Landscape Of Clinical Research Research Articles

Current Trends in Neuroscience Clinical Research and Regulatory Landscape (P7-4.008)

Current Trends in Neuroscience Clinical Research and Regulatory Landscape (P7-4.008)

[Opportunities and challenges in an emerging interdisciplinary research field-cardio-oncology].

The field of oncology has made remarkable progress over the past two decades. With the aging of the population, the number of cancer survivors is increasing. At the same time, cancer therapy-related cardiovascular toxicity (CTR-CVT) has become an important cause that seriously affects the quality of life and survival of cancer patients. In this context, cardio-oncology, an emerging interdisciplinary field, emerged. The types and treatment strategies of oncological diseases are heterogeneous, and the management of cancer patients also requires the participation of multiple disciplines. Currently, there are still insufficient clinical research and evidence-based practice in the field of cardio-oncology, resulting in a lack of standardization in its diagnosis and treatment. Additionally, the training model of physicians in cardio-oncology is still being explored. This article provides a comprehensive exploration of the opportunities and challenges faced by physicians and researchers in the field of cardio-oncology. It also delves into the prevailing landscape of clinical research in China and outlines the future training model for physicians in cardio-oncology.

Clinical research stakeholders’ experiences of clinical research during COVID-19: a qualitative study

BackgroundThe COVID-19 pandemic created a complex high-risk clinical research environment with clinical research activities significantly impacted. Clinical research stakeholders adapted rapidly to new clinical practices; PPE, infection control policies, all while engaging with a more unwell patient demographic. The aim of this study is to explore the experiences of conducting clinical research during COVID-19 with clinical research stakeholders.MethodsThis qualitative study of semi-structured interviews conducted with clinical research stakeholders in an acute Hospital setting across a variety of disciplines; Consultant Geriatrician, Clinical Research Nurse, Occupational Therapy, Physiotherapy. Interviews were fully transcribed prior to reflexive thematic analysis. NVivo software was used to support data management and analysis.ResultsThree main themes were produced; (1) The challenging COVID-19 clinical research landscape, (2) COVID-19 clinical research communication barriers, and (3) Adaptations and learnings from clinical research during COVID-19.ConclusionsThis study explored the experiences of conducting clinical research during COVID-19 with clinical research stakeholders examining challenges faced and adaptations required. The findings inform, equip and support clinical research stakeholders in the event of future adverse public health events.

Clinical outcome assessment trends in clinical trials-Contrasting oncology and non-oncology trials.

Clinical outcome assessments (COAs) are key to patient-centered evaluation of novel interventions and supportive care. COAs are particularly informative in oncology where a focus on how patients feel and function is paramount, but their incorporation in trial outcomes have lagged that of traditional survival and tumor responses. To understand the trends of COA use in oncology and the impact of landmark efforts to promote COA use, we computationally surveyed oncology clinical trials in ClinicalTrials.gov comparing them to the rest of the clinical research landscape. Oncology trials were identified using medical subject heading neoplasm terms. Trials were searched for COA instrument names obtained from PROQOLID. Regression analyses assessed chronological and design-related trends. Eighteen percent of oncology interventional trials initiated 1985-2020 (N = 35,415) reported using one or more of 655 COA instruments. Eighty-four percent of the COA-using trials utilized patient-reported outcomes, with other COA categories used in 4-27% of these trials. Likelihood of COA use increased with progressing trial phase (OR = 1.30, p < 0.001), randomization (OR = 2.32, p < 0.001), use of data monitoring committees (OR = 1.26, p < 0.001), study of non-FDA-regulated interventions (OR = 1.23, p = 0.001), and in supportive care versus treatment-focused trials (OR = 2.94, p < 0.001). Twenty-six percent of non-oncology trials initiated 1985-2020 (N = 244,440) reported COA use; they had similar COA-use predictive factors as oncology trials. COA use increased linearly over time (R = 0.98, p < 0.001), with significant increases following several individual regulatory events. While COA use across clinical research has increased over time, there remains a need to further promote COA use particularly in early phase and treatment-focused oncology trials.

