Publications
217 results found
Phillips R, Sauzet O, Cornelius V, 2020, Statistical methods for the analysis of adverse event data in randomised controlled trials: a scoping review and taxonomy
<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background</jats:bold>Statistical methods for the analysis of harm outcomes in randomised controlled trials (RCTs) are rarely used, and there is a reliance on simple approaches to display information such as in frequency tables. We aimed to identify whether any statistical methods had been specifically developed to analyse prespecified secondary harm outcomes and non-specific emerging adverse events (AEs).<jats:bold>Methods</jats:bold>A scoping review was undertaken to identify articles that proposed original methods or the original application of existing methods for the analysis of AEs that aimed to detect potential adverse drug reactions (ADRs) in phase II-IV parallel controlled group trials. Methods where harm outcomes were the (co)-primary outcome were excluded.Information was extracted on methodological characteristics such as: whether the method required the event to be prespecified or could be used to screen emerging events; and whether it was applied to individual events or the overall AE profile. Each statistical method was appraised and a taxonomy was developed for classification.<jats:bold>Results</jats:bold>Forty-four eligible articles proposing 73 individual methods were included. A taxonomy was developed and articles were categorised as: visual summary methods (8 articles proposing 20 methods); hypothesis testing methods (11 articles proposing 16 methods); estimation methods (15 articles proposing 24 methods); or methods that provide decision-making probabilities (10 articles proposing 13 methods). Methods were further classified according to whether they required a prespecified event (9 articles proposing 12 methods), or could be applied to emerging events (35 articles proposing 61 methods); and if they were (group) sequential methods (10 articles proposing 12 methods) or methods to perform final/one analyses (34 articles proposing 61 met
North M, Bourne S, Green B, et al., 2020, A randomised controlled feasibility trial of E-health application supported care vs usual care after exacerbation of COPD: the RESCUE trial (vol 3, 145, 2020), npj Digital Medicine, Vol: 3, ISSN: 2398-6352
Benzian-Olsson N, Dand N, Chaloner C, et al., 2020, Association of clinical and demographic factors with the severity of Palmoplantar Pustulosis, JAMA Dermatology, Vol: 156, Pages: 1216-1222, ISSN: 2168-6068
Importance Although palmoplantar pustulosis (PPP) can significantly impact quality of life, the factors underlying disease severity have not been studied.Objective To examine the factors associated with PPP severity.Design, Setting, and Participants An observational, cross-sectional study of 2 cohorts was conducted. A UK data set including 203 patients was obtained through the Anakinra in Pustular Psoriasis, Response in a Controlled Trial (2016-2019) and its sister research study Pustular Psoriasis, Elucidating Underlying Mechanisms (2016-2020). A Northern European cohort including 193 patients was independently ascertained by the European Rare and Severe Psoriasis Expert Network (2014-2017). Patients had been recruited in secondary or tertiary dermatology referral centers. All patients were of European descent. The PPP diagnosis was established by dermatologists, based on clinical examination and/or published consensus criteria. The present study was conducted from October 1, 2014, to March 15, 2020.Main Outcomes and Measures Demographic characteristics, comorbidities, smoking status, Palmoplantar Pustulosis Psoriasis Area Severity Index (PPPASI), measuring severity from 0 (no sign of disease) to 72 (very severe disease), or Physician Global Assessment (PGA), measuring severity as 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe).Results Among the 203 UK patients (43 men [21%], 160 women [79%]; median age at onset, 48 [interquartile range (IQR), 38-59] years), the PPPASI was inversely correlated with age of onset (r = −0.18, P = .01). Similarly, in the 159 Northern European patients who were eligible for inclusion in this analysis (25 men [16%], 134 women [84%]; median age at onset, 45 [IQR, 34-53.3] years), the median age at onset was lower in individuals with a moderate to severe PGA score (41 years [IQR, 30.5-52 years]) compared with those with a clear to mild PGA score (46.5 years [IQR, 35-55 years]) (P&t
