Contract Research Research Articles

The Role of NHRC in Regulating Health Research Ethics in Nepal: A Narrative Review

This study aims to chart Nepal's evolution of health research ethics over time and the role of the Nepal Health Research Council (NHRC) in its regulation. This narrative review article mentions the pervasiveness of contract research and the contribution of universities and international organizations in producing data and supporting pilot projects. It further highlights the structural inequalities and limitations of health research in Nepal, including lack of technology, infrastructure, funding, limited access to resources and global scientific networks. It discusses Nepal's emerging regulatory and ethical field, establishing the NHRC and developing ethical guidelines and review committees. The challenges faced by NHRC in terms of capacity and resources and the need to strengthen research ethics monitoring and compliance are also marked. This article also discusses several key challenges and areas of concern regarding research ethics and capacity building in Nepal's health research context. The conflicts arising from defining health research and determining which activities require ethical review are highlighted, especially about programmatic interventions and monitoring and evaluation exercises. The need for comprehensive mapping of health research activities is emphasized as an initial step toward understanding the research landscape. Additionally, issues related to timely ethical reviews, the co-investigator’s role, institutional research capacity, data ownership, publication practices, and the ethical considerations of health and development interventions are discussed. It emphasizes redressing these challenges and promoting responsible research practices in Nepal.

Location of links in the pharmaceutical value chain in Сhina: the role of contract research organizations

Location of links in the pharmaceutical value chain in Сhina: the role of contract research organizations

EE296 Should Hospitals Do Contract Research? Costs, Net Monetary Benefit, and Return on Public Sector Investments in Research at Kuopio University Hospital

EE296 Should Hospitals Do Contract Research? Costs, Net Monetary Benefit, and Return on Public Sector Investments in Research at Kuopio University Hospital

HPR95 Public-Private Partnership Model in Oncology: Business Opportunities for Next Generation Contract Research Organizations in the Context of CancerX

HPR95 Public-Private Partnership Model in Oncology: Business Opportunities for Next Generation Contract Research Organizations in the Context of CancerX

2650. Characteristics of In-Hospital Care and Immediate Post-Discharge Care Status among Older Adults Hospitalized with Respiratory Syncytial Virus Infection, Seasonal Influenza, Acute Myocardial Infarction, and Stroke in the US

Abstract Background Despite increased recognition of the morbidity, mortality, and economic burden of respiratory syncytial virus (RSV) in adults, few studies have documented the status of post-discharge care after RSV hospitalization. This study assessed in-hospital and immediate post-discharge care status in older adults hospitalized with RSV in the US and compared it with other serious medical conditions (influenza, acute myocardial infarction (AMI), and stroke) that have long-standing disease prevention efforts. Methods This retrospective cohort study used data from Premier Healthcare Database between January 1, 2015, to December 31, 2019. Adults aged ≥ 65 years hospitalized due to primary diagnosis of RSV, influenza, AMI, or stroke were included. Discharge statuses were used to categorize the levels of immediate post-discharge care as shown in Figure 1. Descriptive statistics and Sankey diagrams were used to summarize the four cohorts. Results Overall, 2,559 RSV, 174,826 influenza, 208,448 AMI, and 274,102 stroke hospitalizations were identified with similar mean patient ages of 79.8, 76.8, 76.3, and 78.0 years, respectively. Almost all patients ( > 90%) had underlying comorbidities. The mean inpatient length of stay (LOS) was similar in the four cohorts (4.0, 4.4, 3.7, and 4.1 days, respectively), but the prevalence of mechanical ventilator use varied, i.e., 0.4%, 13.7%, 5.9%, and 1.4%, respectively. Intensive Care Unit (ICU) admissions during RSV hospitalizations were infrequent (3.0%) as compared to influenza (16.8%), AMI (24.5%), and stroke (20.5%). The mean ICU LOS for these four cohorts were 2.3, 2.8, 1.7, and 1.7 days in the same order. Immediately following discharge, moderate care was required for 23.9%, 22.9%, 14.1%, and 17.5% of RSV, influenza, AMI, and stroke hospitalizations, respectively. Elevated care was considerably more frequent for stroke hospitalizations (48.1%) than RSV (18.8%), influenza (21.4%), and AMI (19.3%) hospitalizations (Figure 2). Conclusion Older adults discharged from RSV hospitalizations require considerable care with needs comparable to influenza and AMI discharges. Given the substantial care requirements of RSV hospitalizations in older adults, focus on disease prevention efforts for RSV are needed. Disclosures Reiko Sato, PhD, Pfizer Inc: employee|Pfizer Inc: Stocks/Bonds Jennifer Judy, MS, PhD, Pfizer: Stocks/Bonds Kari Yacisin, M.D., Pfizer: Employee|Pfizer: Stocks/Bonds Elizabeth Begier, M.D., M.P.H., Pfizer: EB is an employee of Pfizer, the sponsor of this study|Pfizer: Stocks/Bonds Poorva Sardana, MSc, Pfizer Inc: Contracted Research Neha Agrawal, MA, Pfizer Inc: Contracted Research Anchita Goswami, MSc, Pfizer Inc: Contracted Research Manvi Sharma, RPh, MBA, PhD, Pfizer Inc: Contracted Research

