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PubMed1999

Thrombolytic therapy with streptokinase and tissue plasminogen activator in a patient with suspected acute myocardial infarction: A decision analysis.

Two commonly used thrombolytic agents are streptokinase (SK) and tissue plasminogen activator (t-PA), which have different impacts on the incidence of mortality and thrombolysis-related acute intracranial hemorrhage. A decision-analytic model was developed to compare the use of SK and t-PA in the treatment of a patient with suspected acute myocardial infarction (AMI). The outcome was health-related quality of life as quantified in a measure of utility from the patient's point of view. The model included three outcome states: death, nonfatal yet disabling stroke, and survival with no disabling stroke. The utility for disabling stroke was determined relative to the reference states of no disabling stroke (1.00) and death (0.00) by means of the time trade-off estimation technique. Probabilities were derived from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Artery trial, which revealed that although administering t-PA results in a lower percentage of deaths compared to SK, it may lead to a higher percentage of strokes. A decision tree was constructed to model the options and outcomes. The tree was analyzed by standard decision analytic techniques using SMLTREE software, and the stability of the results was examined as values of parameters were varied systematically in a sensitivity analysis. In the baseline analysis, SK yielded 0.9235, whereas t-PA yielded 0.9329. The sensitivity analysis revealed that if the probability of a disabling stroke attributable to t-PA were greater than 2.08%, SK would yield the higher expected utility. This threshold value, however, was much greater than the probability established in major trials. The administration of t-PA leads to a slightly better outcome than does the administration of SK in a patient with suspected AMI.

Decision Support Techniques↗
PubMed2004

Applications of a parametric model for informative censoring.

In this article, we explore the use of a parametric model (for analyzing survival data) which is defined to allow sensitivity analysis for the presence of informative censoring. The dependence between the failure and the censoring processes is expressed through a parameter delta and a general bias function B(t, theta). We calculate the expectation of the potential bias due to informative censoring, which is an overall measure of how misleading our results might be if censoring is actually nonignorable. Bounds are also calculated for quantities of interest, e.g., parameter of the distribution of the failure process, which do not depend on the choice of the bias function for fixed delta. An application that relates to systematic lupus erythematosus data illustrates how additional information can result in reducing the uncertainty on estimates of the location parameter. Sensitivity analysis on a relative risk parameter is also explored.

Bias↗
PubMed2005

Predicting methyl tert-butyl ether, tert-butyl formate, and tert-butyl alcohol levels in the environment using the fugacity approach.

Through its extensive use as a fuel oxygenate, methyl tert-butyl ether (MTBE) is found nearly ubiquitouslythroughout the environment. To better understand the environmental fate of MTBE, fugacity models are commonly used. However, models developed by the scientific community and by governmental bodies differ in their predictions of relative MTBE concentrations for relevant environmental compartments and of seasonal concentration variations; further, to date they have not considered the formation of transformation products. In this study, the sensitivity of predicted environmental concentrations of MTBE and its two major degradation products, tert-butyl formate (TBF) and tert-butyl alcohol (TBA), to all types of model input parameters is analyzed in a probabilistic sensitivity analysis. This analysis allowed for an assessment of the most influential parameters for predicting soil, water, and air concentrations and thereby provided insight into why previous modeling studies on MTBE differed. Further, the information from the sensitivity analysis was used to parametrize a multispecies transformation model for predicting European concentration levels of MTBE and, for the first time, TBF and TBA. Water and air concentrations of MTBE predicted with the transformation model were in good agreement with measurements of environmental samples. No studies are available on environmental TBF and TBA levels to compare with model predictions; however, the modeling results indicate that, in the water phase, TBA concentrations may reach appreciable levels. One major uncertainty identified regarding the prediction of TBA levels was the fraction of TBA formed from atmospheric MTBE and TBF.

Air Pollutants↗
PubMed1998

An economic appraisal of carbamazepine, lamotrigine, phenytoin and valproate as initial treatment in adults with newly diagnosed epilepsy.