North M, Bourne S, Green B, et al., 2020, A randomised controlled feasibility trial of E-health application supported care vs usual care after exacerbation of COPD: The RESCUE trial, npj Digital Medicine, Vol: 3, Pages: 1-8, ISSN: 2398-6352
Exacerbations of COPD are one of the commonest causes of admission and re-admission to hospital. The role of digital interventions to support self-management in improving outcomes is uncertain. We conducted an open, randomised controlled trial of a digital health platform application (app) in 41 COPD patients recruited following hospital admission with an acute exacerbation. Subjects were randomised to either receive usual care, including a written self-management plan (n=21), or the myCOPD app (n=20) for 90 days. The primary efficacy outcome was recovery rate of symptoms measured by COPD Assessment Test (CAT) score. Exacerbations, readmission, inhaler technique quality of life and patient activation (PAM) scores were also captured by a blinded team. The app 24 was acceptable in this care setting and was used by 17 of the 21 patients with sustained use over the study period. The treatment effect on CAT score was 4.49 (95% CI: -8.41, -0.58) points lower in the myCOPD arm. Patients’ inhaler technique improved in the digital intervention arm (101 improving to 20 critical errors) compared to usual care (100 to 72 errors). Exacerbations tended to be less frequent in the digital arm compared to usual care; 34 vs 18 events. Hospital readmissions risk was numerically lower in the digital intervention arm: OR for readmission 0.383 (95%CI 0.074, 1.987; n=35). In this feasibility study of the digital self-management platform myCOPD, the app has proven acceptable to patients to use and use has improved exacerbation recovery rates, with strong signals of lower re-exacerbation and re-admission rates over 90 days. myCOPD reduced the number of critical errors in inhaler technique compared to usual care with written self-management. This provides a strong basis for further exploration of the use of app interventions in the context of recently hospitalised patients with COPD and informs the potential design of a large multi-centre trial
Crooks M, Elkes J, Storrar W, et al., 2020, Evidence generation for the clinical impact of myCOPD in patients with mild, moderate and newly diagnosed COPD: a randomised controlled trial, ERJ Open Research, Vol: 6, Pages: 1-10, ISSN: 2312-0541
Self-management interventions in COPD aim to improve patients’ knowledge, skills and confidence to make correct decisions, thus improving health status and outcomes. myCOPD is a web-based self-management app known to improve inhaler use and exercise capacity in individuals with more severe COPD. We explored its impact in patients with mild-moderate or recently diagnosed COPD through a 12-week, 34open-label, parallel-group, randomised-controlled trial of myCOPD compared with usual care. The co-primary outcomes were between group differences in mean COPD assessment test (CAT) score at 90 days and critical inhaler errors. Key secondary outcomes were app usage and patient activation measurement (PAM) score. 3860 patients were randomised (29 myCOPD, 31 usual care). Groups were balanced for FEV1% predicted but baseline imbalance between groups for exacerbation frequency and CAT score. There was no significant adjusted mean difference in CAT score at study completion, -1.27 (95% CI -4.47 to 1.92, p=0.44) lower in COPD. However increasing app use associated with greater CAT score improvement. The odds of ≥1 critical inhaler error was lower in the myCOPD arm (adjusted odds ratio of 0.30 (0.09; 431.06, p=0.061)). The adjusted odds ratio for being in a higher PAM level at 90 days was 1.65 (0.46; 5.85) in favour of myCOPD. The small sample size and phenotypic difference between groups limited our ability to demonstrate statistically significant evidence of benefit beyond inhaler technique. However, our findings provide important insights into associations between increased app use and clinically meaningful benefit 48warranting further study in real world settings.
