Independent Research Organization Research Articles

7380 Qualitative Interviews Describing the Patient Experience of Individuals with Generalized Lipodystrophy Enrolled in a Clinical Trial of Mibavademab

Abstract Disclosure: S. Martin: Other; Self; Employee of RTI Health Solutions, an independent nonprofit research organization retained by Regeneron Pharmaceuticals, Inc. to conduct this research. Compensis unconnected to the studies they work on. K. Kosa: Other; Self; Employee of RTI Health Solutions, an independent nonprofit research organization retained by Regeneron Pharmaceuticals, Inc. to conduct this research. Compensis unconnected to the studies they work on. S. Podgrabinska: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. A. Garg: Consulting Fee; Self; Aegerion Pharmaceuticals, Regeneron Pharmaceuticals, Third Rock ventures, Kyttaro, Cello Health, Health Advances. Grant Recipient; Self; Aegerion Pharmaceuticals, Pfizer, Inc., Regeneron Pharmaceuticals, Amryt, Ionis Pharmaceuticals Inc. E.A. Oral: Consulting Fee; Self; Regeneron Pharmaceuticals, Third Rock Ventures, Rejuvenate Inc. Grant Recipient; Self; Regeneron Pharmaceuticals, Amryt Pharmaceuticals, Ionis Pharmaceuticals Inc., Gemphire Therapeutics. Other; Self; Amryt Pharmaceuticals, Novo Nordisk, Rhythm Pharmaceuticals, Fractyl Laboratories, GI Dynamics. I. Yildirim Simsir: None. R.J. Brown: Other; Self; Regeneron Pharmaceuticals. S. Ozen: None. O. Pagovich: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. D. Srinivasan: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. R.J. Sanchez: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. Background: Generalized lipodystrophy (GLD) is characterized by near-total lack of adipose tissue and, consequently, low levels of serum leptin. Mibavademab (REGN4461) is an investigational human monoclonal agonist antibody of the leptin receptor. As part of the phase 2, randomized, double-blind, placebo-controlled study (NCT04159415) of mibavademab, we conducted exit interviews to gather patient experience data specific to GLD and changes experienced during the study. Methods: Between week 52-54, experienced interviewers conducted 45-minute in-depth, semi structured, qualitative phone interviews to understand their GLD-related symptoms/signs, perceptions of any improvements experienced during the study as well as the importance of these improvements. Results: Interviews were conducted with 5 females and 2 males, with a mean age of 19.4 (range:15-23). Most participants reported experiencing hunger-related symptoms (n=6), pain, extreme body temperature sensations (n=5 for each), and fatigue or sleep problems (n=4 for each) prior to them starting the study. While we were interested in symptoms, many participants also reported clinical signs, such as enlarged/fatty liver and hyperglycemia (n=5 for each). Pain was most frequently reported as the most bothersome symptom (n=3) prior to the study. All participants who reported having hunger, pain, extreme body temperatures, hyperglycemia, and fatigue before the study reported improvements after 52 weeks of treatment. Participants generally indicated more than a minimal amount of change. For example, of the 5 participants who reported hunger as a symptom prior to the study and who were asked about the amount of change, all reported either “some” (n=1) or “a lot” of improvement (n=4). Participants, overall, rated each improvement, except body temperature as “very important.” Improvements in extreme body temperature were generally rated by participants as “somewhat important.” When asked which of the reported improvements were most important, changes in hyperglycemia was most frequently reported (n=4) followed by improvements in enlarged or fatty liver (n=2) and pain and hunger (n=1 each). All participants reported they were satisfied (n=2) or very satisfied (n=5) with the study treatment. Conclusions: All participants who reported symptoms of hunger, pain, fatigue, and extreme body temperature, or the clinical biomarker of hyperglycemia before entering the study reported improvements in each of these after treatment. In addition, all participants reported being either satisfied or very satisfied with treatment. This qualitative research provides insight into the patient experience for individuals with GLD and provides an opportunity to further understand and complement the clinical trial results. Presentation: 6/1/2024

An in Vitro Evaluation of the 14-Day Microbial Barrier Property of Exofin High Viscosity Topical Skin Adhesive.

