These results are consistent with the clinical benefits of superior PFS, OS, and deep responses observed with D-Rd compared with Rd and support the use of D-Rd in older pts. Figure 1 Figure 1. Disclosures Perrot: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kumar: Roche-Genentech: Consultancy, Research Funding; Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; Bluebird Bio: Consultancy; Tenebio: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Antengene: Consultancy, Honoraria; Oncopeptides: Consultancy; Beigene: Consultancy; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Plesner: Takeda: Research Funding; Oncopeptides: Other: Advisor, Research Funding; Genentech: Other: Advisor, Research Funding; CSL Behring: Other: Advisor; AbbVie: Other: Advisor, Research Funding; Celgene: Other: Advisor, Research Funding; Janssen: Other: Advisor, Research Funding; Genmab: Research Funding. Orlowski: Amgen, Inc., BioTheryX, Inc., Bristol-Myers Squibb, Celgene, EcoR1 Capital LLC, Genzyme, GSK Biologicals, Janssen Biotech, Karyopharm Therapeutics, Inc., Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, Inc., Sanofi-Aventis, and Takeda P: Consultancy, Honoraria; CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Other: Clinical research funding; Asylia Therapeutics, Inc., BioTheryX, Inc., and Heidelberg Pharma, AG.: Other: Laboratory research funding; Asylia Therapeutics, Inc.: Current holder of individual stocks in a privately-held company, Patents & Royalties; Amgen, Inc., BioTheryX, Inc., Bristol-Myers Squibb, Celgene, Forma Therapeutics, Genzyme, GSK Biologicals, Janssen Biotech, Juno Therapeutics, Karyopharm Therapeutics, Inc., Kite Pharma, Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, I: Membership on an entity's Board of Directors or advisory committees. Moreau: Oncopeptides: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Celgene BMS: Honoraria; Amgen: Honoraria; Abbvie: Honoraria. Bahlis: BMS/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Genentech: Consultancy; GlaxoSmithKline: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria. Nahi: XNK Therapeutics AB: Consultancy. Hulin: Takeda: Honoraria; Sanofi: Honoraria; Celgene/BMS: Honoraria; Janssen: Honoraria; abbvie: Honoraria. Quach: CSL: Consultancy, Membership on an entity's Board of Directors or advisory committees; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen/Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Goldschmidt: Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Incyte: Research Funding; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Johns Hopkins University: Other: Grant; Molecular Partners: Research Funding; MSD: Research Funding; Mundipharma: Research Funding; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Takeda: Consultancy, Research Funding; Adaptive Biotechnology: Consultancy; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Novartis: Honoraria, Research Funding; Dietmar-Hopp-Foundation: Other: Grant; GSK: Honoraria; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding. O'Dwyer: ONK Therapeutics: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Bristol Myers Squibb: Research Funding. Venner: BMS: Honoraria; Amgen: Research Funding; Celgene: Research Funding; Amgen: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Pfizer: Honoraria. Weisel: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. Raje: Celgene, Amgen, Bluebird Bio, Janssen, Caribou, and BMS: Other. Macro: Sanofi: Honoraria; GSK: Honoraria; Takeda: Honoraria, Other: Travel accomodation, Research Funding; Janssen: Honoraria, Other: Travel accomodation, Research Funding; Celgen/BMS: Honoraria. Leleu: Sanofi: Honoraria; Takeda: Honoraria, Other: Non-financial support; Janssen-Cilag: Honoraria; Karyopharm Therapeutics: Honoraria; Merck: Honoraria; Mundipharma: Honoraria; Novartis: Honoraria; Oncopeptides: Honoraria; Gilead Sciences: Honoraria; Celgene: Honoraria; Carsgen Therapeutics Ltd: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; Pierre Fabre: Honoraria; Roche: Honoraria. Liu: Janssen: Current Employment, Current equity holder in publicly-traded company. Fastenau: Janssen: Current Employment, Current equity holder in publicly-traded company. Gries: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Ho: DRG Abacus: Consultancy; Janssen: Consultancy; Emalex Biosciences: Consultancy. Mistry: Janssen: Current Employment, Current equity holder in publicly-traded company. Tromp: Janssen: Current Employment, Current equity holder in publicly-traded company. Delioukina: Janssen: Current Employment. Vermeulen: Janssen: Current Employment, Current equity holder in publicly-traded company. Usmani: Abbvie: Consultancy; Array BioPharma: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; GSK: Consultancy, Research Funding; EdoPharma: Consultancy; Janssen: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy, Research Funding, Speakers Bureau; Merck: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; SkylineDX: Consultancy, Research Funding; Takeda: Consultancy, Research Funding, Speakers Bureau; Janssen Oncology: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau.

