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Cost-effective analysis of hepatitis A prevention in Ireland.

OBJECTIVE: The purpose of this study was to determine the most cost-effective prevention strategy against hepatitis A virus (HAV) infection for healthcare workers and the general population at risk in Ireland. METHODS: Four prevention strategies were compared: active immunization with Havrix Monodose (1440E.U); screening for anti-HAV antibody and then vaccinating; passive immunization; screening for anti-HAV antibody and then passive immunization. The cost-effective ratio was calculated for each prevention strategy. Threshold analysis, sensitivity analysis, and model extension to include indirect cost from work days lost and secondary attack rates through horizontal transmission were also derived. RESULTS: The medical costs were lowest and the infection rate highest when no preventive action was taken. Vaccination was most cost effective when the prevalence of immunity was 45% or less, reducing the infection rate by 98% when compared to nonprevention. Screening before vaccination was most cost effective when the prevalence of immunity was greater than 45%. Passive immunization and screening before passive immunization were not comparable to the other strategies in cost effectiveness. Sensitivity analysis showed that the cost-effective ratio for vaccination was dependent on vaccine price, incidence of HAV, and prevalence of immunity in the target group. Extending the model to include indirect costs further increased the cost effectiveness of vaccination. CONCLUSION: The best cost-effective strategy relates to target group immunity. Where HAV immunity is 45% or less, vaccination is the strategy of choice and when immunity is greater than 45%, then screening followed by vaccination should be used. This study can be used to provide a framework within which choices can be made to achieve better health for less cost.

Adolescent↗

Dexamethasone treatment for acute bacterial meningitis: how strong is the evidence for routine use?

A methodological appraisal of the published randomised controlled trials on the use of dexamethasone as an adjunct treatment in acute bacterial meningitis was carried out to examine whether the available evidence is strong enough to support the routine use of the drug. Studies were eligible for inclusion if they were published in indexed journals after 1966, written in English, and were randomised controlled trials with dexamethasone as adjunct to antimicrobials in patients with acute bacterial meningitis. All studies were extracted and their adherence to eight methodological principles was graded as adequate, inadequate, or unclear. A sensitivity analysis was done to examine the robustness of the conclusions. Seven studies met the eligibility criteria. No report adhered to all the principles. Major threats to validity of the conclusions included potential bias in analysis in all the studies, and lack of adjustment for baseline imbalances in four. Inadequate reporting of adverse effects hindered risk-benefit analysis. Sensitivity analysis showed that the numbers of patients withdrawn from analysis were enough to invalidate the conclusions. It is concluded that the available evidence is not strong enough to support a routine use of dexamethasone in acute bacterial meningitis. Further research is needed to determine the effect of a policy to use dexamethasone early in the management of suspected acute bacterial meningitis. Future studies should adopt a pragmatic approach, be methodologically rigorous, and meticulously measure the risk as well as the benefit of this policy.

Acute Disease↗

Visualization-based analysis of multiparameter models using environment for N-dimensional model analysis.

We present a methodology, based on N-dimensional computer visualization, for analyzing multiparameter models. This approach originally consisted of three steps: behavior analysis, sensitivity analysis, identifiability analysis. We have now developed a new way of calculating sensitivity based on the statistical measure of the coefficient of variation. Furthermore, we extended the methodology through the addition of an extra step, visual regression. Visual regression allows the user to visualize the process of actual parameter identification and presents a combined, empirical view of the first three steps in a single image. Next we applied this methodology to pulmonary capillary-transport models. Finally, we implemented the model analysis process as a stand-alone program. EN-DIMAN, the resulting software, allows researchers to carry out model analysis in a graphical user interface (GUI)-based environment.

Algorithms↗

Potential dangers in the customary methods of conducting meta-analyses. Lack of bias in the meta-analysis of recombinant versus urinary follicle stimulating hormone.

In a meta-analysis of randomized trials comparing recombinant and urinary FSH for ovarian stimulation in infertility treatment cycles, the clinical pregnancy rate per cycle started was significantly higher with recombinant FSH. Before the results of the different trials can be pooled, it is important to determine whether the results are homogeneous so that one can obtain an overall treatment estimate that is without bias. There are several methods to ascertain lack of homogeneity, including logistic regression analysis, sensitivity analysis comparing fixed-effect and random-effect models, testing based in the chi2 distribution, and graphical methods comparing event rates in experimental and treatment groups. These methods all confirmed that the treatment effect was homogeneous across all trials thereby providing assurance that the overall conclusion of the superior efficacy of recombinant FSH compared with urinary FSH is based on an unbiased analysis.

