Effects and determinants of tuberculosis drug stockouts in South Africa.

BACKGROUND: The frequent occurrence of medicine stockouts represents a significant obstacle to tuberculosis control in South Africa. Stockouts can lead to treatment alterations or interruptions, which can impact treatment outcomes. This study investigates the determinants and effects of TB drug stockouts and whether poorer districts are disproportionately affected. METHODS: TB stockout data, health system indicators and TB treatment outcomes at the district level were extracted from the District Health Barometer for the years 2011, 2012 and 2013. Poverty terciles were constructed using the Census 2011 data to investigate whether stockouts and poor treatment outcomes were more prevalent in more impoverished districts. Fixed-effects regressions were used to estimate the effects of TB stockouts on TB treatment outcomes. RESULTS: TB stockouts occurred in all provinces but varied across provinces and years. Regression analysis showed a significant association between district per capita income and stockouts: a 10% rise in income was associated with an 8.50% decline in stockout proportions. In terms of consequences, after controlling for unobserved time invariant heterogeneity between districts, a 10% rise in TB drug stockouts was found to lower the cure rate by 2.10% (p < 0.01) and the success rate by 1.42% (p < 0.01). These effects were found to be larger in poorer districts. CONCLUSIONS: The unequal spread of TB drug stockouts adds to the socioeconomic inequality in TB outcomes. Not only are stockouts more prevalent in poorer parts of South Africa, they also have a more severe impact on TB treatment outcomes in poorer districts. This suggests that efforts to cut back TB drug stockouts would not only improve TB treatment outcomes on average, they are also likely to improve equity because a disproportionate share of this burden is currently borne by the poorer districts.

Will you still need me, will you still feed me when I'm 64? The health impact of caregiving to one's spouse.

Informal care may substitute for formal long-term care that is often publicly funded or subsidized. The costs of informal caregiving are borne by the caregiver and may consist of worse health outcomes and, if the caregiver has not retired, worse labor market outcomes. We estimate the impact of providing informal care to one's partner on the caregiver's health using data from the Survey of Health, Ageing, and Retirement in Europe. We use statistical matching to deal with selection bias and endogeneity. We find that in the short run caregiving has a substantial effect on the health of caregivers and, for female caregivers, on their health care use. These effects should be taken into account when comparing the costs and benefits of formal and informal care provision. The health effects may, however, be short-lived, as we do not find any evidence that they persist after 4 or 7 years.

Two-year bronchodilator treatment in patients with mild airflow obstruction. Contradictory effects on lung function and quality of life.

In a two-year randomized controlled study, we studied the effects of bronchodilator treatment on the lung function and the quality of life in patients with mild airflow obstruction. The patients were randomly divided to receive either continuous or symptomatic bronchodilator treatment. Within these treatment groups, they received salbutamol in the first year and ipratropium bromide in the second or vice versa. In addition, the quality of life of the patients was compared to that of the general population. One hundred and forty-four patients completed the study. When compared to the general population, these patients showed a serious impairment in quality of life. No differences between the two drugs were found, but the results indicated that FEV1 decline in the continuously treated group was significantly larger than in the symptomatically treated group. However, this was not reflected in a significant deterioration of the quality of life in the continuous group as measured by means of the Nottingham Health Profile and the Inventory of Subjective Health. Decline in FEV1 showed no correlation with changes in quality of life scores. This may be due to a relatively rapid adjustment of the patients to a decline in FEV1, as a result of which it has no direct effect on the experienced quality of life. Another reason may be that continuous bronchodilation masks the worsening of the disease. This lack of awareness might in turn be caused by the continuous symptom relief of bronchodilators.

Cost-effectiveness analysis of formoterol versus salmeterol in patients with asthma.

