scholarly journals The COVID-19 Pandemic and Cardiovascular Issues in Clinical Trials: Practical and Regulatory Issues in Remote Monitoring of Cardiac Safety

2021 ◽  
Author(s):  
Elektra J. Papadopoulos ◽  
Kenneth Martin Stein ◽  
Polina Voloshko ◽  
Jonathan Seltzer ◽  
Fortunato Senatore ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Remote Monitoring ◽  
Cardiac Safety ◽  
Regulatory Issues

scholarly journals Use of connected digital products in clinical research following the COVID-19 pandemic: a comprehensive analysis of clinical trials

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e047341
Author(s):  
Caroline Marra ◽  
William J Gordon ◽  
Ariel Dora Stern
Keyword(s):  
Clinical Trials ◽  
Clinical Research ◽  
Outcome Measures ◽  
Remote Monitoring ◽  
Search Algorithm ◽  
Primary Outcome Measure ◽  
Secondary Outcome ◽  
Digital Products ◽  
Clinical Trial Registry ◽  
Before And After

ObjectivesIn an effort to mitigate COVID-19 related challenges for clinical research, the US Food and Drug Administration (FDA) issued new guidance for the conduct of ‘virtual’ clinical trials in late March 2020. This study documents trends in the use of connected digital products (CDPs), tools that enable remote patient monitoring and telehealth consultation, in clinical trials both before and after the onset of the pandemic.DesignWe applied a comprehensive text search algorithm to clinical trial registry data to identify trials that use CDPs for remote monitoring or telehealth. We compared CDP use in the months before and after the issuance of FDA guidance facilitating virtual clinical trials.SettingAll trials registered on ClinicalTrials.gov with start dates from May 2019 through February 2021.Outcome measuresThe primary outcome measure was the overall percentage of CDP use in clinical trials started in the 10 months prior to the pandemic onset (May 2019–February 2020) compared with the 10 months following (May 2020–February 2021). Secondary outcome measures included CDP usage by trial type (interventional, observational), funder type (industry, non-industry) and diagnoses (COVID-19 or non-COVID-19 participants).ResultsCDP usage in clinical trials increased by only 1.65 percentage points, from 14.19% (n=23 473) of all trials initiated in the 10 months prior to the pandemic onset to 15.84% (n=26 009) of those started in the 10 months following (p<0.01). The increase occurred primarily in observational studies and non-industry funded trials and was driven entirely by CDP usage in trials for COVID-19.ConclusionsThese findings suggest that in the short-term, new options created by regulatory guidance to stimulate telehealth and remote monitoring were not widely incorporated into clinical research. In the months immediately following the pandemic onset, CDP adoption increased primarily in observational and non-industry funded studies where virtual protocols are likely medically necessary due to the participants’ COVID-19 diagnosis.

scholarly journals Monitoring advances including consent: learning from COVID-19 trials and other trials running in UKCRC registered clinical trials units during the pandemic

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sharon B. Love ◽  
Emma Armstrong ◽  
Carrie Bayliss ◽  
Melanie Boulter ◽  
Lisa Fox ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Remote Monitoring ◽  
Research Collaboration ◽  
Monitoring Task ◽  
Critical Data ◽  
Site Monitoring ◽  
Clinical Trials Unit ◽  
Third Person ◽  
Trial Monitoring ◽  
The Uk

AbstractThe COVID-19 pandemic has affected how clinical trials are managed, both within existing portfolios and for the rapidly developed COVID-19 trials. Sponsors or delegated organisations responsible for monitoring trials have needed to consider and implement alternative ways of working due to the national infection risk necessitating restricted movement of staff and public, reduced clinical staff resource as research staff moved to clinical areas, and amended working arrangements for sponsor and sponsor delegates as staff moved to working from home.Organisations have often worked in isolation to fast track mitigations required for the conduct of clinical trials during the pandemic; this paper describes many of the learnings from a group of monitoring leads based in United Kingdom Clinical Research Collaboration (UKCRC) Clinical Trials Unit (CTUs) within the UK.The UKCRC Monitoring Task and Finish Group, comprising monitoring leads from 9 CTUs, met repeatedly to identify how COVID-19 had affected clinical trial monitoring. Informed consent is included as a specific issue within this paper, as review of completed consent documentation is often required within trial monitoring plans (TMPs). Monitoring is defined as involving on-site monitoring, central monitoring or/and remote monitoring.Monitoring, required to protect the safety of the patients and the integrity of the trial and ensure the protocol is followed, is often best done by a combination of central, remote and on-site monitoring. However, if on-site monitoring is not possible, workable solutions can be found using only central or central and remote monitoring. eConsent, consent by a third person, or via remote means is plausible. Minimising datasets to the critical data reduces workload for sites and CTU staff. Home working caused by COVID-19 has made electronic trial master files (TMFs) more inviting. Allowing sites to book and attend protocol training at a time convenient to them has been successful and worth pursuing for trials with many sites in the future.The arrival of COVID-19 in the UK has forced consideration of and changes to how clinical trials are conducted in relation to monitoring. Some developed practices will be useful in other pandemics and others should be incorporated into regular use.