Bias↗

Ascertaining the importance of neurons to develop better brain-machine interfaces.

In the design of brain-machine interface (BMI) algorithms, the activity of hundreds of chronically recorded neurons is used to reconstruct a variety of kinematic variables. A significant problem introduced with the use of neural ensemble inputs for model building is the explosion in the number of free parameters. Large models not only affect model generalization but also put a computational burden on computing an optimal solution especially when the goal is to implement the BMI in low-power, portable hardware. In this paper, three methods are presented to quantitatively rate the importance of neurons in neural to motor mapping, using single neuron correlation analysis, sensitivity analysis through a vector linear model, and a model-independent cellular directional tuning analysis for comparisons purpose. Although, the rankings are not identical, up to sixty percent of the top 10 ranking cells were in common. This set can then be used to determine a reduced-order model whose performance is similar to that of the ensemble. It is further shown that by pruning the initial ensemble neural input with the ranked importance of cells, a reduced sets of cells (between 40 and 80, depending upon the methods) can be found that exceed the BMI performance levels of the full ensemble.

Action Potentials↗

Effect(s) of assisted hatching on assisted conception (IVF & ICSI).

BACKGROUND: Failure of implantation and thus conception might result from inability of the blastocyst to escape from its zona pellucida. Artificial disruption of this coat has been proposed as a method of improving the success of assisted conception. OBJECTIVES: To determine whether assisted hatching of embryos facilitates live births, clinical pregnancy and implantation and whether it impacts on negative outcomes (such as miscarriage). SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (26 November 2002), the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2002), MEDLINE (1996 to February 2003), EMBASE (1980 to February 2003) and reference lists of articles. Authors were contacted for missing and/or unpublished data. SELECTION CRITERIA: Trials were identified and independently screened by two reviewers. Randomised controlled trials of AH (mechanical, chemical or laser disruption of the zona pellucida prior to embryo replacement) versus no AH that reported live birth, clinical pregnancy or implantation rates were included. DATA COLLECTION AND ANALYSIS: Qualitative assessments and data extraction were performed independently by two reviewers. Outcomes were extracted as rates and combined using random effects meta-analysis, sensitivity analysis, subgrouping and meta-regression where appropriate. MAIN RESULTS: Twenty-three randomised controlled trials (2572 women) were included. There was no significant difference in the odds of live births in the AH compared with control groups (6 RCTs; OR 1.21, 95% CI 0.82 to 1.78; 161 births from 523 women). Women undergoing assisted hatching were significantly more likely to achieve clinical pregnancy (722 clinical pregnancies in 2175 women, OR 1.63, 95% CI 1.27 to 2.09), however the studies were heterogeneous. Implantation data were difficult to analyse due to the practice of replacing multiple embryos in individual women. The trials provided insufficient data to investigate the impact of assisted hatching on several important outcomes, including monozygotic twinning, embryo damage, congenital and chromosomal abnormalities, and in vitro blastocyst development. REVIEWER'S CONCLUSIONS: There is insufficient evidence to determine any effect of AH on the 'take-home-baby rate' of assisted conception. There are also very few data regarding miscarriage rates and other adverse events. This prevents us from extrapolating the impact of AH on live births from our finding of improved odds of clinical pregnancy.

Embryo Implantation↗

Assisted hatching on assisted conception (IVF & ICSI).

