Study Sponsor Research Articles

Varenicline for Gradual Versus Abrupt Smoking Cessation in Poorly Motivated Smokers With COPD: A Prematurely Terminated Randomized Controlled Trial.

Although smoking is the leading cause of chronic obstructive pulmonary disease (COPD), many patients with COPD smoke, highlighting the need for effective smoking cessation interventions in this population. This study examined the efficacy and safety of varenicline in increasing smoking cessation rates through "gradual" versus "abrupt" cessation in COPD patients with low motivation to quit smoking. A randomized, open label, 30-week, controlled trial (ClinicalTrials.gov identifier: NCT02894957) was conducted between January 2019 and October 2020 at a center in Israel. Smokers with COPD, poorly motivated to quit, were randomized to 6 weeks of varenicline for smoking reduction and a target quit day (TQD) at the end of week 6 (gradual cessation group) or ad libitum smoking for 5 weeks, 1 week of varenicline, and a TQD at the end of week 6 (abrupt cessation group). After the pre-quit phase, both groups received 12-week regular varenicline treatment and 12-week follow-up. Primary outcome was biochemically-validated continuous abstinence for weeks 6-30. Secondary outcomes were: (1) biochemically-confirmed7-day point prevalence abstinence for weeks 4-30, (2) efficient smoking reduction (≥50% in number of cigarettes/day) in the pre-quit phase; and (3) number of cigarettes/day, motivation to quit, and changes in respiratory symptoms and spirometry from baseline through week 30. A drug recall issued by the study sponsor stopped the study after 70/242 (28.9%) patients had been enrolled. The gradual cessation group (n=29) had significantly higher continuous abstinence rates from TQD through week 30 versus the abrupt cessation group (n=41): 20.7% versus 4.9% (odds ratio [OR]=5.09; 95% confidence interval [CI] 0.89-29.17; p=0.048) and higher 7-day point prevalence abstinence levels at all time points but week 18 (p=0.027 at week 6, 0.056 at week 7, and 0.096 at week 9). Motivation to quit increased (p=0.002) and the number of cigarettes/day decreased (p=0.002) over time in both groups. Respiratory symptoms, but not spirometry, improved in both groups at week 30. Treatment was safe and well tolerated. In poorly motivated smokers with COPD, using varenicline for a 6-week gradual smoking cessation before TQD, compared with abrupt cessation, significantly increased quit rates up to 6 months. Results were not affected by the smaller-than-expected sample size. Further studies are needed to confirm these data.

Efficacy and safety of elexacaftor plus tezacaftor plus ivacaftor versus tezacaftor plus ivacaftor in people with cystic fibrosis homozygous for F508del-CFTR: a 24-week, multicentre, randomised, double-blind, active-controlled, phase 3b trial

Elexacaftor plus tezacaftor plus ivacaftor is a triple-combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimen shown to be generally safe and efficacious in people with cystic fibrosis aged 12 years or older with at least one F508del-CFTR allele. We aimed to assess the magnitude and durability of the clinical effects of this triple combination regimen in people with cystic fibrosis homozygous for the F508del-CFTR mutation. We conducted a multicentre, randomised, double-blind, active-controlled, phase 3b trial of elexacaftor plus tezacaftor plus ivacaftor at 35 medical centres in Australia, Belgium, Germany, and the UK. Eligible participants were those with cystic fibrosis homozygous for the F508del-CFTR mutation, aged 12 years or older with stable disease, and with a percent predicted FEV1 of 40-90% inclusive. After a 4-week run-in period, in which participants received tezacaftor 100 mg orally once daily and ivacaftor 150 mg orally every 12 h, participants were randomly assigned (1:1) to receive 24 weeks of either elexacaftor 200 mg orally once daily plus tezacaftor 100 mg orally once daily plus ivacaftor 150 mg orally every 12 h (elexacaftor plus tezacaftor plus ivacaftor group) or tezacaftor 100 mg orally once daily plus ivacaftor 150 mg orally every 12 h (tezacaftor plus ivacaftor group). Randomisation was stratified by percent predicted FEV1, age at screening visit, and whether the participant was receiving CFTR modulators at the time of the screening visit. Patients, investigators, and sponsor's study execution team were masked to treatment assignment. The primary endpoint was the absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score from baseline (ie, at the end of the tezacaftor plus ivacaftor run-in period) up to and including week 24. The key secondary endpoint was the absolute change from baseline in percent predicted FEV1 up to and including week 24; other secondary endpoints were the absolute change from baseline in sweat chloride concentrations up to and including week 24, and safety and tolerability. All endpoints were assessed in all randomised patients who had received at least one dose of their assigned regimen. This study is registered with ClinicalTrials.gov, NCT04105972. Between Oct 3, 2019, and July 24, 2020, 176 participants were enrolled. Following the 4-week tezacaftor plus ivacaftor run-in period, 175 participants were randomly assigned (87 to the elexacaftor plus tezacaftor plus ivacaftor group and 88 to the tezacaftor plus ivacaftor group) and dosed in the treatment period. From baseline up to and including week 24, the mean CFQ-R respiratory domain score increased by 17·1 points (95% CI 14·1 to 20·1) in the elexacaftor plus tezacaftor plus ivacaftor group and by 1·2 points (-1·7 to 4·2) in the tezacaftor plus ivacaftor group (least squares mean treatment difference 15·9 points [95% CI 11·7 to 20·1], p<0·0001), the mean percent predicted FEV1 increased by 11·2 percentage points (95% CI 9·8 to 12·6) in the elexacaftor plus tezacaftor plus ivacaftor group and by 1·0 percentage points (-0·4 to 2·4) in the tezacaftor plus ivacaftor group (least squares mean treatment difference 10·2 percentage points [8·2 to 12·1], p<0·0001), and the mean sweat chloride concentration decreased by 46·2 mmol/L (95% CI 43·7 to 48·7) in the elexacaftor plus tezacaftor plus ivacaftor group and by 3·4 mmol/L (1·0 to 5·8) in the tezacaftor plus ivacaftor group (least squares mean treatment difference -42·8 mmol/L [-46·2 to -39·3], nominal p<0·0001). Most participants (70 [80%] in the elexacaftor plus tezacaftor plus ivacaftor group and 74 [84%] in the tezacaftor plus ivacaftor group) had adverse events that were mild or moderate in severity; serious adverse events occurred in five (6%) of 87 participants in the elexacaftor plus tezacaftor plus ivacaftor group and 14 (16%) of 88 participants in the tezacaftor plus ivacaftor group. One (1%) participant in the elexacaftor plus tezacaftor plus ivacaftor group discontinued treatment due to an adverse event of anxiety and depression. Two (2%) participants in the tezacaftor plus ivacaftor group discontinued treatment due to adverse events of psychotic disorder (n=1) and obsessive-compulsive disorder (n=1). The elexacaftor plus tezacaftor plus ivacaftor regimen was safe and well tolerated, and led to significant and clinically meaningful improvements in respiratory-related quality of life and lung function, as well as improved CFTR function, changes that were durable over 24 weeks and superior to those seen with tezacaftor plus ivacaftor in this patient population. Vertex Pharmaceuticals.

