Mixed Treatment Comparison Research Articles

A mixed treatment comparison of toxicity of gemcitabine combined with different targeted drugs in the treatment of advanced or metastatic pancreatic cancer

ABSTRACTThe mixed treatment comparison study was performed in order to compare the toxicities of Gemcitabine and different targeted drug combinations in the treatment of advanced/metastatic pancreatic cancer (PC). Searches were performed from the inception of PubMed and Cochrane Library databases to February 2017. This study included randomized controlled trials (RCTs) of Gemcitabine and different targeted drug combinations in the treatment of advanced/metastatic PC. Odds ratio (OR) values were calculated by direct and indirect comparisons, and the surface under the cumulative ranking curves (SUCRA) were drawn. A total of six RCTs were finally incorporated into the study. These studies included six therapy regimens: Gemcitabine + Axitinib, Gemcitabine + Trametinib, Gemcitabine + Sorafenib, Gemcitabine + Bevacizumab, Gemcitabine + Erlotinib and Gemcitabine + Tipifarnib. The results showed that Gemcitabine + Axitinib combinations showed lower incidence rates of rashes (all grades) in comparison to Gemcitabine + Trametinib and Gemcitabine + Erlotinib combinations. Compared with Gemcitabine+ Trametinib combinations, Gemcitabine + Axitinib combinations showed lower incidence rates of diarrhea (grade ≥ 3). Moreover, the cluster analyses results revealed that Gemcitabine + Axitinib combinations and Gemcitabine + Sorafenib combinations showed lower incidence rates of hematotoxicity, while Gemcitabine + Axitinib combinations showed lower incidence rates of non-hematotoxicity. Collectively, the data provided strong evidence of Gemcitabine + Axitinib combinations showing lower incidence rates of non-hematotoxicity, and Gemcitabine + Axitinib and Gemcitabine + Sorafenib combinations may have lower incidence rates of hematotoxicity in the treatment of advanced/metastatic PC.

A mixed treatment comparison on efficacy and safety of treatments for spasticity caused by multiple sclerosis: a systematic review and network meta-analysis

Objectives: This study is aimed at providing a quantitative evaluation on different therapies of spasticity caused by multiple sclerosis. Data sources: PubMed and Embase database. Review methods: We searched for randomized controlled trials that met the requirements. Percentages of improved patients’ spasticity scale, mild adverse effect and severe adverse effect were extracted as outcomes. The forest plots accompanied with surface under the cumulative ranking curves were used to reveal the efficacy and safety of these therapies. Results: In all, 23 randomized controlled trials with a total of 2720 patients were included in our study. Cannabinoids and botulinum toxin had shown a significantly better efficacy than placebo in the percentage of improved patients. Botulinum toxin also showed such significant difference compared with tizanidine and baclofen. No significant difference was found in spasticity scale. Cannabinoids, tizanidine and diazepam had significantly more mild adverse effect reports than placebo. Surface under the cumulative ranking curves suggested that cannabinoids, botulinum toxin and transcutaneous electric nerve stimulation were preferable therapies. Conclusions: We recommended botulinum toxin as the optimal intervention for multiple sclerosis–related spasticity. Cannabinoids and transcutaneous electric nerve stimulation could also be considered as multiple sclerosis–related spasticity treatments but their safety remained to be verified.

New Glucose-Lowering Agents for Diabetic Kidney Disease.

The prevalence of diabetes mellitus is increasing and is associated with a range of complications including nephropathy. New antidiabetic agents are sought which also have positive effects to diminish diabetic complications. Examples of promising new classes of such agents are glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose cotransporter 2 inhibitors. In addition to cardiovascular protective effects such as weight loss and decreased blood pressure of some of these agents, there is evidence for renoprotective effects with these agents. This review elaborates on the main results of renoprotective effects of these 3 treatment classes. In conclusion, currently available trials have demonstrated renoprotective effects for certain glucagon-like peptide-1 receptor agonists, liraglutide and semaglutide, and the sodium-glucose cotransporter 2 inhibitors, empagliflozin and canagliflozin. Dipeptidyl peptidase-4 inhibitors did not show a significant renoprotective effect. Nevertheless, larger studies with respect to renoprotective effects of these 3 drug classes are currently being performed, and thus, no conclusions for all of these agents can yet be made.

