The Australasian Radiopharmaceutical Trials Network: Clinical Trials, Evidence, and Opportunity.
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ABSTRACT:
SUBMITTER: Francis RJ
PROVIDER: S-EPMC8729868 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Chronic kidney disease is a major public health problem globally. Despite this, there are fewer high-quality, high-impact clinical trials in nephrology than other internal medicine specialties, which has led to large gaps in evidence. To address this deficiency, the Australasian Kidney Trials Network, a Collaborative Research Group, was formed in 2005. Since then, the Network has provided infrastructure and expertise to conduct patient-focused high-quality, investigator-initiated clinical trials in nephrology. The Network has not only been successful in engaging the nephrology community in Australia and New Zealand but also in forming collaborations with leading researchers from other countries. This article describes the establishment, development, and functions of the Network. The article also discusses the current and future funding strategies to ensure uninterrupted conduct of much needed clinical trials in nephrology to improve the outcomes of patients affected by kidney diseases with cost-effective interventions.
| S-EPMC3898483 | biostudies-literature
Project description:Chemotherapy is one of the most established and effective treatments for almost all types of cancer. However, the elevated toxicity due to the non-tumor-associated effects, development of secondary malignancies, infertility, radiation-induced fibrosis and resistance to treatment limit the effectiveness and safety of treatment. In addition, these multiple factors significantly impact quality of life. Over the last decades, our increased understanding of cancer epigenetics has led to new therapeutic approaches and the promise of improved patient outcomes. Epigenetic alterations are commonly found in cancer, especially the increased expression and activity of histone deacetylases (HDACs). Dysregulation of HDACs are critical to the development and progression of the majority of tumors. Hence, HDACs inhibitors (HDACis) were developed and now represent a very promising treatment strategy. The use of HDACis as monotherapy has shown very positive pre-clinical results, but clinical trials have had only limited success. However, combinatorial regimens with other cancer drugs have shown synergistic effects both in pre-clinical and clinical studies. At the same time, these combinations have enhanced the efficacy, reduced the toxicity and tumor resistance to therapy. In this review, we will examine examples of HDACis used in combination with other cancer drugs and highlight the synergistic effects observed in recent preclinical and clinical studies.
| S-EPMC7516260 | biostudies-literature
Project description:Rare cancers account for 27% of neoplasms diagnosed each year, and 25% of cancer-related deaths in the United States. However, rare cancers show some of the highest response rates to targeted therapies, probably due to identification of oncogenic drivers with little interpatient variability. Although the low incidence of rare cancers makes large-scale randomized trials involving single histologies difficult to perform, drugs have been successfully developed in rare cancers using clinical trial designs that combine microscopic histologies. Such trials are being pursued within the National Clinical Trials Network (NCTN), which possesses unique qualifications to perform widespread molecular screening of tumors for patient enrollment onto therapeutic clinical trials. When larger clinical trials are needed to determine optimum treatment strategies in rare cancers, the NCTN's broad reach in North America and internationally, and their ability to partner with both United States-based and international research organizations, can make these challenging studies feasible.
| S-EPMC4673983 | biostudies-other
Project description:Radiopharmaceutical therapy (RPT) is emerging as a safe and effective targeted approach to treating many types of cancer. In RPT, radiation is systemically or locally delivered using pharmaceuticals that either bind preferentially to cancer cells or accumulate by physiological mechanisms. Almost all radionuclides used in RPT emit photons that can be imaged, enabling non-invasive visualization of the biodistribution of the therapeutic agent. Compared with almost all other systemic cancer treatment options, RPT has shown efficacy with minimal toxicity. With the recent FDA approval of several RPT agents, the remarkable potential of this treatment is now being recognized. This Review covers the fundamental properties, clinical development and associated challenges of RPT.