1702. Disseminated Candidiasis after Candidemia: Epidemiology, Diagnostic Evaluation, and Risk Factors

Abstract Background In patients with candidemia, evaluation for disseminated disease with ophthalmological exam and diagnostic imaging is recommended but not standardized. This study sought to describe practice patterns in the diagnostic evaluation for disseminated disease after candidemia and identify risk factors associated with disseminated candidiasis to improve local management. Methods A retrospective study of all episodes of candidemia diagnosed in patients < 25 years from 2013-2022 at Cincinnati Children’s Hospital Medical Center reported clinical characteristics, microbiology data, and diagnostic testing for dissemination. Disseminated candidiasis was defined as an ophthalmologic exam, echocardiogram or other imaging findings consistent with candidiasis or growth of Candida spp. from a sterile site besides blood. Mixed-effects logistic regression was performed to identify risk factors for disseminated disease. Results 144 episodes of candidemia occurred in 124 patients , with C. albicans (35%) the most commonly identified species (Figure 1). 107/144 (74.3%) episodes underwent evaluation for disseminated candidiasis, with dissemination in 27/107 (25.2%). Of patients with only 1 positive culture, 5/34 (14.7%) had disseminated candidiasis compared to 22/73 (30.1%) with more than 1 positive culture (Figure 2). Ophthalmologic exams and echocardiograms were done in < 70% of workups (Figure 3). History of prematurity (aOR 17.5, 95%CI 3.1-100.4) and solid organ transplantation (aOR 5.3, 95%CI 1.1-24.6) were associated with disseminated candidiasis when controlling for age, sex, underlying disease, and initial antifungal treatment. Each additional day of candidemia significantly increased the odds of dissemination (aOR 1.5, 95%CI 1.2-1.9). Conclusion In this single-center study, most patients with candidemia underwent diagnostic evaluation, though the extent varied. Disseminated disease was common. Prematurity and history of solid organ transplantation were independent risk factors for dissemination as was each additional day of candidemia. Patients with any candidemia should undergo evaluation for dissemination. Multicenter studies are needed to determine the optimal diagnostic evaluation in these high-risk patient groups. Disclosures Grant C. Paulsen, MD, Moderna: Grant/Research Support|Pfizer: Grant/Research Support Lara A. Danziger-Isakov, MD, MPH, Aicuris: Contracted Clinical Research|Ansun Biopharma: Contracted Clinical Research|Astellas: Contracted Clinical Research|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Contracted Clinical Research|Pfizer: Contracted Clinical Research|Roche Diagnostics: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Contracted Clinical Research William R. Otto, MD, MSCE, Moderna: Grant/Research Support

Pharmaceutical sponsors and contract research organization’s perception toward genetic data reuse for future research

