Imperial College London

ProfessorDeborahAshby

Faculty of MedicineSchool of Public Health

Director of the School of Public Health
 
 
 
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Contact

 

+44 (0)20 7594 8704deborah.ashby Website

 
 
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Location

 

153Medical SchoolSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

189 results found

Modi N, Ashby D, Battersby C, Brocklehurst P, Chivers Z, Costeloe K, Draper E, Foster V, Kemp J, Majeed A, Murray J, Petrou S, Rogers K, Santhakumaran S, Saxena S, Statnikov Y, Wong H, Young Aet al., Using routinely recorded clinical data for research: the Medicines for Neonates research programme, Programme Grants for Applied Research, ISSN: 2050-4322

Background: Clinical data offer potential to advance patient care. Neonatal specialised care is a high cost NHS service received by approximately 80,000 newborn infants each year. Objectives: To 1) develop the use of routinely recorded operational clinical data from Electronic Patient Records (EPR), secure national coverage, evaluate and improve the quality of clinical data, and develop their use as a national resource to improve neonatal healthcare and outcomes; test the hypotheses that 2) clinical and research data are of comparable quality; 3) routine NHS clinical assessment at age two-years reliably identifies children with neurodevelopmental impairment; and 4) trial-based economic evaluations of neonatal interventions can be reliably conducted using clinical data; 5) test methods to link NHS datasets; 6) evaluate parent views of personal data in research Design: Six interrelated work-streams; quarterly extractions of predefined data from neonatal EPR; approvals from the National Research Ethics Service, Health Research Authority Confidentiality Advisory Group, Caldicott Guardians and lead neonatal clinicians of participating NHS Trusts Setting: NHS neonatal unitsParticipants: Neonatal clinical teams; parents of babies admitted to NHS neonatal unitsInterventions: In work-stream 3 we employed the Bayley-III scales to evaluate neurodevelopmental status and the Quantitative Checklist of Autism in Toddlers (Q-CHAT) to evaluate social-communication skills. In work-stream 6 we recruited parents with previous experience of a child in neonatal care to assist in the design of a questionnaire directed at the parents of infants admitted to neonatal units. Data sources: Data extracted from the EPR of admissions to NHS neonatal units Main outcomes and results: We created a National Neonatal Research Database (NNRD) containing a defined extract from real-time, point-of-care, clinician-entered EPR from all NHS neonatal units in England, Wales and Scotland (n=200), establish

JOURNAL ARTICLE

Cook JA, Julious SA, Sones W, Hampson L, Hewitt C, Berlin JA, Ashby D, Emsley R, Fergusson DA, Walters SJ, Wilson ECF, MacLennan G, Stallard N, Rothwell JC, Bland M, Brown L, Ramsay CR, Cook A, Armstrong D, Altman D, Vale LDet al., 2018, DELTA(2) guidance on choosing the target difference and undertaking and reporting the sample size calculation for a randomised controlled trial, BMJ-BRITISH MEDICAL JOURNAL, Vol: 363, ISSN: 1756-1833

JOURNAL ARTICLE

Cook JA, Julious SA, Sones W, Hampson LV, Hewitt C, Berlin JA, Ashby D, Emsley R, Fergusson DA, Walters SJ, Wilson ECF, Maclennan G, Stallard N, Rothwell JC, Bland M, Brown L, Ramsay CR, Cook A, Armstrong D, Altman D, Vale LDet al., 2018, DELTA(2) guidance on choosing the target difference and undertaking and reporting the sample size calculation for a randomised controlled trial, TRIALS, Vol: 19, ISSN: 1745-6215

JOURNAL ARTICLE

Antcliffe DB, Burnham KL, Al-Beidh F, Santhakumaran S, Brett SJ, Hinds CJ, Ashby D, Knight JC, Gordon ACet al., 2018, Transcriptomic Signatures in Sepsis and a Differential Response to Steroids: From the VANISH Randomized Trial., Am J Respir Crit Care Med

