scholarly journals Risk-Based Monitoring in Clinical Trials: Past, Present, and Future

2021 ◽  
Author(s):  
Brian Barnes ◽  
Nicole Stansbury ◽  
Debby Brown ◽  
Lauren Garson ◽  
Geoff Gerard ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Risk Indicators ◽  
Remote Site ◽  
Trial Quality ◽  
Site Monitoring ◽  
Source Data Verification ◽  
Landscape Survey ◽  
Trial Monitoring ◽  
The Individual

AbstractRisk-based monitoring (RBM) is a powerful tool for efficiently ensuring patient safety and data integrity in a clinical trial, enhancing overall trial quality. To better understand the state of RBM implementation across the clinical trial industry, the Association of Clinical Research Organizations (ACRO) conducted a landscape survey among its member companies across 6,513 clinical trials ongoing at the end of 2019. Of these trials, 22% included at least 1 of the 5 RBM components: key risk indicators (KRIs), centralized monitoring, off-site/remote-site monitoring, reduced source data verification (SDV), and reduced source document review (SDR). The implementation rates for the individual RBM components ranged 8%–19%, with the most frequently implemented component being centralized monitoring and the least frequently implemented being reduced SDR. When the COVID-19 pandemic emerged in early 2020, additional data were collected to assess its impact on trial monitoring, focusing specifically on trials switching from on-site monitoring to off-site/remote-site monitoring. These mid-pandemic data show that the vast majority of monitoring visits were on-site in February 2020, but an even higher percentage were off-site in April, corresponding with the first peak of the pandemic. Despite this shift, similar numbers of non-COVID-related protocol deviations were detected from February through June, suggesting little or no reduction in monitoring effectiveness. The pre- and mid-pandemic data provide two very different snapshots of RBM implementation, but both support the need to promote adoption of this approach while also highlighting an opportunity to capitalize on the recent shift toward greater RBM uptake in a post-pandemic environment.

Clinical trial monitoring effectiveness: Remote risk-based monitoring versus on-site monitoring with 100% source data verification

2020 ◽  
pp. 174077452097125
Author(s):  
Osamu Yamada ◽  
Shih-Wei Chiu ◽  
Munenori Takata ◽  
Michiaki Abe ◽  
Mutsumi Shoji ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Confidence Interval ◽  
Remote Monitoring ◽  
Remote Monitoring System ◽  
Data Verification ◽  
Critical Data ◽  
Site Monitoring ◽  
Source Data ◽  
Source Data Verification

Background/Aims: Traditional on-site monitoring of clinical trials via frequent site visits and 100% source data verification is cost-consuming, and it still cannot guarantee data quality effectively. Depending on the types and designs of clinical trials, an alternative would be combining several monitoring methods, such as risk-based monitoring and remote monitoring. However, there is insufficient evidence of its effectiveness. This research compared the effectiveness of risk-based monitoring with a remote monitoring system with that of traditional on-site monitoring. Methods: With a cloud-based remote monitoring system called beagle View®, we created a remote risk-based monitoring methodology that focused only on critical data and processes. We selected a randomized controlled trial conducted at Tohoku University Hospital and randomly sampled 11 subjects whose case report forms had already been reviewed by data managers. Critical data and processes were verified retrospectively by remote risk-based monitoring; later, all data and processes were confirmed by on-site monitoring. We compared the ability of remote risk-based monitoring to detect critical data and process errors with that of on-site monitoring with 100% source data verification, including an examination of clinical trial staff workload and potential cost savings. Results: Of the total data points (n = 5617), 19.7% (n = 1105, 95% confidence interval = 18.7–20.7) were identified as critical. The error rates of critical data detected by on-site monitoring, remote risk-based monitoring, and data review by data managers were 7.6% (n = 84, 95% CI = 6.2–9.3), 7.6% (n = 84, 95% confidence interval = 6.2–9.3), and 3.9% (n = 43, 95% confidence interval = 2.9–5.2), respectively. The total number of critical process errors detected by on-site monitoring was 14. Of these 14, 92.9% (n = 13, 95% confidence interval = 68.5–98.7) and 42.9% (n = 6, 95% confidence interval = 21.4–67.4) of critical process errors were detected by remote risk-based monitoring and data review by data managers, respectively. The mean time clinical trial staff spent dealing with remote risk-based monitoring was 9.9 ± 5.3 (mean ± SD) min per visit per subject. Our calculations show that remote risk-based monitoring saved between 9 and 41 on-site monitoring visits, corresponding to a cost of between US$13,500 and US$61,500 per trial site. Conclusion: Remote risk-based monitoring was able to detect critical data and process errors as well as on-site monitoring with 100% source data verification, saving travel time and monitoring costs. Remote risk-based monitoring offers an effective alternative to traditional on-site monitoring of clinical trials.

