Comparative efficacy and safety between amisulpride and olanzapine in schizophrenia treatment and a cost analysis in China: a systematic review, meta-analysis, and cost-minimization analysis.

BACKGROUND: Amisulpride was introduced into China in 2010 as a second-generation atypical antipsychotic, while olanzapine has been on the market since 1999 as one of the leading treatments for schizophrenia in China. Since more Chinese patients are gaining access to amisulpride, the study aims to compare the efficacy, safety, and costs between amisulpride and olanzapine for schizophrenia treatment in China. METHODS: PubMed, Embase, the Cochrane library, China National Knowledge Infrastructure (CNKI) and WanFang database were systematically searched for randomized controlled trials (RCTs) up to July 2018. The Cochrane Risk of Bias tool was utilized to assess the quality of included studies. A meta-analysis was performed to compare the efficacy and safety of amisulpride and olanzapine, followed by a cost-minimization analysis using local drug and medical costs reported in China. RESULTS: Twenty RCTs with 2000 patients were included in the systematic review. There were no significant differences between amisulpride and olanzapine on efficacy measures based on scores from the Positive and Negative Syndrome Scale, the Scale for the Assessment of Negative Symptoms, the Brief Psychiatric Rating Scale and the Clinical Global Impressions-Severity or Improvement. For safety outcomes, amisulpride was associated with lower fasting blood glucose and less abnormal liver functions as well as significantly lower risks of weight gain, constipation, and somnolence; olanzapine was associated with significantly lower risks of insomnia and lactation/amenorrhea/sexual hormone disorder. No significant differences were found in risks of extrapyramidal symptoms (EPS), tremor, akathisia, abnormal corrected QT interval. Cost-minimization analysis showed that amisulpride was likely to be a cost-saving alternative in China, with potential savings of 1358 Chinese Yuan (CNY) per patient for a three-month schizophrenia treatment compared with olanzapine. CONCLUSION: As the first meta-analysis and cost-minimization analysis comparing the efficacy, safety and cost of amisulpride and olanzapine within a Chinese setting, the study suggests that amisulpride may be an effective, well-tolerated, and cost-saving antipsychotic drug alternative in China.

Enabling access to molecular monitoring for chronic myeloid leukemia patients is cost effective in China.

OBJECTIVE: To determine the cost effectiveness of molecular monitoring in patients with chronic myeloid leukemia in the chronic phase (CML-CP) compared to no molecular monitoring from a Chinese payer perspective. METHODS: Analyses were conducted using a semi-Markov model with a 50-year time horizon. Population data from multicenter registry-based studies of Chinese patients with CML-CP informed the model. Transition probabilities were based on time-to-event data from the literature. Utility values were obtained from published studies and were assumed to be the same for patients with and without molecular monitoring. Costs were based on values commonly used in the Chinese healthcare system, including drug acquisition, drug administration, follow-up, treatment for disease progression, molecular monitoring, and terminal care costs, and were in the local currency (2020 Chinese Yuan RMB [¥]). Outcomes were total life-years (LYs) and quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratio. RESULTS: Molecular monitoring was dominant to no molecular monitoring, with increased LYs (1.52) and QALYs (1.90) and costs savings (¥93,840) over a lifetime compared to no monitoring in discounted analyses. The opportunity of patients that receive molecular monitoring to discontinue treatment during treatment-free remission, an opportunity not afforded to those without molecular monitoring, was the principle driver of this result. Results were similar across multiple clinical scenarios. Particularly, molecular monitoring remained dominant even if the proportion of patients achieving deep molecular response (DMR) was reduced by 10%-30%, or the proportion of patients maintaining DMR for 1 year was reduced by 10%-30% or increased by 10%. Cost savings in these scenarios ranged from ¥62,230 to ¥103,964. CONCLUSIONS: Overall, this analysis demonstrates that adherence to guideline recommendations of regular molecular monitoring of patients with CML-CP treated with TKIs provides significant clinical benefit that leads to substantial cost savings compared to no molecular monitoring from the perspective of a Chinese payer. In a time where healthcare systems have limited resources to allocate to optimal patient care, investment in molecular monitoring is an ideal choice for improving patient benefits at a reduced cost.

