Atomoxetine treatment for children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD): a comprehensive meta-analysis of outcomes on parent-rated core symptomatology

Attention-Deficit/Hyperactivity Disorder (ADHD) impacts a significant number of children and adolescents and often leads to deleterious functional impairment. Psychostimulant medication has historically been the first line of pharmacological intervention, though recent years have seen greater attention paid to non-stimulant alternatives. The objective of the present study was to conduct the most comprehensive meta-analysis to date evaluating the efficacy of atomoxetine in reducing core symptomatology of ADHD according to parent report. Selection criteria were applied, and studies were located by searching electronic databases, review of reference sections, and contact with expert researchers; article searching began on 10/01/2013, and the final search was conducted on 09/01/2014. A total of 42 studies met inclusion criteria—33 with control groups and 9 without—for a total sample of 8398 individuals. For those receiving atomoxetine, the summary pre–post (e.g., standardized mean gain) effect size estimate was 1.37 (95% CI [1.24, 1.51], p < .001); atomoxetine was found to statistically significantly outperform control conditions overall (Z = 4.07, p < .001), though results differed by the type of control group; for instance, when comparing atomoxetine to alternative medications as controls, significant differences were no longer present. The non-stimulant atomoxetine led to significant improvement in core ADHD symptomatology and should be considered as a viable pharmacological treatment option for ADHD.     

Safety of 80 antidepressants,antipsychotics, anti‐attention‐deficit/hyperactivity medications and mood stabilizers in children and adolescents with psychiatric disorders: a large scale systematic meta‐review of 78 adverse effects

Mental disorders frequently begin in childhood or adolescence. Psychotropic medications have various indications for the treatment of mental dis­orders in this age group and are used not infrequently off‐label. However, the adverse effects of these medications require special attention during developmentally sensitive periods of life. For this meta‐review, we systematically searched network meta‐analyses and meta‐analyses of randomized controlled trials (RCTs), individual RCTs, and cohort studies reporting on 78 a priori selected adverse events across 19 categories of 80 psychotropic medications – including antidepressants, antipsychotics, anti‐attention‐deficit/hyperactivity disorder (ADHD) medications and mood stabilizers – in children and adolescents with mental disorders. We included data from nine network meta‐analyses, 39 meta‐analyses, 90 individual RCTs, and eight cohort studies, including 337,686 children and adolescents. Data on ≥20% of the 78 adverse events were available for six antidepressants (sertraline, escitalopram, paroxetine, fluoxetine, venlafaxine and vilazodone), eight antipsychotics (risperidone, quetiapine, aripiprazole, lurasidone, paliperidone, ziprasidone, olanzapine and asenapine), three anti‐ADHD medications (methylphenidate, atomoxetine and guanfacine), and two mood stabilizers (valproate and lithium). Among these medications with data on ≥20% of the 78 adverse events, a safer profile emerged for escitalopram and fluoxetine among antidepressants, lurasidone for antipsychotics, methylphenidate among anti‐ADHD medications, and lithium among mood stabilizers. The available literature raised most concerns about the safety of venlafaxine, olanzapine, atomoxetine, guanfacine and valproate. Nausea/vomiting and discontinuation due to adverse event were most frequently associated with antidepressants; sedation, extrapyramidal side effects, and weight gain with antipsychotics; anorexia and insomnia with anti‐ADHD medications; sedation and weight gain with mood stabilizers. The results of this comprehensive and updated quantitative systematic meta‐review of top‐tier evidence regarding the safety of antidepressants, antipsychotics, anti‐ADHD medications and mood stabilizers in children and adolescents can inform clinical practice, research and treatment guidelines.     

