scholarly journals An evaluation of risk-based monitoring in pragmatic trials in UK Clinical Trials Units

Trials ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Daniel Beever ◽  
Lizzie Swaby
Keyword(s):  
Risk Assessment ◽  
Clinical Trials ◽  
Perceived Risk ◽  
Online Survey ◽  
Research Collaboration ◽  
Good Clinical Practice ◽  
Risk Assessments ◽  
Risk Level ◽  
Pragmatic Trials ◽  
The Uk

Abstract Background Good Clinical Practice guidelines issued in 2016 encourage risk-based approaches to monitoring clinical trials. This study compared current risk assessment and monitoring approaches in UK Clinical Trials Units (CTUs) with the published guidance and makes recommendations for risk-based monitoring in pragmatic trials. Methods An online survey of UK Clinical Research Collaboration registered CTUs was administered via email invitation. Forty-nine units were invited, and 23 responded. Respondents were also invited to share copies of risk assessment templates. Results Most CTUs reported using remote combined with on-site monitoring. All reported undertaking a risk assessment for Clinical Trials of Investigational Medicinal Products (CTIMPs) and 21 units did so for non-CTIMPs. Most CTIMP risk assessments used MHRA (Medicines and Healthcare products Regulatory Agency) classifications, although some also employed staff judgement. Almost all units based their monitoring on perceived risk level; this number was higher for CTIMPs (n = 22) than for non-CTIMPs (n = 19). In most cases, monitoring plans were produced. More CTUs revisited risk assessments during trials in CTIMPs (n = 21) than in non-CTIMPs (n = 18). Small numbers of units reviewed the monitoring approach always (n = 4) or sometimes (n = 9) and few used the reflection to guide future monitoring. Conclusions A high proportion of UK CTUs are using risk-based monitoring in the UK, as recommended by guidelines, for both CTIMPs and non-CTIMPs. This has the potential to make trials more efficient and reduce costs. However, there appears to be a lack of reflection on the value of these revised approaches. There may be a benefit in CTUs collaborating nationally to improve processes for reflection and making changes during the life course of a trial.

Applying the risk principle to optimize accuracy and equity in correctional risk assessment: Results From a Simulation

2021 ◽  
pp. 0306624X2098652
Author(s):  
Grant Duwe
Keyword(s):  
Risk Assessment ◽  
Predictive Accuracy ◽  
Ethnic Disparities ◽  
Simulated Data ◽  
Risk Assessments ◽  
Risk Level ◽  
Risk Levels ◽  
Risk Principle ◽  
Changes In Risk ◽  
The Impact

As the use of risk assessments for correctional populations has grown, so has concern that these instruments exacerbate existing racial and ethnic disparities. While much of the attention arising from this concern has focused on how algorithms are designed, relatively little consideration has been given to how risk assessments are used. To this end, the present study tests whether application of the risk principle would help preserve predictive accuracy while, at the same time, mitigate disparities. Using a sample of 9,529 inmates released from Minnesota prisons who had been assessed multiple times during their confinement on a fully-automated risk assessment, this study relies on both actual and simulated data to examine the impact of program assignment decisions on changes in risk level from intake to release. The findings showed that while the risk principle was used in practice to some extent, the simulated results showed that greater adherence to the risk principle would increase reductions in risk levels and minimize the disparities observed at intake. The simulated data further revealed the most favorable outcomes would be achieved by not only applying the risk principle, but also by expanding program capacity for the higher-risk inmates in order to adequately reduce their risk.

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.

scholarly journals Non-tuberculous mycobacterial lung disease in patients with bronchiectasis: perceived risk, severity and guideline adherence in a European physician survey

2020 ◽  
Vol 7 (1) ◽  
pp. e000498 ◽  
Author(s):  
Dirk Wagner ◽  
Jakko van Ingen ◽  
Roald van der Laan ◽  
Marco Obradovic
Keyword(s):  
Lung Disease ◽  
Perceived Risk ◽  
Online Survey ◽  
Respiratory Pathogens ◽  
Drug Resistant ◽  
Physician Survey ◽  
Moderate Risk ◽  
Patient Morbidity ◽  
Increased Risk ◽  
The Uk