BACKGROUND: Failure of implantation and conception may result from an inability of the blastocyst to escape from its outer coat, know as the zona pellucida. In vitro culture conditions and/or advancing maternal age may alter the architecture of the zona pellucida and result in hatching difficulties. Artificial disruption of this coat is known as assisted hatching (AH) has been proposed as a method of improving the success of assisted conception. OBJECTIVES: To determine whether assisted hatching (AH) of embryos facilitates live births and clinical pregnancy and whether it impacts on negative outcomes (such as multiple pregnancy and miscarriage). SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (1 June 2005), the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2005), MEDLINE (1996 to June 2003), EMBASE (1980 to June 2005) and reference lists of articles. Authors were contacted for missing and/or unpublished data. SELECTION CRITERIA: Trials were identified and independently screened by two reviewers. Randomised controlled trials of AH (mechanical, chemical or laser disruption of the zona pellucida prior to embryo replacement) versus no AH that reported live birth, clinical pregnancy or implantation rates were included. DATA COLLECTION AND ANALYSIS: Qualitative assessments and data extraction were performed independently by two reviewers. Outcomes were extracted as rates and combined using random effects meta-analysis, sensitivity analysis, sub grouping and meta-regression where appropriate. MAIN RESULTS: Twenty-three randomised controlled trials consisting of 2668 women reported on 849 pregnancy outcomes. There was no significant difference in the odds of live births in the AH compared with control groups (6 RCTs; OR 1.19 95% CI 0.81 to 1.73; 163 births from 516 women). Women undergoing assisted hatching were significantly more likely to achieve clinical pregnancy (23 RCTs, OR 1.33, 95% CI 1.12 to 1.57). Miscarriage rates per woman were similar in both groups (12 RCTs OR 1.23 (95% CI 0.73 to 2.05). Multiple pregnancy rates per woman was increased in women who were randomised to AH compared with control women (9 RCTs OR 1.83 (95% CI 1.19 to 2.83). The improvement in clinical pregnancy rate means for a clinic with a success rate of 25% could anticipate improving the CPR to between 28 and 39%, all things being equal. The trials provided insufficient data to investigate the impact of assisted hatching on several important outcomes, including monozygotic twinning, embryo damage, congenital and chromosomal abnormalities, and in vitro blastocyst development. AUTHORS' CONCLUSIONS: Despite significantly improved odds of clinical pregnancy, there is insufficient evidence to determine any effect of AH on live birth rates. The increased multiple pregnancy rate is of concern although it likely that with a policy of single embryo transfer this may be lowered. Currently, there is insufficient evidence to recommend assisted hatching.

Embryo Implantation↗

Assisted hatching on assisted conception (IVF & ICSI).

BACKGROUND: Failure of implantation and conception may result from an inability of the blastocyst to escape from its outer coat, know as the zona pellucida. In vitro culture conditions and/or advancing maternal age may alter the architecture of the zona pellucida and result in hatching difficulties. Artificial disruption of this coat is known as assisted hatching (AH) has been proposed as a method of improving the success of assisted conception. OBJECTIVES: To determine whether assisted hatching (AH) of embryos facilitates live births and clinical pregnancy and whether it impacts on negative outcomes (such as multiple pregnancy and miscarriage). SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (1 June 2005), the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2005), MEDLINE (1996 to June 2003), EMBASE (1980 to June 2005) and reference lists of articles. Authors were contacted for missing and/or unpublished data. SELECTION CRITERIA: Trials were identified and independently screened by two reviewers. Randomised controlled trials of AH (mechanical, chemical or laser disruption of the zona pellucida prior to embryo replacement) versus no AH that reported live birth, clinical pregnancy or implantation rates were included. DATA COLLECTION AND ANALYSIS: Qualitative assessments and data extraction were performed independently by two reviewers. Outcomes were extracted as rates and combined using random effects meta-analysis, sensitivity analysis, sub grouping and meta-regression where appropriate. MAIN RESULTS: Twenty-three randomised controlled trials consisting of 2668 women reported on 849 pregnancy outcomes. There was no significant difference in the odds of live births in the AH compared with control groups (6 RCTs; OR 1.19 95% CI 0.81 to 1.73; 163 births from 516 women). Women undergoing assisted hatching were significantly more likely to achieve clinical pregnancy (23 RCTs, OR 1.33, 95% CI 1.12 to 1.57). Miscarriage rates per woman were similar in both groups (12 RCTs OR 1.23 (95% CI 0.73 to 2.05). Multiple pregnancy rates per woman was increased in women who were randomised to AH compared with control women (9 RCTs OR 1.83 (95% CI 1.19 to 2.83). The improvement in clinical pregnancy rate means for a clinic with a success rate of 25% could anticipate improving the CPR to between 28 and 39%, all things being equal. The trials provided insufficient data to investigate the impact of assisted hatching on several important outcomes, including monozygotic twinning, embryo damage, congenital and chromosomal abnormalities, and in vitro blastocyst development. AUTHORS' CONCLUSIONS: Despite significantly improved odds of clinical pregnancy, there is insufficient evidence to determine any effect of AH on live birth rates. The increased multiple pregnancy rate is of concern although it likely that with a policy of single embryo transfer this may be lowered. Currently, there is insufficient evidence to recommend assisted hatching.

Embryo Implantation↗

Management of stage III pressure ulcers in moderately demented nursing home residents.