OBJECTIVE: The aim of this study was to determine the relative economic consequences of treating asthmatics with twice daily dry powder formoterol 12 micrograms as compared with salmeterol 50 micrograms from a societal perspective. DESIGN AND SETTING: A randomised, 6-month, open-label study including 482 patients with asthma was conducted in Italy, Spain, France, Switzerland, the UK and Sweden. Medical costs included the costs of medications, physician services, emergency room visits, hospital admissions and lung function and other tests. Travel costs and costs of production loss were also calculated. Unit prices were estimated from external sources. To pool the costs of the 6 countries, European currencies were converted to US dollars using 1995 exchange rates. Outcome measures were the number of episode-free days (EFDs) and the number of patients reaching a clinically relevant improvement in quality of life as measured using the St. Georges Respiratory Questionnaire. MAIN OUTCOME MEASURES AND RESULTS: There were no significant differences between the 2 treatment arms in the frequency of emergency room visits, hospital admissions, use of rescue medication or contacts with general practitioners (GPs), specialists or nurses. Median medical costs over 6 months were $US828 per patient with formoterol and $US850 with salmeterol. This difference was not statistically significant. In both groups, about 60% of all days were episode-free. Average costs per EFD were about $US9 for both treatments. The average cost per patient reaching a clinically relevant improvement in quality of life was between $US1300 and $US1400. Incremental cost-effectiveness ratios were not calculated because both costs and outcomes were not significantly different. Asthma-related absenteeism ranged between 3 days and 6 months per patient in both groups. CONCLUSIONS: There was no evidence to suggest that either treatment was more cost effective than the other.

Cost effectiveness of inhaled corticosteroid plus bronchodilator therapy versus bronchodilator monotherapy in children with asthma.

In an incremental cost-effectiveness analysis, combined inhaled beta 2-receptor agonist plus inhaled corticosteroid therapy (BA + CS) was compared with inhaled beta 2-agonist plus placebo (BA + PL) in 116 asthmatic children aged 7 to 16 years. Clinical data have been reported previously. To account for the selective withdrawal rate due to pulmonary problems that occurred in the group receiving BA + PL, costs were calculated using 2 approaches: (1) the cumulative cost approach and (2) the patient-year approach. Besides improvements in forced expiratory volume in 1 second (FEV 1) and airway responsiveness expressed as the provocative dose of histamine required to give a 20% fall in FEV 1 (PD 20), the frequency of asthma symptoms and school absenteeism were significantly reduced in the BA + CS group. Annual drug acquisition costs for the group receiving BA + CS were NLG480 higher than for the BA + PL group ($US1 = NLG2.12, 1989 prices). Based on conservative calculations using the cumulative cost approach, annual savings due to reduced healthcare utilisation, excluding the cost of study drugs, by the group receiving BA + CS compared with BA + PL were estimated to be about NLG273 per patient. The incremental cost effectiveness of BA + CS was estimated to be about NLG175 per 10% increase in FEV 1, or somewhat less than NLG10 per symptom-free day gained. The patient-year approach estimated savings due to corticosteroids of about 43% of the costs of BA + PL (95% confidence intervals, 21 to 58%). Savings were larger when the indirect costs that a family incurred during school absenteeism were considered. Addition of an inhaled corticosteroid to an inhaled beta 2-receptor agonist is a cost-effective treatment option that could even result in net healthcare savings.

"A built bed is a filled bed?" An empirical re-examination.

This article provides an empirical re-examination of the relationship between regional hospital bed supply and the utilization of hospital care. It tests the hypothesis that the divergence of findings between studies based on micro-data (at the individual level) and those based on macro-data (at the regional level) is due to aggregation and specification bias. The main conclusion is that neither source of bias can account for the observed differences. Some other possible explanations are put forward. Regardless of the level of aggregation, a positive effect is found of bed supply on length of hospital stay but not on admission rates. This may be the result of major changes which have taken place in the financing of hospital services in the Netherlands during the last decade.

Economic appraisal of asthma and COPD care: a literature review 1980-1991.

Despite the considerable burden and costs of illness and despite the increasing need to set priorities on the basis of efficiency considerations, only 20 economic appraisals of asthma and COPD care have been published during the past 11 years. This paper provides a detailed summary of the cost-effectiveness 'evidence' given by these studies and a discussion of relevant methodological issues. The studies comparing programme costs of delivery methods for oxygen and for aerosol bronchodilator drugs, provide the most straightforward evidence in favour of the concentrator and the metered dose inhaler respectively. There also seems to be evidence in favour of hospital-based home care programmes as compared to community-based home care programs. Health education, especially directed at asthmatic children seems to reduce health care costs and improve attitude, compliance behaviour and self-management skills. Information on the cost-effectiveness of pharmacotherapy and diagnostic technologies, both important interventions in asthma and COPD, was found to be totally lacking.