Objective: This study investigated whether patients with mild to moderately severe dementia or possible Alzheimer's disease (AD) with Mini-Mental State Exam (MMSE) Baseline scores of 10–24 would improve when treated with near-infrared photobiomodulation (PBM) therapy. Background: Animal studies have presented the potential of PBM for AD. Dysregulation of the brain's default mode network (DMN) has been associated with AD, presenting the DMN as an identifiable target for PBM. Materials and methods: The study used 810 nm, 10 Hz pulsed, light-emitting diode devices combining transcranial plus intranasal PBM to treat the cortical nodes of the DMN (bilateral mesial prefrontal cortex, precuneus/posterior cingulate cortex, angular gyrus, and hippocampus). Five patients with mild to moderately severe cognitive impairment were entered into 12 weeks of active treatment as well as a follow-up no-treatment, 4-week period. Patients were assessed with the MMSE and Alzheimer's Disease Assessment Scale (ADAS-cog) tests. The protocol involved weekly, in-clinic use of a transcranial-intranasal PBM device; and daily at-home use of an intranasal-only device. Results: There was significant improvement after 12 weeks of PBM (MMSE, p

Objective This study investigated the suitability of the Montgomery-Asberg Depression Rating Scale (MADRS), with a 24-hour recall period (MADRS-24hr), to assess the rapid onset of the antidepressant effect of a treatment in patients with treatment-resistant depression (TRD). Psychometric properties of the MADRS-24hr were assessed together with qualitative assessment of content validity. Methods Content validity was assessed using semistructured interviews conducted from November 2013 to December 2013 in patients (18-64 years old) with TRD who met DSM-IV diagnostic criteria and health care professionals (HCPs) experienced in treating major depressive disorder and familiar with using the MADRS. The psychometric properties of MADRS-24hr were evaluated using data from 2 randomized clinical studies involving patients with TRD. Results A total of 23 patients (15 [65%] women) with TRD (mean age = 45 years) and 11 HCPs were interviewed. With the exception of reduced sleep, the majority of patients and HCPs reported that the items captured in the MADRS can fluctuate in a 24-hour period. The majority of participants also reported that a meaningful change in depression symptoms could be assessed in a 24-hour recall period, except for reduced sleep and appetite. Assessment of the psychometric properties of the MADRS-24hr showed that this instrument had high internal consistency reliability (Cronbach α of 0.84 and 0.91) and test-retest reliability (intraclass correlation coefficients of 0.96 and 0.91), had construct validity, and was responsive to change following an intervention. Conclusions Overall, results suggest that MADRS-24hr can be used to assess the rapid onset of antidepressant efficacy of a treatment in patients with TRD. Trial registration ClinicalTrials.gov identifiers: NCT01627782 and NCT01640080.

The term professional vision points to the many nuanced ways professionals see. This paper traces the development of a professional vision of a researcher and a teacher looking at classroom practices. The researcher’s interest was to capture and study notable aspects of the teacher’s practice. Through a coding scheme, disparate classroom events were organized and analyzed to yield a researcher’s professional vision of the teacher’s practices. For the teacher, through reviewing the video records of his own classroom practices, his professional vision provided a basis for him to reflect and develop professionally. Leveraging on the work of the researcher, he initiated and transformed his own practices. Their collaboration yielded a mutually informed development of professional vision of classroom practices. In juxtaposing the two developments, the researcher and the teacher’s views can be contrasted, their distinctive interests highlighted and common grounds explored. Some implications for developing profes...

8042Background: ALCYONE, an ongoing multicenter, open-label, Phase 3 trial of subjects with newly diagnosed multiple myeloma not eligible for high-dose chemotherapy with stem cell transplantation d...

