Indirect Comparison Meta-analysis Research Articles

An indirect treatment comparison meta-analysis of digital versus face-to-face cognitive behavior therapy for headache

Cognitive behavioral therapy (CBT) is effective for headache disorders. However, it is unclear whether the emerging digital CBT is noninferior to face-to-face CBT. An indirect treatment comparison (ITC) meta-analysis was conducted to assess the relative effects between them using standard mean differences (SMDs). Effective sample size (ESS) and required sample size (RSS) were calculated to demonstrate the robustness of the results. Our study found that digital CBT had a similar effect on headache frequency reduction (SMD, 0.12; 95%CI, −2.45 to 2.63) compared with face-to-face CBT. The ESS had 84 participants, while the RSS had 466 participants to achieve the same power as a non-inferior head-to-head trial. Digital CBT is as effective as face-to-face CBT in preventing headache disorders. Due to the heterogeneity (I2 = 94.5%, τ2 = 1.83) and the fact that most of the included studies were on migraine prevention, further head-to-head trials are warranted.

Acupuncture versus tricyclic antidepressants in the prophylactic treatment of tension-type headaches: an indirect treatment comparison meta-analysis

BackgroundAcupuncture showed better improvement than sham acupuncture in reducing attack frequency of tension-type headache (TTH), but its effectiveness relative to first-line drugs for TTH is unknown, which impedes the recommendation of acupuncture for patients who are intolerant to drugs for TTH. We aimed to estimate the relative effectiveness between acupuncture and tricyclic antidepressants (TCAs) through indirect treatment comparison (ITC) meta-analysis.MethodsWe searched Ovid Medline, Embase, and Cochrane Library from database inception until April 13, 2023. Randomized controlled trials of TCAs or acupuncture in the prevention of TTH in adults were included. The primary outcome was headache frequency. The secondary outcomes were headache intensity, responder rate, and adverse event rate. Bayesian random-effect models were used to perform ITC meta-analysis, and confidence of evidence was evaluated by using the GRADE approach.ResultsA total of 34 trials involving 4426 participants were included. Acupuncture had similar effect with TCAs in decreasing TTH frequency (amitriptyline: mean difference [MD] -1.29, 95% CI -5.28 to 3.02; amitriptylinoxide: MD -0.05, 95% CI -6.86 to 7.06) and reducing TTH intensity (amitriptyline: MD 2.35, 95% CI -1.20 to 5.78; clomipramine: MD 1.83, 95% CI -4.23 to 8.20). Amitriptyline had a higher rate of adverse events than acupuncture (OR 4.73, 95% CI 1.42 to 14.23).ConclusionAcupuncture had similar effect as TCAs in reducing headache frequency of TTH, and acupuncture had a lower adverse events rate than amitriptyline, as shown by very low certainty of evidence.

Spironolactone versus Eplerenone in Patients with Resistant Hypertension: A Systematic Review and Indirect Meta-analysis

Background: Spironolactone and eplerenone, both mineralocorticoid receptor antagonists (MRAs), have been shown to be effective in the management of resistant hypertension (RH), although there is a lack of randomised controlled trials (RCTs) that directly comparing the two. This systematic review and indirect meta-analysis compares the two MRAs and their effectiveness in lowering blood pressure (BP) in patients with RH. Methods: RCTs comparing eplerenone or spironolactone with a placebo in RH patients were included in the review. The primary outcome was the mean difference (MD) of systolic blood pressure (SBP) and diastolic blood pressure (DBP). The secondary outcome was the MD of serum potassium levels. The pooled estimates of mean BP and mean potassium level difference were then analysed to attain the adjusted indirect comparisons. Results: Six RCTs involving 665 patients were included in the systematic review. The pooled MD of systolic and diastolic BP between eplerenone and placebo showed a reduction of −0.38 (p=0.0007) and −4.45 (p<0.0001), respectively. The pooled MD of systolic and diastolic BP between spironolactone and placebo showed a reduction of −4.82 (p=0.01) and −2.31 (p=0.006), respectively. The pooled MD of serum potassium levels between eplerenone and placebo as well as spironolactone and placebo was 0.16 (p=0.39) and −0.08 (p=0.59), respectively. An indirect comparison meta-analyses of the MD in systolic and diastolic BP (systolic MD 1.66; 95% CI [−3.46–6.78]; p=0.5250 and diastolic MD 2.14; 95% Cl [−0.63–4.91]; p=0.1293) as well as mean serum potassium levels (MD 0.24; 95% Cl, [−0.23–0.71]; p=0.313) between spironolactone and eplerenone, showed no significant difference. Conclusion: Spironolactone and eplerenone showed an equal reduction in systolic and diastolic BP, as well as serum potassium levels in patients with RH.