Treatment compliance or medication adherence in children and adolescents on ADHD medication in clinical practice: results from the COMPLY observational study

Although the efficacy and tolerability of ADHD medications have been investigated fairly extensively, there are very few data comparing the different types of medication (e.g. psychostimulants, non-stimulants) in terms of medication adherence. The primary research objective of the COMPLY observational study was to evaluate medication adherence (i.e. compliance) over 1 year in children and adolescents with ADHD in a routine clinical setting. COMPLY was a prospective 12-month, observational, open-label study that included children and adolescents, aged 6–17 years, with ADHD. Medication adherence (i.e. compliance) was measured using the Pediatric Compliance Self-Rating (PCSR) instrument and using items 1–4 of the Medication Adherence Rating Scale (MARS). A total of 504 patients were enrolled. At baseline, 252 patients (50.0 %) were prescribed non-stimulant (atomoxetine) medication and 247 patients (49.0 %) were prescribed psychostimulant medication. Both types of medication were prescribed concomitantly in five patients (1.0 %). After 12 months, 123 patients (48.8 %) were taking atomoxetine and 176 patients (71.3 %) were taking psychostimulants. Adherence (PCSR score ≥5) was present in both groups (atomoxetine: 67.5 %; psychostimulant: 74.2 %) throughout the observation period. MARS scores declined over time in both groups (atomoxetine: from 3.7 to 2.9; psychostimulant: from 3.6 to 3.1), indicating a deterioration in adherence. There was no statistically significant difference in terms of medication adherence between the two groups.     

A new high performance liquid chromatographic method for quantification of atomoxetine in human plasma and its application for pharmacokinetic study

Atomoxetine is the first, non-stimulant alternative to other stimulant medications used for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). Reported methods for the determination of atomoxetine include expensive liquid chromatography tandem mass spectrometry (LCMS) and high performance liquid chromatography (HPLC) with liquid scintillation counting (LSC) detection. Till date, no method has been reported in literature to determine atomoxetine using HPLC with UV detection. In this paper, we describe a new HPLC method for the determination of atomoxetine using liquid-liquid extraction with tertiary butyl methyl ether and UV detector. This method was found to be linear over the concentration range of 0.05-3.0 microg/ml. The limit of quantification was 0.05 microg/ml. Intra- and inter-day precision was <15% and accuracy was in the range of 95.67-108.80%. Stability studies showed that atomoxetine was stable in human plasma for short- and long-term period for sample preparation and analysis. This method was used for sample analysis in a pharmacokinetic study of atomoxetine (25mg) in five healthy adult female volunteers. The observed mean+/-S.D. pharmacokinetic parameters Cmax, Tmax and AUC(0-t) were 0.40+/-0.06 microg/ml, 3.40+/-0.42 h and 1.34+/-0.52 microg h/ml, respectively.     

Relationship between atomoxetine plasma concentration, treatment response and tolerability in attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder

The purpose of this study was to examine whether atomoxetine plasma concentration predicts attention-deficit/hyperactivity disorder (ADHD) or oppositional defiant disorder (ODD) response. This post-hoc analysis assessed the relationship between atomoxetine plasma concentration and ADHD and ODD symptoms in patients (with ADHD and comorbid ODD) aged 6–12 years. Patients were randomly assigned to atomoxetine 1.2 mg/kg/day (n = 156) or placebo (n = 70) for 8 weeks (Study Period II). At the end of 8 weeks, ODD non-remitters (score >9 on the SNAP-IV ODD subscale and CGI-I > 2) with atomoxetine plasma concentration <800 ng/ml at 2 weeks were re-randomized to either atomoxetine 1.2 mg/kg/day or 2.4 mg/kg/day for an additional 4 weeks (Study Period III). ODD remitters and non-remitters with plasma atomoxetine ≥800 ng/ml remained on 1.2 mg/kg/day atomoxetine for 4 weeks. Patients who received atomoxetine, completed Study Period II, and entered Study Period III were included in these analyses. All the groups demonstrated improvement on the SNAP-IV ODD and ADHD-combined subscales (P < .001). At the end of Study Periods II and III, ODD and ADHD improvement was significantly greater in the remitter group compared with the non-remitter groups. Symptom improvement was numerically greater in the non-remitter (2.4 mg/kg/day compared with the non-remitter 1.2 mg/kg/day) group. Atomoxetine plasma concentration was not indicative of ODD and ADHD improvement after 12 weeks of treatment. ADHD and ODD symptoms improved in all the groups with longer duration on atomoxetine. Results suggest atomoxetine plasma concentration does not predict ODD and ADHD symptom improvement. However, a higher atomoxetine dose may benefit some patients.     