RATIONALE: There remains uncertainty about the role of corticosteroids in sepsis with clear beneficial effects on shock duration but conflicting survival effects. Two transcriptomic sepsis response signatures (SRS) have been identified. SRS1 is relatively immunosuppressed whilst SRS2 is relatively immunocompetent. OBJECTIVES: We aimed to categorized patients based on SRS endotypes to determine if these profiles influenced response to either norepinephrine or vasopressin, or to corticosteroids in septic shock. METHODS: A post-hoc analysis was performed of a double-blind randomized clinical trial in septic shock (VANISH). Patients were included within 6 hours of onset of shock and were randomized to receive norepinephrine or vasopressin followed by hydrocortisone or placebo. Genome-wide gene expression profiling was performed and SRS endotype was determined using a previously established model using seven discriminant genes. MEASUREMENTS AND MAIN RESULTS: Samples were available from 176 patients, 83 SRS1 and 93 SRS2. There was no significant interaction between SRS group and vasopressor assignment (p=0·50). However, there was an interaction between assignment to hydrocortisone or placebo, and SRS endotype (p=0·02). Hydrocortisone use was associated with increased mortality in those with an SRS2 phenotype (OR 7·9, 95%CI 1·6-39·9). CONCLUSIONS: Transcriptomic profile at onset of septic shock was associated with response to corticosteroids. Those with the immuno-competent SRS2 endotype had significantly higher mortality when given corticosteroids compared to placebo. Clinical trial registration available at www.isrctn.com, ID ISRCTN20769191.

JOURNAL ARTICLE

Gordon AC, Santhakumaran S, Al-Beidh F, Orme RML, Perkins GD, Singer M, McAuley DF, Mason AJ, Ward J, O'Dea K, Felton T, Cross M, Best-Lane J, Lexow J, Campbell A, Ashby Det al., 2018, Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis: the LeoPARDS Randomised Controlled Trial, Efficacy and Mechanism Evaluation, ISSN: 2050-4365

Background:In septic shock, cardiovascular resuscitation using catecholamine vasopressors and inotropes is standard therapy but catecholamines have important side-effects. Levosimendan is a calcium-sensitizing drug with inotropic and other properties that may have a role in sepsis.Objectives: In adult septic shock1. Does levosimendan reduce the incidence and severity of acute organ dysfunction ?2. What is the effect of levosimendan on individual organ function ?3. What is the safety profile of levosimendan?Design: Multi-centre, randomised, double-blind, parallel-group, placebo-controlled study.Setting: UK Intensive Care UnitsParticipants: Adult patients who have sepsis and cardiovascular failure requiring vasopressors to maintain blood pressure despite adequate fluid resuscitation.Interventions: Levosimendan 0.05 to 0.2 µg/kg/min vs. placebo for 24 hour, in addition to standard care, within 24 hours of meeting inclusion criteria.Primary outcome measure: Mean SOFA score on ICU after randomisation to a maximum of 28 days.Secondary outcome measures: Time to extubationSurvival upto 6 monthsSerious Adverse EventsResults: 2382 patients were screened at 34 centres, of whom 516 were randomised to treatment, 259 allocated to levosimendan and 257 to placebo. Baseline characteristics were well balanced across treatment arms.There was no significant difference in mean (±SD) SOFA score in the levosimendan group (6.7 ± 4.0) compared with placebo (6.1 ± 3.9); (mean difference 0.61, 95%CI -0.07 to 1.29). 28-day mortality was 34.5% versus 30.9% in the levosimendan and placebo groups respectively (absolute difference 3.6%, 95%CI -4.5 to 11.7). Patients in the levosimendan group were less likely to be successfully extubated over 28 days than the placebo group (hazard ratio 0.77, 95%CI 0.60 to 0.97). More patients in the levosimendan group had supraventricular tachyarrhythmias, (3.1% versus 0.4% absolute difference 2.7%, 95%CI 0.1 to 5.3), but there was no

JOURNAL ARTICLE

Dunning J, Blankley S, Hoang LT, Cox M, Graham CM, James PL, Bloom CI, Chaussabel D, Banchereau J, Brett SJ, Moffatt MF, O'Garra A, Openshaw PJMet al., 2018, Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza, NATURE IMMUNOLOGY, Vol: 19, Pages: 625-+, ISSN: 1529-2908

JOURNAL ARTICLE

Mora-Peris B, Bouliotis G, Ranjababu K, Clarke A, Post FA, Nelson M, Burgess L, Tiraboschi J, Khoo S, Taylor S, Ashby D, Winston Aet al., 2018, Changes in cerebral function parameters with maraviroc-intensified antiretroviral therapy in treatment naive HIV-positive individuals, AIDS, Vol: 32, Pages: 1007-1015, ISSN: 0269-9370