Identification of people with disabilities using participatory rural appraisal and key informants: a pragmatic approach with action potential promoting validity and low cost.

BACKGROUND: Surveys have been the conventional methods used for identification of people with disabilities; however, they have been observed to be expensive and time-consuming that may not be affordable or practical. As a result, the participatory rural appraisal (PRA) and key informant (KI) approaches have been developed and increasingly used in the resource-poor countries. OBJECTIVE: To investigate the strengths and weaknesses of PRA and KI approaches in the identification of people with disability in resource-poor countries. METHOD: A review of published related papers was performed by searching electronic databases including PubMed, Scirus, Health on the Net (HON), Ovid Medline and SOURCE disability database. RESULTS: A total of 11 relevant papers were identified from the literature that used PRA or KI methods or both. The PRA and KI approaches were not only consistently less expensive than conventional surveys, but also observed to be simple and fast for identifying disabilities according to local perceptions, although they were less sensitive. The evidence showed that PRA and KI processes had the benefit of engaging and developing long-term partnerships with the local communities and so the likelihood of positive long-term impact on the community. CONCLUSIONS: The PRA and KI approaches could be fast and cost-effective methods for identifying people with disabilities as an alternative to surveys. They are especially useful when identification is related to subsequent development of community-based services for persons with disabilities. However, surveys were shown to be more sensitive and therefore more accurate for establishing prevalence rates of impairment.

A Caprini Risk Score-Based Cost-Effectiveness Analysis of Enoxaparin for the Thromboprophylaxis of Patients After Nonorthopedic Surgery in a Chinese Healthcare Setting.

BACKGROUND: Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is an important cause of post-surgery morbidity and mortality. However, it is unclear whether thromboprophylaxis with the low-molecular-weight heparin (LMWH) enoxaparin after non-orthopedic surgery could balance the cost and clinical outcomes or not. OBJECTIVES: The purpose of this research was to evaluate the cost-effectiveness of enoxaparin for the universal prophylaxis of VTE and associated long-term complications in patients after non-orthopedic surgery compared with no prevention in a Chinese healthcare setting. METHODS: A decision model, which included both acute VTE and long-term complications, was developed to assess the economic outcomes of the two strategies for patients after non-orthopedic surgery. Quality-adjusted life years (QALYs) and direct medical costs were measured over a 5-year horizon. Incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS: Compared with no prevention, patients under enoxaparin treatment with Caprini risk scores of 3-4, 5-6, 7-8, and ≥ 9 increased by 0.012, 0.017, 0.034, and 0.102 in QALYs, respectively. The results were either that ICERs of thromboprophylaxis with enoxaparin over no prevention were lower than the thresholds or that thromboprophylaxis with enoxaparin was dominant. For patients with a Caprini risk score ≥ 9, thromboprophylaxis with enoxaparin is dominant across the whole drug use duration range. The sensitivity analysis confirmed the results. CONCLUSIONS: As the first analysis evaluating the economic outcomes of enoxaparin in patients undergoing general non-orthopedic surgery, this study suggests that thromboprophylaxis with enoxaparin is highly cost-effective compared with no prevention in patients with Caprini risk score ≥ 3.

Laparoscopic uterosacral nerve ablation for alleviating chronic pelvic pain: a randomized controlled trial.

