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

2021 ◽  
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 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: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 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 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: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 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

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 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.

A multicentre randomized controlled trial on trans-generational attention deficit/hyperactivity disorder (ADHD) in mothers and children (AIMAC): an exploratory analysis of predictors and moderators of treatment outcome

2019 ◽  
Vol 47 (1) ◽  
pp. 49-65 ◽  
Author(s):  
Charlotte Jaite ◽  
Betteke Maria van Noort ◽  
Timo D. Vloet ◽  
Erika Graf ◽  
Viola Kappel ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Specific Treatment ◽  
Externalizing Symptoms ◽  
Control Treatment ◽  
Comorbid Depression ◽  
Adhd Treatment ◽  
Mothers And Children ◽  
Maternal Adhd

Abstract. Objective: We examined predictors and moderators of treatment outcome in mothers and children diagnosed with ADHD in a large multicentre RCT. Method: In total, 144 mother-child dyads with ADHD were randomly assigned to either a maternal ADHD treatment (group psychotherapy and open methylphenidate medication, TG) or to a control treatment (individual counselling without psycho- or pharmacotherapy, CG). After maternal ADHD treatment, parent-child training (PCT) for all mother-child dyads was added. The final analysis set was based on 123 dyads with completed primary outcome assessments (TG: n = 67, CG: n = 56). The primary outcome was the change in each child’s externalizing symptoms. Multiple linear regression analyses were performed. Results: The severity of the child’s externalizing problem behaviour in the family at baseline predicted more externalizing symptoms in the child after PCT, independent of maternal treatment. When mothers had a comorbid depression, TG children showed more externalizing symptoms after PCT than CG children of depressive mothers. No differences between the treatment arms were seen in the mothers without comorbid depression. Conclusions: Severely impaired mothers with ADHD and depressive disorder are likely to need additional disorder-specific treatment for their comorbid psychiatric disorders to effectively transfer the contents of the PCT to the home situation (CCTISRCTN73911400).

Best practice for chronic oedema in community settings: what can we learn?

2020 ◽  
Vol 25 (12) ◽  
pp. 610-614
Author(s):  
Garry Cooper-Stanton
Keyword(s):  
Service Provision ◽  
Best Practice ◽  
Evidence Base ◽  
Community Services ◽  
Guidance Document ◽  
Community Settings ◽  
Tissue Viability ◽  
Delivery Of Care ◽  
Specialist Nurses ◽  
The Uk

There are various opportunities and challenges in the delivery of care to those diagnosed with chronic oedema/lymphoedema. Service provision is not consistent within the UK, and non-specialist nurses and other health professionals may be called on to fill the gaps in this area. The latest best practice guidance on chronic oedema is directed at community services that care for people within their own homes in primary care. This guide was developed in order to increase awareness, knowledge and access to an evidence base. Those involved in its creation cross specialist fields (lymphoedema and tissue viability), resulting in the document covering a number of areas, including an explanation of chronic oedema, its assessment and management and the association between chronic oedema and wet legs. The document complements existing frameworks on the condition and its management and also increases the available tools within chronic oedema management in the community. The present article provides an overview of the guidance document and discusses its salient features.

scholarly journals Improving pragmatic clinical trial design using real-world data

2019 ◽  
Vol 16 (3) ◽  
pp. 273-282 ◽  
Author(s):  
Susan M Shortreed ◽  
Carolyn M Rutter ◽  
Andrea J Cook ◽  
Gregory E Simon
Keyword(s):  
Clinical Trials ◽  
Trial Design ◽  
Suicide Attempts ◽  
Real World Data ◽  
Electronic Health Record Data ◽  
Pragmatic Clinical Trial ◽  
Pragmatic Clinical Trials ◽  
Sample Size Calculations ◽  
Record Data ◽  
Electronic Health