Pharmacological interventions for reducing pain related to immunization or intramuscular injection in children: A mixed treatment comparison network meta-analysis of randomized controlled clinical trials.

Various interventions were observed to reduce pain following vaccination in children. This study is a network meta-analysis comparing pharmacological interventions. Electronic databases were searched for appropriate randomized controlled clinical trials comparing active pharmacological agents to reduce pain following vaccination or intramuscular injection in neonates, infants, or children. Pain score was the primary outcome measure. Random effects model was used for generating pooled estimates. A total of 23 studies were included in the network meta-analysis. Topical eutectic mixture of local anesthetics (EMLA) significantly reduced pain scores. Crying time was also observed to be lower with vapocoolant spray and 25% sucrose and glucose solutions. Quality of the evidence was observed to be either low or very low. Topical EMLA significantly reduce pain following intramuscular injections particularly vaccination. However, due to low grade quality of the evidence, more studies are obligatory.

Tranexamic acid in total hip arthroplasty: Mixed treatment comparisons of randomized controlled trials and cohort studies

BackgroundThe present study is a network meta-analysis of various routes of tranexamic acid (TXA) in patients with total hip arthroplasty (THA). MethodsRandomized controlled trials and cohort studies evaluating TXA in patients with THA were included. Number of patients requiring blood transfusion was the primary outcome. ResultsPooled estimate for TXA use against placebo for blood transfusion rate was 0.30 [0.23, 0.39] favoring TXA. Maximum reduction in the risk of blood transfusion was observed with topical plus intra-operative intravenous TXA. ConclusionCombined topical and intravenous TXA during surgery may perform better than other modes in patients undergoing THA.

Comparison of treatment strategies for femoro-popliteal disease: A network meta-analysis.

We sought to compare treatment strategies in a Bayesian network meta-analysis of randomized controlled trials. Peripheral artery disease (PAD) is a prevalent morbidity that is treated with various strategies. We performed a MEDLINE search for randomized studies comparing at least 2 treatment strategies, including bypass surgery, percutaneous transluminal angioplasty (PTA) balloons, stents, covered stents, drug-eluting stents (DES), and drug-coated balloons (DCB), in patients with native femoro-popliteal disease. Mixed treatment comparison model generation was performed to directly and indirectly compare the strategies in terms of restenosis and target lesion revascularization (TLR) presented as odds ratios (OR, [95% credible intervals]). Twenty-nine studies with 4,820 patients were included in the present study. PTA was the largest group with 1,900 patients, followed by DCB (n = 1,343), bare metal stents (n = 941), covered stents (n = 304), DES (n = 236), and bypass (n = 92). Mean age was 68 ± 9 years, 64% were male, 37% diabetic, and 55% smokers. Mean lesion length was 77 ± 44 mm, and 39% were total occlusions. Bayesian hierarchical random-effects model demonstrated all treatments were significantly better than, or had a trend toward superiority over, PTA, with DCB ranking well in both restenosis (OR = 0.29, [0.17-0.47]) and TLR (OR = 0.31, [0.20-0.46]). Nonetheless, none of the therapies showed superiority in terms of survival or amputations. Treatment of femoro-popliteal disease has significantly evolved in recent years, with higher rates of patency and freedom from TLR. However, the utility of these treatment strategies in terms of reduction of amputations and overall survival remains in question.

Growth factors for diabetic foot ulcers: mixed treatment comparison analysis of randomized clinical trials.