Characteristics and trends of globally registered malignant pleural mesothelioma clinical trials in the past 27 years.

e20544 Background: Malignant pleural mesothelioma (MPM), arising from the serosal lining of the thoracic cavity, is a rare malignancy with limited treatment options and very poor prognosis. Recent progress in immunotherapy and innovative devices have advanced treatment fields of MPM. To help investigators understand the landscape of MPM clinical research, characteristic and trends of globally registered trials in the past decades were analyzed in our study. Methods: This is a cross-sectional analysis of MPM trials registered on ClinicalTrials.gov between January 1996 and December 2022. Characteristics pertaining to trail phase, enrollment number, study design, type, funding source, age of population, trial purpose, and participating country were extracted, and chronological shifts were analyzed. Clinical trial variables were enumerated using descriptive statistics and categorical data were presented as frequencies and percentages. Chi-square trend analysis (Cochran–Armitage trend test) was used to evaluate the trend of MPM trials. Results: 267 registered MPM trials were analyzed involving 40 participating countries among which the United States, the United Kingdom, and Italy were top 3. 8.2% trials were phase 3 and 18.7% were randomized. 74 trials had publications by the December 2022. The trial purposes concerning surgery, radiotherapy, chemotherapy, target therapy, immunotherapy, photodynamic therapy, cryotherapy, tumor treating fields （TTF）and non-anticancer research accounted for 2.6%, 5.2%, 20.2%, 25.5%, 31.1%, 1.1%, 0.7%, 0.7% and 12.7% respectively. In the past 27 years, the numbers of chemotherapy and targeted therapy trials declined while immunotherapy trails steadily escalated (all above ptrend &lt; 0.05). There are no significant changes for the trends of each trial phase. 205 drug therapy trials involved 26 cytotoxic drugs, 44 targeted drugs and 11 immune checkpoint inhibitors and 34 other drugs. Pemetrexed-cisplatin with TTF and ipilimumab-nivolumab have changed the frontline treatment space while improvement for regulatory approvals has been far slower in salvage treatment, with the median overall survival all less than 11 months in phase 3 trials. There are no definitive trials that justify the use of predictive biomarkers for systemic therapy in MPM. Conclusions: Immunotherapy and TTF have reshaped the standard of care landscape over the past 27 years. With the enhanced understanding of molecular characteristics and mechanism of MPM, it is anticipated that ongoing immunotherapy combined with target therapy, chemotherapy or other novel treatment can improve the frontline and post-line therapeutic effect.

Abstract 21: Clinical Trials in Gastroesophageal Cancers: An Analysis of the Global Landscape of Interventional Trials From ClinicalTrials.gov