Exploratory Cost-Effectiveness Analysis of Response-Guided Neoadjuvant Chemotherapy for Hormone Positive Breast Cancer Patients

PurposeGuiding response to neoadjuvant chemotherapy (guided-NACT) allows for an adaptative treatment approach likely to improve breast cancer survival. In this study, our primary aim is to explore the expected cost-effectiveness of guided-NACT using as a case study the first randomized controlled trial that demonstrated effectiveness (GeparTrio trial).ResultsOur exploratory CEA predicted that guided-NACT as proposed by the GeparTrio, costs additional €110, but results in 0.014 QALYs gained per patient. This scenario of guided-NACT was considered cost-effective at any willingness to pay per additional QALY. At the prevailing Dutch willingness to pay threshold (€80.000/QALY) cost-effectiveness was expected with 78% certainty.ConclusionThis exploratory CEA indicated that guided-NACT (as proposed by the GeparTrio trial) is likely cost-effective in treating HR+ EBC women. While prospective validation of the GeparTrio findings is advisable from a clinical perspective, early CEAs can be used to prioritize further research from a broader health economic perspective, by identifying which parameters contribute most to current decision uncertainty. Furthermore, their use can be extended to explore the expected cost-effectiveness of alternative guided-NACT scenarios that combine the use of promising imaging techniques together with personalized treatments.     

An Evaluation on the Efficacy and Safety of Treatments for Attention Deficit Hyperactivity Disorder in Children and Adolescents: a Comparison of Multiple Treatments

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurobehavioral disorders. We carried out this comparison of multiple treatments based on sufficient data in attempt to evaluate the efficacy and safety of ADHD medication for children and adolescents. PubMed, Embase and the Cochrane Database were used to search for relevant articles. Changes in the ADHD Rating Scale (ADHD-RS) scores and the Conners’ Parent Rating Scale-Revised (CPRS) scores were used as outcomes for efficacy. Withdrawals due to all-cause, adverse effects and lack of efficacy were defined as primary outcomes evaluating the safety of such medications. Both pair-wise and network meta-analyses were performed. Efficacy and safety of atomoxetine (ATX), bupropion (BUP), clonidine hydrochloride (CLON), guanfacine extended release (GXR), lisdexamfetamine dimesylate (LDX), and methylphenidate (MPH) were evaluated. LDX has the highest efficacy and a relatively lower rate of adverse effects compared to BUP, CLON and GXR. MPH has the lowest incidence rate of adverse effects and takes second place concerning ADHD-RS scores and third place concerning CPRS scores. ATX has the lowest incidence rate of all-cause withdrawals. The efficacy of ATX seems, however, to be lower than CLON, GXR, LDX and MPH. Adversely, BUP has the highest incidence rate of withdrawals and the second highest probability of causing adverse effects as well as lack of efficacy; therefore it should not be recommended as a treatment for ADHD.     

Cost-Effectiveness of Thrombolysis within 4.5 Hours of Acute Ischemic Stroke in China

Background

Previous economic studies conducted in developed countries showed intravenous tissue-type plasminogen activator (tPA) is cost-effective for acute ischemic stroke. The present study aimed to determine the cost-effectiveness of tPA treatment in China, the largest developing country.

Methods

A combination of decision tree and Markov model was developed to determine the cost-effectiveness of tPA treatment versus non-tPA treatment within 4.5 hours after stroke onset. Outcomes and costs data were derived from the database of Thrombolysis Implementation and Monitor of acute ischemic Stroke in China (TIMS-China) study. Efficacy data were derived from a pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Costs and quality-adjusted life-years (QALYs) were compared in both short term (2 years) and long term (30 years). One-way and probabilistic sensitivity analyses were performed to test the robustness of the results.

Results

Comparing to non-tPA treatment, tPA treatment within 4.5 hours led to a short-term gain of 0.101 QALYs at an additional cost of CNY 9,520 (US$ 1,460), yielding an incremental cost-effectiveness ratio (ICER) of CNY 94,300 (US$ 14,500) per QALY gained in 2 years; and to a long-term gain of 0.422 QALYs at an additional cost of CNY 6,530 (US$ 1,000), yielding an ICER of CNY 15,500 (US$ 2,380) per QALY gained in 30 years. Probabilistic sensitivity analysis showed that tPA treatment is cost-effective in 98.7% of the simulations at a willingness-to-pay threshold of CNY 105,000 (US$ 16,200) per QALY.