Topical growth factors accelerate wound healing in patients with diabetic foot ulcers (DFU). Due to the absence of head-to-head comparisons, we carried out Bayesian network meta-analysis to compare the efficacy and safety of growth factors. Using an appropriate search strategy, randomized controlled trials on topical growth factors compared with standard of care in patients with DFU, were included. Proportion of patients with complete healing was the primary outcome. Odds ratio (95% confidence interval) was used as the effect estimate and random effects model was used for both direct and indirect comparisons. Markov Chain Monte Carlo simulation was used to obtain pooled estimates. Rankogram was generated based on surface under the cumulative ranking curve (SUCRA). A total of 26 studies with 2088 participants and 1018 events were included. The pooled estimates for recombinant epidermal growth factor (rhEGF), autologous platelet rich plasma (PRP), recombinant human platelet-derived growth factor (rhPDGF) were 5.72 [3.34, 10.37], 2.65 [1.60, 4.54] and 1.97 [1.54, 2.55] respectively. SUCRA for rhEGF was 0.95. Sensitivity analyses did not reveal significant changes from the pooled estimates and rankogram. No differences were observed in the overall risk of adverse events between the growth factors. However, the growth factors were observed to lower the risk of lower limb amputation compared to standard of care. To conclude, rhEGF, rhPDGF and autologous PRP significantly improved the healing rate when used as adjuvants to standard of care, of which rhEGF may perform better than other growth factors. The strength of most of the outcomes assessed was low and the findings may not be applicable for DFU with infection or osteomyelitis. The findings of this study needs to be considered with caution as the results might change with findings from head-to-head studies.

Axitinib, cabozantinib, everolimus, nivolumab, sunitinib and best supportive care in previously treated renal cell carcinoma: a systematic review and economic evaluation.

Several therapies have recently been approved for use in the NHS for pretreated advanced or metastatic renal cell carcinoma (amRCC), but there is a lack of comparative evidence to guide decisions between them. To evaluate the clinical effectiveness and cost-effectiveness of axitinib (Inlyta®, Pfizer Inc., NY, USA), cabozantinib (Cabometyx®, Ipsen, Slough, UK), everolimus (Afinitor®, Novartis, Basel, Switzerland), nivolumab (Opdivo®, Bristol-Myers Squibb, NY, USA), sunitinib (Sutent®, Pfizer, Inc., NY, USA) and best supportive care (BSC) for people with amRCC who were previously treated with vascular endothelial growth factor (VEGF)-targeted therapy. A systematic review and mixed-treatment comparison (MTC) of randomised controlled trials (RCTs) and non-RCTs. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes were objective response rates (ORRs), adverse events (AEs) and health-related quality of life (HRQoL). MEDLINE, EMBASE and The Cochrane Library were searched from inception to January and June 2016 for RCTs and non-RCTs, respectively. Two reviewers abstracted data and performed critical appraisals. A fixed-effects MTC was conducted for OS, PFS [hazard ratios (HRs)] and ORR (odds ratios), and all were presented with 95% credible intervals (CrIs). The RCT data formed the primary analyses, with non-RCTs and studies rated as being at a high risk of bias included in sensitivity analyses (SAs). HRQoL and AE data were summarised narratively. A partitioned survival model with health states for pre progression, post progression and death was developed to perform a cost-utility analysis. Survival curves were fitted to the PFS and OS results from the MTC. A systematic review of HRQoL was undertaken to identify sources of health state utility values. Four RCTs (n = 2618) and eight non-RCTs (n = 1526) were included. The results show that cabozantinib has longer PFS than everolimus (HR 0.51, 95% CrI 0.41 to 0.63) and both treatments are better than BSC. Both cabozantinib (HR 0.66, 95% CrI 0.53 to 0.82) and nivolumab (HR 0.73, 95% CrI 0.60 to 0.89) have longer OS than everolimus. SAs were consistent with the primary analyses. The economic analysis, using drug list prices, shows that everolimus may be more cost-effective than BSC with an incremental cost-effectiveness ratio (ICER) of £45,000 per quality-adjusted life-year (QALY), as it is likely to be considered an end-of-life treatment. Cabozantinib has an ICER of £126,000 per QALY compared with everolimus and is unlikely to be cost-effective. Nivolumab was dominated by cabozantinib (i.e. more costly and less effective) and axitinib was dominated by everolimus. Treatment comparisons were limited by the small number of RCTs. However, the key limitation of the analysis is the absence of the drug prices paid by the NHS, which was a limitation that could not be avoided owing to the confidentiality of discounts given to the NHS. The RCT evidence suggests that cabozantinib is likely to be the most effective for PFS and OS, closely followed by nivolumab. All treatments appear to delay disease progression and prolong survival compared with BSC, although the results are heterogeneous. The economic analysis shows that at list price everolimus could be recommended as the other drugs are much more expensive with insufficient incremental benefit. The applicability of these findings to the NHS is somewhat limited because existing confidential patient access schemes could not be used in the analysis. Future work using the discounted prices at which these drugs are provided to the NHS would better inform estimates of their relative cost-effectiveness. This study is registered as PROSPERO CRD42016042384. The National Institute for Health Research Health Technology Assessment programme.

