Search

Your search keyword '"Hellier, Jennifer"' showing total 167 results
Start Over Author "Hellier, Jennifer"
167 results on '"Hellier, Jennifer"'

2. Modelling treatment mechanism for stratified medicine in randomised clinical trials

Author

Hellier, Jennifer, Pickles, Andrew, and Emsley, Richard Andrew

Abstract

Stratified medicine is the targeting of treatment to a person's specific characteristics. Stratified medicine could advance more quickly if analysis models mapped more closely onto elements of treatment mechanism, that also dissected heterogeneity by explaining variation in treatment effects. The overall aim of this thesis is to develop statistical methodology for the analysis of randomised clinical trial data, to better understand mechanisms underlying treatment effects as a platform for stratified medicine. Throughout the thesis, Stata programs are developed to implement the new methodological components. New and current methodology is assessed via simulated trial data using Monte Carlo simulations and clinical trial datasets from mental health are used to demonstrate the methods. I develop statistical methods for survival data that allow insight into the effects underlying treatment response. Initially an inverse Gaussian threshold (IG) model is constructed with two linear predictors and thus two sets of coefficients for covariate effects associated with distance, corresponding to initial disease severity and velocity, corresponding to progression following initiation of treatment. Furthermore, model parameters should have a causal interpretation. A novel extension to instrumental variable (IV) methods is illustrated to remove bias due to individual patient dose titration that is common in drug trials. Both the IG model and IV extension are illustrated using data from the Genome-based Therapeutic Drugs for Depression (GENDEP) trial. It is vital to make better use of the repeated or multivariate data that is often collected in clinical trials but not all analysis frameworks maximise its use. Latent variable methods such as growth curve models offer a parsimonious approach to parameter estimation. When an event of interest can be measured by a continuous outcome crossing a threshold, I develop an extension of a growth curve model to estimate a survival function for the time to reach a threshold value. This modelling approach has the advantage of capturing the clinical complexity of repeated observations, benefits from the flexible growth curve modelling framework, and can improve precision and provide scope for dynamic or updated individual prediction. Extensions to the model estimate a restricted mean survival time outcome, the expected mean time to an event for a given time interval. This has the advantage of clearer causal interpretation and avoids the issues surrounding non-collapsibility of a multiplicative hazard ratio. Multiple moderators or predictive markers can be combined into a single combined moderator index. Two approaches to combine moderators into an index, are contrasted in an illustration of a trial data using the Hyperactivity and Special Educational Needs Study (HSEN) with a qualitative combined moderator. The application of this index is then considered within a Personalised Treatment Recommendation (PTR), an algorithm that maps baseline markers to an optimal treatment decision by comparison with alternative treatment rules. To conclude, I combine several novel elements of the thesis in applying a threshold-crossing model structure, a moderator index and a PTR for maximising the overall expected restricted mean survival time. This work has developed statistical methods to advance stratified medicine by providing insight into treatment mechanisms and heterogeneity, efficiently estimating parameters with a valid casual interpretation, maximising the use of multivariate data, combining elements of heterogeneity into an index and finally presenting treatment rules for use in clinical practice. The methods have been assessed using extensive simulation studies. Their application has shown novel insight in the heterogeneity and underlying mechanism of antidepressant treatment effects and estimates of a dose-response relationship in GENDEP and that a combined index, formed of pre-treatment irritability and parent rated hyperactivity measures, is a moderator for effects of Methylphenidate (compared to placebo) on teacher rated hyperactivity in HSEN.

Published
2021

13. Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial

Author

Banerjee, Sube, Hellier, Jennifer, Dewey, Michael, Romeo, Renee, Ballard, Clive, Baldwin, Robert, Bentham, Peter, Fox, Chris, Holmes, Clive, Katona, Cornelius, Knapp, Martin, Lawton, Claire, Lindesay, James, Livingston, Gill, McCrae, Niall, Moniz-Cook, Esme, Murray, Joanna, Nurock, Shirley, Orrell, Martin, O'Brien, John, Poppe, Michaela, Thomas, Alan, Walwyn, Rebecca, Wilson, Kenneth, and Burns, Alistair