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.

Research with Minors in Germany

2008 ◽  
Vol 15 (2) ◽  
pp. 127-134 ◽  
Author(s):  
Dieter Hart ◽  
Benedikt Buchner
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Research ◽  
German Law ◽  
European Level ◽  
Direct Benefit ◽  
Individual Participant ◽  
Long Time ◽  
The Individual

AbstractThe European GCP Directive has been implemented into German law in sect. 40 ff. AMG (German pharmaceutical law). Unlike the Directive, German pharmaceutical law basically differentiates between three constellations of clinical trials on minors: clinical trials on healthy minors, clinical trials on ill minors with an individual benefit for the individual participant, and clinical trials on ill minors without direct benefit for the individual participant, but with a so-called “group benefit”. Particularly the latter possibility of conducting clinical trials on minors even if no individual benefit can be expected is not a matter of course in Germany since due to historical experiences a sceptical attitude towards clinical research on humans prevailed for a long time. German legislature has availed itself of the option granted by Article 3 of the GCP Directive to establish a higher level of protection of clinical trial subjects than the European level.

scholarly journals Protecting clinical trials in cystic fibrosis during the SARS-CoV-2 pandemic: risks and mitigation measures

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Silke van Koningsbruggen-Rietschel ◽  
Fiona Dunlevy ◽  
Veerle Bulteel ◽  
Kate Hayes ◽  
Anne Verbrugge ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cystic Fibrosis ◽  
Clinical Trials ◽  
Risk Mitigation ◽  
Home Delivery ◽  
Mitigation Measures ◽  
Site Location ◽  
Phone Calls ◽  
Source Data Verification ◽  
The Impact

AbstractThe SARS-CoV-2 pandemic has disrupted clinical trials worldwide. The European Cystic Fibrosis Society-Clinical Trials Network (ECFS-CTN) has tracked clinical trial disruption by surveying its 58 trial sites across 17 European countries and collated information on measures to mitigate the impact of the pandemic and ensure trial continuity. Here, we present recommendations on how to reduce the risk of SARS-CoV-2 exposure to patients and trial staff by implementing remote trial visits where possible, using home assessments, video and phone calls, electronic consent, and home delivery of study drugs. We discuss the practicalities of remote source data verification, protocol amendments, changing trial site location, and staff absences and home working. We outline recommendations on how to protect trial outcomes, including home assessments, safety reporting, protocol deviations, and recruitment challenges. Finally, we discuss the importance of continued access to study drugs via extension trials for some patients. This guidance was co-created from the shared knowledge and experience of sites in our network and was re-distributed directly to all ECFS-CTN sites to help mitigate the impact of further waves of the SARS-CoV-2 pandemic. We will also use this guidance to assist companies, academia, and consortia with future protocol design and risk mitigation plans. This guidance can be applied to clinical trials in other diseases and could help sites that are not supported by clinical trial networks.

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.

Abstract 12662: Differences in Journal Impact Factor(IF) Between Initial and Subsequent Publication of Cardiovascular Clinical Trials-An Analysis From the ClinicalTrials.gov Repository

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jasjit Bhinder ◽  
Saurav Chatterjee ◽  
Franz H Messerli
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Cross Sectional ◽  
Thomson Reuters ◽  
Subsequent Publication ◽  
The Mean ◽  
The Difference ◽  
The Individual ◽  
Sectional Analysis ◽  
Journal Impact

Introduction: After publication of the primary outcome of a clinical trial additional data of interest continue to be published -.To achieve high visibility of their findings most authors tend to select journals with a high IF. The IF is often viewed as a measure of journal quality as a whole. Hypothesis: We compared IF of journals where the primary outcomes from a clinical trial were published to IF of journals where subsequent papers were published. Methods: This was a cross sectional analysis design. We analyzed cardiovascular clinical trials from Clinicaltrials.gov. We did not limit our search by date. We chose clinical trials which had 2 or more published manuscripts in journals with indexed IFs. We queried the Thomson Reuters’ Web of Knowledge to determine the individual IF. Results: Our search returned 72 cardiovascular clinical trials from a query of the Clinicaltrials.gov database. The mean IF of the primary index publication from the trials were 27.01 (95% confidence interval-CI 21.96-32.06); while that from subsequent publications from the same trials were 11.72 (95% CI 8.97-14.47). The mean difference in IF of journals publishing the index and subsequent results was 15.28 (95% 2.11-17.96). There was a strong correlation between the initial publication IF and the IF difference with the subsequent manuscript (p<0.001). Conclusions: The initial publications of cardiovascular trials consistently occur in journals with an IF higher than in subsequent publications. The higher the journal IF of the initial publication the greater the difference in journal IF between initial and subsequent publications.