OBJECTIVE To evaluate the reliability and validity of the Premature Ejaculation Profile (PEP), a self-reported outcome instrument for evaluating domains of PE and its treatment, comprised of four single-item measures, a profile, and an index score. SUBJECTS AND METHODS Data were from men participating in observational studies in the USA (PE, 207 men; non-PE, 1380) and Europe (PE, 201; non-PE, 914) and from men with PE (1238) participating in a phase III randomized, placebo-controlled clinical trial of dapoxetine. The PEP contains four measures: perceived control over ejaculation, personal distress related to ejaculation, satisfaction with sexual intercourse, and interpersonal difficulty related to ejaculation, each assessed on five-point response scales. Test-retest reliability, known-groups validity, and ability to detect a patient-reported global impression of change (PGI) in condition were evaluated for the individual PEP measures and a PEP index score (the mean of all four measures). Profile analysis was conducted using multivariate analysis of variance. RESULTS All PEP measures showed acceptable reliability (intraclass correlation coefficients ranged from 0.66 to 0.83) and mean scores for all measures differed significantly between PE and non-PE groups (P

Introduction. Premature ejaculation (PE) is the most common male sexual dysfunction affecting men and their partners. Lack of community-based data describing this condition limits understand- ing of PE and its outcomes. Aim. To characterize PE in a large population of men with and without PE using patient-reported outcome (PRO) measures elicited from men and their partners. Methods. 4-week, multicenter, observational study of males ( ≥ 18 years) and their female partners in monogamous relationships ( ≥ 6 months). Screening, baseline, and follow-up visits scheduled at 2-week intervals. Clinicians diagnosed PE utilizing DSM-IV-TR criteria. Intravaginal ejaculatory latency time (IELT), measured by a stopwatch held by the partner, was recorded for each sexual intercourse experience. Subject and partner independently assessed PROs: control over ejaculation and satisfaction with sexual intercourse (0 = very poor to 4 = very good), personal distress and interper- sonal difficulty (0 = not at all to 4 = extremely), and severity of PE (0 = none to 3 = severe). Results. Of the total study population (N = 1,587), 207 subjects were diagnosed with PE and 1,380 were assigned to the non-PE group. Median IELT (min) was 1.8 (range, 0-41) for PE and 7.3 (range, 0-53) for non-PE subjects ( P < 0.0001). More PE vs. non-PE subjects gave ratings of "very poor" or "poor" for control over ejaculation (72% vs. 5%; P < 0.0001) and satisfaction with sexual intercourse (31% vs. 1%; P < 0.0001). More subjects in the PE vs. non-PE group gave ratings of "quite a bit" or "extremely" for personal distress (64% vs. 4%; P < 0.0001) and interpersonal difficulty (31% vs. 1%; P < 0.0001). Subject and partner assessments showed similar patterns and correlated moderately (0.36-0.57). Conclusions. PE subjects reported significantly shorter IELT. Overlap in IELT distributions was observed between the PE and non-PE groups, indicating the need for additional PRO measures to characterize PE. Shorter IELT was significantly associated with reduced ejaculatory control and sexual satisfaction and increased distress and interpersonal difficulty.

This paper examines the classroom practices of three teachers teaching mathematics at the 5th grade level in three Singapore schools. Using a video-coding scheme, a series of lessons was coded into relevant phases comprising problem solving, teaching concepts/skills, going over assigned work, and student activities. It explores the teachers’ pedagogical experimentation in their teaching of mathematical problem solving after an analysis of their current practices. It concludes with a review of the effects such changes have on students’ problem solving successes as reflected in pre- and post-problem-solving tests.

240 Background: PROs are used to measure therapeutic impact. The relationship between PROs and clinical outcomes is not well described. Methods: COU-AA-301 (301) and COU-AA-302 (302) were phase 3 trials of abiraterone acetate + prednisone (P) vs P in post-docetaxel and chemotherapy-naïve mCRPC pts, respectively. Using Cox regression models, we explored the association between self-reported fatigue, pain, physical well-being (PWB), functional well-being (FWB), and PC-specific (PCS) signs and symptoms, and OS and rPFS over the first 181 days, regardless of treatment, using data from 301 (N = 1195) and, separately, from 302 (N = 1088). Pts in 301 had more advanced disease and were more symptomatic at entry; pts in 302 were asymptomatic/mildly symptomatic. PRO improvements were assessed for 301 and worsening was assessed for 302. Results: In 301, pts with PRO improvements had reduced risk of death and radiographic progression (p < 0.0001) vs pts with worsening or stable PROs (Table). When all PROs were included in a multivariate (MV) model, all except pain intensity were significantly associated with OS; pain intensity, PWB, and FWB improvements were significantly associated with reduced radiographic progression. Pts in 302 with worsening PROs had greater risk of radiographic progression (p ≤ 0.02) vs pts with improved or stable PROs (Table). When all PRO end points were included in an MV model, worsening PWB remained significantly associated with worse rPFS. There were too few events at cutoff to explore the relationship between PROs and OS in 302. Conclusions: These results reinforce the clinical meaningfulness of self-reported symptoms and suggest that PROs can be used in combination with clinical measures in practice. Clinical trial information: NCT00887198; NCT00638690. [Table: see text]