Towards a reinforced agency role of health insurers in Belgium and The Netherlands.

This article describes some recent developments in health insurance in Belgium and the Netherlands. Both countries are moving towards greater financial responsibility of health insurers by means of risk-adjusted capitation payment systems. Although for the unwary observer it would appear as if both countries were following similar paths towards a common model, the authors make clear that rather different underlying rationales are driving these trends. In the Netherlands, the grand design 'Dekker proposal' for regulated competition has been replaced by a more gradual implementation of reforms with more limited scope. The ultimate goal remains a system of managed competition, albeit only for part of the health care services. In Belgium, prospective risk-adjusted capitation payment has always been at the heart of the original system in principle since its inception, but non-enforcement led to retrospective and inequitable financing in practice. Although the rhetoric of managed competition has never been used explicitly in any Belgian official government policy document, it seems unlikely that putting the insurers at financial risk without simultaneously also reinforcing their agency role by providing instruments for care management-like, for example, selective contracting--is viable in the longer run without jeopardizing the solvency of the insurers. The authors conclude that although the logic of the managed competition model is appealing, the lack of conclusive empirical evidence of success elsewhere makes governments reluctant to surrender their traditional cost containment tools. But making insurers financially accountable without simultaneously providing them with tools to take on the accountability seems useless and illogical.

Statistical analysis of cost outcomes in a randomized controlled clinical trial.

This paper suggests an approach to deal with an estimation problem which is often encountered in analyzing the longitudinal cost data gathered in a clinical trial. The source of that estimation problem is twofold: 1) a considerable number of missing data due to treatment-related withdrawal of severely affected patients with high health care costs in only one the treatment groups and 2) a heavily skewed cost distribution due to rare high-cost events. The approach is illustrated using data from a trial comparing 3 different drug regimes. In order to calculate costs per patient-year in case of selectively missing data we extrapolated the costs of patients with incomplete follow-up. Due to the skewness and the associated large variance in costs per patient-year, these costs cannot be analyzed using common parametric statistical methods relying on underlying normal distributions. A logarithmic transformation was performed to approximate a normal distribution, reduce the impact of extreme values and create similar size variances in the treatment groups. An ordinary least squares regression analysis of transformed data then standardized for differences in patient characteristics between the groups. For the retransformation, the so-called smearing estimate was used. This 'transformation-standardization-retransformation' approach enabled us to provide more consistent and efficient estimates of cost differences that were shown to be statistically significant and judged to be important.

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)

Methodological issues of patient utility measurement. Experience from two clinical trials.

This article explores various methodological issues of patient utility measurement in two randomized controlled clinical trials involving 85 patients with fibromyalgia and 144 with ankylosing spondylitis. In both trials one baseline and two follow-up measurements of the patients' preferences for their own health state and several hypothetical states were performed using the rating scale and the standard gamble methods. It was confirmed that standard gamble scores are consistently higher than rating scale scores for both the experienced and the hypothetical states. The 3-month test-retest reliability for hypothetical states measured by intraclass correlation coefficients ranged from 0.24 to 0.33 for the rating scale and from 0.43 to 0.70 for the standard gamble. Although the reproducibility is not high, the group mean scores are fairly stable over time. Mean standard gamble scores tend to differ depending on the way the measurements are undertaken. Utilities elicited with chained gambles were significantly higher than utilities elicited with basic reference gambles. At the individual level some inconsistent responses occurred. However, more than 70% of these fell within the bounds of the measurement error, which ranged from 0.11 to 0.13 on the standard gamble (0-1 scale) and from 8 to 10 on the rating scale (0-100 scale). The large number of negative utilities for the severe hypothetical state, which was used as an anchor point in the chained gambles, and the magnitude of these negative utilities (down to -19) calls for intensified research efforts to handle these responses in utility calculations.

