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Biomedical subjects

E Fenwick

Publications and source records attributed to E Fenwick.

6 recordsLinked to original sources
PubMed2007

A systematic review and economic model of the clinical effectiveness and cost-effectiveness of docetaxel in combination with prednisone or prednisolone for the treatment of hormone-refractory metastatic prostate cancer.

OBJECTIVES: A systematic review was undertaken and an economic model constructed to evaluate the clinical effectiveness and cost-effectiveness of docetaxel (Taxotere, Sanofi-Aventis) in combination with prednisone/prednisolone for the treatment of metastatic hormone-refractory prostate cancer (mHRPC). The main comparators considered were other established chemotherapy regimens and best supportive care. DATA SOURCES: Twenty-one resources (including MEDLINE, EMBASE and the Cochrane Library) were searched to April 2005. REVIEW METHODS: Two reviewers independently assessed studies for inclusion. Data from included studies were extracted and quality assessed. Where appropriate, outcomes were synthesised using formal analytic approaches. A new economic model was developed in order to establish the cost-effectiveness of docetaxel compared with a range of potential comparators. A separate review was undertaken to identify sources of utility data required to estimate quality-adjusted life-years (QALYs). Sensitivity analyses were also undertaken to explore the robustness of the main analysis to alternative assumptions related to quality of life. Monte Carlo simulation was used to propagate uncertainty in input parameters through the model in such a way that the results of the analysis could be presented with their uncertainty. The impact of uncertainty surrounding the decision was established using value of information and implementation approaches. RESULTS: Seven randomised controlled trials were identified that met the inclusion criteria. A direct comparison of docetaxel plus prednisone versus mitoxantrone plus prednisone in an open-label randomised trial showed improved outcomes for docetaxel plus prednisone in terms of overall survival, quality of life, pain and prostate-specific antigen decline. Two other chemotherapy regimens that included docetaxel: docetaxel plus estramustine and docetaxel plus prednisone plus estramustine, also showed improved outcomes in comparison with mitoxantrone plus prednisone. Indirect comparison suggested that docetaxel plus prednisone seems to be superior to corticosteroids alone in terms of overall survival. Conclusions on cost-effectiveness were primarily informed by the results of the in-house model. This indicated that mitoxantrone plus a corticosteroid is probably cheaper and more effective than corticosteroid alone. Compared with mitoxantrone plus prednisone/prednisolone, the use of docetaxel plus prednisone/prednisolone (3-weekly) appears cost-effective only if the NHS is prepared to pay 33,000 pounds per QALY. The incremental cost-effectiveness ratio associated with docetaxel plus prednisone (3-weekly) remained fairly robust to these variations with estimates ranging from 28,000 pounds to 33,000 pounds per QALY. Value of information analysis revealed that further research is potentially valuable. Given a maximum acceptable ratio of 30,000 pounds per QALY, the expected value of information was estimated to be approximately 13 million pounds. CONCLUSIONS: This systematic review of the research suggests that docetaxel plus prednisone seems to be the most effective treatment for men with mHRPC. The economic model suggests that treatment with docetaxel plus prednisone/prednisolone is cost-effective in patients with mHRPC provided the NHS is prepared to pay 33,000 pounds per additional QALY. Future research should include the direct assessment of quality of life and utility gain associated with different treatments, including the effect of adverse events of treatment, using generic instruments, which are suitable for the purposes of cost-effectiveness analyses.

Antineoplastic Agents↗
PubMed2006

A systematic review of the effectiveness of docetaxel and mitoxantrone for the treatment of metastatic hormone-refractory prostate cancer.

A systematic review was performed to evaluate the clinical effectiveness of docetaxel in combination with prednisolone (docetaxel is licensed in the UK for use in combination with prednisone or prednisolone for the treatment of patients with metastatic hormone-refractory prostate cancer. Prednisone is not used in the UK, but it is reasonable to use docetaxel plus prednisone data in this review of docetaxel plus prednisolone) for the treatment of metastatic hormone-refractory prostate cancer. A scoping search identified a trial of docetaxel plus prednisone vs mitoxantrone plus prednisone, but did not identify any trials comparing docetaxel plus prednisolone/prednisone with any other treatments. Therefore, we considered additional indirect evidence that would enable a comparison of docetaxel plus prednisolone/prednisone with other chemotherapy regimens and active supportive care. Systematic searching (upto April 2005) identified seven randomised controlled trials. One large well-conducted trial assessed docetaxel plus prednisone vs mitoxantrone plus prednisone; this showed statistically significant improvements with 3-weekly docetaxel in terms of overall survival, quality of life, pain response and PSA decline. Two other chemotherapy regimens that included docetaxel with estramustine also showed improved outcomes in comparison with mitoxantrone plus prednisone. Three trials that compared mitoxantrone plus corticosteroids with corticosteroids alone were identified and their results for overall survival combined, which showed very little difference between the two groups. The addition of clodronate to mitoxantrone plus prednisone showed no significant differences in comparison with mitoxantrone plus prednisone alone. The evidence suggests that chemotherapy regimens containing 3-weekly docetaxel are superior to mitoxantrone or corticosteroids alone.