We undertook an economic appraisal of four drugs used in monotherapy during the first 2 years of treatment for newly diagnosed patients with epilepsy: carbamazepine (CBZ), lamotrigine (LTG), phenytoin (PHT), and valproate (VPA). We adopted the cost-minimization model because, although no single trial compares all four drugs directly, the clinical trials comparing two or more of these drugs in newly diagnosed cases show no significant difference in efficacy between the drugs in terms of seizure frequency. Considered in the cost analyses were frequency of side effects, retention rates, medical consultations, inpatient and accident and emergency costs, laboratory investigations, and drug changes. A Delphi panel provided the treatment pathways, including frequency of clinical consultations, second-line monotherapy, and side-effects management. A sensitivity analysis was performed, varying the assumptions on which the calculations were based. Analysis was completed for a prospective, intention-to-treat perspective and also for those patients continuing the initial drug. The direct medical costs of 2-years therapy (intention-to-treat analysis) calculated for each trial were pound sterling 795-829 for CBZ, pound sterling 1,525-2,076 for LTG, pound sterling 736-768 for PHT, and pound sterling 868-884 for VPA. A sensitivity analysis provided similar relative estimates. We found that LTG for newly diagnosed patients is significantly more expensive in direct health service costs incurred. This analysis incorporated seizure control, side effects, and tolerability. We recommend that a similar type of analysis be considered as part of all clinical trials of antiepileptic drugs in which efficacy of outcome is similar as a guide to assess optimal cost effectiveness.

Adult↗
PubMed2002

Cost-effectiveness of a modified care protocol substituting bladder tumor markers for cystoscopy for the followup of patients with transitional cell carcinoma of the bladder: a decision analytical approach.

PURPOSE: Decision analysis models were established to determine the cost-effectiveness of a plan alternating a bladder tumor marker with cystoscopy and cytology at 3-months intervals or modified care versus followup cystoscopy and cytology every 3 months or standard care. MATERIALS AND METHODS: We performed a comprehensive literature review for bladder tumor markers using 1966 to current MEDLINE data and other search engines. Statistical performance data on tumor markers were calculated by hierarchical Bayes meta-analysis with 95% confidence intervals used for the model. Other basic assumptions included cost data on tumor markers, cytology, cystoscopy, transurethral bladder resection and cystectomy as well as recurrence and progression rates from the literature. Decision trees were built with computer software using a 12 and a 24-month model with linear recurrence and progression rate assumptions. RESULTS: Overall specificity for common tumor markers was 73% to 90% and sensitivity was 49% to 77%. As expected, sensitivity increased for higher disease grades and stages. The modified care protocol was more cost-effective than standard care for the 1 and 2-year followups. On 1-year 1-way sensitivity analysis for cost only tumor marker cost, recurrence and progression rates achieved a threshold at which the modified care protocol was as or more expensive as standard care. Modified care was more cost-effective at a tumor marker cost of less than $264. On 2-way sensitivity analysis there was no significant impact of parameters at a wide range of tumor marker costs, recurrence and progression rates. CONCLUSIONS: Using a modified followup protocol in transitional cell carcinoma cases with an initial tumor occurrence using a urine based tumor marker alternating with cystoscopy and/or cytology is cost-effective for a wide range of marker sensitivities, specificities and costs, cystoscopy and/or cytology cost, a 20% to 80% yearly recurrence and a 2% to 40% yearly progression rate. This protocol should be evaluated in a prospective randomized trial to determine whether the financial and emotional benefits outweigh any potential drawbacks.

Biomarkers, Tumor↗
PubMed2003

Simple approaches to assess the possible impact of missing outcome information on estimates of risk ratios, odds ratios, and risk differences.

Often in clinical trials, the primary outcome is binary and the impact of an intervention is summarized using risk ratios (RRs), odds ratios (ORs), or risk differences (RDs). It is typical that in such studies, the binary outcome variable is not observed for some study participants. When there is missing data, it is well known that analyses based on those participants with complete data can be biased unless it can be assumed that the probability of a missing outcome is unrelated to the value of the missing binary outcome (i.e., missing at random). Unfortunately, this assumption cannot be assessed with the data since the missing outcomes, by definition, are not observed. One approach to this problem is to perform a sensitivity analysis to see the degree to which conclusions based only on the complete data would be affected given various degrees of departure from the missing at random assumption. In this paper we provide researchers formulae for doing such a sensitivity analysis. We quantify the departure from the missing at random assumption with a parameter we call the "response probability ratio" (RPR). This is the ratio between the probability of a nonmissing outcome among those with one value of the binary outcome and the probability of a nonmissing outcome among those with the other value of the outcome. Then we provide simple formulae for the estimation of the RRs, ORs, and RDs given any specific values of the RPRs. In addition to being useful for sensitivity analyses, these formulae provide some insight into the conditions that are necessary for bias to occur. In particular, it can be seen that, under certain plausible assumptions, OR estimates based on participants with complete data will be asymptotically unbiased, even if the probability of missing outcome depends on both the treatment and the outcome.

