Predicting Treatment Effects from Surrogate Endpoints in Historical Trials in First-Line Metastatic Castration-Resistant Prostate Cancer.

Surrogate endpoints are becoming increasingly important in health technology assessment, where decisions are based on complex cost-effectiveness models (CEMs) that require numerous input parameters. Daniels and Hughes Surrogate Model was used to predict missing effect estimates in randomized controlled trials (RCTs) evaluating first-line treatments in metastatic castration-resistant prostate cancer (mCRPC) patients. Network meta-analyses (NMAs) were conducted to assess the comparative efficacy of these treatments. Databases were searched (inception to October 2022) using Ovid®. Several grey literature searches were also conducted (PROSPERO: CRD42021283512). Available trial data for radiographic progression-free survival (rPFS) and overall survival (OS) were used to predict the unreported effect of rPFS or OS for relevant comparator treatments. Bayesian NMAs were conducted using observed and predicted treatment effects. Effect estimates and 95% credible intervals were calculated for each comparison. Mean ranks and the probability of being best (p-best) were obtained. Twenty-five RCTs met the eligibility criteria and of these, 8 reported jointly rPFS and OS; while rPFS was predicted for 12 RCTs and 10 comparators, and OS was predicted for 5 RCTs and 6 comparators. A nonstandard dose of docetaxel (docetaxel 50 mg/m2 every 2 weeks) had the highest probability of being the most effective for rPFS (p-best: 59%) and OS (p-best: 48%), followed by talazoparib plus enzalutamide (13% and 19%, respectively). Advanced surrogate modelling techniques allowed obtaining relevant parameter and indirect estimates of previously unavailable data and may be used to populate future CEMs requiring rPFS and OS in first-line mCRPC.

Implementation of virtual academic detailing in North America: A qualitative study.

RATIONALE: The shift toward virtual academic detailing (AD) was accelerated by the COVID-19 pandemic. AIMS AND OBJECTIVES: We aimed to examine the role of external, contextual, and intrinsic programme-specific factors in virtual engagement of healthcare providers (HCPs) and delivery of AD. METHODS: AD groups throughout North America were contacted to participate in semistructured interviews. An interview guide was constructed by adapting the Consolidated Framework for Implementation Research (CFIR). A point of emphasis included strategies AD groups employed for provider engagement while implementing virtual AD programmes. Independent coders conducted qualitative analysis using the framework method. RESULTS: Fifteen AD groups from Canada (n = 3) and the United States (n = 12) participated. Technological issues and training detailers and HCPs were challenges during the transition to virtual AD visits. Restrictions on in-person activities during the pandemic created difficulties engaging HCPs and fewer AD visits. Continuing education was one strategy to incentivize participation, but credits were often not claimed by HCPs. Groups with established networks and prior experience with virtual AD leveraged connections to mitigate disruptions and continue AD visits. Other facilitators included emphasizing contemporary topics, including opioid education beyond fundamental guidelines. Virtual AD had the additional benefit of expanding geographic reach and flexible scheduling with providers. CONCLUSIONS: AD groups across North America have shifted to virtual outreach and delivery strategies. This trend toward virtual AD may aid outreach to vulnerable rural communities, improving health equity. More research is needed on the effectiveness of virtual AD and its future implications.

OFF episode quality of life impact scale (OFFELIA): A new measure of quality of life for off episodes in Parkinson's disease.

INTRODUCTION: OFF Episodes occur in people with Parkinson's disease when their medication wears off, and motor and/or non-motor symptoms emerge. Existing measures used to assess OFF Episodes focus on the time spent in OFF Episodes through diaries or by identifying symptoms, but they are limited in their ability to capture the severity and functional impact of OFF episodes. The aim of this study was to develop and validate a new instrument, called "OFFELIA," that measures the impact of OFF episodes on the quality of life of individuals with Parkinson's disease. METHODS: Participants completed a cross-sectional questionnaire, "Impact and Communication on OFF Periods," while enrolled in the online clinical study Fox Insights. The data collected was used to develop OFFELIA. Psychometric testing was performed on 18 candidate items using classical, exploratory factor analysis, and item response theory methods. RESULTS: 569 individuals with Parkinson's disease completed the questionnaire. All items were retained for the final measure, with 17 items aggregated into two multi-item scales (functioning and psychological well-being) and one item reported separately as it did not function well with the other items (employment). Known group comparisons based on average duration, frequency and unpredictability of OFF episodes indicated that OFFELIA subscales were more sensitive than existing generic and condition-specific measures. CONCLUSION: Initial evidence supports the validity of OFFELIA, a new instrument that assesses the impact of OFF periods on daily life. This instrument can be used in assessing clinical therapeutic strategies targeting OFF episodes in Parkinson's disease.

