The effect of different treatment durations of clopidogrel in patients with non-ST-segment elevation acute coronary syndromes: a systematic review and value of information analysis.

OBJECTIVE: To update the previous systematic review of the use of clopidogrel in combination with aspirin for patients with non-ST-elevation acute coronary syndrome (NSTE-ACS), investigating the optimal duration of treatment and effects of withdrawal from treatment. DATA SOURCES: Ten electronic databases and internet resources were searched from 2003 to February 2007, including MEDLINE, MEDLINE In-Process, EMBASE, BIOSIS, CENTRAL and CINAHL. REVIEW METHODS: Randomised controlled trials (RCTs) of clopidogrel plus aspirin compared with aspirin alone were used to evaluate clinical effectiveness and safety. Inclusion criteria included any comparator trial for duration of treatment studies, and any study design conducted in patients with NSTE-ACS, percutaneous coronary intervention (PCI), stroke, peripheral artery disease (PAD) or ST-elevation myocardial infarction (STEMI) for evidence of rebound on withdrawal of treatment. The existing model was updated to provide a more robust approach to evaluating the cost-effectiveness of alternative durations of clopidogrel and to assess the potential value of further research using value of information approaches. RESULTS: Two RCTs were included for the review of clinical effectiveness and safety. The only RCTs identified that evaluated different durations of clopidogrel treatments were conducted in patients with stroke, PAD, STEMI or PCI. Two small RCTs and one uncontrolled retrospective cohort study were identified for the review of rebound after thienopyridine withdrawal in patients with medically-treated NSTE-ACS. On broadening the criteria, five RCTs, two observational cohorts, nine case series and 33 case reports were identified in patients post-PCI, and two case series and two case reports were identified in patients with stroke, PAD or STEMI. The CURE trial reported that the proportion of patients experiencing cardiovascular death, myocardial infarction or stroke was lower in the clopidogrel group at 30 days [relative risk (RR) 0.79; 95% confidence interval (CI) 0.67-0.92] and from 30 days to 12 months (RR 0.82; 95% CI 0.70-0.95). Clopidogrel seems to be effective in reducing adverse cardiovascular events in patients with NSTE-ACS at intermediate and high risk of ischaemic events, and appears to increase the risk of bleeding when compared with aspirin in patients with intermediate risk of ischaemic events. In terms of the cost-effectiveness of alternative durations of clopidogrel, the updated model reinforced the conclusions from the earlier analysis, i.e. a policy of 12 months of clopidogrel for patients with NSTE-ACS appears to be cost-effective in both 'average' patients and higher-risk patients. The incremental cost-effectiveness (ICER) of 12 months' duration ranged from 13,380 pounds to 20,661 pounds per additional quality-adjusted life-year (QALY) across the different scenarios. For lower-risk patients, treatment beyond 3 months does not appear to be cost-effective. The ICER of 12 months' treatment with clopidogrel varied between 49,436 pounds and 58,691 pounds per QALY. Estimates of expected value of perfect information (EVPI) were higher for the combined analysis and for analysis of high-risk patients alone (between 48.69 million pounds and 108.4 million pounds at a threshold of 30,000 pounds per QALY). At a threshold of 20,000 pounds-30,000 pounds per QALY, total EVPI ranged between 3.27 million pounds and 20.38 million pounds in the lower-risk group. CONCLUSIONS: The review was limited by the lack of available data. There is considerable variation in the costs of uncertainty surrounding the different scenarios and populations considered. The validity of these may also be less reliable in the higher-risk groups owing to changes in clinical practice. An adequately powered, well-conducted RCT that directly compares different durations of clopidogrel treatment in patients with NSTE-ACS would ideally be required to provide more robust evidence in relation to the impact of clopidogrel withdrawal.

The impact of the Calman-Hine report on the processes and outcomes of care for Yorkshire's breast cancer patients.