Abstract Purpose: This study aims to describe the global landscape of clinical research into interventions for gastroesophageal (GE) cancers, which are a leading cause of cancer morbidity and mortality worldwide. We examine trial characteristics, focusing on geographic distribution of trial sites, participation of low-and-middle-income countries (LMICs), and factors associated with premature trial termination. Methods: We queried ClinicalTrials.gov database to identify all completed or terminated Phase III interventional studies investigating GE cancers (esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastroesophageal junctional (GEJ) and gastric adenocarcinoma). All reported characteristics were extracted. Pearson’s chi-square and Fisher’s exact test were used to compare differences in completed and terminated trials. Multivariate logistic regression was used to determine predictors of termination. Results: A total of 179 trials were identified; 90% were therapeutic. Most included sites in Asia (61%), Europe (32%), and North America (23%); few included sites in South America (9%), Africa (4%), and Oceania (9%). 63% of trials included high-income countries (HICs) sites alone; only 7% included sites in lower-middle or low-income countries. Most (70%) focused exclusively on gastric or GEJ adenocarcinoma, 13% on EAC and ESCC, and 9% ESCC alone. 16% (n=29) of trials terminated, most due to accrual difficulties (n=13, 44%). In multivariate analysis, study site number, location, and eligible patient population emerged as predictors of termination. Trials conducted exclusively in the US were more likely to terminate (OR 7.22 [95% CI 1.59-32.69]). Conversely, trials conducted exclusively in LMICs were less likely to terminate (OR 0.04 [95% CI 0.01-0.59] v conducted in HIC alone). Studies on ESCC were more likely to terminate (OR 17.74 [95%CI 1.49-210.69]). Trial design characteristics, intervention characteristics, and funding sources were not associated with termination. Conclusion: Although 80% of GE malignancies occur in LMICs, trial activity disproportionately occurs in HICs. Few trials focus on EAC/ESCC despite being highly fatal, highlighting an unmet need. Geographic location of trial sites emerged as a predictor of trial termination, with studies involving LMICs sites less likely to terminate prematurely. This finding highlights the potential benefit of including LMICs in future clinical trials to advance research for these diseases. Citation Format: Ayo Falade, Oluwatayo Adeoye, Geoffrey Buckle. Clinical Trials in Gastroesophageal Cancers: An Analysis of the Global Landscape of Interventional Trials From ClinicalTrials.gov [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 21.

122 DIAMOND 2.0: Updating a Pioneering Digital Platform for Study Team Workforce Development

OBJECTIVES/GOALS: There is a critical need to provide quality training for study teams. Materials need to be flexible and available at the learner’s preferred time and format. DIAMOND was developed to provide nimble education offerings that respond to the changing landscape of clinical and translational research. METHODS/STUDY POPULATION: In 2018 four CTSA institutions (the University of Michigan, the Ohio State University, Rochester University, and Tufts University) collaborated to launch the DIAMOND portal. Developed as a CTSA-wide web-based platform, DIAMOND allows members of clinical and translational research teams to widely share and access training and education resources. In 2022 a MICHR-led update of DIAMOND used principles of user centered design to improve the platform. New features include updated search functions to quickly find and sort training materials, tagging training materials to the characteristics of a translational scientist, and development of user controlled customized playlists. RESULTS/ANTICIPATED RESULTS: DIAMOND currently includes 217 training resources developed by 30 CTSA hubs and private industry. The platform has over 600 page views per day from users across the U.S. and internationally. DIAMOND includes an easy-to-use form to upload new materials to the platform. Contributors are asked to include key words and select competency domains and characteristics of a translational scientist that apply to their materials. Other new features include tagging materials to streamline and improve search results, the ability to sort materials by competency domain or characteristics of a translational scientist, and the ability for users to create and share customized, personalized playlists. DISCUSSION/SIGNIFICANCE: DIAMOND is an important tool to support workforce development for study teams. Updates to the flexible digital platform meet the needs and preferences of adult learners and busy health professionals. Lessons learned from the design process and future plans for the platform will be explored.

Identifying obstacles hindering the conduct of academic-sponsored trials for drug repurposing on rare-diseases: an analysis of six use cases

BackgroundAcademic-sponsored trials for rare diseases face many challenges; the present paper identifies hurdles in the set-up of six multinational clinical trials for drug repurposing, as use cases.MethodsSix academic-sponsored multinational trials aiming to generate knowledge on rare diseases drug repurposing were used as examples to identify problems in their set-up. Coordinating investigators leading these trials provided feedback on hurdles linked to study, country, and site set up, on the basis of pre-identified categories established through the analysis of previous peer-reviewed publications.ResultsAdministrative burden and lack of harmonization for trial-site agreements were deemed as a major hurdle. Other main identified obstacles included the following: (1) complexity and restriction on the use of public funding, especially in a multinational set up, (2) drug supply, including procurement tendering rules and country-specific requirements for drug stability, and (3) lack of harmonization on regulatory requirements to get trial approvals.ConclusionA better knowledge of the non-commercial clinical research landscape and its challenges and requirements is needed to make drugs—especially those with less commercial gain—accessible to rare diseases patients. Better information about existing resources like research infrastructures, clinical research programs, and counseling mechanisms is needed to support and guide clinicians through the many challenges associated to the set-up of academic-sponsored multinational trials.