Objective: To evaluate a composite measure for chronic pain that balances pain relief with tolerability. Design: Post hoc meta-analysis of three randomized, multicenter, double-blind studies. Participants: Subjects with moderate-to-severe chronic osteoarthritis knee pain or low back pain who had been randomized to receive active treatment with tapentadol extended release (ER; n = 978) or oxycodone controlled release (CR; n = 999). Twenty-two subjects were excluded, mainly because they did not receive treatment. Main outcome measures: We defined the composite measure as GTE 30 percent pain relief without nausea/vomiting/constipation and without discontinuations (GTE 30 percent PRT [pain relief/tolerability]). We also considered GTE 50 percent PRT as well as GTE 30 percent and GTE 50 percent pain relief without any adverse events of any type. To further evaluate GTE 30 percent PRT, we studied its relationship with four patient-reported outcomes: EQ-5D, Physical and Mental Component Summaries of SF-36, Patient Global Impression of Change, and Patient Assessment of Constipation Symptoms. Results: At week 12, tapentadol ER recipients were more likely to have GTE 30 percent PRT than oxycodone CR recipients (OR, 3.15; 95% CI, 2.47, 4.00; p < 0.001). Significant differences were also observed with the other three composite measures (p < 0.001). At week 12, subjects with GTE 30 percent PRT had more favorable changes in all patient-reported outcomes than those without and were more likely to have threshold changes in EQ-5D and SF-36 (all p < 0.001). Conclusions: Tapentadol ER was associated with significantly better composite outcomes than oxycodone CR. Because both pain relief and gastrointestinal tolerability appeared to be related to outcomes, the composite measure may represent a useful tool for comparing opioids that merits further evaluation. Keywords: chronic pain, gastrointestinal tolerability, composite measure, opioid, oxycodone, tapentadol DOI:10.5055/jom.2013.0147

Validated tools to assess opioid-induced constipation (OIC) are needed. The aim of this study was to validate a Bowel Function Diary (BF-Diary) that includes patient-reported outcomes (PROs) associated with OIC.In a multicenter, observational study, opioid-naive or recently untreated (≥ 14 days) adults with nonmalignant, chronic pain who were prescribed oral opioid and usual care completed an electronic diary daily for 2 weeks. Test-retest reliability was assessed. Validity was evaluated for two composite end points--number of spontaneous bowel movements (SBM) and complete SBMs (SCBM)--and for other relevant PROs.Of 238 patients (mean age 54 years, 58% women), 63% reported constipation. The intraclass correlation coefficient for numbers of SBM and SCBM, and other BF-Diary PROs was ≥ 0.71 for all items except stool consistency. Mean (s.d.) number of SBM per week was significantly less in each week for patients with vs. without constipation (5.6 ± 4.3 and 7.3 ± 3.6, respectively over week 1, P=0.0012; similarly, P=0.0096 over week 2). Validity of individual items in the BF-Diary was supported (P0.05, stool consistency; P0.0001, all others).BF-Diary items are generally reliable and valid assessments for OIC research. Specifically, number of SBM is a valid measure for differentiating opioid-treated patients with and without constipation.

Background Although premature ejaculation (PE) is a common male sexual dysfunction, its relevant parameters have not been adequately studied in large community‐based samples. Objective To examine the diagnostic utility of two self‐report questions based on the DSM‐IV‐TR definition of PE and to investigate the relationship between self‐identified PE, sexual functioning, and sexual satisfaction in men. Methods An Internet survey of general health and aspects of sexual functioning and satisfaction was conducted in 2056 males. Subjects were classified as having “probable” or “possible” PE, or as “non‐PE” by survey responses. Results A total of 1158 men met the selection criteria (sexually active in a stable heterosexual relationship), and 189 (16.3%) were classified as having probable PE by reporting they ejaculated before they wished and indicating it was “very much” or “somewhat” a problem. Another 188 (16.2%) men reported ejaculating before they wished but rated their distress lower and were classified as having possible PE. Compared to non‐PE men, those with probable and possible PE reported significantly worse sexual functioning in 6 of 8 study measures. Concern about partner satisfaction was high in all groups. The importance of ejaculatory control and the ability to have intercourse for the desired time was significantly higher in men with PE as compared to non‐PE men ( P Conclusions PE was a common problem, was characterized by a lack of ejaculatory control, and was associated with significant effects on sexual functioning and satisfaction. Additional research on the sensitivity and specificity of these self‐report questions should be pursued.