BACKGROUND: The 1995 Calman-Hine plan outlined radical reform of the UK's cancer services with the aim of improving outcomes and reducing inequalities in National Health Service cancer care. Its main recommendation was to concentrate care into the hands of site-specialist multidisciplinary teams. This study aimed to determine whether these teams improved processes and outcomes of care for breast cancer patients. PATIENTS AND METHODS: All patients diagnosed and treated with breast cancer in the Yorkshire region of the UK from 1995 to 2000 were identified within the Northern and Yorkshire Cancer Registry and Information Service database. Changes in the use of breast-conserving surgery, adjuvant radiotherapy following breast-conserving surgery and 5-year survival were assessed among these patients in relation to their managing breast cancer team's degree of adherence to the manual of cancer service standards (which outlines the specification of the 'ideal' breast cancer team) and the extent of site specialisation of each team's surgeons. RESULTS: Variation was observed in the extent to which the breast cancer teams in Yorkshire had conformed to the Calman-Hine recommendations. Increases in adherence to the recommendations in the manual of cancer service standards were associated with a reduction in the use of breast-conserving surgery [odds ratio (OR) = 0.83, 95% confidence interval (CI) = 0.70-0.98, P < 0.01]. Increases in both surgical specialisation (OR = 1.23, 95% CI = 1.00-1.55, P = 0.06) and adherence to the manual of cancer service standards (OR = 1.22, 95% CI = 0.97-1.52, P = 0.05) were associated with the increased use of radiotherapy following breast-conserving surgery. There was a trend towards improved 5-year survival (hazard ratio = 0.93, 95% CI = 0.86-1.01, P = 0.10) in relation to increasing surgical site specialisation. All these effects were present after adjustment for the casemix factors of age, stage of disease, socio-economic background and year of diagnosis. CONCLUSIONS: The extent of implementation of the Calman-Hine report has been variable and, on the basis of limited clinical and organisational information available, its recommendations appear to be associated with improvements in processes and outcomes of care for breast cancer patients.

The impact of the Calman-Hine report on the processes and outcomes of care for Yorkshire's colorectal cancer patients.

The 1995 Calman-Hine plan outlined radical reform of the UK's cancer services with the aim of improving outcomes and reducing inequalities in NHS cancer care. Its main recommendation was to concentrate care into the hands of site-specialist, multi-disciplinary teams. This study aimed to determine if the implementation of Calman-Hine cancer teams was associated with improved processes and outcomes of care for colorectal cancer patients. The design included longitudinal survey of 13 colorectal cancer teams in Yorkshire and retrospective study of population-based data collected by the Northern and Yorkshire Cancer Registry and Information Service. The population was all colorectal cancer patients diagnosed and treated in Yorkshire between 1995 and 2000. The main outcome measures were: variations in the use of anterior resection and preoperative radiotherapy in rectal cancer, chemotherapy in Dukes stage C and D patients, and five-year survival. Using multilevel models, these outcomes were assessed in relation to measures of the extent of Calman-Hine implementation throughout the study period, namely: (i) each team's degree of adherence to the Manual of Cancer Service Standards (which outlines the specification of the 'ideal' colorectal cancer team) and (ii) the extent of site specialisation of each team's surgeons. Variation was observed in the extent to which the colorectal cancer teams in Yorkshire had conformed to the Calman-Hine recommendations. An increase in surgical site specialisation was associated with increased use of preoperative radiotherapy (OR=1.43, 95% CI=1.04-1.98, P<0.04) and anterior resection (OR=1.43, 95% CI=1.16-1.76, P<0.01) in rectal cancer patients. Increases in adherence to the Manual of Cancer Service Standards was associated with improved five-year survival after adjustment for the casemix factors of age, stage of disease, socioeconomic status and year of diagnosis, especially for colon cancer (HR=0.97, 95% CI=0.94-0.99 P<0.01). There was a similar trend of improved survival in relation to increased surgical site specialisation for rectal cancer, although the effect was not statistically significant (HR=0.93, 95% CI=0.84-1.03, P=0.15). In conclusion, the extent of implementation of the Calman-Hine report has been variable and its recommendations are associated with improvements in processes and outcomes of care for colorectal cancer patients.

Increased incidence of renal parenchymal carcinoma in the Northern and Yorkshire region of England, 1978-1997.

Kidney cancer remains relatively rare, but incidence and mortality rates are reported to be rising steadily across the world. To determine if such increases were occurring in the UK, we examined the rates of incidence and mortality in different histological subtypes of kidney cancer in the Northern and Yorkshire region of England. Details of all 8741 cases diagnosed between 1978 and 1997 were extracted from the population-based Northern and Yorkshire Cancer Registry. For all types of tumour, both incidence and mortality rates increased over the study period. Overall age-standardised incidence rates increased by 86% for renal parenchymal carcinoma (RPC) (80% for males, 90% for females) from 2.8 to 5.2 cases per 100000 (3.8-6.8 male, 2.0-3.8 female). There were incidence increases in all age groups, all Carstairs index groups and in both urban and rural populations. Although increased incidental detection of kidney tumours by improved investigational techniques may account for some of this rise, we believe it unlikely that it accounts for all of the increase observed. Potential aetiological causes for the increased rates include hypertension, smoking, a diet lacking fruit and vegetables, analgesic use and, particularly, obesity.