Caroline Jane Dore

University College London | UCL · Comprehensive Clinical Trials Unit

Background The contribution of the statistician to the design and analysis of a clinical trial is acknowledged as essential. Ability to reconstruct the statistical contribution to a trial requires rigorous and transparent documentation as evidenced by the reproducibility of results. The process of validating statistical programmes is a key requirem...

Clarity and guidance is required with regard to the use of direct oral anticoagulants in antiphospholipid syndrome (APS) patients, within the confines of the recent European Medicines Agency recommendations, discrepant recommendations in other international guidelines and the limited evidence base. To address this, the Lupus Anticoagulant/Antiphosp...

Background Less invasive perinatal and paediatric autopsy methods, such as imaging alongside targeted endoscopy and organ biopsy, may address declining consent rates for traditional autopsy, but their acceptability and accuracy are not known. Objectives The aims of this study were to provide empirical data on the acceptability and likely uptake fo...

OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVEs in RA patients. METHODS: A randomized, double‐blind, placebo‐controlled trial was designed to detect a 32% CVE r...

Objective: We aimed to test the feasibility of using an online parent-completed diagnostic assessment for detecting common mental health disorders in children attending neurology clinics. The assessment does not require intervention by a mental health professional or additional time in the clinic appointment. Setting: Two parallel and related sc...

Background Anogenital warts are the second most common sexually transmitted infection diagnosed in sexual health services in England. About 90% of genital warts are caused by human papillomavirus (HPV) types 6 or 11, and half of episodes diagnosed are recurrences. The best and most cost-effective treatment for patients with anogenital warts is unkn...

Importance While guidance on statistical principles for clinical trials exists, there is an absence of guidance covering the required content of statistical analysis plans (SAPs) to support transparency and reproducibility. Objective To develop recommendations for a minimum set of items that should be addressed in SAPs for clinical trials, develop...

Background Children and young people with chronic neurological conditions have significantly higher rates of mental health disorders than those without a chronic health condition, or those with chronic illnesses that do not involve the CNS. Mental health problems can impact on quality of life as well as on the management and medical consequences of...

Objectives: RA patients receiving TNF inhibitors (TNFi) usually maintain their initial doses. The aim of the Optimizing Treatment with Tumour Necrosis Factor Inhibitors in Rheumatoid Arthritis trial was to evaluate whether tapering TNFi doses causes loss of clinical response. Methods: We enrolled RA patients receiving etanercept or adalimumab an...

During the uploading of data for submission to the EudraCT results database, a discrepancy was identified. It was noted that the number of deaths per group was not consistent with the number in the final report and trial publication. This discrepancy was found to relate to two randomisation numbers. During the trial, the randomisation database had...

Objectives: Designing studies with an internal pilot phase may optimise the use of pilot work to inform more efficient randomised controlled trials (RCTs). Careful selection of preagreed decision or 'progression' criteria at the juncture between the internal pilot and main trial phases provides a valuable opportunity to evaluate the likely success...

Objective: Painful knee osteoarthritis (KOA) has been associated with joint inflammation. There is, however, little literature correlating signs of localized inflammation with contrast-enhanced (CE) magnetic resonance imaging (MRI) of synovium. This study examined the relationship between clinical and functional markers of localized knee inflammat...

Objective: To determine whether modifying an outcome definition to remove subjective elements reduced bias in a trial that could not use blinded outcome assessment. Study setting and design: Re-analysis of an open-label trial comparing a restrictive vs. liberal transfusion strategy for gastrointestinal bleeding. The usual definition of the prima...

Objective: Epidemiological data suggest low serum 25-hydroxyvitamin D3 (25-OH-D3) levels are associated with radiological progression of knee osteoarthritis (OA). This study aimed to assess whether vitamin D supplementation can slow the rate of progression. Method: A 3-year, double-blind, randomised, placebo-controlled trial of 474 patients aged...

Objectives Sickle With Ibuprofen and Morphine (SWIM) trial was designed to assess whether co-administration of ibuprofen (a non-steroidal anti-inflammatory drug) resulted in a reduction of opioid consumption delivered by patient-controlled analgesia (PCA) for acute pain in sickle cell disease. Design A randomised, placebo-controlled, double-blind t...

Background: Parenteral nutrition is central to the care of very immature infants. Current international recommendations favor higher amino acid intakes and fish oil-containing lipid emulsions. Objective: The aim of this trial was to compare1) the effects of high [immediate recommended daily intake (Imm-RDI)] and low [incremental introduction of...

Parenteral nutrition (PN) is central to the care of very immature infants. Early intakes of higher amounts of amino acids and the use of lipid emulsions containing fish oils are recommended by current international recommendations. Objective To confirm the safety and demonstrate efficacy of the immediate introduction of the recommended daily intak...

Background Recruitment to clinical trials is often problematic, with many trials failing to recruit to their target sample size. As a result, patient care may be based on suboptimal evidence from underpowered trials or non-randomised studies. Methods For many conditions patients will require treatment on several occasions, for example, to treat sy...

