A post hoc analysis of Projected Retained Ability Scores (PRAS) for the longitudinal assessment of cognitive functioning in patients with neuronopathic mucopolysaccharidosis II receiving intrathecal idursulfase-IT.

BACKGROUND: Norm-based scores used to assess cognitive ability have clinical value when describing functioning of patients with neuronopathic disorders compared with unaffected, same-age peers. However, they have limitations when used to assess change in cognitive ability between two timepoints, especially in children with severe cognitive decline. Calculation of Projected Retained Ability Scores (PRAS) is a novel method developed to characterize absolute change in norm-based ability test scores. In this analysis, PRAS were calculated post hoc for children with mucopolysaccharidosis II (MPS II; Hunter syndrome) and early cognitive impairment in a 52-week phase 2/3 randomized controlled trial (RCT) and its extension study of intrathecal idursulfase (idursulfase-IT). Patients completing the first year of the extension after receiving idursulfase-IT in the RCT and extension (n = 32 of 34 enrolled) or the extension only (n = 15 of 15 enrolled) were categorized according to changes in Differential Ability Scales, Second Edition, General Conceptual Ability (DAS-II GCA) scores and PRAS at 1 and 2 years. Analyses were conducted in the overall population and a subpopulation aged < 6 years at baseline (idursulfase-IT in the RCT and extension [n = 27] and extension only [n = 12]). RESULTS: PRAS methodology differentiated patients with decreases in DAS-II GCA scores into three separate categories reflecting below-average cognitive growth rates, plateauing cognitive development, and deteriorating cognitive functioning. After 1 year in the RCT, 72.4% of patients who initiated idursulfase-IT had above-average or average cognitive growth rates in DAS-II GCA scores compared with 53.3% of those who did not receive idursulfase-IT; 6.9% versus 20.0% experienced deteriorating cognitive functioning. Similar results were seen in children aged < 6 years: 76% (idursulfase-IT group) versus 50% (no idursulfase-IT) had above-average or average cognitive growth rates in DAS-II GCA scores; 4% versus 17% had deteriorating cognitive functioning. The difference in the distributions of cognitive categories at 1 year in children aged < 6 years was significant (p = 0.048). At 2 years, the proportions of patients in different cognitive categories were more similar between treatment groups. CONCLUSIONS: PRAS methodology may help to differentiate changes in cognitive development in MPS II, and therefore may represent a valuable addition to existing approaches for interpreting changes in cognitive scores over time. TRIAL REGISTRATION: ClinicalTrials.gov NCT02055118 (registration date: 4 February 2014) and NCT02412787 (registration date: 9 April 2015).

Agomelatine Drug Utilisation Study in Selected European Countries: A Multinational, Observational Study to Assess Effectiveness of Risk-Minimisation Measures.

BACKGROUND: Hepatotoxic reactions are an important identified risk listed in the agomelatine risk management plan. This post-authorisation safety study evaluated the effectiveness of additional risk-minimisation measures (aRMMs) for agomelatine. OBJECTIVE: The objective of this study was to evaluate, among physicians prescribing agomelatine and their patients, liver function monitoring adherence, compliance with contraindications and patients' reasons for non-compliance with liver monitoring. METHODS: A non-interventional cohort study was conducted among adults initiating agomelatine in routine clinical practice in Denmark, France, Germany and Spain through a retrospective medical record abstraction (MRA) before and after implementation of aRMMs and a cross-sectional patient survey. RESULTS: Fifty-four sites contributed data on 437 and 404 patients in the before- and after-RMM periods, and 237 patients completed the survey. No patient had cirrhosis in either study period; 98.2% of patients in the before- and 98.0% in the after-RMM period had no active liver disease reported at initiation or during treatment. Compliance to contraindicated medications was > 99% in both periods. The adherence to the liver-monitoring regimen was similar in both periods (15.1% before RMM and 16.3% after RMM). In the after-RMM period, 25.2% of patients had a liver test before or at treatment initiation; 61.5% had a liver test during treatment. Among patients surveyed who did not have a blood test before treatment initiation or during treatment, the most frequently cited reason was a test ordered but not yet performed. CONCLUSIONS: The overall adherence to liver-monitoring recommendations remained weakly influenced by aRMMs. However, patients treated with agomelatine are in compliance with relevant contraindications.