Abstract Background: Pharmaceutical sponsors and Contract research organization plays vital role in the preparation and implementation of clinical trials and give rise to ethical predicaments that pertain to various aspects such as general or genetic consent, optional research, storage and utilization of genetic data and specimens, as well as disclosure of research findings to study participants. Objective: The current investigation is to assess the knowledge, attitudes, and practices of Clinical Research Organizations and Pharmaceutical Sponsors in relation to re-use of genetic research data for future research. Study Participants and Methodology: A cross-sectional study conducted on pharmaceutical sponsor and their representatives from the metro cities, India. Results: The present research encompassed N=50 of pharmaceutical sponsors and contract research organizations. Among these, 84% evinced cognizance regarding the re-use of genetic data in clinical trials. Furthermore, 62% of pharmaceutical sponsors and contract research organizations articulated apprehensions with respect to ethical and legal quandaries might arise due to the re-use of genomic data. Discussion: A considerable proportion of participants are a willingness to share and reuse genetic data for future studies. However, it is observed that the perception towards practice is low, particularly in relation to the return of genetic results and ethical concerns while storing genetic samples. Conclusion: There are presently no universally accepted international Conference on Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines in place for the management of genetic sampling and data at the global level. In India, however, ICMR regulations exist to provide direction for the use of biological materials and datasets in research.

A community effort in SARS-CoV-2 drug discovery.

The COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against COVID-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find 'consensus compounds'. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments.

PSX-21 Evaluation of the Effect of Extended-Term Delivery of Local Anesthetic on Mitigating the Pain Caused By Castration

Abstract The objective of this study was to evaluate the effects of the extended-term delivery of anesthesia on the physiological and behavioral signs of pain caused by band castration in 1-month-old bull calves. Forty-eight calves (37.04 ± 8.98 days of age) were homogenously assigned by age to one of three band castration protocols (n = 16/protocol); 1) regular elastrator bands (REG), 2) regular elastrator bands preceded by two 2-mL injections of lidocaine (REG+L; LIDO-2 with epinephrine, Rafter 8 Products Inc, Calgary, Canada), and 3) lidocaine elastrator bands (LBAND; Care-Ring, Chinook Contract Research Inc., Calgary, Canada). During the castration procedure, two observers scored (from 1 to 10) how much pain each animal was experiencing (visual analog score, VAS), number of body shakes and leg kicks for each calf. Calves were weighed on d -1, 0, 14, 28, 42, and 56. Hair cortisol concentration was measured on d -1, 28, and 56. Saliva cortisol concentration was measured right after castration, 60, 120, 240 minutes after castration, on d 1 and weekly thereafter until d 56. Flight speed (FS) was recorded on d -1, right after castration, 60, 120, 240 minutes after castration, d 1, and weekly thereafter until d 56. Calf behaviors in the pen indicative of pain and discomfort were recorded on d 0, 1, and weekly thereafter until d 56. The REG+L calves tended to have decreased (P = 0.09) VAS scores than REG calves. The average daily gain was greater (P < 0.01) from d 42 to 56 than from d 1 to 42, and from d 1 to 28 compared with d 28 to 42 in all treatment groups. The REG calves had decreased (P < 0.01) hair cortisol concentrations than both REG+L and LBAND calves. Saliva cortisol concentrations were greater (P < 0.01) 60 minutes after castration than any other sample time in all treatment groups. There was an interaction between treatment and time (P = 0.04), where only LBAND had a greater FS immediately after castration compared with d -1. When calves were observed in the pen there were no treatment effects (P > 0.10) but only time differences (P < 0.05) in the frequency of head turns, oral behaviors, tail flicks, and number of standing and walking bouts. The behavioral and physiological parameters assessed showed expected results on the effects of band castrating calves, while the administration of lidocaine via REG+L or LBAND did not show any pain mitigation effect compared with the standard industry banding method (REG).