Conclusions

Intravenous tPA treatment within 4.5 hours is highly cost-effective for acute ischemic strokes in China.     

Factors predicting treatment adherence in patients with adult attention-deficit/hyperactivity disorder: a preliminary study

This study aimed to elicit patient- and treatment-related factors that can potentially predict treatment adherence in adult ADHD. Subjects who were over 18 and received a diagnosis of ADHD were included in the study. Chart review data of 102 subjects regarding demographics, medications, comorbidities, concomitant medications and domains of functional impairment were collected, and predictors were assessed using a binominal logistical regression model. One hundred and two patients (78.4 % male) with a mean age of 28.8 (SD = 9.8, range = 18–55) years were enrolled in the study. Childhood diagnosis of ADHD, agents used for treatment (MPH or atomoxetine), individual domains of dysfunction and use of additional psychotropic drugs were not found to be related to treatment adherence. Patients with a university education and those referred for family history of ADHD were more likely to adhere to treatment (p = 0.05 and 0.03, respectively). On the other hand, reasons for referral other than ADHD were significantly more frequently related to non-adherence (p = 0.02). Treatment noncompliance remains a significant problem despite therapeutic effects of medications. Identification of predictors of non-adherence can lead to heightened awareness of special populations at risk. We have found that prior awareness on ADHD (via past history/media/friends) leading to self/clinician referral to rule out ADHD and pervasiveness of symptoms across functional domains led to better compliance in our sample. Future research with prospective design utilizing objective tools for adherence is required.     

Is emotion recognition the only problem in ADHD? effects of pharmacotherapy on face and emotion recognition in children with ADHD

The objectives of this study were to evaluate both face and emotion recognition, to detect differences among attention deficit and hyperactivity disorder (ADHD) subgroups, to identify effects of the gender and to assess the effects of methylphenidate and atomoxetine treatment on both face and emotion recognition in patients with ADHD. The study sample consisted of 41 male, 29 female patients, 8–15 years of age, who were diagnosed as having combined type ADHD (N = 26), hyperactive/impulsive type ADHD (N = 21) or inattentive type ADHD (N = 23) but had not previously used any medication for ADHD and 35 male, 25 female healthy individuals. Long-acting methylphenidate (OROS-MPH) was prescribed to 38 patients, whereas atomoxetine was prescribed to 32 patients. The reading the mind in the eyes test (RMET) and Benton face recognition test (BFRT) were applied to all participants before and after treatment. The patients with ADHD had a significantly lower number of correct answers in child and adolescent RMET and in BFRT than the healthy controls. Among the ADHD subtypes, the hyperactive/impulsive subtype had a lower number of correct answers in the RMET than the inattentive subtypes, and the hyperactive/impulsive subtype had a lower number of correct answers in short and long form of BFRT than the combined and inattentive subtypes. Male and female patients with ADHD did not differ significantly with respect to the number of correct answers on the RMET and BFRT. The patients showed significant improvement in RMET and BFRT after treatment with OROS-MPH or atomoxetine. Patients with ADHD have difficulties in face recognition as well as emotion recognition. Both OROS-MPH and atomoxetine affect emotion recognition. However, further studies on the face and emotion recognition are needed in ADHD.     

Predictors of relapse or maintenance of response in pediatric and adult patients with attention-deficit/hyperactivity disorder following discontinuation of long-term treatment with atomoxetine

