Changing pattern of referral to a diabetes clinic following implementation of the new UK GP contract

BACKGROUND: The aim of this study was to determine the impact of the new GMS contract on referral patterns to a secondary care diabetes clinic. All new patient referrals received from primary care to a hospital diabetes service were surveyed. No significant change in referrals was seen 6 months after implementation of the GMS contract. There was, however, an increase in referrals for poor glycaemic control after implementation of the new GMS contract, and the glycaemic threshold for referral with poor glycaemic control has reduced (9.7% versus 10.6%, P = 0.006, mean difference = 0.9% [95% confidence interval = 0.4 to 1.3%]).     

Spurious trends in coronary heart disease incidence: unintended consequences of the new GP contract?

Comparisons of the same patient data in 2004 and 2006 downloads of the DIN-LINK UK primary care database demonstrated unexpected differences in the rates of coronary heart disease between the datasets. Incidence rates were lower between 1996-2003 in the new (2006) download. Patient record checks demonstrated that coronary heart disease codes had been removed in the new download during the run-up to the new contract. Planners need to be aware of such issues when evaluating trends in CHD or other similar conditions.     

GP job satisfaction in view of contract reform: a national survey

BACKGROUND: Job satisfaction has been associated with intentions to quit and aspects of quality of care. In 2001, GP job satisfaction in England had fallen to its lowest point for over a decade. AIM: To assess GP job satisfaction and stressors immediately prior to implementation of the 2004 contract. DESIGN OF STUDY: National survey of a random sample of GPs. SETTING: England. METHOD: One thousand, nine hundred and fifty principal and salaried GPs surveyed in February 2004 were compared with 1828 principals surveyed in 1998 and 1841 principal and salaried GPs surveyed in 2001. Job satisfaction and stressor scores were adjusted for 2004 age-sex distributions. Determinants of overall satisfaction were examined through ordinary least squares regression. RESULTS: The 2004 response rate was 53%. GPs were most dissatisfied with hours of work, recognition for good work and remuneration, and experienced most pressure from paperwork, increasing workloads and having insufficient time. The majority of doctors were satisfied with their job overall. Satisfaction was higher than in 2001 and approximately the same as in 1998. Overall stress in 2004 was lower than in 2001 but still higher than in 1998. After allowing for personal, practice and job characteristics, higher satisfaction was associated with lower job stress, involvement in decision making, increasing job interest and ability to meet conflicting demands. CONCLUSIONS: Despite recent initiatives to enhance workforce capacity and working lives for GPs, workload, time pressures and job control remain potential areas of concern. Addressing such issues may be key to maintaining morale as the new contract is implemented.     

Physicochemical and Functional Comparability Between the Proposed Biosimilar Rituximab GP2013 and Originator Rituximab

Background

Regulatory approval for a biosimilar product is provided on the basis of its comparability to an originator product. A thorough physicochemical and functional comparability exercise is a key element in demonstrating biosimilarity. Here we report the characterization of a proposed biosimilar rituximab (GP2013) and originator rituximab.

Objective

To compare GP2013 with originator rituximab using an extensive array of routine analytical and extended characterization methods.

Methods

Primary and higher order protein structures were analyzed using a variety of methods that included high-performance liquid chromatography electrospray ionization mass spectrometry (HPLC-ESI-MS), peptide mapping with UV and MS detection, circular dichroism (CD), Fourier transform infrared (FTIR) spectroscopy, hydrogen deuterium exchange (HDX) MS, 1D ¹H nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography and differential scanning calorimetry (DSC). Charge and amino acid modifications were assessed using cation exchange chromatography (CEX) and peptide mapping using reversed-phase (RP) HPLC. Boronate affinity chromatography was used to determine the relative amount of glycation. Glycans were identified and quantified after 2-aminobenzamide (2-AB) labeling and separation using normal phase HPLC with fluorescence and MS detection, respectively. Glycan site occupancy was determined using reducing capillary electrophoresis with sodium dodecyl sulfate (CE-SDS). Size heterogeneity was determined using reducing and non-reducing CE-SDS, size exclusion chromatography (SEC) and asymmetric flow field flow fractionation (AF4). Biological characterization included a series of bioassays (in vitro target binding, antibody-dependent cell-mediated cytotoxicity [ADCC], complement-dependent cytotoxicity [CDC] and apoptosis) and surface plasmon resonance (SPR) Fc receptor binding assays.

Results

Intact mass analysis of GP2013 and the heavy and light chains using RP HPLC–ESI–MS revealed the expected molecular mass of rituximab. The amino acid sequence was shown to be identical between GP2013 and the originator rituximab. Further sequence confirmation using RP-HPLC-UV/MS peptide mapping showed non-distinguishable chromatograms for Lys-C digested GP2013 and originator rituximab. The higher order structure of GP2013 was shown to be indistinguishable from originator rituximab using a large panel of redundant and orthogonal methods. GP2013 and originator rituximab were comparable with regard to charge variants, specific amino acid modifications and the glycan pattern. GP2013 was also shown to have similar purity, aggregate and particle levels when compared with the originator. Functionally, and by using a comprehensive set of bioassays and binding assays covering a broad range of rituximab’s functional activities, GP2013 could not be distinguished from originator rituximab.

Conclusion

GP2013 was shown to be physicochemically highly similar to originator rituximab at the level of primary and higher order structure, post-translational modifications and size variants. An extensive functional characterization package indicated that GP2013 has the same biological properties as originator rituximab.