Background: Wound closure is a critical aspect of medical care, and the choice of closure methods plays a pivotal role in preventing infections. Traditional sutures and staples can introduce foreign material into the wound, increasing the risk of infection. Adhesives offer a potential alternative by providing a physical barrier against microorganisms. Objective: To assess the microbial barrier properties of Exofin High Viscosity Topical Skin Adhesive (HVTSA), a novel adhesive system, against a range of challenge organisms. Methods: This study, conducted by the independent research organization NAMSA (North American Science Associates, LLC), aimed to evaluate the effectiveness of Exofin HVTSA as a microbial barrier. This study was carried out by an independent research organization NAMSA. Challenge organisms, including Staphylococcus aureus, Staphylococcus epidermidis, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Escherichia coli, Candida albicans, and Aspergillus brasiliensis, were used to evaluate the adhesive's effectiveness. Inocula of each organism were placed on cured Exofin HVTSA test articles and observed for 14 days. Positive and negative control plates were included to validate the effectiveness of the challenge organisms and assess the absence of contamination. Results: Exofin HVTSA demonstrated effective microbial barrier properties against all challenge organisms, except Pseudomonas aeruginosa. No growth or color change was observed for Staphylococcus aureus, Staphylococcus epidermidis, MRSA, Escherichia coli, Candida albicans, and Aspergillus brasiliensis over the 14-day observation period. Pseudomonas aeruginosa exhibited no growth, but showed a color change in two out of five replicates on day 14. Conclusion: Exofin HVTSA demonstrated effective microbial barrier properties for 14 days against a range of common wound pathogens, suggesting its potential as a safe and effective alternative to traditional wound closure methods. Further research is warranted to investigate its efficacy in clinical settings.

Deficits and opportunities, pivots and shifts for scaling-up voluntary medical male circumcision in Uganda: a qualitative reflexive thematic analysis study

Despite voluntary medical male circumcision (VMMC) being a cost-effective intervention for preventing HIV transmission, its scale-up has faced challenges. Several interventions to address these challenges in priority countries, including Uganda, have not yielded the desired results. This cross-sectional qualitative study aimed to explore the factors that affect the demand for VMMC and identify possible solutions. Semi-structured phone interviews were conducted with 29 males aged at least 18 and not more than 65 drawn randomly from a database representative of the general population maintained by an independent research organisation. Reflexive thematic analysis was conducted, and data analysis was done using NVivo version 12. The results were presented in narrative format with supporting quotes. The study received ethical and regulatory clearance to be conducted in Uganda. The average age of the respondents was 28 years. Almost all respondents had some education, and most lived in rural areas. Two themes were generated, namely, 1) deficits and opportunities for VMMC, which are issues that currently hinder the uptake of VMMC but, if addressed, would lead to better demand, and 2) pivots and shifts for VMMC, which are changes that need to be made to improve the uptake of VMMC. We found that several challenges, including myths, misconceptions, health system gaps, and uncertainties about the postoperative period, hindered the uptake of VMMC. Pivots and shifts for improving the uptake of VMMC include intensifying VMMC campaigns, addressing inequities, and addressing access barriers. We concluded that several challenges, including myths and misconceptions, health system-related gaps, and uncertainties in the post-circumcision period, persist and negatively impact the scale-up of VMMC in Uganda. VMMC beneficiaries have plausible proposals for addressing challenges. The Uganda Ministry of Health should address the myths, misconceptions, health system-related gaps, and uncertainties about the postoperative period and should involve VMMC beneficiaries in reviewing interventions to address gaps.

Establishment and development of the Center of Plant Systems Biology and Biotechnology in Plovdiv, Bulgaria

The Bulgarian research landscape, presented mainly by the research institutes that are part of the Bulgarian Academy of Sciences and the Agricultural Academy, needs diversification to match the research and innovation potential of the other European Union (EU) countries. This article describes the establishment of the Center of Plant Systems Biology and Biotechnology (CPSBB), a new innovative type of independent research organization that is changing the research landscape in Bulgaria. Supported by the EU Commission, Bulgarian Government, and Plovdiv Municipality, CPSBB has quickly become the leading plant science institute in Bulgaria, creating knowledge in diverse fields such as bioinformatics, biotechnology, genetics and genomics, metabolomics, and systems biology. We outline the organizational structure of CPSBB, the development of its infrastructure, and its scientific productivity. Finally, we compare CPSBB with other similar research establishments in Europe and we conclude that such new types of institutes have a bright future in Bulgaria due to their operational flexibility, productivity, and connections with academia and industry.