Cro S, Morris TP, Kahan BC, et al., 2020, A four-step strategy for handling missing outcome data in randomised trials affected by a pandemic, BMC Medical Research Methodology, Vol: 20, ISSN: 1471-2288
BackgroundThe coronavirus pandemic (Covid-19) presents a variety of challenges for ongoing clinical trials, including an inevitably higher rate of missing outcome data, with new and non-standard reasons for missingness. International drug trial guidelines recommend trialists review plans for handling missing data in the conduct and statistical analysis, but clear recommendations are lacking.MethodsWe present a four-step strategy for handling missing outcome data in the analysis of randomised trials that are ongoing during a pandemic. We consider handling missing data arising due to (i) participant infection, (ii) treatment disruptions and (iii) loss to follow-up. We consider both settings where treatment effects for a ‘pandemic-free world’ and ‘world including a pandemic’ are of interest.ResultsIn any trial, investigators should; (1) Clarify the treatment estimand of interest with respect to the occurrence of the pandemic; (2) Establish what data are missing for the chosen estimand; (3) Perform primary analysis under the most plausible missing data assumptions followed by; (4) Sensitivity analysis under alternative plausible assumptions. To obtain an estimate of the treatment effect in a ‘pandemic-free world’, participant data that are clinically affected by the pandemic (directly due to infection or indirectly via treatment disruptions) are not relevant and can be set to missing. For primary analysis, a missing-at-random assumption that conditions on all observed data that are expected to be associated with both the outcome and missingness may be most plausible. For the treatment effect in the ‘world including a pandemic’, all participant data is relevant and should be included in the analysis. For primary analysis, a missing-at-random assumption – potentially incorporating a pandemic time-period indicator and participant infection status – or a missing-not-at-random assumption with a poorer response may b
Ue KL, Hunter H, Cornelius V, et al., 2020, Preliminary results of a phase II trial of peanut oral immunotherapy in adults, European-Academy-of-Allergology-and-Clinical-Immunology Digital Congress (EAACI), Publisher: WILEY, Pages: 301-301, ISSN: 0105-4538
Phillips R, Cornelius V, 2020, Understanding current practice, identifying barriers and exploring priorities for Adverse Event analysis in Randomised Controlled Trials: an online, cross-sectional survey of statisticians from academia and industry, BMJ Open, Vol: 10, ISSN: 2044-6055
Objectives To gain a better understanding of current adverse event (AE) analysis practices and the reasons for the lack of use of sophisticated statistical methods for AE data analysis in randomised controlled trials (RCTs), with the aim of identifying priorities and solutions to improve practice.Design A cross-sectional, online survey of statisticians working in clinical trials, followed up with a workshop of senior statisticians working across the UK.Participants We aimed to recruit into the survey a minimum of one statistician from each of the 51 UK Clinical Research Collaboration registered clinical trial units (CTUs) and industry statisticians from both pharmaceuticals and clinical research organisations.Outcomes To gain a better understanding of current AE analysis practices, measure awareness of specialist methods for AE analysis and explore priorities, concerns and barriers when analysing AEs.Results Thirty-eight (38/51; 75%) CTUs, 5 (5/7; 71%) industry and 21 attendees at the 2019 Promoting Statistical Insights Conference participated in the survey. Of the 64 participants that took part, 46 participants were classified as public sector participants and 18 as industry participants. Participants indicated that they predominantly (80%) rely on subjective comparisons when comparing AEs between treatment groups. Thirty-eight per cent were aware of specialist methods for AE analysis, but only 13% had undertaken such analyses. All participants believed guidance on appropriate AE analysis and 97% thought training specifically for AE analysis is needed. These were both endorsed as solutions by workshop participants.Conclusions This research supports our earlier work that identified suboptimal AE analysis practices in RCTs and confirms the underuse of more sophisticated AE analysis approaches. Improvements are needed, and further research in this area is required to identify appropriate statistical methods. This research provides a unanimous call for the development
