Dataset Information

Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry.

ABSTRACT: OBJECTIVE:Phase IV trials are often used to investigate drug safety after approval. However, little is known about the characteristics of contemporary phase IV clinical trials and whether these studies are of sufficient quality to advance medical knowledge in pharmacovigilance. We aimed to determine the fundamental characteristics of phase IV clinical trials that evaluated drug safety using the ClinicalTrials.gov registry data. METHODS:A data set of 19?359 phase IV clinical studies registered in ClinicalTrials.gov was downloaded. The characteristics of the phase IV trials focusing on safety only were compared with those evaluating both safety and efficacy. We also compared the characteristics of the phase IV trials in three major therapeutic areas (cardiovascular diseases, mental health and oncology). Multivariable logistic regression was used to evaluate factors associated with the use of blinding and randomisation. RESULTS:A total of 4772 phase IV trials were identified, including 330 focusing on drug safety alone and 4392 evaluating both safety and efficacy. Most of the phase IV trials evaluating drug safety (75.9%) had enrolment <300 with 96.5% <3000. Among these trials, 8.2% were terminated or withdrawn. Factors associated with the use of blinding and randomisation included the intervention model, clinical specialty and lead sponsor. CONCLUSIONS:Phase IV trials evaluating drug safety in the ClinicalTrials.gov registry were dominated by small trials that might not have sufficient power to detect less common adverse events. An adequate sample size should be emphasised for phase IV trials with safety surveillance as main task.

SUBMITTER: Zhang X

PROVIDER: S-EPMC5168517 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry.

Zhang Xinji X Zhang Yuan Y Ye Xiaofei X Guo Xiaojing X Zhang Tianyi T He Jia J

BMJ open 20161123 11

<h4>Objective</h4>Phase IV trials are often used to investigate drug safety after approval. However, little is known about the characteristics of contemporary phase IV clinical trials and whether these studies are of sufficient quality to advance medical knowledge in pharmacovigilance. We aimed to determine the fundamental characteristics of phase IV clinical trials that evaluated drug safety using the ClinicalTrials.gov registry data.<h4>Methods</h4>A data set of 19 359 phase IV clinical studie ...[more]

PMID: 27881517

Similar Datasets

Project description:The records of 208.777 (100%) clinical trials registered at ClinicalTrials.gov were downloaded on the 19th of February 2016. Phase II and III trials including patients with glioblastoma were selected for further classification and analysis. Based on the disease settings, trials were classified into three groups: newly diagnosed glioblastoma, recurrent disease and trials with no differentiation according to disease setting. Furthermore, we categorized trials according to the experimental interventions, the primary sponsor, the source of financial support and trial design elements. Trends were evaluated using the autoregressive integrated moving average model. Two hundred sixteen (0.1%) trials were selected for further analysis. Academic centers (investigator initiated trials) were recorded as primary sponsors in 56.9% of trials, followed by industry 25.9%. Industry was the leading source of monetary support for the selected trials in 44.4%, followed by 25% of trials with primarily academic financial support. The number of newly initiated trials between 2005 and 2015 shows a positive trend, mainly through an increase in phase II trials, whereas phase III trials show a negative trend. The vast majority of trials evaluate forms of different systemic treatments (91.2%). In total, one hundred different molecular entities or biologicals were identified. Of those, 60% were involving drugs specifically designed for central nervous system malignancies. Trials that specifically address radiotherapy, surgery, imaging and other therapeutic or diagnostic methods appear to be rare. Current research in glioblastoma is mainly driven or sponsored by industry, academic medical oncologists and neuro-oncologists, with the majority of trials evaluating forms of systemic therapies. Few trials reach phase III. Imaging, radiation therapy and surgical procedures are underrepresented in current trials portfolios. Optimization in research portfolio for glioblastoma is needed.

Project description:BackgroundLow back pain (LBP) affects nearly 4 out of 5 individuals during their lifetime and is the leading cause of disability globally. Digital therapeutics are emerging as effective treatment options for individuals experiencing LBP. Despite the growth of evidence demonstrating the benefits of these therapeutics in reducing LBP and improving functional outcomes, little data has been systematically collected on their safety profiles.ObjectiveThis study aims to evaluate the safety profile of a multidisciplinary digital therapeutic for LBP, the Kaia App, by performing a comprehensive assessment of reported adverse events (AEs) by users as captured by a standardized process for postmarket surveillance.MethodsAll users of a multidisciplinary digital app that includes physiotherapy, mindfulness techniques, and education for LBP (Kaia App) from 2018 to 2019 were included. Relevant messages sent by users via the app were collected according to a standard operating procedure regulating postmarket surveillance of the device. These messages were then analyzed to determine if they described an adverse event (AE). Messages describing an AE were then categorized based on the type of AE, its seriousness, and its relatedness to the app, and they were described by numerical counts. User demographics, including age and gender, and data on app use were collected and evaluated to determine if they were risk factors for increased AE reporting.ResultsOf the 138,337 active users of the Kaia App, 125 (0.09%) reported at least one AE. Users reported 0.00014 AEs per active day on the app. The most common nonserious AE reported was increased pain. Other nonserious AEs reported included muscle issues, unpleasant sensations, headache, dizziness, and sleep disturbances. One serious AE, a surgery, was reported. Details of the event and its connection to the intervention were not obtainable, as the user did not provide more information when asked to do so; therefore, it was considered to be possibly related to the intervention. There was no relationship between gender and AE reporting (P>.99). Users aged 25 to 34 years had reduced odds (odds ratio [OR] 0.31, 95% CI 0.08-0.95; P=.03) of reporting AEs, while users aged 55 to 65 years (OR 2.53, 95% CI 1.36-4.84, P=.002) and ≥75 years (OR 4.36, 95% CI 1.07-13.26; P=.02) had increased odds. AEs were most frequently reported by users who had 0 to 99 active days on the app, and less frequently reported by users with more active days on the app.ConclusionsThis study on the Kaia App provides the first comprehensive assessment of reported AEs associated with real-world use of digital therapeutics for lower back pain. The overall rate of reported AEs was very low, but significant reporting bias is likely to be present. The AEs reported were generally consistent with those described for in-person therapies for LBP.