Abstract CT129: A phase 1 dose escalation study of a novel coupled CAR T cell therapy, GCC19CART, for patients with metastatic colorectal cancer

Abstract Background: GCC19CART, the first clinical candidate from the CoupledCAR solid tumor platform, is designed to overcome the limitations of conventional CAR T-cells in solid tumor malignancies by pairing solid tumor CAR T-cells with CD19-targeting CAR T-cells to amplify the proliferation and activation of the solid tumor CAR T component. GCC19CART targets guanylate cyclase-C (GCC), which is reported to be expressed in the metastatic lesions of 70%-80% of subjects with colorectal cancers and largely restricted to the intestinal tract. A Phase 1 investigator-initiated clinical trial conducted in China showed preliminary efficacy with an overall response rate (ORR) at dose level 1 (1x106 CAR T-cells/kg) of 15.4% ORR (2/13) and 50% ORR (4/8) in dose level 2 (2x106 CAR T-cells/kg). Common side effects included cytokine release syndrome (CRS) and diarrhea/colitis. Immune effector cell-associated neurotoxicity syndrome (ICANS) was seen in a smaller proportion of patients. A phase 1 study was initiated in the United States in August 2022 for patients with metastatic colorectal cancer refractory to standard of care chemotherapy. As of a data cutoff on ​November 1, 2023, 4 subjects have been treated in the initial dose level. Methods: Subjects were initially screened for GCC expression; this requirement was later discontinued when immunohistochemistry studies revealed that the frequency of positive GCC expression exceeded 95%. Eligible subjects underwent leukapheresis, a single dose of lymphodepleting chemotherapy (fludarabine 30mg/m2 and cyclophosphamide 300mg/m2) 3 days prior to infusion, and then administration of a single infusion of GCC19CART. Responses were assessed by RECIST v1.1 by site investigator review and an independent third-party imaging contract research organization. Results: 4 subjects have been dosed at level 1 (1x106 cells/kg) and completed the DLT period at the time of data cutoff. The most common adverse events were CRS in 4/4 subjects (Grade 1: 2/4 (50%) or Grade 2: 2/4 (50%)) and diarrhea in 3/4 subjects (Grade 1: 1/4 (25%), Grade 2: 1/4 (25%), or Grade 3: 1/4 (25%)). Three out of four patients had a mild tremor (Grade 1) that resolved with corticosteroids and no other evidence of neurotoxicity. The combined overall response rate (ORR) was 50% (2/4) by independent review. Two subjects demonstrated a partial response (PR) while 1 additional subject had partial metabolic response (PMR) on PET/CT with stable disease (SD) and 1 patient had progressive disease per RECIST 1.1. Per site investigator review, the ORR was 25%, with 1 confirmed PR and 3 SD assessed as best response. The median PFS was 3.8 months in the dose level 1 group. Conclusions: Preliminary results demonstrate that GCC19CART has meaningful clinical activity and an acceptable safety profile in refractory metastatic colorectal cancer. This trial is ongoing and updated data will be presented, including from patients treated at dose level 2 (2x106 CAR T-cells/kg). Clinical trial information: NCT05319314. Citation Format: Bridget P. Keenan, Christopher H. Lieu, Marwan Fakih, Dongqi Chen, Lucy Lu, Eric Rowinsky, Victor Lu, Lei Xiao, Alan P. Venook, Benjamin Schlechter. A phase 1 dose escalation study of a novel coupled CAR T cell therapy, GCC19CART, for patients with metastatic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT129.

A systematic assessment on the influence of probiotics on patients with Inflammatory Bowel Disorder

Inflammatory bowel disease (IBD) causes persistent mucosal inflammation, and mounting evidence points to the intestinal microbiota's critical involvement in this process. New molecular techniques have also helped to identify dysbiosis in these individuals. Many potential probiotic product action mechanisms counteract IBD etiological causes. The study aimed to explain the benefits of probiotics for IBD and thoroughly evaluate current trials using probiotics to treat IBD in grownups. A specific search was done using specified keywords on October 1, 2011, using the supplied date range. Only English-language, full-text articles on clinical results for adult patients were addressed. Based on disease type and disease activity, the 41 eligible studies were classified. Pooled odds ratios were calculated only when there were many available randomized controlled trials per probiotic for a particular patient group. According to well-designed randomized controlled studies, few probiotics are effective in treating IBD at this time. It was only feasible to conduct meta-analyses on a limited number of studies, which yielded an overall risk ratio of 2.70 for inducing remission in active U.C. with Bifido fermented milk versus placebo or no adjuvant treatment. Very Specific Lactic Acid Bacteria (VSL#3) enables people to go into remission active U.C. compared to placebo. To support the favorable outcomes for inactive ulcerative colitis (U.C.), it is still a need to conduct better-conducted investigations in regard to the variety of drug VSL#3 in patients with both active and dormant U.C. U.C. based on intention-to-treat analyses by many independent research organizations. According to the existing data, probiotic usage in Crohn’s Disease (CD) has yet to be shown. The location and subtypes of certain diseases should be the focus of future research. Selecting probiotic strains for certain disease entities and illness sites will be easier with more knowledge of the mechanisms of probiotic strains and the etiology of IBD.

Establishment and development of the Center of Plant Systems Biology and Biotechnology in Plovdiv, Bulgaria.

