T Walley

BACKGROUND: There is an acknowledged gap between research findings and their implementation in clinical practice despite the existence of effective educational interventions. OBJECTIVES: Our aim was to identify what is impeding GPs from pursuing currently recognized good practice and implementing evidence-based guidelines in their management of hypertension in the elderly. METHOD: We carried out a qualitative study using semi-structured interviews conducted during focus group outreach visits to 34 GPs from nine practices in Merseyside involved in an educational programme designed to improve the management of hypertension in the elderly. RESULTS: Several barriers to the implementation of evidence-based guidelines in the management of hypertension in the elderly were identified. These included: doubts about the applicability of trial data to particular patients; the poor adherence of GPs to practice protocols; ageist attitudes of some GPs; the effect of time pressure and financial considerations making the subject a low priority; the absence of an effective computer system; and the absence of an educational mentor. All participants demonstrated a very positive attitude to practice-based education. They also welcomed external audit data, which compared their performance with that of other practices. Single-handed GPs were particularly enthusiastic about this approach as it provided them with the peer pressure they lacked. CONCLUSIONS: In order to bridge the gap between research and practice, educators need to address the various 'barriers to change' amongst practitioners.

OBJECTIVES: To assess the comparative clinical effectiveness and cost-effectiveness of adalimumab, etanercept and infliximab for the treatment of ankylosing spondylitis (AS). DATA SOURCES: Major electronic databases were searched up to November 2005. Unpublished evidence such as conference abstracts, reviews of published economic evaluations, and company submissions to the National Institute for Health and Clinical Excellence (NICE) were also reviewed. REVIEW METHODS: The assessment was conducted according to accepted procedures for conducting and reporting systematic reviews and economic evaluations. Full economic evaluations that compared two or more options for treatment and considered both costs and consequences were eligible for inclusion in the economic literature review. RESULTS: Nine placebo controlled randomised controlled trials (RCTs) were included in the review of clinical effects. These included two studies of adalimumab, five of etanercept and two of infliximab in comparison with placebo (along with conventional management). No RCTs directly comparing anti-tumour necrosis factor-alpha (TNF-alpha) agents were identified. Meta-analyses were conducted for data on Assessment in Ankylosing Spondylitis (ASAS) (20, 50 and 70% improvement), mean change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and mean change in Bath Ankylosing Spondylitis Functional Index (BASFI) at 12 weeks following initiation of anti-TNF-alpha therapy or placebo for all three drugs. Meta-analyses were also conducted at 24 weeks for etanercept and infliximab. Each meta-analysis of anti-TNF-alpha therapy demonstrated statistically significant advantages over placebo, although there was no significant difference between individual anti-TNF-alpha agents. At 12 weeks, ASAS 50% responses were 3.6-fold more likely with anti-TNF-alpha treatment than placebo. Compared with baseline, BASDAI scores were reduced by close to 2 points at 12 weeks. Functional scores (BASFI) were reduced at 12 weeks. Six full economic evaluations (two peer-reviewed published papers, four abstracts) were included in the review. The conclusions among economic evaluations were mixed, although the balance of evidence indicates that over short time-frames anti-TNF-alpha therapies are unlikely to be considered cost-effective. The limitations of the clinical outcome data impose restrictions on the economic assessment of cost-effectiveness. Direct unbiased RCT evidence is only available in the short term. Current assessment tools are limited and at present BASDAI and BASFI are the best available, although not designed for, or ideal for, use in economic evaluations. The review of the three models submitted to NICE identified a number of inherent flaws and errors. The incremental cost-effectiveness ratios (ICERs) of etanercept and adalimumab were roughly similar, falling below an assumed willingness-to-pay threshold of 30,000 pounds. The ICER for infliximab was in the range of 40,000-50,000 pounds per quality-adjusted life-year (QALY). The short-term (12-month) model developed by this report's authors confirmed the large front-loading of costs with a result that none of the three anti-TNF-alpha agents appears cost-effective at the current acceptable threshold, with infliximab yielding much poorer economic results (57,000-120,000 pounds per QALY). The assumptions of the short-term model were used to explore the cost-effectiveness of the use of anti-TNF-alpha agents in the long term. This model is far more speculative than the first since trends and parameter values must be projected far beyond the available evidence. Sensitivity analyses reveal wide variations in estimates of cost over the long term although it is considered unlikely that costs will decrease over time. CONCLUSIONS: The review of clinical data related to the three drugs (including conventional treatment) compared with conventional treatment plus placebo indicates that in the short term (12-24 weeks), the three treatments are clinically effective in relation to assessment of ASAS, BASDAI and BASFI. Indirect comparisons of treatments were limited and did not show a significant difference in effectiveness between the three agents. The short-term economic assessment indicates that none of the three anti-TNF-alpha agents is likely to be considered cost-effective at current acceptability thresholds, with infliximab consistently the least favourable option. There is an absence of evidence concerning a number of limiting factors related to patients suffering from AS, the disease itself and its treatment. In order to obtain robust estimates of the longer term clinical effectiveness and cost-effectiveness of anti-TNF-alpha agents for AS, clinical trials that aim to address these limiting factors need to be conducted.

AIMS: To describe trends in utilization and prescribing of statins and other lipid lowering drugs across Europe from data in routine administrative databases. METHODS: Observational study in EU member states and Norway. Comparison of annual utilization data for lipid lowering agents by class and drug from national administrative databases for reimbursement over the period 1997-2003, measured in DDDs per 1000 inhabitants/day. Prescribed daily doses (PDD) of statins obtained from a commercial database (IMS Health) for 2000 and 2003, and used to calculate numbers of "patient treatment days" (PTD) in each country in each year. Analysis of PTD to explain increased utilization of statins. RESULTS: Use of lipid lowering agents varied among countries (in 2003, highest in Ireland and Norway, and lowest in Italy), but increased in all countries studied (between 2000 and 2003 by 274% in Ireland and by 56% in France). This increase was entirely due to increases in statin use. Prescribed daily doses of statins increased in all countries for which data was available between 2000 and 2003, but still usually fell below the doses used in the major trials of statins. As a result, the numbers of PTDs increased to a lesser extent than suggested by utilization (e.g. by 192% in Ireland and by 35% in France). One-third of the total rise in utilization was explained by increased PDD, and two-thirds by an increase in numbers of PTDs. Statins dominated the markets in all countries, although fibrates remained strong in France and Belgium (approximately 25% of all lipid lowering agents) and to a lesser extent Germany (10%). CONCLUSIONS: Use of statins across Europe has increased hugely over the study period. Some of the increase in use is due to higher prescribed daily doses, but two-thirds is due to increases in numbers of patient days of treatment, either due to more patients treated or less likely to better compliance.