Ethical implications of procedural or protocol adjustments to clinical research involving the participation of human subjects during the COVID-19 pandemic

Abstract The current coronavirus disease 2019 (COVID-19) pandemic has led to essential adjustments in clinical research involving human subjects. The pandemic is substantially affecting most procedures of ongoing, as well as new clinical trials related to diseases other than COVID-19. Procedural changes and study protocol modifications may significantly impact ethically salient fundamentals, such as the risk-benefit profile and safety of clinical trial participants, which raise key ethical challenges the subject-matter experts must face. This article aims to acquaint a wide audience of clinical research professionals, ethicists, as well as the general public interested in this topic with the legal, ethical and practical considerations in the field of clinical trials during the COVID-19 pandemic and to support the clinical researchers and study sponsors to fulfil their responsibilities in conducting clinical trials in a professional way that does not conflict with any legal or ethical obligations.

Costs associated with the administration of erythropoiesis-stimulating agents for the treatment of anemia in patients with non-dialysis-dependent chronic kidney disease: a US societal perspective.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia due to chronic kidney disease (CKD). In addition to drug acquisition costs, the administration of ESAs can include direct and indirect costs due to the needle-based route of administration (eg, time spent by health care staff administering therapy, and patients' and caregivers' time spent receiving or assisting with therapy). However, a comprehensive assessment of the costs associated with the administration of ESAs is lacking. OBJECTIVE: To estimate the excess costs associated with the needle-based administration of ESAs for the treatment of anemia due to non-dialysis-dependent (NDD) CKD in the United States in 2019 from a societal perspective. METHODS: Excess costs associated with ESA administration were estimated as the sum of annual costs that could be avoided with the introduction of an oral treatment with comparable safety and efficacy to ESAs. Cost components included direct health care costs, transportation costs, and work productivity loss costs from the perspective of both patients and caregivers (as applicable). Costs were estimated based on scientific publications, governmental agencies, and the results of a recent survey of US patients and caregivers of patients with anemia and CKD. The setting of the administration (ie, at home vs in clinic), frequency of administration, and insurance type were considered. RESULTS: At the societal level, annual excess costs associated with ESA administration were estimated at $2.5 billion in the United States in 2019, based on an estimated 462,005 patients with anemia and NDD-CKD treated with ESAs. Overall, 94.4% ($2.4 billion) of these costs were incurred from in-clinic ESA administration. When stratifying costs by insurance type, Medicare-insured patients accounted for 79.4% ($2.0 billion) of total annual excess costs. The largest contributor to total annual excess costs was direct health care costs ($1.4 billion, 54.9%), followed by patient work productivity loss costs ($846 million, 33.9%), caregiver work productivity loss costs ($197 million, 7.9%), and transportation costs ($81 million, 3.3%). Total annual excess costs of in-clinic administration ranged from $2,572 per patient receiving monthly administration to $20,948 per patient receiving thrice-weekly administration, while the total annual excess costs of at-home administration ranged from $1,123 per patient receiving monthly administration to $2,109 per patient receiving thrice-weekly administration. At the ESA administration level (ie, for each ESA administration), total excess costs were estimated at $128 per in-clinic ESA administration and $7 per at-home ESA administration, excluding monitoring costs. CONCLUSIONS: The needle-based administration of ESAs in patients with NDD-CKD is associated with a substantial economic burden. The introduction of an oral treatment has the potential to result in important cost savings from a societal perspective. DISCLOSURES: This study was funded by Otsuka Pharmaceutical Development & Commercialization, Inc., and Akebia Therapeutics, Inc. The study sponsors participated in the study design, data collection, analysis, interpretation of the data, writing of the report, and in the decision to submit the manuscript for publication. Gauthier-Loiselle, Cloutier, Serra, Bungay, and Guérin are employees of Analysis Group, Inc., a consulting firm that received funding from Otsuka Pharmaceutical Development & Commercialization, Inc., for the conduct of this study. Michalopoulos was an employee of Otsuka Pharmaceutical Development & Commercialization, Inc., at the time the study was conducted. Szabo is an employee of Akebia Therapeutics, Inc.