Pharmacological interventions for premature ejaculation: A mixed treatment comparison network meta-analysis of randomized clinical trials

Pharmacological interventions for premature ejaculation: A mixed treatment comparison network meta-analysis of randomized clinical trials

Materials used for indirect pulp treatment in primary teeth: a mixed treatment comparisons meta-analysis.

This study aimed to systematically review the literature to address the question regarding the influence of different materials in the clinical and radiographic success of indirect pulp treatment in primary teeth. A literature search was carried out for articles published prior to January 2017 in PubMed/MEDLINE, CENTRAL, Scopus, TRIP and ClinicalTrials databases; relevant articles included randomized clinical trials that compared materials used for indirect pulp treatment in primary teeth. Two reviewers independently selected the studies and extracted the data. The effects of each material on the outcome (clinical and radiographic failures) were analyzed using a mixed treatment comparisons meta-analysis. The ranking of treatments according to their probability of being the best choice was also calculated. From 1,088 potentially eligible studies, 11 were selected for full-text analysis, and 4 were included in the meta-analysis. In all papers, calcium hydroxide liner was used as the control group versus an adhesive system, resin-modified glass ionomer cement or placebo. The follow-up period ranged from 24 to 48 months, with dropout rates of 0-25.7%. The material type did not significantly affect the risk of failure of the indirect pulp treatment. However, calcium hydroxide presented a higher probability of failure. In conclusion, there is no scientific evidence showing the superiority of any material used for indirect pulp treatment in primary teeth.

Meta-Analysis of Culprit-Only Versus Multivessel Percutaneous Coronary Intervention in Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Coronary Disease

Recently, several randomized controlled trials (RCT) in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) have compared a strategy of routine multivessel percutaneous coronary intervention (PCI) performed either as a single procedure or as staged procedures to culprit-only PCI. All of these trials have been underpowered for clinical end points. We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for RCT comparing multivessel PCI with culprit-only PCI in patients with STEMI and MVD. The primary efficacy outcome was the composite rate of death or MI. Other efficacy outcomes included death, MI, and repeat revascularization. Safety outcomes were contrast-associated acute kidney injury, stroke, and major bleeding. Pairwise direct comparison and mixed-treatment comparison network meta-analyses were performed. Eleven trials that enrolled 3,150 patients with a total of 5,296 patient-years of follow-up were included. In direct comparison meta-analysis, single-procedure multivessel PCI was associated with a reduction in the risk of death or MI (rate ratio [RR] = 0.52; 95% confidence interval [CI] 0.37 to 0.73; p <0.001), due to less death (RR = 0.64; 95% CI 0.40 to 1.02; p = 0.06) and MI (RR = 0.42; 95% CI 0.25 to 0.69; p <0.0001) compared with culprit-only PCI. No heterogeneity (I2 = 0) was present between studies. In contrast, staged multivessel PCI did not significantly reduce death or MI compared with culprit-only PCI. Both multivessel PCI strategies reduced the risk of repeat revascularization without significant differences in safety outcomes. Results were consistent in the mixed-treatment comparison meta-analysis. In conclusion, the present meta-analysis suggests that single-procedure multivessel PCI may be the preferred strategy in patients with STEMI and MVD.

Tecfidera® (delayed-release dimethylfumarate) in the treatment of relapsing-remitting multiple sclerosis

