Rebecca Harvey

Preventing the progression to type 2 diabetes mellitus in adults at high risk: a systematic review and network meta-analysis of lifestyle, pharmacological and surgical interventions.

AIMS Individuals with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) have an increased risk of progression to Type 2 diabetes mellitus. The objective of this review was to quantify the effectiveness of lifestyle, pharmacological and surgical interventions in reducing the progression to Type 2 diabetes mellitus in people with IFG or IGT. METHODS A systematic review was carried out. A network meta-analysis (NMA) of log-hazard ratios was performed. Results are presented as hazard ratios and the probabilities of treatment rankings. RESULTS 30 studies were included in the NMA. There was a reduced hazard of progression to Type 2 diabetes mellitus associated with all interventions versus standard lifestyle advice; glipizide, diet plus pioglitazone, diet plus exercise plus metformin plus rosiglitazone, diet plus exercise plus orlistat, diet plus exercise plus pedometer, rosiglitazone, orlistat and diet plus exercise plus voglibose produced the greatest effects. CONCLUSIONS Lifestyle and some pharmacological interventions are beneficial in reducing the risk of progression to Type 2 diabetes mellitus. Lifestyle interventions require significant behaviour changes that may be achieved through incentives such as the use of pedometers. Adverse events and cost of pharmacological interventions should be taken into account when considering potential risks and benefits.

A systematic review, evidence synthesis and meta-analysis of quantitative and qualitative studies evaluating the clinical effectiveness, the cost-effectiveness, safety and acceptability of interventions to prevent postnatal depression.

BACKGROUND Postnatal depression (PND) is a major depressive disorder in the year following childbirth, which impacts on women, their infants and their families. A range of interventions has been developed to prevent PND. OBJECTIVES To (1) evaluate the clinical effectiveness, cost-effectiveness, acceptability and safety of antenatal and postnatal interventions for pregnant and postnatal women to prevent PND; (2) apply rigorous methods of systematic reviewing of quantitative and qualitative studies, evidence synthesis and decision-analytic modelling to evaluate the preventive impact on women, their infants and their families; and (3) estimate cost-effectiveness. DATA SOURCES We searched MEDLINE, EMBASE, Science Citation Index and other databases (from inception to July 2013) in December 2012, and we were updated by electronic alerts until July 2013. REVIEW METHODS Two reviewers independently screened titles and abstracts with consensus agreement. We undertook quality assessment. All universal, selective and indicated preventive interventions for pregnant women and women in the first 6 postnatal weeks were included. All outcomes were included, focusing on the Edinburgh Postnatal Depression Scale (EPDS), diagnostic instruments and infant outcomes. The quantitative evidence was synthesised using network meta-analyses (NMAs). A mathematical model was constructed to explore the cost-effectiveness of interventions contained within the NMA for EPDS values. RESULTS From 3072 records identified, 122 papers (86 trials) were included in the quantitative review. From 2152 records, 56 papers (44 studies) were included in the qualitative review. The results were inconclusive. The most beneficial interventions appeared to be midwifery redesigned postnatal care [as shown by the mean 12-month EPDS score difference of -1.43 (95% credible interval -4.00 to 1.36)], person-centred approach (PCA)-based and cognitive-behavioural therapy (CBT)-based intervention (universal), interpersonal psychotherapy (IPT)-based intervention and education on preparing for parenting (selective), promoting parent-infant interaction, peer support, IPT-based intervention and PCA-based and CBT-based intervention (indicated). Women valued seeing the same health worker, the involvement of partners and access to several visits from a midwife or health visitor trained in person-centred or cognitive-behavioural approaches. The most cost-effective interventions were estimated to be midwifery redesigned postnatal care (universal), PCA-based intervention (indicated) and IPT-based intervention in the sensitivity analysis (indicated), although there was considerable uncertainty. Expected value of partial perfect information (EVPPI) for efficacy data was in excess of £150M for each population. Given the EVPPI values, future trials assessing the relative efficacies of promising interventions appears to represent value for money. LIMITATIONS In the NMAs, some trials were omitted because they could not be connected to the main network of evidence or did not provide EPDS scores. This may have introduced reporting or selection bias. No adjustment was made for the lack of quality of some trials. Although we appraised a very large number of studies, much of the evidence was inconclusive. CONCLUSIONS Interventions warrant replication within randomised controlled trials (RCTs). Several interventions appear to be cost-effective relative to usual care, but this is subject to considerable uncertainty. FUTURE WORK RECOMMENDATIONS Several interventions appear to be cost-effective relative to usual care, but this is subject to considerable uncertainty. Future research conducting RCTs to establish which interventions are most clinically effective and cost-effective should be considered. STUDY REGISTRATION This study is registered as PROSPERO CRD42012003273. FUNDING The National Institute for Health Research Health Technology Assessment programme.