Bias↗
PubMed2003

Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival.

There is no standard treatment for patients with unresectable hepatocellular carcinoma (HCC). Survival benefits derived from medical interventions are controversial. The aim of this systematic review was to assess the evidence of the impact of medical treatments on survival. Randomized controlled trials (RCTs) that were published as full papers assessing survival for primary treatments of HCC were included. MEDLINE, the Cochrane Library, CANCERLIT, and a manual search from 1978 to May 2002 were used. The primary end point was survival, and the secondary end point was response to treatment. Estimates of effect were calculated according to the random effects model. Sensitivity analysis included methodological quality. We identified 61 randomized trials, but only 14 met the criteria to perform a meta-analysis assessing arterial embolization (7 trials, 545 patients) or tamoxifen (7 trials, 898 patients). Arterial embolization improved 2-year survival compared with control (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32-0.89; P =.017). Sensitivity analysis showed a significant benefit of chemoembolization with cisplatin or doxorubicin (OR, 0.42; 95% CI, 0.20-0.88) but none with embolization alone (OR, 0.59; 95% CI, 0.29-1.20). Overall, treatment induced objective responses in 35% of patients (range, 16%-61%). Tamoxifen showed no antitumoral effect and no survival benefits (OR, 0.64; 95% CI, 0.36-1.13; P =.13), and only low-quality scale trials suggested 1-year improvement in survival. In conclusion, chemoembolization improves survival of patients with unresectable HCC and may become the standard treatment. Treatment with tamoxifen does not modify the survival of patients with advanced disease.

Carcinoma, Hepatocellular↗
PubMed2002

Phase-modulation scatterometry.

Phase-modulation scatterometry is a metrology technique for determining, by means of a phase modulator as a key device, the parameters of gratings. The main source of error to be dealt with are the fluctuations of the phase-modulation amplitude. The grating zeroth-order reflectance modulated by the phase modulator is converted into a signal by the photodetector. The measurables are the direct term and the first two harmonics of the signal. For experimental data fitting, we used the ratio of the harmonics over the direct term because it significantly improves the accuracy. A sensitivity analysis was performed for two samples, one real and one theoretical, to find the measurement configuration that insures optimum determination precision for the grating parameters. For the real sample, comparison of the theoretical predictions for sensitivity with the actual values showed a good agreement. For both samples the sensitivity analysis indicated subnanometric precision for the critical dimension (grating linewidth).

Journal Article↗
PubMed2006

Flying high: a theoretical analysis of the factors limiting exercise performance in birds at altitude.

The ability of some bird species to fly at extreme altitude has fascinated comparative respiratory physiologists for decades, yet there is still no consensus about what adaptations enable high altitude flight. Using a theoretical model of O(2) transport, we performed a sensitivity analysis of the factors that might limit exercise performance in birds. We found that the influence of individual physiological traits on oxygen consumption (Vo2) during exercise differed between sea level, moderate altitude, and extreme altitude. At extreme altitude, haemoglobin (Hb) O(2) affinity, total ventilation, and tissue diffusion capacity for O(2) (D(To2)) had the greatest influences on Vo2; increasing these variables should therefore have the greatest adaptive benefit for high altitude flight. There was a beneficial interaction between D(To2) and the P(50) of Hb, such that increasing D(To2) had a greater influence on Vo2 when P(50) was low. Increases in the temperature effect on P(50) could also be beneficial for high flying birds, provided that cold inspired air at extreme altitude causes a substantial difference in temperature between blood in the lungs and in the tissues. Changes in lung diffusion capacity for O(2), cardiac output, blood Hb concentration, the Bohr coefficient, or the Hill coefficient likely have less adaptive significance at high altitude. Our sensitivity analysis provides theoretical suggestions of the adaptations most likely to promote high altitude flight in birds and provides direction for future in vivo studies.