We identified relapse/maintenance-of-response (MOR) predictors following discontinuation of long-term atomoxetine treatment in pediatric and adult patients with attention-deficit/hyperactivity disorder (ADHD) and assessed correlations between ADHD symptoms and quality of life (QoL). Post hoc analyses of data from two randomized, double-blind, placebo-controlled, phase 3 withdrawal studies in patients with ADHD meeting predefined response criteria before randomization. Study 1: patients (N = 163; 6–15 years) received atomoxetine (1.2–1.8 mg/kg/day) for 1 year, followed by randomization to atomoxetine (n = 81) or placebo (n = 82) for 6 months. Study 2: patients (N = 524; 18–50 years) received atomoxetine (80–100 mg/day) for ~6 months, followed by randomization to atomoxetine (n = 266) or placebo (n = 258) for ~6 months. Placebo patients were used for the analyses. Relapse: ≥50% worsening of prerandomization improvement in ADHD symptoms and ≥2 level severity increase on the Clinical Global Impression-Severity (CGI-S) scale at 2 consecutive visits; MOR: retaining ≥75% of prerandomization symptom improvement and CGI-S ≤ 2 at all visits (study 1); retaining ≥70% of prerandomization symptom improvement and CGI-S ≤ 3 at all visits (study 2). In adults, statistically significantly (P ≤ .05) increased likelihood of relapse was associated with prerandomization presence of Conners’ Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator-Rated:Screening Version (CAARS-Inv:SV) items “difficulty awaiting turn” and “careless mistakes.” In pediatric patients, less MOR was associated with prerandomization presence of ADHD Rating Scale-IV-Parent Version Investigator-Rated item “does not listen”; in adults, less MOR was associated with prerandomization presence of CAARS-Inv:SV items “loses things” and “difficulty awaiting turn.” Changes in patients’ QoL after withdrawal from atomoxetine moderately correlated with changes in ADHD symptoms in pediatric patients and mildly in adults.     

A Cost-Effectiveness Analysis of the Swedish Universal Parenting Program All Children in Focus

Objective

There are few health economic evaluations of parenting programs with quality-adjusted life-years (QALYs) as the outcome measure. The objective of this study was, therefore, to conduct a cost-effectiveness analysis of the universal parenting program All Children in Focus (ABC). The goals were to estimate the costs of program implementation, investigate the health effects of the program, and examine its cost-effectiveness.

Methods

A cost-effectiveness analysis was conducted. Costs included setup costs and operating costs. A parent proxy Visual Analog Scale was used to measure QALYs in children, whereas the General Health Questionnaire-12 was used for parents. A societal perspective was adopted, and the incremental cost-effectiveness ratio was calculated. To account for uncertainty in the estimate, the probability of cost-effectiveness was investigated, and sensitivity analyses were used to account for the uncertainty in cost data.

Results

The cost was €326.3 per parent, of which €53.7 represented setup costs under the assumption that group leaders on average run 10 groups, and €272.6 was the operating costs. For health effects, the QALY gain was 0.0042 per child and 0.0027 per parent. These gains resulted in an incremental cost-effectiveness ratio for the base case of €47 290 per gained QALY. The sensitivity analyses resulted in ratios from €41 739 to €55 072. With the common Swedish threshold value of €55 000 per QALY, the probability of the ABC program being cost-effective was 50.8 percent.

Conclusion

Our analysis of the ABC program demonstrates cost-effectiveness ratios below or just above the QALY threshold in Sweden. However, due to great uncertainty about the data, the health economic rationale for implementation should be further studied considering a longer time perspective, effects on siblings, and validated measuring techniques, before full scale implementation.     

Atomoxetine-Induced Increases in Monoamine Release in the Prefrontal Cortex are Similar in Spontaneously Hypertensive Rats and Wistar-Kyoto Rats

Spontaneously hypertensive rats (SHRs) are used as a model for attention-deficit/hyperactivity disorder (ADHD), since SHRs are hyperactive and show defective sustained attention in behavioral tasks. The psychostimulants amphetamine and methylphenidate and the selective norepinephrine reuptake inhibitor atomoxetine are used as ADHD medications. The effects of high K⁺ stimulation or psychostimulants on brain norepinephrine or dopamine release in SHRs have been previously studied both in vitro and in vivo, but the effects of atomoxetine on these neurotransmitters have not. The present study examined the effects of administration of atomoxetine on extracellular norepinephrine, dopamine, and serotonin levels in the prefrontal cortex of juvenile SHRs and Wistar-Kyoto (WKY) rats. Baseline levels of prefrontal norepinephrine, dopamine, and serotonin were similar in SHRs and WKY rats. Systemic administration of atomoxetine (3 mg/kg) induced similar increases in prefrontal norepinephrine and dopamine, but not serotonin, levels in both strains. Furthermore, there was no difference in high K⁺-induced increases in extracellular norepinephrine, dopamine, and serotonin levels in the prefrontal cortex between SHRs and WKY rats. These findings indicate that monoamine systems in the prefrontal cortex are similar between SHRs and WKY rats.     