Economic evaluation of antifungal agents in the treatment of toenail onychomycosis in Germany.

BACKGROUND: The strategies for the management of onychomycosis have changed since the availability of the newer generation of antifungal agents, particularly, itraconazole and terbinafine. Itraconazole (1-week pulse) therapy may have higher efficacy and an improved adverse-effects profile compared to the continuous therapy regimen. OBJECTIVE: We performed a pharmacoeconomic evaluation of the most commonly used treatments in Germany for toenail onychomycosis from a health care payer perspective. METHODS: A 5-step approach was used. Firstly, the purpose of the study, the comparator drugs, their dosage regimens and the time frame of the analysis were defined. Next, the medical practice and resource consumption patterns associated with the treatment of onychomycosis were identified. In step III, a meta-analysis was used to determine the relative efficacy of the comparator drugs. In step IV, a decision tree of the treatment algorithms was constructed for each comparator. The expected cost analysis and cost-effectiveness analysis were also performed. Finally, a sensitivity analysis was carried out. RESULTS: For the four main comparator drugs used to treat toenail onychomycosis in Germany, the clinical response rates (clinical cure plus marked improvement) at the end of the follow-up period (month 12 after starting therapy) were, for itraconazole (1-week pulse dosing): 89.8 +/- 3% (mean +/- SE), terbinafine: 79.4 +/- 10%, itraconazole (continuous dosing): 77.5 +/- 9%, and ciclopirox nail varnish: 55 +/- 5%. Itraconazole (1-week pulse dosing) was most cost-effective at DM 1,107 per successful treatment, followed by oral terbinafine at DM 1,224, ciclopirox nail varnish and itraconazole (continuous dosing). Sensitivity analyses indicated that itraconazole (1-week pulse dosing) and terbinafine had similar cost-effectiveness ratios. CONCLUSION: Itraconazole is an effective, broad-spectrum triazole used as continuous or pulse therapy in the treatment of onychomycosis. Itraconazole (1-week pulse) and terbinafine are the most cost-effective therapies for toenail onychomycosis.

Comparison of performance of four instruments in evaluating the effects of salmeterol on asthma quality of life.

Quality of life measures are increasingly used as important efficacy endpoints in studies of drugs for asthma. The purpose of this study was to assess both the sensitivity to change and the construct validity of four different quality of life instruments in patients with asthma. In a double-blind, parallel group study, 120 moderate asthma patients, aged between 18-70 yrs, received either inhaled salmeterol 50 micrograms b.i.d. or inhaled salbutamol 400 micrograms b.i.d. In addition to respiratory outcomes, quality of life was measured at a 6 weeks follow-up using: 1) Asthma Quality of Life Questionnaire (AQLQ); 2) Living With Asthma Questionnaire (LWAQ); 3) Sickness Impact Profile (SIP); 4) Rating Scale (RS); and Standard Gamble (SG) utilities. Salmeterol led to significant improvements over salbutamol on virtually all clinical outcomes. Although all the quality of life instruments showed the same trend in favour of salmeterol, only the AQLQ and RS utilities showed significantly greater improvement on salmeterol than on salbutamol. Except for the AQLQ, the correlation between change in lung function and change in quality of life was generally low. Whereas, the AQLQ correlated well with the patient's overall assessment of efficacy (r = 0.64), the LWAQ, SIP and utilities failed to show such a correlation. The AQLQ showed the best correlation with symptom scores. The cross-sectional correlation between the AQLQ and the LWAQ was 0.73, whereas the longitudinal correlation was only 0.29. The SG generally showed poor correlation with other measures, including the RS. In conclusion, patients given salmeterol showed a greater improvement in quality of life compared to patients given salbutamol. Of the disease-specific questionnaires the Asthma Quality of Life Questionnaire was found to be more responsive to change than the Living With Asthma Questionnaire and showed greater validity. Of the generic instruments, the rating scale utilities were most responsive. The Standard Gamble showed poor correlation with other measures.