Chis Ster AM, Cornelius V, Cro S, 2020, Current approaches to handling rescue medication in asthma and eczema randomized controlled trials are inadequate: a systematic review., Journal of Clinical Epidemiology, Vol: 125, Pages: 148-157, ISSN: 0895-4356
OBJECTIVES: The objective of this study was to examine how rescue medication is defined, reported, and accounted for in randomized controlled trials (RCTs) in eczema and asthma populations. STUDY DESIGN AND SETTING: This is a systematic review of phase II/III RCTs evaluating monoclonal antibodies for treating chronic eczema or asthma. A search of EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials was conducted to identify eligible RCTs. RESULTS: Sixty published RCTs were identified, of which 60 (100%) allowed use of rescue medication but only 28 (47%) reported its use. Twenty-seven (45%) articles summarized rescue use by arm, with an average of 25% (95% CI (17%, 36%)) greater use in the placebo arm. Nine (15%) trials undertook an analysis that adjusted the primary treatment effect estimate for rescue medication use, but 8 of these used a suboptimal approach using single imputation, including 4 which used "last observation carried forward" after setting postrescue data to missing. CONCLUSION: Rescue medication use in eczema and asthma trials evaluating monoclonal antibodies is often permitted, but not routinely reported. There is evidence of imbalance in rescue use between arms, but few articles attempted to estimate a rescue-adjusted treatment effect. In trials that did, the methods used were suboptimal which could introduce bias.
Hadfield DJ, Rose L, Reid F, et al., 2020, Neurally adjusted ventilatory assist versus pressure support ventilation: a randomized controlled feasibility trial performed in patients at risk of prolonged mechanical ventilation., Critical Care (UK), Vol: 24, Pages: 1-20, ISSN: 1364-8535
BACKGROUND: The clinical effectiveness of neurally adjusted ventilatory assist (NAVA) has yet to be demonstrated, and preliminary studies are required. The study aim was to assess the feasibility of a randomized controlled trial (RCT) of NAVA versus pressure support ventilation (PSV) in critically ill adults at risk of prolonged mechanical ventilation (MV). METHODS: An open-label, parallel, feasibility RCT (n = 78) in four ICUs of one university-affiliated hospital. The primary outcome was mode adherence (percentage of time adherent to assigned mode), and protocol compliance (binary-≥ 65% mode adherence). Secondary exploratory outcomes included ventilator-free days (VFDs), sedation, and mortality. RESULTS: In the 72 participants who commenced weaning, median (95% CI) mode adherence was 83.1% (64.0-97.1%) and 100% (100-100%), and protocol compliance was 66.7% (50.3-80.0%) and 100% (89.0-100.0%) in the NAVA and PSV groups respectively. Secondary outcomes indicated more VFDs to D28 (median difference 3.0 days, 95% CI 0.0-11.0; p = 0.04) and fewer in-hospital deaths (relative risk 0.5, 95% CI 0.2-0.9; p = 0.032) for NAVA. Although overall sedation was similar, Richmond Agitation and Sedation Scale (RASS) scores were closer to zero in NAVA compared to PSV (p = 0.020). No significant differences were observed in duration of MV, ICU or hospital stay, or ICU, D28, and D90 mortality. CONCLUSIONS: This feasibility trial demonstrated good adherence to assigned ventilation mode and the ability to meet a priori protocol compliance criteria. Exploratory outcomes suggest some clinical benefit for NAVA compared to PSV. Clinical effectiveness trials of NAVA are potentially feasible and warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01826890. Registered 9 April 2013.