Economic burden of attention-deficit/hyperactivity disorder among adults in the United States: a societal perspective.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with substantial clinical burden as individuals transition to adulthood, including higher rates of comorbidities, mortality, incarceration, and psychiatric hospitalizations than in individuals without ADHD. These higher rates likely contribute to substantial economic burden as well. OBJECTIVE: To provide a comprehensive evaluation of the economic burden associated with ADHD in the US adult population. METHODS: Direct health care costs were obtained by using claims data from the IBM MarketScan Research Databases (January 1, 2017, through December 31, 2018). Direct non-health care costs and indirect costs were estimated on the basis of the literature and government publications. Excess costs incurred by adults with ADHD during 2018 were evaluated from a societal perspective; per-patient costs were extrapolated to the national level. RESULTS: An estimated 8.7 million adults live with ADHD in the United States, resulting in a total societal excess cost attributable to ADHD of $122.8 billion ($14,092 per adult). Excess costs of unemployment ($66.8 billion; 54.4%) comprised the largest proportion of the total, followed by productivity loss ($28.8 billion; 23.4%) and health care services ($14.3 billion; 11.6%). CONCLUSIONS: ADHD in adults is associated with substantial economic burden. DISCLOSURES: This study was funded by Otsuka Pharmaceutical Development & Commercialization, Inc. (Otsuka). The study sponsor contributed to and approved the study design, participated in the interpretation of data, and reviewed and approved the manuscript. Schein is an employee of Otsuka. Gagnon-Sanschagrin, Davidson, Kinkead, Cloutier, Guérin, and Lefebvre are employees of Analysis Group, Inc., a consulting company that provided paid consulting services to Otsuka to develop and conduct this study and write the manuscript. Adler has received research support from Shire/Takeda, Sunovion, and Otsuka; consulting fees from Bracket, Shire/Takeda, Sunovion, Otsuka, the State University of New York (SUNY), the National Football League (NFL), and Major League Baseball (MLB); and royalty payments (as inventor) from New York University (NYU) for license of adult ADHD scales and training materials. Childress has received research support from Allergan, Takeda/Shire, Emalex, Akili, Ironshore, Arbor, Aevi Genomic Medicine, Neos Therapeutics, Otsuka, Pfizer, Purdue, Rhodes, Sunovion, Tris, KemPharm, Supernus, and the US Food and Drug Administration; was on the advisory board of Takeda/Shire, Akili, Arbor, Cingulate, Ironshore, Neos Therapeutics, Otsuka, Pfizer, Purdue, Adlon, Rhodes, Sunovion, Tris, Supernus, and Corium; received consulting fees from Arbor, Ironshore, Neos Therapeutics, Purdue, Rhodes, Sunovion, Tris, KemPharm, Supernus, Corium, Jazz, and Tulex Pharma; received speaker fees from Takeda/Shire, Arbor, Ironshore, Neos Therapeutics, Pfizer, Tris, and Supernus; and received writing support from Takeda/Shire, Arbor, Ironshore, Neos Therapeutics, Pfizer, Purdue, Rhodes, Sunovion, and Tris. Part of the material in this study was presented as a poster at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2021 Virtual Meeting; May 17-20, 2021.

372 Association of tumor mutation burden (TMB) and genomic alterations (GA) with clinical outcomes in Chinese patients with advanced solid tumors treated with tislelizumab

BackgroundStudies have demonstrated correlation of GA and TMB with clinical efficacy of an anti-programmed cell death protein-1 (PD-1) therapy, but this correlation has not yet been demonstrated in Chinese patients treated with tislelizumab (anti-PD-1 antibody). We report the association between TMB, GA, and the clinical efficacy of tislelizumab in Chinese patients with different tumor types from a Phase 1/2 study (NCT04068519).MethodsChinese patients with advanced solid tumors who received tislelizumab monotherapy and had available tissues for genomic testing (BurningRock OncoScreen Plus 520 NGS panel) were eligible. Patients were classified as having hyper-amplification (HA) if their genome harbored ≥1 amplified gene with a copy number &gt;5. Logistic regression was used to analyze the association of TMB with objective response rate (ORR) and Cox proportional hazard was used to determine the association of TMB with progression-free survival (PFS) and overall survival (OS).ResultsA total of 156 patients were evaluable. TMB was higher in responders (R) versus non-responders (NR) (median [m] TMB: 9.3 vs 6.2 mut/Mb, p=0.003). TMB-H was defined as ≥8 mut/Mb according to the receiver operating characteristic curve. Patients in the TMB-H group showed superior clinical benefit compared with the TMB-L group (table 1). Further GA analysis showed a trend toward a higher frequency of HA in NR (40.00%; 16/40) compared with R (28.78%; 5/18), in the TMB-H group. A total of 33.33% (10/30) of these amplified genes in NR belonged to the RTK-RAS-PI3K signaling pathway. When TMB-H patients with HA in this pathway were excluded, ORR reached 37.78%.Abstract 372 Table 1Median study follow-up and clinical efficacy dataNE, non-estimableConclusionsTMB-H status was associated with improved clinical efficacy of tislelizumab in Chinese patients with advanced solid tumors, consistent with other PD-1 inhibitors. These observations support TMB-H as a potential predictive biomarker for response to tislelizumab in this patient population. HA in the RTK-RAS-PI3K pathway may be associated with resistance mechanisms to anti-PD-1 therapy, even in patients with TMB-H tumors.AcknowledgementsEditorial writing support for the development of this abstract, under direction of the authors, was provided by Louise Oakes, PhD, of Ashfield MedComms, an Ashfield Health company, and was funded by BeiGene Ltd.Trial RegistrationNCT04068519Ethics ApprovalThis study was conducted according to the ethical principles of the Declaration of Helsinki, Good Clinical Practice guidelines, the principles of informed consent and the requirements of the public registration of clinical trials. Written informed consent was obtained from each patient prior to screening. The protocol was approved by the institutional ethics committee and was monitored by the investigators and study sponsor.

MP09-03 EVOLUTION OF THE ZENFLOW SPRING SYSTEM: A NOVEL NITINOL IMPLANT FOR BENIGN PROSTATIC HYPERPLASIA (BPH)

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Surgical Therapy & New Technology II (MP09)1 Sep 2021MP09-03 EVOLUTION OF THE ZENFLOW SPRING SYSTEM: A NOVEL NITINOL IMPLANT FOR BENIGN PROSTATIC HYPERPLASIA (BPH) Peter Chin, Lauro Salvador Gomez Guerra, Peter Gilling, Juan José Galán Maraboto, Rodrigo Perez Becerra, and Janelle Brennan Peter ChinPeter Chin More articles by this author , Lauro Salvador Gomez GuerraLauro Salvador Gomez Guerra More articles by this author , Peter GillingPeter Gilling More articles by this author , Juan José Galán MarabotoJuan José Galán Maraboto More articles by this author , Rodrigo Perez BecerraRodrigo Perez Becerra More articles by this author , and Janelle BrennanJanelle Brennan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001982.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The Zenflow Spring® System (Zenflow, South San Francisco, CA, USA) is a novel, minimally-invasive device designed to relieve LUTS associated with BPH. The permanent Spring Implant is delivered transurethrally to the prostatic urethra using a flexible cystoscope. If needed, the implant is uniquely designed for complete transurethral removability using standard urological instruments. We present the technology and evolution of the Zenflow Spring System. METHODS: The first-generation Spring Implant consisted of a single 3-ring nitinol coil. Under flexible cystoscopic guidance, the device was deployed in the prostatic urethra to produce an outward force and increase the patency of the prostatic urethral lumen. Experience from the first-in-human study led to a new Spring System design including a custom delivery system, an integrated and proprietary single-use flexible cystoscope, and additional implant sizes. RESULTS: The initial feasibility study confirmed both acute and long-term potential benefit of the Spring Implant as viable treatment option for BPH. Eleven subjects were successfully implanted with no unanticipated serious adverse events. Symptom improvement was observed and shown to be durable up to 3 years in most of the subjects treated. Mean IPSS change was -10.8 (-43%) at 3 months (p <0.001) and -10.6 (-42%) at 36 months, (p <0.001). Explant procedures were successfully performed when needed, transurethrally, up to 32 months post-procedure. The Zenflow Spring System, currently under clinical investigation in Mexico, New Zealand, and Australia, has enhanced visualization, placement accuracy, and urethral fit, demonstrating preliminary safety and effectiveness results. CONCLUSIONS: Preliminary safety and effectiveness results from the first-generation Spring System support the long-term durability of the Spring Implant. Design changes made as a result of the first-in-human study have significantly improved the procedural experience while continuing to demonstrate treatment success. These initial clinical experiences support the continued evaluation of the Zenflow Spring System as a minimally-invasive treatment alternative for patients with LUTS associated with BPH. Source of Funding: Study was funded solely by the study sponsor, Zenflow, Inc © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e160-e160 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Peter Chin More articles by this author Lauro Salvador Gomez Guerra More articles by this author Peter Gilling More articles by this author Juan José Galán Maraboto More articles by this author Rodrigo Perez Becerra More articles by this author Janelle Brennan More articles by this author Expand All Advertisement Loading ...

