Current controversies in cost effectiveness analysis of osteoporosis therapies.
Explore the source record for details and available documents.
Cost-Benefit Analysis↗
Biomedical subjects
D Coyle
Publications and source records attributed to D Coyle.
Inhibition of the intrinsic NAD+ glycohydrolase activity of CD38 by carbocyclic NAD analogues.
Carba-NAD and pseudocarba-NAD are carbocyclic analogues of NAD+ in which a 2,3-dihydroxycyclopentane methanol replaces the beta-d-ribonucleotide ring of the nicotinamide riboside moiety of NAD+ [Slama and Simmons (1988) Biochemistry 27, 183-193]. These carbocyclic NAD+ analogues, related to each other as diastereomers, have been tested as inhibitors of the intrinsic NAD+ glycohydrolase activity of human CD38, dog spleen NAD+ glycohydrolase, mouse CD38 and Aplysia californica cADP-ribose synthetase. Pseudocarba-NAD, the carbocyclic dinucleotide in which l-2,3-dihydroxycyclopentane methanol replaces the d-ribose of the nicotinamide riboside moiety of NAD+, was found to be the more potent inhibitor. Pseudocarba-NAD was shown to inhibit the intrinsic NAD+ glycohydrolase activity of human CD38 competitively, with Ki=148 microM determined for the recombinant extracellular protein domain and Ki=180 microM determined for the native protein expressed as a cell-surface enzyme on cultured Jurkat cells. Pseudocarba-NAD was shown to be a non-competitive inhibitor of the purified dog spleen NAD+ glycohydrolase, with Kis=47 miroM and Kii=198 microM. Neither pseudocarba-NAD nor carba-NAD inhibited mouse CD38 or Aplysia californica cADP-ribose synthetase significantly at concentrations up to 1 mM. The results underscore significant species differences in the sensitivity of these enzymes to inhibition, and indicate that pseudocarba-NAD will be useful as an inhibitor of the enzymic activity of human but not mouse CD38 in studies using cultured cells.
ADP-ribosyl Cyclase↗
Trials and tribulations. Emerging issues in designing economic evaluations alongside clinical trials.
Decisions relating to designing and implementing economic evaluations alongside clinical trials are dependent on a number of issues initial consideration should focus on whether an economic evaluation is appropriate, whether a randomized controlled trial (RCT) is a suitable vehicle, and whether the design of the specific RCT is appropriate for integration of economic evaluation. If an economic evaluation is appropriate, decisions are required on how economic data are to be collected and analyzed. This paper discusses these and other issues and, where appropriate, provides recommendations for future studies.
Costs and Cost Analysis↗
The role of pilot studies in the economic evaluation of health technologies.
An increasing number of economic evaluations are being conducted alongside clinical trials. While this practice offers the prospect of collecting comprehensive and accurate cost data, it requires considerable time and effort. In the case of clinical data, key analytic decisions such as which data to collect and sample size are often made with reference to smaller (pilot) trials. However, this approach is not normally followed in the case of economic evaluation. This study was based on a recently completed health technology assessment comparing conventional radiotherapy with continuous hyperfractionated accelerated radiotherapy (CHART) for patients with head and neck cancer or carcinoma of the bronchus. In the full health technology assessment, cost data were available for 526 head and neck patients (314 CHART and 212 conventional therapy) and 286 bronchus patients (175 CHART and 109 conventional therapy). In order to simulate a pilot study, data were extracted for the patients recruited to both trials in the first 3 months. These were then compared with the full data set in order to assess whether such a pilot study would have given useful guidance on: a) the usefulness of undertaking a full study; b) the sample size required; and c) the important resource items for which comprehensive data collection would be required. Pilot studies can be helpful in determining the likely advantages of undertaking full economic evaluations and in identifying important resource items. Therefore, it is important that clinical researchers and research funding bodies create the necessary time window to enable such studies to take place. However, formal sample size calculations are more difficult to perform on limited data, since they also require knowledge of the unit cost (or prices) to be attached to the resource items and the correlation between costs and clinical effects.
Bronchial Neoplasms↗
Cost-effectiveness analysis in oncology.
Physicians are faced with a burgeoning literature of economic studies. However, most physicians have little training in evaluating economic research. Economic studies involve a comparison of the costs and benefits of alternative treatment options. To be of use for medical decision making, they should meet appropriate methodological standards. These include clear specification of the research question and the perspective from which the study is being undertaken, comparison of relevant treatment options, identification and quantification of all important costs and benefits, the use of discounting to allow for time preferences for costs and benefits, and sensitivity analyses to test the robustness of the study's results. Unfortunately, not all adhere to these principles. Physicians need to be able to understand and critically assess the quality of economic studies, and the applicability of the results to their own situation, in order to participate in medical policy decisions.
