Comparative effectiveness and safety of pharmacological and non-pharmacological interventions for insomnia: an overview of reviews.

BACKGROUND: This review aimed to assess the existing evidence regarding the clinical effectiveness and safety of pharmacological and non-pharmacological interventions in adults with insomnia and identify where research or policy development is needed. METHODS: MEDLINE, Embase, PsycINFO, The Cochrane Library, and PubMed were searched from inception until June 14, 2017, along with relevant gray literature sites. Two reviewers independently screened titles/abstracts and full-text articles, and a single reviewer with an independent verifier completed charting, data abstraction, and quality appraisal. RESULTS: A total of 64 systematic reviews (35 with meta-analysis) were included after screening 5024 titles and abstracts and 525 full-text articles. Eight of the included reviews were rated as high quality using the Assessment of Multiple Systematic Reviews 2 (AMSTAR2) tool, and over half of the included articles (n = 40) were rated as low or critically low quality. Consistent evidence of effectiveness across multiple outcomes based on more than one high- or moderate quality review with meta-analysis was found for zolpidem, suvorexant, doxepin, melatonin, and cognitive behavioral therapy (CBT), and evidence of effectiveness across multiple outcomes based on one high-quality review with meta-analysis was found for temazepam, triazolam, zopiclone, trazodone, and behavioral interventions. These interventions were mostly evaluated in the short term (< 16 weeks), and there was very little harms data available for the pharmacological interventions making it difficult to evaluate their risk-benefit ratio. CONCLUSIONS: Assuming non-pharmacological interventions are preferable from a safety perspective CBT can be considered an effective first-line therapy for adults with insomnia followed by other behavioral interventions. Short courses of pharmacological interventions can be supplements to CBT or behavioral therapy; however, no evidence regarding the appropriate duration of pharmacological therapy is available from these reviews. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017072527.

Budget impact analysis of the use of oral and intravenous anti-cancer drugs for the treatment of HER2-positive metastatic breast cancer.

OBJECTIVES: Two anti-cancer drugs are currently approved for the treatment of HER2-positive metastatic breast cancer (MBC): trastuzumab-based therapy (TBT) administered intravenously as first line therapy until disease progression and lapatinib, an oral self-administered dual therapy with capecitabine (L+C) as second intention for patients who continue to progress despite TBT. In current practice, TBT is still prescribed beyond disease progression. In addition to medical reasons, the difficulty to switch eligible patients to oral drugs may also be explained by economic reasons. Thus, we aimed at comparing the budgetary impact of TBT and L+C for progressing HER2+MBC after TBT from the French Health Insurance perspective. METHODS: A budget impact analysis was performed on a 3-year time horizon (2012-2014) to simulate a dynamic cohort of 4182 HER2-positive patients with a progressing MBC treated with TBT (73%) and L + C (27%). The model was adjusted on progression-free survival (PFS). Office visits, clinical evaluations, drug acquisition, administration costs, and transportation costs obtained from the literature and published databases were considered. RESULTS: In the base case analysis (2012), the annual treatment cost per patient for TBT (€36,077) was 2-times higher than that of L + C (€17,165). Using L + C for all patients (n = 4182) would avoid €34.8 million of drug administration and transportation costs. Hospital costs represented 1% vs 88%, while community costs represented 99% vs 12% of L + C and TBT treatment costs, respectively. The lack of direct comparison PFS and treatment dosage modification data were the main limitations. However, no major changes from baseline results were observed from sensitivity analyses. CONCLUSIONS: Despite a slightly higher acquisition cost, the treatment cost of L + C remains lower than that of TBT, and it is the only approved anti-HER2 treatment for HER2-positive patients with progressing MBC. Based on this, it seems important to consider the potential savings for Health Insurance with the use of oral drug due to the reduction of outpatient hospitalizations. Such reductions may result in a subsequent budget reduction for hospitals, but may also provide those facing acute medical activity with opportunities to better manage other diseases whose treatment cannot be externalized.

Economic evaluation of a 100% whey-based partially hydrolyzed infant formula in the prevention of atopic dermatitis among Swiss children.