CONTEXT: Chronic pelvic pain is a common condition with a major effect on health-related quality of life, work productivity, and health care use. Operative interruption of nerve trunks in the uterosacral ligaments by laparoscopic uterosacral nerve ablation (LUNA) is a treatment option for patients with chronic pelvic pain. OBJECTIVE: To assess the effectiveness of LUNA in patients with chronic pelvic pain. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of 487 women with chronic pelvic pain lasting longer than 6 months without or with minimal endometriosis, adhesions, or pelvic inflammatory disease, who were recruited to the study by consultant gynecological surgeons from 18 UK hospitals between February 1998 and December 2005. Follow-up was conducted by questionnaires mailed at 3 and 6 months and at 1, 2, 3, and 5 years. INTERVENTION: Bilateral LUNA or laparoscopy without pelvic denervation (no LUNA); participants were blinded to the treatment allocation. MAIN OUTCOME MEASURES: The primary outcome was pain, which was assessed by a visual analogue scale. Data concerning the 3 types of pain (noncyclical pain, dysmenorrhea, and dyspareunia) were analyzed separately as was the worst pain level experienced from any of these 3 types of pain. The secondary outcome was health-related quality of life, which was measured using a generic instrument (EuroQoL EQ-5D and EQ-VAS). RESULTS: After a median follow-up of 69 months, there were no significant differences reported on the visual analogue pain scales for the worst pain (mean difference between the LUNA group and the no LUNA group, -0.04 cm [95% confidence interval {CI}, -0.33 to 0.25 cm]; P = .80), noncyclical pain (-0.11 cm [95% CI, -0.50 to 0.29 cm]; P = .60), dysmenorrhea (-0.09 cm [95% CI, -0.49 to 0.30 cm]; P = .60), or dyspareunia (0.18 cm [95% CI, -0.22 to 0.62 cm]; P = .40). No differences were observed between the LUNA group and the no LUNA group for quality of life. CONCLUSION: Among women with chronic pelvic pain, LUNA did not result in improvements in pain, dysmenorrhea, dyspareunia, or quality of life compared with laparoscopy without pelvic denervation. TRIAL REGISTRATION: controlled-trials.com Identifier: ISRCTN41196151.

Assessing the Burden of Type 2 Diabetes in China Considering the Current Status-Quo Management and Implications of Improved Management Using a Modeling Approach.

BACKGROUND: Recent estimates from the International Diabetes Federation Diabetes Atlas have quantified the total annual expenditure for diabetes in China to be between 354 and 611 billion Chinese yuan (¥) (2015). OBJECTIVES: To use a modeling approach to assess the current and possible future diabetes burden in China on the basis of the current standard of type 2 diabetes (T2D) management (status quo [SQ]) and a series of hypothetical improved management strategies. METHODS: The IQVIA CORE Diabetes Model was used to evaluate the economic burden of T2D in China on the basis of assumptions reflecting the current SQ of T2D management and a number of stepwise improvements. SQ was defined as a scenario in which T2D diagnosis is delayed by 4 years, treatment escalation to maintain glucose control occurs at a 9% glycated hemoglobin (HbA1c) threshold, and there is an overall 60% adherence rate. Stepwise improvements considered immediate diagnosis, declining levels of HbA1c escalation thresholds to 7.0%, and improvements in adherence rate to 80% and 100%. The CORE Diabetes Model was applied on per-capita level to project lifetime costs and clinical outcomes of newly diseased T2D individuals in the Chinese setting. Model outcomes were subsequently annualized and extrapolated to Chinese national level considering the total number of diagnosed individuals with T2D in China. RESULTS: The total annual direct costs attributable to diagnosed T2D in China reflecting current SQ management were estimated at ¥621 billion. Scenarios exploring stepwise improvements from SQ estimated annual net savings of ¥35, ¥35, ¥60, ¥71, ¥75, and ¥106 billion for scenarios exploring immediate diagnosis, HbA1c threshold reductions to 8.0% and 7.0%, adherence rate increase to 80% and 100%, and cardiovascular risk factor control in concordance with clinical guidelines, respectively. Net savings resulted from reduced costs to treat diabetes complications (¥38, ¥67, ¥124, ¥141, ¥161, and ¥212 billion) and excess treatment costs alongside stepwise management improvements (¥4, ¥32, ¥65, ¥69, ¥86, and ¥107 billion). Per-capita life expectancy was increased by 0.26, 0.68, 1.33, 1.47, 1.69, and 3.21 years, respectively. CONCLUSIONS: Improved T2D management strategies can help to decrease the financial burden of the disease and increase life expectancy of individuals with T2D.