Cost-Benefit Analysis↗
The problem of protocol driven costs in pharmacoeconomic analysis.
The increasing number of economic evaluations of healthcare interventions and of drug therapies in particular has been well documented. Surveys of the quality of studies have demonstrated that standards of conduct of such studies have not similarly increased. Concerns over the standards have led to increased calls that economic analyses be more closely linked to randomised controlled clinical trials (RCT). Seven potential threats to the external validity of results limit the generalisability of studies based on RCTs. One such threat is the existence of protocol driven costs. There are two main types of protocol driven costs. Protocol prescribed costs arise as a result of resource use mandated by the clinical trial design. Protocol derived costs occur when increased clinical investigations mandated by trial protocols lead to atypical disease management. Methods to control for protocol driven costs within pharmacoeconomic study designs are available. Modelling studies can be based on data within clinical trials combined with observational data representing more typical resource use. The adoption of pragmatic clinical trial designs provide greater external validity though reduced internal validity. Refinements to explanatory clinical trials can also lead to reduced protocol driven costs. The extent that current studies control for such costs is unclear due to the lack of transparency in the reporting of study methods. A review of published studies found little consideration of protocol driven costs although in several studies there was evidence of their existence. Future studies conducted alongside RCTs should explicitly address how the issue of protocol driven costs was handled within the study framework.
Economics, Pharmaceutical↗
Costs and benefits of routine follow-up after curative treatment for endometrial cancer.
OBJECTIVE: To examine the costs of routine outpatient follow-up after curative treatment of endometrial cancer, and to determine whether this leads to early detection of recurrence or survival. The impact of specific disease characteristics on survival is examined. DESIGN: Retrospective chart review, and calculation of costs. SETTING: Ottawa Regional Cancer Centre-Civic Division (ORCC-C). PATIENTS: All 432 patients referred to the ORCC-C with endometrial cancer between 1982 and 1991 who received treatment with curative intent and who continued with routine follow-up. RESULTS: Cancer recurred in 50 patients (11.57%). There was no statistically significant difference in overall survival between patients with symptomatic and asymptomatic recurrences, or between those with recurrences detected during routine follow-up visits or in the interval between routine visits. Of 4830 Papanicolaou (Pap) smears performed routinely, cancer was detected in 6 cases. The mean cost of the routine follow-up procedures for each patient with a recurrence was $19,200. CONCLUSION: Intensive follow-up of women with endometrial cancer does not result in improved survival. A prospective randomized study is warranted to evaluate other potential benefits of follow-up, such as improved quality of life or decreased morbidity. There is no economic or clinical justification for the routine use of the Pap smear in the follow-up of patients with endometrial cancer. The potential benefits of routine follow-up in endometrial cancer and other types of cancer with favourable prognoses warrant critical evaluation.
Aged↗
Costs of conventional radical radiotherapy versus continuous hyperfractionated accelerated radiotherapy (CHART) in the treatment of patients with head and neck cancer or carcinoma of the bronchus. Medical Research Council CHART Steering Committee.
The objective of this study was to compare the costs of treatment with continuous hyperfractionated accelerated radiotherapy (CHART) and those of conventional radiotherapy for patients with (1) head and neck cancer and (2) carcinoma of the bronchus. The study was conducted concurrently with two multicentre randomized controlled trials. Data were collected on the use of hospital and community service resources and patients' travel for treatment. Data on resource use up to 3 months after entry to the study were available for 526 head and neck patients (314 receiving CHART and 212 conventional therapy) and 284 bronchus patients (175 CHART and 109 conventional therapy). For patients with head and neck cancer, CHART cost Pounds 1092 (P < 0.001; 95% CI 763-1421) more than conventional therapy. For patients with carcinoma of the bronchus, CHART was also more costly, with a cost differential of Pounds 698 (P < 0.001; 95% CI 392-1003). The magnitude of the cost differentials could be reduced if the working hours of radiotherapy departments were rearranged and all hospitals had access to hostel facilities. The results of this cost analysis will help to facilitate a decision about whether the benefits of CHART, as determined by the clinical trials, are worth the additional costs of hospital-based resource use. The collection of detailed patient-specific resource-use data from a number of centres allows the determination of ways for reducing the cost differential between therapies and making CHART a more cost effective treatment alternative.
Adult↗
Constructing health state preference values from descriptive quality of life outcomes: mission impossible?