Background Pragmatic clinical trials often use automated data sources such as electronic health records, claims, or registries to identify eligible individuals and collect outcome information. A specific advantage that this automated data collection often yields is having data on potential participants when design decisions are being made. We outline how this data can be used to inform trial design. Methods Our work is motivated by a pragmatic clinical trial evaluating the impact of suicide-prevention outreach interventions on fatal and non-fatal suicide attempts in the 18 months after randomization. We illustrate our recommended approaches for designing pragmatic clinical trials using historical data from the health systems participating in this study. Specifically, we illustrate how electronic health record data can be used to inform the selection of trial eligibility requirements, to estimate the distribution of participant characteristics over the course of the trial, and to conduct power and sample size calculations. Results Data from 122,873 people with patient health questionnaire (PHQ) responses, recorded in their electronic health records between 1 July 2010 and 31 March 2012, were used to show that the suicide attempt rate in the 18 months following completion of the questionnaire varies by response to item nine of the PHQ. We estimated that the proportion of individuals with a prior recorded elevated PHQ (i.e. history of suicidal ideation) would decrease from approximately 50% at the beginning of a trial to about 5%, 50 weeks later. Using electronic health record data, we conducted simulations to estimate the power to detect a 25% reduction in suicide attempts. Simulation-based power calculations estimated that randomizing 8000 participants per randomization arm would allow 90% power to detect a 25% reduction in the suicide attempt rate in the intervention arm compared to usual care at an alpha rate of 0.05. Conclusions Historical data can be used to inform the design of pragmatic clinical trials, a strength of trials that use automated data collection for randomizing participants and assessing outcomes. In particular, realistic sample size calculations can be conducted using real-world data from the health systems in which the trial will be conducted. Data-informed trial design should yield more realistic estimates of statistical power and maximize efficiency of trial recruitment.

scholarly journals Effectiveness of a digital therapeutic as adjunct to treatment with medication in pediatric ADHD

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Scott H. Kollins ◽  
Ann Childress ◽  
Andrew C. Heusser ◽  
Jacqueline Lutz
Keyword(s):  
Video Game ◽  
Primary Outcome ◽  
Rating Scale ◽  
Stimulant Medication ◽  
Additional Treatment ◽  
Adhd Medication ◽  
Open Label ◽  
Serious Adverse Events ◽  
Treatment Benefit ◽  
Hyperactivity Disorder

AbstractSTARS-Adjunct was a multicenter, open-label effectiveness study of AKL-T01, an app and video-game-based treatment for inattention, as an adjunct to pharmacotherapy in 8–14-year-old children with attention-deficit/hyperactivity disorder (ADHD) on stimulant medication (n = 130) or not on any ADHD medication (n = 76). Children used AKL-T01 for 4 weeks, followed by a 4-week pause and another 4-week treatment. The primary outcome was change in ADHD-related impairment (Impairment Rating Scale (IRS)) after 4 weeks. Secondary outcomes included changes in IRS, ADHD Rating Scale (ADHD-RS). and Clinical Global Impressions Scale—Improvement (CGI-I) on days 28, 56, and 84. IRS significantly improved in both cohorts (On Stimulants: −0.7, p < 0.001; No Stimulants: −0.5, p < 0.001) after 4 weeks. IRS, ADHD-RS, and CGI-I remained stable during the pause and improved with a second treatment period. The treatment was well-tolerated with no serious adverse events. STARS-Adjunct extends AKL-T01’s body of evidence to a medication-treated pediatric ADHD population, and suggests additional treatment benefit.

scholarly journals Prior National Drug Abuse Treatment Clinical Trials Network (CTN) opioid use disorder trials as background and rationale for NIDA CTN-0100 “optimizing retention, duration and discontinuation strategies for opioid use disorder pharmacotherapy (RDD)”

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Matisyahu Shulman ◽  
Roger Weiss ◽  
John Rotrosen ◽  
Patricia Novo ◽  
Elizabeth Costello ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Extended Release ◽  
Primary Outcome ◽  
Opioid Use Disorder ◽  
Drug Abuse Treatment ◽  
Opioid Use ◽  
National Drug ◽  
Retention In Treatment ◽  
Abuse Treatment