PURPOSE: To determine whether the myocutaneous flap procedure, the preferred treatment for young patients with stage III pressure ulcers, is appropriate for moderately demented nursing home residents. SUBJECTS AND METHODS: A model of the treatment decision was created using the decision-tree format. The probabilities of treatment outcomes in the decision tree were derived from the literature. Utilities for treatment outcomes were obtained from five internists, five geriatricians, six nurse practitioners, five plastic surgeons, and six lay people. RESULTS: A majority in each group of respondents favored surgery, according to the decision analysis. Sensitivity analysis showed that surgery was preferred unless its success rate was less than 30%, or the rate of healing with conservative measures was at least 40%, which are unlikely values. Economic analysis demonstrated that surgery was $17,000 more expensive than conservative therapy. CONCLUSION: The myocutaneous flap procedure is preferred by the majority of relevant decision makers when cost is not a consideration. The relative underutilization of surgery in practice has many possible explanations. The most likely are the failure of providers to appreciate the morbidity of pressure ulcers and the reluctance of practitioners to perform expensive procedures on demented patients.

Aged↗

A visualization-based analysis method for multiparameter models of capillary tissue-exchange.

In order to successfully use a model for parameter identification, it must be carefully analyzed. Current analysis methods, however, are ad hoc and provide only partial information. We extended these methods through the application of stacked dimensions, a scientific visualization method. The end result of our extensions are multi-dimensional parametric model-images. These images depict a model as a function of all its parameters in a single graphic. We applied parametric model-images to model verification (behavioral analysis), sensitivity analysis, and identifiability analysis. We applied our methodology to the evaluation of pulmonary vascular capillary-transport models. Results have shown that the visualization-based method provides a more complete view of a model's behavior and its other characteristics. Furthermore, our method has also proven to be more computationally efficient than the traditional approaches.

Capillary Permeability↗

A physiologically based pharmacokinetic (PB/PK) model for multiple exposure routes of soman in multiple species.

A physiologically based pharmacokinetic (PB/PK) model has been developed in advanced computer simulation language (ACSL) to describe blood and tissue concentration-time profiles of the C(+/-)P(-) stereoisomers of soman after inhalation, subcutaneous and intravenous exposures at low (0.8-1.0 x LD(50)), medium (2-3 x LD(50)) and high (6 x LD(50)) levels of soman challenge in three species (rat, guinea pig, marmoset). Allometric formulae were used to compute the compartment volumes, blood flow rates, tidal volume and respiratory rate based upon total animal weight. Blood/tissue partition coefficients for soman, initial carboxylesterase and acetylcholinesterase levels and the rate constants for interactions between soman and these enzymes were species-dependent and were obtained from in vitro measurements reported in the literature. The model incorporated arterial and venous blood, lung, kidney, liver, richly perfused, poorly perfused and fat tissue compartments as well as subcutaneous and nasal exposure site compartments. First-order absorption from linearly filled soman deposits into metabolizing exposure site compartments was employed to model subcutaneous and inhalation exposures. The model was validated by comparing the predicted and observed values for C(+/-)P(-)-soman in arterial blood at various times following exposure and by regression analysis. Sensitivity analysis was used to determine the effects of perturbations in the model parameters on the time-course of arterial C(-)P(-)-soman concentrations for different exposure routes. In our evaluation of 28 datasets, predicted values were generally within 95% confidence limits of the observed values, and regression coefficients comparing predicted and observed data were greater than 0.85 for 95% of the intravenous and subcutaneous datasets and 25% of the inhalation datasets. We conclude that the model predicts the soman toxicokinetics for doses >or=1 x LD(50) for intravenous and subcutaneous exposures and inhalation exposures of 8 min or less sufficiently well to allow its use in the modeling of bioscavenger protection.

Administration, Inhalation↗

The Pediatric Quality Appraisal Questionnaire: an instrument for evaluation of the pediatric health economics literature.

