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Biomedical subjects

A Briggs

Publications and source records attributed to A Briggs.

At least 19 recordsLinked to original sources
PubMed2006

Cost-effectiveness of using prognostic information to select women with breast cancer for adjuvant systemic therapy.

OBJECTIVES: To investigate the cost-effectiveness of using prognostic information to identify patients with breast cancer who should receive adjuvant therapy. DATA SOURCES: Electronic databases from 1980 through to February 2002. A survey of clinical practice in UK cancer centres and units. Large retrospective dataset containing data on prognostic factors, treatments and outcomes for women with early breast cancer treated in Oxford. REVIEW METHODS: Between six and nine databases were searched by an information expert. Evidence-based methods were used to review and select those studies and the quality of each included paper was assessed using standard assessment tools reported in the literature or piloted and developed for this study. A survey of clinical practice in UK cancer centres and units was carried out to ensure that conclusions drawn from the report could be implemented. These data, along with the information gathered in the systematic reviews, informed the methodological approach adopted for the health economic modelling. An illustrative framework was developed for incorporating patient-level prediction within a health economic decision model. This framework was applied to a large retrospective dataset containing data on prognostic factors, treatments and outcomes for women with early breast cancer treated in Oxford. The data were used to estimate directly a parametric regression-based risk equation, from which a prognostic index was developed, and prognosis-specific estimates of the baseline breast cancer hazard could be observed. Published estimates of treatment effects, health service treatment costs and utilities were used to construct a decision analytic framework around this risk equation, thus enabling simulation of the effectiveness and cost-effectiveness of adjuvant therapy for all possible combinations of prognostic factors included in the model. RESULTS: The lack of good-quality systematic reviews and well-conducted studies of prognostic factors in breast cancer is a striking finding. There are no registers of studies of prognostic factors or of reviews of prognostic studies. Many of the reviews used weak methods, primary studies are similar with poor methodology and reporting of results. In addition, there is much variation in patient populations, assay methods, analysis of results, definitions used and reporting of results. Most studies appear to be retrospective and some use inappropriate methods likely to inflate outcomes such as optimising cut points and failing to test the results in an independent population. Very few reviews used meta-analysis to conduct a pooled analysis and to provide an estimate of the average size of any association. Instead, most reviews relied on vote counting. Although many prognostic models for breast cancer have been published, remarkably few have been re-examined by independent groups in independent settings. The few validation studies have been carried out on ill-defined samples, sometimes of smaller size and short follow-up, and sometimes using different patient outcomes when validating a model. The evidence from the validation studies shows support for the prognostic value of the Nottingham Prognostic Index (NPI). No new prognostic factors have been shown to add substantially to those identified in the 1980s. Improvement of this index depends on finding factors that are as important as, but independent of, lymph node, stage and pathological grade. The NPI remains a useful clinical tool, although additional factors may enhance its use. We accepted that hormone receptor status (ER) for hormonal therapy such as tamoxifen and prediction of response to trastuzumab by HER2 did not require systematic review, as the mechanism of action of these drugs requires intact receptors. There was no clear evidence that other factors were useful predictors of response and survival. The survey confirmed pathological nodal status, tumour grade, tumour size and ER status as the most clinically important factors for consideration when selecting women with early breast cancer for adjuvant systemic therapy in the UK. The protocols revealed that although UK cancer centres appear to be using the same prognostic and predictive factors when selecting women to receive adjuvant therapy, much variation in clinical practice exists. Some centres use protocols based upon the NPI whereas others do not use a single index score. Within NPI and non-NPI users, between-centre variability exists in guidelines for women for whom the benefits are uncertain. Consensus amongst units appears to be greatest when selecting women for adjuvant hormone therapy with the decision based primarily upon ER or progesterone receptor status rather than combinations of a number of factors. Guidelines as to who should receive adjuvant chemotherapy, however, were found to be much less uniform. Searches of the literature revealed only five published papers that had previously examined the cost-effectiveness of using prognostic information for clinical decision-making. These studies were of varying quality and highlight the fact that economic evaluation in this area appears still to be in its infancy. By combining methodologies used in determining prognosis with those used in health economic evaluation, it was possible to illustrate an approach for simulating the effectiveness (survival and quality-adjusted survival) and the cost-effectiveness associated with the decision to treat individual women or groups of women with different prognostic characteristics. The model showed that effectiveness and cost-effectiveness of adjuvant systemic therapy have the potential to vary substantially depending upon prognosis. For some women therapy may prove very effective and cost-effective, whereas for others it may actually prove detrimental (i.e. the reductions in health-related quality of life outweigh any survival benefit). CONCLUSIONS: Outputs from the framework constructed using the methods described here have the potential to be useful for clinicians, attempting to determine whether net benefits can be obtained from administering adjuvant therapy for any presenting woman; and also for policy makers, who must be able to determine the total costs and outcomes associated with different prognosis based treatment protocols as compared with more conventional treat all or treat none policies. A risk table format enabling clinicians to look up a patient's prognostic factors to determine the likely benefits (survival and quality-adjusted survival) from administering therapy may be helpful. For policy makers, it was demonstrated that the model's output could be used to evaluate the cost-effectiveness of different treatment protocols based upon prognostic information. The framework should also be valuable in evaluating the likely impact and cost-effectiveness of new potential prognostic factors and adjuvant therapies.

