Validation of a menstrual pictogram and a daily bleeding diary for assessment of uterine fibroid treatment efficacy in clinical studies.

BACKGROUND: To evaluate the psychometric and measurement properties of two patient-reported outcome instruments, the menstrual pictogram superabsorbent polymer-containing version 3 (MP SAP-c v3) and Uterine Fibroid Daily Bleeding Diary (UF-DBD). Test-retest reliability, criterion, construct validity, responsiveness, missingness and comparability of the MP SAP-c v3 and UF-DBD versus the alkaline hematin (AH) method and a patient global impression of severity (PGI-S) were analyzed in post hoc trial analyses. RESULTS: Analyses were based on data from up to 756 patients. The full range of MP SAP-c v3 and UF-DBD response options were used, with score distributions reflecting the cyclic character of the disease. Test-retest reliability of MP SAP-c v3 and UF-DBD scores was supported by acceptable intraclass correlation coefficients when stability was defined by the AH method and Patient Global Impression of Severity (PGI-S) scores (0.80-0.96 and 0.42-0.94, respectively). MP SAP-c v3 and UF-DBD scores demonstrated strong and moderate-to-strong correlations with menstrual blood loss assessed by the AH method. Scores increased in monotonic fashion, with greater disease severities, defined by the AH method and PGI-S scores; differences between groups were mostly statistically significant (P < 0.05). MP SAP-c v3 and UF-DBD were sensitive to changes in disease severity, defined by the AH method and PGI-S. MP SAP-c v3 and UF-DBD showed a lower frequency of missing patient data versus the AH method, and good agreement with the AH method. CONCLUSIONS: This evidence supports the use of the MP SAP-c v3 and UF-DBD to assess clinical efficacy endpoints in UF phase III studies replacing the AH method.

The economic burden of bronchiectasis - known and unknown: a systematic review.

BACKGROUND: The increasing prevalence and recognition of bronchiectasis in clinical practice necessitates a better understanding of the economic disease burden to improve the management and achieve better clinical and economic outcomes. This study aimed to assess the economic burden of bronchiectasis based on a review of published literature. METHODS: A systematic literature review was conducted using MEDLINE, Embase, EconLit and Cochrane databases to identify publications (1 January 2001 to 31 December 2016) on the economic burden of bronchiectasis in adults. RESULTS: A total of 26 publications were identified that reported resource use and costs associated with management of bronchiectasis. Two US studies reported annual incremental costs of bronchiectasis versus matched controls of US$5681 and US$2319 per patient. Twenty-four studies reported on hospitalization rates or duration of hospitalization for patients with bronchiectasis. Mean annual hospitalization rates per patient, reported in six studies, ranged from 0.3-1.3, while mean annual age-adjusted hospitalization rates, reported in four studies, ranged from 1.8-25.7 per 100,000 population. The average duration of hospitalization, reported in 12 studies, ranged from 2 to 17 days. Eight publications reported management costs of bronchiectasis. Total annual management costs of €3515 and €4672 per patient were reported in two Spanish studies. Two US studies reported total costs of approximately US$26,000 in patients without exacerbations, increasing to US$36,00-37,000 in patients with exacerbations. Similarly, a Spanish study reported higher total annual costs for patients with > 2 exacerbations per year (€7520) compared with those without exacerbations (€3892). P. aeruginosa infection increased management costs by US$31,551 to US$56,499, as reported in two US studies, with hospitalization being the main cost driver. CONCLUSIONS: The current literature suggests that the economic burden of bronchiectasis in society is significant. Hospitalization costs are the major driver behind these costs, especially in patients with frequent exacerbations. However, the true economic burden of bronchiectasis is likely to be underestimated because most studies were retrospective, used ICD-9-CM coding to identify patients, and often ignored outpatient burden and cost. We present a conceptual framework to facilitate a more comprehensive assessment of the true burden of bronchiectasis for individuals, healthcare systems and society.

The Cost of Unintended Pregnancies in Canada: Estimating Direct Cost, Role of Imperfect Adherence, and the Potential Impact of Increased Use of Long-Acting Reversible Contraceptives.