Adjuvant treatment patterns and outcomes in patients with stage IB-IIIA non-small cell lung cancer in France, Germany, and the United Kingdom based on the LuCaBIS burden of illness study.

OBJECTIVES: To inform health-technology assessments of new adjuvant treatments, we describe treatment patterns in patients with complete resection of stage IB-IIIA non-small cell lung cancer (NSCLC) in France, Germany, and the United Kingdom (UK). MATERIALS AND METHODS: Data were collected via medical record abstraction. Patients were aged ≥18 years with completely resected stage IB-IIIA NSCLC, diagnosed between 01 January 2009 and 31 December 2011. Median follow-up was 26 months. Adjuvant treatment patterns and clinical outcomes were summarized descriptively. RESULTS: Among the 831 patients studied, 239 (29%) had stage IB disease, 179 (22%) had stage IIA disease, 165 (20%) had stage IIB disease, and 248 (30%) had stage IIIA disease. Adjuvant systemic therapy was received by 402 patients (48.4%), (France, 61.8%; Germany, 51.9%; UK, 33.4%). Use of adjuvant therapy increased with increasing stage of disease. Cisplatin/vinorelbine and carboplatin/vinorelbine were the most frequently prescribed adjuvant regimens. Median disease-free survival was 48.0 months (95% confidence interval [CI] 42.3-not estimable); the 25th percentile was 13.2 months (95% CI, 11.0-15.3). 204 patients (24%) died during the follow-up period. The median overall survival was not reached, the 25th percentile was 31.2 months (95% CI 26.8-36.0 months). 272 patients (33%) had disease recurrence during the follow-up period. For 86 of those patients, the first recurrence was local or regional with no distant metastasis and 14 had further progression to metastatic disease during the follow-up time. For the other 186 patients, the first recurrence involved distant metastases. A total of 200 patients had metastatic disease at any time during study follow-up. CONCLUSIONS: Less than half the patients with stage IB-IIIA NSCLC in this observational study received adjuvant systemic therapy. A high rate of first recurrence with distant metastatic disease was observed, emphasising the need for more effective systemic adjuvant therapies in this population.

Economic burden of resected (stage IB-IIIA) non-small cell lung cancer in France, Germany and the United Kingdom: A retrospective observational study (LuCaBIS).

OBJECTIVES: New adjuvant treatments are being developed for patients with resected non-small cell lung cancer (NSCLC). Due to scarcity of real-world data available for treatment costs and resource utilization, health technology and cost-effectiveness assessments can be limited. We estimated the burden and cost-of-illness associated with completely resected stage IB-IIIA NSCLC in France, Germany and the United Kingdom (UK). MATERIALS AND METHODS: Eligible patients were aged ≥18 years with completely resected stage IB-IIIA NSCLC between August 2009 and July 2012. Patients (living or deceased) were enrolled at clinical sites by a systematic sampling method. Data were obtained from medical records and patient surveys. Direct, indirect and patient out-of-pocket expenses were estimated by multiplying resource use by country-specific unit costs. National annual costs were estimated based on disease prevalence data available from published sources. RESULTS: 39 centers provided data from 831 patients of whom patient surveys were evaluable in 306 patients. Median follow-up was 26 months. The mean total direct costs per patient during follow-up were: €19,057 (France), €14,185 (Germany), and €8377 (UK). The largest cost drivers were associated with therapies received (€12,375 France; €3694 UK), and hospitalization/emergency costs (€7706 Germany). Monthly direct costs per patient were the highest during the distant metastasis/terminal illness phase in France (€15,562) and Germany (€6047) and during the adjuvant treatment period in the UK (€2790). Estimated mean total indirect costs per patient were: €696 (France), €2476 (Germany), and €1414 (UK). Estimates for the annual national direct cost were €478.4 million (France), €574.6 million (Germany) and €325.8 million (UK). CONCLUSION: To our knowledge, this is the first comprehensive study describing the burden of illness for patients with completely resected stage IB-IIIA NSCLC. The economic burden was substantial in all three countries. Treatment of NSCLC is associated with large annual national costs, mainly incurred during disease progression.