Drugs and convalescent plasma therapy for COVID-19: a survey of the interventional clinical studies in Italy after 1 year of pandemic

BackgroundThe 2019 novel coronavirus disease (COVID-19) pandemic has highlighted the importance of health research and fostered clinical research as never before. A huge number of clinical trials for potential COVID-19 interventions have been launched worldwide. Therefore, the effort of monitoring and characterizing the ongoing research portfolio of COVID-19 clinical trials has become crucial in order to fill evidence gaps that can arise, define research priorities and methodological issues, and eventually, formulate valuable recommendations for investigators and sponsors. The main purpose of the present work was to analyze the landscape of COVID-19 clinical research in Italy, by mapping and describing the characteristics of planned clinical trials investigating the role of drugs and convalescent plasma for treatment or prevention of COVID-19 disease.MethodsDuring an 11-month period between May 2020 and April 2021, we performed a survey of the Italian COVID-19 clinical trials on therapeutic and prophylactic drugs and convalescent plasma. Clinical trials registered in the Italian Medicines Agency (AIFA) and ClinicalTrials.gov websites were regularly monitored. In the present paper, we report an analysis of study design characteristics and other trial features at 6 April 2021.ResultsNinety-four clinical trials planned to be carried out in Italy were identified. Almost all of them (91%) had a therapeutic purpose; as for the study design, the majority of them adopted a parallel group (74%) and randomized (76%) design. Few of them were blinded (33%). Eight multiarm studies were identified, and two of them were multinational platform trials. Many therapeutic strategies were investigated, mostly following a drug repositioning therapeutic approach.ConclusionsOur study describes the characteristics of COVID-19 clinical trials planned to be carried out in Italy over about 1 year of pandemic emergency.High level quality clinical trials were identified, although some weaknesses in study design and replications of experimental interventions were observed, particularly in the early phase of the pandemic.Our findings provide a critical view of the clinical research strategies adopted for COVID-19 in Italy during the early phase of the pandemic. Further actions could include monitoring and follow-up of trial results and publications and focus on non-pharmacological research areas.

Ethical considerations around volunteer payments in a malaria human infection study in Kenya: an embedded empirical ethics study

Human Infection Studies (HIS) have emerged as an important research approach with the potential to fast track the global development of vaccines and treatments for infectious diseases, including in low resource settings. Given the high level of burdens involved in many HIS, particularly prolonged residency and biological sampling requirements, it can be challenging to identify levels of study payments that provide adequate compensation but avoid ‘undue’ levels of inducement to participate. Through this embedded ethics study, involving 97 healthy volunteers and other research stakeholders in a malaria HIS programme in Kenya, and using in-depth interviews, focus group discussions and observations during and after a malaria HIS, we give a grounded account of ethical issues emerging in relation to study payments in this setting. While careful community, national, international scientific and ethics review processes meant that risks of serious harm were highly unlikely, the levels of motivation to join HIS seen could raise concerns about study payments being too high. Particular value was placed on the reliability, rather than level, of study payment in this setting, where subsistence livelihoods are common. Study volunteers were generally clear about the study aims at the point of recruitment, and this knowledge was retained over a year later, although most reported experiencing more burdens than anticipated at enrolment. Strict study screening procedures, regular clinical and laboratory monitoring of volunteers, with prompt treatment with antimalarial at predetermined endpoints suggested that the risks of serious harm were highly unlikely. Ethical concerns emerged in relation to volunteers’ attempts to conceal symptoms, hoping to prolong residency periods and increase study payments; and volunteers making decisions that compromised important family relationships and personal values. Our findings support an interpretation that, although study volunteers were keen to join the study to access cash payments, they also paid attention to other features of the study and the general clinical research landscape, including levels of risk associated with study participation. Overall, our analysis shows that the ethical concerns emerging from the study payments can be addressed through practical measures, hinged on reducing burdens and strengthening communication, raising important issues for research policy and planning.