Adjuvants, Pharmaceutic↗
PubMed2005

Cost-utility analyses of intensive blood glucose and tight blood pressure control in type 2 diabetes (UKPDS 72).

AIMS/HYPOTHESIS: This study estimated the economic efficiency (1) of intensive blood glucose control and tight blood pressure control in patients with type 2 diabetes who also had hypertension, and (2) of metformin therapy in type 2 diabetic patients who were overweight. METHODS: We conducted cost-utility analysis based on patient-level data from a randomised clinical controlled trial involving 4,209 patients with newly diagnosed type 2 diabetes conducted in 23 hospital-based clinics in England, Scotland and Northern Ireland as part of the UK Prospective Diabetes Study (UKPDS). Three different policies were evaluated: intensive blood glucose control with sulphonylurea/insulin; intensive blood glucose control with metformin for overweight patients; and tight blood pressure control of hypertensive patients. Incremental cost : effectiveness ratios were calculated based on the net cost of healthcare resources associated with these policies and on effectiveness in terms of quality-adjusted life years gained, estimated over a lifetime from within-trial effects using the UKPDS Outcomes Model. RESULTS: The incremental cost per quality-adjusted life years gained (in year 2004 UK prices) for intensive blood glucose control was 6,028 UK pounds, and for blood pressure control was 369 UK pounds. Metformin therapy was cost-saving and increased quality-adjusted life expectancy. CONCLUSIONS/INTERPRETATION: Each of the three policies evaluated has a lower cost per quality-adjusted life year gained than that of many other accepted uses of healthcare resources. The results provide an economic rationale for ensuring that care of patients with type 2 diabetes corresponds at least to the levels of these interventions.

Adult↗
PubMed2004

A model to estimate the lifetime health outcomes of patients with type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model (UKPDS no. 68).

AIMS/HYPOTHESIS: The aim of this study was to develop a simulation model for type 2 diabetes that can be used to estimate the likely occurrence of major diabetes-related complications over a lifetime, in order to calculate health economic outcomes such as quality-adjusted life expectancy. METHODS: Equations for forecasting the occurrence of seven diabetes-related complications and death were estimated using data on 3642 patients from the United Kingdom Prospective Diabetes Study (UKPDS). After examining the internal validity, the UKPDS Outcomes Model was used to simulate the mean difference in expected quality-adjusted life years between the UKPDS regimens of intensive and conventional blood glucose control. RESULTS: The model's forecasts fell within the 95% confidence interval for the occurrence of observed events during the UKPDS follow-up period. When the model was used to simulate event history over patients' lifetimes, those treated with a regimen of conventional glucose control could expect 16.35 undiscounted quality-adjusted life years, and those receiving treatment with intensive glucose control could expect 16.62 quality-adjusted life years, a difference of 0.27 (95% CI: -0.48 to 1.03). CONCLUSIONS/INTERPRETATIONS: The UKPDS Outcomes Model is able to simulate event histories that closely match observed outcomes in the UKPDS and that can be extrapolated over patients' lifetimes. Its validity in estimating outcomes in other groups of patients, however, remains to be evaluated. The model allows simulation of a range of long-term outcomes, which should assist in informing future economic evaluations of interventions in type 2 diabetes.