BackgroundPatients with bronchiectasis are at increased risk of developing non-tuberculous mycobacteria lung disease (NTM-LD), and published guidelines recommend regular testing for NTM infection in this patient population.ObjectiveThis study aimed to survey physicians managing patients with bronchiectasis to understand the perceived risk of NTM to their patients, perceived disease severity and frequency of testing for NTM.MethodsThe study comprised an online survey of hospital-based physicians in the UK, Germany, Italy, France and the Netherlands. The target group were hospital-based physicians who had managed at least 10 adult patients with bronchiectasis over the preceding 12 months.ResultsIn total, 280 physicians completed the survey. Most (87%) thought their patients to be at particular risk of NTM, although it was perceived as a moderate risk versus other respiratory pathogens. Most perceived NTM-LD to impact patient morbidity (84%), and 61% indicated that NTM-LD significantly impacted mortality. 68% of all respondents did not test for NTM prior to initiating macrolide monotherapy, despite guidelines recommending testing. The perceived risk of and screening for NTM varied among countries.ConclusionsThe study demonstrates that physicians understand the risk of NTM-LD and associated morbidity in patients with bronchiectasis; however, a minority do not perceive that NTM-LD significantly affects mortality. Greater awareness of the need to test for NTM infection before initiating macrolide monotherapy for bronchiectasis is essential due to potential emergence of drug-resistant NTM.

scholarly journals Clinical Trials and the Drive to Material Standardisation

2017 ◽  
pp. 30-44 ◽  
Author(s):  
Catherine M. Montgomery
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
External Validity ◽  
Three Dimensions ◽  
Material Objects ◽  
Pragmatic Trials ◽  
Positive Effects ◽  
Ethnographic Data ◽  
The Uk

There have long been calls to reduce the bureaucratization of clinical trials and make them more ‘sensible’, with the focus on approvals and guidelines. Here, I focus on the mundane environments of a multi-centre clinical trial to ask how ‘sensible’ it is to standardize trials at the level of material objects. Drawing on ethnographic data collected in the UK, South Africa and Vietnam, I present three vignettes of material standardisation. While acknowledging some positive effects, I argue that standardising in this way may be antithetical to sustainable and relevant clinical research.  Three dimensions of this are discussed: 1) the external validity of evidence from pragmatic trials 2) the gap between experimentation and implementation and 3) long-term site capacity to conduct research.  Drawing on the literature on ‘situated standardisation’, the paper concludes by suggesting a greater acknowledgement of the need for trials not only to be ‘sensible’ but also ‘situated’.

scholarly journals Monitoring in practice – How are UK academic clinical trials monitored? A survey

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Sharon B. Love ◽  
Victoria Yorke-Edwards ◽  
Sarah Lensen ◽  
Matthew R. Sydes
Keyword(s):  
Clinical Trials ◽  
Online Survey ◽  
Research Collaboration ◽  
Phase Iii ◽  
European Medicines Agency ◽  
Final Decision ◽  
Evidence Based ◽  
Conducting Phase ◽  
Central Monitoring ◽  
Site Monitoring

Abstract Background Despite the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) encouraging the use of risk-based monitoring for trials in 2013, there remains a lack of evidence-based guidelines on how to monitor. We surveyed the academic United Kingdom Clinical Research Collaboration (UKCRC) registered clinical trials units (CTUs) to find out their policy on monitoring of phase III randomised clinical trials of an investigational medicinal product (CTIMPs). Methods An online survey of monitoring policy with sections on the CTU, central monitoring and on-site monitoring was sent to all 50 UKCRC registered CTUs in November 2018. Descriptive data analysis and tabulations are reported using the total number answering each question. Results A total of 43/50 (86%) of CTUs responded with 38 conducting phase III randomised CTIMP trials. Of these 38 CTUs, 34 finished the survey. Most CTUs (36/37, 97%) use a central monitoring process to guide, target or supplement site visits. More than half (19/36, 53%) of CTUs do not use an automated monitoring report when centrally monitoring trials and all units use trial team knowledge to make a final decision on whether an on-site visit is required. A total of 31/34 (91%) CTUs used triggers to decide whether or not to conduct an on-site monitoring visit. On-site, a mixture of source data verification and checking of processes was carried out. The CTUs overwhelmingly (27/34, 79%) selected optimising central monitoring as their most pressing concern. Conclusion The survey showed a wide variation in phase III randomised CTIMP trial monitoring practices by academic clinical trials units within a single research-active country. We urgently need to develop evidence-based regulator-agreed guidance for CTUs on best practice for both central and on-site monitoring and to develop tools for all CTUs to use.

scholarly journals Risk assessment and antibiotic prescribing decisions in children presenting to UK primary care with cough: a vignette study

BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e035761
Author(s):  
Martine Nurek ◽  
Brendan C Delaney ◽  
Olga Kostopoulou
Keyword(s):  
Risk Assessment ◽  
Primary Care ◽  
Prediction Rule ◽  
Clinical Prediction Rule ◽  
Decision Makers ◽  
Risk Assessments ◽  
Antibiotic Prescribing ◽  
Illness Duration ◽  
Clinical Vignettes ◽  
The Uk

ObjectivesThe validated ‘STARWAVe’ (Short illness duration, Temperature, Age, Recession, Wheeze, Asthma, Vomiting) clinical prediction rule (CPR) uses seven variables to guide risk assessment and antimicrobial stewardship in children presenting with cough. We aimed to compare general practitioners’ (GPs) risk assessments and prescribing decisions to those of STARWAVe and assess the influence of the CPR’s clinical variables.SettingPrimary care.Participants252 GPs, currently practising in the UK.DesignGPs were randomly assigned to view four (of a possible eight) clinical vignettes online. Each vignette depicted a child presenting with cough, who was described in terms of the seven STARWAVe variables. Systematically, we manipulated patient age (20 months vs 5 years), illness duration (3 vs 6 days), vomiting (present vs absent) and wheeze (present vs absent), holding the remaining STARWAVe variables constant.Outcome measuresPer vignette, GPs assessed risk of hospitalisation and indicated whether they would prescribe antibiotics or not.ResultsGPs overestimated risk of hospitalisation in 9% of vignette presentations (88/1008) and underestimated it in 46% (459/1008). Despite underestimating risk, they overprescribed: 78% of prescriptions were unnecessary relative to GPs’ own risk assessments (121/156), while 83% were unnecessary relative to STARWAVe risk assessments (130/156). All four of the manipulated variables influenced risk assessments, but only three influenced prescribing decisions: a shorter illness duration reduced prescribing odds (OR 0.14, 95% CI 0.08 to 0.27, p<0.001), while vomiting and wheeze increased them (ORvomit 2.17, 95% CI 1.32 to 3.57, p=0.002; ORwheeze 8.98, 95% CI 4.99 to 16.15, p<0.001).ConclusionsRelative to STARWAVe, GPs underestimated risk of hospitalisation, overprescribed and appeared to misinterpret illness duration (prescribing for longer rather than shorter illnesses). It is important to ascertain discrepancies between CPRs and current clinical practice. This has implications for the integration of CPRs into the electronic health record and the provision of intelligible explanations to decision-makers.

scholarly journals How to Interpret an Investigator’s Brochure for Meaningful Risk Assessment: Results of an AGAH Discussion Forum

2021 ◽  
Author(s):  
Jens Rengelshausen ◽  
Kerstin Breithaupt-Groegler ◽  
Frank Donath ◽  
Katharina Erb-Zohar ◽  
Tim Hardman ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Clinical Trials ◽  
Online Survey ◽  
Human Subjects ◽  
Safety Information ◽  
Discussion Forum ◽  
Clinical Safety ◽  
Human Pharmacology ◽  
Benefit Risk Assessment ◽  
Assessment Bias

Abstract Purpose A discussion forum was hosted by the Association for Applied Human Pharmacology (AGAH e.V.) to critically debate how to interpret and optimise the Investigator’s Brochure (IB) for meaningful risk assessment of early clinical trials. Materials and Methods Four topics were specifically discussed: deficiencies/uncertainties in IBs, guidance for the investigator, reference safety information, and potential risks for human subjects associated with inadequate non-clinical safety assessment in the IB. In each case, 43 participants took part in a real-time online survey with pre-defined questions to capture the audience’s opinion. Results The ‘Summary of Data and Guidance for the Investigator’ was considered as the section of the IB with the highest need for improvement with emphasis on readability, comprehensibility, timeliness of data, and appropriateness for risk assessment. It was suggested that the IB should at least be signed by the sponsor’s scientist responsible for the content on pharmacology and toxicology. It was agreed that sponsors should consider thoroughly whether changes to an IB constitute a substantial amendment, and that the IB should include a section on the change history. Non-clinical pharmacology studies with negative outcomes should be reported in the IB in order to avoid assessment bias. The reference safety information for expectedness assessment of suspected serious adverse reactions should be provided as a stand-alone section of the IB. Conclusion The overall consensus was that an optimised presentation of data will ensure the best possible understanding of a compound’s characteristics and an optimal benefit-risk assessment which will safeguard the participants in clinical trials.

scholarly journals Utilising benefit-risk assessments within clinical trials—a protocol for the BRAINS project

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Nikki Totton ◽  
Steven Julious ◽  
Dyfrig Hughes ◽  
Jonathan Cook ◽  
Katie Biggs ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Trial Design ◽  
Primary Outcome ◽  
Risk Assessments ◽  
Control Treatment ◽  
Guidance Document ◽  
List Type ◽  
Publicly Funded ◽  
Web Based ◽  
The Uk