Baricitinib or Tocilizumab? Treatment of Patients Hospitalized With Severe COVID-19.

Baricitinib or Tocilizumab? Treatment of Patients Hospitalized With Severe COVID-19.

Vaginal progesterone gel vs. capsule for preterm birth prevention: an indirect comparison meta-analysis

Vaginal progesterone gel vs. capsule for preterm birth prevention: an indirect comparison meta-analysis

Comparative efficacy of amitriptyline, duloxetine and pregabalin for treating fibromyalgia in adults: an overview with network meta-analysis.

Treatment recommendations for fibromyalgia (FM) include a range of predominantly pharmacological treatment options designed to ensure the maintenance of symptoms and improvement in the quality of life of these patients. Our aim is to identify and compare the efficacy of amitriptyline (AMT), duloxetine (DLX), and pregabalin (PGB) for reducing pain intensity by 30% (R30%) and 50% (R50%) in adult patients with fibromyalgia. The review was conducted in the Medline/PubMed, Cochrane Library, and Embase databases up to February 2022. This study included systematic reviews (SR) of randomized clinical trials (RCTs) targeting adult patients over 18years of age diagnosed with fibromyalgia according to the criteria of scientific societies, which include the basic clinical diagnosis characterized by the presence of pressure sensitivity in at least 11 of the 18 tender points, in addition to the presence of widespread musculoskeletal pain for a period longer than 3months and a general assessment of the patient's health status. Pregnant women and children or adolescents were excluded. The Rob 2.0 tool from the Cochrane Collaboration was used to assess the risk of bias in RCTs. The quality of evidence of the reviews included was assessed according to the Grading of Recommendations Assessment, Development and Evaluation-GRADE. A meta-analysis for the evidence network was performed using the Bayesian approach, which allows simultaneous comparison of all treatment options (medication and dose). The different treatments were ranked according to the response rate according to the surface under the curve (SUCRA), which was expressed as a percentage. The results were presented in tables and figures. The protocol with the detailed methods was registered in PROSPERO (CRD42021229264). Eight systematic reviews were identified, and, from these, 15 clinical trials comparing AMT (n = 273), DLX (n = 2595), and PGB (n = 3,506) against placebo were selected. For the outcome R30%, PGB 450mg was superior to DLX 30mg and PGB 150mg, while DLX 20mg and 30mg were not superior to placebo. For the outcome R50%, AMT 25mg was superior to all other alternatives evaluated. The calculation of the SUCRA indicated that PGB 450mg was the best performance option for R30% and AMT 25mg for R50%. PGB 150mg was the drug with the worst performance in the two outcomes evaluated. The drugs evaluated showed benefits for pain reduction in patients with fibromyalgia. In the absence of direct comparison studies, indirect comparison meta-analyses are an important resource for assisting in clinical decision-making. Our data only provide an indicator of the effectiveness of the three drugs evaluated, but as with other health conditions, tolerability and safety are important for the decision-making process and clinical management. In this regard, we encourage caution in interpreting our data.

Eluxadoline Versus Antispasmodics in the Treatment of Irritable Bowel Syndrome: An Adjusted Indirect Treatment Comparison Meta-analysis.