Cas-Clover Editing Efficiency and Off-Target Activity in Human Hepatocytes at the KLKB1 Locus

Cutting-edge gene editing holds enormous promise for tackling devastating genetic diseases like hereditary angioedema (HAE). Here, we describe the efficient inactivation of the gene encoding pre-kallikrein, KLKB1, using our proprietary Cas-CLOVER™ high-fidelity nuclease with our non-viral, lipid nanoparticle (LNP) delivery system. Genetic inactivation of KLKB1 is an alternative clinical approach that provides durable relief to both Type I and II HAE. HAE is a rare genetic disease characterized by subcutaneous and submucosal edema, with swelling of the upper respiratory tract posing a life-threatening situation. Type I and II HAE are the most common types and are caused by mutations in the SERPING1 gene, which leads to compromised production or function of the C1 protease inhibitor. Strategies for treatment and prophylaxis include the restoration of C1 inhibitor function, or downstream antagonism of active plasma kallikrein. Safe and effective gene editing of KLKB1 could be a viable alternative for patients not adequately responding to the current standard of care. However, gene editing approaches must demonstrate an exquisitely high level of fidelity for optimal safety. To demonstrate such an approach with Cas-CLOVER, multiple guide RNAs (gRNA) targeting the human KLKB1 gene were screened in human hepatoma cell lines to identify gRNA pairs with optimal editing. Next, we evaluated KLKB1 protein reduction in primary human hepatocytes (PHH) that were incubated with LNPs encapsulating Cas-CLOVER mRNA along with each gRNA pair. Lead candidate gRNAs showed robust KLKB1 editing in a dose-responsive manner, achieving >65% editing and >85% reduction in KLKB1 protein secreted into culture medium at 0.5 ug/mL (EC90). To evaluate Cas-CLOVER off-target activity, oligo incorporation by iGUIDE was carried out by a licensed contract research organization. In this assay, double-stranded oligodeoxyribonucleotides (dsODNs) were co-electroporated with Cas-CLOVER mRNA, along with our lead KLKB1 gRNA pair, in the Huh7 cell line, and candidate off-target sites were identified by Illumina next-generation sequencing. Off-target activity was assessed by amplicon-seq at the eight top sites nominated by iGUIDE. In PHHs treated with 0.5 ug/mL of Cas-CLOVER LNPs, off-target editing was detected in 3/8 sites at very low levels (<0.25%). Remarkably, this low level of off-target editing remained unchanged when PHHs were treated with 10-fold higher concentrations of Cas-CLOVER LNP. For further evaluation of our platform, we sought to determine KLKB1 editing efficiency and fidelity in a mouse model of liver humanization. TK-Nog mice engrafted with PHHs were treated with a single intravenous injection of an LNP formulation co-encapsulating Cas-CLOVER mRNA and our lead KLKB1 gRNA pair. Amplicon-seq analysis demonstrated that 60% of KLKB1 alleles in the liver were edited. Importantly, no off-target editing was detected among the top eight sites identified by iGUIDE, including the three off-target sites validated in cultured PHHs. Next, we evaluated efficacy and tissue specificity of our platform in wild type mice. C57BL/6 male and female mice were dosed with LNP encapsulating Cas-CLOVER mRNA and mouse Klkb1-targeting gRNAs. A single intravenous LNP injection achieved high Klkb1 editing (>50% of haploid genomes) in the liver and >80% reduction in serum pre-kallikrein levels. No Klkb1 editing was detected in gonads. In summary, these results highlight the efficacy and specificity of our high-fidelity Cas-CLOVER gene editing platform that enables targeted and therapeutically relevant kallikrein reduction in a fully non-viral manner. These data provide a promising foundation for the development of a highly specific gene editing therapy for HAE.

Early career researchers and mental health: Observational study of challenge and wellbeing.