Nitrous oxide for the treatment of psychiatric disorders: A systematic review of the clinical trial landscape.

To systematically review published research studies and ongoing clinical trials investigating nitrous oxide (N2 O) in psychiatric disorders, providing an up-to-date snapshot of the clinical research landscape. A comprehensive literature search was conducted for studies published until June 2021 using the OVID databases (MEDLINE, Embase, APA PsycInfo) and the clinical trial registries (ClinicalTrials.gov, ICTRP). In total, five relevant published articles were identified, among which four investigated N2 O for depression. One single-dose randomized controlled trial (RCT) for treatment-resistant depression (TRD), one triple crossover RCT comparing 50% vs. 25% N2 O for TRD, and one repeated-dose RCT for major depressive disorder (MDD) suggest that N2 O has preliminary feasibility with rapid-acting effects on symptoms of depression. From the public registries, 10 relevant ongoing clinical trials were identified. They aim to explore the use of N2 O for MDD, post-traumatic stress disorder, bipolar disorder, obsessive-compulsive disorder, and suicidal ideation. To date, the typical treatment protocol parameters were a single session of 50% N2 O delivered for 60min, although the concentration of 25% is also being explored. Projected enrolment numbers for ongoing trials (M=55.0) were much higher than sample sizes for published studies (M=13.0), suggesting that there potentially will be more large-scale RCTs published in the next few years. Preliminary studies support the feasibility of administering N2 O for depression; however, appropriate blinding is a critical challenge. Larger-scale RCTs with repeated doses of N2 O and follow-up times beyond 1month are needed to confirm the feasibility, therapeutic efficacy, and sustainability of response.

Mapping Pediatric Oncology Clinical Trial Collaborative Groups on the Global Stage.

PURPOSEThe global pediatric oncology clinical research landscape, particularly in Central and South America, Africa, and Asia, which bear the highest burden of global childhood cancer cases, is less characterized in the literature. Review of how existing pediatric cancer clinical trial groups internationally have been formed and how their research goals have been pursued is critical for building global collaborative research and data-sharing efforts, in line with the WHO Global Initiative for Childhood Cancer.METHODSA narrative literature review of collaborative groups performing pediatric cancer clinical research in each continent was conducted. An inventory of research groups was assembled and reviewed by current pediatric cancer regional and continental leaders. Each group was narratively described with identification of common structural and research themes among consortia.RESULTSThere is wide variability in the structure, history, and goals of pediatric cancer clinical trial collaborative groups internationally. Several continental regions have longstanding endogenously-formed clinical trial groups that have developed and published numerous adapted treatment regimens to improve outcomes, whereas other regions have consortia focused on developing foundational database registry infrastructure supported by large multinational organizations or twinning relationships.CONCLUSIONThere cannot be a one-size-fits-all approach to increasing collaboration between international pediatric cancer clinical trial groups, as this requires a nuanced understanding of local stakeholders and resources necessary to form partnerships. Needs assessments, performed either by local consortia or in conjunction with international partners, have generated productive clinical trial infrastructure. To achieve the goals of the Global Initiative for Childhood Cancer, global partnerships must be sufficiently granular to account for the distinct needs of each collaborating group and should incorporate grassroots approaches, robust twinning relationships, and implementation science.