| S-EPMC7390460 | biostudies-literature
Project description:BackgroundStakeholders across the clinical trial enterprise have expressed concern that the current clinical trial enterprise is unsustainable. The cost and complexity of trials have continued to increase, threatening our ability to generate reliable evidence essential for making appropriate decisions concerning the benefits and harms associated with clinical interventions. Overcoming this inefficiency rests on improving protocol design, trial planning, and quality oversight.MethodsThe Clinical Trials Transformation Initiative convened a project to evaluate methods to prospectively build quality into the scientific and operational design of clinical trials ("quality-by-design"), such that trials are feasible to conduct and important errors are prevented rather than remediated. A working group evaluated aspects of trial design and oversight and developed the Clinical Trials Transformation Initiative quality-by-design principles document, outlining a series of factors generally relevant to the reliability of trial conclusions and to patient safety. These principles were then applied and further refined during a series of hands-on workshops to evaluate their utility in facilitating proactive, cross-functional dialogue, and decision-making about trial design and planning. Following these workshops, independent qualitative interviews were conducted with 19 workshop attendees to explore the potential challenges for implementing a quality-by-design approach to clinical trials. The Clinical Trials Transformation Initiative project team subsequently developed recommendations and an online resource guide to support implementation of this approach.ConclusionThe Clinical Trials Transformation Initiative quality-by-design principles provide a framework for assuring that clinical trials adequately safeguard participants and provide reliable information on which to make decisions on the effects of treatments. The quality-by-design workshops highlighted the value of active discussions incorporating the different perspectives within and external to an organization (e.g. clinical investigators, research site staff, and trial participants) in improving trial design. Workshop participants also recognized the value of focusing oversight on those aspects of the trial where errors would have a major impact on participant safety and reliability of results. Applying the Clinical Trials Transformation Initiative quality-by-design recommendations and principles should enable organizations to prioritize the most critical determinants of a trial's quality, identify non-essential activities that can be eliminated to streamline trial conduct and oversight, and formulate appropriate plans to define, avoid, mitigate, monitor, and address important errors.
| S-EPMC4952025 | biostudies-literature
Project description:The neuroprotective effects of estrogen have been demonstrated consistently in cellular and animal studies but the evidence in women remains conflicted. We explored the window of opportunity hypothesis in relation to cognitive aging and dementia. In particular, we reviewed existing literature, reanalyzed some of our data, and combined results graphically. Current evidence suggests that estrogen may have beneficial, neutral, or detrimental effects on the brain depending on age at the time of treatment, type of menopause (natural versus medically or surgically induced), or stage of menopause. The comparison of women who underwent bilateral oophorectomy with referent women provided evidence for a sizeable neuroprotective effect of estrogen before age 50 years. Several case-control studies and cohort studies also showed neuroprotective effects in women who received estrogen treatment (ET) in the early postmenopausal stage (most commonly at ages 50-60 years). The majority of women in those observational studies had undergone natural menopause and were treated for the relief of menopausal symptoms. However, recent clinical trials by the Women's Health Initiative showed that women who initiated ET alone or in combination with a progestin in the late postmenopausal stage (ages 65-79 years) experienced an increased risk of dementia and cognitive decline regardless of the type of menopause. The current conflicting data can be explained by the window of opportunity hypothesis suggesting that the neuroprotective effects of estrogen depend on age at the time of administration, type of menopause, and stage of menopause. Therefore, women who underwent bilateral oophorectomy before the onset of menopause or women who experienced premature or early natural menopause should be considered for hormonal treatment until approximately age 51 years.
| S-EPMC3046246 | biostudies-literature
Project description:Interventional clinical studies can provide the highest levels of evidence and generate significant results on specific investigational medicinal products or medical devices. In order to have powerful studies, attain unquestionable results and make significant discoveries, the number of patients enrolled must be high. Therefore, multinational, randomised clinical trials are necessary. The multicentre, multinational recruitment of subjects in investigator-initiated clinical trials (IICTs) increases their logistical burden, justifying the need for specific infrastructures to ease implementation. Herein, we provide for the first time an overview of the facts and figures concerning IICTs, existing infrastructures' capacity for interventional clinical research, and scientific performance of investigators in a European country, Portugal. We aim to highlight the relevance and need for investing in European infrastructures such as the European Clinical Research Infrastructure Network (ECRIN) for multinational IICTs. A public, non-profit organisation, ECRIN facilitates the conduct of multinational clinical trials in Europe by coordinating scientific partners and their networks, and providing advice, management services and tools to enhance collaboration. Currently in Portugal, few multinational randomised IICTs are coordinated by national investigators. This is most likely due to the lack of human resources dedicated to clinical trials in clinical research centres (CRCs) as well as the scarcity of professional academic clinical trial units (CTUs) providing logistics and management services at non-profit rates. With the data shown, we expect to trigger the development of similar studies in other European countries and stress the impact of government support for IICTs.