The impact of medical insurance coverage and molecular monitoring frequency on outcomes in chronic myeloid leukemia: real-world evidence in China.

OBJECTIVES: Imatinib (Glivec) has been covered by critical disease insurance for treatment of chronic myeloid leukemia (CML) in Jiangsu province of China since 2013. Further, free molecular monitoring has been provided to patients at top clinical centers as part of a pilot study that has changed the local treatment pattern and outcomes of patients with CML. This study evaluates the impact of medical insurance coverage and the molecular monitoring frequency on outcomes of patients with CML treated at a central hospital in Jiangsu, China, according to patient-level data. METHODS: The study investigated 335 CML patients receiving medical treatment in a central hospital between January 1, 2011 and December 31, 2014. Demographic and clinical characteristics were extracted from the patients' clinical records. Univariate and multivariate analyses using the logistic regression model were performed to identify the differences in outcomes of major molecular response (MMR) or complete cytogenetic response (CCyR) between patients who were insured vs uninsured, or between patients with frequency of PCR monitoring ≤2 times vs ≥3 times per year. RESULTS: Both the achievement of MMR (BCR-ABLIS ≤0.1%) (50.4% vs 37.5%) and CCyR (80.7% vs 62.8%) at 12 months have shown significant differences that favored patients with insurance coverage of imatinib, while there was no significant difference in the outcome of BCR-ABLIS ≤1% between insured and non-insured groups (56.0% vs 51.3%) at 6 months. The long-term results at 24 months demonstrated that there was a statistically significant difference in MMR rates between the group with 3 or more PCR monitoring tests per year and the group of patients with 2 or less PCR tests per year (76.9% vs 52.2%). CONCLUSIONS: The study findings suggest that CML patients benefit from insurance coverage of imatinib and higher frequency (≥3) of regularly scheduled molecular monitoring PCR in China.

Societal implications of medical insurance coverage for imatinib as first-line treatment of chronic myeloid leukemia in China: a cost-effectiveness analysis.

OBJECTIVES: Imatinib (Glivec) and nilotinib (Tasigna) have been covered by critical disease insurance in Jiangsu province of China since 2013, which changed local treatment patterns and outcomes of patients with chronic myeloid leukemia (CML). This study evaluated the long-term cost-effectiveness of insurance coverage with imatinib as the first-line treatment for patients with CML in China from a societal perspective. METHODS: A decision-analytic model based on previously published and real-world evidence was applied to simulate and evaluate the lifetime clinical and economic outcomes associated with CML treatments before and after imatinib was covered by medical insurance. Incremental cost-effectiveness ratio (ICER) was calculated with both costs and quality-adjusted life years (QALYs) discounted at 3% annually. Different assumptions of treatment benefits and costs were taken to address uncertainties and were tested with sensitivity analyses. RESULTS: In base case analysis, both cost and effectiveness of CML treatments increased after imatinib was covered by the medical insurance; on average, the incremental QALY and cost were 5.5 and ¥277,030 per patient in lifetime, respectively. The ICER of insurance coverage with imatinib was ¥50,641, which is less than the GDP per capita of China. Monte Carlo simulation resulted in the estimate of 100% probability that the insurance coverage of imatinib is cost-effective. Total cost was substantially saved at 5 years after patients initiated imatinib treatment with insurance coverage compared to no insurance coverage, the saved cost at 5 years was ¥99,565, which included the cost savings from both direct (e.g. cost of bone marrow or stem cell transplant) and indirect costs (e.g. productivity loss of patients and care-givers). CONCLUSIONS: The insurance coverage of imatinib is very cost-effective in China, according to the local cost and clinical data in Jiangsu province. More importantly, the insurance coverage of imatinib and nilotinib have changed the treatment patterns of CML patients, thus dramatically increasing life expectancy and quality-of-life (QoL) saving on productivity losses for both CML patients and their caregivers.

