Target plasma factor levels for personalized treatment in haemophilia: a Delphi consensus statement.

BACKGROUND: Prophylactic replacement with factor concentrate is the optimal treatment for persons with severe haemophilia to avoid or minimize bleeding. This ultimately prevents or reduces joint disease and improves life expectancy and quality of life towards values matching those in the normal population. However, uncertainty still exists around the optimal regimens to be prescribed for prophylaxis. An increasing number of treating physicians and patients are showing interest in patient-tailored approaches to prophylaxis, which aim to harmonize the prophylaxis regimen with the patients' bleeding phenotype, levels of physical activity and a variety of other variables. METHODS: A modified Delphi technique was adopted to generate consensus. The expert panel met in person to set the objectives, be trained on the Delphi technique and agree on the desired level of consensus. Three iterations were used to identify the targets, the scenarios and their combinations. RESULTS: Twenty-eight scenarios and eight target levels were identified and used to issue recommendations. The panel reached the desired level of consensus on positive or negative recommendations. Areas where consensus was not reached were identified and proposed as areas for future research. Prospective assessment of the validity of most of the proposed targets is recommended. CONCLUSIONS: We have generated, by expert consensus, target plasma levels of factor concentrate to be used to tailor treatment for persons with haemophilia.

The clinical relevance and newsworthiness of NIHR HTA-funded research: a cohort study.

OBJECTIVE: To assess the clinical relevance and newsworthiness of the UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme funded reports. STUDY DESIGN: Retrospective cohort study. SETTING: The cohort included 311 NIHR HTA Programme funded reports publishing in HTA in the period 1 January 2007-31 December 2012. The McMaster Online Rating of Evidence (MORE) system independently identified the clinical relevance and newsworthiness of NIHR HTA publications and non-NIHR HTA publications. The MORE system involves over 4000 physicians rating publications on a scale of relevance (the extent to which articles are relevant to practice) and a scale of newsworthiness (the extent to which articles contain news or something clinicians are unlikely to know). MAIN OUTCOME MEASURES: The proportion of reports published in HTA meeting MORE inclusion criteria and mean average relevance and newsworthiness ratings were calculated and compared with publications from the same studies publishing outside HTA and non-NIHR HTA funded publications. RESULTS: 286/311 (92.0%) of NIHR HTA reports were assessed by MORE, of which 192 (67.1%) passed MORE criteria. The average clinical relevance rating for NIHR HTA reports was 5.48, statistically higher than the 5.32 rating for non-NIHR HTA publications (mean difference=0.16, 95% CI 0.04 to 0.29, p=0.01). Average newsworthiness ratings were similar between NIHR HTA reports and non-NIHR HTA publications (4.75 and 4.70, respectively; mean difference=0.05, 95% CI -0.18 to 0.07, p=0.402). NIHR HTA-funded original research reports were statistically higher for newsworthiness than reviews (5.05 compared with 4.64) (mean difference=0.41, 95% CI 0.18 to 0.64, p=0.001). CONCLUSIONS: Funding research of clinical relevance is important in maximising the value of research investment. The NIHR HTA Programme is successful in funding projects that generate outputs of clinical relevance.

Can computerized clinical decision support systems improve diabetes management? A systematic review and meta-analysis.

AIMS: To systematically review randomized trials that assessed the effects of computerized clinical decision support systems in ambulatory diabetes management compared with a non-computerized clinical decision support system control. METHODS: We included all diabetes trials from a comprehensive computerized clinical decision support system overview completed in January 2010, and searched EMBASE, MEDLINE, INSPEC/COMPENDEX and Evidence-Based Medicine Reviews (EBMR) from January 2010 to April 2012. Reference lists of related reviews, included articles and Clinicaltrials.gov were also searched. Randomized controlled trials of patients with diabetes in ambulatory care settings comparing a computerized clinical decision support system intervention with a non-computerized clinical decision support system control, measuring either a process of care or a patient outcome, were included. Screening of studies, data extraction, risk of bias and quality of evidence assessments were carried out independently by two reviewers, and discrepancies were resolved through consensus or third-party arbitration. Authors were contacted for any missing data. RESULTS: Fifteen trials were included (13 from the previous review and two from the current search). Only one study was at low risk of bias, while the others were of moderate to high risk of bias because of methodological limitations. HbA1c (3 months' follow-up), quality of life and hospitalization (12 months' follow-up) were pooled and all favoured the computerized clinical decision support systems over the control, although none were statistically significant. Triglycerides and practitioner performance tended to favour computerized clinical decision support systems although results were too heterogeneous to pool. CONCLUSIONS: Computerized clinical decision support systems in diabetes management may marginally improve clinical outcomes, but confidence in the evidence is low because of risk of bias, inconsistency and imprecision.