Raad H, Cornelius V, Chan S, et al., 2020, An evaluation of inverse probability weighting using the propensity score for baseline covariate adjustment in smaller population randomised controlled trials with a continuous outcome, BMC Medical Research Methodology, Vol: 20, Pages: 1-12, ISSN: 1471-2288
BackgroundIt is important to estimate the treatment effect of interest accurately and precisely within the analysis of randomised controlled trials. One way to increase precision in the estimate and thus improve the power for randomised trials with continuous outcomes is through adjustment for pre-specified prognostic baseline covariates. Typically covariate adjustment is conducted using regression analysis, however recently, Inverse Probability of Treatment Weighting (IPTW) using the propensity score has been proposed as an alternative method. For a continuous outcome it has been shown that the IPTW estimator has the same large sample statistical properties as that obtained via analysis of covariance. However the performance of IPTW has not been explored for smaller population trials (< 100 participants), where precise estimation of the treatment effect has potential for greater impact than in larger samples.MethodsIn this paper we explore the performance of the baseline adjusted treatment effect estimated using IPTW in smaller population trial settings. To do so we present a simulation study including a number of different trial scenarios with sample sizes ranging from 40 to 200 and adjustment for up to 6 covariates. We also re-analyse a paediatric eczema trial that includes 60 children.ResultsIn the simulation study the performance of the IPTW variance estimator was sub-optimal with smaller sample sizes. The coverage of 95% CI’s was marginally below 95% for sample sizes < 150 and ≥ 100. For sample sizes < 100 the coverage of 95% CI’s was always significantly below 95% for all covariate settings. The minimum coverage obtained with IPTW was 89% with n = 40. In comparison, regression adjustment always resulted in 95% coverage. The analysis of the eczema trial confirmed discrepancies between the IPTW and regression estimators in a real life small population setting.ConclusionsThe IPTW variance e
Sin J, Henderson C, Cornelius V, et al., 2020, COPe-support-a multi-component digital intervention for family carers for people affected by psychosis: study protocol for a randomized controlled trial, BMC Psychiatry, Vol: 20, Pages: 1-14, ISSN: 1471-244X
BackgroundPsychosis often causes significant distress and impacts not only in the individuals, but also those close to them. Many relatives and friends (‘carers’) provide long-term support and need resources to assist them. We have co-produced a digital mental health intervention called COPe-support (Carers fOr People with Psychosis e-support) to provide carers with flexible access to high quality psychoeducation and interactive support from experts and peers. This study evaluates the effectiveness of COPe-support to promote mental wellbeing and caregiving experiences in carers.MethodsThis study is a single-blind, parallel arm, individually randomized controlled trial (RCT) comparing COPe-support, with attention control. Both groups continue to receive usual care. COPe-support provides interactive web-based psychoeducation on psychosis-related issues, wellbeing-promotion and network support through forums. The attention-control is a non-interactive online information resource pack. Carers living in England are eligible if they provide at least weekly support to a family member or close friend affected by psychosis, and use internet communication (including emails) daily. All trial procedures are run online, including collection of outcome measurements which participants will directly input into our secure platform. Following baseline assessment, a web-based randomization system will be used to allocate 360 carers to either arm. Participants have unlimited access to the allocated condition for 40 weeks. Data collection is at three time points (10, 20, and 40 weeks after randomization). Analyses will be conducted by trial statisticians blinded to allocation. The primary outcome is mental wellbeing measured by Warwick Edinburgh Mental Wellbeing Scale (WEMWBS), at 20 weeks. As well as an intention-to-treat analysis, a complier average causal effect (CACE) analysis will be conducted to estimate the intervention effect in participants who
Cro S, Patel P, Barker J, et al., 2020, A randomised placebo controlled trial of anakinra for treating pustular psoriasis: statistical analysis plan for stage two of the APRICOT trial, Trials, Vol: 21, ISSN: 1745-6215
Background:Current treatment options for Palmoplantar Pustulosis (PPP), a debilitating chronic skin disease which affects the hands and feet, are limited. The Anakinra for Pustular psoriasis: Response in a Controlled Trial (APRICOT) aims to determine the efficacy of anakinra in the treatment of PPP. This article describes the statistical analysis plan for the final analysis of this two-staged trial, which was determined prior to unblinding and database lock. This is an update to the published protocol and stage one analysis plan.Methods:APRICOT is a randomised, double-blind, placebo-controlled trial of anakinra versus placebo, with two stages and an adaptive element. Stage one compared treatment arms to ensure proof-of-concept and determined the primary outcome for stage two of the trial. The primary outcome was selected to be the change in Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. Secondary outcomes include other investigator-assessed efficacy measures of disease severity, participant-reported measures of efficacy and safety measures. This manuscript describes in detail the outcomes, sample size, general analysis principles, the pre-specified statistical analysis plan for each of the outcomes, the handling of missing outcome data and the planned sensitivity and supplementary analyses for the second stage of the APRICOT trial.Discussion:This statistical analysis plan was developed in compliance with international trial guidelines and is published to increase transparency of the trial analysis. The results of the trial analysis will indicate whether anakinra has a role in the treatment of PPP.Trial registration:ISCRTN, ISCRTN13127147. Registered on 1 August 2016. EudraCT Number 2015-003600-23. Registered on 1 April 2016.
