Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial

Background: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Findings: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar. Interpretation: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status

Information systems in clinical research : categorization and evaluation of information systems and development of a guide for choosing the appropriate information system

Διπλωματική εργασία--Πανεπιστήμιο Μακεδονίας, Θεσσαλονίκη, 2019.The development of information systems used in clinical research is constantly increasing, as their advantages are widely acknowledged. Although many researchers have introduced information systems which can be used during a clinical study’s process, a scarcity of information systems accommodating the complete process has been detected. Based on this finding, twenty-three (23) information systems and ontologies used in clinical research were retrieved, based on certain criteria. The information systems and ontologies were then categorized and evaluated based on categorization and evaluation tools. Finally, the result was the synthesis of the eligible-for-evaluation information systems and the development of a guide for choosing the appropriate information system during each step of a clinical trial; the data provided by each information system were identified. Unfortunately, some information systems and ontologies were excluded from the synthesis due to lack of information regarding the evaluation criteria. Therefore, future research should proceed with retrieving this information and developing a guide which will consider more information systems, especially for conducting observational studies

Risk management in clinical trials clinical research sites

RESUMO: Introdução: Com o aumento da complexidade e exigência dos estudos clínicos com intervenção, torna-se urgente melhorar o seu desempenho, alcançando o melhor resultado com menos recursos. A gestão de risco é crucial para o sucesso de um estudo e deve ser garantida por todas as partes envolvidas. Porém, é notória a falta de diretrizes e ferramentas desenvolvidas ou adaptadas especificamente para os centros de investigação clínica que permitam melhorar o seu desempenho através da implementação de medidas de mitigação. Objetivos: Os principais objetivos deste projeto de investigação são 1) avaliar as atuais metodologias de gestão de risco utilizadas pelos centros de investigação clínica portugueses e 2) desenvolver uma ferramenta que auxilie a priorização das ações nos centros com base nos processos mais críticos. Metodologia: Foi realizado um inquérito a 46 centros de investigação clínica portugueses identificados através do RNEC e da PtCRIN. Além disso, tendo por base o RACT da Transcelerate, foi desenvolvida uma ferramenta de gestão de risco, adaptada para a utilização pelos centros de investigação clínica. Resultados e Discussão: Os resultados do inquérito mostram que, embora 57% dos centros afirmem usar uma ferramenta de gestão de risco, apenas nove (19,6%) têm um instrumento que permite captar a análise de risco de forma sistemática. A ferramenta desenvolvida é simples, dinâmica e direcionada para as operações realizadas pelos centros de investigação. Espera-se que facilite a identificação de riscos bem como a sua priorização com base no seu impacto e probabilidade. Uma lista de possíveis ações de mitigação foi incluída. Conclusões: A implementação da ferramenta desenvolvida pode ter um impacto significativo no desempenho dos centros de investigação, apoiando a tomada de decisões e promovendo a eficiência. Este trabalho pretende ser um ponto de partida para mudar o paradigma dos estudos clínicos, incentivando um papel mais proativo na gestão das operações pelos centros de investigação e fomentando a competitividade de Portugal na captação de investimento.ABSTRACT: Background: With the clinical trials becoming more complex and resourcedemanding, it is necessary to improve performance, that is, to achieve the desired result with fewer resources. Effective risk management by each involved party is crucial to the success of a clinical trial. However, there is a lack of guidance and tools specifically developed or adapted to the use of clinical research sites. Such a tool will allow sites to take ownership of their responsibilities and drive their performance within the clinical trials, implementing measures to mitigate the risks. Aims: The main objectives of this research project are to 1) assess the current risk management methodologies used by Portuguese clinical research sites and 2) develop a tool that seeks to help clinical trials teams to prioritise their actions based on the most critical processes. Methodology: A survey, created to assess the risk management practices, was conducted among 46 Portuguese sites identified through RNEC and PtCRIN . Moreover, a risk management tool was developed based on Transcelerate’s RACT and adapted to the operations under clinical research sites' scope. Results and Discussion: The surveys’ answers show that, although 57% of sites affirmed to have a risk management tool, only nine sites (19.6%) have a structured tool or document to capture the analysis of risks systematically at the site level. A simple, dynamic and flexible risk management tool targeted to sites was developed. It is expected to facilitate risk identification and prioritisation according to its probability and impact. A detailed list of possible mitigations strategies was included in this tool. Conclusions: The developed tool's implementation may significantly impact the clinical trials’ performance by supporting decision-making and promoting efficiency. This work intends to be a starting point to change the clinical trials’ mindset by encouraging a more proactive role in managing the clinical trials operations at the site level and fostering the competitiveness of the Portuguese sites in attracting investment for clinical research

INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4) : study protocol for a randomized controlled trial

Background: Early pre-hospital initiation of blood pressure (BP) lowering could improve outcomes for patients with acute stroke, by reducing hematoma expansion in intracerebral hemorrhage (ICH), and time to reperfusion treatment and risk of intracranial hemorrhage in ischemic stroke (IS). We present the design of the fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4). Methods: A multi-center, ambulance-delivered, prospective, randomized, open-label, blinded endpoint (PROBE) assessed trial of pre-hospital BP lowering in 3116 hypertensive patients with suspected acute stroke at 50+ sites in China. Patients are randomized through a mobile phone digital system to intensive BP lowering to a target systolic BP of < 140 mmHg within 30 min, or guideline-recommended BP management according to local protocols. After the collection of in-hospital clinical and management data and 7-day outcomes, trained blinded assessors conduct telephone or face-to-face assessments of physical function and health-related quality of life in participants at 90 days. The primary outcome is the physical function on the modified Rankin scale at 90 days, analyzed as an ordinal outcome with 7 categories. The sample size was estimated to provide 90% power (α = 0.05) to detect a 22% reduction in the odds of a worse functional outcome using ordinal logistic regression. Discussion: INTERACT4 is a pragmatic clinical trial to provide reliable evidence on the effectiveness and safety of ambulance-delivered hyperacute BP lowering in patients with suspected acute stroke. Trial registration: ClinicalTrials.gov NCT03790800. Registered on 2 January 2019; Chinese Trial Registry ChiCTR1900020534. Registered on 7 January 2019. All items can be found in this protocol paper

Exploring data quality monitoring procedures in the clinical research setting: Insights from clinical studies

To learn about human health, clinical research studies are conducted. A substantial concern for all clinical research studies is the failure to collect, process and present good quality data. Poor data quality may stem from error. International guidelines have identified that it is an essential need to monitor study activity to ensure that the rights, safety and wellbeing of participants are protected. However, the guidelines provide limited insight on how to perform monitoring procedures including the nature and extent of monitoring needed to ensure quality. Without clear guidance, this leaves clinical researchers confused about the most appropriate quality assurance and control procedures. The central hypothesis of this thesis is that despite the wide variations, exploration and evaluation of appropriate data quality monitoring procedures in clinical research studies will provide guidance toward developing a “fit-for-use” data quality monitoring framework (DQMF). This hypothesis was tested in five key studies using an explanatory sequential design guided by the Data- Information-Knowledge-Wisdom (DIKW) model as the theoretical framework

Point-of-care testing and treatment of sexually transmitted infections to improve birth outcomes in high-burden, low-income settings: Study protocol for a cluster randomized crossover trial (the WANTAIM Trial, Papua New Guinea) [version 1; peer review: 1 approved, 1 approved with reservations]

Background: Chlamydia trachomatis , Neisseria gonorrhoeae , Trichomonas vaginalis and bacterial vaginosis have been associated with preterm birth and low birth weight, and are highly prevalent among pregnant women in many low- and middle-income settings. There is conflicting evidence on the potential benefits of screening and treating these infections in pregnancy. Newly available diagnostic technologies make it possible, for the first time, to conduct definitive field trials to fill this knowledge gap. The primary aim of this study is to evaluate whether antenatal point-of-care testing and immediate treatment of these curable sexually transmitted and genital infections (STIs) leads to reduction in preterm birth and low birth weight. Methods : The Women and Newborn Trial of Antenatal Interventions and Management (WANTAIM) is a cluster-randomised crossover trial in Papua New Guinea to compare point-of-care STI testing and immediate treatment with standard antenatal care (which includes the WHO-endorsed STI ‘syndromic’ management strategy based on clinical features alone without laboratory confirmation). The unit of randomisation is a primary health care facility and its catchment communities. The primary outcome is a composite measure of two events: the proportion of women and their newborns in each trial arm, who experience either preterm birth (delivery <37 completed weeks of gestation as determined by ultrasound) and/or low birth weight (<2500 g measured within 72 hours of birth). The trial will also evaluate neonatal outcomes, as well as the cost-effectiveness, acceptability and health system requirements of this strategy, compared with standard care. Conclusions: WANTAIM is the first randomised trial to evaluate the effectiveness, cost-effectiveness, acceptability and health system requirements of point-of-care STI testing and treatment to improve birth outcomes in high-burden settings. If the intervention is proven to have an impact, the trial will hasten access to these technologies and could improve maternal and neonatal health in high-burden settings worldwide. Registration: ISRCTN37134032