The landscape of clinical trials research in inherited eye disease

AbstractPurposeRecent increased understanding of molecular and genetic causes of many inherited eye diseases opens the way to novel therapeutic interventions. The key to drug discovery is in delivering precision targets for treatment that open a therapeutic index over toxicity. We set out to define what type of treatments are emerging, against what targets, and how the trial pipeline is progressing.MethodsWe selected 8 major inherited eye diseases where the primary genetic cause has been established, to identify potential therapeutic target. Data scrutiny and analysis of the clinical trials database on clinicaltrials.gov was performed from 20/3/2021 to 30/4/2021.ResultsWe identified 92 trials, of which 33 trials (35.9%) are ongoing or recruiting. Of these 92 trials, 44 trials (47.8%) are completed (but only 14 (31.8%) of these have posted results). 15 trials (16.3%) have an unknown status or are terminated. 52% of the trials are in North America, followed by 29% in Europe and 19% in other parts of the world. Drug intervention accounts for 44% of the trials and 20% are classified as biological intervention. Gene therapy accounts for 13% and 1% are combination intervention trials. Device intervention accounts for 9% with procedure intervention e.g., stem cell transplantation accounting for further 8%. The remaining 5% is classified as others intervention e.g. diet. Some of the trials are in more than 1 phases; 34 of the trials have phase 1 included, 37 trials have phase 2 included and only 10 trials have phase 3 included and this declines to only 1 trial with phase 4 included(a total decrease of 90%). Out of the 15 terminated or status unknown trials, 5 trials are in both phase 1 &amp; 2, 3 trials are only in phase 1, 4 trials are only in phase 2 and 1 trial is only in phase 3. 2 trials are N/A due to device intervention. Combining the data, 8 trials with phase 1 testing included are terminated or with unknown status; 9 trials with phase 2 testing included are terminated or with unknown status. 1 trial with phase 3 testing included is terminated.ConclusionsCurrent and future clinical trials in the genetic eye diseases with molecular targets identified have a promising future but the pipeline of translation from phase 1, 2 trials to phase 3 is slow. Nevertheless, the last 5 years has seen a significant increase in therapeutic trials in inherited eye diseases.

Characteristics and trends of globally registered glioma clinical trials in the past 16 years.

Background:Advancement in the treatment of glioma has been vacant since temozolomide has proved its therapeutic value in glioblastoma in 2005.Aim:To help investigators understand the landscape of glioma clinical research, we analyzed the characteristics and trends of globally registered glioma trials in the past decades.Methods:This is a cross-sectional analysis of glioma trials registered on ClinicalTrials.gov between January 2006 and December 2021. Characteristics regarding phase, enrollment number, study design and type, funding source, tumor site, pathology, patient status, age of population, trial purpose, and participating country were abstracted, and chronological shifts were analyzed.Results:There were 1531 registered glioma trials involved 58 participating countries. The trial purpose concerning surgery, radiotherapy, chemotherapy, targeted therapy, tumor-treating fields, immunotherapy, other antiglioma therapy and non-antiglioma research trial accounts for 3.5%, 6.5%, 9.5%, 28.9%, 2.0%, 16.4%, 12.5%, and 20.6%, respectively. In the past 16 years, the numbers of chemotherapy and targeted therapy trials declined; tumor-treating fields and immune checkpoint inhibitor application trials sprang at the latter half period; Immunotherapy, other antiglioma therapy and non-antiglioma research trials escalated (all above ptrend < 0.005). The trend also showed the phased trials registered diminishingly and that the trials which focused on glioblastoma registered incrementally (those two ptrend < 0.05). Among 784 drug therapy trials, it was included 45 cytotoxic drugs, 186 targeted drugs, 19 immune checkpoint inhibitors, 78 other drugs, and five immunomodulatory drugs. Two trials belonged to Bayesian adaptive randomized design. By the end of December 2021, 309 trials had publications. Only everolimus and tumor-treating fields exhibited meaningful survival benefit in specific glioma patients in phase 3 trials.Conclusion:Meaningful effective treatments regarding drugs or methods for glioma were difficult to be found. Bayesian adaptive platform trials may accelerate clinical research in glioma. Development of novel treatment modalities for glioma is still challenged.

Characteristics of registered clinical trials assessing strategies of medication errors prevention. An unusual cross sectional analysis.