JOURNAL ARTICLE

Santhakumaran S, Statnikov Y, Gray D, Battersby C, Ashby D, Modi Net al., 2018, Survival of very preterm infants admitted to neonatal care in England 2008-2014: time trends and regional variation, ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION, Vol: 103, Pages: F208-F215, ISSN: 1359-2998

JOURNAL ARTICLE

Achana F, Petrou S, Khan K, Gaye A, Modi Net al., 2018, A methodological framework for assessing agreement between cost-effectiveness outcomes estimated using alternative sources of data on treatment costs and effects for trial-based economic evaluations, EUROPEAN JOURNAL OF HEALTH ECONOMICS, Vol: 19, Pages: 75-86, ISSN: 1618-7598

JOURNAL ARTICLE

Quinn K, Traboni C, Penchala SD, Bouliotis G, Doyle N, Libri V, Khoo S, Ashby D, Weber J, Nicosia A, Cortese R, Pessi A, Winston Aet al., 2017, A first-in-human study of the novel HIV-fusion inhibitor C34-PEG(4)-Chol, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322

JOURNAL ARTICLE

Sydes MR, Ashby D, 2017, Data Authorship as an Incentive to Data Sharing, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 377, Pages: 402-402, ISSN: 0028-4793

JOURNAL ARTICLE

Saunders P, Tsipouri V, Keir GJ, Ashby D, Flather MD, Parfrey H, Babalis D, Renzoni EA, Denton CP, Wells AU, Maher TMet al., 2017, Rituximab versus cyclophosphamide for the treatment of connective tissue disease-associated interstitial lung disease (RECITAL): study protocol for a randomised controlled trial, TRIALS, Vol: 18, ISSN: 1745-6215

JOURNAL ARTICLE

Martyn M, Liu X, Wilhelm-Benartzi C, Brown R, Ashby Det al., 2017, Issues with over-fitting in predictive models produced for stratified medicine: a case study on an ovarian cancer trial, Publisher: BIOMED CENTRAL LTD, ISSN: 1745-6215

CONFERENCE PAPER

Santhakumaran S, Mason AJ, Gordon AC, Ashby Det al., 2017, Bayesian methods for informative missingness in longitudinal intensive care data, Publisher: BIOMED CENTRAL LTD, ISSN: 1745-6215

CONFERENCE PAPER

Tsipouri V, Saunders P, Keir GJ, Ashby D, Fletcher SV, Gibbons M, Szigeti M, Parfrey H, Renzoni EA, Denton CPet al., 2017, Rituximab versus cyclophosphamide for the treatment of connective tissue disease associated interstitial lung disease (RECITAL): a randomised controlled trial, Publisher: BIOMED CENTRAL LTD, ISSN: 1745-6215

CONFERENCE PAPER

Embleton A, Ashby D, Flemyng E, Langhorne P, Meurer WJ, South A, Sydes Met al., 2017, If a tree falls in a forest: abstract view statistics as a measure of research impact, Publisher: BIOMED CENTRAL LTD, ISSN: 1745-6215

CONFERENCE PAPER

Mason A, Winston A, Ashby D, 2017, Developing a Bayesian adaptive design for a phase I clinical trial: a case study for a novel HIV treatment, Publisher: BIOMED CENTRAL LTD, ISSN: 1745-6215

CONFERENCE PAPER

Bird SM, Strang J, Ashby D, Podmore J, Robertson JR, Welch S, Meade AM, Parmar MKBet al., 2017, External data required timely response by the Trial Steering-Data Monitoring Committee for the NALoxone InVEstigation (N-ALIVE) pilot trial, CONTEMPORARY CLINICAL TRIALS COMMUNICATIONS, Vol: 5, Pages: 100-106, ISSN: 2451-8654

JOURNAL ARTICLE

Wilhelm-Benartzi CS, Mt-Isa S, Fiorentino F, Brown R, Ashby Det al., 2017, Challenges and methodology in the incorporation of biomarkers in cancer clinical trials, CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, Vol: 110, Pages: 49-61, ISSN: 1040-8428

JOURNAL ARTICLE

Lane A, Metcalfe C, Young GJ, Peters TJ, Blazeby J, Avery KNL, Dedman D, Down L, Mason MD, Neal DE, Hamdy FC, Donovan JL, ProtecT Study groupet al., 2016, Patient-reported outcomes in the ProtecT randomized trial of clinically localized prostate cancer treatments: study design, and baseline urinary, bowel and sexual function and quality of life., BJU Int, Vol: 118, Pages: 869-879