Estágio em gestão de dados clínicos numa clinical research organization

Mestrado em Biomedicina FarmacêuticaThe aim of this report is to describe the training activities carried out at the Data Management Sub-Unit of Eurotrials, Scientific Consultants, as part of the 2nd year of the Master’s Program in Pharmaceutical Medicine. This internship was focused on the development of skills and on gaining experience in Clinical Data Management activities. Over the course of this internship, I had the opportunity to build upon the knowledge obtained in the Bachelor’s Degree in Biomedical Sciences and in the Master’s Program in Pharmaceutical Medicine. Concepts, requirements and practices related to Clinical Data Management were explored and strengthened throghout. Furthermore, an unique perspective on the lifecycle of clinical research projects was obtained – that of a CRO. Besides the acquisition of theoretical knowledge, this training period was paramount for the development of a number of social and personal skills that contributed for my profissional growth within the host institution. This document begins by a description of the theoretical principles that set the ground for the Clinical Data Manager’s work. Then, the generic and specific training elements of the curricular training are detailed. After presenting my training activities, I discuss the various challenges I had to overcome during these 9 months. Finally, some personal remarks and conclusions are presented.Este relatório tem como objetivo descrever as atividades de estágio realizadas na Unidade de Gestão de Dados da Eurotrials, Consultores Científicos, como parte do 2º ano do Mestrado em Biomedicina Farmacêutica. Este estágio focou-se no desenvolvimento de competências e obtenção de experiência em atividades de Gestão de Dados Clínicos. No decurso do estágio tive oportunidade de complementar o conhecimento obtido na Licenciatura em Ciências Biomédicas e no Mestrado em Biomedicina Farmacêutica. Foram aprofundados e explorados os conceitos, requisitos e práticas inerentes à Gestão de Dados Clínicos e obteve-se uma visão única do ciclo de vida de um projeto de investigação clínica – a de uma CRO. Para além da aquisição de conhecimentos teóricos, este período de estágio foi fundamental para o desenvolvimento de um conjunto de aptidões sociais e pessoais que contribuíram para o meu crescimento profissional dentro da instituição de acolhimento. O presente documento começa por expôr os príncipios teóricos que servem de base à atividade do Gestor de Dados Clínicos. Seguidamente, são detalhados os componentes genéricos e específicos de treino adquiridos durante o período de estágio. Depois da apresentação das atividades de estágio, são discutidos os vários desafios enfrentados e é feito um balanço pessoal desta experiência

Evaluation of Capacity for Best Practice of Clinical Vaccine Research in Western Kenya

African institutions that perform health research need to continuously evaluate their practices in order to ensure compliance with international standards of good clinical practice (GCP). This mixed-methods study, undertaken at one clinical research site in Western Kenya, was an evaluation of GCP compliance at the site, research participants\u27 satisfaction with research procedures, and research participants\u27 comprehension of informed consent. The qualitative portion of the study involved audit of the site\u27s compliance with GCP standards. The quantitative portion was an assessment of participant satisfaction and informed consent comprehension, undertaken through interviews with a sample of 297 participants. Thematic analysis of the qualitative data showed that the site\u27s performance conformed with GCP standards. Descriptive statistical analysis of the quantitative data showed that the majority of study participants were content with study procedures. A majority understood those parts of the informed consent process related to study duration and purpose but not those parts of the informed consent process related to the purpose and benefits of the study. Univariate chi square analysis showed no statistically significant differences in the level of satisfaction by age, occupation, or level of education, and there were no statistically significant differences in the level of informed consent comprehension by duration in the study or staff levels of experience. Implications for positive social change include guiding future health research capacity-building efforts in Africa toward better compliance with GCP standards and development of higher quality of informed consent procedures