Published
2011
Full Text
View/download PDF

14. Using a pragmatically adapted, low-cost contingency management intervention to promote heroin abstinence in individuals undergoing treatment for heroin use disorder in UK drug services (PRAISE): a cluster randomised trial

Author

Metrebian, Nicola, primary, Weaver, Tim, additional, Goldsmith, Kimberley, additional, Pilling, Stephen, additional, Hellier, Jennifer, additional, Pickles, Andrew, additional, Shearer, James, additional, Byford, Sarah, additional, Mitcheson, Luke, additional, Bijral, Prun, additional, Bogdan, Nadine, additional, Bowden-Jones, Owen, additional, Day, Edward, additional, Dunn, John, additional, Glasper, Anthony, additional, Finch, Emily, additional, Forshall, Sam, additional, Akhtar, Shabana, additional, Bajaria, Jalpa, additional, Bennett, Carmel, additional, Bishop, Elizabeth, additional, Charles, Vikki, additional, Davey, Clare, additional, Desai, Roopal, additional, Goodfellow, Claire, additional, Haque, Farjana, additional, Little, Nicholas, additional, McKechnie, Hortencia, additional, Mosler, Franziska, additional, Morris, Jo, additional, Mutz, Julian, additional, Pauli, Ruth, additional, Poovendran, Dilkushi, additional, Phillips, Elizabeth, additional, and Strang, John, additional

Published
2021
Full Text
View/download PDF

18. Do interictal spikes drive epileptogenesis?

Author

Staley, Kevin, Hellier, Jennifer L., and Dudek, F. Edward

Subjects
Axons -- Growth -- Usage, Electroencephalography -- Usage, Epilepsy -- Diagnosis, Psychology and mental health, Company growth, Diagnosis, Usage, Growth
Abstract

Interictal spikes are periodic, very brief bursts of neuronal activity that are observed in the electroencephalogram of patients with chronic epilepsy. These spikes are useful diagnostically, but we do not [...]

Published
2005

20. Cost-effectiveness analyses for mirtazapine and sertraline in dementia: randomised controlled trial

Author

Romeo, Renee, Knapp, Martin, Hellier, Jennifer, Dewey, Michael, Ballard, Clive, Baldwin, Robert, Bentham, Peter, Burns, Alistair, Fox, Chris, Holmes, Clive, Katona, Cornelius, Lawton, Claire, Lindesay, James, Livingston, Gill, McCrae, Niall, Moniz-Cook, Esme, Murray, Joanna, Nurock, Shirley, OʼBrien, John, Poppe, Michaela, Thomas, Alan, Walwyn, Rebecca, Wilson, Kenneth, and Banerjee, Sube

Published
2013

22. Sertraline and Mirtazapine Versus Placebo in Subgroups of Depression in Dementia: Findings From the HTA-SADD Randomized Controlled Trial

Author

Zuidersmar, Marij, Chua, Kia-Chong, Hellier, Jennifer, Oude Voshaar, Richard, Banerjee, Sube, HTA-SADD Investigator Group, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), and Clinical Cognitive Neuropsychiatry Research Program (CCNP)

Subjects
Male, medicine.medical_specialty, SYMPTOMS, SAMPLE, Mirtazapine, Subgroup analysis, latent class analyses, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, MEDICATION, Double-Blind Method, law, Alzheimer Disease, Internal medicine, Sertraline, medicine, MANAGEMENT, Dementia, Humans, Depression (differential diagnoses), mirtazapine, ALZHEIMER-DISEASE, Aged, Aged, 80 and over, 030214 geriatrics, business.industry, sertraline, Depression, medicine.disease, EFFICACY, Confidence interval, Antidepressive Agents, Psychiatry and Mental health, England, randomized controlled trial, Female, Geriatrics and Gerontology, business, medicine.drug, dementia
Abstract