A Comparative Review of Erythropoiesis Stimulating Agents

2008 ◽  
Vol 21 (6) ◽  
pp. 424-430
Author(s):  
Nicole L. Metzger ◽  
Kerry E. Francis ◽  
Stacy A. Voils
Keyword(s):  
Chronic Kidney Disease ◽  
Clinical Trials ◽  
Kidney Disease ◽  
Tumor Progression ◽  
Safety And Efficacy ◽  
Regulatory Issues ◽  
Erythropoiesis Stimulating Agents ◽  
Disease States ◽  
Comparative Review ◽  
The Us

Erythropoiesis stimulating agents have been used for more than a decade in patients with chronic kidney disease, malignancy, and other disease states where anemia is common. Recently, several clinical trials have questioned the safety and efficacy of these agents. Thrombosis and increase in tumor progression as well as a potential increase in mortality have been noted in some trials and have generated growing concern regarding whether these agents should remain on the US market. Subsequently, reimbursement from some payers for erythropoiesis stimulating agent administration has become somewhat restrictive. We address the pharmacology, pharmacokinetics, pharmacodynamics, safety, efficacy, and pharmacoeconomics of erythropoiesis stimulating agents as well as emerging regulatory issues pertaining to the administration of erythropoiesis stimulating agents.

Regulatory issues for clinical trials at EORTC

2002 ◽  
Vol 38 ◽  
pp. 142-146 ◽  
Author(s):  
A.J. Baeyens ◽  
D. Lacombe
Keyword(s):  
Clinical Trials ◽  
Regulatory Issues

Aplidin Cardiac Safety Analysis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4820-4820
Author(s):  
Arturo Soto-Matos ◽  
Sergio Szyldergemajn ◽  
Javier Gomez ◽  
Sonia Extremera ◽  
Bernardo Miguel-Lillo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Trials ◽  
Multivariate Analysis ◽  
Drug Exposure ◽  
Single Agent ◽  
Fatal Outcome ◽  
Healthy Population ◽  
Qtc Interval ◽  
Cardiac Safety ◽  
Frequent Type

Abstract Abstract 4820 Background Aplidin (plitidepsin) is a cyclic depsipeptide of marine origin, with activity in relapsed/refractory multiple myeloma and T-cell NHL[1],[2]. Some depsipeptides have been linked to increased cardiac toxicity in the literature[3]. PharmaMar Pharmacovigilance and Clinical Trials Data Management databases were reviewed for cardiac adverse events (CAEs) occurring during clinical trials evaluating plitidepsin as single-agent as of November 2008. Data were analyzed for potential risk factors associations with the occurrence of CAE by univariate and multivariate logistic regression analyses. Results Forty-six of the 578 patients (8.0%) treated had at least one CAE. Eleven patients of 578 (1.9%) had CAE related to plitidepsin, none of them with fatal outcome. CAEs were retrospectively classified into 3 main groups after clinical review of all available data. The most frequent type of CAE were rhythm abnormalities (RA) (n=31; 5.4%), whereas atrial fibrillation (AF)/flutter accounted for most cases (n=15; 2.6%). Most events occurred randomly during plitidepsin treatment. Of note, no cases of life-threatening ventricular arrhythmias have been reported to date. The myocardial injury events (MI) (n=17; 3.0%) included possible ischemic related events as well as non-ischemic events. Finally, miscellaneous events (M) (n=6; 1.0%) included all other cardiac events that did not fit into the aforementioned categories. None of the M events was related to plitidepsin Demographic, clinical and pharmacological variables were explored by univariate and multivariate analysis. Significant association was found with prostate or pancreas cancer diagnosis (p=0.002), known baseline cardiac risk factors (p=0.002), myalgia at baseline (p=0.004), lower hemoglobin levels (p= 0.006) and ≥ grade 2 hypokalemia (p=0.006). Multivariate analysis confirmed all these associations. Importantly, treatment related variables, such as plitidepsin dose, number of cycles or schedule of administration did not result in any statistically significant association. Serial ECGs performed before and after plitidepsin administration (n=136) did not show any relevant effect on QTc interval. None of the PK parameters analyzed (Cmax and AUC from day 0 to day 28) had any significant impact on the probability of developing a CAE. Conclusions CAEs observed to date in plitidepsin trials fit into three clinical categories. The most frequent type observed was AF/atrial flutter, although its incidence was not different to what is reported in age-matched healthy population[4]. All other events were relatively infrequent. No dose-cumulative pattern was observed; moreover, neither plitidepsin dose nor schedule was associated with occurrence of CAEs. Relevant predisposing factors identified in univariate and multivariate analyses were related to patient's baseline and/or disease-related characteristics rather than to drug exposure or treatment-related variables. Data available on 578 adult patients with advanced cancer treated with singe-agent plitidepsin support a favorable cardiac safety profile. Disclosures: Soto-Matos: PharmaMar SAU: Employment. Szyldergemajn:PharmaMar SAU: Employment. Gomez:PharmaMar SAU: Employment. Extremera:PharmaMar SAU: Employment. Miguel-Lillo:PharmaMar SAU: Employment. Alfaro:PharmaMar SAU: Employment. Coronado:PharmaMar SAU: Employment. Lardelli:PharmaMar SAU: Employment. Roy:PharmaMar SAU: Employment. Corrado:PharmaMar SAU: Employment. Yovine:PharmaMar SAU: Employment. Kahatt:PharmaMar SAU: Employment.