Descriptive quality of life questionnaires are commonly administered in clinical trials, to evaluate outcomes from the patient's perspective alongside conventional clinical measures. When expressed in single index form as health state preference values (HSPVs), quality of life information is also relevant to economic evaluations. By combining HSPVs with survival information, quality adjusted life years (QALYs) may be derived for cost-utility analysis. Although HSPVs are rarely measured prospectively in cancer clinical trials, the UK Medical Research Council Cancer Therapy Committee recommends the routine administration of two specific quality of life questionnaires: the Rotterdam Symptom Checklist and the Hospital Anxiety Depression Scale. This study explores two potential methods for secondary derivation of HSPVs from these instruments, using data gathered in a clinical trial of two forms of radiotherapy for non-small cell cancer of the bronchus. The first method, secondary mapping to existing utility scales, was found to be infeasible from the above questionnaires. The second method used factor analysis to summarize the descriptive quality of life data collected through the questionnaires. This revealed five distinct factors prevalent in the trial population. Using these factors, simplified health state scenarios were developed from which direct measurement of HSPVs was feasible. As the resulting HSPVs and any QALYs that may be derived from them are cancer specific, their potential value in informing resource allocation would be limited to decisions within oncology services.
Carcinoma, Non-Small-Cell Lung↗
Costing substance misuse services.
AIMS: To develop a methodology for obtaining the detailed costs of different substance misuse services and illustrate some of the specific problems by means of a case study. DESIGN: Data on the resources required, clinical activity, and patient characteristics for one year were combined to provide detailed costs for different types of clinical events and patients. SETTING: The clinical services of a publicly funded addiction unit in a large industrial city in the UK. The unit provides for alcohol and other drug misusers mainly on an outpatient basis but with inpatient care. PARTICIPANTS: Over 1500 patients were included in the analysis with 75 per cent being male, and 80 per cent aged between 20 and 49. Nearly half of the clients had alcohol as their main drug of misuse with opiate users being the next largest group. MEASUREMENT: Detailed costing by event and patient was possible as the staff type and time taken for each event were routinely recorded. A cost for each individual event was estimated and summed for each individual patient to give a cost estimate by patient for the financial year 1992/3. FINDINGS: Core treatment outpatient events had an average cost of Pounds 48, with new assessments costing Pounds 87 but these averages hid high variations. The average cost per year for those receiving only outpatient care was Pounds 358; it was Pounds 1857 for those receiving both outpatient and inpatient care. Opiate misusers were on average more costly than alcohol misusers. The costs were skewed with 10 per cent of patients accounting for 56 per cent of the total annual costs. CONCLUSIONS: Dealing with costs of non attendance, including all resource use, and coping with large individual variations in costs across individuals and intervention types are the main problems in devising cost figures. Cost data are useful but need to be combined with outcome data if they are to be used to improve patient services.
Adult↗
Increasing demands to consider both the benefits and costs of cancer treatment in decision relating to resource allocation.
Explore the source record for details and available documents.
Humans↗
Developmental responses of amphibians to solar and artificial UVB sources: a comparative study.
Many amphibian species, in widely scattered locations, currently show population declines and/or reductions in range, but other amphibian species show no such declines. There is no known single cause for these declines. Differential sensitivity to UVB radiation among species might be one contributing factor. We have focused on amphibian eggs, potentially the most UVB-sensitive stage, and compared their resistance to UVB components of sunlight with their levels of photolyase, typically the most important enzyme for repair of the major UV photoproducts in DNA, cyclobutane pyrimidine dimers. Photolyase varied 100-fold among eggs/oocytes of 10 species. Among three species-Hyla regilla, Rana cascadae, and Bufo boreas-for which resistance of eggs to solar UVB irradiance in their natural locations was measured, hatching success correlated strongly with photolyase. Two additional species, Rana aurora and Ambystoma gracile, now show similar correlations. Among the low-egg-photolyase species, R. cascadae and B. boreas are showing declines, and the status of A. gracile is not known. Of the two high-photolyase species, populations of H. regilla remain robust, but populations of R. aurora are showing declines. To determine whether levels of photolyase or other repair activities are affected by solar exposures during amphibian development, we have initiated an extended study of H. regilla and R. cascadae, and of Xenopus laevis, laboratory-reared specimens of which previously showed very low photolyase levels. Hyla regilla and R. cascadae tadpoles are being reared to maturity in laboratories supplemented with modest levels of UV light or light filtered to remove UVB wavelengths. Young X. laevis females are being reared indoors and outdoors. Initial observations reveal severe effects of both UVA and UVB light on H. regilla and R. cascadae tadpoles and metamorphs, including developmental abnormalities and high mortalities. Assays of photolyase levels in the skins of young animals roughly parallel previous egg/oocyte photolyase measurements for all three species.
Amphibians↗
Statistical analysis in pharmacoeconomic studies. A review of current issues and standards.