Amputation, Surgical↗
PubMed2003

Contemporary understanding and management of reflux and constipation in the general population and pregnancy: a consensus meeting.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) and constipation have a major impact on public health; however, the wide variety of treatment options presents difficulties for recommending therapy. Lack of definitive guidelines in pharmacy and general practice medicine further exacerbates the decision dilemma. AIMS: To address these issues, a panel of experts discussed the principles and practice of treating GERD and constipation in the general population and in pregnancy, with the aim of developing respective treatment guidelines. RESULTS: The panel recommended antacids 'on-demand' as the first-line over-the-counter treatment in reflux, and as rescue medication for immediate relief when reflux breaks through with proton pump inhibitors. Calcium/magnesium-based antacids were recommended as the treatment of choice for pregnant women because of their good safety profile. In constipation, current data do not distinguish a hierarchy between polyethylene glycol (PEG)-based laxatives and other first-line treatments, although limitations are associated with stimulant- and bulk-forming laxatives. Where data are available, PEG is superior to lactulose in terms of efficacy. In pregnancy, PEG-based laxatives meet the criteria for the ideal treatment. CONCLUSIONS: The experts developed algorithms that present healthcare professionals with clear treatment options and management strategies for GERD and constipation in pharmacy and general practice medicine.

Adult↗
PubMed2003

Comparative pharmacokinetic study of high-dose etoposide and etoposide phosphate in patients with lymphoid malignancy receiving autologous stem cell transplantation.

The pharmacokinetics of two etoposide (E) formulations were evaluated in patients with refractory hematologic malignancies receiving high-dose conditioning with autologous stem cell transplantation. Patients were randomized to either E at 800 mg/m(2) (containing polysorbate 80 and polyethylene glycol) or etoposide phosphate (EP) at 910 mg/m(2) on days -7 and -5, prior to melphalan, 80 mg/m(2) on day -5. On day -3, EP was repeated. Plasma E was analyzed after each formulation on days -7 and -5 to compare intrapatient pharmacokinetics. In total, 10 patients were treated: four each with multiple myeloma or Hodgkin's disease and two with non-Hodgkin's lymphoma. Mucositis was the major toxicity with seven patients. EP first produced grade 3 mucositis. There was no procedure-related mortality and eight patients remained alive 1 year post-transplant. Cumulative etoposide exposure (AUC) was slightly greater with EP (P=0.056). Conversely, the volume of distribution was slightly, 33%, larger (P=0.052) and clearance was increased with the E infusion (P=0.14). As none of the differences reached statistical significance, both E formulations appear to be pharmacokinetically equivalent in the high-dose transplant setting. The combination of high-dose EP with melphalan is an active preparative regimen prior to ABMT for hematologic malignancies.

Adult↗
PubMed2003

The impact of diabetes-related complications on healthcare costs: results from the United Kingdom Prospective Diabetes Study (UKPDS Study No. 65).