Health care resource use analysis of paliperidone palmitate 3 month injection from two phase 3 clinical trials.

OBJECTIVE: The objective of this study was to compare occupational status and health care resource use between treatment groups in clinical trials 3012 (PP3M versus placebo) and 3011 (PP3M versus PP1M). METHODS: Occupational status was assessed at each study visit. Logistic regressions modeled the probability of hospitalization during the double-blind phase. RESULTS: At the start of each study, a low percentage of patients were full-time employed or gainfully self-employed (approximately 10% in trial 3012 and 11%-13% in trial 3011). Improvement from baseline in occupational status was slightly higher in the PP3M group than in placebo or PP1M groups. The odds of a hospitalization for psychiatric and social reasons during 1 year was 7.74 (95% CI, 2.39-25.05; p < .001) for a patient on placebo compared with the odds of hospitalization during 1 year for a patient on PP3M. No statistically significant difference was observed between PP3M and PP1M (odds ratio, 1.16; 95% CI, 0.70-1.93). Very similar results were observed for hospitalizations due to psychiatric reasons only, within each trial. CONCLUSIONS: In both trials, most patients were unemployed and not seeking work or were retired at open-label baseline, and only a small number of patients changed their occupational status during the trials. In trial 3012, subjects who received placebo had significantly higher odds of hospitalization for either psychiatric and social reasons or for psychiatric reasons alone compared with subjects who received PP3M. In contrast, in trial 3011, the odds of hospitalizations were not significantly different between PP3M and PP1M.

Comparative cost-effectiveness analysis of voriconazole and fluconazole for prevention of invasive fungal infection in patients receiving allogeneic hematopoietic cell transplants.

PURPOSE: The cost-effectiveness of voriconazole versus fluconazole prophylaxis against fungal infections in hematopoietic cell transplant (HCT) recipients is investigated. METHODS: A decision-analytic model was developed to estimate the drug costs associated with planned or supplemental prophylaxis and empirical therapy and the costs of treating suspected or documented invasive fungal infections (IFIs) in HCT recipients. Published clinical trial data on 599 patients who received 100-180 days of prophylactic therapy with voriconazole or fluconazole were used to model specified IFI-prevention and mortality outcomes; 6-month, 12-month, and lifetime incremental cost-effectiveness ratios (ICERs) were estimated, with a bootstrap analysis performed to reffect the uncertainty of the clinical trial data. RESULTS: Estimated mean total prophylaxis and IFI-related costs associated with voriconazole versus fluconazole prophylaxis over 12 months were higher in the entire study population and among patients receiving HCT for diagnoses other than acute myeloid leukemia (AML) but were not significantly different for patients with AML. The cost per IFI avoided ($66,919) and the cost per life-year gained ($5,453) were lower among patients with AML who received voriconazole relative to the full study population. ICERs were more favorable for voriconazole over a 6-month time frame and when modeling was conducted using generic price data. Assuming a threshold value of $50,000 for one year of life gained, the calculated probability of voriconazole being cost-effective was 33% for the full study population and 85% for the AML subgroup. CONCLUSION: The decision model indicated that voriconazole prophylaxis was cost-effective for patients undergoing allogeneic HCT for AML.

Drug reimbursement recommendations by the National Institute for Health and Clinical Excellence: have they impacted the National Health Service budget?

OBJECTIVE: Determine whether reimbursement restrictions recommended by the National Institute for Health and Clinical Excellence (NICE) have impacted the United Kingdom (UK) National Health Service (NHS) budget. METHODS: Data were abstracted from NICE guidance documents and costing statements through March 2011. Estimated maximum and adjusted potential budget impact (PBI) on the NHS was derived using estimates of the UK marketing-approved population and the annual cost for the new drug. Descriptive and logistic analyses were used to estimate the correlation between the degree of restrictions on reimbursement recommended by NICE for each new drug indication and the PBI controlling for clinical effectiveness and cost-effectiveness. RESULTS: PBI was significantly correlated with the degree of reimbursement restrictions. In descriptive analysis, the adjusted PBI for drugs that were recommended without restrictions was £20.3 million (SD = 22.2) compared with £49.8 million (SD = 90.8) for those recommended with restrictions and £71.1 million (SE = 99.9) for those not recommended. In logistic analysis, the odds ratio for less restrictive reimbursement was 0.848 (95% CI, 0.762-0.945) for each £20 million increase in the adjusted PBI. Results were similar using the maximum PBI. CONCLUSIONS: After controlling for clinical effectiveness and cost-effectiveness, the degree of reimbursement restriction recommended by NICE remains significantly correlated with the PBI, despite that fact that the NICE decision process does not consider budget impact. This correlation might be due to NICE consideration of effectiveness and cost-effectiveness for subgroups of the approved population.