The impact of race on survival in metastatic prostate cancer: a systematic literature review.

BACKGROUND: Prostate cancer (PC) is the second most diagnosed cancer in men worldwide. While racial and ethnic differences exist in incidence and mortality, increasing data suggest outcomes by race among men with newly diagnosed PC are similar. However, outcomes among races beyond Black/White have been poorly studied. Moreover, whether outcomes differ by race among men who all have metastatic PC (mPC) is unclear. This systematic literature review (SLR) provides a comprehensive synthesis of current evidence relating race to survival in mPC. METHODS: An SLR was conducted and reported in accordance with PRISMA guidelines. MEDLINE®, Embase, and Cochrane Library using the Ovid® interface were searched for real-world studies published from January 2012 to July 2022 investigating the impact of race on overall survival (OS) and prostate cancer-specific mortality (PCSM) in patients with mPC. A supplemental search of key congresses was also conducted. Studies were appraised for risk of bias. RESULTS: Of 3228 unique records identified, 62 records (47 full-text and 15 conference abstracts), corresponding to 54 unique studies (51 United States and 3 ex-United States) reporting on race and survival were included. While most studies showed no difference between Black vs White patients for OS (n = 21/27) or PCSM (n = 8/9), most showed that Black patients demonstrated improved OS on certain mPC treatments (n = 7/10). Most studies found no survival difference between White patients and Hispanic (OS: n = 6/8; PCSM: n = 5/6) or American Indian/Alaskan Native (AI/AN) (OS: n = 2/3; PCSM: n = 5/5). Most studies found Asian patients had improved OS (n = 3/4) and PCSM (n = 6/6) vs White patients. CONCLUSIONS: Most studies found Black, Hispanic, and AI/AN patients with mPC had similar survival as White patients, while Black patients on certain therapies and Asian patients showed improved survival. Future studies are needed to understand what aspects of race including social determinants of health are driving these findings.

Perceptions of prescription opioids among marginalized patients with hematologic malignancies in the context of the opioid epidemic: a qualitative study.

PURPOSE: Opioids are essential for treating pain in hematologic malignancies (HM), yet are heavily stigmatized in the era of the opioid epidemic. Stigma and negative attitudes towards opioids may contribute to poorly managed cancer pain. We aimed to understand patient attitudes towards opioids for HM pain management, particularly among historically marginalized populations. METHODS: We interviewed a convenience sample of 20 adult patients with HM during outpatient visits at an urban academic medical center. Semi-structured interviews were audio-recorded, transcribed, and qualitatively analyzed using the framework method. RESULTS: Among 20 participants, 12 were female and half were Black. Median age was 62 (interquartile range = 54-68). HM diagnoses included multiple myeloma (n = 10), leukemia (n = 5), lymphoma (n = 4), and myelofibrosis (n = 1). Eight themes emerged from interviews that seemed to influence HM-related pain self-management, including (1) fear of opioid-related harms, (2) opioid side effects and harms to health, (3) fatalism and stoicism, (4) perceived value of opioids for HM-related pain, (5) low perceived susceptibility to opioid-related harms and externalizing blame, (6) preferences for non-opioid pain management approaches, (7) trust in providers and opioid accessibility, and (8) external sources of pain management support and information. CONCLUSIONS: This qualitative study demonstrates that fears and stigmatized views of opioids can conflict with marginalized patients' needs to manage debilitating HM-related pain. Negative attitudes towards opioids were shaped by the opioid epidemic and reduced willingness to seek out or use analgesics. IMPLICATIONS FOR CANCER SURVIVORS: These findings help expose patient-level barriers to optimal HM pain management, revealing attitudes, and knowledge to be targeted by future pain management interventions in HM.

Sustained Virologic Response Rates Before and After Removal of Sobriety Restriction for Hepatitis C Virus Treatment Access.