AIMS: To develop a model for estimating the immediate and long-term healthcare costs associated with seven diabetes-related complications in patients with Type 2 diabetes participating in the UK Prospective Diabetes Study (UKPDS). METHODS: The costs associated with some major complications were estimated using data on 5102 UKPDS patients (mean age 52.4 years at diagnosis). In-patient and out-patient costs were estimated using multiple regression analysis based on costs calculated from the length of admission multiplied by the average specialty cost and a survey of 3488 UKPDS patients' healthcare usage conducted in 1996-1997. RESULTS: Using the model, the estimate of the cost of first complications were as follows: amputation pound 8459 (95% confidence interval pound 5295, pound 13 200); non-fatal myocardial infarction pound 4070 ( pound 3580, pound 4722); fatal myocardial infarction pound 1152 ( pound 941, pound 1396); fatal stroke pound 3383 ( pound 1935, pound 5431); non-fatal stroke pound 2367 ( pound 1599, pound 3274); ischaemic heart disease pound 1959 ( pound 1467, pound 2541); heart failure pound 2221 ( pound 1690, pound 2896); cataract extraction pound 1553 ( pound 1320, pound 1855); and blindness in one eye pound 872 ( pound 526, pound 1299). The annual average in-patient cost of events in subsequent years ranged from pound 631 ( pound 403, pound 896) for heart failure to pound 105 ( pound 80, pound 142) for cataract extraction. Non-in-patient costs for macrovascular complications were pound 315 ( pound 247, pound 394) and for microvascular complications were pound 273 ( pound 215, pound 343) in the year of the event. In each subsequent year the costs were, respectively, pound 258 ( pound 228, pound 297) and pound 204 ( pound 181, pound 255). CONCLUSIONS: These results provide estimates of the immediate and long-term healthcare costs associated with seven diabetes-related complications.

Ambulatory Care↗
PubMed2001

Interlayer transport in the highly anisotropic misfit-layer superconductor [(LaSe)(1.14)](NbSe(2)).

The interlayer transport in a two-dimensional superconductor can reveal a peak in the temperature as well as the magnetic field dependence of the resistivity near the superconducting transition. The experiment was performed on the highly anisotropic misfit-layer superconductor [(LaSe)(1.14)](NbSe(2)) with T(c) of 1.2 K. The effect is interpreted within the tunneling mechanism of the charge transport across the Josephson-coupled layers via two parallel channels--the quasiparticles and the Cooper pairs. Similar behavior can be found in the high-T(c) cuprates but there it is inevitably interfering with the anomalous normal state. The upper critical magnetic field can be obtained from the interlayer tunneling conductance.

Journal Article↗
PubMed2001

An open, randomised, multi-centre study comparing the safety and efficacy of sitafloxacin and imipenem/cilastatin in the intravenous treatment of hospitalised patients with pneumonia.

This was a phase II, randomised, open-label, multi-centre study to assess the safety, tolerability, and efficacy of sitafloxacin (DU-6859a, 400 mg once daily) compared with imipenem (imipenem/cilastatin, 500 mg three times daily) in the treatment of hospitalised patients with pneumonia. Patients (n=69) were entered into the study in the intent-to-treat group, 35 in the sitafloxacin and 34 in the imipenem group. Patients (n=65) were included in the clinically evaluable population and 42 in the bacteriologically evaluable population. Baseline demographic data and clinical characteristics were similar for both treatment groups and across all patient populations. The incidence, severity and type of adverse events were similar in both treatment groups. The frequency of adverse events, which were considered to be related to the study of drugs was low and generally similar between the two groups. Mild transient increases in alanine aminotransferase and alkaline phosphatase occurred in the sitafloxacin treatment group, but there were no apparent trends in the other serum enzyme levels. The clinical response at the first and second follow-up assessments indicated that 94-97% of patients in the clinically evaluable population and 91% of patients in the intent-to-treat population were classified as cured in both treatment groups. The bacteriological response was classified as satisfactory for all patients (100%) in the bacteriologically evaluable population in the imipenem treatment group and satisfactory for 90 and 95% of cases at the first and second follow-up assessments in the bacteriologically evaluable population in the sitafloxacin treatment group, respectively. In conclusion, for the treatment of pneumonia, sitafloxacin was considered as safe and as tolerable as imipenem and preliminary data from this study suggest that it may have similar efficacy.