The increasing number of economic evaluations of healthcare interventions, and of drug therapies in particular, has been well documented. However, surveys have demonstrated that standards of conduct of such studies have not similarly increased. Of particular concern is the lack of development or even consideration of statistical techniques in the reporting of studies. This article addresses issues that must be considered both in the conduct and in the assessment of the quality of studies. Throughout the paper, examples of pharmacoeconomic analyses are used to illustrate the points made. Recommendations for the conduct of future pharmacoeconomic studies are given. Such recommendations specifically relate to the level of testing that is conducted, the choice of statistical tests and the manner in which statistical significance is reported. In addition, existing methods for the statistical analysis of cost-effectiveness ratios and for the determination of sample size in economic evaluations are discussed, and a partial solution to this issue is offered.
Cost-Benefit Analysis↗
Ambulatory blood pressure measurement and the occurrence of hypertensive organ involvement.
Target organ involvement in hypertensive patients carries a poor prognosis, especially echocardiographically demonstrated left ventricular hypertrophy. Conventional blood pressure measurement correlates with target organ damage and mortality. 24-Hour ambulatory blood pressure measurement (ABPM) is a better predictor of target organ involvement than conventional blood pressure measurement, but there is as yet only scant evidence that 24-hour ABPM predicts mortality. The techniques for assessing target organ involvement and the superiority of ABPM over conventional measurement in predicting target organ damage are reviewed. It is argued that if 24-hour ABPM predicts target organ damage better than conventional measurement, then the likelihood is that it will also be a better predictor of mortality than conventional measurement. The studies underway to determine this important issue are reviewed.
Arteries↗
European School of Oncology Advisory report to the Commission of the European Communities for the "Europe Against Cancer Programme" cost-effectiveness in cancer care.
Explore the source record for details and available documents.
Cost-Benefit Analysis↗
The economic burden of glaucoma in the UK. The need for a far-sighted policy.
Explore the source record for details and available documents.
Age Distribution↗
A new audiovisual technique for recording blood pressure in research: the Sphygmocorder.
OBJECTIVE: To devise a method of blood pressure measurement capable of being substituted for the fallible human observer in validation of blood pressure measuring devices. DESIGN: A number of components used to measure blood pressure have been combined innovatively with audiovisual recording technology to produce a system, named the Sphygmocorder, which consists of a mercury sphygmomanometer, an occluding cuff, an inflation source, a stethoscope, a microphone capable of detecting Korotkoff sounds, a camcorder and a display screen. METHODS: To determine the accuracy of the Sphygmocorder against the trained human observer, the Sphygmocorder has been validated in three separate studies in which three devices for self-measurement of blood pressure, the Omron HEM-705CP, the Phillips HP5332 and the Nissei DS-175, were being validated against two trained observers in 85 subjects with a wide range of blood pressure according to the protocol of the British Hypertension Society. RESULTS: The Sphygmocorder was as accurate as at least one of the observers in each of the validation studies and therefore allows replacement of trained observers by the new device. CONCLUSION: The Sphygmocorder, which retains the time-honoured technique of blood pressure measurement with a mercury sphygmomanometer and an auscultating observer, and provides, in addition, objective evidence of the measurement recorded, which can be stored and re-examined, can be used as a substitute for human observers in validation studies of blood pressure-measuring devices.
Blood Pressure Determination↗
Use of lambda gt11 to identify antigenic components of equine herpesvirus 4.
A library of the equine herpesvirus 4 (EHV-4) genome was constructed in the lambda gt11 expression vector. Recombinant bacteriophage expressing EHV-4 antigens as beta-galactosidase fusion proteins were detected with rabbit antiserum raised against EHV-4 virions and convalescent horse serum. EHV-4 DNA sequences contained in the immunopositive recombinants were used as hybridization probes for mapping the genes encoding the antigens on the viral genome. The DNA sequence of the probes was determined. Screening the library with rabbit antiserum led to the identification of 40 recombinants, 26 of which were further characterized. Determination of the DNA sequence of the EHV-4 inserts revealed that 23 of the recombinants encode an identical portion of glycoprotein gB. Two of the recombinants encode a portion of the previously unidentified EHV-4 homologue of the EHV-1 immediate early protein. The EHV-4 insert of the remaining recombinant encodes a portion of the previously unidentified EHV-4 homologue of herpes simplex virus 1 (HSV-1) UL36, a tegument protein. Screening the library with horse serum led to the identification of three recombinants, one of which encodes the same gB sequence as the gB recombinant recognized with the rabbit serum. The other two contain overlapping sequences that encode a portion of EHV-4 gX.
Alphaherpesvirinae↗