ClinicalTrials.gov is the oldest and largest of these registries. Through this, the researchers can explore and monitor the clinical research landscape. In the last decades, the number of Medline-indexed publications on adverse events and medication errors have increased exponentially. The aims were to define the prevalence of clinical trials that have as outcome the medication errors and to describe the characteristics of these trials, including their distribution across countries, and publication rate. A cross-sectional analysis of all clinical trials reporting as primary outcome medication errors identified through ClincialTrials.gov. Among 5.881 trials, only 1,68% focused on intervention to improve medication safety process and prevent medication errors. 25,3% of clinical trials included had their primary outcome changed (p= ,005). Recording study results in ClinicalTrials.gov was associated with trials that had their primary outcome changed (OR: ,060; 95% C.I.: ,007 - ,541). Only few interventional trials were totally compliant with the ICMJE policy. For all trials completed in our sample, in mean 7,44 months (median: 12 months) elapsed between study completion and the first publication in Medline showing the trial's identification number. This study demonstrates several strengths of using ClinicalTrials.gov to track intervention to improve medication safety process. It is unknown how many trials are designed to focus on medication errors. However, 1,68% of trials focused on intervention to improve medication safety process.

[Progress of Immune Checkpoint Inhibitors 
in the Treatment of Advanced Pulmonary Neuroendocrine Tumors].

肺神经内分泌肿瘤（pulmonary neuroendocrine tumors, PNETs）是一种源于肺神经内分泌细胞的上皮性肿瘤，约占原发性肺肿瘤的20%，包括典型类癌、非典型类癌、小细胞癌和大细胞神经内分泌癌。这四类PNETs之间的形态学和临床特征具有较大的异质性。免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）已在多种实体瘤中被证实具有很强的抗肿瘤活性。晚期PNETs治疗方案在过去十年内已有了很大的发展，但ICIs在PNETs领域的应用才刚刚起步。本文主要阐述目前PNETs中ICIs临床试验和研究的格局以及免疫检查点抑制剂治疗相关标志物的现状。

The right time for senescence.

Cellular senescence is a highly complex and programmed cellular state with diverse and, at times, conflicting physiological and pathological roles across the lifespan of an organism. Initially considered a cell culture artifact, senescence evolved from an age-related circumstance to an intricate cellular defense mechanism in response to stress, implicated in a wide spectrum of biological processes like tissue remodelling, injury and cancer. The development of new tools to study senescence in vivo paved the way to uncover its functional roles in various frameworks, which are sometimes hard to reconcile. Here, we review the functional impact of senescent cells on different organismal contexts. We provide updated insights on the role of senescent cells in tissue repair and regeneration, in which they essentially modulate the levels of fibrosis and inflammation, discussing how “time” seems to be the key maestro of their effects. Finally, we overview the current clinical research landscape to target senescent cells and contemplate its repercussions on this fast-evolving field.

Personalized and long-term electronic informed consent in clinical research: stakeholder views

BackgroundThe landscape of clinical research has evolved over the past decade. With technological advances, the practice of using electronic informed consent (eIC) has emerged. However, a number of challenges hinder the successful and widespread deployment of eIC in clinical research. Therefore, we aimed to investigate the views of various stakeholders on the potential advantages and challenges of eIC.MethodsSemi-structured interviews were conducted with 39 participants from 5 stakeholder groups from across 11 European countries. The stakeholder groups included physicians, patient organization representatives, regulator representatives, ethics committee members, and pharmaceutical industry representatives, and all were involved in clinical research. Interviews were analyzed using the framework method.ResultsInterviewees identified that a powerful feature of eIC is its personalized approach as it may increase participant empowerment. However, they identified several ethical and practical challenges, such as ensuring research participants are not overloaded with information and offering the same options to research participants who would prefer a paper-based informed consent rather than eIC. According to the interviewees, eIC has the potential to establish efficient long-term interactions between the research participants and the research team in order to keep the participants informed during and after the study. Interviewees emphasized that a personal interaction with the research team is of utmost importance and this cannot be replaced by an electronic platform. In addition, interviewees across the stakeholder groups supported the idea of having a harmonized eIC approach across the European Member States.ConclusionsInterviewees reported a range of design and implementation challenges which needs to be overcome to foster innovation in informing research participants and obtaining their consent electronically. It was considered important that the implementation of eIC runs alongside the face-to-face contact between research participants and the research team. Moreover, interviewees expect that eIC could offer the opportunity to enable a personalized approach and to strengthen continuous communication over time. If successfully implemented, eIC may facilitate the engagement of research participants in clinical research.

