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Health Technology Assessment... Feb 2010The National Institute for Health and Clinical Excellence (NICE) was reviewing its previous guidance on continuous subcutaneous insulin infusion (CSII). The review... (Review)
Review
BACKGROUND
The National Institute for Health and Clinical Excellence (NICE) was reviewing its previous guidance on continuous subcutaneous insulin infusion (CSII). The review provided an assessment of evidence which had been published since the previous NICE appraisal (TA 151) in 2007.
OBJECTIVES
To examine the clinical effectiveness and cost-effectiveness of using CSII to treat diabetes. To update the previous assessment report by reviewing evidence that has emerged since the last appraisal, and to take account of developments in alternative therapies, in particular the long-acting analogue insulins, which cause fewer problems with hypoglycaemia.
DATA SOURCES
A systematic review of the literature and an economic evaluation were carried out. The bibliographic databases used were MEDLINE and EMBASE, 2002 to June 2007. The Cochrane Library (all sections), the Science Citation Index (for meeting abstracts only) and the website of the 2007 American Diabetes Association were also searched.
REVIEW METHODS
The primary focus for type 1 diabetes mellitus (T1DM) was the comparison of CSII with multiple daily injection (MDI), based on the newer insulin analogues, but trials of neutral protamine Hagedorn (NPH)-based MDI that had been published since the last assessment were identified and described in brief. For type 2 diabetes mellitus (T2DM), all trials of MDI versus CSII were included, whether the long-acting insulin was analogue or not, because there was no evidence that analogue-based MDI was better than NPH-based MDI. Trials that were shorter than 12 weeks were excluded. Information on the patients' perspectives was obtained from four sources: the submission from the pump users group--Insulin Pump Therapy (INPUT); interviews with parents of young children who were members of INPUT; some recent studies; and from a summary of findings from the previous assessment report. Economic modelling used the Center for Outcomes Research (CORE) model, through an arrangement with the NICE and the pump manufacturers, whose submission also used the CORE model.
RESULTS
The 74 studies used for analysis included eight randomised controlled trials (RCTs) of CSII versus analogue-based MDI in either T1DM or T2DM, eight new (since the last NICE appraisal) RCTs of CSII versus NPH-based MDI in T1DM, 48 observational studies of CSII, six studies of CSII in pregnancy, and four systematic reviews. The following benefits of CSII were highlighted: better control of blood glucose levels, as reflected by glycated haemoglobin (HbA1c) levels, with the size of improvement depending on the level before starting CSII; reduction in swings in blood glucose levels, and in problems due to the dawn phenomenon; fewer problems with hypoglycaemic episodes; reduction in insulin dose per day, thereby partly off-setting the cost of CSII; improved quality of life, including a reduction in the chronic fear of severe hypoglycaemia; more flexibility of lifestyle--no need to eat at fixed intervals, more freedom of lifestyle and easier participation in social and physical activity; and benefits for the patients' family. The submission from INPUT emphasised the quality of life gains from CSII, as well as improved control and fewer hypoglycaemic episodes. Also, there was a marked discrepancy between the improvement in social quality of life reported by successful pump users, and the lack of convincing health-related quality of life gains reported in the trials. With regard to economic evaluation, the main cost of CSII is for consumables, such as tubing and cannulas, and is about 1800-2000 pounds per year. The cost of the pump, assuming 4-year life, adds another 430-720 pounds per annum. The extra cost compared with analogue-based MDI averages 1700 pounds. Most studies, assuming a reduction in HbA1c level of 1.2%, found CSII to be cost-effective.
LIMITATIONS
The most important weakness of the evidence was the very small number of randomised trials of CSII against the most modern forms of MDI, using analogue insulins.