Early career researchers (ECRs) are a strategic sector in the academic community because they represent a scientific incubator for future academic scholars. Recently, growing evidence suggests that relevant doctoral researchers work under elevated levels of stress and frustration and that this has a significant impact on their personal health and research output and their future career development. This study aimed to analyse the well-being and mental health within ECR, focusing on coping strategies for stress, and to contribute and exploit a conceptual framework tailored to the academic context considering the specifics and challenges of academia. Participants were 134 young early career academics (mean age = 30.6; SD = 4.38; range = 25-40 years) enrolled via institutional email. A 94-item questionnaire was created using Survey Monkey and distributed between October and December 2022. The survey assessment was based on three parts: (1) sociodemographic data, (2) psychological assessment, and (3) research skills design. Our findings highlighted a general trend toward negative psychological dimensions in ECRs: PhD students and research contracts appeared to be stressed, anxious, and depressed. Moreover, they had segmented ECRs: PhD students showed higher levels of depression, anxiety, and stress than research contracts, highlighting reduced positive outcomes in psychological dimensions, as well as lower ability to manage emotional experiences and then to be perseverant for long-term goals and motivation. Our findings highlight that mental health in ECRs is a challenge that needs to be addressed in academia. New and innovative ways of encouraging help-seeking must be developed and implemented to address policy changes, communication activities, training, and health-promotion activities through the circulation of experience, sharing actions, and strategies to foster healthy academics by raising awareness, implementing interventions, or engaging professionals concerning mental health in academia.

How Supervisors Can Support Doctoral Students to Publish and Not Perish in Academia

“Publish or perish” is a term used for the culture adopted in universities, whereby academic members of staff, typically although not exclusively on research and teaching contracts, are required to publish research. Minimum levels of quantity and quality may apply and these may be included in key performance indicators and annual staff reviews to ensure compliance. Whilst this culture has been reported in universities for nearly a century, most recently it has cascaded down to doctoral students who are increasingly expected to publish and otherwise disseminate research during their studies (i.e., research outside of that which is to be submitted in their thesis). This entry relates primarily to doctoral students in a UK setting and studying a monograph route (rather than a published papers submission) in the humanities. It further explores the role played by supervisors to help doctoral students to publish, and in turn the help and guidance supervisors need to offer as support. Many of the findings explored in this entry apply equally beyond the parameters noted above, and, as demonstrated in the literature, international students and institutions are facing similar issues.

Academic contributions to the development of evidence and policy systems: an EPPI Centre collective autoethnography

BackgroundEvidence for policy systems emerging around the world combine the fields of research synthesis, evidence-informed policy and public engagement with research. We conducted this retrospective collective autoethnography to understand the role of academics in developing such systems.MethodsWe constructed a timeline of EPPI Centre work and associated events since 1990. We employed: Transition Theory to reveal emerging and influential innovations; and Transformative Social Innovation theory to track their increasing depth, reach and embeddedness in research and policy organisations.FindingsThe EPPI Centre, alongside other small research units, collaborated with national and international organisations at the research-policy interface to incubate, spread and embed new ways of working with evidence and policy. Sustainable change arising from research-policy interactions was less about uptake and embedding of innovations, but more about co-developing and tailoring innovations with organisations to suit their missions and structures for creating new knowledge or using knowledge for decisions. Both spreading and embedding innovation relied on mutual learning that both accommodated and challenged established assumptions and values of collaborating organisations as they adapted to closer ways of working. The incubation, spread and embedding of innovations have been iterative, with new ways of working inspiring further innovation as they spread and embedded. Institutionalising evidence for policy required change in both institutions generating evidence and institutions developing policy.ConclusionsKey mechanisms for academic contributions to advancing evidence for policy were: contract research focusing attention at the research-policy interface; a willingness to work in unfamiliar fields; inclusive ways of working to move from conflict to consensus; and incentives and opportunities for reflection and consolidating learning.

Validation of low-volume sampling devices for pharmacokinetic analysis: technical and logistical challenges and solutions.

