scholarly journals Should RECOVERY have used Response Adaptive Randomization? Evidence from a simulation study

2021 ◽  
Author(s):  
Tamir Sirkis ◽  
Jack Bowden ◽  
Benjamin Jones
Keyword(s):  
Statistical Power ◽  
Controlled Trial ◽  
Design Feature ◽  
Recruitment Rate ◽  
Ethical Question ◽  
Adaptive Randomization ◽  
Study Power ◽  
Randomised Controlled ◽  
The Impact ◽  
Patient Subgroups

Abstract Background The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial is aimed at addressing the urgent need to find effective treatments for patients hospitalised with suspected or confirmed COVID-19. The trial has had many successes, including discovering that dexamethasone is effective at reducing COVID-19 mortality, the first treatment to reach this milestone in a randomised controlled trial. Despite this, it continues to use standard or `fixed’ randomization (FR) to allocate patients to treatments. We assessed the impact of implementing response adaptive randomization (RAR) within RECOVERY using an array of performance measures, to learn if it could be beneficial going forward. This design feature has recently been implemented within the REMAP-CAP trial.Methods Trial data was simulated to closely match the data for patients allocated to either standard care or dexamethasone in the RECOVERY trial from March-June 2020, representing two out of five arms tested throughout this period. Two forms of FR and two forms of RAR were tested. Randomization strategies were performed at the whole trial level as well as within three pre-specified patient subgroups defined by patients’ respiratory support level.ResultsRAR strategies led to more patients being given dexamethasone and a lower mortality rate in the trial. Subgroup specific RAR reduced mortality rates even further. RAR did not induce any meaningful bias in treatment effect estimates, but reduced statistical power compared to FR, with subgroup level adaptive randomizations exhibiting the largest power reduction.ConclusionsUsing RAR within RECOVERY could have resulted in fewer deaths in the trial. However, a larger trial would have been needed to attain the same study power. This could potentially have prolonged the time to full approval of the drug, unless RAR itself led to an increased recruitment rate. Deciding how to balance the needs of patients within a trial and future patients who have yet to fall ill is an important ethical question of our time. RAR deserves to be considered as a design feature in future trials of COVID-19 and other diseases.

scholarly journals Should RECOVERY have used Response Adaptive Randomization? Evidence from a simulation study

2021 ◽  
Author(s):  
Tamir Sirkis ◽  
Jack Bowden ◽  
Benjamin Jones
Keyword(s):  
Statistical Power ◽  
Controlled Trial ◽  
Design Feature ◽  
Recruitment Rate ◽  
Ethical Question ◽  
Adaptive Randomization ◽  
Study Power ◽  
Randomised Controlled ◽  
The Impact ◽  
Patient Subgroups

Abstract Background The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial is aimed at addressing the urgent need to find effective treatments for patients hospitalised with suspected or confirmed COVID-19. The trial has had many successes, including discovering that dexamethasone is effective at reducing COVID-19 mortality, the first treatment to reach this milestone in a randomised controlled trial. Despite this, it continues to use standard or `fixed’ randomization (FR) to allocate patients to treatments. We assessed the impact of implementing response adaptive randomization (RAR) within RECOVERY using an array of performance measures, to learn if it could be beneficial going forward. This design feature has recently been implemented within the REMAP-CAP trial. Methods Trial data was simulated to closely match the data for patients allocated to either standard care or dexamethasone in the RECOVERY trial from March-June 2020, representing two out of five arms tested throughout this period. Two forms of FR and two forms of RAR were tested. Randomization strategies were performed at the whole trial level as well as within three pre-specified patient subgroups defined by patients’ respiratory support level. Results RAR strategies led to more patients being given dexamethasone and a lower mortality rate in the trial. Subgroup specific RAR reduced mortality rates even further. RAR did not induce any meaningful bias in treatment effect estimates, but reduced statistical power compared to FR, with subgroup level adaptive randomizations exhibiting the largest power reduction. Conclusions Using RAR within RECOVERY could have resulted in fewer deaths in the trial. However, a larger trial would have been needed to attain the same study power. This could potentially have prolonged the time to full approval of the drug, unless RAR itself led to an increased recruitment rate. Deciding how to balance the needs of patients within a trial and future patients who have yet to fall ill is an important ethical question of our time. RAR deserves to be considered as a design feature in future trials of COVID-19 and other diseases.

scholarly journals 71 Ultrasound directed reduction of Colles’ type distal radial fractures in ED (UDiReCT): a feasibility randomized controlled trial