CONCLUSIONS
Based on the totality of evidence, using observational studies to supplement the limited data from randomised trials against best MDI, CSII provides some advantages over MDI in T1DM for both children and adults. However, there was no evidence that CSII is better than analogue-based MDI in T2DM or in pregnancy. Further trials with larger numbers and longer durations comparing CSII and optimised MDI in adults, adolescents and children are needed. In addition, there should be a trial of CSII versus MDI with similar provision of structured education in both arms. A trial is also needed for pregnant women with pre-existing diabetes, to investigate using CSII to the best effect.
Topics: Adult; Aged; Child; Child, Preschool; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Female; Humans; Infusions, Subcutaneous; Insulin; Male; Treatment Outcome; United Kingdom
PubMed: 20223123
DOI: 10.3310/hta14110 -
Basic & Clinical Pharmacology &... Aug 2008Anaphylactic reactions caused by injection of protamine sulfate during cardiac surgery are a well-known complication. A systematic literature review was therefore... (Review)
Review
Anaphylactic reactions caused by injection of protamine sulfate during cardiac surgery are a well-known complication. A systematic literature review was therefore conducted to gather evidence of the knowledge concerning these side effects, and to see if any prospective randomized studies supported this. Studies investigating the effect of protamine sulfate in human beings were extracted from MEDLINE, Embase and the Cochrane Library, retrieving 487 articles. Abstracts were evaluated by both authors, and referred articles not found in the primary search were furthermore extracted from reviews and case reports, resulting in a total of 272 relevant articles. Of these, 9 retrospective studies and 16 prospective studies were performed in an evidence-based manner. However, only 3 of the 16 prospective articles had an optimal design as far as inclusion criteria, randomization, and description of symptoms were concerned. Incidence of anaphylactic reactions in the prospective studies was 0.69% compared to 0.19% in the retrospective studies, but caution should be taken due to a pronounced heterogeneity of those studies. One study found heparinase I unsuitable as replacement for protamine sulfate. Overall, our findings support the low incidence of anaphylactic reactions reported in previous studies, but of note only few prospective investigations was conducted on the subject. Our study also emphasizes the need for critical appraisal of many routine procedures: in all aspects of medical care, systematic literature review conducted in a well-structured, repeated manner should be given high priority.
Topics: Anaphylaxis; Heparin Antagonists; Humans; Prospective Studies; Protamines; Randomized Controlled Trials as Topic
PubMed: 18816305
DOI: 10.1111/j.1742-7843.2008.00274.x -
The Cochrane Database of Systematic... Apr 2007Despite indications from epidemiological trials that higher blood glucose concentrations are associated with a higher risk for developing micro- and macrovascular... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite indications from epidemiological trials that higher blood glucose concentrations are associated with a higher risk for developing micro- and macrovascular complications, evidence for a beneficial effect of antihyperglycaemic therapy in patients with type 2 diabetes mellitus is conflicting. Two large studies, the United Kingdom Prospective Diabetes Study (UKPDS) and the University Group Diabetes Program (UGDP), did not find a reduction of cardiovascular endpoints through improvement of metabolic control. The theoretical benefits of newer insulin analogues might result in fewer macrovascular and microvascular events.
OBJECTIVES
To assess the effects of long-term treatment with long-acting insulin analogues (insulin glargine and insulin detemir) compared to NPH insulin in patients with type 2 diabetes mellitus.
SEARCH STRATEGY
Studies were obtained from computerised searches of MEDLINE, EMBASE, The Cochrane Library and communication with experts in the field as well as insulin producing companies.
SELECTION CRITERIA
Studies were included if they were randomised controlled trials in adults with diabetes mellitus type 2 and had a trial duration of at least 24 weeks.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data. Pooling of studies by means of random-effects meta-analyses was performed.
MAIN RESULTS
Six studies comparing insulin glargine to NPH (Neutral Protamine Hagedorn) insulin and two studies comparing insulin detemir to NPH insulin were identified. In these trials, 1715 patients were randomised to insulin glargine and 578 patients to insulin detemir. Duration of the included trials ranged from 24 to 52 weeks. Metabolic control, measured by glycosylated haemoglobin A1c (HbA1c) as a surrogate endpoint, and adverse effects did not differ in a clinical relevant way between treatment groups. While no statistically significant difference for severe hypoglycaemia rates was shown in any of the trials, the rate of symptomatic, overall and nocturnal hypoglycaemia was statistically significantly lower in patients treated with either insulin glargine or detemir. No evidence for a beneficial effect of long-acting analogues on patient-oriented outcomes like mortality, morbidity, quality of life or costs could be obtained.