A Model-Based Economic Evaluation of Biologic and Non-Biologic Options for the Treatment of Adults with Moderately-to-Severely Active Ulcerative Colitis after the Failure of Conventional Therapy

BackgroundUlcerative colitis (UC) is the most common form of inflammatory bowel disease in the UK. Medical management aims to induce and maintain remission and to avoid complications and the necessity for surgical intervention. Colectomy removes the source of inflammation but is associated with morbidity and mortality. Newer anti-tumour necrosis factor (TNF)-α therapies may improve medical outcomes, albeit at an increased cost.ObjectiveOur objective was to assess the incremental cost effectiveness of infliximab, adalimumab and golimumab versus conventional therapy and surgery from a National Health Service (NHS) and Personal Social Services (PSS) perspective over a lifetime horizon.MethodsA Markov model was developed with health states defined according to whether the patient is alive or dead, current treatments received, history of colectomy and level of disease control. Transition probabilities were derived from network meta-analyses (NMAs) of trials of anti-TNF-α agents in the moderate-to-severe UC population. Health utilities, colectomy rates, surgical complications and resource use estimates were derived from literature. Unit costs were drawn from standard costing sources and literature and were valued at year 2013/2014 values.ResultsFor patients in whom surgery is an option, colectomy is expected to dominate all medical treatment options. For patients in whom colectomy is not an option, infliximab and golimumab are expected to be ruled out due to dominance, whilst the incremental cost-effectiveness ratio (ICER) for adalimumab versus conventional treatment is expected to be approximately £50,278 per quality-adjusted life-year (QALY) gained.ConclusionsBased on the NMAs, the ICERs for anti-TNF-α therapy versus conventional treatment or surgery are expected to be at best, in excess of £50,000 per QALY gained. The cost effectiveness of withdrawing biologic therapy upon remission and re-treating relapse is unknown.

Preventing the Progression to Type 2 Diabetes Mellitus in Adults at High Risk: A Systematic Review And Network Meta-Analysis of Lifestyle, Pharmacological and Surgical Interventions

a b s t r a c t Aims: Individuals with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) have an increased risk of progression to Type 2 diabetes mellitus. The objective of this review was to quantify the effectiveness of lifestyle, pharmacological and surgical interventions in reducing the progression to Type 2 diabetes mellitus in people with IFG or IGT. Methods: A systematic review was carried out. A network meta-analysis (NMA) of loghazard ratios was performed. Results are presented as hazard ratios and the probabilities of treatment rankings. Results: 30 studies were included in the NMA. There was a reduced hazard of progression to Type 2 diabetes mellitus associated with all interventions versus standard lifestyle advice; glipizide, diet plus pioglitazone, diet plus exercise plus metformin plus rosiglitazone, diet plus exercise plus orlistat, diet plus exercise plus pedometer, rosiglitazone, orlistat and diet plus exercise plus voglibose produced the greatest effects. Conclusions: Lifestyle and some pharmacological interventions are beneficial in reducing the risk of progression to Type 2 diabetes mellitus. Lifestyle interventions require significant behaviour changes that may be achieved through incentives such as the use of pedometers. Adverse events and cost of pharmacological interventions should be taken into account when considering potential risks and benefits.