scholarly journals Ethical Issues of Chemoprevention Clinical Trials

1997 ◽  
Vol 4 (2) ◽  
pp. 142-149 ◽  
Author(s):  
Victor G. Vogel ◽  
Lisa S. Parker
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Medicine ◽  
Ethical Issues ◽  
Healthy Individuals ◽  
Ethical Considerations ◽  
Risks And Benefits ◽  
New Type ◽  
Conflicting Interests ◽  
Trial Monitoring

Background Chemoprevention of malignancy is a new concept in clinical medicine, and little is written about the ethics of identifying and enrolling eligible subjects in chemoprevention clinical trials. Methods The authors identify the ethical issues raised in the conduct of clinical chemoprevention trials and review the ethical considerations that should guide clinical researchers in the design and conduct of this new type of clinical trial. Results The ethics of chemoprevention clinical trials are complicated because (1) chemoprevention lies at the intersection of disease management and health promotion, (2) there are conflicting interests competing in these trials, and (3) multiple values play a role in determining the nature and magnitude of the risks and benefits of chemoprevention of cancer. Ethical questions related to these trials concern the enrollment of healthy individuals rather than cancer patients, confidentiality in recruitment, the enrollment of “high-risk” subjects, randomization, informed consent, trial monitoring, and competing outcomes and toxicities. Conclusions These issues will be resolved with the accumulating clinical experience and ethical deliberations that accompany ongoing clinical chemoprevention research studies.

scholarly journals Sex, Permanent Drug Discontinuation, and Study Retention in Clinical Trials

Circulation ◽  
2021 ◽  
Vol 143 (7) ◽  
pp. 685-695 ◽  
Author(s):  
Emily S. Lau ◽  
Eugene Braunwald ◽  
David A. Morrow ◽  
Robert P. Giugliano ◽  
Elliott M. Antman ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Study Drug ◽  
Similar Proportion ◽  
Trial Participation ◽  
Drug Discontinuation ◽  
Random Effects Models ◽  
Cardiovascular Outcome Trials ◽  
Study Drug Discontinuation ◽  
The Individual

Background: Women are underrepresented across cardiovascular clinical trials. Whether women are more likely than men to prematurely discontinue study drug or withdraw consent once enrolled in a clinical trial is unknown. Methods: Eleven phase 3/4 TIMI (Thrombolysis in Myocardial Infarction) trials were included (135 879 men and 51 812 women [28%]). The association between sex and premature study drug discontinuation and withdrawal of consent were examined by multivariable logistic regression after adjusting for potential confounders in each individual trial and combining the individual point estimates in random effects models. Results: After adjusting for baseline differences, women had 22% higher odds of premature drug discontinuation (adjusted odds ratio [OR adj ], 1.22 [95% CI, 1.16–1.28]; P <0.001) compared with men. Qualitatively consistent results were observed for women versus men in the placebo arms (OR adj , 1.20 [95% CI, 1.13–1.27]) and active therapy arms (OR adj , 1.23 [95% CI, 1.17–1.30)]; there was some evidence for regional heterogeneity ( P interaction <0.001). Of those who stopped study drug prematurely, a similar proportion of men and women in the active arm stopped because of an adverse event (36% for both; P =0.60). Women were also more likely to withdraw consent compared with men (OR adj , 1.26 [95% CI, 1.17–1.36]; P <0.001). Conclusions: Women were more likely than men to prematurely discontinue study drug and withdraw consent across cardiovascular outcome trials. Premature study drug discontinuation was not explained by baseline differences by sex or a higher proportion of adverse events. Future trials should better capture reasons for drug discontinuation and withdrawal of consent to understand barriers to continued study drug use and clinical trial participation, particularly among women.

Consenting to bio-risk: xenotransplantation and the law

Legal Studies ◽  
2005 ◽  
Vol 25 (3) ◽  
pp. 404-430 ◽  
Author(s):  
Sara Fovargue
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Infectious Diseases ◽  
Potential Benefit ◽  
Genetically Engineered ◽  
Third Parties ◽  
Genetic Technologies ◽  
Alternative Sources ◽  
The 1960S ◽  
The Individual

Research into alternative sources of organs for transplantation, including the use of organs from non-human genetically engineered animals, has occurred since the introduction of allotransplantation in the 1960s. Xenotransplantation is different from other developing genetic technologies because whilst the potential benefit is to the individual, the possible risks are to society as a whole. The risks include the transmission of unknown and currently indeterminable infectious diseases. This article explores whether the current regulator framework is able to address this issue and, in particular, whether ‘first-party’ consent to involvement in a clinical trial is a sufficient to protect third parties from harm. The competence of a xeno-recipient to consent is also considered, and it is suggested that, at the very least, public debate and participation in deciding whether clinical trials should be permitted must occur, because by allowing xenotransplant trials to help an individual, the risks will be borne by all.

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