Safety Monitoring Committees Research Articles

Interactive medical and safety monitoring in clinical trials with clinDataReview: a validated and open-source reporting tool.

Continuous medical and safety monitoring of subject data during a clinical trial is a critical part of evaluating the safety of trial participants and as such is governed by protocol procedures and regulatory guidelines to meet the trial's intended objectives. We present an open-source validated graphical tool (clinDataReview R package) which provides access to the trial data with drill-down to individual patient profiles. The tool incorporates functionalities that facilitate detection of error and data inconsistencies requiring follow-up. It supports regular medical monitoring and oversight as well as safety monitoring committees with interactive tables and listings alongside graphical visualizations of the primary safety data in reports. An implementation example is given where the tool is used to deliver validated outputs following FDA/EMA guidelines. As such, this tool enables a more efficient, interactive, and reproducible review of safety data collected during an ongoing clinical trial.

In Pursuit of Meaningfulness in the Biomedical Literature – Notes from a Scrap Booklet

"guestProfessor Søren M. Bentzen is the Director of the Division of Biostatistics and Bioinformatics, Department of Epidemiology and Public Health, University of Maryland School of Medicine, USA, and he is also an Adjunct Professor of Radiobiology and Medical Physics, University of Copenhagen, Denmark. Dr. Bentzen received a Master of Sciences in physics and mathematics, a PhD in medical image analysis, and he is a doctor of medical science in quantitative clinical radiobiology. He was one of the leaders of the Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) initiative, and serves as a member of the Pediatric Normal Tissue Effects in the Clinic (PENTEC) steering committee. He was also a member of the American Society for Radiation Oncology (ASTRO) Task Forces to develop evidence-based guidelines on the appropriate fractionation for whole breast irradiation and for localized prostate cancer. He has served as chair or member of 17 (seven currently active) Independent Data and Safety Monitoring Committees or Trial Steering Committees and as co-chair for Translational Research for two Radiation Therapy Oncology Group (RTOG) phase III trials. He has published more than 500 original papers and book chapters, has presented >370 invited lectures, and he currently serves on 10 international cancer journal editorial boards. His main research interests include bioeffect modeling; biomathematics; applied biostatistics; clinical trial design; evidence-based medicine; late effects of radiotherapy; clinical radiobiology; integration of data from genomics, proteomics, and molecular imaging into novel therapeutic"

The disease-specific clinical trial network for primary ciliary dyskinesia: PCD-CTN.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients.

Heterologous SARS‐CoV‐2 vaccinations in patients with B‐cell lymphoid malignancies

Heterologous <scp>SARS‐CoV</scp>‐2 vaccinations in patients with B‐cell lymphoid malignancies

Development proposals of Human Research Protection Program.

China's ethics committees alone are unable to meet the growing need for human participant protection. Several scandals in recent years indicate weaknesses in the protection of human participants in China. The aim of the study is to summarize the status and problems of human research protection program in China and to explore its establishment proposals at national and hospital levels. To conduct literature retrieval, Chinese National Knowledge Infrastructure, Chinese Biomedical Document Database, and English databases Web of Science and PubMed were searched; laws, guidelines, and regulations were also searched on web by Google and Chinese search engine Baidu. No data were collected from human participants, and ethical review was not required. There are problems for China's Human Research Protection Program, such as weak relevant legal systems, insufficient administrative supervision, and incompetent ethics committee capacities. To fully protect human participants, China should promote the development of Human Research Protection Program, which can formulate ethics-related laws, improve regulations for the protection of the safety and rights of human participants, strengthen supervision, and enforce compensation for human participants. Owing to the frequency with which human participants are recruited in hospitals in China, hospitals can utilize existing ethics committees and establish data and safety monitoring committees, quality control, fund and contract management, and conflict of interest management offices. As a growing program, it remains necessary to learn from the experience of developed countries with high ethics standards and reformulate them to fit China's conditions to explore potential future development. The program will also be an experience for other developing countries. Human Research Protection Program can strengthen communication and coordination among various hospital departments to effectively protect the rights and welfare of human participants.

Anti-CD20 immunosuppressive disease-modifying therapies and COVID-19

Anti-CD20 immunosuppressive disease-modifying therapies and COVID-19

Ethical and research governance approval across Europe: Experiences from three European palliative care studies

Background: Research requires high-quality ethical and governance scrutiny and approval. However, when research is conducted across different countries, this can cause challenges due to the differing ethico-legal framework requirements of ethical boards. There is no specific guidance for research which does not involve non-medicinal products. Aim: To describe and address differences in ethical and research governance procedures applied by research ethics committees for non-pharmaceutical palliative care studies including adult participants in collaborative European studies. Design: An online survey analysed using descriptive statistics. Setting/participants: Eighteen principal investigators in 11 countries conducting one of three European-funded studies. Results: There was variation in practice including whether ethical approval was required. The time to gain full approvals differed with the United Kingdom having governance procedures that took the longest time. Written consent was not required in all countries nor were data safety monitoring committees for trials. There were additional differences in relation to other data management issues. Conclusion: Researchers need to take the differences in research approval procedures into account when planning studies. Future research is needed to establish European-wide recommendations for policy and practice that dovetail ethical procedures and enhance transnational research collaborations.