Adolescent↗
PubMed2001

Pharmacokinetics and absolute bioavailability of sitafloxacin, a new fluoroquinolone antibiotic, in healthy male and female Caucasian subjects.

1. The aim was to compare the pharmacokinetics of sitafloxacin from a capsule formulation (dose of 500 mg sitafloxacin) and an intravenous (i.v.) formulation infused over 1 h (dose of 400 mg sitafloxacin) in healthy male and female subjects and to estimate the absolute bioavailability of sitafloxacin from the capsule formulation. 2. Following oral administration, sitafloxacin was rapidly absorbed, with a mean maximum concentration in plasma of 4.65 microgml(-1) occuring at median tmax = 1.25 h giving a mean AUC(0-infinity) = 28.1 microg h ml(-1). For the i.v. administration, a mean Cmax = 5.53 microm(-1) occurred at the end of the 1-h infusion with a mean AUC(0-infinity) = 25.4 microg h ml(-1). The mean terminal elimination half-life was 7.0 h (oral) and 6.6 h (i.v.). For the oral and i.v. formulations, the mean total plasma clearance was 296 and 263 mlmin(-1), respectively and the mean volume of distribution was 180 and 150 litres, respectively. 3. Within 48 h post-dose, approximately 61% (range 22-86%) of the administered dose was excreted unchanged in urine following capsule administration, compared with approximately 75% (range 42-101%) following the i.v. formulation. For both formulations, the renal clearance of sitafloxacin (means of 181 and 198 ml min(-1) for the capsule and i.v. doses, respectively) implies active tubular secretion of the drug. 4. The absolute bioavailability of sitafloxacin from the capsule formulation was high at 89%, with a 95% CI of 84-94%. The intersubject variability (CV%) in the sitafloxacin AUC(0-infinity) for the capsule was low at 18.6%. 5. Gender differences in the pharmacokinetics of sitafloxacin were small and would not warrant dose adjustment. 6. The findings show that the capsule formulation offers good oral bioavailability and merits further clinical evaluation of sitafloxacin as an orally effective fluoroquinolone antibacterial.

Administration, Oral↗
PubMed2000

Cost effectiveness of initial endoscopy for dyspepsia in patients over age 50 years: a randomised controlled trial in primary care.

BACKGROUND: Dyspepsia can be managed by initial endoscopy and treatment based on endoscopic findings, or by empirical prescribing. We aimed to determine the cost effectiveness of initial endoscopy compared with usual management in patients with dyspepsia over age 50 years presenting to their primary care physician. METHODS: 422 patients were recruited and randomly assigned to initial endoscopy or usual management. Primary outcomes were effect of treatment on dyspepsia symptoms and cost effectiveness. Secondary outcomes were quality of life and patient satisfaction. Total costs were calculated from individual patient's use of resources with unit costs applied from national data. Statistical analysis of uncertainty on incremental cost-effectiveness ratio (ICER) was done along with a sensitivity analysis on unit costs with cost-effectiveness acceptability curves. FINDINGS: In the 12 months following recruitment, 213 (84%) patients had an endoscopy compared with 75 (41%) controls. Initial endoscopy resulted in a significant improvement in symptom score (p=0.03), and quality of life pain dimension (p=0.03), and a 48% reduction in the use of proton pump inhibitors (p=0.005). The ICER was Pound Sterling1728 (UK Pound Sterling) per patient symptom-free at 12 months. The ICER was very sensitive to the cost of endoscopy, and could be reduced to Pound Sterling165 if the unit cost of this procedure fell from Pound Sterling246 to Pound Sterling100. INTERPRETATION: Initial endoscopy in dyspeptic patients over age 50 might be a cost-effective intervention.

Aged↗
PubMed2000

Centre-specific or average unit costs in multi-centre studies? Some theory and simulation.