PD23-06 12-MONTH INTERIM RESULTS OF THE MULTICENTER, PROSPECTIVE, SINGLE-ARM STUDY WITH THE ZENFLOW SPRING SYSTEM: A NOVEL MINIMALLY-INVASIVE TREATMENT FOR LUTS ASSOCIATED WITH BPH

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Surgical Therapy & New Technology IV (PD23)1 Sep 2021PD23-06 12-MONTH INTERIM RESULTS OF THE MULTICENTER, PROSPECTIVE, SINGLE-ARM STUDY WITH THE ZENFLOW SPRING SYSTEM: A NOVEL MINIMALLY-INVASIVE TREATMENT FOR LUTS ASSOCIATED WITH BPH Peter Gilling, Janelle Brennan, Peter Chin, Lauro Salvador Gomez Guerra, Rodrigo Perez Becerra, and Juan José Galán Maraboto Peter GillingPeter Gilling More articles by this author , Janelle BrennanJanelle Brennan More articles by this author , Peter ChinPeter Chin More articles by this author , Lauro Salvador Gomez GuerraLauro Salvador Gomez Guerra More articles by this author , Rodrigo Perez BecerraRodrigo Perez Becerra More articles by this author , and Juan José Galán MarabotoJuan José Galán Maraboto More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002016.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The Zenflow Spring System (Zenflow, Inc., South San Francisco, CA, USA) is a minimally-invasive treatment for LUTS secondary to BPH, delivered transurethrally to the prostatic urethra through a custom flexible system. The 12-month interim analysis of 42 subjects enrolled in a multicenter, prospective, single-arm evaluation of safety, performance, and effectiveness of the Zenflow Spring System in relieving symptoms of BPH, are presented below. METHODS: The study included subjects ≥45 years of age with baseline IPSS score ≥13, QoL score ≥3, and prostate volume 25-80 cc. Follow-up assessments for effectiveness and safety were conducted at 2 weeks, 1, 3, 6, and 12 months and will continue annually through 60 months. RESULTS: Procedural success was achieved in 90% (38/42) of subjects enrolled. 12-month follow up data for 35 subjects is presented below. These subjects experienced statistically significant improvements in IPSS, QoL, and peak flow rate at all time points, through 12 months. Cystoscopy was performed at 3 and 12 months post implant with no evidence of encrustation. Reports of pain were few, mild, and transient. There was no impact on sexual function nor reports of ejaculatory dysfunction. Most patients did not require postoperative catheterization outside of standard of care treatment. Six SAEs were reported in 6 subjects. Four occurred in roll-in subjects who were among the first to receive treatment with the new generation of the device. It is highly probable these events are tied to the learning curve. Five subjects were explanted over the course of 12 months: 3 subjects due to urinary retention, 2 for lack of effectiveness and 1 for unrelated ureter carcinoma that prevented continuation in the trial. CONCLUSIONS: 12-month interim results suggest that the Zenflow Spring System provides a rapid and durable improvement in BPH symptoms and patient quality of life. Source of Funding: Study was funded solely by the study sponsor, Zenflow, Inc © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e422-e422 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Peter Gilling More articles by this author Janelle Brennan More articles by this author Peter Chin More articles by this author Lauro Salvador Gomez Guerra More articles by this author Rodrigo Perez Becerra More articles by this author Juan José Galán Maraboto More articles by this author Expand All Advertisement PDF downloadLoading ...

Association of Postoperative Clinical Outcomes With Sarcopenia, Frailty, and Nutritional Status in Older Patients With Colorectal Cancer: Protocol for a Prospective Cohort Study.

BackgroundOlder patients account for a significant proportion of patients undergoing colorectal cancer surgery and are vulnerable to a number of preoperative risk factors that are not often present in younger patients. Further, three preoperative risk factors that are more prevalent in older adults include frailty, sarcopenia, and malnutrition. Although each of these has been studied in isolation, there is little information on the interplay between them in older surgical patients. A particular area of increasing interest is the use of urine metabolomics for the objective evaluation of dietary profiles and malnutrition.ObjectiveHerein, we describe the design, cohort, and standard operating procedures of a planned prospective study of older surgical patients undergoing colorectal cancer resection across multiple institutions in the United Kingdom. The objectives are to determine the association between clinical outcomes and frailty, nutritional status, and sarcopenia.MethodsThe procedures will include serial frailty evaluations (Clinical Frailty Scale and Groningen Frailty Indicator), functional assessments (hand grip strength and 4-meter walk test), muscle mass evaluations via computerized tomography morphometric analysis, and the evaluation of nutritional status via the analysis of urinary dietary biomarkers. The primary feasibility outcome is the estimation of the incidence rate of postoperative complications, and the primary clinical outcome is the association between the presence of postoperative complications and frailty, sarcopenia, and nutritional status. The secondary outcome measures are the length of hospital stay, 30-day hospital readmission rate, and mortality rate at days 30 and 90.ResultsOur study was approved by the National Health Service Research Ethics Committee (reference number: 19/WA/0190) via the Integrated Research Application System (project ID: 231694) prior to subject recruitment. Cardiff University is acting as the study sponsor. Our study is financially supported through an external, peer-reviewed grant from the British Geriatrics Society and internal funding resources from Cardiff University. The results will be disseminated through peer-review publications, social media, and conference proceedings.ConclusionsAs frailty, sarcopenia, and malnutrition are all areas of common derangement in the older surgical population, prospectively studying these risk factors in concert will allow for the analysis of their interplay as well as the development of predictive models for those at risk of commonly tracked surgical complications and outcomes.International Registered Report Identifier (IRRID)PRR1-10.2196/16846