Mortality Among Men with Advanced Prostate Cancer Excluded from the ProtecT Trial.

BACKGROUND: Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates. OBJECTIVE: To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial. DESIGN, SETTING, AND PARTICIPANTS: Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox's proportional hazards regression. RESULTS AND LIMITATIONS: Of the 492 men excluded from the ProtecT cohort, 37 (8%) had metastases (N1, M0=5, M1=32) and 305 had locally advanced disease (62%). The median PSA was 17µg/l. Treatments included radical prostatectomy (RP; n=54; 11%), radiotherapy (RT; n=245; 50%), androgen deprivation therapy (ADT; n=122; 25%), other treatments (n=11; 2%), and unknown (n=60; 12%). There were 49 PCa-specific deaths (10%), of whom 14 men had received radical treatment (5%); and 129 all-cause deaths (26%). In matched ProtecT and ACN cohorts, 37 (9%) and 64 (16%), respectively, died of PCa, while 89 (22%) and 103 (26%) died of all causes. ProtecT men had a 45% lower risk of death from PCa compared to matched cases (hazard ratio 0.55, 95% confidence interval 0.38-0.83; p=0.0037), but mortality was similar in those treated radically. The nonrandomised design is a limitation. CONCLUSIONS: Men with PSA-detected advanced PCa excluded from ProtecT and treated radically had low rates of PCa death at 7.4-yr follow-up. Among men who underwent nonradical treatment, the ProtecT group had a lower rate of PCa death. Early detection through PSA testing, leadtime bias, and group heterogeneity are possible factors in this finding. PATIENT SUMMARY: Prostate cancer that has spread outside the prostate gland without causing symptoms can be detected via prostate-specific antigen testing and treated, leading to low rates of death from this disease.

Oseltamivir Treatment for Children with Influenza-Like Illness in China: A Cost-Effectiveness Analysis.

BACKGROUND: Influenza is a common viral respiratory infection that causes epidemics and pandemics in the human population. Oseltamivir is a neuraminidase inhibitor-a new class of antiviral therapy for influenza. Although its efficacy and safety have been established, there is uncertainty regarding whether influenza-like illness (ILI) in children is best managed by oseltamivir at the onset of illness, and its cost-effectiveness in children has not been studied in China. OBJECTIVE: To evaluate the cost-effectiveness of post rapid influenza diagnostic test (RIDT) treatment with oseltamivir and empiric treatment with oseltamivir comparing with no antiviral therapy against influenza for children with ILI. METHODS: We developed a decision-analytic model based on previously published evidence to simulate and evaluate 1-year potential clinical and economic outcomes associated with three managing strategies for children presenting with symptoms of influenza. Model inputs were derived from literature and expert opinion of clinical practice and research in China. Outcome measures included costs and quality-adjusted life year (QALY). All the interventions were compared with incremental cost-effectiveness ratios (ICER). RESULTS: In base case analysis, empiric treatment with oseltamivir consistently produced the greatest gains in QALY. When compared with no antiviral therapy, the empiric treatment with oseltamivir strategy is very cost effective with an ICER of RMB 4,438. When compared with the post RIDT treatment with oseltamivir, the empiric treatment with oseltamivir strategy is dominant. Probabilistic sensitivity analysis projected that there is a 100% probability that empiric oseltamivir treatment would be considered as a very cost-effective strategy compared to the no antiviral therapy, according to the WHO recommendations for cost-effectiveness thresholds. The same was concluded with 99% probability for empiric oseltamivir treatment being a very cost-effective strategy compared to the post RIDT treatment with oseltamivir. CONCLUSION: In the Chinese setting of current health system, our modelling based simulation analysis suggests that empiric treatment with oseltamivir to be a cost-saving and very cost-effective strategy in managing children with ILI.