Integrating Parents in Neonatal and Pediatric Research

Background: Parents and their infants are the beneficiaries of neonatal and pediatric research, but in the past they have been excluded from most stages of research projects. As a result, many projects may fail to produce the most worthwhile information for parents and families. Lately, veteran resource parents and patients have been increasingly integrated in research initiatives. Methods: Benchmarking of neonatal and pediatric research initiatives where resource parents and/or ex neonatal patients have helped to optimize pediatric research. We review ways in which resource parents/patients can be involved in research, with examples and practical ideas of how to proceed. Results: Resource parents/patients can be collaborators in research and be integrated in many steps: prioritizing research projects, designing trials, determining the outcomes of interest, ethics review, developing and improving consent procedures, collection and interpretation of data, participation in data safety monitoring committees, publication of results, and presentation to peer groups. Some of the strategies for integration of stakeholders in clinical research are more complex, may involve risk and require more training than others. Conclusion: We suggest that groups wanting to involve parents in their research endeavors start with simpler tasks that entail less risk and develop teams of resource parents who have differing interests and abilities. Quality control of programs is essential, such as frequently giving and obtaining feedback from resource parents/patients and researchers. In the future, integration of resource parents/patients into every step of clinical research will be essential to ensure that parent and family important outcomes are examined.

University of Pennsylvania 10th annual conference on statistical issues in clinical trials: Current issues regarding data and safety monitoring committees in clinical trials (morning panel session).

University of Pennsylvania 10th annual conference on statistical issues in clinical trials: Current issues regarding data and safety monitoring committees in clinical trials (morning panel session).

University of Pennsylvania 10th annual conference on statistical issues in clinical trials: Current issues regarding data and safety monitoring committees in clinical trials (afternoon panel session).

University of Pennsylvania 10th annual conference on statistical issues in clinical trials: Current issues regarding data and safety monitoring committees in clinical trials (afternoon panel session).

Proceedings of the University of Pennsylvania 10th annual conference on statistical issues in clinical trials: Current issues regarding Data and Safety Monitoring Committees in clinical trials

Proceedings of the University of Pennsylvania 10th annual conference on statistical issues in clinical trials: Current issues regarding Data and Safety Monitoring Committees in clinical trials

Jay Herson. Data and Safety Monitoring Committees in Clinical Trials, 2nd Edition. Boca Raton: CRC Press

Jay Herson. Data and Safety Monitoring Committees in Clinical Trials, 2nd Edition. Boca Raton: CRC Press

Data and Safety Monitoring Committees in Clinical Trials

The book by Dr. Herson is written amazingly well. The book concentrates on pharmaceutical industry-sponsored confirmatory clinical trials and can serve as excellent sources of knowledge for all the...

Lessons learnt from enrolment and follow up of pregnant women and their infants in clinical trials in South Africa, a low-middle income country

IntroductionInfectious causes are a significant contributor to morbidity and mortality in neonates and young infants. Immunization of pregnant women to protect the mother and/or her infant is gaining momentum due to the benefits of this strategy demonstrated in numerous implemented strategies (Maternal and Neonatal Tetanus Elimination Initiative) and clinical trials.Reluctance by regulators, participants and healthcare providers to include pregnant women in clinical trials is considerable, but reducing. Infectious disease burden, and therefore need for interventions to reduce morbidity and mortality in mothers and infants, is highest in low-middle income countries (LMIC), however, reliable background data on adverse pregnancy outcomes and lack of experience in clinical trials and community opinions on immunization during pregnancy are not well documented. MethodsWe used our experiences in conducting two clinical studies in pregnant women in South Africa to illustrate the challenges experienced and lessons learnt which may benefit others working in the maternal immunization field. ResultsAccurate gestational age assessment, which is essential for clinical trials, is challenging in LMIC due to limited access to early ultrasound examinations, and unreliable assessment by history (last menstrual period date) and physical examination (symphyseal-fundal height).Concomitant administration of recommended vaccines has previously been avoided in clinical trials; however, this limitation could impact the potentially beneficial interventions that participants can access during antenatal care.Women in LMIC have a higher burden of concomitant illnesses (e.g. HIV infection, malaria and anaemia) and adverse pregnancy outcomes (e.g. stillbirth) than pregnant women in higher income countries. Availability of local data is essential for safety monitoring committees to identify vaccine-related adverse event triggers. ConclusionImmunization of pregnant women to reduce disease burden in them and their infants is promising, and women in high-risk settings should be included in trials (Clinical trial registry number: ‘Study A’: NCT01193920, ‘Study B’: NCT01888471).

Meta-analysis of intracranial hemorrhage in acute coronary syndromes: incidence, predictors, and clinical outcomes.