Project description:BackgroundThe process of assuring the safety of medical devices is constrained by reliance on voluntary reporting of adverse events. We evaluated a strategy of prospective, active surveillance of a national clinical registry to monitor the safety of an implantable vascular-closure device that had a suspected association with increased adverse events after percutaneous coronary intervention (PCI).MethodsWe used an integrated clinical-data surveillance system to conduct a prospective, propensity-matched analysis of the safety of the Mynx vascular-closure device, as compared with alternative approved vascular-closure devices, with data from the CathPCI Registry of the National Cardiovascular Data Registry. The primary outcome was any vascular complication, which was a composite of access-site bleeding, access-site hematoma, retroperitoneal bleeding, or any vascular complication requiring intervention. Secondary safety end points were access-site bleeding requiring treatment and postprocedural blood transfusion.ResultsWe analyzed data from 73,124 patients who had received Mynx devices after PCI procedures with femoral access from January 1, 2011, to September 30, 2013. The Mynx device was associated with a significantly greater risk of any vascular complication than were alternative vascular-closure devices (absolute risk, 1.2% vs. 0.8%; relative risk, 1.59; 95% confidence interval [CI], 1.42 to 1.78; P<0.001); there was also a significantly greater risk of access-site bleeding (absolute risk, 0.4% vs. 0.3%; relative risk, 1.34; 95% CI, 1.10 to 1.62; P=0.001) and transfusion (absolute risk, 1.8% vs. 1.5%; relative risk, 1.23; 95% CI, 1.13 to 1.34; P<0.001). The initial alerts occurred within the first 12 months of monitoring. Relative risks were greater in three prespecified high-risk subgroups: patients with diabetes, those 70 years of age or older, and women. All safety alerts were confirmed in an independent sample of 48,992 patients from April 1, 2014, to September 30, 2015.ConclusionsA strategy of prospective, active surveillance of a clinical registry rapidly identified potential safety signals among recipients of an implantable vascular-closure device, with initial alerts occurring within the first 12 months of monitoring. (Funded by the Food and Drug Administration and others.).

Project description:BackgroundThe TREATgermany registry collects data from children, adolescents, and adults with moderate-to-severe atopic dermatitis (AD) in Germany. For this purpose, clinical and patient-reported outcomes, the course of the disease, and applied therapies are observed.MethodsTREATgermany recruits patients with moderate-to-severe AD according to the diagnostic criteria of the UK Working Party, an "Objective Scoring for Atopic Dermatitis" (oSCORAD) > 20 and/or currently antiinflammatory systemic treatment for AD or previous anti-inflammatory systemic treatment for AD within past 24 months before inclusion. No study related interventions will be performed. Currently, 59 dermatological practices, clinics, and university hospitals are participating in TREATgermany (as of May 2021). Based on the interim analysis of October 13, 2020, patient characteristics were described from 4,373 documented visits of adult participants (n = 1,025).ResultsThe mean age at inclusion in TREATgermany was 42 years, 57.7% of patients were men (n = 591) and 42.3% were women (n = 434). According to oSCORAD, 85.8% of those included suffered from moderate-to-severe AD. At baseline visit, 744 patients had already received one or more systemic treatments for AD (glucocorticosteroids n = 600, ciclosporin A (CSA) n = 307, dupilumab n = 98). 597 patients received dupilumab during their participation in TREATgermany, 134 patients received CSA.ConclusionWith the increasing number of recruitment centers (October 2020: 38 centers; May 2021: 59 centers), TREATgermany can continue to make an important contribution to health services research for patients with moderate-to-severe AD. The registry fulfills the methodological requirements of IQWiG for the collection and processing of healthcare-related data. With the successful and expected approval of further systemic treatments, these can be compared in terms of efficacy and safety in the future. In addition, with the recruitment of children and adolescents started in 2021, this patient group can also be observed.

Dataset Information

Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry.

Publications

Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets