Biomedical subjects

Nicola J Cooper

Publications and source records attributed to Nicola J Cooper.

12 recordsLinked to original sources

PubMed2007

Evidence-based sample size calculations based upon updated meta-analysis.

Meta-analyses of randomized controlled trials (RCTs) provide the highest level of evidence regarding the effectiveness of interventions and as such underpin much of evidence-based medicine. Despite this, meta-analyses are usually produced as observational by-products of the existing literature, with no formal consideration of future meta-analyses when individual trials are being designed. Basing the sample size of a new trial on the results of an updated meta-analysis which will include it, may sometimes make more sense than powering the trial in isolation. A framework for sample size calculation for a future RCT based on the results of a meta-analysis of the existing evidence is presented. Both fixed and random effect approaches are explored through an example. Bayesian Markov Chain Monte Carlo simulation modelling is used for the random effects model since it has computational advantages over the classical approach. Several criteria on which to base inference and hence power are considered. The prior expectation of the power is averaged over the prior distribution for the unknown true treatment effect. An extension to the framework allowing for consideration of the design for a series of new trials is also presented. Results suggest that power can be highly dependent on the statistical model used to meta-analyse the data and even very large studies may have little impact on a meta-analysis when there is considerable between study heterogeneity. This raises issues regarding the appropriateness of the use of random effect models when designing and drawing inferences across a series of studies.

Anti-Bacterial Agents↗

PubMed2007

Predicting costs over time using Bayesian Markov chain Monte Carlo methods: an application to early inflammatory polyarthritis.

This article focuses on the modelling and prediction of costs due to disease accrued over time, to inform the planning of future services and budgets. It is well documented that the modelling of cost data is often problematic due to the distribution of such data; for example, strongly right skewed with a significant percentage of zero-cost observations. An additional problem associated with modelling costs over time is that cost observations measured on the same individual at different time points will usually be correlated. In this study we compare the performance of four different multilevel/hierarchical models (which allow for both the within-subject and between-subject variability) for analysing healthcare costs in a cohort of individuals with early inflammatory polyarthritis (IP) who were followed-up annually over a 5-year time period from 1990/1991. The hierarchical models fitted included linear regression models and two-part models with log-transformed costs, and two-part model with gamma regression and a log link. The cohort was split into a learning sample, to fit the different models, and a test sample to assess the predictive ability of these models. To obtain predicted costs on the original cost scale (rather than the log-cost scale) two different retransformation factors were applied. All analyses were carried out using Bayesian Markov chain Monte Carlo (MCMC) simulation methods.

Adult↗

PubMed2006

Mixed comparison of stroke prevention treatments in individuals with nonrheumatic atrial fibrillation.

BACKGROUND: We aimed to identify different stroke prevention treatments for atrial fibrillation assessed in randomized controlled trials and to compare them within a single evidence synthesis framework. METHODS: We updated the Cochrane review on anticoagulants and antiplatelet therapy for nonrheumatic atrial fibrillation to include randomized controlled trials published between January 2000 and March 2005 identified via the CENTRAL database and MEDLINE. A mixed-treatment comparison method was used to combine direct within-trial, between-treatment comparisons with indirect trial evidence while maintaining randomization. RESULTS: Data were combined from 19 clinical trials that included 17 833 patients randomized to 9 treatment strategies, including placebo. For prevention of ischemic stroke, adjusted standard-dose warfarin sodium (relative rate [RR], 0.35; 95% credible interval [CrI], 0.24 to 0.52), adjusted low-dose warfarin (RR, 0.35; 95% CrI, 0.19 to 0.60), ximelagatran (RR, 0.34; 95% CrI, 0.18 to 0.61), and aspirin (RR, 0.64; 95% CrI, 0.44 to 0.88) were all associated with a significantly lower rate of ischemic stroke compared with placebo. For major and fatal bleeding episodes, there was some evidence of an increased risk for all treatments but none were statistically significant. Assuming a baseline risk of 51 ischemic stroke events per 1000 person-years, it can be estimated that adjusted standard-dose warfarin could prevent 28 (95% CrI, -37 to -19) ischemic strokes at the expense of 11 (95% CrI, -1 to +39) major or fatal bleeding episodes. In comparison, aspirin could prevent 16 (95% CrI, -26 to -5) ischemic strokes at the expense of 6 (95% CrI, -3 to +27) major or fatal bleeding episodes. CONCLUSIONS: A lower rate of ischemic stroke and a higher rate of major bleeding episodes were found to be associated with oral anticoagulants compared with aspirin, and both anticoagulants and aspirin were found to be associated with a reduction in the rate of stroke compared with placebo.

Anticoagulants↗

PubMed2005

A Bayesian approach to evaluating net clinical benefit allowed for parameter uncertainty.

BACKGROUND AND OBJECTIVE: Although randomized controlled trials (RCTs) are conducted to establish whether novel interventions work on average in the patient population, there is a growing desire to move to a more individualized approach to evaluation. The potential benefits and harms of a treatment policy may differ between individuals. If these benefits and harms are not evaluated distinctly, and in a quantitative framework, transparency can be lost in the decision-making process. METHODS: Glasziou and Irwig have outlined the concept of net clinical treatment benefit for identifying the patients for whom the potential benefits of treatment outweigh the possible side effects. This study revisits the decision whether to use warfarin to treat atrial fibrillation. In this analysis, RCT and various sorts of observational data are synthesized. RESULTS: This reanalysis brings into question the conclusions of the original analysis on who would benefit from warfarin; however, caution is advised, due to limitations in the quality of life data available. CONCLUSION: A fully realized Bayesian implementation of the model is presented. This provides a framework for including uncertainty related to the estimation of all model parameters, and permits both direct probability statements and credible intervals for specific patient groups to be expressed.

Anticoagulants↗

PubMed2005

The use of systematic reviews when designing studies.

BACKGROUND: The importance of systematic reviews in identifying gaps in the evidence base and providing a quantitative basis for informing new research initiatives is widely acknowledged, but little is known about what actually happens in practice. Our objective was to assess the use made of results of reviews in the designing of new studies. METHODS: Of all Cochrane reviews published in 1996, those updated in 2002 or 2003 were identified. Authors of trials added in the updates were contacted and asked if use had been made of the 1996 Cochrane or other reviews in designing their study. RESULTS: Of 32 authors of studies newly included in 33 Cochrane reviews which met our inclusion criteria, 24 (75%) responded. Eleven (46%) respondents were aware of the relevant Cochrane review at the time they designed their study. In eight (33%) cases the design of the new study had been influenced by a review; in two (8%) this was the relevant Cochrane review. CONCLUSIONS: Cautious interpretation of these results is necessary, but it is apparent that the proportion of study investigators using Cochrane or other systematic reviews in designing their new studies was very limited. Inclusion of encouragement in publication or application guidelines to consider and cite review results is desirable.

Clinical Trials as Topic↗

PubMed2005

Clinical and cost-effectiveness of a new nurse-led continence service: a randomised controlled trial.

BACKGROUND: Continence services in the UK have developed at different rates within differing care models, resulting in scattered and inconsistent services. Consequently, questions remain about the most cost-effective method of delivering these services. AIM: To evaluate the impact of a new service led by a continence nurse practitioner compared with existing primary/secondary care provision for people with urinary incontinence and storage symptoms. DESIGN OF STUDY: Randomised controlled trial with a 3- and 6-month follow-up in men and women (n = 3746) aged 40 years and over living in private households (intervention [n = 2958]; control [n = 788]). SETTING: Leicestershire and Rutland, UK. METHOD: The continence nurse practitioner intervention comprised a continence service provided by specially trained nurses delivering evidence-based interventions using predetermined care pathways. They delivered an 8-week primary intervention package that included advice on diet and fluids; bladder training; pelvic floor awareness and lifestyle advice. The standard care arm comprised access to existing primary care including GP and continence advisory services in the area. Outcome measures were recorded at 3 and 6 months post-randomisation. RESULTS: The percentage of individuals who improved (with at least one symptom alleviated) at 3 months was 59% in the intervention group compared with 48% in the standard care group (difference of 11%, 95% CI = 7 to 16; P<0.001) The percentage of people reporting no symptoms or 'cured' was 25% in the intervention group and 15% in the standard care group (difference of 10%, 95% CI = 6 to 13, P = 0.001). At 6 months the difference was maintained. There was a significant difference in impact scores between the two groups at 3 and 6 months. CONCLUSIONS: The continence nurse practitioner-led intervention reduced the symptoms of incontinence, frequency, urgency and nocturia at 3 and 6 months; impact was reduced; and satisfaction with the new service was high.

Adult↗

PubMed2004

Benefits and harms associated with hormone replacement therapy: clinical decision analysis.

OBJECTIVE: To evaluate harms and benefits associated with use of combined hormone replacement therapy (HRT) for five years in women with different baseline risks for breast cancer. DESIGN: Probabilistic clinical decision analysis. SETTING: Hypothetical population of white UK women aged 50 years with different baseline risks for breast cancer. MAIN OUTCOME MEASURE: Gain or loss in quality adjusted life years (QALYs). RESULTS: Women free of menopausal symptoms showed a net harm from HRT use, which increased for increasing baseline risk of breast cancer. Those with a baseline risk of 1.2% would expect a loss in QALYs of 0.4 months (- 0.03 QALYs, 95% credibility interval - 0.05 to - 0.01). The main analysis showed HRT to be on average beneficial in women with symptoms, with benefit decreasing with increasing baseline risk of breast cancer. The results were sensitive to the assumed value of quality of life with menopausal symptoms, therefore a contour plot was developed to show the probability of net harm for a range of different values and baseline risks. CONCLUSIONS: HRT for primary prevention of chronic diseases in women without menopausal symptoms is unjustified. Perceived quality of life in women with symptoms should be taken into account when deciding on HRT. Thus, a decision analysis tailored to an individual woman is more appropriate in clinical practice than a population based approach.

Aged↗

PubMed2004

Comprehensive decision analytical modelling in economic evaluation: a Bayesian approach.

Decision analytical models are widely used in economic evaluation of health care interventions with the objective of generating valuable information to assist health policy decision-makers to allocate scarce health care resources efficiently. The whole decision modelling process can be summarised in four stages: (i) a systematic review of the relevant data (including meta-analyses), (ii) estimation of all inputs into the model (including effectiveness, transition probabilities and costs), (iii) sensitivity analysis for data and model specifications, and (iv) evaluation of the model. The aim of this paper is to demonstrate how the individual components of decision modelling, outlined above, may be addressed simultaneously in one coherent Bayesian model (sometimes known as a comprehensive decision analytical model) and evaluated using Markov Chain Monte Carlo simulation implemented in the specialist software WinBUGS. To illustrate the method described, it is applied to two illustrative examples: (1) The prophylactic use of neurominidase inhibitors for the prevention of influenza. (2) The use of taxanes for the second-line treatment of advanced breast cancer. The advantages of integrating the four stages outlined into one comprehensive decision analytical model, compared to the conventional 'two-stage' approach, are discussed.

Adolescent↗

PubMed2003

Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised controlled trials.

OBJECTIVE: To review the clinical effectiveness of oseltamivir and zanamivir for the treatment and prevention of influenza A and B. DESIGN: Systematic review and meta-analyses of randomised controlled trials. DATA SOURCES: Published studies were retrieved from electronic bibliographic databases; supplementary data were obtained from the manufacturers. SELECTION OF STUDIES: Randomised controlled, double blind trials that were published in English, had data available before 31 December 2001, evaluated treatment or prevention of naturally occurring influenza with zanamivir or oseltamivir (if given using the formulation and dosage licensed for clinical use), and reported at least one end point of relevance. REVIEW METHODS: The main outcome measures were the median time to the alleviation of symptoms (for treatment trials) and number of flu episodes avoided (for prevention trials). Three population groups were defined: children aged 12 years and under; otherwise healthy individuals aged 12 to 65 years; and "high risk" individuals (those with certain chronic medical conditions or aged 65 years and older). RESULTS: Seventeen treatment trials and seven prevention trials identified met the inclusion criteria. All trials included compared one of the drugs against placebo or standard care. Treatment of children, otherwise healthy individuals, and high risk populations with zanamivir reduced the median duration of symptoms in days respectively by 1.0 (95% confidence interval 0.5 to 1.5), 0.8 (0.3 to 1.3), and 0.9 (-0.1 to 1.9) for the intention to treat population. The corresponding results, in days, for oseltamivir were 0.9 (0.3 to 1.5), 0.9 (0.3 to 1.4), and 0.4 (-0.7 to 1.4). The effect of giving zanamivir and oseltamivir prophylactically resulted in a relative reduction of 70-90% in the odds of developing flu, depending on the strategy adopted and the population studied. CONCLUSIONS: Evidence from randomised controlled trials consistently supports the view that both oseltamivir and zanamivir are clinically effective for treating and preventing flu. However, evidence is limited for the treatment of certain populations and for all prevention strategies.