Patient recruitment is a major challenge for randomised trials. Reviews of publicly funded UK trials have found that 45 to 69% fail to recruit to target. This increases costs, delays results, and adversely impacts on the feasibility of conducting trials for conditions where there is a limited patient pool. For some conditions a patient requires tre...

Until recently, insufficient attention has been paid to the fact that surgical interventions are complex. This complexity has several implications, including the way in which surgical interventions are described and delivered in trials. In order for surgeons to adopt trial findings, interventions need to be described in sufficient detail to enable...

The variable-flow flow driver (FD; EME) and continuous-flow bubble (Fisher-Paykel) continuous positive airway pressure (CPAP) systems are widely used. As these differ in cost and technical requirements, determining comparative efficacy is important particularly where resources are limited. We performed a randomised, controlled, equivalence trial of...

The objective of our study was to compare quantitative maximum breast mass stiffness on shear-wave elastography (SWE) with histopathologic outcome. From September 2008 through September 2010, at 16 centers in the United States and Europe, 1647 women with a sonographically visible breast mass consented to undergo quantitative SWE in this prospective...

Transfusion thresholds for acute upper gastrointestinal bleeding are controversial. So far, only three small, underpowered studies and one single-centre trial have been done. Findings from the single-centre trial showed reduced mortality with restrictive red blood cell (RBC) transfusion. We aimed to assess whether a multicentre, cluster randomised...

Introduction: The current mainstay of the treatment of thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation with vitamin K antagonists (VKAs) such as warfarin. Non-VKA oral anticoagulants (NOACs), which include rivaroxaban, have been shown to be effective and safe compared with warfarin for the treatment of venous thromboembolis...

Ciclosporin and MTX are used in idiopathic inflammatory myopathies (DM and PM) when patients incompletely respond to glucocorticoids. Their effectiveness is unproved in randomized controlled trials (RCTs). We evaluated their benefits in a placebo-controlled factorial RCT. A 56-week multicentre factorial-design double-blind placebo-controlled RCT co...

Background: Blinded outcome assessment is recommended in open-label trials to reduce bias, however it is not always feasible. It is therefore important to find other means of reducing bias in these scenarios. Methods: We describe two randomised trials where blinded outcome assessment was not possible, and discuss the strategies used to reduce th...

Objectives & Background Transfusion thresholds for upper gastrointestinal bleeding (UGIB) are controversial. Observational studies suggest associations between liberal red blood cell (RBC) transfusion and adverse outcome. A recent trial reported increased mortality following liberal transfusion. We delivered a cluster randomised trial to evaluate t...

Adjustment for prognostic covariates can lead to increased power in the analysis of randomized trials. However, adjusted analyses are not often performed in practice. We used simulation to examine the impact of covariate adjustment on 12 outcomes from 8 studies across a range of therapeutic areas. We assessed (1) how large an increase in power can...

Lumbar spinal stenosis is a common cause of back pain that can also give rise to pain in the buttock, thigh or leg, particularly when walking. Several possible treatments are available, of which surgery appears to be best at restoring function and reducing pain. Surgical outcome is not ideal, and a sizeable proportion of patients do not regain good...

Background: Lumbar spinal stenosis is a common cause of back pain that can also give rise to pain in the buttock, thigh or leg, particularly when walking. Several possible treatments are available, of which surgery appears to be best at restoring function and reducing pain. Surgical outcome is not ideal, and a sizeable proportion of patients do no...

As part of a randomised controlled study into the post-operative management of spinal surgery, this qualitative sub-study sought to explore the patients’ experience of the healthcare system and their perceptions of how the system had worked for them, with a view to establishing more appropriate care pathways and improved support materials for patie...

The majority of studies of surgical outcome focus on measures of function and pain. Increasingly, however, the desire to include domains such as patients' satisfaction and expectations had led to the development of simple measures and their inclusion into clinical studies. The purpose of this study was to determine patients' pre-operative expectati...

Background Previous research has suggested an association between more liberal red blood cell (RBC) transfusion and greater risk of further bleeding and mortality following acute upper gastrointestinal bleeding (AUGIB). Methods and design The Transfusion in Gastrointestinal Bleeding (TRIGGER) trial is a pragmatic cluster-randomised feasibility tri...

Acute upper gastrointestinal bleeding (AUGIB) is the commonest reason for hospitalization with hemorrhage in the UK and the leading indication for transfusion of red blood cells (RBCs). Observational studies suggest an association between more liberal RBC transfusion and adverse patient outcomes, and a recent randomised trial reported increased fur...

Blood flow, colour Doppler ultrasound, low back pain

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items:Recommendations for Interventional Trials) 2013...

Background: Following non-variceal upper gastrointestinal bleeding (NVUGIB), 10-15 per cent of patients experience further bleeding. Although surgery has been the traditional salvage therapy, there is renewed interest in transcatheter arterial embolization (TAE). This study examined the use, clinical characteristics and outcomes of patients receiv...

Study design: Prospective, clinical, noninvasive imaging study. Objective: To quantify normal lumbar artery hemodynamics and develop a reference range and lumbar artery hemodynamics in patients with low back pain. Summary of background data: Blood supply to the lumbar spinal tissues, intraosseous capillary circulation, and avascular interverte...