Kelleher MM, Cro S, Cornelius V, et al., 2020, Skincare interventions in infants for preventing eczema and food allergy, Cochrane Database of Systematic Reviews, Vol: 2020
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:. Primary objective. To assess the effects of skincare interventions, such as emollients, for prevention of eczema and food allergy in infants. Secondary objectives. To ascertain whether active skincare interventions, commenced in early infancy, influence risk of developing eczema or food allergy To identify features of the study populations such as age, hereditary risk and adherence to the interventions, which are associated with the greatest treatment benefit or harm for both eczema and food allergy.
Chan S, Cornelius V, Cro S, et al., 2020, Treatment effect of omalizumab on severe pediatric atopic dermatitis: The ADAPT randomized clinical trial, JAMA Pediatrics, Vol: 174, Pages: 29-37, ISSN: 2168-6203
Importance: Systemic treatments for severe childhood atopic dermatitis have limited evidence and/or are unlicensed. Despite the efficacy of anti-IgE medication (omalizumab) in the treatment of atopy, no large randomized studies in childhood atopic dermatitis have been published. Objective: To determine the effectiveness of omalizumab in treating severe atopic dermatitis in children. Design, Setting, and Participants: The Atopic Dermatitis Anti-IgE Pediatric Trial (ADAPT) was a 24-week single-center, double-blind, placebo-controlled randomized clinical trial with a 24-week follow-up. Conducted from November 20, 2014, to August 31, 2017, at Guy's and St Thomas' Hospital NHS Foundation Trust and King's College London in the United Kingdom, this trial recruited participants after a screening visit. Eligible participants (n = 62) were aged 4 to 19 years and had severe eczema (with objective Scoring Atopic Dermatitis [SCORAD] index >40) that was unresponsive to optimum therapy. Statistical analysis was conducted using the intention-to-treat principle. Interventions: Subcutaneous omalizumab or placebo for 24 weeks. The drug manufacturer's dosing tables were used to determine the dosage based on total IgE (30-1500 IU/mL) and body weight (in kilograms) at randomization. Main Outcomes and Measures: Objective SCORAD index after 24 weeks of treatment. Results: In total, 62 children (mean [SD] age, 10.3 [4.2] years; 32 (52%) were male) were randomized to either omalizumab (n = 30) or placebo (n = 32). Five participants withdrew from treatment (4 [13%] from the placebo group, and 1 [3%] from the omalizumab group). Follow-up attendance was 97% at week 24 and 98% at week 48. After adjustment for baseline objective SCORAD index, age, and IgE level, the mean difference in objective SCORAD index improvement between groups at week 24 was -6.9 (95% CI, -12.2 to -1.5; P = .01), significantly favoring omalizumab therapy and reflec
Ue KL, Hunter H, Cornelius V, et al., 2019, Correlation of Ara h 2 immunoglobulin E level with reactivity threshold in peanut-allergic adults, Publisher: WILEY, Pages: 1647-1647, ISSN: 0954-7894
Sanfilippo KRM, McConnell B, Cornelius V, et al., 2019, A study protocol for testing the feasibility of a randomised stepped wedge cluster design to investigate a Community Health Intervention through Musical Engagement (CHIME) for perinatal mental health in The Gambia., Pilot Feasibility Stud, Vol: 5, Pages: 1-8, ISSN: 2055-5784