Association between industry sponsorship and author conflicts of interest with outcomes of systematic reviews and meta-analyses of interventions for opioid use disorder

IntroductionAuthor conflicts of interest (COI) and industry sponsorship may lead to biased research results and conclusions. Considering the direct influence that systematic reviews have on patient care, including the management of patients being treated for opioid use disorders (OUD), these studies should be free of industry bias. Thus, we sought to determine whether a relationship exists between COI and the favorability of systematic review outcomes using a sample of systematic reviews regarding OUD interventions. MethodsWe searched MEDLINE and Embase for systematic reviews and meta-analysis related to OUD treatment. The study team performed all data extraction in a masked duplicate fashion. We searched for undisclosed COI for each systematic review author in 3 databases––the CMS Open Payments database, Dollars for Profs, and the United States Patent and Trademark Office (USPTO). The research team quantified results using descriptive statistics. We evaluated associations between review characteristics using Fisher's exact tests, when possible. ResultsThis article includes seventeen systematic reviews and meta-analyses with 81 authors. We found that 25 authors (30.9%) had some form of COI, and 22 (of 25, 88.0%) authors had an undisclosed COI. However, no significant association existed between COI and favorability of results and conclusions. Notably, two systematic reviews (of 17; 11.76%) were industry-sponsored. Similarly, we found no association between the study sponsor source and the favorability of systematic review results and conclusions. ConclusionsOur results suggest the favorability of systematic review results and conclusions are not influenced by author COI or industry sponsorship. However, nearly one-fourth of authors had an undisclosed COI, further emphasizing the need for standardization and adherence to COI disclosure policies within addiction medicine literature.

Development and implementation of standardized study performance metrics for a VA healthcare system clinical research consortium

The cost of conducting clinical trials is continuously increasing and is driven in large part by the time and resources required to activate trials and reach accrual targets. The impact of low enrollment in a clinical trial can negatively affect the validity of study results and delay its generalizability to the broader population. Quality is a multidimensional concept which could relate to the design, conduct, and analysis of a trial, its clinical relevance, protection/safety of study participants, or quality of reporting. Furthermore, the quality of controlled trials is of obvious relevance to systematic reviews and if the “raw material” or “data” is flawed then the conclusions of systematic reviews cannot be trusted. To date, the literature surrounding the establishment of standardized study enrollment and quality metrics to assess site performance in clinical trial consortiums is scarce. The lack of these metrics presents challenges to study site teams, sponsors, and other clinical research enterprise key stakeholders for adequately monitoring and evaluating study site performance as it relates to fulfilling trial enrollment and quality goals.The Department of Veterans Affairs (VA) Cooperative Studies Program (CSP) Network of Dedicated Enrollment Sites (NODES) undertook an effort to determine the feasibility of establishing and implementing standardized study enrollment and quality metrics for a clinical research consortium (NODES) as a tool to evaluate its performance. In this manuscript, we describe the development and implementation of standardized study enrollment and quality metrics to assess site performance across studies in our clinical research consortium.

Ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer (IPATential150): a multicentre, randomised, double-blind, phase 3 trial

The PI3K/AKT and androgen-receptor pathways are dysregulated in metastatic castration-resistant prostate cancers (mCRPCs); tumours with functional PTEN-loss status have hyperactivated AKT signalling. Dual pathway inhibition with AKT inhibitor ipatasertib plus abiraterone might have greater benefit than abiraterone alone. We aimed to compare ipatasertib plus abiraterone with placebo plus abiraterone in patients with previously untreated mCRPC with or without tumour PTEN loss. We did a randomised, double-blind, phase 3 trial at 200 sites across 26 countries or regions. Patients aged 18 years or older with previously untreated asymptomatic or mildly symptomatic mCRPC who had progressive disease and Eastern Collaborative Oncology Group performance status of 0 or 1 were randomly assigned (1:1; permuted block method) to receive ipatasertib (400 mg once daily orally) plus abiraterone (1000 mg once daily orally) and prednisolone (5 mg twice a day orally) or placebo plus abiraterone and prednisolone (with the same dosing schedule). Patients received study treatment until disease progression, intolerable toxicity, withdrawal from the study, or study completion. Stratification factors were previous taxane-based therapy for hormone-sensitive prostate cancer, type of progression, presence of visceral metastasis, and tumour PTEN-loss status by immunohistochemistry. Patients, investigators, and the study sponsor were masked to the treatment allocation. The coprimary endpoints were investigator-assessed radiographical progression-free survival in the PTEN-loss-by-immunohistochemistry population and in the intention-to-treat population. This study is ongoing and is registered with ClinicalTrials.gov, NCT03072238. Between June 30, 2017, and Jan 17, 2019, 1611 patients were screened for eligibility and 1101 (68%) were enrolled; 554 (50%) were assigned to the placebo-abiraterone group and 547 (50%) to the ipatasertib-abiraterone group. At data cutoff (March 16, 2020), median follow-up duration was 19 months (range 0-33). In the 521 (47%) patients who had tumours with PTEN loss by immunohistochemistry (261 in the placebo-abiraterone group and 260 in the ipatasertib-abiraterone group), median radiographical progression-free survival was 16·5 months (95% CI 13·9-17·0) in the placebo-abiraterone group and 18·5 months (16·3-22·1) in the ipatasertib-abiraterone group (hazard ratio [HR] 0·77 [95% CI 0·61-0·98]; p=0·034; significant at α=0·04). In the intention-to-treat population, median progression-free survival was 16·6 months (95% CI 15·6-19·1) in the placebo-abiraterone group and 19·2 months (16·5-22·3) in the ipatasertib-abiraterone group (HR 0·84 [95% CI 0·71-0·99]; p=0·043; not significant at α=0·01). Grade 3 or higher adverse events occurred in 213 (39%) of 546 patients in the placebo-abiraterone group and in 386 (70%) of 551 patients in the ipatasertib-abiraterone group; adverse events leading to discontinuation of placebo or ipatasertib occurred in 28 (5%) in the placebo-abiraterone group and 116 (21%) in the ipatasertib-abiraterone group. Deaths due to adverse events deemed related to treatment occurred in two patients (<1%; acute myocardial infarction [n=1] and lower respiratory tract infection [n=1]) in the placebo-abiraterone group and in two patients (<1%; hyperglycaemia [n=1] and chemical pneumonitis [n=1]) in the ipastasertb-abiraterone group. Ipatasertib plus abiraterone significantly improved radiographical progression-free survival compared with placebo plus abiraterone among patients with mCRPC with PTEN-loss tumours, but there was no significant difference between the groups in the intention-to-treat population. Adverse events were consistent with the known safety profiles of each agent. These data suggest that combined AKT and androgen-receptor signalling pathway inhibition with ipatasertib and abiraterone is a potential treatment for men with PTEN-loss mCRPC, a population with a poor prognosis. F Hoffmann-La Roche and Genentech.