Adjustment of Treatment Effect for Covariates in Clinical Trials: Statistical and Regulatory Issues

2000 ◽  
Vol 34 (2) ◽  
pp. 511-523 ◽  
Author(s):  
Dongsheng Tu ◽  
Katherine Shalay ◽  
Joseph Pater
Keyword(s):  
Clinical Trials ◽  
Treatment Effect ◽  
Regulatory Issues

scholarly journals Monitoring Advances Including Consent; Learning from COVID-19 Trials and Other Trials Running in UKCRC Registered Clinical Trials Units During the COVID-19 Pandemic

2020 ◽  
Author(s):  
Sharon Love ◽  
Emma Armstrong ◽  
Carrie Bayliss ◽  
Melanie Boulter ◽  
Lisa Fox ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Remote Monitoring ◽  
Monitoring Task ◽  
Critical Data ◽  
Site Monitoring ◽  
Clinical Trials Unit ◽  
Third Person ◽  
Trial Monitoring ◽  
The Uk ◽  
Staff Resource

Abstract BackgroundThe COVID-19 pandemic has affected how clinical trials are managed, both within existing portfolios and for the rapidly developed COVID-19 trials. Sponsors or delegated organisations responsible for monitoring trials have needed to consider and implement alternative ways of working due to the national infection risk necessitating restricted movement of staff and public, reduced clinical staff resource as research staff moved to clinical areas, and amended working arrangements for sponsor and sponsor delegates as staff moved to working from home. Organisations have often worked in isolation to fast track mitigations required for the conduct of clinical trials during the pandemic; this paper describes many of the learnings from a group of monitoring leads based in UKCRC Clinical Trials Unit (CTUs) within the UK.MethodsThe UKCRC Monitoring Task and Finish Group comprising monitoring leads from 9 CTUs, met repeatedly to identify how COVID-19 had affected clinical trial monitoring. Informed consent is included as a specific issue within this paper, as review of completed consent documentation is often required within trial monitoring plans (TMPs). Monitoring is defined as involving on-site monitoring, central monitoring or/and remote monitoring. ResultsMonitoring, required to protect the safety of the patients, the integrity of the trial and ensure the protocol is followed, is often best done by a combination of central, remote and on-site monitoring. However, if on-site monitoring is not possible, workable solutions can be found using only central or central and remote monitoring. eConsent, consent by a third person, or via remote means is plausible. Minimising datasets to the critical data reduces workload for sites and CTU staff. Home working caused by COVID-19 has made electronic trial master files (TMF’s) more inviting. Allowing sites to book and attend protocol training at a time convenient to them has been successful and worth pursuing for trials with many sites in the future.ConclusionsThe arrival of COVID-19 in the UK has forced consideration of and changes to how clinical trials are conducted in relation to monitoring. Some developed practices will be useful in other pandemics and others should be incorporated into regular use.

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