Abstract Background Depending on the treatment to be investigated, a clinical trial could be designed to assess objectives of superiority, equivalence or non-inferiority. The design of the study is affected by many different elements including the control treatment, the primary outcome and associated relationships. In some studies, there could be more than one outcome of interest. In these situations, benefit-risk methodologies could be used to assess the outcomes simultaneously and consider the trade-off between the benefits against the risks of a treatment. Benefit-risk is used within the regulatory industry but seldom included within publicly funded clinical trials within the UK. This project aims to gain an expert consensus on how to select the appropriate trial design (e.g. superiority) and when to consider including benefit-risk methods. Methods The project will consist of four work packages: A web-based survey to elicit current experiences and opinions, A rapid literature review to assess any current recommendations, A two-day consensus workshop to gain agreement on the recommendations, and Production of a guidance document. Discussion The aim of the project is to provide a guideline for clinical researchers, grant funding bodies and reviewers for grant bodies for how to select the most appropriate trial design and when it is appropriate to consider using benefit-risk methods. The focus of the guideline will be on publicly funded trials however, the vision is that the work will be applicable across research settings and we will connect with other organisations and committees as appropriate.

scholarly journals Utilising Benefit-Risk Assessments within Clinical Trials – A Protocol for the BRAINS project

2020 ◽  
Author(s):  
Nikki Totton ◽  
Steven Julious ◽  
Dyfrig Hughes ◽  
Jonathan Cook ◽  
Katie Biggs ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Trial Design ◽  
Primary Outcome ◽  
Risk Assessments ◽  
Control Treatment ◽  
Guidance Document ◽  
Publicly Funded ◽  
Treatment Benefit ◽  
Web Based ◽  
The Uk

Abstract Background Depending on the treatment to be investigated, a clinical trial could be designed to assess objectives of: superiority; equivalence or non-inferiority. The design of the study is affected by many different elements including: the control treatment, the primary outcome and associated relationships. In some studies, there could be more than one outcome of interest. In these situations, benefit-risk methodologies could be used to assess the outcomes simultaneously and consider the trade-off of the benefits against the risks of a treatment. Benefit-risk is used within the regulatory industry but seldom included within publicly funded clinical trials within the UK. This project aims to gain an expert consensus on how to select the appropriate trial design (e.g. superiority) and when to consider including benefit-risk methods. Methods The project will consist of four work packages: 1. A web-based survey to elicit current experiences and opinions, 2. A rapid literature review to assess any current recommendations, 3. A two-day consensus workshop to gain agreement on the recommendations, 4. Production of a guidance document. Discussion The aim of the project is to provide a guideline for clinical researchers, grant funding bodies and reviewers for grant bodies for how to select the most appropriate trial design and when it is appropriate to consider using benefit-risk methods. The focus of the guideline will be on publicly funded trials, however, the vision is the work will be applicable across research settings and we will connect with other organisations and committees as appropriate.

scholarly journals Evidence-Based Caries Management for All Ages-Practical Guidelines

2021 ◽  
Vol 2 ◽  
Author(s):  
John D. B. Featherstone ◽  
Yasmi O. Crystal ◽  
Pamela Alston ◽  
Benjamin W. Chaffee ◽  
Sophie Doméjean ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Clinical Trials ◽  
Dental Caries ◽  
Clinical Outcomes ◽  
Assessment System ◽  
Risk Level ◽  
Caries Risk ◽  
Caries Risk Assessment ◽  
Management Procedures ◽  
Caries Management

Introduction: The purpose of the present paper is to provide step-by-step guidelines for dental healthcare providers to manage dental caries based upon caries risk assessment (CRA) for ages 0–6 years and 6 years through adult. The manuscript reviews and updates the CAMBRA (caries management by risk assessment) system which includes CRA and caries management recommendations that are guided by the assessed risk level.Caries Risk Assessment: CAMBRA CRA tools (CRAs) have been evaluated in several clinical outcomes studies and clinical trials. Updated CAMBRA CRAs for ages 0–6 years and 6 years through adult are provided. These CRAs have been refined by the addition of a quantitative method that will aid the health care provider in determining the caries risk of individuals.Caries Management Based Upon Risk Assessment: Guidelines for individualized patient care are provided based upon the caries risk status, results of clinical exams and responses of the patient to questions in the CRA. These guidelines are based upon successful outcomes documented in several clinical outcomes studies and clinical trials. The paper includes a review of successful caries management procedures for children and adults as previously published, with additional emphasis on correct use of silver diamine fluoride (SDF) for children. The caries management plan for each individual is based upon reducing the caries risk factors and enhancing the protective factors with the additional aid of behavior modification. Beneficially altering the caries balance is coupled with minimal intervention restorative dentistry, if appropriate. These methods are appropriate for the management of dental caries in all patients.

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