An examination of the clinical benefits and cost-effectiveness of tocolytic replacement following recurrent preterm labor.

We examined pregnancy outcomes in women receiving nifedipine tocolysis having recurrent preterm labor (RPTL). Singleton gestations enrolled for outpatient nursing surveillance and prescribed nifedipine tocolysis were identified (N = 4748). Women hospitalized for RPTL at <35 weeks then resuming outpatient surveillance were included (N = 1366). Pregnancy outcomes of women resuming nifedipine (N = 830) were compared with those having an alteration in treatment to continuous subcutaneous terbutaline (N = 536). Overall, 56.7% (2692/4748) experienced RPTL. Half (50.7%) were stabilized and resumed outpatient surveillance with nifedipine or continuous subcutaneous terbutaline. Infants from women resuming nifedipine versus those with alteration of treatment to terbutaline were more likely to deliver at <35 weeks (28.0% versus 13.8%), weigh <2500 g (32.9% versus 20.3%), and require a stay in the neonatal intensive care unit (34.0% versus 23.1%), all P < 0.001. Alteration of tocolytic treatment following RPTL resulted in a decreased incidence of preterm birth and low birth weight, resulting in less admission to the neonatal intensive care unit and fewer nursery days.

A real-life cost-effectiveness evaluation of budesonide/formoterol maintenance and reliever therapy in asthma.

OBJECTIVE: To evaluate direct asthma-related costs in Swedish primary care in a real-life setting. DESIGN: 12-month open-label study. SETTING: Swedish primary care in a real-life setting. PARTICIPANTS: 1776 patients with persistent asthma. INTERVENTIONS: Patients with persistent asthma were randomised to one of three treatments: a free adjustable combination of budesonide (100-400 microg/inhalation) and formoterol (4.5 or 9 microg/inhalation) via separate inhalers plus terbutaline as needed; budesonide/formoterol (160/4.5 microg or 80/4.5 microg, two inhalations twice daily) plus terbutaline as needed; budesonide/formoterol (160/4.5 microg or 80/4.5 microg, one inhalation twice daily or two inhalations once daily), for maintenance plus additional inhalations as needed. Doses depended on previous inhaled corticosteroid dose. Patients attended the clinic at 0, 1.5, and 12 months. Telephone interviews were conducted at 4, 6, 8, and 10 months. MAIN OUTCOME MEASURES: The primary endpoint was direct asthma-related healthcare costs. RESULTS: Statistically significant reductions in annual direct costs per patient were observed with budesonide/formoterol maintenance and reliever therapy compared with the free adjustable combination of budesonide and formoterol (-13%, P<0.001) and fixed-dose budesonide/formoterol plus terbutaline (-20%, P<0.001). Time to first severe exacerbation did not differ significantly across treatment groups, with a mean reduction of 28% versus the free adjustable combination of budesonide and formoterol (P=0.076). Patients receiving budesonide/formoterol maintenance and reliever therapy used a significantly lower daily dose of budesonide compared with the conventional (P<0.001). CONCLUSIONS: This study reports direct cost savings with budesonide/formoterol maintenance and reliever therapy compared with conventional treatment regimens with at least equivalent efficacy.

Budesonide/formoterol as maintenance and reliever treatment compared to fixed dose combination strategies - a Canadian economic evaluation.

OBJECTIVE: To compare the cost-effectiveness of budesonide/formoterol in a single inhaler used as Maintenance and Reliever Therapy (SMART) versus fixed higher-dose budesonide/formoterol plus as-needed terbutaline reliever (FHDBF) or fixed dose fluticasone/salmeterol plus as-needed terbutaline reliever (FDFS) in controlling asthma in adults and adolescents. METHODS: An economic evaluation was conducted by applying Canadian costs to the results of a large (N=3,335) international randomized, double-blind, controlled trial in which health resource utilization was prospectively collected. Although no Canadian subjects were enrolled in this clinical trial, it was assumed that the results would apply to Canadian patients. Primary outcome measurements included time to first exacerbation and the number of severe exacerbations. Costs included direct medical costs (physician/emergency room visits, hospitalizations, asthma drug costs) and productivity (absenteeism). The time horizon was six months, which corresponded to the duration of the trial. Prices were obtained from 2006 Canadian sources. Both healthcare and societal perspectives were considered. Deterministic univariate sensitivity analyses were conducted. RESULTS: In the clinical trial, SMART was superior to FHDBF and FDFS with respect to total number of severe exacerbations (RR 0.72; 95% CI 0.57, 0.90; p=0.0048; RR 0.61; 95% CI 0.49, 0.76; p<0.001, respectively). Exacerbation rates (reported as events per patient per 6 months) were 0.12 for SMART, 0.16 for FHDBF, and 0.19 for FDFS. All treatments provided similar improvements in lung function, asthma control days and asthma-related quality of life. The mean cost per patient per 6 months was $545 in the SMART arm versus $690 in the FHDBF arm and $842 in the FDFS arm from the healthcare perspective; and $676 for SMART, $838 for FHDBF, and $954 for FDFS from the societal perspective. SMART was dominant (more effective, less expensive) in the base case analysis from both the healthcare and societal perspectives. The results were robust under sensitivity testing. CONCLUSIONS: The SMART strategy, which allows budesonide/formoterol to be used as both maintenance and reliever medication, is dominant over the alternate strategies of fixed higher dose budesonide and formoterol plus as-needed terbutaline or fixed dose salmeterol and fluticasone plus as-needed terbutaline.