| S-EPMC5935898 | biostudies-other
Project description:BACKGROUND:With the second largest tuberculosis (TB) burden globally, China is committed to actively engage in international TB clinical trials to contribute to global TB research. However, lack of research capacity among local sites has been identified as a barrier. MAIN TEXT:The China Tuberculosis Clinical Trials Consortium (CTCTC) was initiated by Beijing Chest Hospital with investment from the US National Institutes of Health and technical support from Family Health International 360 in 2013, as a nationwide collaborative clinical trial network to strengthen selected clinical site research capacity and attract TB clinical trials. The program aims to: 1) recruit leading hospitals that care for TB patients; 2) conduct on-site assessment to identify capacity gaps and needs for improvement; 3) design and deliver capacity building activities; 4) attract and deliver high quality results for TB clinical trials. A total of 24 sites have joined CTCTC, covering 20 provinces in China. Twenty-two sites have been accredited by the National Medical Products Administration (NMPA) to be qualified to conduct TB clinical trials. The onsite assessment, extensive trainings among the CTCTC sites and young investigators have resulted in better understanding and improvement of the site capacity in conducting TB clinical trials. The establishment and growth of the CTCTC network has benefited from the good leadership, effective international cooperation and local commitment. Issues in human resources, regulatory environment and sustainability have been challenging the network from continuing growth. Clinical researchers have full-time clinical responsibilities in China and it is thus important to build a cadre of other human resources to assist. The regulatory environment is becoming friendlier in China to introduce international clinical trials to the CTCTC network. CONCLUSIONS:The CTCTC, with mature management structure and sustainable development model, which are distilled five key lessons for other developing countries or investigators of interest. They are the respectively using assessment-based approach to design tailored training package, understanding the availability of clinical researchers, providing solutions to maintain sustainability, understanding local regulatory environments and working with an international organization with local on-site team, respectively. Although, the experiences and capacity of China's TB hospitals in conducting clinical research vary. Considerable efforts to continue building the capacity are still needed, although the gap is smaller for a few top-tier hospitals.
| S-EPMC7229594 | biostudies-literature
Project description:Purpose of reviewThe COVID-19 pandemic has had a devastating impact on virtually all aspects of the healthcare system, including oncology clinical trials. The purpose of this review is to describe the impact of the pandemic on national breast cancer clinical trials.Recent findingsOf the 61 breast cancer-specific cooperative group breast cancer clinical trials open to accrual during the pandemic, 32% of them received supplementary tailored guidance regarding current and foreseeable challenges for clinical sites and investigators due to COVID-19. Many clinical trial sites reported decreases in enrollment and accrual, drastic disruptions to protocol, and challenges related to research infrastructure, staff burden, and assuring social distancing.SummaryThe challenges early in pandemic led to many operational changes in clinical trials, including use of electronic consent for enrollment, telemedicine visits, and mail order pharmacy. The pandemic highlighted aspects of breast cancer clinical trial that could be modernized while maintaining research integrity.
| S-EPMC8112880 | biostudies-literature
Project description:BackgroundDrug-drug interactions (DDIs) in subjects enrolling in clinical trials can impact not only safety of the patient but also study drug outcomes and data validity. This makes it critical to adequately screen and manage DDIs. The study objective was to determine the prevalence of DDIs involving study medications in subjects enrolling in National Clinical Trials Network (NCTN) clinical trials at a single institution. DDIs were evaluated based on study protocol recommendations for concomitant medication use (i.e. exclude, avoid or use caution), screening via DDI tool, and pharmacist review.MethodsSubjects enrolled in NCTN trials of commercially available agents between January 2013 and August 2017 were included if a complete medication list was available. Complete medication lists were collected from the date of enrollment or the next available date then screened utilizing protocol guidance and the DDI screening tool, Lexicomp® Drug Interactions (Wolters Kluwer, Hudson, OH). Interactions were reviewed for clinical relevance: defined as a DDI that would require a medication change to ensure study agent safety and efficacy at enrollment.ResultsOne hundred and twenty-eight subjects enrolled in 35 clinical trials were included. Protocol guidance detected 15 unique DDI pairs that should be avoided or used with caution in 10.2% (13/128) of subjects. The majority of these subjects did not have a clinically relevant DDI (69.2%, 9/13) based on pharmacist review. Lexicomp® detected moderate to major DDIs in 24.2% (31/128) of subjects, with 9.4% (12/128) having a clinically relevant DDI.ConclusionsThis study confirms a high prevalence of DDIs present in subjects enrolling in oncology clinical trials. Further efforts should be made to improve methods to detect and manage DDIs in patients enrolling on clinical trials to ensure patient safety and trial data validity.
| S-EPMC6249716 | biostudies-literature