BackgroundLittle is known about the incidence, predictors, or outcomes of intracranial hemorrhage (ICH) in patients with non–ST-segment elevation acute coronary syndromes (NSTE ACS). We aimed to determine the incidence and timing of ICH, characterize the location of ICH, and identify independent baseline predictors of ICH in NSTE ACS patients.Methods and ResultsWe pooled patient-level data from 4 contemporary antithrombotic therapy trials. Multivariable modeling identified independent predictors of ICH. ICHs were adjudicated by a clinical events committee. Of 37 815 patients, 135 (0.4%) had an ICH. The median (25th, 75th percentiles) follow-up was 332 (184, 434) days but differed across trials. Locations of ICH were intracerebral (50%), subdural (31%), subarachnoid (18.5%), and intraventricular (11%). Independent predictors of ICH were older age (HR per 10 years, 1.61; 95% CI, 1.35 to 1.91); prior stroke/transient ischemic attack; HR, 1.95; 95% CI, 1.14 to 3.35), higher systolic blood pressure; HR per 10 mm Hg increase, 1.09; 95% CI, 1.01 to 1.18), and larger number of antithrombotic agents (HR per each additional agent, 2.06; 95% CI, 1.49 to 2.84). Of all ICHs, 45 (33%) were fatal.ConclusionsIn patients with NSTE ACS enrolled in recent clinical trials of antithrombotic therapies, ICH was uncommon. Patients with older age, prior transient ischemic attack/stroke, higher systolic blood pressure, or larger number of antithrombotic agents were at increased risk. One-third of patients with ICH died. These data may be useful to trialists and data and safety monitoring committees for trial conduct and monitoring.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov/. Unique identifiers: TRACER: NCT00527943, PLATO: NCT00391872, APPRAISE-2: NCT00831441, TRILOGY ACS: NCT00699998.

Should Sponsors and DSMBs Share Interim Results Across Trials?

Increasing numbers of multinational clinical trials have generated new ethical obligations of research sponsors and their DSMBs. Although sponsors and DSMBs clearly have ethical obligations to protect subjects in their trials, future patients, and the integrity of their trial, the obligations they have to protect subjects in other trials have been overlooked. When interim results from clinical trials can significantly affect the conduct of other trials and the welfare of the subjects in those trials, sponsors and DSMBs may have obligations to disclose results to the relevant parties. We propose that sponsors and DSMBs routinely work together in advance to develop a plan for disclosing relevant information in cases where it is necessary to protect the welfare of subjects in other trials. Channels of communication between sponsors, DSMBs, IRBs, and others involved in similar and concurrent trials will better protect both research participants and the integrity of the research enterprise.

Data and safety monitoring committees in clinical trials, Herson J (2009) ISBN: 9781420070378; 173 pages + xviii; £54.99, $89.95 Chapman and Hall/CRC;http://www.crcpress.com

Data and safety monitoring committees in clinical trials, Herson J (2009) <i>ISBN: 9781420070378; 173 pages + xviii; £54.99, $89.95 Chapman and Hall/CRC;</i>http://www.crcpress.com

Data and Safety Monitoring Committees in Clinical Trials

Data and Safety Monitoring Committees in Clinical Trials

Data and Safety Monitoring Committees in Clinical Trials by HERSON, J.

Data and Safety Monitoring Committees in Clinical Trials by HERSON, J.

Results of the Avonex Combination Trial (ACT) in relapsing-remitting MS

To assess the safety, tolerability, and efficacy of interferon beta-1a (IFNbeta-1a) combined with methotrexate (MTX), i.v. methylprednisolone (IVMP), or both in patients with relapsing-remitting multiple sclerosis (RRMS) with continued disease activity on IFNbeta-1a monotherapy. Eligibility criteria included RRMS, Expanded Disability Status Scale score 0-5.5, and > or = 1 relapse or gadolinium-enhancing MRI lesion in the prior year on IFNbeta-1a monotherapy. Participants continued weekly IFNbeta-1a 30 microg i.m. and were randomized in a 2 x 2 factorial design to adjunctive weekly placebo or MTX 20 mg p.o., with or without bimonthly IVMP 1,000 mg/day for 3 days. The primary endpoint was new or enlarged T2 lesion number at month 12 vs baseline. The study was industry-supported, collaboratively designed, and governed by an investigator Steering Committee with independent Advisory and Data Safety Monitoring committees. Study operations, MRI analyses, and aggregated data were managed by an academic coordinating center. The 313 participants had clinical and MRI characteristics typical of RRMS. Combinations of IFNbeta-1a with MTX or IVMP were generally safe and well tolerated. Although trends suggesting modest benefit were seen for some outcomes for IVMP, the results did not demonstrate significant benefit for either adjunctive therapy. The data suggested IVMP reduced anti-IFNbeta neutralizing antibody titers. This trial did not demonstrate benefit of adding low-dose oral methotrexate or every other month IV methylprednisolone to interferon beta-1a in relapsing-remitting multiple sclerosis.