The Bulgarian research landscape, presented mainly by the research institutes that are part of the Bulgarian Academy of Sciences and the Agricultural Academy, needs diversification to match the research and innovation potential of the other European Union (EU) countries. This article describes the establishment of the Center of Plant Systems Biology and Biotechnology (CPSBB), a new innovative type of independent research organization that is changing the research landscape in Bulgaria. Supported by the EU Commission, Bulgarian Government, and Plovdiv Municipality, CPSBB has quickly become the leading plant science institute in Bulgaria, creating knowledge in diverse fields such as bioinformatics, biotechnology, genetics and genomics, metabolomics, and systems biology. We outline the organizational structure of CPSBB, the development of its infrastructure, and its scientific productivity. Finally, we compare CPSBB with other similar research establishments in Europe and we conclude that such new types of institutes have a bright future in Bulgaria due to their operational flexibility, productivity, and connections with academia and industry.

Evolution of an Independent Research Institution: A Reflective Analysis

This article examines the idea of institutions and the elements of the process of institutionalisation, using the features of and experiences in an independent research organisation, which was established in 1998, in India. The author, using her experience of heading this organisation for nearly 13 years, and drawing from the Scott’s three pillar approach, reflects on the aspects of why and how an organisation becomes an institution, and what the joys and challenges of leading the process of institution building are. She argues that institution-building is a continuous process where Scott’s three pillars support each other, and change over time and space. The real test of an organisation in becoming an institution is in the capacity to respond to the emergent needs both inside the organisation, and to the external environment, while managing to work as per the vision and perceived mandate, maintain order and stability, within given resources and legal frameworks that guide the functioning of the organisation. Using her own experiences, she identifies plurality as the most important principle that helped in the process of institutionalisation in this case.

Timnit Gebru: seeking to promote diversity and ethics in AI

Learning outcomes This case is designed to enable students to understand the role of women in artificial intelligence (AI); understand the importance of ethics and diversity in the AI field; discuss the ethical issues of AI; study the implications of unethical AI; examine the dark side of corporate-backed AI research and the difficult relationship between corporate interests and AI ethics research; understand the role played by Gebru in promoting diversity and ethics in AI; and explore how Gebru can attract more women researchers in AI and lead the movement toward inclusive and equitable technology. Case overview/synopsis The case discusses how Timnit Gebru (She), a prominent AI researcher and former co-lead of the Ethical AI research team at Google, is leading the way in promoting diversity, inclusion and ethics in AI. Gebru, one of the most high-profile black women researchers, is an influential voice in the emerging field of ethical AI, which identifies issues based on bias, fairness, and responsibility. Gebru was fired from Google in December 2020 after the company asked her to retract a research paper she had co-authored about the pitfalls of large language models and embedded racial and gender bias in AI. While Google maintained that Gebru had resigned, she said she had been fired from her job after she had raised issues of discrimination in the workplace and drawn attention to bias in AI. In early December 2021, a year after being ousted from Google, Gebru launched an independent community-driven AI research organization called Distributed Artificial Intelligence Research (DAIR) to develop ethical AI, counter the influence of Big Tech in research and development of AI and increase the presence and inclusion of black researchers in the field of AI. The case discusses Gebru’s journey in creating DAIR, the goals of the organization and some of the challenges she could face along the way. As Gebru seeks to increase diversity in the field of AI and reduce the negative impacts of bias in the training data used in AI models, the challenges before her would be to develop a sustainable revenue model for DAIR, influence AI policies and practices inside Big Tech companies from the outside, inspire and encourage more women to enter the AI field and build a decentralized base of AI expertise. Complexity academic level This case is meant for MBA students. Social implications Teaching Notes are available for educators only. Subject code CCS 11: Strategy

Key Issues Affecting the Inclusion of Alt Text in Scholarly PDF Publications

Abstract Alternative (alt) text descriptions for images in digital publications provide comparable information for people who cannot effectively see the visuals. They are relied upon by people who are blind or who have a moderate to severe visual impairment and who use assistive technologies. However, consistent provision of alt text is proving challenging for publishers because of the required changes in workflow, budgeting, and resourcing; in particular, scholarly publications contain high numbers of images requiring alt text. Most industry knowledge-sharing and studies on alt text in scholarly PDFs focus on large and medium-sized publishers and high JIF titles. To explore key issues affecting the consistent inclusion of alt text in publications produced by small and non-profit publishers this study uses the case of a UK-based independent research organization. Drawing on PDF analyses and a focus group discussion with publishing staff, the article makes recommendations for similar organizations seeking to publish alt text.