ObjectiveStudies have shown that antidepressants are no better than placebo in treating depression in dementia. The authors examined antidepressant efficacy in subgroups of depression in dementia with different depressive symptom profiles.MethodsThis study focuses on exploratory secondary analyses on the randomized, parallel-group, double-blind, placebo-controlled Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) trial. The setting included old-age psychiatry services in nine centers in England. The participants included 326 patients meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association probable/possible Alzheimer disease criteria, and Cornell Scale for Depression in Dementia (CSDD) scores of 8 or more. Intervention was placebo (n = 111), sertraline (n = 107), or mirtazapine (n = 108). Latent class analyses (LCA) on baseline CSDD items clustered participants into symptom-based subgroups. Mixed-model analysis evaluated CSDD improvement at 13 and 39 weeks by randomization in each subgroup.ResultsLCA yielded 4 subgroups: severe (n = 34), psychological (n = 86), affective (n = 129), and somatic (n = 77). Mirtazapine, but not sertraline, outperformed placebo in the psychological subgroup at week 13 (adjusted estimate: –2.77 [standard error (SE) 1.16; 95% confidence interval: –5.09 to –0.46]), which remained, but lost statistical significance at week 39 (adjusted estimate: –2.97 [SE 1.59; 95% confidence interval: –6.15 to 0.20]). Neither sertraline nor mirtazapine outperformed placebo in the other subgroups.ConclusionBecause of the exploratory nature of the analyses and the small sample sizes for subgroup analysis there is the need for caution in interpreting these data. Replication of the potential effects of mirtazapine in the subgroup of those with depression in dementia with “psychological” symptoms would be valuable. These data should not change clinical practice, but future trials should consider stratifying types of depression in dementia in secondary analyses.

Published
2019

27. A randomised controlled trial of a cognitive behavioural intervention for women who have menopausal symptoms following breast cancer treatment (MENOS 1): Trial protocol

Author

Hellier Jennifer, Smith Melanie, Mann Eleanor, and Hunter Myra S

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background This trial aims to evaluate the effectiveness of a group cognitive behavioural intervention to alleviate menopausal symptoms (hot flushes and night sweats) in women who have had breast cancer treatment. Hot flushes and night sweats are highly prevalent but challenging to treat in this population. Cognitive behaviour therapy has been found to reduce these symptoms in well women and results of an exploratory trial suggest that it might be effective for breast cancer patients. Two hypotheses are tested: Compared to usual care, group cognitive behavioural therapy will: 1. Significantly reduce the problem rating and frequency of hot flushes and nights sweats after six weeks of treatment and at six months post-randomisation. 2. Improve mood and quality of life after six weeks of treatment and at six months post-randomisation. Methods/Design Ninety-six women who have completed their main treatment for breast cancer and who have been experiencing problematic hot flushes and night sweats for over two months are recruited into the trial from oncology and breast clinics in South East London. They are randomised to either six weekly group cognitive behavioural therapy (Group CBT) sessions or to usual care. Group CBT includes information and discussion about hot flushes and night sweats in the context of breast cancer, monitoring and modifying precipitants, relaxation and paced respiration, stress management, cognitive therapy for unhelpful thoughts and beliefs, managing sleep and night sweats and maintaining changes. Prior to randomisation women attend a clinical interview, undergo 24-hour sternal skin conductance monitoring, and complete questionnaire measures of hot flushes and night sweats, mood, quality of life, hot flush beliefs and behaviours, optimism and somatic amplification. Post-treatment measures (sternal skin conductance and questionnaires) are collected six to eight weeks later and follow-up measures (questionnaires and a use of medical services measure) at six months post-randomisation. Discussion MENOS 1 is the first randomised controlled trial of cognitive behavioural therapy for hot flushes and night sweats that measures both self-reported and physiologically indexed symptoms. The results will inform future clinical practice by developing an evidence-based, non-medical treatment, which can be delivered by trained health professionals. Trial Registration Current Controlled Trials ISRCTN13771934

Published
2011
Full Text
View/download PDF

28. Effectiveness and Cost-Effectiveness of Adjunctive Personalised Psychosocial Intervention in Treatment-Resistant Opioid Agonist Therapy: A Pragmatic, Open-Label, Randomised Controlled Trial

Author

Marsden, John, primary, Stillwell, Garry, additional, James, Kirsty, additional, Shearer, James, additional, Byford, Sarah, additional, Hellier, Jennifer, additional, Kelleher, Michael, additional, Kelly, Joanna, additional, Murphy, Caroline, additional, and Mitcheson, Luke, additional

Published
2018
Full Text
View/download PDF

30. Additional file 2: of The NOURISHED randomised controlled trial comparing mentalisation-based treatment for eating disorders (MBT-ED) with specialist supportive clinical management (SSCM-ED) for patients with eating disorders and symptoms of borderline personality disorder

Author

Robinson, Paul, Hellier, Jennifer, Barrett, Barbara, Barzdaitiene, Daiva, Bateman, Anthony, Bogaardt, Alexandra, Clare, Ajay, Somers, Nadia, O’Callaghan, Aine, Goldsmith, Kimberley, Kern, Nikola, Schmidt, Ulrike, Morando, Sara, Ouellet-Courtois, Catherine, Roberts, Alice, Skårderud, Finn, and Fonagy, Peter

Abstract

CONSORT 2010 checklist. (DOCX 209 kb)

Published
2016
Full Text
View/download PDF

31. Additional file 1: Figure S1. of The NOURISHED randomised controlled trial comparing mentalisation-based treatment for eating disorders (MBT-ED) with specialist supportive clinical management (SSCM-ED) for patients with eating disorders and symptoms of borderline personality disorder

Author

Robinson, Paul, Hellier, Jennifer, Barrett, Barbara, Barzdaitiene, Daiva, Bateman, Anthony, Bogaardt, Alexandra, Clare, Ajay, Somers, Nadia, O’Callaghan, Aine, Goldsmith, Kimberley, Kern, Nikola, Schmidt, Ulrike, Morando, Sara, Ouellet-Courtois, Catherine, Roberts, Alice, Skårderud, Finn, and Fonagy, Peter

Abstract

Unadjusted mean EDE and ZAN score by treatment group for all post randomisation time points and baseline (time 0). Lowest score if best. Error bars show 95Â % CI. EDE Eating Disorder Examination, ZAN Zanarini Rating Scale. (DOCX 74 kb)

Published
2016
Full Text
View/download PDF

32. An economic evaluation of contingency management for completion of hepatitis B vaccination in those on treatment for opiate dependence

Author

Rafia, Rachid, Dodd, Peter J., Brennan, Alan, Meier, Petra S., Hope, Vivian D., Ncube, Fortune, Byford, Sarah, Tie, Hiong, Metrebian, Nicola, Hellier, Jennifer, Weaver, Tim, and Strang, John

Subjects
Research Report, Liver Cirrhosis, economic, Carcinoma, Hepatocellular, incentives, Cost-Benefit Analysis, viral hepatitis, Economic, injecting, Incentives, Methadone maintenance program, Humans, Hepatitis B Vaccines, opiates, Viral hepatitis, Mortality, Substance Abuse, Intravenous, Randomized Controlled Trials as Topic, Motivation, Vaccination, Decision Trees, Liver Neoplasms, Injecting, Disease Management, Research Reports, Health Care Costs, Contingency management, methadone maintenance program, vaccination, Hepatitis B, Opioid-Related Disorders, Markov Chains, United Kingdom, Liver Transplantation, Opiates, Quality-Adjusted Life Years
Abstract

Aims: To determine whether the provision of contingency management using financial incentives to improve hepatitis B vaccine completion in people who inject drugs entering community treatment represents a cost-effective use of health-care resources. Design: A probabilistic cost-effectiveness analysis was conducted, using a decision-tree to estimate the short-term clinical and health-care cost impact of the vaccination strategies, followed by a Markov process to evaluate the long-term clinical consequences and costs associated with hepatitis B infection. Settings and participants: Data on attendance to vaccination from a UK cluster randomized trial. Intervention: Two contingency management options were examined in the trial: fixed versus escalating schedule financial incentives. Measurement: Life-time health-care costs and quality-adjusted life years discounted at 3.5% annually; incremental cost-effectiveness ratios. Findings: The resulting estimate for the incremental life-time health-care cost of the contingency management strategy versus usual care was £21.86 [95% confidence interval (CI) = -£12.20 to 39.86] per person offered the incentive. For 1000 people offered the incentive, the incremental reduction in numbers of hepatitis B infections avoided over their lifetime was estimated at 19 (95% CI = 8-30). The probabilistic incremental cost per quality adjusted life-year gained of the contingency management programme was estimated to be £6738 (95% CI = £6297-7172), with an 89% probability of being considered cost-effective at a threshold of £20000 per quality-adjusted life years gained (97.60% at £30000). Conclusions: Using financial incentives to increase hepatitis B vaccination completion in people who inject drugs could be a cost-effective use of health-care resources in the UK as long as the incidence remains above 1.2%.