Adaptation, Physiological↗
PubMedDate not supplied

[Economic assessment of the implementation of a parenteral nutrition protocol for patients undergoing intestinal resection by a multidisciplinary team].

OBJECTIVE: An economic assessment on the impact of total parenteral nutrition guidelines developed by the Hospital Nutrition Committee for patients undergoing intestinal resection and implemented by a nutritional support multidisciplinary team, was conducted. METHOD: A comparative retrospective study of two consecutive annual periods before and after the implementation of total parenteral nutrition guidelines for patients undergoing intestinal resection developed by the Nutrition Committee was carried out. Cost-effectiveness analysis from the hospital perspective was performed with the pharmacoeconomic program Pharma-Decision Hospital. Effectiveness was assessed as nutritional gain and safety profile; as well as determination of the costs of acquisition, preparation, administration, monitoring and nutritional complications. Sensitivity analysis (+/-20%) of effectiveness and hospital stay. RESULTS: Among 326 patients hospitalized for intestinal resection, 69 out of 172 (40%) received parenteral nutrition during the early period, versus 40 out of 154 (26%) after the surgery procedure (p < 0.01). In 79% of the patients with parenteral nutrition, the adequacy of the indication was assessed, being adequate in 51.7% and 56.7%, respectively (p = 0.66). Nutritional gain before and after surgery was similar (78.3 vs. 82.5%, p > 0.05), with patients having less episodes of hypophosphatemia postoperatively (60 vs. 38%). Mean total cost per patient before and after surgery was 9,180.81 and 7,871.96, respectively. The sensitivity analysis confirmed the above results. CONCLUSIONS: The development of total parenteral nutrition guidelines by the Nutrition Committee for surgical patients undergoing intestinal resection and their implementation by a multidisciplinary team improved the use of parenteral nutrition and reduced associated costs, with the same nutritional evolution.

Aged↗
PubMed2026

High-Sensitivity ctDNA Analysis Uncovers Relevant Signals Missed by NGS in Pancreatic Cancer.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) carries high mortality despite multimodal therapy, and improved biomarkers are needed to guide perioperative care. This study evaluated the prognostic significance of Kirsten rat sarcoma virus (KRAS)-mutant circulating tumor DNA (ctDNA) detected by next-generation sequencing (NGS) and digital droplet PCR (ddPCR) in localized PDAC. EXPERIMENTAL DESIGN: In this prospective cohort study (2020-2024), patients with localized PDAC undergoing neoadjuvant chemotherapy (NAC) were enrolled across multiple sites within Northwestern Medicine. Blood samples for ctDNA were assessed at diagnosis, after NAC, and after resection using tumor-agnostic NGS and ddPCR targeting KRAS G12D/V/R mutations. Overall survival (OS) was assessed using Kaplan-Meier analysis. RESULTS: The cohort included 106 patients. At diagnosis, KRAS ctDNA was detected in 17.2% (17/99) by NGS and 64.9% (63/97) by ddPCR. Detection by both platforms was associated with shorter OS, with the higher-sensitivity ddPCR assay providing greater prognostic discrimination by identifying additional patients with poor outcomes not captured by NGS (NGS median OS 11.2 vs. 30.5 months, P < 0.001; ddPCR median OS 24.7 vs. 70.9 months, P = 0.004). Stratified by detection method, median OS was shortest in patients with ctDNA detected by both NGS and ddPCR (10.9 months), longest in those not detected by either platform (40.7 months), and intermediate in patients detected only by ddPCR (26.9 months; P < 0.001). CONCLUSIONS: In localized PDAC, KRAS-mutant ctDNA detected by NGS or ddPCR was associated with worse survival. ddPCR identified additional patients missed by NGS. Integrating ddPCR with NGS ctDNA measures may improve perioperative risk stratification, although validation is needed before clinical implementation.

Humans↗
PubMed1998

Computer simulation to estimate the effectiveness of carotid endarterectomy.