Prognostic factors of improvement in health-related quality of life in atomoxetine-treated children and adolescents with attention-deficit/hyperactivity disorder,based on a pooled analysis

The objective of this study is to identify prognostic factors of treatment response to atomoxetine in improvement of health-related quality of life (HR-QoL), measured by the Child Health and Illness Profile-Child Edition Parent Report Form (CHIP-CE PRF) Achievement and Risk Avoidance domains, in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Pooled data from 3 placebo-controlled trials and separate data from 3 open-label trials of atomoxetine in children and adolescents with ADHD were analyzed using logistic regression methods. Based on baseline impairment in the Achievement and/or Risk Avoidance domains (CHIP-CE PRF < 40 points), 2 subsamples of subjects were included. Treatment outcome was categorized as <5 points or ≥5 points increase in the CHIP-CE PRF Achievement and Risk Avoidance domains. Data of 190 and 183 subjects from the pooled sample, and 422 and 355 subjects from the open-label trials were included in the analysis of Achievement and Risk Avoidance domains. Baseline CHIP-CE subdomain scores proved to be the most robust prognostic factors for treatment outcome in both domains, based on data from the pooled sample of double-blind studies and from the individual open-label studies (odds ratios [OR] 0.74–1.56, p < 0.05; OR < 1, indicating a worse baseline score associated with worse odds of responding). Initial treatment response (≥25 % reduction in ADHD Rating Scale scores in the first 4–6 weeks) was another robust prognostic factor, based on data from the open-label studies (OR 2.99–6.19, p < 0.05). Baseline impairment in HR-QoL and initial treatment response can be early prognostic factors of atomoxetine treatment outcome in HR-QoL in children and adolescents with ADHD.     

Atomoxetine response in the inattentive and combined subtypes of attention deficit hyperactivity disorder: a retrospective chart review

The DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 1994, American Psychiatric Association) describes attention deficit hyperactivity disorder (ADHD) as a heterogeneous disorder; providing diagnostic criteria for three subtypes: hyperactive/impulsive (ADHD/HI), inattentive (ADHD/I), and combined type (ADHD/C). Differences among the subtypes are well defined, but there may be also differences in terms of treatment responses. The aim of this study is to assess the responses of ADHD/I and ADHD/C to atomoxetine treatment. The medical records of the January–June 2012 term, first time referrals to outpatient clinic, were reviewed, and 37 ADHD diagnosed primary school age children (18 ADHD/I, 19 ADHD/C) that were treated with atomoxetine were determined. Thirty-five of them who completed 8 weeks of treatment duration were recruited for the study. The children with an ADHD medication use history in 2 months time prior to onset of treatment and/or the children receiving additional psychopharmacologic treatment to atomoxetine were excluded. Baseline and eighth week assessment, records were evaluated. Efficacy assessments included Turgay DSM-IV ADHD Screening and Rating Scale parent and teacher forms (T-DSM-IV) and Clinical Global Impression Scale-Severity and Improvement subscales. Safety assessments included laboratory and body weight assessments, ECG, heart rate, and blood pressure evaluations (baseline and eighth week) along a scale filled by the parents at the eighth week to review side effects. Atomoxetine was found to be effective in both ADHD/I and ADHD/C groups. Atomoxetine also decreased the opposition defiance subscale scores of T-DSM-IV (both parent and teacher forms), whereas it was not found to make statistically significant difference in the conduct disorder subscale scores. Mean difference in 8-week time in T-DSM-IV hyperactivity subscale and total scores of parent and teacher forms; inattention subscale scores of only parent forms and the CGI- severity subscale scores; differed significantly among the ADHD/I and ADHD/C groups; that ADHD/C types responded better to medication. Results of this study revealed that atomoxetine is effective both in ADHD/I and ADHD/C subtypes. ADHD/C types may be responding better to atomoxetine treatment than the ADHD/I subtypes.     