Antineoplastic Agents, Hormonal↗
PubMed2001

Representing uncertainty: the role of cost-effectiveness acceptability curves.

Decision-making in health care is inevitably undertaken in a context of uncertainty concerning the effectiveness and costs of health care interventions and programmes. One method that has been suggested to represent this uncertainty is the cost-effectiveness acceptability curve. This technique, which directly addresses the decision-making problem, has advantages over confidence interval estimation for incremental cost-effectiveness ratios. However, despite these advantages, cost-effectiveness acceptability curves have yet to be widely adopted within the field of economic evaluation of health care technologies. In this paper we consider the relationship between cost-effectiveness acceptability curves and decision-making in health care, suggest the introduction of a new concept more relevant to decision-making, that of the cost-effectiveness frontier, and clarify the use of these techniques when considering decisions involving multiple interventions. We hope that as a result we can encourage the greater use of these techniques.

Confidence Intervals↗
PubMed2000

Assessing quality in decision analytic cost-effectiveness models. A suggested framework and example of application.

Despite the growing use of decision analytic modelling in cost-effectiveness analysis, there is a relatively small literature on what constitutes good practice in decision analysis. The aim of this paper is to consider the concept of 'validity' and 'quality' in this area of evaluation, and to suggest a framework by which quality can be demonstrated on the part of the analyst and assessed by the reviewer and user. The paper begins by considering the purpose of cost-effectiveness models and argues that the their role is to identify optimum treatment decisions in the context of uncertainty about future states of the world. The issue of whether such models can be defined as 'scientific' is considered. The notion that decision analysis undertaken at time t can only be considered scientific if its outputs closely predict the results of a trial undertaken at time t + 1 is rejected as this ignores the need to make decisions on the basis of currently available evidence. Rather, the scientific characteristic of decision models is based on the fact that, in principle at least, such analyses can be falsified by comparison of two states of the world, one where resource allocation decisions are based on formal decision analysis and the other where such decisions are not. This section of the paper also rejects the idea of exact codification of scientific method in general, and of decision analysis in particular, as this risks rejecting potentially valuable models, may discourage the development of novel methods and can distort research priorities. However, the paper argues that it is both possible and necessary to develop a framework for assessing quality in decision models. Building on earlier work, various dimensions of quality in decision modelling are considered: model structure (disease states, options, time horizon and cycle length); data (identification, incorporation, handling uncertainty); and consistency (internal and external). Within this taxonomy a (nonexhaustive) list of questions about quality is suggested which are illustrated by their application to a specific published model. The paper argues that such a framework can never be prescriptive about every aspect of decision modelling. Rather, it should encourage the analyst to provide an explicit and comprehensive justification of their methods, and allow the user of the model to make an informed judgment about the relevance, coherence and usefulness of the analysis.

Clinical Trials as Topic↗
PubMed1990

ThioTEPA pharmacokinetics during intravesical chemotherapy and the influence of Tween 80.

A pharmacokinetic study of randomised crossover design was carried out in which eight patients with recurrent stage pTa or pT1 transitional cell carcinoma of the bladder were given thioTEPA (30 mg) in distilled water or in 10% (v/v) Tween 80 (30 ml) intravesically for 2 h, followed 3 months later by the alternative treatment. ThioTEPA and its primary metabolite, TEPA, were measured in plasma and urine using a sensitive and specific chromatographic assay. Large differences between patients were observed in the proportion of thioTEPA absorbed, ranging from 20%-78%. Peak plasma levels of thioTEPA were observed within 1 h of intravesical administration. By 2 h after administration the plasma levels of TEPA were similar to those of thioTEPA and, in contrast to those of the parent compound, remained at a similar level over the next 4 h. The rate of absorption of thioTEPA was not influenced by Tween 80, but it did cause statistically significant increases in mean peak plasma levels (from 101 to 154 ng/ml) and mean AUC values (from 0.376 to 0.496 micrograms h per ml) and a decrease in the mean half-life (from 1.83 to 1.25 h). To obtain plasma levels similar to those achieved after instillation with thioTEPA alone, the dose should be reduced with Tween 80.

Absorption↗