While low-volume sampling technologies offer numerous advantages over venipuncture, implementation in clinical trials poses technical and logistical challenges. Bioanalytical methods were validated for measuring the concentration of crenezumab and etrolizumab in dried blood samples collected using Mitra and Tasso-M20. The data generated demonstrate that the concentrations of crenezumab and etrolizumab in dried blood collected by either device could be determined using calibrators prepared in serum. Drug concentrations from dried blood were converted to serum concentrations using patient hematocrit levels. Contract Research Organizationexperience in sample handling and analysis allowed us to compare differences between various low-volume sampling technologies. This study evaluated challenges and presented potential solutions for use of different low-volume sampling technologies for pharmacokineticanalysis.

Kuršėnų Stasio Anglickio progimnazijos pedagogų komandinio darbo analizė

The pedagogues could realise the goals set to the educational organisation and achieve high and qualitative work results solely by acting in a professional and coherent manner. For this, the cooperation inside and outside the organisation is required. Therefore, it is important that the pedagogues of educational organisations acquire the basics of teamwork. Relevance of the topic is conveyed by means of a contract research in order to assess the teamwork in the educational organisation. Theoretical aspect of the article topic was revealed by analysis and generalization of the scientific literature by Lithuanian and foreign authors as well as by the latest articles in the research area. The „Team Plus“ testing method was selected for the diagnostic research. Upon analysis of the scientific sources it was established that the main and the most essential advantages of the teamwork include more qualitative work results, lower labour costs, more opportunities to reveal personal talents, openness to innovations, flexibility and ability to adapt to changes, and a better emotional state of the members. The conducted diagnostic research revealed that expression of the teamwork in the teams working in the educational organisation is more positive than negative. The obtained results of the research may be significant for development and formation of teams in educational organisations. Keywords: team, teamwork, teamwork analysis, educational organisation.

Organisational, legal and financial bases for scientific activity in higher education institutions of the Ministry of Internal Affairs of Ukraine: problems and solutions based on mathematical and statistical methodology

The work is devoted to the problem of improving the current legislation of Ukraine, in particular, in the area of organisation of contractual scientific research, financing of scientific activities, and testing the results of these activities for further implementation in the work of enterprises, institutions and organisations subordinated to the Ministry of Internal Affairs of Ukraine. The current legal framework on this issue has been analysed. Attention has been paid to the main practical problems and the main ways of solving them have been proposed, taking into account the use of mathematical calculations to establish criteria based on the proposed parameters. The statistics of trends in the development of publication activity of the institutions of the Ministry of Internal Affairs of Ukraine in the Scopus database have been considered.
 Despite a significant number of domestic publications on the main directions of development and prospects of science in the system of the Ministry of Internal Affairs of Ukraine, the relevance of funding scientific activities, improving material and technical support, and social protection of researchers of higher education institutions of the Ministry of Internal Affairs of Ukraine has at most been merely mentioned among the problems of modern Ukrainian science. Regarding the research of foreign scholars in the field of mechanisms of organisation and financing of scientific activities, it can be noted that the most common type of funding is grants, and therefore most studies are devoted to grant applications and their impact, as well as the problems of filling the funding budget, innovations in equitable funding, etc. Thus, the central issue of this article has not been studied.
 The solutions to several problematic issues in this area have been proposed, including: introduction of a new funding mechanism, in particular, under the conditions of contractual research; organisation of special research competitions for institutions of the Ministry of Internal Affairs of Ukraine; creation of the Unified State Register of Scientific Research in the system of the Ministry of Internal Affairs of Ukraine; development of the online platform “Science in the MIA System” to allow customers to submit applications for research and development work, monitor data by potential contractors and hold a transparent competition; introduce a new mechanism for testing and obtaining acts of implementation in scientific activities.
 The ideas and proposals for the introduction of new organisational and legal frameworks for scientific research in the system of the Ministry of Internal Affairs of Ukraine are an attempt to introduce a practical mechanism for the rational and most productive use of the scientific potential of departmental institutions and establishments to ensure the security of the State, protection of human rights and freedoms, combating crime, maintaining public safety and order, applying positive foreign experience in these areas, as well as the creation of innovative methods and technologies that can compete with similar achievements in the international scientific space.