OBJECTIVE: Unintended pregnancies (UPs) are associated with a significant cost burden, but the full cost burden in Canada is not known. The objectives of this study were to quantify the direct cost of UPs in Canada, the proportion of cost attributable to UPs and imperfect contraceptive adherence and the potential cost savings with increased uptake of long-acting reversible contraceptives (LARCs). METHODS: A cost model was constructed to estimate the annual number and direct costs of UP in women aged 18 to 44 years. Adherence-associated UP rates were estimated using perfect- and typical-use contraceptive failure rates. Change in annual number of UPs and impact on cost burden were projected in three scenarios of increased LARC usage. One-way sensitivity analyses were conducted to assess the impact of key variables on scenarios of increased LARC use. RESULTS: There are more than 180 700 UPs annually in Canada. The associated direct cost was over $320 million. Fifty-eight percent (58%) of UPs occurred in women aged 20 to 29 years at an annual cost of $175 million; 82% of this cost ($143 million) was attributable to contraceptive non-adherence. Increased LARC uptake produced cost savings of over $34 million in all three switching scenarios; the largest savings ($35 million) occurred when 10% of oral contraceptive users switched to LARCs. The minimum duration of LARC usage required before cost savings was realized was 12 months. CONCLUSION: The cost of UPs in Canada is significant and much of it can be attributed to imperfect contraceptive adherence. Increased LARC uptake may reduce contraceptive non-adherence, thereby reducing rates of UP and generating significant cost savings, particularly in women aged 20 to 29.

Objectif : Les grossesses non planifiées (GNP) sont associées à un fardeau financier considérable; au Canada, l'ampleur de ce fardeau demeure inconnue. Cette étude avait pour objectif de quantifier les coûts directs des GNP au Canada, la proportion des coûts liés aux GNP attribuables à une observance imparfaite du schéma posologique contraceptif et les économies potentielles associées à un accroissement de l'utilisation de modes de contraception réversible à action prolongée (CRAP). Méthodes : Un modèle de coût a été conçu pour estimer le nombre annuel de GNP et leurs coûts directs chez les femmes âgées de 18 à 44 ans. Les taux de GNP associés à l'observance ont été estimés au moyen des taux d'échec de la contraception en utilisation parfaite et en utilisation typique. Les modifications du nombre annuel de GNP et les effets sur le fardeau financier ont été projetés dans le cadre de trois scénarios prévoyant un accroissement du recours aux modes de CRAP. Des analyses simples de la variance en matière de sensibilité ont été menées pour évaluer les effets de variables clés sur les scénarios prévoyant un accroissement du recours aux modes de CRAP. Résultats : On compte plus de 180 700 GNP chaque année au Canada. Les coûts directs qui leur sont associés sont de plus de 320 millions de dollars. Cinquante-huit pour cent (58 %) des GNP se sont manifestées chez des femmes de 20 à 29 ans, ce qui représente un coût annuel de 175 millions de dollars; 82 % de ce coût (143 millions de dollars) étaient attribuables à la non-observance du schéma posologique contraceptif. L'accroissement du recours aux modes de CRAP a généré des économies de plus de 34 millions de dollars dans le cadre des trois scénarios de transition envisagés; les économies les plus importantes (35 millions de dollars) ont été constatées dans le cadre du scénario prévoyant que 10 % des utilisatrices de contraceptifs oraux adopteraient un mode de CRAP. La durée minimale d'utilisation d'un mode de CRAP nécessaire pour l'obtention d'économies était de 12 mois. Conclusion : Au Canada, le coût des GNP est considérable; de plus, une bonne partie de ce coût est attribuable à une observance imparfaite du schéma posologique contraceptif. L'accroissement du recours aux modes de CRAP pourrait mener à une baisse du taux de non-observance du schéma posologique contraceptif, ce qui entraînerait une baisse des taux de GNP et générerait des économies considérables, particulièrement chez les femmes de 20 à 29 ans.

Cost-effectiveness analysis of a low-dose contraceptive levonorgestrel intrauterine system in Sweden.

OBJECTIVE: To evaluate the cost-effectiveness of a novel intrauterine system, levonorgestrel intrauterine system 13.5 mg vs. oral contraception, in women at risk of unintended pregnancy. DESIGN: Cost-effectiveness model using efficacy and discontinuation data from published articles. SETTING: Societal perspective including direct and indirect costs. POPULATION: Women at risk of unintended pregnancy using reversible contraception. METHODS: An economic analysis was conducted by modeling the different health states of women using contraception over a 3-year period. Typical use efficacy rates from published articles were used to determine unintended pregnancy events. Discontinuation rates were used to account for method switching. MAIN OUTCOME MEASURES: Cost-effectiveness was evaluated in terms of the incremental cost per unintended pregnancy avoided. In addition, the incremental cost per quality-adjusted life-year was calculated. RESULTS: Levonorgestrel intrauterine system 13.5 mg generated costs savings of € 311,000 in a cohort of 1000 women aged 15-44 years. In addition, there were fewer unintended pregnancies (55 vs. 294) compared with women using oral contraception. CONCLUSION: Levonorgestrel intrauterine system 13.5 mg is a cost-effective method when compared with oral contraception. A shift in contraceptive use from oral contraception to long-acting reversible contraception methods could result in fewer unintended pregnancies, quality-adjusted life-year gains, as well as cost savings.