The paediatric cancer clinical research landscape in Spain: a 13-year multicentre experience of the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP).

Early phase trials are crucial in developing innovative effective agents for childhood malignancies. We report the activity in early phase paediatric oncology trials in Spain from its beginning to the present time and incorporate longitudinal data to evaluate the trends in trial characteristics and recruitment rates. Members of SEHOP were contacted to obtain information about the open trials at their institutions. The study period was split into two equal periods for analysis: 2007-2013 and 2014-2020. Eighty-one trials and two molecular platforms have been initiated. The number of trials has increased over the time of the study for all tumour types, with a predominance of trials available for solid tumours (66%). The number of trials addressed to tumours harbouring specific molecular alterations has doubled during the second period. The proportion of industry-sponsored compared to academic trials has increased over the same years. A total of 565 children and adolescents were included, with an increasing trend over the study period. For international trials, the median time between the first country study approval and the Spanish competent authority approval was 2months (IQR 0-6.5). Fourteen out of 81 trials were sponsored by Spanish academic institutions. The number of available trials, and the number of participating patients, has increased in Spain from 2007. Studies focused on molecular-specific targets are now being implemented. Barriers to accessing new drugs for all ranges of age and cancer diseases remain. Additionally, opportunities to improve academic research are still required in Spain.

Oncology clinical research landscape in Middle East and North Africa (MENA) region: Challenges and proposed solutions.

e13567 Background: Similar to other regions of the world, cancer incidence in Middle East and North Africa (MENA) is rising, which has been attributed to increased life expectancy and adoption of western lifestyle habits. Conducting clinical trials in the region is important to assess efficacy and safety of oncology medications in the specific population (response to drugs can be impacted by genetics, demographics and lifestyle factors). Although the MENA comprises around 5% of the global population, the region only participates in approximately 3% of clinical trials worldwide. It is important to understand the challenges in conducting trials in MENA and identify strategies to overcome these in order to facilitate advances in clinical research in the region. Methods: A literature review was conducted (via e.g. PubMed and ClinicalTrials.gov) to understand the current oncology clinical research landscape in MENA (from Jan 2015-Dec 2020), with the aim of identifying key challenges and potential strategies to overcome these. Results: Conduct of oncology clinical trials (phases 1-4) has risen in recent years in MENA, from 47 trials in 2015 to 53 trials in 2020. Despite the presence of various research-favourable factors in MENA (large patient pool, high demand for medication, lower clinical trial operational costs, compliance with ICH-GCP standards), the region still falls behind other countries in clinical research. Key factors identified as challenges in conducting clinical trials in MENA include the research infrastructure and patient awareness/understanding of research. We propose the following strategies to support the advancement of clinical research in the region: (1) Enhance research infrastructure through bolstering national clinical research networks and supporting collaboration between healthcare institutes, academia and the pharma industry; (2) Diversify methods of patient engagement (e.g. patient advisory groups and social media networks) and provide education on pros/cons of participating in research to raise awareness and improve trial participation rates; and (3) Improve availability of comprehensive oncology registries to enhance understanding of disease burden and support clinical research. Conclusions: The conduct of oncology clinical trials in MENA is increasing, yet the region is still under-represented in the global clinical trial market, despite its significant potential. The advancement of clinical research in the region will require a multi-level approach, involving collaboration between multiple stakeholders including the pharma industry, regulators, government, and healthcare professionals.