Establishment and development of the Center of Plant Systems Biology and Biotechnology in Plovdiv, Bulgaria

The Bulgarian research landscape, presented mainly by the research institutes that are part of the Bulgarian Academy of Sciences and the Agricultural Academy, needs diversification to match the research and innovation potential of the other European Union (EU) countries. This article describes the establishment of the Center of Plant Systems Biology and Biotechnology (CPSBB), a new innovative type of independent research organization that is changing the research landscape in Bulgaria. Supported by the EU Commission, Bulgarian Government, and Plovdiv Municipality, CPSBB has quickly become the leading plant science institute in Bulgaria, creating knowledge in diverse fields such as bioinformatics, biotechnology, genetics and genomics, metabolomics, and systems biology. We outline the organizational structure of CPSBB, the development of its infrastructure, and its scientific productivity. Finally, we compare CPSBB with other similar research establishments in Europe and we conclude that such new types of institutes have a bright future in Bulgaria due to their operational flexibility, productivity, and connections with academia and industry.

Can group‐based strategies increase community resilience? Longitudinal predictors of sustained participation in Covid‐19 mutual aid and community support groups

AbstractMutual aid groups have been a critical part of the coronavirus disease‐2019 (Covid‐19) response and continue to address the needs of people in their communities. To understand how mutual aid and similar community support groups can be sustained over time, we test the idea that using group‐based strategies initiates psychological trajectories that shape future participation. We conducted a preregistered longitudinal survey among Covid‐19 mutual aid and community support volunteers in the United Kingdom (nWave 1 = 600, May 2021; nWave 2 = 299, July–August 2021) who were registered panelists of an independent research organization. Assessments included measures of group‐based strategies, collective participation predictors, participation experience, and sustained participation. Volunteers engaged in a wide range of support activities including shopping, emotional support provision, and deliveries. Two group‐based strategies—group alliances and group horizontality—longitudinally predicted sustained participation. In addition, sense of community responsibility and burnout were longitudinal predictors of sustained participation. Importantly, predictors of sustained participation diverged for volunteers with different levels of volunteering experience. Our findings highlight group‐based strategies as a potential resource for organizers seeking to sustain participation. Use can be tailored depending on the profiles of individual Covid‐19 mutual aid volunteers. These findings have significance beyond Covid‐19 as they are relevant to sustaining community resilience more generally.

A phase 1 dose escalation study of GCC19CART: A novel coupled CAR therapy for patients with metastatic colorectal cancer.

3547 Background: GCC19CART, the first clinical candidate from the CoupledCAR solid tumor platform, is designed to overcome the limitations of conventional CAR T-cells in solid tumor malignancies by pairing solid tumor CAR T-cells with CD19 targeting CAR T-cells to amplify the proliferation and activation of the solid tumor CAR T component. GCC19CART targets guanylate cyclase-C (GCC), which is expressed in the metastatic lesions of 70%-80% of subjects with colorectal cancers and largely restricted to the intestinal tract. A Phase 1 investigator-initiated clinical trial is underway in China for patients with relapsed or refractory metastatic colorectal cancer who have received at least 2 prior lines of therapy. As of a data cutoff on Jan 28, 2023 21 subjects have been enrolled in 2 dose escalation groups at 5 hospitals in China. Methods: Subjects are screened for GCC expression by immunohistochemistry. Eligible subjects undergo leukapheresis, a single dose of lymphodepleting chemotherapy (fludarabine 30mg/m2 and cyclophosphamide 300mg/m2) 3 days prior to infusion, and then administration of a single infusion of GCC19CART at one of two preassigned doses: 1x106 or 2x106 CAR T-cells/kg. All responses were confirmed by an independent third-party imaging contract research organization. Results: 13 subjects have been enrolled to dose level 1 (1x106 cells/kg) and 8 subjects have been enrolled to dose level 2 (2x106 cells/kg). The most common adverse events were cytokine release syndrome (CRS) in 21/21 subjects (Grade 1 19/21 (90.48%) or Grade 2 2/21 (9.52%)) and diarrhea in 21/21 subjects (Grade 1 6/21 (28.57%) Grade 2 5/21 (23.81%) Grade 3 9/21 (42.86%) or Grade 4 1/21 (4.76%)). All patients with grade 3 and higher side effects were well managed. Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 2/21 (9.52%) subjects at Grade 3 or 4 and resolved with corticosteroids. The combined overall response rate (ORR) for both dose levels was 28.6% (6/21). For dose level 1, overall response rate (ORR) was 15.4% (2/13). Two subjects demonstrated a partial response (PR) while 3 additional subjects had partial metabolic response (PMR) on PET/CT with stable disease (SD) or progressive disease (PD) per RECIST 1.1. For dose level 2, The ORR was 50% (4/8). 4 subjects demonstrated a PR and 2 additional subjects had PMR on PET/CT with SD per RECIST 1.1.The median PFS was 1.9 months in the dose 1 group and 6.3 months in the dose 2 group. The median overall survival was 13.3 months in the dose 1 group and 18.3 months in the dose 2 group. Conclusions: Preliminary results demonstrate that GCC19CART has meaningful dose-dependent clinical activity and an acceptable safety profile in relapsed or refractory metastatic colorectal cancer. This trial is ongoing and updated data will be presented. A Phase 1 trial of GCC19CART in the US has opened for accrual and is expected to enroll patients in mid-2022. Clinical trial information: ChiCTR2000040645 .