Good clinical practices in the bioanalytical laboratory.

Despite the existence of good clinical practice guidelines, the way in which they are applied to the bioanalytical laboratory remains unclear. Aspects of patient confidentiality, informed consent and subject withdrawal; addressing unblinding associated with sample analysis, including repeat analysis and incurred sample reanalysis; or the differences in responsibilities between the sponsor and contract research organization are not articulated by the US FDA within the bioanalytical setting, and for most bioanalytical laboratories this remains a gap in their standard operating procedures. The aim of this article is to identify and clarify the aspects of the good clinical practices that are applicable to the bioanalytical laboratory when conducting bioanalysis with clinical samples, and to address potential gaps in the bioanalytical laboratory when it comes to clinical sample bioanalysis.

The Changing Landscape for Human Absorption, Metabolism, and Excretion: Practical Experiences From a Data Analysis of 500 Studies.

Coincidental with the intensified regulatory and industry focus on the design and conduct of human absorption, metabolism, and excretion (hAME) studies in the past 12 months, we have recently completed our 500th cohort involving radiolabeled test item administration to humans. Here, we build upon a recent industry white paper in this journal1 and share some of our own experiences as a Contract Research Organization based upon collaborations with numerous pharma companies and their differing approaches to design and timing, to add further context to the discussion regarding hAME studies and the pivotal role that drug metabolism and pharmacokinetics plays. In this article, we explore how both changing relationships within the industry and shifting regulatory guidelines are impacting strategies, and compare EU and US pre-study approval requirements, before evaluating the trends from over 500 studies conducted at our global facilities conducted over more than 30 years. We conclude with a review of how improved technical capabilities and strategies are influencing the design and conduct of hAME studies, before speculating on some of the driving factors which may shape the direction they take in the future.

The limits to upgrading and value capture in R&D global value chains: Indian and Chinese contract R&D firms in the integrated circuit design and pharmaceutical global value chains

This article analyzes the interaction between lead firms and Chinese and Indian contract research and development (R&D) firms in integrated circuit (IC) and chemistry-based pharmaceutical global value chains (GVCs) in order to delineate what factors influenced the upgrading and value capture outcomes of these contract R&D firms in the two sectors. There are five main findings. First, the two sectors differed significantly in terms of the upgrading of contract R&D firms’ activities and capabilities. More upgrading was found in chemistry-based pharmaceuticals than in ICs. Second, in both industries, lead firms utilized a range of strategies to control and limit upgrading and value capture by contract R&D firms. Third, level of R&D uncertainty (risk) and lead firms’ level of market access control informed the strategies of lead firms. Lead firms generally adopted strategies to limit upgrading by contract R&D firms except in two situations: where R&D risk was high so that lead firms wished to offload costly risks onto contract R&D firms and where lead firms had significant market access control to limit value capture by upgrading contract R&D firms. Fourth, the strategies to limit upgrading included minimizing the flow of information possible in modular linkages and discouraging IP development by contract R&D firms. Fifth, the lead firm strategies to limit value capture included limiting upgrading and thus any associated potential value capture, enhancing lead firm bargaining leverage, and controlling market access via established market channels and continual engagement with regulatory agencies in relevant markets.

SNMMI Clinical Trials Network Research Series for Technologists: Imaging Contract Research Organizations, Nuclear Medicine Technologists, and the Role They Play in Medical Imaging Research.

Clinical imaging research is a fast-growing, complex, and integral part of drug and therapy discovery and development. Research sponsors rely on outside vendors to manage their trials and deliver results they hope will demonstrate the efficacy of their product. Specialized vendors known as imaging contract research organizations have teams of highly trained and specialized professionals who lend their expertise to all aspects of imaging research management, of which nuclear medicine technologists are key team members. This article is part of the Clinical Trials Network Research Series for Technologists and will help provide an overview of an imaging research study from initiation to data delivery and the roles that nuclear medicine technologists and other imaging professionals play.