Understanding the Preferences of Patients and Caregivers for Relapsed/Refractory Multiple Myeloma Treatment: A Mixed-Mode Patient-Centric Approach

Understanding the Preferences of Patients and Caregivers for Relapsed/Refractory Multiple Myeloma Treatment: A Mixed-Mode Patient-Centric Approach

Expert Elicitation of Long-Term Survival for Pediatric Acute Lymphoblastic Leukemia Patients Receiving CTL019 in Eliana Phase II Study

Introduction: Decision-makers need to understand long-term outcomes to assess cost-effectiveness of new treatments. In the absence of long-term data from clinical trials, current practice to extrapolate overall survival (OS) is typically based on how well the model fits to the observed data without formally involving clinical experts to evaluate the plausibility of the results. At best, 1-2 clinicians may be asked to select the most ‘realistic’ model. Therefore, a more systematic and transparent process is needed to ensure clinical expertise is fully integrated in an unbiased manner. In the global multicenter ELIANA trial (NCT02435849) for CTL019 (chimeric antigen receptor T-cell (CAR-T therapy)), OS data has been reported, but only up to 1.5 years. In the absence of expert opinion regarding long-term OS, the predicted OS varies dramatically depending on the model used to extrapolate the observed data. The aim of this study was to estimate expected OS based on observed data from ELIANA and expert elicited OS rates at 2 years, 3 years, 4 years, and 5 years for patients with relapsed or refractory B-cell pediatric acute lymphoblastic leukemia (r/r/ pALL) treated with CTL019.Methods: A prospective qualitative research study was performed incorporating semi-structured interviews, adapted from the SHeffield ELicitation Framework. Pediatric oncologists and hematologists experienced with CAR-T therapies were recruited. Experts and the study sponsor were not identified to one another. Relevant evidence regarding the patient population from the CTL019 trials, historical first-line pALL data, and historical data on r/r/ pALL for FDA approved interventions was summarized to provide a common basis for expert judgments. Facilitators guided experts through a web-based application for the elicitation of OS rates at 2, 3, 4, and 5 years for patients treated with CTL019 in the ELIANA trial. Experts were first asked to estimate upper and lower plausible limits and then the most likely actual OS value at each time point. Results from each expert were combined with the observed data from ELIANA using time-to-event parametric models (i.e. fractional polynomials) in a Bayesian framework that accounted for each expert's uncertainty in their estimates, which produced an overall distribution of OS over time. In addition, the model was fully extrapolated assuming patients followed general population mortality, adjusted for having had pALL (standard mortality rate=15.2 based on Armstrong 2016).Results: Of the 19 clinical experts contacted, 7 participated in the final elicitation exercise. During a follow-up group meeting, experts agreed that the Gompertz model fit to the observed trial data reflected an appropriate consensus distribution for their estimates. When a Gompertz model was fit to the observed data (up to 1.5 years) and each expert's elicited data (24 to 60 months), the most likely values of OS for patients from the ELIANA trial treated with CTL019 at 2, 3, 4, and 5 years were estimated to be approximately 67.5% (Credible intervals (CrI): 49.5%, 83.1%), 61.1% (39.5%, 81.3%), 57.2% (31.5%, 80.7%), and 54.9% (24.5%, 80.5%) (Figure 1). In the fully extrapolated model, the 10-year OS is estimated to be 52.4% (CrI: 23.4%, 76.9%) with a median survival of approximately 13.4 years (CrI: 1.96, 35.5). Results were similar to OS rates from a phase I/II single-center study (NCT01626495) at 2 years (61%) and slightly higher at three years (52%).Conclusions: Predictions based on observed data and expert elicitations suggest that more than half of the patients in the ELIANA trial treated with CLT019 will survive up to five years. This study provides an example of how expert opinion can be elicited and synthesized with observed survival data using a transparent and unbiased process, which captures expert uncertainty and ensures that projected long-term survival is clinical plausible.Disclaimer: The study was sponsored by Novartis Pharmaceuticals Corporation [Display omitted] DisclosuresCope:Precision Health Economics: Employment; Novartis Pharmaceuticals Corporation: Consultancy. Ayers:Precision Health Economics: Employment; Novartis Pharmaceuticals Corporation: Consultancy. Shih:Precision Health Economics: Employment; Novartis Pharmaceuticals Corporation: Consultancy. Zhang:Novartis Pharmaceuticals Corporation: Employment. Jansen:Novartis Pharmaceuticals Corporation: Consultancy; Precision Health Economics: Employment. Batt:Precision Health Economics: Consultancy; Novartis Pharmaceuticals Corporation: Consultancy; Bayer: Consultancy.