OBJECTIVES: Until November 1, 2018, Illinois Medicaid restricted coverage of hepatitis C virus (HCV) medication to patients with sobriety from alcohol and illicit substances for ≥12 months. This policy limited treatment access for patients with a high risk of HCV transmission, despite clinical trial and real-world data demonstrating high sustained virologic response (SVR) rates among patients with substance use. The objective of this study was to compare HCV SVR rates between patients treated before and after removal of the Illinois Medicaid sobriety restriction. METHODS: We performed a retrospective cohort study of Medicaid-insured patients who completed direct-acting antiviral treatment at an urban, academic medical center in Illinois from January 1, 2014, through October 21, 2020. The primary endpoint was SVR. We compared group characteristics using χ2 or Fisher exact tests for categorical variables and Wilcoxon rank-sum tests for continuous variables. We used logistic regression to compare SVR rates before and after the policy change, adjusting for differences between groups. RESULTS: A total of 496 patients (348 pre-policy change; 148 post-policy change) started treatment; excluding loss to follow-up/early discontinuation, SVR rates were 95.4% (309 of 324) pre-policy change and 97.1% (134 of 138) post-policy change. SVR rates did not differ after adjusting for the use of historic HCV regimens and the higher cirrhosis rate in the pre-policy change group compared with the post-policy change group (odds ratio = 0.98; 95% CI, 0.32-3.67). CONCLUSION: HCV SVR rates were similar before and after removal of the Illinois Medicaid sobriety restriction, regardless of group differences. Results support HCV treatment regardless of documented sobriety to facilitate progress toward HCV elimination.

Findings from a Roundtable Discussion with US Stakeholders on Valuation of the EQ-5D-Y-3L.

OBJECTIVES: The International Valuation Protocol for the valuation of the EQ-5D-Y-3L provides baseline guidance, but country-specific context is also important. This study aimed to obtain US stakeholders' input on key considerations for youth valuation in the US. METHODS: A total of 14 stakeholders representing various backgrounds were identified via the investigators' networks. A 2-h online meeting was held to discuss (1) the need for a US value set for the EQ-5D-Y-3L; (2) willingness to pay more for quality-adjusted life-year (QALY) gains for children versus adults; (3) sampling strategies; (4) framing perspectives; and (5) other challenges. The session was recorded, transcribed, and summarized. RESULTS: Several stakeholders supported paying more for QALY gains for children in recognition of their potential future contributions to society, as well as to avoid potential undervaluation and promote access to innovative treatments. Concerns regarding possible double counting, lack of data to showcase long-term benefits, and dangers of paying more for certain subgroups were also expressed. Most of the stakeholders felt that adolescents could relate to a 10-year-old's perspective better than adults and were capable of self-completing valuation tasks, and thus should be directly included in the valuation study. There were concerns that adults would be inconsistent in their views about a 10-year-old, partly depending on their status as a parent. CONCLUSIONS: US stakeholders provided insights relevant to youth valuation in a US context and were open to continued dialogue with investigators. This study could be useful to investigators who are conducting youth valuation studies in different countries and seeking stakeholder input.

Drugs to Be Used With a Filter for Preparation and/or Administration-2019.

This chart is an update to the 2012 article published in Hospital Pharmacy on injectable drugs to be used with a filter. To update the chart, drugs approved from December 2011 to April 2019 were reviewed to determine if they require filtration and drugs included in the 2012 table were reviewed for accuracy. Readers are urged to review national standards of practice for information about clinical situations that warrant the use of a filter for medication preparation or administration, independent of the drug being given, and the reader should consult the Food and Drug Administration (FDA)-approved prescribing information for the most up-to-date information.

PKCδ-targeted intervention relieves chronic pain in a murine sickle cell disease model.

Pain is a life-long symptom in sickle cell disease (SCD) and a predictor of disease progression and mortality, but little is known about its molecular mechanisms. Here, we characterized pain in a targeted knockin mouse model of SCD (TOW mouse) that exclusively expresses human alleles encoding normal α- and sickle ß-globin. TOW mice exhibited ongoing spontaneous pain behavior and increased sensitivity to evoked pain compared with littermate control mice expressing normal human hemoglobins. PKCδ activation was elevated in the superficial laminae of the spinal cord dorsal horn in TOW mice, specifically in GABAergic inhibitory neurons. Functional inhibition and neuron-specific silencing of PKCδ attenuated spontaneous pain, mechanical allodynia, and heat hyperalgesia in TOW mice. Furthermore, we took a hematopoietic stem cell transplantation approach to generating a SCD model in PKCδ-deficient mice. Neither spontaneous pain nor evoked pain was detected in the mice lacking PKCδ despite full establishment of SCD phenotypes. These findings support a critical role of spinal PKCδ in the development of chronic pain in SCD, which may become a potential target for pharmacological interventions.