Published
2015

33. A multicentre randomiSed controlled TRial of IntraVEnous immunoglobulin compared with standard therapy for the treatment of transverse myelitis in adults and children (STRIVE)

Author

Absoud, Michael, primary, Brex, Peter, additional, Ciccarelli, Olga, additional, Diribe, Onyinye, additional, Giovannoni, Gavin, additional, Hellier, Jennifer, additional, Howe, Rosemary, additional, Holland, Rachel, additional, Kelly, Joanna, additional, McCrone, Paul, additional, Murphy, Caroline, additional, Palace, Jackie, additional, Pickles, Andrew, additional, Pike, Michael, additional, Robertson, Neil, additional, Jacob, Anu, additional, and Lim, Ming, additional

Published
2017
Full Text
View/download PDF

34. Effectiveness of adjunctive, personalised psychosocial intervention for non-response to opioid agonist treatment: Study protocol for a pragmatic randomised controlled trial

Author

Marsden, John, primary, Stillwell, Garry, additional, Hellier, Jennifer, additional, Brown, Anne Marie, additional, Byford, Sarah, additional, Kelleher, Michael, additional, Kelly, Joanne, additional, Murphy, Caroline, additional, Shearer, James, additional, and Mitcheson, Luke, additional

Published
2017
Full Text
View/download PDF

35. The NOURISHED randomised controlled trial comparing mentalisation-based treatment for eating disorders (MBT-ED) with specialist supportive clinical management (SSCM-ED) for patients with eating disorders and symptoms of borderline personality disorder

Author

Robinson, Paul, primary, Hellier, Jennifer, additional, Barrett, Barbara, additional, Barzdaitiene, Daiva, additional, Bateman, Anthony, additional, Bogaardt, Alexandra, additional, Clare, Ajay, additional, Somers, Nadia, additional, O’Callaghan, Aine, additional, Goldsmith, Kimberley, additional, Kern, Nikola, additional, Schmidt, Ulrike, additional, Morando, Sara, additional, Ouellet-Courtois, Catherine, additional, Roberts, Alice, additional, Skårderud, Finn, additional, and Fonagy, Peter, additional

Published
2016
Full Text
View/download PDF

37. An economic evaluation of contingency management for completion of hepatitis B vaccination in those on treatment for opiate dependence

Author

Rafia, Rachid, primary, Dodd, Peter J., additional, Brennan, Alan, additional, Meier, Petra S., additional, Hope, Vivian D., additional, Ncube, Fortune, additional, Byford, Sarah, additional, Tie, Hiong, additional, Metrebian, Nicola, additional, Hellier, Jennifer, additional, Weaver, Tim, additional, and Strang, John, additional

Published
2016
Full Text
View/download PDF

38. Thiazolides as Novel Antiviral Agents: I. Inhibition of Hepatitis B Virus Replication

Author

Stachulski, Andrew V., Pidathala, Chandrakala, Row, Eleanor C., Sharma, Raman, Berry, Neil G., Iqbal, Mazhar, Bentley, Joanne, Allman, Sarah A., Edwards, Geoffrey, Helm, Alison, Hellier, Jennifer, Korba, Brent E., Semple, J. Edward, and Rossignol, Jean-Francois

Subjects
Hepatitis B virus, Virion, Quantitative Structure-Activity Relationship, Hep G2 Cells, In Vitro Techniques, Virus Replication, Amides, Antiviral Agents, Article, Rats, Thiazoles, Dogs, Glucuronides, Salicylamides, Animals, Humans, Prodrugs
Abstract