Acetamides↗

PubMed2003

Modelling the cost effectiveness of interferon beta and glatiramer acetate in the management of multiple sclerosis. Commentary: evaluating disease modifying treatments in multiple sclerosis.

OBJECTIVE: To evaluate the cost effectiveness of four disease modifying treatments (interferon betas and glatiramer acetate) for relapsing remitting and secondary progressive multiple sclerosis in the United Kingdom. DESIGN: Modelling cost effectiveness. SETTING: UK NHS. PARTICIPANTS: Patients with relapsing remitting multiple sclerosis and secondary progressive multiple sclerosis. MAIN OUTCOME MEASURES: Cost per quality adjusted life year gained. RESULTS: The base case cost per quality adjusted life year gained by using any of the four treatments ranged from pound 42,000 (66,469 dollars; 61,630 euro) to pound 98,000 based on efficacy information in the public domain. Uncertainty analysis suggests that the probability of any of these treatments having a cost effectiveness better than pound 20,000 at 20 years is below 20%. The key determinants of cost effectiveness were the time horizon, the progression of patients after stopping treatment, differential discount rates, and the price of the treatments. CONCLUSIONS: Cost effectiveness varied markedly between the interventions. Uncertainty around point estimates was substantial. This uncertainty could be reduced by conducting research on the true magnitude of the effect of these drugs, the progression of patients after stopping treatment, the costs of care, and the quality of life of the patients. Price was the key modifiable determinant of the cost effectiveness of these treatments.

Cost-Benefit Analysis↗

PubMed2003

Development of resource-use and expenditure questionnaires for use in rheumatology research.

OBJECTIVE: To develop a self-completion and postal resource-use and expenditure questionnaire for use in economic studies of early inflammatory polyarthritis (IP). METHODS: Identification of cost-generating events associated with early IP through a literature review and focus groups of IP patients and their partners. The information obtained was used to inform the development of self-completion postal resource-use and expenditure data collection instruments/questionnaires in terms of structure and content. Finally, the developed questionnaire was pilot-tested and validated in populations in 2 geographically different areas. RESULTS: The main cost categories identified through the focus groups, and used in the development of the questionnaires, included forgone leisure time and activities, reliance on other people, life events, emotions, help with everyday chores, travel, and over-the-counter medication. Pilot-testing the questionnaires resulted in high unit and item response rates, and high acceptability and ease of completion by respondents, as well as generalizability to different geographical settings. Where possible, collected data were validated against alternative data sources, and agreement was good. CONCLUSION: Overall, resource-use and expenditure questionnaires developed in this study were shown to be highly acceptable to respondents, easy to complete, and generalizable to different geographical settings within the UK.

Arthritis↗

PubMedDate not supplied

Use of Bayesian Markov Chain Monte Carlo methods to model cost-of-illness data.

It is well known that the modeling of cost data is often problematic due to the distribution of such data. Commonly observed problems include 1) a strongly right-skewed data distribution and 2) a significant percentage of zero-cost observations. This article demonstrates how a hurdle model can be implemented from a Bayesian perspective by means of Markov Chain Monte Carlo simulation methods using the freely available software WinBUGS. Assessment of model fit is addressed through the implementation of two cross-validation methods. The relative merits of this Bayesian approach compared to the classical equivalent are discussed in detail. To illustrate the methods described, patient-specific non-health-care resource-use data from a prospective longitudinal study and the Norfolk Arthritis Register (NOAR) are utilized for 218 individuals with early inflammatory polyarthritis (IP). The NOAR database also includes information on various patient-level covariates.

Arthritis↗