Comparative efficacy and safety of treatments for localised prostate cancer: an application of network meta-analysis.

CONTEXT: There is ongoing uncertainty about the optimal management of patients with localised prostate cancer. OBJECTIVE: To evaluate the comparative efficacy and safety of different treatments for patients with localised prostate cancer. DESIGN: Systematic review with Bayesian network meta-analysis to estimate comparative ORs, and a score (0-100%) that, for a given outcome, reflects average rank order of superiority of each treatment compared against all others, using the Surface Under the Cumulative RAnking curve (SUCRA) statistic. DATA SOURCES: Electronic searches of MEDLINE without language restriction. STUDY SELECTION: Randomised trials comparing the efficacy and safety of different primary treatments (48 papers from 21 randomised trials included 7350 men). DATA EXTRACTION: 2 reviewers independently extracted data and assessed risk of bias. RESULTS: Comparative efficacy and safety evidence was available for prostatectomy, external beam radiotherapy (different types and regimens), observational management and cryotherapy, but not high-intensity focused ultrasound. There was no evidence of superiority for any of the compared treatments in respect of all-cause mortality after 5 years. Cryotherapy was associated with less gastrointestinal and genitourinary toxicity than radiotherapy (SUCRA: 99% and 77% for gastrointestinal and genitourinary toxicity, respectively). CONCLUSIONS: The limited available evidence suggests that different treatments may be optimal for different efficacy and safety outcomes. These findings highlight the importance of informed patient choice and shared decision-making about treatment modality and acceptable trade-offs between different outcomes. More trial evidence is required to reduce uncertainty. Network meta-analysis may be useful to optimise the power of evidence synthesis studies once data from new randomised controlled studies in this field are published in the future.

Overall similarity and consistency assessment scores are not sufficiently accurate for predicting discrepancy between direct and indirect comparison estimates.

OBJECTIVES: Indirect comparison methods have been increasingly used to assess the effectiveness of different interventions comparatively. This study evaluated a Trial Similarity and Evidence Consistency Assessment (TSECA) framework for assessing key assumptions underlying the validity of indirect comparisons. STUDY DESIGN AND SETTING: We applied the TSECA framework to 94 Cochrane Systematic Reviews that provided data to compare two interventions by both direct and indirect comparisons. Using the TSECA framework, two reviewers independently assessed and scored trial similarity and evidence consistency. A detailed case study provided further insight into the usefulness and limitations of the framework proposed. RESULTS: Trial similarity and evidence consistency scores obtained using the assessment framework were not associated with statistically significant inconsistency between direct and indirect estimates. The case study illustrated that the assessment framework could be used to identify potentially important differences in participants, interventions, and outcome measures between different sets of trials in the indirect comparison. CONCLUSION: Although the overall trial similarity and evidence consistency scores are unlikely to be sufficiently accurate for predicting inconsistency between direct and indirect estimates, the assessment framework proposed in this study can be a useful tool for identifying between-trial differences that may threaten the validity of indirect treatment comparisons.

Assessing and comparing the outcome measures for the rehabilitation of adults with communication disorders in randomised controlled trials: an International Classification of Functioning, Disability and Health approach.

PURPOSE: To identify the assessment instruments and relevant outcome measures used in randomised clinical trials (RCTs) relating to interventions for adults with communication disorders, and then examine and compare the domains of the outcome measures using the International Classification of Functioning, Disability and Health (ICF) as a reference tool. METHOD: Published RCTs with primary focus on the effectiveness of rehabilitation for adults with communication disorders were systematically reviewed. Identified RCTs were examined for all the assessments used as outcome measures. Distinctions were made between the use of standardised assessment tools and non-standardised empirical measures. The key concepts examined by the outcome measures were then linked to the ICF using the established ICF linking rules. RESULTS: The systematic review included 24 RCTs in which 11 trials used non-standardised empirical assessment as the outcome measure, and 18 trials included standardised instruments as the outcome measure. It is clear that all the identified items and meaningful concepts from the assessment used in the included studies can be linked to the ICF categories. Of the 108 linked level-two ICF categories, 53% were linked to 'body functions', 36% to 'activity and participation' and 9% to 'environmental factors'. CONCLUSIONS: A wide range of outcome measures have been used in RCTs of interventions for adults with communications disorders. The ICF provides a clarifying framework for systematically gathering and examining the information about the content of outcome measures and then can be used as a common reference to identify and compare the domains of the outcome measures. The high proportion of elements relating to body functions raises some questions about the purpose and aims of the interventions.

