Christian Frois

Inhaled corticosteroids or long-acting β-agonists alone or in fixed-dose combinations in asthma treatment: A systematic review of fluticasone/budesonide and formoterol/salmeterol

BACKGROUND Inhaled corticosteroids (ICSs) and long-acting inhaled beta(2)-agonists (LABAs) are recommended treatment options for asthma. OBJECTIVE This review compares the clinical effectiveness and tolerability of the ICSs fluticasone propionate and budesonide and the LABAs formoterol fumarate and salmeterol xinafoate administered alone or in combination. METHODS A systematic review of the clinical studies available on MEDLINE (database period, 1950-September 2009) was conducted to assess English-language randomized controlled trials in children and adults with asthma. Treatment outcomes included lung function, symptom-free days (SFDs), use of rescue/reliever medications, asthma exacerbations, and tolerability profile. RESULTS Use of fluticasone was associated with significantly greater improvement in lung function and better asthma symptom control than budesonide. Similarly, formoterol was associated with significantly greater improvement in lung function and better asthma symptom control (as measured by less rescue medication use and more SFDs) compared with salmeterol. Single inhaler combination regimens (budesonide/ formoterol and fluticasone/salmeterol) were frequently more effective in improving all treatment outcomes than either monotherapy alone. Across all comparisons, a review of studies in adults and children did not find statistically significant differences in outcomes between the ICS and LABA therapies considered in this research. In general, no differences in tolerability profiles were reported between the ICS and LABA options, although the risk for growth retardation was lower with fluticasone than budesonide and with budesonide/formoterol than with budesonide monotherapy. CONCLUSIONS In this systematic review, fluticasone and formoterol appear to provide improved therapeutic benefits versus budesonide and salmeterol, respectively. Both fluticasone/salmeterol and budesonide/ formoterol combination therapies appeared to be associated with greater improvements in outcomes measures than the corresponding ICS and LABA monotherapies.

Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis.

Objective To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM). Design This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO. Outcome measures Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed. Results 41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: −0.08; 95% credible interval (CrI): −0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; −0.28 to 0.32), degludec (−0.12; −0.42 to 0.20) and premixed insulin (0.26; −0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; −0.31 to 1.71), NPH (−0.76; −1.75 to 0.21) and degludec (−0.63; −1.63 to 0.35), but significantly lower compared with premixed insulin (−1.83; −2.85 to −0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings. Conclusions NMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia compared with NPH and premixed insulin, with glycaemic control comparable to available basal insulin comparators.

Treatment patterns and economic burden of metastatic and recurrent locally-advanced head and neck cancer patients

Abstract Objective: To characterize treatment patterns and measure the economic burden associated with metastatic (mHNC) and recurrent, locally-advanced head and neck cancer (rHNC). Methods: Administrative claims from Medicare- and privately-insured individuals during 2004–2008 were used in this retrospective database study of patients with advanced HNC. Patients diagnosed with HNC were matched 1:1 to cancer-free controls to measure the incremental economic burden of HNC. Outcomes of interest were measured during the 6 months following the date of a secondary tumor diagnosis for metastatic patients or the date of a diagnosis indicating rHNC. To assess treatment patterns, HNC patients were evaluated for the use frequency of treatments (radiotherapy, chemotherapy and surgery). Costs were reported in 2008 US

For a Step Change to Curb the Obesity Epidemic

from a third-party payer perspective and were analyzed using generalized linear models and two-part regression models adjusting for differences in age and baseline Charlson Comorbidity Index (excluding cancer diagnoses) between the HNC and control cohorts. Components of cost included inpatient, outpatient and other medical services as well as pharmacy costs. Results: The mHNC cohort consisted of 1042 patients and the rHNC cohort included 324 patients. The most common treatments for mHNC patients were supportive care (90.2%), radiation therapy (48.5%), surgery (41.9%) and chemotherapy (38.3%). Patients with rHNC frequently received HNC-related supportive care (71.0%), radiation therapy (67.9%) and chemotherapy (27.2%); HNC-related surgery was infrequent (12.7%) during the study period. The 6-month incremental adjusted total costs were