Performance Evaluation of SARS-CoV-2 Viral Transport Medium Produced by Bangladesh Reference Institute for Chemical Measurements.

A viral transport medium (VTM) was developed following the Centers for Disease Control and Prevention, USA (US-CDC) standard operating procedure (SOP) DSR-052-05 with necessary improvisation and was used for storing coronavirus disease 2019 (COVID-19) swab specimens. Considering Bangladesh's supply chain and storage conditions, improvisation was essential for extending sample storage time while retaining efficiency. In-house VTM was produced using Hank's balanced salt solution (HBSS) supplemented with 1% bovine serum albumin V (BSA), 0.5 µg /mL of gentamicin sulfate, and 100 µg/mL of fluconazole. The produced VTM composition, quality, sterility, specificity, and efficiency were verified in-house and through an independent contract research organization (CRO). An accelerated stability study projected that under the recommended temperature (4 °C), it would remain stable for four months and preserve samples for over a month. The real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) test detected the targeted N gene and ORF1ab gene from the VTM stored samples. Our VTM is equally as effective as the Sansure Biotech VTM in keeping SARS-CoV-2 RNA specimens detectable in rRT-PCR (100% sensitivity and specificity in random and blinded samples). In conclusion, the BRiCM VTM will make the battle against pandemics easier by effectively collecting and storing nasopharyngeal and oropharyngeal swabs for COVID-19 detection.

COVID-19 vaccination and the skin to deltoid MUSCLE distance in adults with diabetes.

To estimate the proportion of adult diabetics with a skin to deltoid muscle distance (SDMD) of >25 mm, representing a distance greater than the standard needle length used for intramuscular COVID-19 vaccination, and to assess whether anthropometric measurements predict ultrasound SDMD measurements.Design: Non-interventional cross-sectional study.Setting: Single site, non-clinical setting, Wellington, New Zealand.Participants: One hundred participants (50 females) aged at least 18 years diagnosis with diabetes. All participants completed the study. The proportions of participants with a SDMD >25mm and a SDMD >20mm (indicating that the needle would not have penetrated at least 5mm into the deltoid, which is considered necessary to ensure deposition of vaccine into muscle); the relationship between anthropometric measurements (body weight, body height, body mass index (BMI), skinfold thickness, arm circumference) and SDMD measured by ultrasound. The proportion (95%CI) of participants with a SDMD >25mm was 6/100; 6% (2.2 to 12.6), and the proportion with a SDMD >20mm was 11% (5.6 to 18.8), of which 9/11 had a BMI ≥30kg/m2 and 9/11 were female. The strongest relationships between anthropometric measurements and SDMD were with arm circumference (r=0.76, P<0.001) and BMI (r=0.73, P<0.001). Arm circumference and BMI were the best predictors of SDMD measurements with AUC for ROC curves of 0.99 and 0.94 above the 25 mm cut point, 0.97 and 0.89 above the 20 mm cut point respectively. The standard needle length of 25mm is likely to be insufficient to ensure deposition of COVID-19 vaccine within the deltoid muscle in a small but important proportion of obese adults with diabetes. Arm circumference and BMI are simple measurements that could identify those that need a long needle to ensure successful intramuscular vaccine administration. Ruth Maud Ring Spencer Estate; Health Research Council of New Zealand (Independent Research Organisation).

Safety, tolerability, and efficacy of zavegepant 10 mg nasal spray for the acute treatment of migraine in the USA: a phase 3, double-blind, randomised, placebo-controlled multicentre trial