Cost-Effectiveness Analysis of Acupuncture,Counselling and Usual Care in Treating Patients with Depression: The Results of the ACUDep Trial

Background

New evidence on the clinical effectiveness of acupuncture plus usual care (acupuncture) and counselling plus usual care (counselling) for patients with depression suggests the need to investigate the health-related quality of life and costs of these treatments to understand whether they should be considered a good use of limited health resources.

Methods and Findings

The cost-effectiveness analyses are based on the Acupuncture, Counselling or Usual care for Depression (ACUDep) trial results. Statistical analyses demonstrate a difference in mean quality adjusted life years (QALYs) and suggest differences in mean costs which are mainly due to the price of the interventions. Probabilistic sensitivity analysis is used to express decision uncertainty. Acupuncture and counselling are found to have higher mean QALYs and costs than usual care. In the base case analysis acupuncture has an incremental cost-effectiveness ratio (ICER) of £4,560 per additional QALY and is cost-effective with a probability of 0.62 at a cost-effectiveness threshold of £20,000 per QALY. Counselling compared with acupuncture is more effective and more costly with an ICER of £71,757 and a probability of being cost-effective of 0.36. A scenario analysis of counselling versus usual care, excluding acupuncture as a comparator, results in an ICER of £7,935 and a probability of 0.91.

Conclusions

Acupuncture is cost-effective compared with counselling or usual care alone, although the ranking of counselling and acupuncture depends on the relative cost of delivering these interventions. For patients in whom acupuncture is unavailable or perhaps inappropriate, counselling has an ICER less than most cost-effectiveness thresholds. However, further research is needed to determine the most cost-effective treatment pathways for depressed patients when the full range of available interventions is considered.     

The Cost-Effectiveness Analysis of Teleglaucoma Screening Device

Glaucoma is the leading cause of irreversible vision loss and costs the American economy $2.9 billion. Teleglaucoma remotely detects glaucoma improving access to ophthalmic care in rural areas. It helps manage glaucoma more efficiently to preserve vision and reduce healthcare costs. A cost-effectiveness analysis was conducted using healthcare provider or third-party payer perspective within rural Canada. The study population were patients at-risk of glaucoma which includes those with diabetes and/or hypertension, family history of glaucoma, adults older than 50 years, and concurrent ocular conditions in rural Alberta. Markov modelling was used to model glaucoma health states. Effectiveness was measured in Quality-Adjusted Life Years (QALYs) and costs were used in Canadian dollars. Using TreeAge Pro 2009, incremental cost-effectiveness ratios (ICER) were developed in dollars per QALYs. Deterministic and probabilistic sensitivity analyses were performed to assess the factors affecting cost-effectiveness. Teleglaucoma had a 20% increase in ophthalmologist-referral rate; it reduced patient travel times by 61 hours and physician wait times by 30% in comparison to in-person examination (standard of care). Teleglaucoma costs $872 per patient screened which was 80% less than in-person examination. Teleglaucoma had a greater incremental effectiveness providing an additional 0.12 QALY per patient examination. It was more sensitive (86.5%) and less specific (78.6%) than in-person examination. Teleglaucoma was more cost-effective than in-person examination with an ICER of-$27,460/QALY. This indicated that teleglaucoma will save $27, 460 for each additional QALY gained. Long term benefits showed teleglaucoma prevents 24% cases of glaucoma blindness after 30 years. Teleglaucoma demonstrated improved health outcomes, as well as, cost benefits. It increases access to ophthalmic care and improves healthcare service efficiency, specifically in rural areas. Teleglaucoma is more cost-effective than current in-person examination and can improve the quality of life in glaucoma patients.     

Cost effectiveness analysis of a randomised trial of acupuncture for chronic headache in primary care

Objective To evaluate the cost effectiveness of acupuncture in the management of chronic headache.Design Cost effectiveness analysis of a randomised controlled trial.Setting General practices in England and Wales.Participants 401 patients with chronic headache, predominantly migraine.Interventions Patients were randomly allocated to receive up to 12 acupuncture treatments over three months from appropriately trained physiotherapists, or to usual care alone.Main outcome measure Incremental cost per quality adjusted life year (QALY) gained.Results Total costs during the one year period of the study were on average higher for the acupuncture group (£403; $768; €598) than for controls (£217) because of the acupuncture practitioners'' costs. The mean health gain from acupuncture during the one year of the trial was 0.021 quality adjusted life years (QALYs), leading to a base case estimate of £9180 per QALY gained. This result was robust to sensitivity analysis. Cost per QALY dropped substantially when the analysis incorporated likely QALY differences for the years after the trial.Conclusions Acupuncture for chronic headache improves health related quality of life at a small additional cost; it is relatively cost effective compared with a number of other interventions provided by the NHS.     