Premature ejaculation (PE) is the most common male sexual dysfunction affecting men and their partners. Lack of community-based data describing this condition limits understanding of PE and its outcomes.To characterize PE in a large population of men with and without PE using patient-reported outcome (PRO) measures elicited from men and their partners.4-week, multicenter, observational study of males (or =18 years) and their female partners in monogamous relationships (or =6 months). Screening, baseline, and follow-up visits scheduled at 2-week intervals. Clinicians diagnosed PE utilizing DSM-IV-TR criteria. Intravaginal ejaculatory latency time (IELT), measured by a stopwatch held by the partner, was recorded for each sexual intercourse experience. Subject and partner independently assessed PROs: control over ejaculation and satisfaction with sexual intercourse (0 = very poor to 4 = very good), personal distress and interpersonal difficulty (0 = not at all to 4 = extremely), and severity of PE (0 = none to 3 = severe). Results. Of the total study population (N = 1,587), 207 subjects were diagnosed with PE and 1,380 were assigned to the non-PE group. Median IELT (min) was 1.8 (range, 0-41) for PE and 7.3 (range, 0-53) for non-PE subjects (P0.0001). More PE vs. non-PE subjects gave ratings of "very poor" or "poor" for control over ejaculation (72% vs. 5%; P0.0001) and satisfaction with sexual intercourse (31% vs. 1%; P0.0001). More subjects in the PE vs. non-PE group gave ratings of "quite a bit" or "extremely" for personal distress (64% vs. 4%; P0.0001) and interpersonal difficulty (31% vs. 1%; P0.0001). Subject and partner assessments showed similar patterns and correlated moderately (0.36-0.57).PE subjects reported significantly shorter IELT. Overlap in IELT distributions was observed between the PE and non-PE groups, indicating the need for additional PRO measures to characterize PE. Shorter IELT was significantly associated with reduced ejaculatory control and sexual satisfaction and increased distress and interpersonal difficulty.

The plate method outlined in Chapter 61: Microbial Limit Tests of the U.S. Pharmacopeia (USP 61) provides very specific guidance for assessing total aerobic bioburden in pharmaceutical articles. This methodology, while comprehensive, lacks the flexibility to be useful in all situations. By studying the plate method as a special case within a more general family of assays, the effects of each parameter in the guidance can be understood. Using a mathematical model to describe the plate counting procedure, a statistical framework for making more definitive statements about total aerobic bioburden is developed. Such a framework allows the laboratory scientist to adjust the USP 61 methods to satisfy specific practical constraints. In particular, it is shown that the plate method can be conducted, albeit with stricter acceptance criteria, using a test specimen quantity that is smaller than the 10 g or 10 mL prescribed in the guidance. Finally, the interpretation of results proffered by the guidance is re-examined within this statistical framework and shown to be overly aggressive.

Background Multicentric Castleman’s disease (MCD) is a rare lymphoproliferative disorder driven by dysregulated interleukin-6 production. MCD has a poor prognosis, and treatment is generally noncurative and aimed at symptom relief. Siltuximab is a novel, monoclonal interleukin-6 antibody recently shown to be effective in a registration clinical trial. MCD symptoms, such as fatigue, pain, and weakness, are most appropriately quantified using patient-reported outcome (PRO) measures. We assessed the effect of siltuximab on patient perception of symptoms, functional status, and wellbeing using PRO instruments. Methods We analyzed results of a randomized, double-blind trial comparing siltuximab 11 mg/kg every 3 weeks with placebo to treat MCD. Subjects (N = 79) completed the recently developed MCD–Symptom Scale (MCD–SS), the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT–Fatigue) scale, and the Short Form (SF)-36 at predetermined time points throughout the treatment period. Scores were compared at baseline and over time between the treatment arms and PRO instruments. Results At baseline, the mean number of symptoms reported was 9.2 (standard deviation 3.76) out of 16 total, as measured by the MCD–SS. Fatigue was a key symptom across all PRO instruments. Siltuximab-treated subjects reported early improvements in symptoms compared with subjects in the placebo arm on both the MCD–SS and FACIT–Fatigue scale. Statistically significant improvements in five SF-36 domains were observed in siltuximab-treated patients, namely role physical, role emotional, vitality, bodily pain, and mental health. Conclusions Patients with MCD commonly report impairments in functioning, wellbeing, and fatigue at baseline. Siltuximab-treated patients reported significant improvements in these outcomes after treatment. Electronic supplementary material The online version of this article (doi:10.1007/s40271-015-0120-5) contains supplementary material, which is available to authorized users.