2020 ◽  
Vol 37 (12) ◽  
pp. 835.3-836
Author(s):  
Hamza Malik ◽  
Andrew Appelboam ◽  
Gordon Taylor ◽  
Daryl Wood ◽  
Karen Knapp
Keyword(s):  
Data Collection ◽  
Controlled Trial ◽  
Wrist Fracture ◽  
Recruitment Rate ◽  
Feasibility Trial ◽  
Point Of Care Ultrasound ◽  
Distal Radial Fractures ◽  
Definitive Trial ◽  
Randomised Controlled

Aims/Objectives/BackgroundWrist fractures are among the commonest injuries seen in the emergency department (ED). Around 25% of these injuries have Colles’ type fracture displacement and undergo manipulation in the ED. In the UK, these manipulations are typically done ‘blind’ without real time imaging and recent observational studies show that over 40% of the injuries go on to require surgical fixation (due to inadequate initial reduction or re-displacement). Point of care ultrasound has been used to guide and improve wrist fracture reductions but it’s effect on subsequent outcome is not established. We set up and ran the UK’s first randomised controlled feasibility trial comparing standard and ultrasound guided ED wrist fracture manipulations to test a definitive trial protocol, data collection and estimate recruitment rate towards a future definitive trial.Methods/DesignWe conducted a 1:1, single blind, parallel group, randomised controlled feasibility trial in two UK hospitals. Adults with Colles’ type distal radial fractures requiring manipulation in the ED were recruited by supervising emergency physicians supported by network research nurses. Participants were randomised to ultrasound directed fracture manipulation (intervention) or standard care with sham ultrasound (controls). The trial was run through Exeter Clinical Trials Unit and consent, randomisation and data collection conducted electronically in REDCap cloud. All participants were followed up at 6 weeks to record any surgical intervention and also underwent baseline and 3 month quality of life (EQ-5D-5L) and wrist function (Patient Rated Wrist Evaluation (PRWE) assessments.Results/ConclusionsWe recruited 47 patients in total, with 23 randomised to the interventional arm and 24 randomised to the control arm. We were able to follow up 100% of the patients for the 6 week follow up. Data analysis and results will be presented at the time of the conference.

scholarly journals Examining the impact of oral hygiene advice and/or scale and polish on periodontal disease: the IQuaD cluster factorial randomised controlled trial

BDJ ◽  
2021 ◽  
Vol 230 (4) ◽  
pp. 229-235
Author(s):  
Jan Clarkson ◽  
Craig Ramsay ◽  
Thomas Lamont ◽  
Beatriz Goulao ◽  
Helen Worthington ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Periodontal Disease ◽  
Oral Hygiene ◽  
Controlled Trial ◽  
Randomised Controlled ◽  
The Impact

scholarly journals The effect of sertraline on emotional processing: secondary analyses of the PANDA randomised controlled trial

2021 ◽  
pp. 1-8
Author(s):  
Norin Ahmed ◽  
Jessica K. Bone ◽  
Gemma Lewis ◽  
Nick Freemantle ◽  
Catherine J. Harmer ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Emotional Processing ◽  
Statistical Power ◽  
Controlled Trial ◽  
Negative Information ◽  
Small Samples ◽  
Double Blind ◽  
Treatment Allocation ◽  
Randomised Controlled ◽  
Cognitive Neuropsychological

Abstract Background According to the cognitive neuropsychological model, antidepressants reduce symptoms of depression and anxiety by increasing positive relative to negative information processing. Most studies of whether antidepressants alter emotional processing use small samples of healthy individuals, which lead to low statistical power and selection bias and are difficult to generalise to clinical practice. We tested whether the selective serotonin reuptake inhibitor (SSRI) sertraline altered recall of positive and negative information in a large randomised controlled trial (RCT) of patients with depressive symptoms recruited from primary care. Methods The PANDA trial was a pragmatic multicentre double-blind RCT comparing sertraline with placebo. Memory for personality descriptors was tested at baseline and 2 and 6 weeks after randomisation using a computerised emotional categorisation task followed by a free recall. We measured the number of positive and negative words correctly recalled (hits). Poisson mixed models were used to analyse longitudinal associations between treatment allocation and hits. Results A total of 576 participants (88% of those randomised) completed the recall task at 2 and 6 weeks. We found no evidence that positive or negative hits differed according to treatment allocation at 2 or 6 weeks (adjusted positive hits ratio = 0.97, 95% CI 0.90–1.05, p = 0.52; adjusted negative hits ratio = 0.99, 95% CI 0.90–1.08, p = 0.76). Conclusions In the largest individual placebo-controlled trial of an antidepressant not funded by the pharmaceutical industry, we found no evidence that sertraline altered positive or negative recall early in treatment. These findings challenge some assumptions of the cognitive neuropsychological model of antidepressant action.