Cost-Effectiveness of New Cardiac and Vascular Rehabilitation Strategies for Patients with Coronary Artery Disease

Objective

Peripheral arterial disease (PAD) often hinders the cardiac rehabilitation program. The aim of this study was evaluating the relative cost-effectiveness of new rehabilitation strategies which include the diagnosis and treatment of PAD in patients with coronary artery disease (CAD) undergoing cardiac rehabilitation.

Data Sources

Best-available evidence was retrieved from literature and combined with primary data from 231 patients.

Methods

We developed a Markov decision model to compare the following treatment strategies: 1. cardiac rehabilitation only; 2. ankle-brachial index (ABI) if cardiac rehabilitation fails followed by diagnostic work-up and revascularization for PAD if needed; 3. ABI prior to cardiac rehabilitation followed by diagnostic work-up and revascularization for PAD if needed. Quality-adjusted-life years (QALYs), life-time costs (US $), incremental cost-effectiveness ratios (ICER), and gain in net health benefits (NHB) in QALY equivalents were calculated. A threshold willingness-to-pay of $75 000 was used.

Results

ABI if cardiac rehabilitation fails was the most favorable strategy with an ICER of $44 251 per QALY gained and an incremental NHB compared to cardiac rehabilitation only of 0.03 QALYs (95% CI: −0.17, 0.29) at a threshold willingness-to-pay of $75 000/QALY. After sensitivity analysis, a combined cardiac and vascular rehabilitation program increased the success rate and would dominate the other two strategies with total lifetime costs of $30 246 a quality-adjusted life expectancy of 3.84 years, and an incremental NHB of 0.06 QALYs (95%CI:−0.24, 0.46) compared to current practice. The results were robust for other different input parameters.

Conclusion

ABI measurement if cardiac rehabilitation fails followed by a diagnostic work-up and revascularization for PAD if needed are potentially cost-effective compared to cardiac rehabilitation only.     

Economic Appraisal of Ontario's Universal Influenza Immunization Program: A Cost-Utility Analysis

Background

In July 2000, the province of Ontario, Canada, initiated a universal influenza immunization program (UIIP) to provide free seasonal influenza vaccines for the entire population. This is the first large-scale program of its kind worldwide. The objective of this study was to conduct an economic appraisal of Ontario''s UIIP compared to a targeted influenza immunization program (TIIP).

Methods and Findings

A cost-utility analysis using Ontario health administrative data was performed. The study was informed by a companion ecological study comparing physician visits, emergency department visits, hospitalizations, and deaths between 1997 and 2004 in Ontario and nine other Canadian provinces offering targeted immunization programs. The relative change estimates from pre-2000 to post-2000 as observed in other provinces were applied to pre-UIIP Ontario event rates to calculate the expected number of events had Ontario continued to offer targeted immunization. Main outcome measures were quality-adjusted life years (QALYs), costs in 2006 Canadian dollars, and incremental cost-utility ratios (incremental cost per QALY gained). Program and other costs were drawn from Ontario sources. Utility weights were obtained from the literature. The incremental cost of the program per QALY gained was calculated from the health care payer perspective. Ontario''s UIIP costs approximately twice as much as a targeted program but reduces influenza cases by 61% and mortality by 28%, saving an estimated 1,134 QALYs per season overall. Reducing influenza cases decreases health care services cost by 52%. Most cost savings can be attributed to hospitalizations avoided. The incremental cost-effectiveness ratio is Can$10,797/QALY gained. Results are most sensitive to immunization cost and number of deaths averted.

Conclusions

Universal immunization against seasonal influenza was estimated to be an economically attractive intervention. Please see later in the article for the Editors'' Summary