Inconsistency between direct and indirect comparisons of competing interventions: meta-epidemiological study.

OBJECTIVE: To investigate the agreement between direct and indirect comparisons of competing healthcare interventions. DESIGN: Meta-epidemiological study based on sample of meta-analyses of randomised controlled trials. Data sources Cochrane Database of Systematic Reviews and PubMed. Inclusion criteria Systematic reviews that provided sufficient data for both direct comparison and independent indirect comparisons of two interventions on the basis of a common comparator and in which the odds ratio could be used as the outcome statistic. MAIN OUTCOME MEASURE: Inconsistency measured by the difference in the log odds ratio between the direct and indirect methods. RESULTS: The study included 112 independent trial networks (including 1552 trials with 478,775 patients in total) that allowed both direct and indirect comparison of two interventions. Indirect comparison had already been explicitly done in only 13 of the 85 Cochrane reviews included. The inconsistency between the direct and indirect comparison was statistically significant in 16 cases (14%, 95% confidence interval 9% to 22%). The statistically significant inconsistency was associated with fewer trials, subjectively assessed outcomes, and statistically significant effects of treatment in either direct or indirect comparisons. Owing to considerable inconsistency, many (14/39) of the statistically significant effects by direct comparison became non-significant when the direct and indirect estimates were combined. CONCLUSIONS: Significant inconsistency between direct and indirect comparisons may be more prevalent than previously observed. Direct and indirect estimates should be combined in mixed treatment comparisons only after adequate assessment of the consistency of the evidence.

Clinical effectiveness of treatment with hyperbaric oxygen for neonatal hypoxic-ischaemic encephalopathy: systematic review of Chinese literature.

OBJECTIVES: To investigate the clinical effectiveness of treatment with hyperbaric oxygen for neonates with hypoxic-ischaemic encephalopathy. This treatment is frequently used in China but much less often in the West. DATA SOURCES: Western (Cochrane controlled trials register and database of systematic reviews, Medline, Embase, CINAHL, and HealthSTAR) and Chinese (China Hospital Digital Library, Chinese Medical Journal Network) databases and hand search of Chinese journals. No language restrictions. REVIEW METHODS: Randomised or quasi-randomised controlled trials of treatment with hyperbaric oxygen compared with "usual care" in term neonates with hypoxic-ischaemic encephalopathy. Outcomes included mortality and long term neurological sequelae. Standardised forms were used to extract and compare data. Criteria of York Centre for Reviews and Dissemination were used to assess quality. Analysis was mainly qualitative but included meta-analysis. RESULTS: 20 trials were found, mainly from Chinese sources. The reporting quality of trials was poor by Western (CONSORT) standards. Treatment with hyperbaric oxygen had better outcomes than the comparator in almost all trials. The odds ratios of the meta-analyses were 0.26 (95% confidence interval 0.14 to 0.46) for mortality and 0.41 (0.27 to 0.61) for neurological sequelae. CONCLUSION: Treatment with hyperbaric oxygen possibly reduces mortality and neurological sequelae in term neonates with hypoxic-ischaemic encephalopathy. Because of the poor quality of reporting in all trials and the possibility of publication bias, an adequately powered, high quality randomised controlled trial is needed to investigate these findings. The Chinese medical literature may be a rich source of evidence to inform clinical practice and other systematic reviews.