OBJECTIVES: To investigate the benefit of carotid endarterectomy relative to medical treatment, by comparing the outcome for different groups of patients following transient ischaemic attacks. METHODS: A Markov model was used to describe the survival and quality of life of patients treated for a transient ischaemic attack. The benefit is measured in terms of quality adjusted life months (QALMs). The outcome was estimated using a computer simulation with parameters based on published studies on the probability of events following treatment. The benefit of carotid endarterectomy was explored using a baseline set of parameters and a sensitivity analysis. RESULTS: The baseline scenario of a 65-year-old male patient with the model factors set at an intermediate level showed a benefit for surgery of 3 QALMs compared with medical treatment alone. The sensitivity analysis showed that the most favourable combination of factors had a benefit of 13.4 QALMs and the least favourable a loss of 2 QALMs. Of all 128 factor combinations, 79.9% showed a benefit for surgery, 5.5% showed equal benefit, and 15.6% showed a benefit for medical treatment. CONCLUSIONS: Computer simulations have the potential for deriving estimates of benefit for different patient groups from the results of clinical trials. Combined with reliable information on costs, the technique could also demonstrate variations in cost-effectiveness for these groups. For patients following a transient ischaemic attack, the results from this simulation and limited cost information suggest that carotid endarterectomy is unlikely to be a cost-effective intervention in the UK for many patient groups despite a reduction in the risk of stroke.

Aged↗
PubMed2002

An evidence-based estimate of appropriate radiotherapy utilization rate for breast cancer.

PURPOSE: Current estimates of the proportion of cancer patients who will require radiotherapy (RT) are based almost entirely on expert opinion. We sought to use an evidence-based approach to estimate the proportion of incident cases of breast cancer that will require RT at any point in the evolution of the illness. METHODS AND MATERIALS: We undertook a systematic review of the literature to identify indications for RT for breast cancer and to ascertain the level of evidence that supported each indication. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of breast cancer patients. The effect of sampling error on the estimated appropriate rate of RT was calculated mathematically, and the effect of systematic error was estimated by sensitivity analysis. RESULTS: It was estimated that 66.4% +/- 4.8% of breast cancer patients develop one or more indications for RT at some point in the course of the illness. The plausible range for this rate was 56.3%-72.4% on sensitivity analysis. Of all breast cancer patients, 57.3% +/- 4.7% require RT in their initial treatment and 9.1% +/- 1.0% do so later for recurrence or progression. The proportion of patients who ever require RT is stage dependent: 39.8% +/- 1.1% in ductal carcinoma in situ; 68.6% +/- 4.1% in Stage I invasive carcinoma; 81.5% +/- 2.3% in Stage II; 95.3% +/- 0.3% in Stage III; and 63.7% +/- 0.3% in Stage IV. CONCLUSION: This method provides a rational starting point for the long-term planning of RT services and for the audit of access to RT at the population level. By completing such evaluations in the major cancer sites, it will be possible to estimate the appropriate RT treatment rate for the cancer population as a whole.

Algorithms↗
PubMed1998

Should endomyocardial biopsy be performed for detection of myocarditis? A decision analytic approach.

BACKGROUND: Performance of endomyocardial biopsy (EMB) to diagnose myocarditis in patients with dilated cardiomyopathy is controversial because of a lack of evidence favoring immunosuppressive therapy. In spite of advances in heart failure treatment, dilated cardiomyopathy carries a poor prognosis, and myocardial inflammation and viral infection are potential therapeutic targets. METHODS: We used decision analysis to determine the efficacy (5-year risk reduction in mortality or transplantation) that a treatment for myocarditis would require to favor a biopsy-guided approach over conventional therapy. Literature-based estimates included prevalence of myocarditis among patients with dilated cardiomyopathy with or without borderline myocarditis (16% and 11%, respectively); probability of 5-year transplantation-free survival (55%); sensitivity (50% and 63%, respectively), specificity (95.4%), and mortality rate (0.4%) of EMB; side effects resulting in withdrawal of immunosuppressive treatment (4%); and a 6-month mortality rate for immunosuppressive treatment (0.1%). All estimates were varied to determine impact on model results (sensitivity analysis). RESULTS: A therapy that decreased the rate of death or transplantation by 12.7% and 7.1% for patients without or with borderline myocarditis, respectively, favored EMB. Sensitivity analysis indicated that therapeutic efficacy was influenced by myocarditis prevalence and biopsy-related death, but not by accuracy of biopsy or probability of immunosuppressive therapy side effects. Randomized trials powered to detect 7% and 25% reductions in death and transplantation would require 5790 and 380 end points, respectively. CONCLUSION: Decreasing the rate of death or transplantation by 7.1% offsets therapy side effects, EMB-related death, and inaccuracies in histologic diagnosis. Prospective randomized trials of treatments for myocarditis may be more feasible during periods of high prevalence or with more sensitive diagnostic techniques.