OBJECTIVE: A pharmacoeconomic analysis was undertaken to determine costs, consequences, and cost-effectiveness of a partially hydrolyzed 100% whey-based infant formula, NAN-HA®, manufactured by Nestlé S.A, Switzerland (PHF-W), branded under BEBA HA® in Switzerland, in the prevention of atopic dermatitis (AD) in 'at risk' Swiss children when compared to standard cow's milk formula (SF). METHODS: Based on a 12-month time horizon including 6 months of formula consumption, an economic model was developed synthesizing treatment pathways, resource utilization, and costs associated with the treatment of AD in healthy 'at risk' Swiss newborns who could not be exclusively breastfed. Model inputs were retrieved from the literature, official formularies, and expert opinion. The treatment pathways considered a medical treatment approach, supplemented in some instances by a change of formula. The final outcome was the expected cost per avoided case of AD, yielding an incremental cost effectiveness ratio (ICER) for PHF-W vs SF. Outcomes were presented from three perspectives: the Swiss public healthcare system (MOH), the subject's family, and society (SOC). A secondary analysis compared PHF-W to whey-based extensively hydrolyzed formula (EHF) in prevention. RESULTS: The model yielded 1653 avoided AD cases by selecting PHF-W over SF in a birth cohort of 22,933 'at risk' infants. The base case analyses generated an expected ICER of CHF 982 from the MOH perspective as well as savings of CHF 2202 and CHF 1220 from the family and SOC perspectives, respectively. PHF-W yielded CHF 11.4M savings against EHF when the latter was assumed to be used in prevention. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. CONCLUSION: Under a range of assumptions, this analysis has established the dominance from the family and societal perspectives and cost-effectiveness from the MOH perspective of PHF-W vs SF in the prevention of AD among 'at risk' Swiss infants.

Economic evaluation of a 100% whey-based partially hydrolyzed infant formula in the prevention of atopic dermatitis among Danish children.

OBJECTIVE: A pharmacoeconomic analysis was undertaken to determine costs, consequences, and cost-effectiveness of a brand of partially hydrolyzed 100%-whey formula manufactured by Nestlé (PHF-W), in the prevention of atopic dermatitis (AD) in 'at risk' Danish children compared to extensively hydrolyzed formula (EHF-Whey or Casein). METHODS: Given the non-significant differences between PHF-W and EHF, the base case analytic approach amounted to a cost-minimization analysis (CMA) reporting the difference in formula acquisition costs over the period of formula consumption for the population of interest. However, sensitivity analyses (SAs) were undertaken to explore applying the nominal efficacy of PHF-W and EHF, thus leading to a cost-effectiveness analysis (CEA). Hence, an economic model based on a 12-month time horizon was developed synthesizing treatment pathways, resource utilization, and costs associated with the treatment of AD in the population of interest. The final economic outcome of the SAs was the incremental cost per avoided case (ICER) defined as the expected cost per avoided case of AD for PHF-W vs EHF, determined from three perspectives: the Ministry of Health (MOH), the family of the subject, and society (SOC). RESULTS: In the base case CMA, savings of DKK 9 M, DKK 20 M, and DKK 29 M were generated for PHF-W vs EHF from the MOH, family, and SOC perspectives. In the sensitivity CEA, PHF-W was dominant over EHF-Whey from all perspectives, while EHF-Casein displayed against PHF-W unattractive ICERs of DKK 315,930, DKK 408,407, and DKK 724,337 from the MOH, family, and SOC perspectives. Probabilistic SAs indicated that PHF-W was 86% likely to be dominant over EHF-Whey, whereas EHF-Casein had no likelihood of dominating PHF-W. CONCLUSION: Under a range of assumptions, this analysis demonstrated the attractiveness of PHF-W vs both types of EHF in the prevention of AD among 'at risk' Danish infants who are not or cannot be exclusively breastfed.

Methylnaltrexone in the treatment of opioid-induced constipation in cancer patients receiving palliative care: willingness-to-pay and cost-benefit analysis.

CONTEXT: When laxative regimens have failed, methylnaltrexone may be indicated for the relief of opioid-induced constipation (OIC) in patients with advanced illness receiving palliative care. OBJECTIVES: A cost-benefit analysis (CBA), based on a willingness-to-pay (WTP) approach, was performed to determine if methylnaltrexone should be added to the formulary list of drugs being reimbursed by third-party payers in Canada for the treatment of cancer patients in palliative care suffering from OIC. METHODS: The WTP study had two components: a decision board explaining treatment options (Component A) and a questionnaire to measure individual WTP using a bidding game approach (Component B). Component A had two options: Option 1 (laxatives only) and Option 2 (laxatives+methylnaltrexone injection). Only participants choosing Option 2 were invited to complete Component B. The results of the WTP survey were then incorporated into a CBA. Within a hypothetical cohort, additional monthly premiums that individuals were willing to pay for methylnaltrexone were compared with the monthly costs to the insurer for providing methylnaltrexone to all patients who would potentially be using it. RESULTS: Four hundred one Canadians, of age 18 years and older, were surveyed and yielded a WTP in additional monthly insurance premiums of Canadian dollar (CAD) $8.65 (95% confidence interval: CAD$6.17-CAD$11.13). The CBA resulted in additional CAD$89,307 with a cost of CAD$139,840 and benefits of CAD$229,147. A set of 10,000 Monte Carlo simulations resulted in average CBA savings of CAD$145,011 with a 99.86% probability of dominance. CONCLUSION: The present CBA provides pharmacoeconomic evidence for the adoption of methylnaltrexone for treating OIC in terminally ill cancer patients.