Safety and efficacy of pioglitazone for the delay of cognitive impairment in people at risk of Alzheimer's disease (TOMMORROW): a prognostic biomarker study and a phase 3, randomised, double-blind, placebo-controlled trial

The identification of people at risk of cognitive impairment is essential for improving recruitment in secondary prevention trials of Alzheimer's disease. We aimed to test and qualify a biomarker risk assignment algorithm (BRAA) to identify participants at risk of developing mild cognitive impairment due to Alzheimer's disease within 5 years, and to evaluate the safety and efficacy of low-dose pioglitazone to delay onset of mild cognitive impairment in these at-risk participants. In this phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group study, we enrolled cognitively healthy, community living participants aged 65-83 years from 57 academic affiliated and private research clinics in Australia, Germany, Switzerland, the UK, and the USA. By use of the BRAA, participants were grouped as high risk or low risk. Participants at high risk were randomly assigned 1:1 to receive oral pioglitazone (0·8 mg/day sustained release) or placebo, and all low-risk participants received placebo. Study investigators, site staff, sponsor personnel, and study participants were masked to genotype, risk assignment, and treatment assignment. The planned study duration was the time to accumulate 202 events of mild cognitive impairment due to Alzheimer's disease in White participants who were at high risk (the population on whom the genetic analyses that informed the BRAA development was done). Primary endpoints were time-to-event comparisons between participants at high risk and low risk given placebo (for the BRAA objective), and between participants at high risk given pioglitazone or placebo (for the efficacy objective). The primary analysis included all participants who were randomly assigned, received at least one dose of study drug, and had at least one valid post-baseline visit, with significance set at p=0·01. The safety analysis included all participants who were randomly assigned and received at least one dose of study medication. An efficacy futility analysis was planned for when approximately 33% of the anticipated events occurred in the high-risk, White, non-Hispanic or Latino group. This trial is registered with ClinicalTrials.gov, NCT01931566. Between Aug 28, 2013, and Dec 21, 2015, we enrolled 3494 participants (3061 at high risk and 433 at low risk). Of those participants, 1545 were randomly assigned to pioglitazone and 1516 to placebo. 1104 participants discontinued treatment (464 assigned to the pioglitazone group, 501 in the placebo high risk group, and 139 in the placebo low risk group). 3399 participants had at least one dose of study drug or placebo and at least one post-baseline follow-up visit, and were included in the efficacy analysis. 3465 participants were included in the safety analysis (1531 assigned to the pioglitazone group, 1507 in the placebo high risk group, and 427 in the placebo low risk group). In the full analysis set, 46 (3·3%) of 1406 participants at high risk given placebo had mild cognitive impairment due to Alzheimer's disease, versus four (1·0%) of 402 participants at low risk given placebo (hazard ratio 3·26, 99% CI 0·85-12·45; p=0·023). 39 (2·7%) of 1430 participants at high risk given pioglitazone had mild cognitive impairment, versus 46 (3·3%) of 1406 participants at high risk given placebo (hazard ratio 0·80, 99% CI 0·45-1·40; p=0·307). In the safety analysis set, seven (0·5%) of 1531 participants at high risk given pioglitazone died versus 21 (1·4%) of 1507 participants at high risk given placebo. There were no other notable differences in adverse events between groups. The study was terminated in January, 2018, after failing to meet the non-futility threshold. Pioglitazone did not delay the onset of mild cognitive impairment. The biomarker algorithm demonstrated a 3 times enrichment of events in the high risk placebo group compared with the low risk placebo group, but did not reach the pre-specified significance threshold. Because we did not complete the study as planned, findings can only be considered exploratory. The conduct of this study could prove useful to future clinical development strategies for Alzheimer's disease prevention studies. Takeda and Zinfandel.

Underreporting of race/ethnicity in COVID-19 research

ObjectivesAlthough racial/ethnic disparities in healthcare have long been recognized, recent discourse around structural racism will hopefully lead to improved transparency surrounding these issues. Despite the disproportionate impact of COVID-19 on racial/ethnic minorities, the extent and reliability of race reporting in COVID research is unclear. MethodsCOVID-19 research published in three top medical journals during the first wave of the COVID-19 pandemic was reviewed and assessed for race reporting and proportional representation. ResultsOf the 95 manuscripts that were identified, 56 reporting on 252,262 patients met eligibility. Thirty-five (62.5%) did not report race distribution and 15 (26.7%) did not report ethnicity. There was no difference based on journal (P = 0.87), study sponsor (P = 0.41), whether the study was retrospective or prospective (P = 0.33), or observational vs interventional (P = 0.11). Studies with ≥250 patients were more likely to report on race (OR 4.01, 95% CI: 1.12–14.37, P = 0.027), and North American (USA and Canada) studies were more likely than European studies (OR 7.88, 95% CI: 1.73–37.68, P = 0.006) to report on race. COVID-19 research mirrored USA COVID-19 racial incidence; however, both showed higher distribution of COVID-19 infection among Blacks and a smaller proportion of Whites compared to the USA population. This suggests that research is broadly representing infection rates and that social determinants of health are impacting racial distribution of infection. ConclusionsDespite increasing awareness of racial disparities and inequity, COVID-19 research during the first wave of the pandemic lacked appropriate racial/ethnicity reporting. However, research mirrored COVID-19 incidence in the USA, with an increased burden of infection among Black individuals.

Uczestnictwo pacjenta w badaniu klinicznym a opieka w POZ

Clinical trials are research studies that involve patients. Their purpose is to check whether the new treatment is safe and how effective it is. Comprehensive primary health care is not provided as part of clinical trials. Most clinical trials provide relatively short-term treatment for certain conditions. Patient participation in a clinical trial is voluntary and free of charge. At each stage of the clinical trial, the patient has the right to obtain information about his health from the doctor. Treatment costs (e.g., cost of study drugs, specialist tests, and medical care) are borne by the study sponsor. Not every willing patient can be included in a clinical trial, because each trial has a precisely defined so-called inclusion criteria and exclusion criteria. The doctor checks all the conditions a patient must meet to be included in the study and all the factors that make it impossible to take part in the study. It should be very clearly stated that, in accordance with the requirements of Good Clinical Practice (GCP), only the attending physician (researcher) is entitled to include the participant in the clinical trial, so he will make the final decision (1) Thanks to the cooperation of the family doctor with the research team, the participant will be he was sure that his other medications and treatments did not conflict with the protocol in the proposed clinical trial. Therefore, the patient's participation in the clinical trial and care provided in a primary care center are very important.

Final report of Breast Cancer Care Registry at the Kenyatta National Hospital, Nairobi.