Pricing of Pharmaceuticals: Current Trends and Outlook and the Role of Comparative Effectiveness Research

60,414 per patient for mHNC and

Outcomes-Based Contracting Experience: Research Findings from U.S. and European Stakeholders

21,141 per patient for rHNC (p < 0.0001). Approximately 46–58% of the incremental cost was attributable to outpatient visits, 27–37% to inpatient costs and 11–13% to pharmacy, depending on the HNC cohort. Limitations: The identification of mHNC/rHNC was based on diagnosis codes and treatment patterns with the limitation of the claims database. Conclusions: Metastatic and recurrent, locally-advanced HNC patients frequently receive cancer-related treatments and incur substantial economic burden.

Perceptions and prescribing considerations among US psychiatrists regarding drug–drug interactions associated with oral atypical antipsychotics

Rising obesity levels worldwide have been of increasing public concern since the late 1990s and are now responsible for over one-quarter of total healthcare expenditures in the USA [1]. This special issue of PharmacoEconomics examines a particularly challenging set of issues, with an economic focus: why is the obesity epidemic and its unique burden still growing uncontrolled? how have past efforts to curb it fared? and what other actions are needed to succeed in controlling the epidemic? Contributors to the issue cover a broad range of topics, experience, and perspectives related to obesity. Taken together these articles give some sense of the urgency, challenges, and opportunity for action in this field.

Impact of atypical long-acting injectable versus oral antipsychotics on rehospitalization rates and emergency room visits among relapsed schizophrenia patients: a retrospective database analysis

The pricing of biopharmaceuticals has recently received increasing attention, with many calling into question the current model, particularly following the fiscal crunch that occurred in the wake of the 2008 financial crisis. In this article, we review the key elements of a global biopharmaceutical pricing approach – including its specificities compared to other product pricing, the approaches currently used to price biopharmaceuticals around the world, and the role of comparative effectiveness research (CER) – and discuss key trends and the potential future outlook for the pricing of pharmaceuticals. We argue that – despite significant payer pushback, negative press, and other challenges – the current pharmaceutical pricing model has been extremely successful in delivering transformative new medicines and there does not appear to be a credible alternative model. This is no small feat given the considerable uncertainty and complexity involved in biopharmaceutical decision-making for both payers and manufacturers. At the same time, some adjustments to the current pricing model and CER are identified as necessary to address current access hurdles and payer concerns. In particular, we discuss how the European Union payer-directed pricing model needs to evolve, and how innovators must become more adept at evaluating and communicating appropriately the value of their therapy, to ensure that patients worldwide can benefit from drug innovations without undue delay or barriers to access or reimbursement.

Factors Associated with Adherence to the HEDIS Quality Measure in Medicaid Patients with Schizophrenia.