AbstractOpioid use disorder continues to be a significant problem in the United States and worldwide. Three medications—methadone, buprenorphine, and extended-release injectable naltrexone,— are efficacious for treating opioid use disorder (OUD). However, the utility of these medications is limited, in part due to poor rates of retention in treatment. In addition, minimum recovery milestones and other factors that influence when and whether individuals can safely discontinue medications are unknown. The National Drug Abuse Treatment Clinical Trials Network (CTN) study “Optimizing Retention, Duration, and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy” (RDD; CTN-0100) will be among the largest clinical trials on treatment of OUD yet conducted, consisting of two phases, the Retention phase, and the Duration-Discontinuation phase. The Retention phase, open to patients initiating treatment, will test different doses and formulations of buprenorphine (standard dose sublingual, high dose sublingual, or extended-release injection), and a digital therapeutic app delivering contingency management and cognitive behavioral counseling on the primary outcome of retention in treatment. The Discontinuation phase, open to patients in stable remission from OUD and choosing to discontinue medication (including participants from the Retention phase or from the population of patients treated at the clinical site, referred by an outside prescriber or self-referred) will study different tapering strategies for buprenorphine (sublingual taper vs taper with injection buprenorphine), and a digital therapeutic app which provides resources to promote recovery, on the primary outcome of relapse-free discontinuation of medication. This paper describes how the RDD trial derives from two decades of research in the CTN. Initial trials (CTN-0001; CTN-0002; CTN-0003) focused on opioid detoxification, showing buprenorphine-naloxone was effective for detoxification, but that acute detoxification did not appear to be an effective treatment strategy. Trials on comparative effectiveness of medications for opioid use disorder (MOUD) (CTN-0027; CTN-0030; and CTN-0051) highlighted the problem of dropout from treatment and few trials defined retention on MOUD as the primary outcome. Long-term follow-up studies on those patient samples demonstrated the importance of long-term continuation of medication for many patients to sustain remission. Overall, these trials highlight the potential of a stable research infrastructure such as CTN to advance treatment effectiveness through a programmatic succession of large clinical trials.

scholarly journals Parkinson’s Patients’ Tolerance for Risk and Willingness to Wait for Potential Benefits of Novel Neurostimulation Devices: A Patient-Centered Threshold Technique Study

2021 ◽  
Vol 6 (1) ◽  
pp. 238146832097840
Author(s):  
Brett Hauber ◽  
Brennan Mange ◽  
Mo Zhou ◽  
Shomesh Chaudhuri ◽  
Heather L. Benz ◽  
...  
Keyword(s):  
Trial Design ◽  
Patient Characteristics ◽  
Risk Tolerance ◽  
Level Of Evidence ◽  
Treatment Benefit ◽  
Study Results ◽  
Potential Benefits ◽  
Risk Thresholds ◽  
Time Motor ◽  
Threshold Technique

Background. Parkinson’s disease (PD) is neurodegenerative, causing motor, cognitive, psychological, somatic, and autonomic symptoms. Understanding PD patients’ preferences for novel neurostimulation devices may help ensure that devices are delivered in a timely manner with the appropriate level of evidence. Our objective was to elicit preferences and willingness-to-wait for novel neurostimulation devices among PD patients to inform a model of optimal trial design. Methods. We developed and administered a survey to PD patients to quantify the maximum levels of risks that patients would accept to achieve potential benefits of a neurostimulation device. Threshold technique was used to quantify patients’ risk thresholds for new or worsening depression or anxiety, brain bleed, or death in exchange for improvements in “on-time,” motor symptoms, pain, cognition, and pill burden. The survey elicited patients’ willingness to wait to receive treatment benefit. Patients were recruited through Fox Insight, an online PD observational study. Results. A total of 2740 patients were included and a majority were White (94.6%) and had a 4-year college degree (69.8%). Risk thresholds increased as benefits increased. Threshold for depression or anxiety was substantially higher than threshold for brain bleed or death. Patient age, ambulation, and prior neurostimulation experience influenced risk tolerance. Patients were willing to wait an average of 4 to 13 years for devices that provide different levels of benefit. Conclusions. PD patients are willing to accept substantial risks to improve symptoms. Preferences are heterogeneous and depend on treatment benefit and patient characteristics. The results of this study may be useful in informing review of device applications and other regulatory decisions and will be input into a model of optimal trial design for neurostimulation devices.

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