Objective: Eluxadoline is a newly approved drug for irritable bowel syndrome (IBS), but it has rarely been compared with positive controls. We aimed to compare eluxadoline with antispasmodics in the treatment of IBS. Methods: We searched the OVID Medline, Embase, and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials (RCTs) comparing eluxadoline or antispasmodics with placebo. The search was conducted from 1 January 1980, to 1 September 2020, without any language restrictions. The primary efficacy outcome was the relief of abdominal pain, defined by a reduction of pain scores of at least 30% from baseline. The secondary efficacy outcome was the relief of global IBS symptoms, defined by a composite response of a decrease in abdominal pain and improvement in stool consistency on the same day for at least 50% of the days assessed. The data were pooled using a random-effects model. Outcome estimates were pooled by using Risk Ratios (RRs) and P-scores. Results: Forty-two trials with 8,457 participants were included from 45 articles. Compared with placebo, each of drotaverine, pinaverium, alverine combined with simethicone (ACS) and eluxadoline 100 mg was highly effective in the relief of abdominal pain, with drotaverine [RR, 2.71 (95% CI, 1.70 to 4.32), P-score = 0.95] ranking first. Drotaverine, otilonium, cimetropium, pinaverium, and eluxadoline 100 mg had significantly high the relief of global IBS symptomss, for which drotaverine [RR, 2.45 (95% CI, 1.42 to 4.22), P-score = 0.95] was ranked first. No significant difference was found between these interventions. Pinaverium had a significantly higher the relief of global IBS symptoms than eluxadoline [RR, 1.72 (95% CI, 1.33 to 2.21)] on sensitivity analysis. However, no significant difference was found in the number of adverse events between each intervention and the placebo. Conclusion: Our network meta-analysis showed that eluxadoline 100 mg was at least as effective as antispasmodics in relieving abdominal pain in IBS. But eluxadoline had more reported adverse events. Antispasmodics are still the first choice for the treatment of IBS.

POSA116 Cost-Utility of Ribociclib As the First-Line Treatment in Postmenopausal Women with Advanced/Metastatic Breast Cancer, Hormone Receptor Positive and Human Epidermal Growth Factor Receptor-2 Negative in Colombia

To estimate the cost-utility of ribociclib as the first-line treatment in postmenopausal women with advanced/metastatic breast cancer, Hormone Receptor positive (HR+) and HER2-, from the perspective of the Colombian health system. A partitioned survival model was built with pre-progression, post-progression and death health states, according to the areas under the curve for the survival functions, with a 40-year time horizon. Direct medical costs for medicines and their administration, monitoring, handling of adverse events and terminal care were included; a local expert validated resource usage. The sources of costs were price control circulars, SISMED, ISS and SOAT tariff manuals, and the database of sufficiency (values in USD 2021: 1 USD = 3,770.9 COP). The probabilities of the events were based on a systematic review and the hazard ratios of survival were estimated with an indirect comparison meta-analysis. Health utility values were extracted from the literature. A 5% discount rate was applied for outcomes and costs. Health effects were valued as Quality Adjusted Life Years (QALY). Cost-effectiveness was analyzed against a range of willingness to pay thresholds in a probabilistic sensitivity analysis type acceptability curve. In the base case, average values per patient are: USD$ 22,919.90/2.92 QALY for fulvestrant, USD$ 79,385.04/3.17 QALY for ribociclib+letrozole, USD$ 84,735.61/3.17 QALY for palbociclib+letrozole and USD$ 110,699.86/3.47 QALY for ribociclib+fulvestrant. Ribociclib+letrozole is a dominant alternative to palbociclib+letrozole and between a willingness to pay of USD$ 0.0-84,064 is the alternative with the highest probability of cost-effectiveness. Ribociclib+fulvestrant has the greater effectiveness among all alternatives and has extended dominance over ribociclib+letrozole; however, its incremental cost-effectiveness ratio exceeds the three times gross domestic product per capita threshold (USD$ 16,728.36). Ribociclib+letrozole is a cost-effective and cost-saving alternative to the Colombian health system, as a first-line treatment in postmenopausal women with advanced/metastatic breast cancer, HR+ and HER2-.