We report the syntheses and activities of a wide range of thiazolides [viz., 2-hydroxyaroyl-N-(thiazol-2-yl)amides] against hepatitis B virus replication, with QSAR analysis of our results. The prototypical thiazolide, nitazoxanide [2-hydroxybenzoyl-N-(5-nitrothiazol-2-yl)amide, NTZ] 1 is a broad spectrum antiinfective agent effective against anaerobic bacteria, viruses, and parasites. By contrast, 2-hydroxybenzoyl-N-(5-chlorothiazol-2-yl)amide 3 is a novel, potent, and selective inhibitor of hepatitis B replication (EC(50) = 0.33 μm) but is inactive against anaerobes. Several 4'- and 5'-substituted thiazolides show good activity against HBV; by contrast, some related salicyloylanilides show a narrower spectrum of activity. The ADME properties of 3 are similar to 1; viz., the O-acetate is an effective prodrug, and the O-aryl glucuronide is a major metabolite. The QSAR study shows a good correlation of observed EC(90) for intracellular virions with thiazolide structural parameters. Finally we discuss the mechanism of action of thiazolides in relation to the present results.

Published
2011

39. Drug use, health and social outcomes of hard-to-treat heroin addicts receiving supervised injectable opiate treatment: secondary outcomes from the Randomized Injectable Opioid Treatment Trial (RIOTT)

Author

Metrebian, Nicola, primary, Groshkova, Teodora, additional, Hellier, Jennifer, additional, Charles, Vikki, additional, Martin, Anthea, additional, Forzisi, Luciana, additional, Lintzeris, Nicholas, additional, Zador, Deborah, additional, Williams, Hugh, additional, Carnwath, Tom, additional, Mayet, Soraya, additional, and Strang, John, additional

Published
2014
Full Text
View/download PDF

41. Study Protocol for a randomized controlled trial of mentalization based therapy against specialist supportive clinical management in patients with both eating disorders and symptoms of borderline personality disorder

Author

Robinson, Paul, primary, Barrett, Barbara, additional, Bateman, Anthony, additional, Hakeem, Az, additional, Hellier, Jennifer, additional, Lemonsky, Fenella, additional, Rutterford, Clare, additional, Schmidt, Ulrike, additional, and Fonagy, Peter, additional

Published
2014
Full Text
View/download PDF

44. Thiazolides as Novel Antiviral Agents. 2. Inhibition of Hepatitis C Virus Replication

Author

Stachulski, Andrew V., primary, Pidathala, Chandrakala, additional, Row, Eleanor C., additional, Sharma, Raman, additional, Berry, Neil G., additional, Lawrenson, Alexandre S., additional, Moores, Shelley L., additional, Iqbal, Mazhar, additional, Bentley, Joanne, additional, Allman, Sarah A., additional, Edwards, Geoffrey, additional, Helm, Alison, additional, Hellier, Jennifer, additional, Korba, Brent E., additional, Semple, J. Edward, additional, and Rossignol, Jean-Francois, additional

Published
2011
Full Text
View/download PDF

45. Thiazolides as Novel Antiviral Agents. 1. Inhibition of Hepatitis B Virus Replication

Author

Stachulski, Andrew V., primary, Pidathala, Chandrakala, additional, Row, Eleanor C., additional, Sharma, Raman, additional, Berry, Neil G., additional, Iqbal, Mazhar, additional, Bentley, Joanne, additional, Allman, Sarah A., additional, Edwards, Geoffrey, additional, Helm, Alison, additional, Hellier, Jennifer, additional, Korba, Brent E., additional, Semple, J. Edward, additional, and Rossignol, Jean-Francois, additional

Published
2011
Full Text
View/download PDF

49. A novel apparatus for lateral fluid percussion injury in the rat

Author

Frey, Lauren C., primary, Hellier, Jennifer, additional, Unkart, Cheri, additional, Lepkin, Aaron, additional, Howard, Allyson, additional, Hasebroock, Kendra, additional, Serkova, Natalie, additional, Liang, LiPing, additional, Patel, Manisha, additional, Soltesz, Ivan, additional, and Staley, Kevin, additional

Published
2009
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results