Retraction The abstract by Othieno-Abinya et al entitled, “Final report of Breast Cancer Care Registry at the Kenyatta National Hospital, Nairobi,” published in the Journal of Clinical Oncology 39, no. 15 suppl (May 20, 2021) e12552-e12552, was retracted by the authors as it did not meet the study sponsor's prior scientific verification and approval. This abstract was retracted on June 29, 2021. e12552 Background: Breast cancer is the commonest cancer among women in Kenya. We wanted to examine breast cancer seen at the Kenyatta National Hospital in relation to local factors that influence prognosis and quality of life, local variations in treatment and outcomes; describe the clinical care patterns, monitor the safety of the therapies provided to patients in a routine clinic setting. Methods: A prospective study of patients with breast cancer between 11.08.2011 and 11.09.2014 inclusive. Data included demographic details, diagnostic and staging procedures, stage, treatment and outcome. Estimates of relative survival used period approach. hi-square tests and analysis of variance (ANOVA) were utilised to make comparisons. Cross sectional data are presented in proportions, means and medians. Results: Four hundred patients were included, age range 20 to 83, median 49 years. Out 312, 65 (20.8%) were obese. Eight of 397 (2%) were smokers and 22(5.5%) took alcohol. Early disease was diagnosed in 269 out of 354 (76%) and metastatic disease in 85(24%). Breast lump presented in 388 out of 400 (97%), breast pain in 104 out of 388 (26.8%). Fifteen of 394 (3.8%) had second breast cancer, 4 (1%) had had ovarian cancer and 9 (2.3%) had had had other malignancy. History of breast cancer in first and second-degree relative was elicited in 41 out of 394 (10.4%). Ductal carcinoma NOS was commonest in 343 (88.2%), lobular carcinoma in 9(2.5%). Cases by T stage were T1 - 25(7.2%), T2 -130(37.4%), T3 - 96(27.6%), T4 - 87(25%). Of 322 cases, 187(58.1%) were ER positive and 175 (54.4%) PR positive. Her2 positive cases were 78 out of 322 (24.2%). Neo adjuvant and adjuvant chemotherapy mainly consisted of combinations of cyclophosphamide and doxorubicin [AC] +/- a taxane[AC→T] ( mainly by medical oncologists) or AC+ 5-FU [CAF] (mainly by clinical oncologists). Of 305 cases 272 (89.2%) completed adjuvant therapy, 8(2.6%) died during treatment. Median overall survival was 57.1 months (95% CI; 55.6 to 59.5 months). For metastatic disease, median PFS was worse for patients &lt; 40 years. Conclusions: Pathology and biology mirrored global situation, over 75% of patients had non metastatic disease. A significant proportion of early disease patients did not complete treatment.

Racial and Ethnic Disparities in Primary Open-Angle Glaucoma Clinical Trials

The disease burden for primary open-angle glaucoma (POAG) is highest among racial/ethnic minority groups, particularly Black individuals. The prevalence of POAG worldwide is projected to increase from 52.7 million in 2020 to 79.8 million in 2040, a 51.4% increase attributed mainly to Asian and African individuals. Given this increase, key stakeholders need to pay particular attention to creating a diverse study population in POAG clinical trials. To assess the prevalence of racial/ethnic minorities in POAG clinical research trials compared with White individuals. This meta-analysis consisted of publicly available POAG clinical trials using ClinicalTrials.gov, PubMed, and Drugs@FDA from 1994 to 2019. Randomized clinical trials that reported on interventions for POAG and included demographic subgroups including sex and race/ethnicity. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 2 independent reviewers extracted study-level data for a random-effects meta-analysis. A third person served as the tiebreaker on study selection. Microsoft Excel 2016 (Microsoft Corporation) and SAS, version 9.4 (SAS Institute) were used for data collection and analyses. The primary outcomes were the prevalence of each demographic subgroup (White, Black, Hispanic/Latino, other race/ethnicity groups, and female or male) in each trial according to the trial start year, study region, and study sponsor. Participation rates are expressed as percentages. A total of 105 clinical trials were included in the meta-analysis, including 33 428 POAG clinical trial participants (18 404 women [55.1%]). Overall, 70.7% were White patients, 16.8% were Black patients, 3.4% were Hispanic/Latino patients, and 9.1% were individuals of other races/ethnicities, including Asian, Native Hawaiian or Pacific Islander, American Indian or Alaska Native, and unreported as defined by the US Census. The mean (SD) numbers of participants by race/ethnicity were 236.5 (208.2) for White, 58.4 (70.0) for Black, 29.9 (71.1) for Hispanic/Latino, and 31.1 (94.3) for other race/ethnicity. According to the test for heterogeneity using the Cochrane Risk of Bias tool, the I2 statistic was 98%, indicating high heterogeneity of outcomes in the included trials. A multiple linear regression analysis was performed to assess any trend and significance between participation by Black individuals and the year the study started, the region in which the study took place, and the study sponsor. There was no significant increase of Black participant enrollment from 1994 to 2019 (r2 = 0.11; P = .17) and no significant association between Black participant enrollment and clinical trial region (r2 = 0.16; P = .50), but there was a significant association between Black participant enrollment and study sponsor (r2 = 0.94; P = .03). This meta-analysis found that compared with White individuals, individuals from racial/ethnic minority groups had a very low participation rate in POAG clinical trials despite having a higher prevalence among the disease population. Despite measures to increase clinical trial diversity, there has not been a significant increase in clinical trial participation among Black individuals, the group most affected by this disease; this disparity in POAG clinical trial representation can raise questions about the true safety and efficacy of approved medical interventions for this disease and should prompt further research on how to increase POAG clinical trial diversity.

COMPASSIONATE USE OF INVESTIGATIONAL DRUG DURING EMERGENCY CONDITIONS AND ASSOCIATED ETHICAL ASPECTS, CHALLENGES, AND BENEFITS

“Compassionate Use,” also known as expanded access, is a method by which patients with a life-threatening or seriously debilitating disease that has no satisfactory treatment alternatives can gain access to new drugs outside the context of a clinical trial. Compassionate use (CU) of unlicensed drugs serves the need of patients with the serious debilitating disease in the absence of alternative approved therapies. CU does allow limited access to new products currently in clinical trials. However, it must be remembered that there are strict guidelines to follow. As with any new drug-device or treatment, there are strict guidelines determined by the Food and Drug Administration and study sponsor, especially for CU. This article contains the use of an investigational drug in emergencies, which are the ethical aspects for getting approval, the major challenges in taking a compassionate drug, and the benefits for dying patients.