A cost decision analysis of 4 tocolytic drugs.

OBJECTIVE: The purpose of this study was to determine the optimal tocolytic agent, based on a cost decision analysis. STUDY DESIGN: A PubMed search of commonly used tocolytics was performed to determine the probability of adverse events. Cost for an agent was determined by acquisition cost and the probability and cost of adverse events. A decision tree was constructed to determine which tocolytic had the lowest total costs, with subsequent sensitivity analysis. RESULTS: A total of 19 clinical trials combined for a cohort of 1073 patients (indomethacin, 176 patients; magnesium sulfate, 451 patients; nifedipine, 176 patients; and terbutaline, 270 patients). The probability of adverse events was 57.9% for terbutaline, 22.0% for magnesium sulfate, 27.2% for nifedipine, and 11.4% for indomethacin. Nifedipine ($16.75) and indomethacin ($15.40) were the least expensive treatment options, compared with magnesium sulfate ($197.90) and terbutaline ($399.02) because of the cost of monitoring and treating adverse events. CONCLUSION: If one elects a tocolytic, both nifedipine and indomethacin should be the agents of choice, based on a cost decision analysis.

Continuous subcutaneous terbutaline administration prolongs pregnancy after recurrent preterm labor.

OBJECTIVE: This study was undertaken to study the effectiveness of continuous subcutaneous terbutaline (SQT) in the home after recurrent preterm labor (RPTL). STUDY DESIGN: Women with RPTL at less than 32 weeks' gestation were treated with continuous SQT administered in the home compared with matched control patients. RESULTS: Fifteen SQT patients were compared with 45 women (3:1) treated with no tocolytic therapy after hospitalization. Gestational age at delivery more than 37 weeks (53% vs 4%), percentage delivered at less than 32 weeks (0% vs 47%), overall and pregnancy prolongation (49.8 +/- 19.2 days vs 24.5 +/- 12.8 days) were all significantly better in the study group (P <.001). The total number of maternal hospital days (9.8 +/- 2.1 vs 15.9 +/- 7.4, P <.0001), duration of NICU stay (1.9 +/- 4.9 vs 19.8 +/- 29.3 days, P <.001), and total cost for newborn care (6,995 +/- 14,822 US dollars vs 62,033 +/- 89,978 US dollars, P <.002) favored the study patients. For every dollar spent on SQT, there was a savings of 4.67 US dollars in newborn hospital costs for control patients. CONCLUSION: In this small study, the use of SQT significantly prolongs pregnancy, decreases serious neonatal complications, and reduces the duration of hospitalization for both mother and infant, as well as neonatal costs.

A cost-effectiveness study comparing the as-needed use of formoterol (Oxis) and terbutaline (Bricanyl) in patients with moderate to severe asthma.

This study evaluated the economic and health-related consequences of the as-needed use of a long-acting beta2-agonist with fast onset (formoterol, Oxis Turbuhaler 4.5 microg) versus a short-acting beta2-agonist (terbutaline, Bricanyl Turbuhaler 0.5 mg) in patients with moderate to severe asthma. A multi-national (Sweden, Norway, The Netherlands and Greece), multi-centre (35 centres), randomized, double-blind clinical trial was conducted using 362 patients on inhaled steroids during a 12-week period. The effectiveness results were pooled and the total costs included estimates for beta2-agonists, inhaled steroids, oral steroids, physician visits and sick-leave. The 182 patients in the formoterol group had 14,404 days of exposure and 29 severe exacerbations, and the 180 patients in the terbutaline group had 13,655 days of exposure and 48 severe exacerbations. The terbutaline group had 62% more severe exacerbations than the formoterol group (P=0.039), based on exposure time. Per patient, the calculated total costs were SEK 3386 for the formoterol group and SEK 3709 for the terbutaline group over the 12-week period. The conclusion is that the use of Oxis Turbuhaler instead of Bricanyl Turbuhaler for as-needed treatment is a more effective treatment generating cost savings from a societal perspective.