Relationship between financial impact and coverage of drugs in Australia.

OBJECTIVES: The aim of this study was to estimate the relationship between the financial impact of a new drug and the recommendation for reimbursement by the Australian Pharmaceutical Benefits Advisory Committee (PBAC). METHODS: Data in the PBAC summary database were abstracted for decisions made between July 2005 and November 2009. Financial impact-the upper bound of the values presented in the PBAC summary database-was categorized as ≤A$0, >A$0 up to A$10 million, A$10 million up to A$30 million, and >A$30 million per year. Descriptive, logistic, survival, and recursive partitioning decision analyses were used to estimate the relationship between the financial impact of a new drug indication and the recommendation for reimbursement. Multivariable analyses controlled for other clinical and economic variables, including cost per quality-adjusted life-year gained. RESULTS: Financial impact was a significant predictor of the recommendation for reimbursement. In the logistic analysis, the odds ratios of reimbursement for drug submissions with financial impacts ≥A$10 million to ≥A$30 million or >A$0 to

A controlled trial of a Quit and Win contest.

PURPOSE: To evaluate the impact of a state-of-the-art Quit and Win contest on tobacco quit rates at 3, 6, and 12 months after the 30-day quit period. DESIGN: Quasi-experimental with a volunteer sample of 494 Quit and Win contest registrants (treatment group) and 512 randomly selected tobacco users not exposed to the promotional media campaign (control group). Intervention included a 30-day quit period to be eligible for large cash prizes; provider advice via weekly mailings; online and telephone quit assistance; media campaign; and community support. SETTING: Community-based intervention in Kentucky. SUBJECTS: A total of 1006 adult tobacco users. MEASURES: Quit rates were measured using 7-day point prevalence for tobacco use. Urine cotinine measurements confirmed self-reported quitting. RESULTS: Treatment group participants were significantly more likely than controls to experience quitting during the 1-year follow-up, as determined by both self-report and urine confirmation. After adjusting for baseline differences in demographics, tobacco use, and stage of change, those in the treatment group had 2.6 times the odds of reporting quitting in the postintervention period and 5.3 times the odds of experiencing quitting confirmed by urine cotinine, relative to controls. Women, minorities, and low-income tobacco users had equal odds of quitting as men, whites, and those with higher incomes. CONCLUSIONS: That the contest was minimally intensive and yielded a relatively high, quit rate demonstrates the potential effectiveness of the intervention.

Effectiveness of a quit and win contest with a low-income population.

BACKGROUND: In a two-group quasi-experimental study, we evaluated the impact of a quit and win contest on quitting among low-income tobacco users and identified contest elements used by successful quitters. Low-income tobacco users have been largely untouched by tobacco cessation approaches. METHODS: A volunteer sample of 248 low-income tobacco users were recruited from quit and win contest registrants (treatment group). A random sample of 290 low-income tobacco users who had not entered the contest were recruited using random digit dialing (control group). Telephone interviews were conducted with both groups at baseline, 3, 6, and 12 months. Seven-day point prevalence measured self-reported quitting and urine cotinine assessed confirmed quitting. RESULTS: On average, quit and win study participants were 3.5 times more likely than controls to self-report quitting and 12.8 times more likely to demonstrate confirmed quitting after controlling for baseline differences in stage of change, age, education, and marital status. The use of specific contest elements was not related to successful quitting. CONCLUSIONS: The overall quit rates in the treatment group were higher than those in the control group. The results are promising given that low-income tobacco users are generally less likely to succeed in quitting.