Background: Perinatal mental health problems affect up to one in five women worldwide. Mental health problems in the perinatal period are a particular challenge in low- and middle-income countries (LMICs) where they can be at least twice as frequent as in higher-income countries. It is thus of high priority to develop new low-cost, low-resource, non-stigmatising and culturally appropriate approaches to reduce symptoms of anxiety and depression perinatally, for the benefit of both mother and child. Music-centred approaches may be particularly useful in The Gambia since a range of musical practices that specifically engage pregnant women and new mothers already exist. Methods: This protocol is for a study to examine the feasibility of undertaking a stepped wedge trial to test how a Community Health Intervention through Musical Engagement (CHIME) could be beneficial in alleviating perinatal mental distress in The Gambia. In this study, we plan to recruit 120 pregnant women (n = 60 intervention, n = 60 control) at four antenatal clinics over two 6-week stepped sequences. Women in the intervention will participate in weekly group-singing sessions, led by local Kanyeleng singing groups, for 6 weeks. The control group will receive standard care. We will assess symptoms of anxiety and depression using the Edinburgh Postnatal Depression Scale (EPDS) and the Self-Reporting Questionnaire (SRQ-20). The feasibility of the design will be assessed through recruitment, retention and attrition rates of participants, clinics' adherence to the schedule and completeness of data by site. Qualitative interviews and video and audio recordings will be used to evaluate the acceptability of the intervention. Discussion: This feasibility trial will allow us to determine whether a larger trial with the same intervention and target group is feasible and acceptable in The Gambia. Trial registration: Retrospectively registered (24/01/2019) with Pan African Clinica
Phillips R, Cornelius V, Cro S, et al., 2019, The use of visual analytics for clinical trial safety outcomes: a methodological review, 5th International Clinical Trials Methodology Conference, Publisher: BMC
Phillips R, Cornelius V, Sauzet O, 2019, Opportunities and experiences of accessing pharmaceutical individual patient data for statistical research, 5th International Clinical Trials Methodology Conference, Publisher: BMC
Phillips R, Cornelius V, Sauzet O, 2019, An evaluation and application of statistical methods designed to analyse adverse event data in RCTs, 5th International Clinical Trials Methodology Conference, Publisher: BMC
Chen T, Li C, Wang Y, et al., 2019, Overestimation of Event Rate and Target Difference among Randomized Clinical in sample size calculations Trials: a cross-sectional survey review, Publisher: BMC
Ster AMC, Cornelius V, Cro S, 2019, Statistical approaches to adjust for the use of rescue medication in randomised controlled trials, Publisher: BMC
Cro S, Chan S, Cornelius V, 2019, Controlled multiple imputation: an accessible flexible tool for estimating hypothetical estimands in clinical trials, Publisher: BMC
Babalis D, Saglani S, Cornelius V, 2019, To fund or not to fund a paediatric severe asthma trial: that is the question, Publisher: BMC
Sanfilippo KRM, Cornelius V, McConnell B, et al., 2019, Testing the Feasibility of a Complex Intervention for Perinatal Mental Health in The Gambia, Publisher: BMC
Cornelius V, Cro S, 2019, Designing trials for small populations, Publisher: BMC
Cornelius V, Johnston CL, 2019, The enhanced peri-operative care for high-risk patients trial: an independent discussion and commentary, British Journal of Anaesthesia, Vol: 123, Pages: 261-266, ISSN: 0007-0912
Sayar Z, Czuprynska J, Patel JP, et al., 2019, What are the difficulties in conducting randomised controlled trials of thromboprophylaxis in myeloma patients and how can we address these? Lessons from apixaban versus LMWH or aspirin as thromboprophylaxis in newly diagnosed multiple myeloma (TiMM) feasibility clinical trial, Journal of Thrombosis and Thrombolysis, Vol: 48, Pages: 315-322, ISSN: 0929-5305