Clinical and cost-effectiveness of continuous subcutaneous terbutaline versus oral tocolytics for treatment of recurrent preterm labor in twin gestations.

OBJECTIVE: To compare the clinical and cost-effectiveness of treating recurrent preterm labor with continuous subcutaneous terbutaline versus oral tocolytics in twin gestations. STUDY DESIGN: In a retrospective, matched-cohort design, twin pregnancies treated as outpatients with continuous subcutaneous terbutaline were identified from a perinatal database, then matched 1:1 by gestational age at recurrent preterm labor to those receiving oral tocolytics. There were 353 patients per treatment group. A cost model was used to compare antepartum hospital, nursery, and outpatient charges. RESULTS: Infants of the subcutaneous terbutaline group had greater gestational age at delivery, higher birth weights, and less frequent neonatal intensive care unit admission. Charges for antepartum hospitalization and nursery were significantly less in the subcutaneous terbutaline group, while charges for outpatient services were less for the oral group. Mean total estimated charges were US$17,109 less for those receiving subcutaneous terbutaline. CONCLUSION: Improved clinical outcomes and decreased nursery utilization suggest cost-effectiveness of outpatient continuous subcutaneous terbutaline versus oral tocolytics for the treatment of recurrent preterm labor.

Cost-effectiveness of inhaled beta-agonists v. oral salbutamol in asthma: a randomized double-blind cross-over study.

BACKGROUND: Oral beta-stimulants are widely used in the management of chronic asthma in India, in spite of evidence suggesting the superiority of inhaled medication in achieving maximum bronchodilatation. An economic evaluation was performed in a randomized double-blind cross-over trial to evaluate the role of adjuvant oral beta-stimulants in the treatment of asthma. METHODS: Patients who had seasonal or perennial asthma and were using metered dose inhalers for control of symptoms were randomly selected for the study. They received either 4 mg of oral salbutamol or placebo as adjuvant treatment. During the study they controlled their symptoms by adjusting the dose of the inhaler medication. A cost minimization technique was used to assess the economic impact of this intervention in the treatment and control periods. A sensitivity analysis was performed to assess the robustness of the conclusions. RESULTS: The mean cost was significantly greater in the treatment period and a patient lost approximately Rs 20 per month (CI: 13 to 27; p = 0.001) as a result of the adjuvant treatment. There was no significant difference in the quality of life or peak expiratory flow rate during the two periods. The patients also noted mild but significantly increased tremors (p = 0.01) and palpitations (p = 0.001) during the treatment period. There was no treatment-to-period interaction. CONCLUSION: Adjuvant oral beta-agonists do not improve the quality of life or bronchodilatation in asthmatics using an inhaled beta-agonist for control of symptoms.

Costs and effects of inhaled corticosteroids and bronchodilators in asthma and chronic obstructive pulmonary disease.

The objective of this study was to determine the costs and effects of combined bronchodilator and anti-inflammatory therapy. In a 2.5-yr randomized controlled study, combined beta 2-agonist/corticosteroid therapy (BA + CS) and combined beta 2-agonist/anticholinergic therapy (BA + AC) were compared with beta 2-agonist/placebo therapy (BA + PL). Included in the study were 274 patients 18 to 60 yr of age with moderately severe obstructive airways disease. The main clinical endpoints were lung function, hyperresponsiveness, restricted activity days, and symptom-free days. The economic endpoints were the costs of health care utilization. Compared with BA + PL, BA + CS led to significant improvements in FEV1, PC20, and symptom-free days. BA + AC did not differ from BA + PL in this respect. The respective annual acquisition costs of BA + CS, BA + AC, and BA + PL were 532 US$, 277 US$, and 156 US$. Thus, BA + CS costs 376 US$ more than BA + PL. However, compared with BA + PL therapy, BA + CS led to statistically significant savings in other health care costs of about 175 US$ (95% CI from 46 to 303 US$). Thus, more than half of the additional costs of adding the inhaled corticosteroid are compensated for by a reduction in the costs of other health care services. Overall, inhaled corticosteroids lead to a small but net increase in health care costs of 201 US$ per patient per year.(ABSTRACT TRUNCATED AT 250 WORDS)