OBJECTIVES: To present the baseline patient-reported outcome measures (PROMs) in the Prostate Testing for Cancer and Treatment (ProtecT) randomized trial comparing active monitoring, radical prostatectomy and external-beam conformal radiotherapy for localized prostate cancer and to compare results with other populations. MATERIALS AND METHODS: A total of 1643 randomized men, aged 50-69 years and diagnosed with clinically localized disease identified by prostate-specific antigen (PSA) testing, in nine UK cities in the period 1999-2009 were included. Validated PROMs for disease-specific (urinary, bowel and sexual function) and condition-specific impact on quality of life (Expanded Prostate Index Composite [EPIC], 2005 onwards; International Consultation on Incontinence Questionnaire-Urinary Incontinence [ICIQ-UI], 2001 onwards; the International Continence Society short-form male survey [ICSmaleSF]; anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), generic mental and physical health (12-item short-form health survey [SF-12]; EuroQol quality-of-life survey, the EQ-5D-3L) were assessed at prostate biopsy clinics before randomization. Descriptive statistics are presented by treatment allocation and by men's age at biopsy and PSA testing time points for selected measures. RESULTS: A total of 1438 participants completed biopsy questionnaires (88%) and 77-88% of these were analysed for individual PROMs. Fewer than 1% of participants were using pads daily (5/754). Storage lower urinary tract symptoms were frequent (e.g. nocturia 22%, 312/1423). Bowel symptoms were rare, except for loose stools (16%, 118/754). One third of participants reported erectile dysfunction (241/735) and for 16% (118/731) this was a moderate or large problem. Depression was infrequent (80/1399, 6%) but 20% of participants (278/1403) reported anxiety. Sexual function and bother were markedly worse in older men (65-70 years), whilst urinary bother and physical health were somewhat w

JOURNAL ARTICLE

Mason AJ, Gonzalez-Maffe J, Quinn K, Doyle N, Legg K, Norsworthy P, Trevelion R, Winston A, Ashby Det al., 2016, Developing a Bayesian adaptive design for a phase I clinical trial: a case study for a novel HIV treatment, Statistics in Medicine, Vol: 36, Pages: 754-771, ISSN: 1097-0258

The design of phase I studies is often challenging, because of limited evidence to inform study protocols. Adaptive designs are now well established in cancer but much less so in other clinical areas. A phase I study to assess the safety, pharmacokinetic profile and antiretroviral efficacy of C34-PEG4-Chol, a novel peptide fusion inhibitor for the treatment of HIV infection, has been set up with Medical Research Council funding. During the study workup, Bayesian adaptive designs based on the continual reassessment method were compared with a more standard rule-based design, with the aim of choosing a design that would maximise the scientific information gained from the study. The process of specifying and evaluating the design options was time consuming and required the active involvement of all members of the trial's protocol development team. However, the effort was worthwhile as the originally proposed rule-based design has been replaced by a more efficient Bayesian adaptive design. While the outcome to be modelled, design details and evaluation criteria are trial specific, the principles behind their selection are general. This case study illustrates the steps required to establish a design in a novel context.

JOURNAL ARTICLE

Bicknell CD, Kiru G, Falaschetti E, Powell JT, Poulter NRet al., 2016, An evaluation of the effect of an angiotensin-converting enzyme inhibitor on the growth rate of small abdominal aortic aneurysms: a randomized placebo-controlled trial (AARDVARK), EUROPEAN HEART JOURNAL, Vol: 37, Pages: 3213-3221, ISSN: 0195-668X

JOURNAL ARTICLE

Johnston SL, Szigeti M, Cross M, Brightling C, Chaudhuri R, Harrison T, Mansur A, Robison L, Sattar Z, Jackson D, Mallia P, Wong E, Corrigan C, Higgins B, Ind P, Singh D, Thomson NC, Ashby D, Chauhan Aet al., 2016, Azithromycin for Acute Exacerbations of Asthma The AZALEA Randomized Clinical Trial, JAMA INTERNAL MEDICINE, Vol: 176, Pages: 1630-1637, ISSN: 2168-6106

JOURNAL ARTICLE

Gordon AC, Perkins GD, Singer M, McAuley DF, Orme RML, Santhakumaran S, Mason AJ, Cross M, Al-Beidh F, Best-Lane J, Brealey D, Nutt CL, McNamee JJ, Reschreiter H, Breen A, Liu KD, Ashby Det al., 2016, Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 375, Pages: 1638-1648, ISSN: 0028-4793