OBJECTIVES: Currently there is no tool available to adequately appraise the quality of the pediatric health economics literature. A comprehensive pediatric-specific instrument would be valuable in informing allocation decisions related to pediatric interventions and services. The goal of this study was to develop the Pediatric Quality Appraisal Questionnaire (PQAQ). METHODS: A draft instrument was constructed from published checklists and questionnaires. New questions pertaining to the pediatric population were incorporated. An expert panel reviewed the draft instrument and the proposed scoring scheme for face and content validity. A revised version was pilot tested by three independent appraisers. After addressing discrepancies in scores, a final version was created and subjected to interrater and test-retest reliability assessment. RESULTS: The 57 items in the final PQAQ were mapped onto 14 domains: economic evaluation, comparators, target population, time horizon, perspective, costs and resource use, outcomes, quality of life, analysis, discounting, incremental analysis, sensitivity analysis, conflict of interest, and conclusions. Among the 57 items, 46 have response options that are scored from 0 to 1. Interrater reliability was 0.75 (95% confidence interval [CI] 0.66-0.81) and test-retest reliability was 0.92 (95% CI 0.71-0.98). CONCLUSIONS: The PQAQ is a comprehensive instrument demonstrating face and content validity and strong interrater and test-retest reliability in the appraisal of pediatric economic evaluations. This tool will be valuable to health economists, methods researchers, and policy decision makers involved in allocation decisions for pediatric health care.

Bibliometrics↗

Meta-analyses of randomized controlled trials.

A new type of research, termed meta-analysis, attempts to analyze and combine the results of previous reports. We found 86 meta-analyses of reports of randomized controlled trials in the English-language literature. We evaluated the quality of these meta-analyses, using a scoring method that considered 23 items in six major areas--study design, combinability, control of bias, statistical analysis, sensitivity analysis, and application of results. Only 24 meta-analyses (28 percent) addressed all six areas, 31 (36 percent) addressed five, 25 (29 percent) addressed four, 5 (6 percent) addressed three, and 1 (1 percent) addressed two. Of the 23 individual items, between 1 and 14 were addressed satisfactorily (mean +/- SD, 7.7 +/- 2.7). We conclude that an urgent need exists for improved methods in literature searching, quality evaluation of trials, and synthesizing of the results.

Clinical Trials as Topic↗

The impact of assisted hatching on live birth rates and outcomes of assisted conception: a systematic review.

BACKGROUND: During the past decade in the UK, only one in six cycles of assisted conception has resulted successfully in a live birth. Assisted hatching (AH) has been proposed to improve outcome. This systematic review of randomized controlled trials addresses primary outcomes of live birth, clinical pregnancy and embryo implantation. METHODS: Trials on post-fertilization disruption of the zona pellucida were identified from the Cochrane Controlled Trials Register, MEDLINE, EMBASE and published bibliographies. Outcomes were analysed using random effects meta-analysis, sensitivity analysis, sub-grouping and meta-regression. RESULTS: Of 23 included trials recruiting 2572 women, only six reported live birth data. AH had no significant effect on live birth (OR 1.21, 95% CI 0.82-1.78). There was a significant benefit of AH on clinical pregnancy (OR 1.63, 95% CI 1.27-2.09), especially in the sub-group of women with previous failure of assisted conception (OR 2.33, 95% CI 1.63-3.34). Meta-regression suggested that AH might be more useful in older women. Implantation data were not considered valid for statistical analysis. The methodological quality of included trials was sub-optimal. CONCLUSIONS: AH probably enhances clinical pregnancy, especially in women with previous failure of assisted conception treatment and in older women; however, trials were of poor quality and so may be biased. Better quality trials reporting live birth are required to confirm any positive effects on the 'take-home-baby rate'.

Abortion, Spontaneous↗

Randomized controlled trials in long-term care residents with dementia: a systematic review.

OBJECTIVE: To evaluate the quality of reporting of randomized controlled trials for pharmacologic interventions in long-term care residents with dementia. DATA SOURCES: We performed electronic searches of AMED, CINAHL, E-PSYCHE, Cochrane Controlled Trials Register, and MEDLINE. We also searched the reference lists of included studies and bibliographies of relevant review articles. STUDY SELECTION: All randomized controlled trials for pharmacologic interventions in patients with dementia residing in long-term care facilities. DATA ABSTRACTION: We abstracted data independently, in duplicate, using a data abstraction sheet and a quality checklist. DATA SYNTHESIS: Fifteen trials met inclusion criteria. Five trials lacked institutional ethical review, while two lacked informed consent. Eleven trials gave adequate description of withdrawals and 14 trials reported adverse events adequately. We found incomplete reporting of methods of randomization, allocation concealment, restriction, blinding, sample size estimation and intention-to-treat analysis. Sensitivity analysis indicated that reporting of allocation concealment was associated with increased quality of trial according to the quality scale (P = 0.007). CONCLUSIONS: Clinicians and the public do not have high-quality information to guide pharmacologic decision making for long-term care residents with dementia. The reporting quality is highly variable in the trials reviewed, and concerns exist surrounding the conduct of several trials.

