Economic Evaluation of Tocilizumab Monotherapy Compared to Adalimumab Monotherapy in the Treatment of Severe Active Rheumatoid Arthritis

AbstractObjectivesTo estimate the cost-effectiveness of tocilizumab (TCZ) monotherapy (Mono) versus adalimumab (ADA) Mono from the US payer perspective in patients with rheumatoid arthritis for whom methotrexate is inappropriate.MethodsWe compared TCZ Mono (8 mg/kg monthly) with ADA Mono (40 mg every other week), using efficacy results from a head-to-head study, ADalimumab ACTemrA (ADACTA). We calculated the incremental cost per responder (achievement of American College of Rheumatology [ACR] 20% improvement criteria, ACR 50% improvement criteria, ACR 70% improvement criteria, or low disease activity score) for TCZ versus ADA at 6 months. A patient-level simulation was used to estimate the lifetime incremental cost per quality-adjusted life-year (QALY) of initiating treatment with TCZ Mono versus ADA Mono. Both drugs are followed by an etanercept-certolizumab-palliative care sequence. Nonresponders discontinue at 6 months; responders experience a constant probability of discontinuation. Discontinuers move to the next treatment. ACR responses produce changes in the Health Assessment Questionnaire (HAQ) score. We mapped the HAQ score to utility to estimate QALYs. Costs include those related to hospitalization and those related to treatment (drug acquisition, administration, and monitoring). Probabilistic and one-way sensitivity analyses were conducted, along with several scenario analyses.ResultsCompared with ADA, TCZ was more effective, with an estimated 6-month incremental cost ranging from $6,570 per additional low disease activity score achiever to$14,265 per additional ACR 70% improvement criteria responder. The lifetime incremental cost-effectiveness ratio was $36,944/QALY.ConclusionsTCZ Mono is projected to be cost-effective compared with ADA Mono in patients with severe rheumatoid arthritis for whom methotrexate is not appropriate, from a US payer perspective

Practitioner and researcher perspectives on the utility of ecological momentary assessment in mental health care:A survey study

Background: Ecological momentary assessment (EMA) is a scientific self-monitoring method to capture individuals' daily life experiences. Early on, EMA has been suggested to have the potential to improve mental health care. However, it remains unclear if and how EMA should be implemented. This requires an in-depth investigation of how practitioners and researchers view the implementation of EMA. Objective: Explore the perspectives of mental health practitioners and EMA researchers on the utility of EMA for mental health care. Methods: Practitioners (n = 89; psychiatrists, psychologists, psychiatric nurses) and EMA researchers (n = 62) completed a survey about EMA in clinical practice. This survey addressed EMA goals for practitioner and patient, requirements regarding clinical use of EMA, and (dis)advantages of EMA compared to treatment-as-usual. t-Tests were used to determine agreement with each statement and whether practitioners' and researchers' views differed significantly. Linear regression was used to explore predictors of goals and preferences (e.g., EMA experience). Results: Practitioners and researchers considered EMA to be a useful clinical tool for diverse stages of care. They indicated EMA to be most useful for gaining insight into the context specificity of symptoms (55.0 %), whereas receiving alerts when symptoms increase was rated the least useful (11.3 %, alerts is in 95 % of bootstrap iterations between rank 8 and 10). Compared to treatment-as-usual, EMA was considered easier to use (M = 4.87, t = 5.30, p < .001) and interpret (M = 4.52, t = 3.61, p < .001), but also more burdensome for the patient (M = 4.48, t = 3.17, p < .001). Although participants preferred personalization of the EMA diary, they also suggested that EMA should cost practitioners and patients limited time. The preference for creating personalized EMA was related to the level of experience with EMA. Finally, they highlighted the need for practitioner training and patient full-time access to the EMA feedback. Conclusions: This survey study demonstrated that practitioners and researchers expect EMA to have added value for mental health care. Concrete recommendations for implementation of EMA are formulated. This may inform the development of specific clinical applications and user-friendly EMA software

Safety and tolerability of flexible dosages of prolonged-release OROS methylphenidate in adults with attention-deficit/hyperactivity disorder

The osmotic release oral system (OROS) methylphenidate formulation is a prolonged-release medication for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. We conducted a seven-week open-label extension of a double-blind study to assess the safety and tolerability of OROS methylphenidate in a flexible dose regimen (18–90 mg daily) for the treatment of adults diagnosed with ADHD (N =370). Medication was adjusted to optimize efficacy and tolerability for each patient. Adverse events, vital signs, and laboratory parameters were assessed. Most patients (337; 91%) completed the seven-week treatment and the final dispensed dose was 18 mg (8%), 36 mg (29%), 54 mg (34%), 72 mg (20%), or 90 mg (9%). Adverse events were reported in 253 (68%) patients and most were mild or moderate in severity; most frequently reported included headache (17%), decreased appetite (13%), and insomnia (11%). Adverse events were rarely serious (<1%; 2/370). Small mean increases in systolic and diastolic blood pressure (both 2.4 mmHg) and pulse (3.2 bpm) were observed. Body weight decreased slightly (−1.5 kg). The results provide additional support for the safety and tolerability of prolonged-release OROS methylphenidate in a flexible dose regimen (18–90 mg/day) for the treatment of adults with ADHD

Functional improvement and correlations with symptomatic improvement in adults with attention deficit hyperactivity disorder receiving long-acting methylphenidate