Direct costs of unintended pregnancy in Spain.

OBJECTIVE: The aim of the study was to estimate the burden and direct medical costs of unintended pregnancy to the public payer in Spain. METHODS: An economic model evaluating the costs and outcomes of contraceptive use over a 1-year period was constructed for women in Spain aged 15 to 44 years at risk of pregnancy. Model inputs were derived from published literature and national survey data. Outcomes evaluated included: (i) the annual number of unintended pregnancy events and their cost; (ii) the proportion of unintended pregnancy events and their cost due to non-adherence; and (iii) the use and cost of contraceptive methods in Spain. RESULTS: Of the total number of pregnancies, 35% are estimated to be unintended and are associated with a direct cost burden of €292.8 million per year. Most unintended pregnancies (26%) occur in women aged 30 to 34 years, whilst 69% of the total cost burden is estimated to be attributable to poor adherence to contraceptive methods. CONCLUSIONS: The cost associated with unintended pregnancy is high. The major proportion of the burden is estimated to be attributable to imperfect adherence and is likely avoidable. Shifts in patterns of contraceptive use, combined with measures to improve adherence, could have a substantial and positive impact on this burden.

Direct costs of unintended pregnancy in the Russian federation.

BACKGROUND: In 2010, almost every third pregnancy in Russia was terminated, indicating that unintended pregnancy (UP) is a public health problem. OBJECTIVE: The aim of this study was to estimate the direct cost of UP to the healthcare system in Russia and the proportion attributable to using unreliable contraception. METHODS: A cost model was built, adopting a generic payer perspective with a 1-year time horizon. The analysis cohort was defined as women of childbearing age between 18 and 44 years actively seeking to avoid pregnancy. Model inputs were derived from published sources or government statistics with a 2012 cost base. To estimate the number of UPs attributable to unreliable methods, the model combined annual typical use failure rates and age-adjusted utilization for each contraceptive method. Published survey data was used to adjust the total cost of UP by the number of UPs that were mistimed rather than unwanted. Scenario analysis considered alternate allocation of methods to the reliable and unreliable categories and estimate of the burden of UP in the target sub-group of women aged 18-29 years. RESULTS: The model estimated 1,646,799 UPs in the analysis cohort (women aged 18-44 years) with an associated annual cost of US$783 million. The model estimated 1,019,371 UPs in the target group of 18-29 years, of which 88 % were attributable to unreliable contraception. The total cost of UPs in the target group was estimated at approximately US$498 million, of which US$441 million could be considered attributable to the use of unreliable methods. CONCLUSION: The cost of UP attributable to use of unreliable contraception in Russia is substantial. Policies encouraging use of reliable contraceptive methods could reduce the burden of UP.

Achieving cost-neutrality with long-acting reversible contraceptive methods.

OBJECTIVES: This analysis aimed to estimate the average annual cost of available reversible contraceptive methods in the United States. In line with literature suggesting long-acting reversible contraceptive (LARC) methods become increasingly cost-saving with extended duration of use, it aimed to also quantify minimum duration of use required for LARC methods to achieve cost-neutrality relative to other reversible contraceptive methods while taking into consideration discontinuation. STUDY DESIGN: A three-state economic model was developed to estimate relative costs of no method (chance), four short-acting reversible (SARC) methods (oral contraceptive, ring, patch and injection) and three LARC methods [implant, copper intrauterine device (IUD) and levonorgestrel intrauterine system (LNG-IUS) 20 mcg/24 h (total content 52 mg)]. The analysis was conducted over a 5-year time horizon in 1000 women aged 20-29 years. Method-specific failure and discontinuation rates were based on published literature. Costs associated with drug acquisition, administration and failure (defined as an unintended pregnancy) were considered. Key model outputs were annual average cost per method and minimum duration of LARC method usage to achieve cost-savings compared to SARC methods. RESULTS: The two least expensive methods were copper IUD ($304 per women, per year) and LNG-IUS 20 mcg/24 h ($308). Cost of SARC methods ranged between $432 (injection) and $730 (patch), per women, per year. A minimum of 2.1 years of LARC usage would result in cost-savings compared to SARC usage. CONCLUSIONS: This analysis finds that even if LARC methods are not used for their full durations of efficacy, they become cost-saving relative to SARC methods within 3 years of use. IMPLICATIONS: Previous economic arguments in support of using LARC methods have been criticized for not considering that LARC methods are not always used for their full duration of efficacy. This study calculated that cost-savings from LARC methods relative to SARC methods, with discontinuation rates considered, can be realized within 3 years.