The present health technology assessment (HTA) evaluates the clinical and economic profile of delayed-release dimethylfumarate (DMF, also known as gastro-resistant DMF) in the treatment of relapsing-remitting multiple sclerosis (RRMS) in Italy. Chapter 1 briefly introduces the condition (multiple sclerosis and, more specifically, the relapsing-remitting form) and provides an overall description of the main therapeutic options for physicians, in terms of clinical evidence, regulatory status in Europe and approval status and reimbursement (refunding) criteria in Italy. In the next sections (Chapters 2-5), key-topics regarding RRMS are analysed: epidemiology, clinical burden, quality of life/social impact and the economic implications for healthcare services, patients and society. In Chapter 6, the clinical evidence supporting the use of DMF in RRMS is summarized. Data from phase III randomized clinical trials (DEFINE, CONFIRM), plus the pooled post-hoc analysis of the two studies, were evaluated to assess the level of clinical benefit provided by DMF. Finally, in Chapter 7, a review of the health economic evidence assessing DMF is performed, with a specific focus on Italy. Overall, the methodological quality of registration studies, together with the robustness and consistency of the study results, support the conclusion that DMF is an effective and safe treatment for RRMS. The economic assessment of DMF in Italy, based on cost-effectiveness and budget impact analyses (adopting clinical input data from a mixed treatment comparison and economic input data relative to the Italian healthcare setting), confirm that DMF is a cost-effective and economically sustainable treatment for the Italian National Healthcare Service. These findings are in line with the results of most international publications and the assessments from well-recognized HTA agencies (e.g. NICE/SMC). In summary, both the clinical and economic evidence analyzed in this HTA substantiate DMF as an important therapeutic option for the treatment of RRMS.

Pharmacological interventions for preventing acute mountain sickness: a network meta-analysis and trial sequential analysis of randomized clinical trials

Background: Individuals ascending to high altitude are at a risk of getting acute mountain sickness (AMS). The present study is a network meta-analysis comparing all the interventions available to prevent AMS.Methods: Electronic databases were searched for randomized clinical trials evaluating the use of drugs to prevent AMS. Incidence of AMS was the primary outcome and incidence of severe AMS, paraesthesia (as side effect of acetazolamide use), headache and severe headache, and oxygen saturation were the secondary outcomes. Odds ratio [95% confidence interval] was the effect estimate for categorical outcomes and weighted mean difference for oxygen saturation. Random effects model was used to derive the direct and mixed treatment comparison pooled estimates. Trial sequential analysis and grading of the evidence for key comparisons were carried out.Results: A total of 24 studies were included. Acetazolamide at 125, 250 and 375 mg twice daily, dexamethasone and ibuprofen had statistically significant lower incidence of AMS compared to placebo. All the above agents except ibuprofen were also observed to significantly reduce the incidence of severe AMS. Acetazolamide alone or in combination with Ginkgo biloba were associated with lower incidence of headache, but higher risk of paraesthesia. Acetazolamide at 125 mg and 375 mg twice daily significantly reduce the incidence of severe headache as like ibuprofen. Trial sequential analysis indicates that the current evidence is adequate for the incidence of AMS only for acetazolamide 125 and 250 mg twice daily. Similarly, the strength of evidence for acetazolamide 125 and 250 mg twice daily was moderate while it was either low or very low for all other comparisons.Conclusions: Acetazolamide at 125, 250 and 375 mg twice daily, ibuprofen and dexamethasone significantly reduce the incidence of AMS of which adequate evidence exists only for acetazolamide 125 and 250 mg twice daily therapy. Acetazolamide 125 mg twice daily could be the best in the pool considering the presence of enough evidence for preventing AMS and associated with lower incidence of paraesthesia.Key messagesAcetazolamide 125, 250 and 375 mg twice daily, dexamethasone and ibuprofen reduce the incidence of AMS in high altitudes.Adequate evidence exists supporting the use of acetazolamide 125 mg and 250 mg twice daily for preventing AMS of which acetazolamide 125 mg twice daily could be the best.

Venous thromboembolism prophylaxis in medically ill patients: a mixed treatment comparison meta-analysis.