PURPOSE To determine potential impact of shear-wave elastography (SWE) on reclassification of sonographic BI-RADS 3 breast masses to BI-RADS 2. Previous reports indicate that upgrading BI-RADS 3 masses suspicious on SWE to biopsy (BI-RADS 4a) is appropriate. METHOD AND MATERIALS From 9/2008 to 9/2010, across 16 centers in Europe and USA, 1647 wome...

Hintergrund und Studienziele: Der Nutzen der therapeutischen Endoskopie bei der nicht varikösen oberen gastrointestinalen Blutung (NVOGIB) ist unbestritten. Der optimale Zeitpunkt hingegen ist unklar. Ziel der vorliegenden Studie war die Untersuchung des Zusammenhangs zwischen Endoskopiezeitpunkt und klinischem Behandlungsergebnis bei Patienten mit...

Objective: Anti-inflammatory therapies are effective analgesics for OA. This study determined whether low-dose oral prednisolone (PNL) was an effective analgesic for hand OA. Methods: This was a randomized, double-blind, placebo-controlled trial of people with ACR criteria hand OA and baseline hand pain visual analogue scale (VAS) of >40/100 mm....

Despite the established efficacy of therapeutic endoscopy, the optimum timeframe for performing endoscopy in patients with nonvariceal upper gastrointestinal bleeding (NVUGIB) remains unclear. The aim of the current audit study was to examine the relationship between time to endoscopy and clinical outcomes in patients presenting with NVUGIB. This s...

This study aims to examine the utility of von Willebrand factor (vWF) as a biomarker in lcSSc, in particular the ability of vWF to predict the future development of disease manifestations in this disease. vWFAg concentrations were measured in the serum of patients with lcSSc at baseline and at 3 years, during the QUINs trial [Prevention of Vascular...

Verkorte weergave Are subjective clinical findings and objective clinical tests related to the motion characteristics of low back pain subjects? [Journal of Orthopaedic and Sports Physical Therapy 1998;28(6):370-6]

Objective The authors performed a randomised trial in very preterm small-for-gestational age (SGA) babies to determine if prophylaxis with granulocyte-macrophage colony-stimulating factor (GM-CSF) improves outcomes (the PROGRAMS trial). Despite increased neutrophil counts following GM-CSF, the authors reported no significant difference in neonatal...

This study evaluated an evidence-based education booklet developed for patients undergoing spinal surgery which was used as a treatment intervention in a multi-centre, factorial, randomised controlled trial (FASTER: Function after spinal treatment, exercise and rehabilitation) investigating the post-operative management of spinal surgery patients....

To determine whether adding shear-wave (SW) elastographic features could improve accuracy of ultrasonographic (US) assessment of breast masses. From September 2008 to September 2010, 958 women consented to repeat standard breast US supplemented by quantitative SW elastographic examination in this prospective multicenter institutional review board-a...

To evaluate intra- and interobserver reproducibility of shear wave elastography (SWE) for breast masses. For intraobserver reproducibility, each observer obtained three consecutive SWE images of 758 masses that were visible on ultrasound. 144 (19%) were malignant. Weighted kappa was used to assess the agreement of qualitative elastographic features...

This study invited patients to evaluate the content and style of a rehabilitation program used as an intervention in a multicenter, factorial, randomized controlled trial of the postoperative management of spinal surgery patients. To determine the acceptability and content of the rehabilitation program. The use of rehabilitation after spinal surger...

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Individual compartments of abdominal adiposity and lipid content within the liver and muscle are differentially associated with metabolic risk factors, obesity and insulin resistance. Subjects with greater intra-abdominal adipose tissue (IAAT) and hepatic fat than predicted by clinical indices of obesity may be at increased risk of metabolic diseas...

Maternal overweight and obesity are associated with adverse offspring outcome in later life. The causal biological effectors are uncertain. Postulating that initiating events may be alterations to infant body composition established in utero, we tested the hypothesis that neonatal adipose tissue (AT) content and distribution and liver lipid are inf...

Cost-effectiveness analysis alongside a factorial randomized controlled trial. To assess the cost-effectiveness of a rehabilitation program and/or an education booklet each compared with usual care for the postoperative management of patients undergoing discectomy or lateral nerve root decompression surgery. There is little knowledge about the cost...

To assess the prevalence of disease-specific autoantibodies in patients with limited cutaneous systemic sclerosis (lcSSc). Sera from 180 patients with lcSSc were analyzed for antinuclear antibody (ANA). Clinical characteristics were compared in the presence or absence of specific autoantibodies. SSc-specific antibodies were detected in 135 patients...

IntroductionTransfusion of red blood cells (RBCs) is a cornerstone for managing AUGIB. There has been a paradigm shift over the last decade in critical care and surgery with several studies associating RBC transfusion with adverse patient outcomes. Most relevant to decision making are recent data suggesting an association between early RBC transfus...

This was a multicenter, factorial, randomized, controlled trial on the postoperative management of spinal surgery patients, with randomization stratified by surgeon and operative procedure. This study sought to determine whether the functional outcome of two common spinal operations could be improved by a program of postoperative rehabilitation tha...