Biopsy↗
PubMed2002

Cost-effectiveness analysis of alternative strategies for palliation of distal biliary obstruction after a failed cannulation attempt.

OBJECTIVES: Occasionally alternative techniques such as precut sphincterotomy or percutaneous transhepatic cholangiography (PTC) are required to achieve access to the common bile duct. Tradeoffs exist, however, with respect to their complications and costs. Some experts believe that precut sphincterotomy should not be performed at all. We aimed to compare the cost-effectivenesses of metallic biliary stent placement after an initial failed cannulation attempt at ERCP utilizing precut sphincterotomy and placement utilizing PTC for palliation of jaundice. A cost-effectiveness analysis was performed, as viewed from the societal perspective. METHODS: A decision analysis model was designed comparing precut sphincterotomy and PTC approaches for placement of a metallic biliary stent for palliation of jaundice in a patient with inoperable malignant distal biliary obstruction in whom an initial attempt at ERCP cannulation had failed. Baseline probabilities, obtained from the published literature, were varied through plausible ranges using sensitivity analysis. Charges were based on Medicare professional plus facility fees or diagnosis-related group rates for out- and inpatients, respectively. The outcome measured was cost per year of life. RESULTS: Sensitivity analysis showed that precut sphincterotomy with subsequent PTC, if necessary, was the most cost-effective strategy provided the precut complication rate was <51% ($9,033/yr), versus $14,741/yr for PTC. CONCLUSIONS: Precut sphincterotomy followed by PTC (if necessary) is the most cost-effective strategy for palliative biliary stenting in the setting of malignant distal biliary obstruction after a failed ERCP attempt. The endoscopic approach is best practiced by experienced endoscopists who minimize precut complication rates.

Catheterization↗
PubMed2000

Pharmacoeconomic analysis of ciclopirox nail lacquer solution 8% and the new oral antifungal agents used to treat dermatophyte toe onychomycosis in the United States.