Aged↗

Causality between genetically predicted type 2 diabetes and ankle fracture risk: A 2-sample Mendelian randomization study.

It has been proven that diabetes mellitus plays an important role in the occurrence and development of joint fractures. In this study, a 2-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationship between diabetes and ankle fractures. We pooled the data from the published genome-wide association studies. Diabetes mellitus type 2 was derived from pooled genome-wide association study data of 655,666 European individuals (61,714 patients and 1178 controls). Data on ankle fractures were derived from pooled genome-wide association study data in a total of 460,340 European individuals (6479 patients and 453,861 controls). Using diabetes-associated loci as instrumental variables, we used inverse variance weighting, MR-Egger, weighted median, simple multivariate analysis and weighted multivariate analysis to evaluate the association between diabetes and ankle fracture risk. Reverse MR analysis was performed on the Diabetes mellitus type 2 that were found to be causally associated with ankle fractures in forward MR analysis. Sensitivity analysis was used to evaluate the robustness of the results. Statistical analysis showed a significant causal relationship between diabetes and ankle fractures (inverse variance weighting: OR = 1.07, 95% CI = 1.01-1.32, P = .02). Diabetes mellitus is associated with an increased risk of ankle fracture. The results of MR analysis can be used as a guide for the screening of diabetes and ankle fractures, which is helpful to improve the awareness of screening, early diagnosis and early treatment.

Humans↗

The causal effect of gut microbiota on hepatic encephalopathy: a mendelian randomization analysis.

BACKGROUND: There is growing evidence for a relationship between gut microbiota and hepatic encephalopathy (HE). However, the causal nature of the relationship between gut microbiota and HE has not been thoroughly investigated. METHOD: This study utilized the large-scale genome-wide association studies (GWAS) summary statistics to evaluate the causal association between gut microbiota and HE risk. Specifically, two-sample Mendelian randomization (MR) approach was used to identify the causal microbial taxa for HE. The inverse variance weighted (IVW) method was used as the primary MR analysis. Sensitive analyses were performed to validate the robustness of the results. RESULTS: The IVW method revealed that the genus Bifidobacterium (OR = 0.363, 95% CI: 0.139-0.943, P = 0.037), the family Bifidobacteriaceae (OR = 0.359, 95% CI: 0.133-0.950, P = 0.039), and the order Bifidobacteriales (OR = 0.359, 95% CI: 0.133-0.950, P = 0.039) were negatively associated with HE. However, no causal relationship was observed among them after the Bonferroni correction test. Neither heterogeneity nor horizontal pleiotropy was found in the sensitivity analysis. CONCLUSION: Our MR study demonstrated a potential causal association between Bifidobacterium, Bifidobacteriaceae, and Bifidobacteriales and HE. This finding may provide new therapeutic targets for patients at risk of HE in the future.

Mendelian Randomization Analysis↗

Clinical economics in clinical trials: the measurement of cost and outcomes in the assessment of clinical services through clinical trials.

As the population ages and more expensive high-technology services become available, health care costs continue to spiral upward. Because the financial resources for health care are limited, economic analysis can help to evaluate expenditures and set priorities. Economic analysis of medical technology or medical care evaluates a medical service by comparing its dollar cost with its dollar benefit (cost-benefit), by measuring its dollar cost in relation to its outcomes (cost-effectiveness) as well as in relation to its utility or quality-adjusted outcomes (cost-utility), or simply by tabulating the costs involved (cost-identification). Direct costs are generated as services are provided. In addition, patients' productivity is affected, and these costs can be considered, especially in determining the benefit of a service that decreases morbidity or mortality. Intangible costs are those of pain, suffering, and grief. The point of view, or perspective, of the study determines the costs and benefits that will be measured in the analysis. Sensitivity analysis, which can evaluate the stability of the conclusions to the data used, is an important assessment within economic analysis. Economic analysis of new pharmaceutical therapies is increasingly being incorporated into clinical trials. Although there are some limitations of pharmacoeconomic information in clinical studies of drug safety and efficacy, these trials are often the only opportunity for economic data collection before adoption and reimbursement decisions are made. Validation after the drug has been introduced should complement economic information developed from clinical trials.

Clinical Trials as Topic↗