The American College of Chest Physicians guidelines recommend unfractionated heparin (UFH), low molecular weight heparins (LMWHs) or fondaparinux for prevention of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), in medically-ill patients. Direct oral anticoagulants (DOACs) have been evaluated relative to enoxaparin for VTE prophylaxis though head-to-head comparisons of these agents are lacking. Therefore, we conducted a mixed treatment comparisons meta-analysis to evaluate the safety and efficacy of established treatments and DOACs for VTE prophylaxis in medically-ill patients. A comprehensive literature search was conducted to identify randomized trials evaluating UFH, LMWHs or DOACS for the prevention of VTE in medically ill patients. Articles were retrieved and cross-referenced for additional trials, evaluated and entered into ADDIS (version 1.16.6) to generate direct and indirect treatment comparisons for VTE, DVT, PE, death from any cause, and bleeding. Ten articles were included and eight anticoagulants were evaluated in a treatment network representing data on 28,382 patients. We found each treatment had similar efficacy in preventing VTE, DVT, PE, death from any cause and each had similar risk of minor and major bleeding. Overall, placebo was associated with more VTE and DVT events compared to LMWHs and DOACs. We found that UFH, LMWHs and DOACs are comparable in preventing VTE, DVT, PE, and death from any cause and in association with minor and major bleeding. Anticoagulant selection for VTE prophylaxis in medically-ill patients should be individualized by patient characteristics, risks and preferences along with specific pharmacokinetic and pharmacodynamic considerations.

Issues Encountered When Modelling The Long Term Clinical Effectiveness Of Treatments From Short Term Trials Using Second-Line Treatments For Advanced Or Metastatic Renal Cell Carcinoma (AMRCC) As An Example

Long term effectiveness data on progression-free survival (PFS) and overall survival (OS) are rarely available from efficacy trials. Methods to estimate the expected PFS and OS using a range of survival models were explored up to 30 years for patients receiving axitinib, cabozantinib, everolimus, nivolumab, and BSC for second-line amRCC. Several parametric survival models, including cubic splines, were fitted to the everolimus and nivolumab groups of the CheckMate 025 trial to provide baseline curves for PFS and OS. Model fit was assessed using the Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC), as well as clinical expert opinion to assess the plausibility of extrapolations. Hazard ratios (HRs), derived from a mixed treatment comparison (MTC), were applied to the everolimus curves to produce estimates for cabozantinib and BSC. A reliable HR could not be derived for axitinib due to a violation of proportional hazards (PH), as well as patient cross-over in the TARGET trial. Therefore, it was assumed that axitinib was equivalent to everolimus. For OS, there were slight differences in the AIC and BIC statistics across the treatment groups, but the best fitting model was considered to be the Weibull. For PFS, the best fitting model was the 2-knot spline, clearly indicated by the lowest AIC and BIC for both everolimus and nivolumab. The Weibull models produced a mean OS of 26.5, 38.1, 26.5, 30.3 and 15.0 months, for axitinib, cabozantinib, everolimus, nivolumab and BSC, respectively. The equivalent values for the 2-knot spline PFS models were 7.9, 15.9, 7.9, 10.8 and 2.8 months, respectively. The assumption of PH can be a limitation when comparing multiple treatments across different trials using an MTC. Practical solutions such as choosing the appropriate “baseline” trial and assuming clinical equivalence, where plausible, can help mitigate concerns in some cases.

PSY2 - Systematic Review and Meta-Analysis of The Efficacy And Safety Of Amfepramone and Mazindol As A Monotherapy for The Treatment of Obese or Overweight Patients

The aim of this study was to evaluate efficacy and safety of amfepramone, fenproporex and mazindol as a monotherapy for the treatment of obese or overweight patients. A systematic review of primary studies was conducted, followed by a direct meta-analysis (random effect) and mixed treatment comparison. Medline and other databases were searched. Heterogeneity was explored through I2 associated with a p-value. Of 739 identified publications, 25 were included in the meta-analysis. The global evaluation of Cochrane resulted in 19 studies with a high level of bias and six with unclear risk. Due to the lack of information in primary studies, direct meta-analyses were conducted only for amfepramone and mazindol. Compared to placebo, amfepramone resulted in higher weight loss in the short-term (<180 days; mean difference (MD) -1.281 kg; p<0.05; I2: 0.0%; p=0.379) and long-term (≥180 days; MD -6.518 kg; p<0.05; I2: 0.0%; p=0.719). Only studies with long-term follow up reported efficacy in terms of abdominal circumference and 5-10% weight reduction. These results corroborated the finding that the efficacy of amfepramone is greater than that of placebo. Treatment with mazindol showed greater short-term weight loss than that with placebo (MD -1.721 kg; p<0.05; I2: 0.9%; p=0.388). However, metabolic outcomes were poorly described, preventing a meta-analysis. A mixed treatment comparison corroborated the direct meta-analysis. Considering the high level of risk of bias and the absence of important published outcomes for anti-obesity therapy assessments, this study found that the evaluated drugs showed poor evidence of efficacy in the treatment of overweight and obese patients. Robust safety data were not identified to suggest changes in their regulatory status.

