A family of six structurally related heteroleptic copper(I) complexes of the form of [Cu(N^N)(P^P)]+ bearing a 2,9-dimethyl-1,10-phenanthroline diimine (N^N) ligand and a series of electronically tunable xantphos (P^P) ligands have...

Exploration of chemical composition and structural configuration space is the central problem in crystal structure prediction. Even in limiting structure space to a single structure type, many different compositions and...

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of rituximab for the first-line treatment of stage III/IV follicular non-Hodgkin’s lymphoma (FNHL) based upon the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The manufacturer’s scope restricts the intervention to rituximab in combination with CVP (cyclophosphamide, vincristine and prednisolone) (R-CVP); the only comparator used was CVP alone. The evidence from the one included randomised controlled trial (RCT) suggests that the addition of rituximab to a CVP chemotherapy regimen has a positive effect on the outcomes of time to treatment failure, disease progression, overall tumour response, duration of response and time to new lymphoma treatment in patients with stage III/IV FNHL compared with CVP alone. Adverse events were comparable between the two arms. This study was confirmed as the only relevant RCT. The economic analyses provided by the manufacturer were modelled using a three-state Markov model with with the health states being defined as progression-free survival (PFS), progressed (in which patients have relapsed) and death (which is an absorbing state). The model generated results for a cohort of patients with an initial age of 53 and makes no distinction between men and women. The model is basic in design, with several serious design flaws and key parameter values that are probably incompatible. Attempting to rectify the identified errors and limitations of the model did not increase the incremental cost-effectiveness ratio (ICER) above £30,000. Although the cost-effectiveness results obtained appear to be compelling in support of R-CVP compared with CVP for the trial population the results may not be so convincing for a more representative population. The results of the ERG analysis on the impact of age suggest that ICERs increase steadily with age, as the proportion of PFS that can be converted to overall survival (OS) is diminished by rising mortality rates in the general population. For the most extreme scenario (no OS gain) the ICER appears to remain below £30,000 per QALY gained. On balance the evidence indicates that R-CVP is more cost-effective than CVP. The guidance issued by NICE in July 2006 as a result of the STA states that rituximab within its licensed indication (in combination with cyclophosphamide, vincristine and prednisolone) is recommended as an option for the treatment of symptomatic stage III/IV follicular non-Hodgkin’s lymphoma in previously untreated patients.

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Exploration of chemical composition and structural configuration space is the central problem in crystal structure prediction. Even in limiting structure space to a single structure type, many different compositions and configurations are possible. In this work, we attempt to address this problem using an extension to the existing ChemDASH code in which variable compositions can be explored. We show that ChemDASH is an efficient method for exploring a fixed-composition space of spinel structures and build upon this to include variable compositions in the Mn-Fe-Zn-O spinel phase field. This work presents the first basin-hopping crystal structure prediction method that can explore variable compositions.