Cost of unintended pregnancy in Norway: a role for long-acting reversible contraception.

OBJECTIVES: The objective of this study was to quantify the cost burden of unintended pregnancies (UPs) in Norway, and to estimate the proportion of costs due to imperfect contraceptive adherence. Potential cost savings that could arise from increased uptake of long-acting reversible contraception (LARC) were also investigated. METHODS: An economic model was constructed to estimate the total number of UPs and associated costs in women aged 15-24 years. Adherence-related UP was estimated using 'perfect use' and 'typical use' contraceptive failure rates. Potential savings from increased use of LARC were projected by comparing current costs to projected costs following a 5% increase in LARC uptake. RESULTS: Total costs from UP in women aged 15-24 years were estimated to be 164 million Norwegian Kroner (NOK), of which 81.7% were projected to be due to imperfect contraceptive adherence. A 5% increase in LARC uptake was estimated to generate cost savings of NOK 7.2 million in this group. CONCLUSIONS: The cost of UP in Norway is substantial, with a large proportion of this cost arising from imperfect contraceptive adherence. Increased LARC uptake may reduce the UP incidence and generate cost savings for both the health care payer and contraceptive user.

Cost-effectiveness analysis of levonorgestrel-releasing intrauterine system (LNG-IUS) 13.5 mg in contraception.

BACKGROUND: Levonorgestrel-releasing intrauterine system (LNG-IUS) 13.5 mg (total content) is a low-dose levonorgestrel intrauterine system for up to 3 years of use. This analysis evaluated the cost-effectiveness of LNG-IUS 13.5 mg in comparison with short-acting reversible contraceptive (SARC) methods in a cohort of young women in the United States from a third-party payer's perspective. STUDY DESIGN: A state transition model consisting of three mutually exclusive health states -- initial method, unintended pregnancy (UP) and subsequent method -- was developed. Cost-effectiveness of LNG-IUS 13.5 mg was assessed vs. SARC methods in a cohort of 1000 women aged 20-29 years. SARC methods comprise oral contraceptives (OC), ring, patch and injections, which are the methods commonly used by this cohort. Failure and discontinuation probabilities were based on published literature, contraceptive uptake was determined by the most recent data from the National Survey of Family Growth, and costs were taken from standard US databases. One-way sensitivity analysis was conducted around key inputs, while scenario analysis assessed a comparison between LNG-IUS 13.5 mg and the existing IUS, LNG-IUS 20 mcg/24 h. The key model output was cost per UP avoided. RESULTS: Compared to SARC methods, initiating contraception with LNG-IUS 13.5 mg resulted in fewer UP (64 UP vs. 276 UP) and lower total costs ($1,283,479 USD vs. $1,862,633 USD, a 31% saving) over the 3-year time horizon. Results were most sensitive to the probability of failure on OC, the probability of LNG-IUS 13.5 mg discontinuation and the cost of live births. Scenario analysis suggests that further cost savings may be generated with the initiation of LNG-IUS 20 mcg/24 h in place of SARC methods. CONCLUSIONS: From a third-party payer perspective, LNG-IUS 13.5 mg is a more cost-effective contraceptive option than SARC. Therefore, women switching from current SARC use to LNG-IUS 13.5 mg are likely to generate cost savings to third-party health care payers, driven principally by decreased UP-related expenditures and long-term savings in contraceptive costs.

The cost-effectiveness of the levonorgestrel-releasing intrauterine system for the treatment of idiopathic heavy menstrual bleeding in the United States.