Intranasal formulations can provide treatment options for people with migraine in whom oral drugs are ineffective, slow-acting, or intolerable because of nausea and vomiting. Zavegepant, an intranasally administered small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, was previously assessed in a phase 2/3 trial. This phase 3 trial aimed to compare the efficacy, tolerability, safety, and timecourse of response for zavegepant nasal spray with placebo in the acute treatment of migraine. This double-blind, randomised, placebo-controlled, multicentre phase 3 trial, conducted at 90 academic medical centres, headache clinics, and independent research facilities in the USA, recruited adults (aged ≥18 years) with a history of two to eight moderate or severe migraine attacks per month. Participants were randomly assigned (1:1) to zavegepant 10 mg nasal spray or matching placebo and self-treated a single migraine attack of moderate or severe pain intensity. Randomisation was stratified by the use or non-use of preventive medication. Study centre personnel entered eligible participants into the study using an interactive web response system that was operated and managed by an independent contract research organisation. All participants, investigators, and the funder were masked to group assignment. The coprimary endpoints, freedom from pain and freedom from the most bothersome symptom at 2 h after the treatment dose, were assessed in all randomly assigned participants who took the study medication, had a migraine attack of moderate or severe pain intensity at baseline, and provided at least one evaluable post-baseline efficacy datapoint. Safety was analysed in all randomly assigned participants who received at least one dose. The study is registered with ClinicalTrials.gov, number NCT04571060, and is closed to accrual. Between Oct 27, 2020, and Aug 20, 2021, 1978 participants were recruited and assessed for eligibility. 1405 participants were eligible (703 were assigned to zavegepant and 702 to placebo), and 1269 were included in the efficacy analysis set (623 in the zavegepant group and 646 in the placebo group). 2 h after the treatment dose, more participants in the zavegepant group than in the placebo group had pain freedom (147 [24%] of 623 participants vs 96 [15%] of 646 participants, risk difference 8·8 percentage points, 95% CI 4·5-13·1; p<0·0001) and freedom from their most bothersome symptom (247 [40%] vs 201 [31%], risk difference 8·7 percentage points, 3·4-13·9; p=0·0012). The most common adverse events in either treatment group (≥2%) were dysgeusia (129 [21%] of 629 in the zavegepant group vs 31 [5%] of 653 in the placebo group), nasal discomfort (23 [4%] vs five [1%]), and nausea (20 [3%] vs seven [1%]). No signal of hepatotoxicity due to zavegepant was identified. Zavegepant 10 mg nasal spray was efficacious in the acute treatment of migraine, with favourable tolerability and safety profiles. Additional trials are needed to establish the long-term safety and consistency of effect across attacks. Biohaven Pharmaceuticals.

Impact of the reporting source on Platelet Inhibition and Treatment Outcomes (PLATO) trial deaths.

Platelet Inhibition and Clinical Outcomes (PLATO) was a multicenter, randomized double-blind trial assessing efficacy and safety of ticagrelor versus clopidogrel in patients with acute coronary syndrome. The reported mortality benefit of ticagrelor in the PLATO trial has been challenged for over decade, and never confirmed in later trials. To compare if there were any differences when deaths were reported to the FDAby the sponsors or by independent Contract Research Organizations (CRO). We obtained the complete PLATO deaths dataset reported to the FDA and revealed that some events were inaccurately reported favoring ticagrelor. The entire FDA list contains precisely detailed 938 PLATO deaths. The CRO reported outcomes from the USA, Russia, Georgia, and most of Ukraine, while sites in 39 other countries were controlled by the trial sponsors. We compared vascular- (code "11"), non-vascular- (code "12"), and unknown (code "97") deaths triaged by the reporting source. Overall, most PLATO deaths were vascular (n=677), less non-vascular (n=159) andunexpectedly many of "other" (n=7) or "unknown" (n=95) origin reported either by sponsors (n=807) or CRO (n=131). The trial sponsors reported more clopidogrel deaths from vascular (313 vs.239), non-vascular (86 vs.58) and unknown (53 vs. 26) causes.In contrast, CRO-monitored sites reported significantly (72 vs. 53; p<0.01) more ticagrelordeaths than after clopidogrel from vascular (51 vs.39), non-vascular (8 vs.7) and unknown (10 vs. 4) causes. Deaths were reported differently by sponsors and CRO within the same trial. Since some deaths were misreported by PLATO sponsors, only the CRO data seems mostly reliable. Among all countries, the CRO - reported PLATO-USA outcomes represent the largest and most realistic dataset of realistic evidence suggesting ticagrelor inferiority to clopidogrel for all primary endpoint components including vascular death.