Costing issues are increasingly being addressed in multi-centre studies. In this paper, two methods for collecting costing information are compared within a simulated clinical trial setting. One method estimates average treatment costs by applying unit costs averaged across treatment centres to centre-specific volumes of resource use. The second uses centre-specific information for both the unit costs and the resource volumes, and then averages across centres. Using a pre-specified production relation between the different volumes of resource use, and simulating changes in unit costs, it is shown that these two methods result in statistically different estimates of average treatment costs. This finding holds, regardless of the degree of substitutability between the resource volumes, except when considerable uncertainty surrounds treatment centre responses to relative changes in unit costs. The findings suggest that a more cautious approach should be adopted in the collection, calculation and interpretation of treatment costs in multi-centre studies.

Computer Simulation↗
PubMed2000

Life-expectancy projection by modelling and computer simulation (UKPDS 46).

A method is described for estimating the life-expectancy of cohorts of type 2 diabetic patients, based on computer simulation from a parametric model. The method can be used where non-parametric methods, such as the Kaplan-Meier estimate, fail due to lack of the data. The simulation algorithm combines observed and modelled information to estimate the life-expectancy implications of event rates observed within a study. The use of bootstrap methods to estimate confidence intervals is discussed. The methods are illustrated with results that have been previously published, without derivation, in a health economic analysis of tight blood pressure (BP) control in the UK Prospective Diabetes Study (UKPDS), and the application to other health economic analyses of UKPDS data is discussed.

Algorithms↗
PubMed1999

Impact of osteoarthritis and analgesic treatment on quality of life of an elderly population.

UNLABELLED: To determine the quality of life of elderly patients with osteoarthritis (OA) compared with that of their peers with no chronic illnesses and to investigate the associations between analgesic use and quality of life. SUBJECTS: Patients >65 years of age with OA taking analgesics with (n = 33) and without (n = 26) comorbidities, and control patients with no chronic illness and not taking analgesics (n = 37). METHODS: Quality of life was assessed by the SF-36 and level of pain was measured by a visual analog scale. Multiple regression analysis was used to determine the medication characteristics and additional patient factors significantly associated with SF-36 scores. RESULTS: OA patients had significantly (p < 0.05) lower scores than control patients in all quality-of-life domains. OA patient scores were lowest for the domains of role-physical, bodily pain, and physical functioning. OA patients with comorbidities also had poorer general and mental health. Pain- and analgesic-related factors were significantly (p < 0.05) associated with physical health status, reduced vitality, general health, and social functioning. A better quality of life was associated with noncompliance, fewer visits to the physician, and taking oral nonsteroidal antiinflammatory agents. Presence of adverse drug reactions and sleep disturbance did not influence SF-36 scores significantly. CONCLUSIONS: Quality of life of elderly OA patients with and without additional comorbidities was significantly poorer than that of their healthy peers, particularly in the domains associated with physical status, but also affecting vitality, social functioning, and general health. Level of pain suffered and perceived effectiveness of analgesic medication in pain control were important factors associated with quality of life.

Aged↗
PubMed1998

Confidence intervals or surfaces? Uncertainty on the cost-effectiveness plane.

Although cost-effectiveness analysis is not new, it is only recently that economic analysis has been conducted alongside clinical trials. Whereas in the past economic analysts most often used sensitivity analysis to examine the implications of uncertainty for their results, the existence of patient-level data on costs and effects opens up the possibility of statistical analysis of uncertainty. Unfortunately, ratio statistics can cause problems for standard statistical methods of confidence interval estimation. The recent health economics literature contains a number of suggestions for estimating confidence limits for ratios. In this paper, we begin by reviewing the different methods of confidence interval estimation with a view to providing guidance concerning the most appropriate method. We go on to argue that the focus on confidence interval estimation for cost-effectiveness ratios in the recent literature has been concerned more with problems of estimation than with problems of decision-making. We argue that decision-makers are most likely to be interested in one-sided tests of hypothesis and that confidence surfaces are better suited to such tests than confidence intervals. This approach is consistent with decision-making on the cost-effectiveness plane and with the cost-effectiveness acceptability curve approach to presenting uncertainty due to sampling variation in stochastic cost-effectiveness analyses.

Confidence Intervals↗