Routine thromboprophylaxis (TP) in newly-diagnosed multiple myeloma (NDMM) patients comprises either aspirin for standard risk patients or low molecular weight heparin for high risk patients. Studies using DOACs in cancer patients include few with myeloma. The aim of this feasibility clinical trial was to establish the foundations for creating a multicentre trial and identify any safety concerns with apixaban. Patient perspectives were sought. NDMM patients were stratified according to VTE risk and randomised to either standard TP or apixaban 2.5 mg BD and reviewed every 3 weeks throughout their chemotherapy. Two focus groups were carried out on 2 occasions at King’s College Hospital and Guy’s Hospital, London. Each lasted an hour, were recorded, transcribed and themes explored using NVivo 11. Ten patients were recruited, 2 considered high risk and received apixaban and 8 standard risk; 4 randomised to aspirin and 4 to apixaban. Five patients and 2 carers participated in the focus groups. There were no major bleeding or VTE events. Patients were not aware of the thrombotic risk associated with cancer. There is a lack of both written and verbal information on this topic. Myeloma patients were happy to be included in more than one trial simultaneously. Our study provides information on the difficulties facing physicians and patients on obtaining evidence of the safety of DOACs in the context of myeloma. Despite patients being happy to co-recruit into thromboprophylaxis trials along with chemotherapy trials this is not current practice.
Gimeno H, Brown R, Lin JP, et al., 2019, AUGMENTING FUNCTIONAL PERFORMANCE FOLLOWING DEEP BRAIN STIMULATION WITH A COGNITIVE APPROACH FOR INDIVIDUALS WITH HYPERKINETIC MOVEMENT DISORDERS, Publisher: SAGE PUBLICATIONS LTD, Pages: 52-53, ISSN: 0308-0226
Chen T, Li C, Qin R, et al., 2019, Comparison of clinical trial changes in primary outcome and reported intervention effect size between trial registration and publication., JAMA Network Open, Vol: 2, Pages: 1-12, ISSN: 2574-3805
Importance: Primary outcome change could threaten the validity of a clinical trial; however, evidence about the consequences on the reported intervention effect size is unclear. Objectives: To examine the status of randomized clinical trials whose primary outcome changed between trial registration and publication and to quantify the association of this change with the reported intervention effect size. Design, Setting, and Participants: In this cross-sectional study on the primary report of randomized clinical trials with clear prospectively registered primary outcomes, PubMed and Embase were searched for articles published between January 1, 2011, and December 31, 2015. The search was conducted in January 2016, identifying randomized clinical trials and the combination of keywords and text words related to registry. Main Outcomes and Measures: Based on the developed approach, trials were classified as having primary outcome change when there was a major discrepancy between the registered and published primary outcomes. Intervention effect was estimated or recalculated using the odds ratio (OR) for each comparison. Each component OR is structured so that an OR is less than 1 if the intervention group has a more favorable result than the control group. The ratio of ORs (ROR), which is the summary OR for trials with primary outcome change divided by those without, and its 95% CI were calculated, with a value less than 1 indicating a larger reported intervention effect size in trials with primary outcome change than those without. Results: Among 29 749 searched articles (28 810 MEDLINE and 939 Embase), 1488 articles were randomly selected for review. Of 389 trials with clear primary outcomes prospectively described in the registry (416 outcomes reported), 33.4% (130 of 389) of trials had at least 1 primary outcome change. Most (66 of 130) of the changes were either not reporting or omitting the primary outcome. In total, 338 trials (365 outcomes and 487 comparisons) we
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.