JOURNAL ARTICLE

Mason MD, Moore R, Jones G, Lewis G, Donovan JL, Neal DE, Hamdy FC, Lane JA, Staffurth JN, ProtecT Study Groupet al., 2016, Radiotherapy for Prostate Cancer: is it 'what you do' or 'the way that you do it'? A UK Perspective on Technique and Quality Assurance., Clin Oncol (R Coll Radiol), Vol: 28, Pages: e92-e100

AIMS: The treatment of prostate cancer has evolved markedly over the last 40 years, including radiotherapy, notably with escalated dose and targeting. However, the optimal treatment for localised disease has not been established in comparative randomised trials. The aim of this article is to describe the history of prostate radiotherapy trials, including their quality assurance processes, and to compare these with the ProtecT trial. MATERIALS AND METHODS: The UK ProtecT randomised trial compares external beam conformal radiotherapy, surgery and active monitoring for clinically localised prostate cancer and will report on the primary outcome (disease-specific mortality) in 2016 following recruitment between 1999 and 2009. The embedded quality assurance programme consists of on-site machine dosimetry at the nine trial centres, a retrospective review of outlining and adherence to dose constraints based on the trial protocol in 54 participants (randomly selected, around 10% of the total randomised to radiotherapy, n = 545). These quality assurance processes and results were compared with prostate radiotherapy trials of a comparable era. RESULTS: There has been an increasingly sophisticated quality assurance programme in UK prostate radiotherapy trials over the last 15 years, reflecting dose escalation and treatment complexity. In ProtecT, machine dosimetry results were comparable between trial centres and with the UK RT01 trial. The outlining review showed that most deviations were clinically acceptable, although three (1.4%) may have been of clinical significance and were related to outlining of the prostate. Seminal vesicle outlining varied, possibly due to several prostate trials running concurrently with different protocols. Adherence to dose constraints in ProtecT was considered acceptable, with 80% of randomised participants having two or less deviations and planning target volume coverage was excellent. CONCLUSION: The ProtecT trial quality assurance re

JOURNAL ARTICLE

Gordon AC, Mason AJ, Thirunavukkarasu N, Perkins GD, Cecconi M, Cepkova M, Pogson DG, Aya HD, Anjum A, Frazier GJ, Santhakumaran S, Ashby D, Brett SJet al., 2016, Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock The VANISH Randomized Clinical Trial, JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, Vol: 316, Pages: 509-518, ISSN: 0098-7484

JOURNAL ARTICLE

Uthaya S, Liu X, Babalis D, Dore CJ, Warwick J, Bell J, Thomas L, Ashby D, Durighel G, Ederies A, Yanez-Lopez M, Modi Net al., 2016, Nutritional Evaluation and Optimisation in Neonates: a randomized, double-blind controlled trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition, AMERICAN JOURNAL OF CLINICAL NUTRITION, Vol: 103, Pages: 1443-1452, ISSN: 0002-9165

JOURNAL ARTICLE

Quinn K, Bouliotis G, Doyle N, Winston A, Ashby D, Weber J, Libri V, Amara A, Back D, Penchala SD, Khoo S, Nelson M, Jones R, Cortese R, Pessi Aet al., 2016, A first-in-human study, in HIV-positive men, of the novel HIV-fusion inhibitor C34-PEG4-Chol, Publisher: WILEY-BLACKWELL, Pages: 18-18, ISSN: 1464-2662

CONFERENCE PAPER

Hughes D, Waddingham E, Mt-Isa S, Goginsky A, Chan E, Downey GF, Hallgreen CE, Hockley KS, Juhaeri J, Lieftucht A, Metcalf MA, Noel RA, Phillips LD, Ashby D, Micaleff Aet al., 2016, Recommendations for benefit-risk assessment methodologies and visual representations, PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Vol: 25, Pages: 251-262, ISSN: 1053-8569

JOURNAL ARTICLE

Hallgreen CE, Mt-Isa S, Lieftucht A, Phillips LD, Hughes D, Talbot S, Asiimwe A, Downey G, Genov G, Hermann R, Noel R, Peters R, Micaleff A, Tzoulaki I, Ashby Det al., 2016, Literature review of visual representation of the results of benefit-risk assessments of medicinal products, PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Vol: 25, Pages: 238-250, ISSN: 1053-8569

JOURNAL ARTICLE

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