Meta-analysis of a partially hydrolysed 100%-whey infant formula vs. extensively hydrolysed infant formulas in the prevention of atopic dermatitis.

OBJECTIVES: This study presents previously unpublished point and cumulative incidence rates and relative risks (RRs) for comparing a partially hydrolysed 100% whey-based infant formula, NAN-HA * (PHF-W) to extensively hydrolysed whey- (EHF-Whey) or casein-based (EHF-Casein) infant formulas in the prevention of atopic dermatitis (AD) in infants who cannot be breastfed exclusively. It also outlines methods to convert the above-mentioned data as well as data comparing PHF-W to cows' milk formula (SF) into inputs to be applied to a pharmacoeconomic model. * NAN-HA is a registered trade name of Nestlé SA, Switzerland. METHODS: The incidence rates and RRs were obtained from a meta-analysis which analysed efficacy for PHF-W vs. EHF but did not present those. It took into consideration any relevant randomized controlled trial which compared the use of PHF-W with SF or EHF for the prevention of allergies. The primary outcomes of interest were the incidence, cumulative incidence and period prevalence of allergic manifestations and of AD in particular. Fifteen studies had been included for analysis of which six studies explored PHF-W vs. EHF. These results and PHF-W vs. SF data were adapted for inputs into a pharmacoeconomic model which used a spreadsheet decision-analytic economic model based on 3-month cycles to explore the cost-effectiveness of PHF-W vs. SF and EHF. Weights were applied to the incidence rates and RRs for each reported time period which were then adapted into 3-month indicators. RESULTS: This meta-analysis for PHF-W (557 patients) vs. EHF-Whey (559 patients) yielded RR of 0.75 (0.54, 1.05) and 0.80 (0.63, 1.02) at 0-12 months and at 0-36 months, respectively. Corresponding RRs for PHF-W vs. EHF-Casein (580 patients) were 1.06 (0.74, 1.53) at 0-12 months and 1.13 (0.87, 1.47) at 0-36 months. CONCLUSION: It appears that the efficacy of PHF-W falls within the range of that of both EHF formulas (whey and casein) and allows the application of these results in a pharmacoeconomic model.

Economic evaluation of a 100% whey-based, partially hydrolysed formula in the prevention of atopic dermatitis among French children.

OBJECTIVE: A pharmacoeconomic analysis was performed to determine costs, consequences and cost effectiveness of a partially hydrolysed 100% whey-based infant formula, NAN HA, manufactured by Nestlé S.A, Switzerland (PHF-W) and branded under Nidal Excel HA in France, in the prevention of atopic dermatitis (AD) in 'at risk' children when compared to standard cows' milk formula (SF) in France. METHODS: A decision-analytic economic model depicting AD treatment pathways, as well as resource utilisation and costs associated with the treatment of AD in healthy yet 'at risk' French newborns who cannot be exclusively breastfed was constructed for a 12-month time horizon, including an initial 6 months of intervention with formula consumption. Model inputs were based on the literature, official formularies and expert opinion. The modelled treatment pathways included a dietary management approach (formula change), a medical treatment approach and a combination thereof. The final outcome was the expected cost per avoided case of AD, yielding an incremental cost per avoided case (ICER) of AD when comparing subjects who used PHF-W versus SF. Outcomes were presented from three perspectives: the French Ministry of Health (MOH), the subjects' family and society as a whole. A secondary analysis also compared PHF-W to extensively hydrolysed formula (EHF) in prevention. RESULTS: The number of avoided AD cases by selecting PHF-W over SF was 13,356 cases in a birth cohort of 185,298 'at risk' infants. The base case analysis, at 65% reimbursement, yielded expected ICERs of €1343, € -624 (savings) and €719 from the MOH, family and societal perspectives, respectively. From all three perspectives, the highest cost was attributable to formula. In case of a 35% reimbursement rate for PHF-W, the ICER was €615 from the MOH perspective, while the use of PHF-W was cost neutral at 10% reimbursement. PHF-W was cost-saving against EHF (€98-€116 million savings depending on type of EHF), when this latter was used in prevention. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. CONCLUSION: Under a certain range of assumptions, this analysis based on predictive modelling has established the cost effectiveness of PHF-W in the prevention of AD in infants.