Item does not contain fulltextBACKGROUND: Data on the relationship between core symptoms and daily functioning in adults with attention deficit hyperactivity disorder (ADHD) are limited. Daily functioning was assessed as part of an open-label extension, and associations with symptom scores were evaluated. METHOD: After a 5-week double-blind study with adults with ADHD receiving osmotic-controlled release oral delivery system (OROS) methylphenidate (MPH) 18, 36 or 72 mg/day, or placebo, participants were eligible for a 7-week open-label extension in which all patients received OROS MPH. Data for the Conners' Adult ADHD Rating Scale - Observer: Screening Version (CAARS-O:SV) (primary endpoint) have been presented previously. Secondary endpoints included the observer self-reported short version of the CAARS (CAARS-S:S) and the Clinical Global Impressions - Severity Scale (CGI-S). Daily functioning and quality of life were assessed using the Sheehan Disability Scale (SDS) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) respectively. In post-hoc analyses, changes in CAARS-O:SV were evaluated in subgroups. Relationships between symptom and functional outcomes were evaluated in a multivariate regression analysis. RESULTS: A total of 370 patients entered the open-label extension. Significant improvements from baseline in CAARS-O:SV were similar regardless of sex, ADHD subtype, prior treatment or psychiatric co-morbidity. Significant improvements from double-blind baseline were also seen for the CAARS-S:S, CGI-S, SDS and Q-LES-Q. Improvements in the CAARS-O:SV Hyperactivity/Impulsivity subscale were associated with improvements in SDS total and subscale scores, and in the Q-LES-Q score at open-label endpoint. Improvements in CAARS-O:SV Inattention subscale and CGI-S scores were not significantly associated with functional changes. CONCLUSIONS: Improvements in ADHD symptoms relating to hyperactivity and impulsivity in adults receiving OROS MPH are associated with improvements in daily functioning and quality of life.1 januari 201

The dynamics of aggregate planning

Recent software developments in system modelling via transfer function analysis now enables a much broader understanding of the dynamics of aggregate planning to be gained. In particular it opens up the possibility of exploiting filter theory as a focal point during algorithm design. This is particularly attractive in view of the fact that we have established, via transfer function models, that there is commonality between HMMS and the order-up-to replenishment rules used extensively within both local and global supply chains. Filter theory allows us to relate these dynamics directly to present-day production planning strategy as observed in much industrial practice. It covers the spectrum of production strategies recently identified as preferred industrial practice. These strategies range from 'level scheduling' (i.e. lean production) right through to 'pure chase' (i.e. agile manufacture) with appropriate simple algorithmic control support via APIOBPCS software

The impact of information enrichment on the Bullwhip effect in supply chains: A control engineering perspective

This paper examines the beneficial impact of information sharing in multi-echelon supply chains. We compare a traditional supply chain, in which only the first stage in the chain observes end consumer demand and upstream stages have to base their forecasts on incoming orders, with an information enriched supply chain where customer demand data (e.g. EPOS data) is shared throughout the chain. Two types of replenishment rules are analysed: order-up-to (OUT) policies and smoothing policies (policies used to reduce or dampen variability in the demand). For the class of OUT policies, we will show that information sharing helps to reduce the bullwhipeffect (variance amplification of ordering quantities in supply chains) significantly, especially at higher levels in the chain. However, the bullwhip problem is not completely eliminated and it still increases as one moves up the chain. For the smoothing policies, we show that information sharing is necessary to reduce order variance at higher levels of the chain. The methodology is based on control systems engineering and allows us to gain valuable insights into the dynamic behaviour of supply chain replenishment rules. We also introduce acontrolengineering based measure to quantify the variance amplification (bullwhip) or variance reduction

Measuring and avoiding the bullwhip effect: A control theoretic approach

An important contributory factor to the bullwhip effect (i.e. the variance amplification of order quantities observed in supply chains) is the replenishment rule used by supply chain members. First the bullwhip effect induced by the use of different forecasting methods in order-up-to replenishment policies is analysed. Variance amplification is quantified and we prove that the bullwhip effect is guaranteed in the order-up-to model irrespective of the forecasting method used. Thus, when production is inflexible and significant costs are incurred by frequently switching production quantities up and down, order-up-to policies may no longer be desirable or even achievable. In the second part of the paper a general decision rule is introduced that avoids variance amplification and succeeds in generating smooth ordering patterns, even when demand has to be forecasted. The methodology is based on control systems engineering and allows important insights to be gained about the dynamic behaviour of replenishment rules

Cognitive biases to healthy and unhealthy food words predict change in BMI

The current study explored the predictive value of cognitive biases to food cues (assessed by emotional Stroop and dot probe tasks) on weight change over a 1-year period. This was a longitudinal study with undergraduate students (N = 102) living in shared student accommodation. After controlling for the effects of variables associated with weight (e.g., physical activity, stress, restrained eating, external eating, and emotional eating), no effects of cognitive bias were found with the dot probe. However, for the emotional Stroop, cognitive bias to unhealthy foods predicted an increase in BMI whereas cognitive bias to healthy foods was associated with a decrease in BMI. Results parallel findings in substance abuse research; cognitive biases appear to predict behavior change. Accordingly, future research should consider strategies for attentional retraining, encouraging individuals to reorient attention away from unhealthy eating cues