scholarly journals Mii-vitaliSe: a pilot randomised controlled trial of a home gaming system (Nintendo Wii) to increase activity levels, vitality and well-being in people with multiple sclerosis

BMJ Open ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. e016966 ◽  
Author(s):  
Sarah Thomas ◽  
Louise Fazakarley ◽  
Peter W Thomas ◽  
Sarah Collyer ◽  
Sarah Brenton ◽  
...  
Keyword(s):  
Physical Activity ◽  
Multiple Sclerosis ◽  
Controlled Trial ◽  
Well Being ◽  
Recruitment Rate ◽  
Controlled Study ◽  
Activity Levels ◽  
Nintendo Wii ◽  
Serious Adverse Events ◽  
Randomised Controlled

ObjectivesWhile the health and well-being benefits of physical activity are recognised, people with multiple sclerosis (MS) often face greater barriers than the general population. The Nintendo Wii potentially offers a fun, convenient way of overcoming some of these. The aim was to test the feasibility of conducting a definitive trial of the effectiveness and cost-effectiveness of Mii-vitaliSe; a home-based, physiotherapist-supported Nintendo Wii intervention.DesignA single-centre wait-list randomised controlled study.SettingMS service in secondary care.ParticipantsAmbulatory, relatively inactive people with clinically confirmed MS.InterventionThirty participants were randomised to receive Mii-vitaliSe either immediately (for 12 months) or after a 6-month wait (for 6 months). Mii-vitaliSe consisted of two supervised Nintendo Wii familiarisation sessions in the hospital followed by home use (Wii Sports, Sports Resort and Fit Plus software) with physiotherapist support and personalised resources.OutcomesIncluded self-reported physical activity levels, quality of life, mood, self-efficacy, fatigue and assessments of balance, gait, mobility and hand dexterity at baseline, 6 and 12 months. Interviews (n=25) explored participants’ experiences and, at study end, the two Mii-vitaliSe facilitators’ experiences of intervention delivery (main qualitative findings reported separately).ResultsMean (SD) age was 49.3 (8.7) years, 90% female, with 47% diagnosed with MS <6 years ago and 60% new to active gaming. The recruitment rate was 31% (95% CI 20% to 44%). Outcome data were available for 29 (97%) at 6 months and 28 (93%) at 12 months. No serious adverse events were reported during the study. Qualitative data indicated that Mii-vitaliSe was well-received. Mean Wii use across both groups over the initial 6-month intervention period was twice a week for 27 min/day. Mean cost of delivering Mii-vitaliSe was £684 per person.DiscussionMii-vitaliSe appears acceptable and a future trial feasible and warranted. These findings will inform its design.Trial registrationISRCTN49286846

Feasibility study of a communication and education asthma intervention for general practitioners in Australia

2010 ◽  
Vol 16 (1) ◽  
pp. 75 ◽  
Author(s):  
Smita Shah ◽  
Brett G. Toelle ◽  
Susan M. Sawyer ◽  
Jessica K. Roydhouse ◽  
Peter Edwards ◽  
...  
Keyword(s):  
General Practitioners ◽  
Controlled Trial ◽  
Communication Strategies ◽  
Asthma Management ◽  
Doctor Patient Communication ◽  
Children With Asthma ◽  
The Usa ◽  
Randomised Controlled ◽  
Communication Behaviours ◽  
The Impact

The Physician Asthma Care Education (PACE) program significantly improved asthma prescribing and communication behaviours of primary care paediatricians in the USA. We tested the feasibility and acceptability of a modified PACE program with Australian general practitioners (GP) and measured its impact on self-reported consulting behaviours in a pilot study. Recruitment took place through a local GP division. Twenty-five GP completed two PACE Australia workshops, which incorporated paediatric asthma management consistent with Australian asthma guidelines and focussed on effective communication strategies. Program feasibility, usefulness and perceived benefit were measured by questionnaires before the workshop and 1 month later, and an evaluation questionnaire after each workshop. GP were universally enthusiastic and supportive of the workshops. The most useful elements they reported were communication skills, case studies, device demonstrations and the toolkit provided. GP self reports of the perceived helpfulness of the key communication strategies and their confidence in their application and reported frequency of use increased significantly after the workshops. The PACE program shows promise in improving the way in which Australian GP manage asthma consultations, particularly with regard to doctor–patient communication. The impact of the modified PACE Australia program on the processes and outcomes of GP care of children with asthma is now being measured in a randomised controlled trial.

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