OBJECTIVES: Heavy menstrual bleeding negatively impacts the health and quality of life of about 18 million women in the United States. Although some studies have established the clinical effectiveness of heavy menstrual bleeding treatments, few have evaluated their cost-effectiveness. Our objective was to evaluate the cost-effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) compared with other therapies for idiopathic heavy menstrual bleeding. METHODS: We developed a model comparing the clinical and economic outcomes (from a US payer perspective) of three broad initial treatment strategies over 5 years: LNG-IUS, oral agents, or surgery. Up to three nonsurgical treatment lines, followed by up to two surgical lines, were allowed; unintended pregnancy was possible, and women could discontinue any time during nonsurgical treatments. Menstrual blood loss of 80 ml or more per cycle determined treatment failure. RESULTS: Initiating treatment with LNG-IUS resulted in the fewest hysterectomies (6 per 1000 women), the most quality-adjusted life-years (3.78), and the lowest costs ($1137) among all the nonsurgical strategies. Initiating treatment with LNG-IUS was also less costly than surgery, resulted in fewer hysterectomies (vs. 9 per 1000 for ablation) but was associated with fewer quality-adjusted life-years gained per patient (vs. 3.80 and 3.88 for ablation and hysterectomy, respectively). Sensitivity analyses confirmed these results. CONCLUSIONS: LNG-IUS resulted in the lowest treatment costs and the fewest number of hysterectomies performed over 5 years compared with all other initial strategies and resulted in the most quality-adjusted life-years gained among nonsurgical options. Initial treatment with LNG-IUS is the least costly and most effective option for women desiring to preserve their fertility.

Burden of unintended pregnancy in the United States: potential savings with increased use of long-acting reversible contraception.

BACKGROUND: This study evaluated the total costs of unintended pregnancy (UP) in the United States (US) from a third-party health care payer perspective and explored the potential role for long-acting reversible contraception (LARC) in reducing UP and resulting health care expenditure. STUDY DESIGN: An economic model was constructed to estimate direct costs of UP as well as the proportion of UP costs that could be attributed to imperfect contraceptive adherence. The model considered all women requiring reversible contraception in the US: the pattern of contraceptive use and the rates of UP were derived from published sources. The costs of UP in the United States and the proportion of total cost that might be avoided by improved adherence through increased use of LARC were estimated. RESULTS: Annual medical costs of UP in the United States were estimated to be $4.6 billion, and 53% of these were attributed to imperfect contraceptive adherence. If 10% of women aged 20-29 years switched from oral contraception to LARC, total costs would be reduced by $288 million per year. CONCLUSIONS: Imperfect contraceptive adherence leads to substantial UP and high, avoidable costs. Improved uptake of LARC may generate health care cost savings by reducing contraceptive non-adherence.

Intercountry assessment of the impact of severe premenstrual disorders on work and daily activities.

We explored the effects of premenstrual symptoms in women suffering from moderate-to-severe premenstrual syndrome/premenstrual dysphoric disorder (PMS/PMDD) on work productivity, absenteeism, and daily life activities in a large, worldwide exploratory study. Women aged 15-45 years from 19 countries in North America, Latin America, Europe, Asia, and Australia were screened for suspected PMS and PMDD and invited to participate in this 2-month web-based survey. Overall, 4,032 women completed all administered questionnaires and represent the analysis set. Women suffering from moderate-to-severe PMS/PMDD had increased work absenteeism and work productivity impairment due to premenstrual symptoms relative to those with mild PMS/no perceived symptoms.

Explorative evaluation of the impact of severe premenstrual disorders on work absenteeism and productivity.

PURPOSE: To assess the effects of premenstrual disorders on work productivity and absenteeism in the multinational Impact study. METHODS: Women aged 15-45 years were screened for suspected premenstrual dysphoric disorders (PMDD) and premenstrual syndrome (PMS) and invited to participate in this web-based study. Based on the Daily Record of Severity of Problems (DRSP) questionnaire, symptoms were assessed prospectively over 2 months. Participants were categorized as having no perceived symptoms/mild PMS or moderate-to-severe PMS/PMDD based on a validated algorithm. Work productivity impairment and absenteeism were assessed retrospectively using the Premenstrual Symptoms Screening Tool (PSST) and a modified version of the Work Productivity and Activity Impairment (WPAI) questionnaire. Work productivity impairment was also assessed prospectively over 2 months using the DRSP questionnaire. RESULTS: Overall 1,477 women started the study-of these, 822 (56%) completed the study as planned and represent the full analysis set. Employed women with moderate-to-severe PMS/PMDD had higher rate of productivity impairment on the modified version of the WPAI questionnaire (values >/=7) relative to those with no perceived symptoms/mild PMS (adjusted odds ratio, 3.12; 95% confidence interval, 1.75-5.57). Similar outcomes were obtained for impairment of working productivity or efficiency using the PSST scale (value 4). The mean number of days on the DRSP with at least moderate reduction in productivity or efficiency in daily routine was higher for women with moderate-to-severe PMS/PMDD (5.6 vs. 1.1). Women with moderate-to-severe PMS/PMDD had a higher rate of absenteeism (>8hours per cycle; 14.2% vs. 6.0%). CONCLUSION: Moderate-to-severe PMS/PMDD seems to be associated with work productivity impairment and increased absenteeism, and thus poses a potential economic burden.