How Beneficial Is Individual Patient Data In A Mixed Treatment Comparison?

How Beneficial Is Individual Patient Data In A Mixed Treatment Comparison?

Evaluating The Clinical Effectiveness of Trastuzumab Emtansine (T-DM1) Versus All Other Treatments For Previously Treated, Unresectable, HER2-Positive Metastatic Breast Cancer (MBC): A Mixed Treatment Comparison (MTC)

Evaluating The Clinical Effectiveness of Trastuzumab Emtansine (T-DM1) Versus All Other Treatments For Previously Treated, Unresectable, HER2-Positive Metastatic Breast Cancer (MBC): A Mixed Treatment Comparison (MTC)

Mortality and operator experience with vascular access for percutaneous coronary intervention in patients with acute coronary syndromes: A pairwise and network meta-analysis of randomized controlled trials

BackgroundRecently, several meta-analyses of randomized controlled trials (RCTs) have shown that transradial access (TRA) reduces mortality compared to transfemoral access (TFA). However, a critical appraisal of these RCTs suggests that the findings could have resulted from a greater incidence of adverse events in the TFA groups rather than a beneficial effect of TRA. MethodsScientific databases and websites were searched for RCTs. Patients were divided into groups based on access type and whether the operator was a radial expert (RE) or non-radial expert (NRE). The groups were TFA-RE, TFA-NRE, TRA-RE, and TRA-NRE. Both a traditional meta-analysis and a network meta-analysis using mixed-treatment comparison models were performed. ResultsData from 13 trials including 15,615 patients were analyzed. The mortality rate for TFA-RE (3.54%) was more than double compared to TFA-NRE (1.61%). In pairwise meta-analysis, TFA-RE was associated with increased risk of mortality (RR: 1.72, 95% CI: 1.13–2.62; p=0.011) compared to TFA-NRE. In subgroup analysis, TFA-RE was associated with increased mortality (RR: 1.70, 95% CI: 1.24–2.34; p=0.001) compared to TRA, but TRA-NRE was not. Similarly, in mixed comparison models, TFA-RE was associated with increased mortality compared to TRA-NRE, TRA-RE, and TFA-NRE, but TFA-NRE was not, compared to TRA-RE and TRA-NRE. ConclusionRecently-reported survival differences between TRA and TFA may have been driven by adverse events in the TFA groups of the RCTs rather than a beneficial effect of TRA. This issue needs further investigation before labeling radial access a lifesaving procedure in invasively-managed patients with ACS.

Interventions for humeral shaft fractures: mixed treatment comparisons of clinical trials.

Nowadays, five main therapeutic options are used in treating humeral shaft fractures: external fixation, open reduction and plate osteosynthesis (ORPO), minimally invasive plate osteosynthesis (MIPO), dynamic compression plate (DCP), and intramedullary nail (IMN). Aiming to provide reliable evidence for clinical selection, we designed a network meta-analysis (NMA) to evaluate the efficacy of these treatments. NMA was conducted on Bayesian framework with software R 3.3.2 and STATA 13.0. Nonunion rate, radial nerve palsy rate, union time, complication rate, and infection rate were considered as primary outcomes. Mean operation time was the secondary outcome. The outcomes were measured by odds ratio (OR) value and corresponding 95% credible intervals (CrIs) or mean difference (MD) with 95% CrIs. Surface under cumulative ranking curve (SUCRA) was calculated to show the ranking probability of each treatment. Our results indicated that ORPO had a higher risk of radial nerve palsy than MIPO (OR=2.83, 95% CrIs=1.28-6.23), and DCP had a better performance in preventing complications than IMN (OR=0.31, 95% CrIs=0.11-0.84); no other significant difference were observed. According to the SUCRA results, MIPO had a high-ranking probability in almost all outcomes, while external fixation had lowest values in the majority of outcomes. We recommended MIPO as the optimal treatment for humeral shaft fractures after taking all outcomes into consideration; IMN was also recommended for its relatively good performance, but its complication still needed to be noticed.