BACKGROUND: Recently a novel topical nail lacquer, ciclopirox solution 8%, has been approved for the treatment of onychomycosis. OBJECTIVE: This was undertaken to determine the most cost-effective treatment for the treatment of dermatophyte onychomycosis of the toes in the United States in 2000. METHODS: The nature of the problem was defined. The drug comparators were ciclopirox nail lacquer, terbinafine, itraconazole (pulse), itraconazole (continuous), fluconazole, and griseofulvin. A decision analytic model that reflected the manner in which pedal tinea unguium is managed was produced. Studies that have evaluated the efficacy of the nail lacquer and the oral antifungal agents for this indication were identified. Appropriate studies were used in a meta-analysis to determine the mycologic and clinical response rates when the drug comparators are used for the treatment for toe dermatophyte onychomycosis. For each drug comparator a cost of regimen analysis was carried out. This is the sum of the drug acquisition cost, the cost of medical management, and the cost of managing adverse effects. Next, the expected cost of management was calculated, disease free days were determined, and a sensitivity analysis was conducted. RESULTS: For each comparator the meta-analytic average mycologic cure (MC) rate and clinical response (CR) rates were: ciclopirox nail lacquer (MC: 52.6 +/- 4.2%, CR: 52.4 +/- 9.0%), griseofulvin (MC: 41.1 +/- 20.4%, CR: 33.7 +/- 14.1%), itraconazole (continuous) (MC: 66.3 +/- 4.2%, CR: 70.3 +/- 4.2%), itraconazole (pulse) (MC: 70.8 +/- 5.7%, CR: 73.6 +/- 4.6%), terbinafine (MC: 77.2 +/- 4.0%, CR: 75.3 +/- 2.9%), and fluconazole (MC: 65.6 +/- 7.1%, CR: 66.5 +/- 11.7%). The cost of regimen for the drug comparators was: ciclopirox nail lacquer $325.2, griseofulvin $1413.1, itraconazole (continuous) $1410.2, itraconazole (pulse) $811.7, terbinafine $890.1, and fluconazole $966.8. The cost/mycologic cure rate and expected cost/expected symptom free day were, ciclopirox nail lacquer ($618.2, 1.69), griseofulvin $3438.2, 5.3), itraconazole (continuous) ($2126.9, 3.52), itraconazole (pulse) ($1146.4, 2.01), terbinafine ($1153.0, 2.14), and fluconazole ($1473.7, 2.10). The relative cost-effectiveness was ciclopirox nail lacquer 1.00, itraconazole (pulse) 1.19, fluconazole 1.24, terbinafine 1.27, itraconazole (continuous) 2.08, and griseofulvin 3.13. Sensitivity analysis indicated that ciclopirox nail lacquer was a cost effective alternative compared with the oral regimens of terbinafine, itraconazole (continuous), and griseofulvin when clinical response rate was used as the primary efficacy parameter. CONCLUSION: Ciclopirox nail lacquer solution 8% is a recent addition to the armamentarium of therapies available to the physician and patient for the treatment of onychomycosis. The nail lacquer is a cost effective agent compared with the oral antifungal therapies, terbinafine, itraconazole, fluconazole, and griseofulvin.

Administration, Oral↗
PubMed2004

Economic evaluation of misoprostol in the treatment of early pregnancy failure compared to curettage after an expectant management.

BACKGROUND: The increased pressure on health care expenses implies that physicians should consider economic aspects as part of the clinical decision-making process. Direct and indirect costs of a strategy starting with misoprostol in treatment of early pregnancy failure as compared to curettage is therefore performed. METHODS: We performed a cost-minimization analysis alongside a multicentre randomized trial. Clinical data and data on the use of medical resources were obtained from a randomized trial comparing misoprostol and curettage, which had shown that misoprostol reduced the need for curettage in 53%. In a sensitivity analysis the percentage of women who needed curettage after misoprostol varied between 25 and 90%. RESULTS: Direct costs per case were significantly lower in the misoprostol group (mean 433) than in the curettage group (mean 683) (mean difference 250, 95% CI 184 to 316, P < 0.001). These significant differences existed under a wide range of alternative assumptions about unit costs. The differences in direct cost in favour of misoprostol were large for women who had complete evacuation after initial misoprostol treatment as compared to those who needed additional curettage after failed misoprostol. Mean indirect costs were equal for both groups (misoprostol mean 486; curettage mean 428; mean difference 60, 95% CI -61 to 179, P = 0.51). The mean total costs for a strategy starting with misoprostol was 915 versus 1107 for curettage, with a mean difference between both groups of 192 (95% CI 33 to 351, P = 0.04). An increase of the complete evacuation rates for initial misoprostol therapy to 90% in the sensitivity analysis increased the cost difference between misoprostol and curettage to 550. CONCLUSION: The use of misoprostol for early pregnancy failure after failed expectant management is less costly than curettage.

Abortifacient Agents, Nonsteroidal↗
PubMed1997

Computational methods for probabilistic decision trees.

Decision tree models may be more realistic if branching probabilities (and possibly utilities) are represented as distributions rather than point estimates. However, numerical analysis of such "probabilistic" trees is more difficult. This study employed the Mathematica computer algebra system to implement and verify previously described probabilistic methods. Both algebraic approximations and Monte Carlo simulation methods were used; in particular, simulations with beta, logistic-normal, and triangular distributions for branching probabilities were compared. Algebraic and simulation methods of sensitivity analysis were also implemented and compared. Computation required minimal programming and was reasonably fast using Mathematica on a standard personal computer. This study verified previously published results, including methods of sensitivity analysis. Changing the input distributional form had little effect. Computation is no longer a significant barrier to the use of probabilistic methods for analysis of decision trees.

Computer Simulation↗