Evaluation of the Fast Prior Authorization Technology Highway

BackgroundPrior authorization (PA) is a utilization management tool used by health plans and pharmacy benefit managers where the payer requires additional documentation from health care providers before authorization of payment for a medication or procedure. PA processes are hypothesized to be more efficient if electronic transmission is utilized instead of manual submission. ObjectiveTo evaluate the impact of electronic PA (ePA) on approval rate and time to decision and to assess health care provider perception of using ePA. MethodsAmerica’s Health Insurance Plans selected 2 technology companies, Availity and Surescripts, and used an independent research organization (Research Triangle Institute [RTI]) to conduct a provider survey and analyze over 40,000 PA transactions from participating health plans. RTI examined processing time, provider experience, and other measures for PAs both before and after provider implementation of ePA. ResultsProviders used these tools for roughly 62% of PAs in the 6 months after implementation. The median time from PA request to decision fell from 18.7 hours to 5.7 hours. Providers using ePA reported observing some benefits relative to the number of phone calls and faxes required after ePA implementation. ConclusionThe primary benefit of ePA implementation was reduced time to decision. Additional benefits may occur with greater adoption since 38% of PAs were still manual after implementation of ePA.

Willingness to share anonymised routinely collected clinical health data in Switzerland: a cross-sectional survey.

Routinely collected health data (or real-world data) from hospitals is becoming increasingly important to advance medical progress. Anonymisation of these data facilitates data sharing processes. This allows stakeholders of the healthcare system to compliantly access this anonymised data to address epidemiological questions, advance precision medicine, support drug development or address other medical needs. As the willingness of the general Swiss population to share anonymised health data has been uncertain, a survey was conducted to better understand their perception of sharing such data for research purposes. The present survey focused on the re-use (secondary use) of hospital-derived health data in anonymised form. A cross-sectional survey was conducted in a representative random sample (n = 1006) of the general Swiss population. The general population was contacted by phone between 14 September and 3 October 2020. The survey was also conducted in an additional population with chronic disease (n = 225) via an online panel. An independent research organisation (gfs-zürich) was commissioned to conduct the survey. The survey participation was anonymous and voluntary. The demographic composition of the interviewed participants from the general population was specifically constructed to be representative of the 18+-year-old French- and German-speaking population of Switzerland, according to the quota features gender, age and language region. Representativeness of the chronic disease population is unclear. 71% of the general population and 81% of the chronic disease group reported that they would share their anonymised health data for medical research. The drivers were mainly of an altruistic nature. Hurdles concern mainly data protection issues, potential misuse or disadvantages, e.g., by health insurers. About 56% of the general population would like to be better informed about the use of their personal health data, and 69% spontaneously reported health authorities as the stakeholder responsible for providing such information. The survey showed that the Swiss population is willing to share anonymised health data given that some key concerns are addressed. Our findings underline that a better understanding of the standards and processes around health data privacy and transparent data usage is important to build trust in the public eye. An open dialogue is required to develop a common consent on data governance for Switzerland, which would allow health data sharing with third parties. This open dialogue should involve all stakeholders of the healthcare system, so as to strive towards both a more personalised and a more sustainable Swiss healthcare system.

Consuming a Protein and Fiber-Based Supplement Preload Promotes Weight Loss and Alters Metabolic Markers in Overweight Adults in a 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial

BackgroundHigher protein and fiber diets promote weight management and metabolic health. ObjectivesThis study aimed to determine if greater weight loss and positive changes in metabolic outcomes could be achieved with twice-daily consumption of a high-protein and fiber-based multi-ingredient nutritional shake (HPF) compared with an isocaloric low-protein, lower fiber-based placebo (LPF). MethodsStudy procedures were conducted by an independent research organization under clinicaltrials.gov registration NCT03057873. Healthy overweight and obese adults [n = 206; BMI (kg/m2): 27–35; 70% female] were randomly assigned to HPF or LPF. All participants were prescribed an energy-restricted diet (500 kcal/d less than energy needs) and consumed a HPF (17 g protein, 6 g fiber) or LPF (1 g protein, 3 g fiber) shake 30 min before breakfast and lunch for 12 wk. Primary outcomes included body weight and total body fat percentage. Blood samples were collected at days (D) 0, 28, 56, and 84 for secondary analyses related to metabolic markers of health. ResultsAlthough weight loss occurred in both groups, HPF had greater weight loss at D84 compared with LPF (–3.3 kg vs. –1.8 kg, P < 0.05). Percentage body fat decreased in both groups (HPF: –1.33%, LPF: –1.09%; P < 0.001) with no differences between groups. Serum total cholesterol, LDL cholesterol, and oxidized LDL decreased between –5.1% to –8.3%, whereas adiponectin increased over time in both groups; these changes occurred to a greater extent in HPF compared with LPF (all P < 0.05). ConclusionsA multi-ingredient HPF nutritional supplement shake consumed as a preload before breakfast and lunch positively influenced weight management and metabolic outcomes in overweight adults compared with an LPF placebo. These findings suggest that specific nutrient factors (i.e., potentially including protein, fiber, and bioactive content) other than calorie reduction alone influence the success of a weight-loss regimen. This trial was registered at www.clinicaltrials.gov as NCT03057873,