AUTHORS' CONCLUSIONS
Our analysis suggests, if at all only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2 treated with "basal" insulin regarding symptomatic nocturnal hypoglycaemic events. Until long-term efficacy and safety data are available, we suggest a cautious approach to therapy with insulin glargine or detemir.
Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Randomized Controlled Trials as Topic
PubMed: 17443605
DOI: 10.1002/14651858.CD005613.pub3 -
Health Technology Assessment... Nov 2004To evaluate the use of insulin glargine in its licensed basal-bolus indication in terms of both clinical and cost-effectiveness. (Review)
Review
OBJECTIVES
To evaluate the use of insulin glargine in its licensed basal-bolus indication in terms of both clinical and cost-effectiveness.
DATA SOURCES
Electronic databases.
REVIEW METHODS
A systematic review of the literature, involving a range of databases, was performed to identify all papers relating to insulin glargine.
RESULTS
Nineteen studies met the inclusion criteria but full reports were available for only six. For type 1 diabetes patients, insulin glargine appears to be more effective than neutral protamine Hagedorn (NPH) in reducing fasting blood glucose (FBG) but not in reducing glycosylated haemoglobin (HbA1c) and there is some evidence that both insulins are as effective as each other in both FBG and HbA1c control. For type 2 patients for whom oral antidiabetic agents provide inadequate glycaemic control, there is no evidence that insulin glargine is more effective than NPH in reducing either FBG or HbA1c and some evidence that both insulins are as effective as each other in both FBG and HbA1c control. Evidence for control of hypoglycaemia is equivocal. In studies where insulin glargine is demonstrated to be superior to NPH in controlling nocturnal hypoglycaemia, this may be only apparent when compared with once-daily NPH and not twice-daily NPH. Further, this superiority of glargine over NPH in the control of nocturnal hypoglycaemia may relate to one formulation of insulin glargine (HOE901[80]) and not another (HOE901[30]). There is no conclusive evidence that insulin glargine is superior to NPH in controlling symptomatic hypoglycaemia and severe hypoglycaemia. Insufficient data are available to conclude whether insulin glargine is different from each of the commonly used NPH dosing regimens: once daily and more than once daily. Given the lack of a published evidence base for the cost-effectiveness of insulin glargine, the economic review concentrates on a review of the industry submission and an amended model. Three economic models are provided in the submission, two relating to type 1 diabetes and one relating to type 2 diabetes. All three models compare the cost--utility of insulin glargine against NPH insulin. In general, the structures of the models are poor and in all three models, mistakes relating to assumptions and calculations have been made. The assessment team believe that the cost per QALY estimates generated by the Aventis model may be an underestimate for several reasons. The cost-effectiveness of insulin glargine in both type 1 and type 2 diabetes is highly sensitive to the amount of utility associated with reducing the fear of hypoglycaemia.
CONCLUSIONS
The evidence suggests that, compared with NPH insulin, insulin glargine is effective in reducing the number of nocturnal hypoglycaemic episodes, especially when compared with once-daily NPH. There appears to be no improvement in long-term glycaemic control and therefore insulin glargine is unlikely to reduce the incidence of the long-term microvascular and cardiovascular complications of diabetes. Further research into insulin glargine is needed that addresses the quality of life issues associated with fear of hypoglycaemia and also the economic impact of balance of HbA1c control and incidence of hypoglycaemia achieved in practice. Studies examining the economic evidence on insulin glargine should be published.
Topics: Adult; Aged; Cost-Benefit Analysis; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Models, Economic; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 15525480
DOI: 10.3310/hta8450