BACKGROUND Outcomes-based contracts (OBCs), a type of risk-sharing arrangement (RSA), have emerged as a promising avenue for payers to engage with pharmaceutical manufacturers to share risk and improve patient access to medicines via evaluation of real-world outcomes. OBJECTIVE To assess the level of recent OBC activity and stakeholder perceptions of these arrangements, as well as the outlook for future OBC activity from a payer and manufacturer perspective in the United States and EU-5 (France, Germany, Italy, Spain, and the United Kingdom). METHODS Using a structured questionnaire, interviews were conducted with 27 experts, including 14 U.S. payers, 5 EU-5 national payers, and 8 manufacturer pricing/market access executives (4 U.S., 4 EU-5). We also used the University of Washingtons Performance Based Risk-Sharing (PBRS) database and other targeted publicly available information. RESULTS Publicly disclosed information on OBCs understates the level of OBC activity, since many arrangements are confidential. Overall, U.S. and EU-5 interviewees generally expected that 2 to 3 times more OBCs would be implemented in the next 5 years than in the previous 5 years. Key drivers included the introduction of a national OBC framework in Spain, potentially a similar framework in the United Kingdom, a growing sickness fund activity in Germany, and a U.S. movement towards accountable care. Motivation for OBCs varied markedly across markets and stakeholders, with operational feasibility noted as a significant hurdle in the United States and France. Along with improving health outcomes, cost and financial risk reduction were the primary OBC motivators for payers, while potential access or reimbursement gains were key factors for manufacturers. CONCLUSIONS Using direct input from U.S. and EU-5 payer and pharmaceutical manufacturer decision makers, this research suggests that high OBC growth is expected in the EU-5 and, to a more moderate extent, in the United States, particularly if clear, simpler OBC frameworks can be developed. DISCLOSURES This study was funded by Novartis Pharmaceuticals. Novartis employees were involved in all aspects of this study. Vegesna and Sasane are employed by and own stock in Novartis. Nazareth and Ko were employees of Novartis at the time of this study. Frois, Demean, Carpenter, and Wu are or have been employed by Analysis Group, which received a grant from Novartis for this research. Navarro received consulting fees from Novartis for his involvement in this research. Study concept and design were contributed by Sasane, Frois, Nazareth, and Wu. Navarro, Demean, and Frois took the lead in data collection, assisted by Carpenter, Ko, and Nazareth. Data interpretation was provided by Frois, Carpenter, Nazareth, and Ko, along with Sasane, Demean, Wu, and Navarro. The manuscript was written by Frois, Demean, Nazareth, and Ko, along with Sasane, Carpenter, Wu, and Navarro, and revised by Frois, Ko, and Vegesna, along with Sasane, Nazareth, Wu, and Navarro.

Outcomes-Based Pricing And Reimbursement Arrangements For Pharmaceutical Products In The Us And Eu-5: Payer And Manufacturer Experience And Outlook

Abstract Objective: Contemporary literature has demonstrated the potential for drug–drug interactions (DDIs) with oral atypical antipsychotic (OAA) agents. However, less is known about psychiatrists’ perceptions about DDIs when prescribing OAAs. This study addresses this gap by surveying US psychiatrists about their perceptions of DDI when prescribing a new OAA. Methods: An online survey of 131 US psychiatrists was conducted to assess if considerations of DDIs were taken into account when prescribing a new OAA within their practice and prescribing patterns. For each survey question, results are presented as the proportion of psychiatrists in each rating category. Data were collected on physicians’ awareness and concern about DDIs when prescribing OAAs, perception of frequency and severity of OAA-related DDIs, and methods of monitoring and preventing OAA-related DDIs. Results: Of the psychiatrists surveyed, 9.2% considered themselves well-informed (rating of 10/10) about OAA-related DDIs. In the 3-month period preceding the survey date, psychiatrists reported that on average 7.5 (SD 12.4) of their patients experienced a potentially OAA-related DDI event which represented an average of 2.5% (SD 4.8%) of their total number of patients. In all, 19.8% of the psychiatrists reported they were currently tracking the level of confirmed OAA-related DDI events in their practices; these psychiatrists reported a mean 21.1% incidence rate of confirmed DDI events experienced by patients starting a new OAA therapy in their practice. The psychiatrists ranked the risks of cardiovascular events and of neurological impairment as the two most frequent and severe potential DDI events to consider when prescribing a new OAA, in combination with selective serotonin reuptake inhibitors, mood stabilizers, and antihypertensive agents, the drugs most frequently associated with the most severe OAA-related DDIs. Conclusions: Psychiatrists, on recall of recent cases, perceive DDI events to be frequent in patients starting a new OAA therapy. While there appears to be some awareness of DDI-related issues among psychiatrists, this survey of psychiatrists perceptions suggests the need for systematic tracking of OAA-related DDI events and additional psychiatrist training on optimal OAA choice to prevent DDIs.