Comparison of monoclonal antibodies targeting CD38, SLAMF7 and PD-1/PD-L1 in combination with Bortezomib/Immunomodulators plus dexamethasone/prednisone for the treatment of multiple myeloma: an indirect-comparison Meta-analysis of randomised controlled trials

BackgroundMany clinical trials have assessed the effect and safety of monoclonal antibodies (MAbs) in combination with proteasome inhibitors or immunomodulators plus dexamethasone/prednisone for the treatment of multiple myeloma (MM). The treatment outcomes of comparing different MAbs in combination with the above-mentioned agents remained unclear. We performed the meta-analysis to indirectly compare the effect and safety of MAbs targeting CD38, SLAMF7, and PD-1/PD-L1 in combination with bortezomib/immunomodulators plus dexamethasone/prednisone for patients with MM.MethodsWe searched thoroughly in the databases for randomised controlled trials (RCTs) in which at least one of the three MAbs were included. We included eleven eligible RCTs with 5367 patients in the meta-analysis. Statistical analysis was carried out using StataMP14 and Indirect Treatment Comparisons software.ResultsWe calculated hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and relative risk (RR) for overall response rate, complete response (CR) or better, very good partial response (VGPR) or better, VGPR, partial response, stable disease, and grade 3 or higher adverse events among the three groups. The HRs for PFS of the CD38 group vs SLAMF7 group, CD38 group vs PD-1/PD-L1 group, and SLAMF7 group vs PD-1/PD-L1 group were 0.662 (95%CI 0.543–0.806), 0.317 (95%CI 0.221–0.454), and 0.479 (95%CI 0.328–0.699), respectively. The HR for OS of the CD38 group vs SLAMF7 group was 0.812 (95%CI 0.584–1.127). The RR for CR or better in the CD38 group vs SLAMF7 group was 2.253 (95%CI 1.284–3.955). The RR for neutropenia of the CD38 group vs SLAMF7 group was 1.818 (95%CI 1.41–2.344).ConclusionsTreatment with the CD38 group had longer PFS and better treatment response than that with the SLAMF7 or PD-1/PD-L1 group. In addition, the SLAMF7 group prolonged PFS compared with the PD-1/PD-L1 group and was associated with a lower incidence of grade 3 or higher neutropenia than the CD38 and PD-1/PD-L1 group. In conclusion, MAbs targeting CD38 are the best, followed by those targeting SLAMF7; MAbs targeting PD-1/PD-L1 are the worst when in combination with bortezomib/immunomodulators plus dexamethasone/prednisone for the treatment of MM.

Indirect treatment comparison of solriamfetol, modafinil, and armodafinil for excessive daytime sleepiness in obstructive sleep apnea.

Excessive daytime sleepiness associated with obstructive sleep apnea affects 9%-22% of continuous positive airway pressure-treated patients. An indirect treatment comparison meta-analysis was performed to compare efficacy and safety of medications (solriamfetol, modafinil, and armodafinil) approved to treat excessive daytime sleepiness associated with obstructive sleep apnea. Efficacy and safety measures assessed in this indirect treatment comparison included Epworth Sleepiness Scale (ESS), 20-minute Maintenance of Wakefulness Test (MWT20), Clinical Global Impression of Change (CGI-C), Functional Outcomes of Sleep Questionnaire (FOSQ), and incidence of treatment-emergent adverse events (any, serious, or leading to discontinuation). A systematic literature review identified 6 parallel-arm, placebo-controlled randomized controlled trials that randomized 1,714 total participants to placebo, solriamfetol, modafinil, or armodafinil. In this indirect treatment comparison, all comparators were associated with greater improvements than placebo on the ESS, MWT20, and CGI-C after 4, 8, and 12 weeks of treatment. Relative to comparators and placebo at 12 weeks, solriamfetol at 150 mg or 300 mg had the highest probabilities of improvement in the ESS, MWT20, and CGI-C. Modafinil (200 or 400 mg) and solriamfetol (150 or 300 mg) were associated with greater improvement on the FOSQ than placebo at 12 weeks. Less than 2% of patients using placebo or comparators experienced serious or discontinuation-related treatment-emergent adverse events. The results of this indirect treatment comparison show 12 weeks of treatment with solriamfetol, modafinil, and armodafinil resulted in varying levels of improvement on the ESS, MWT20, and CGI-C and similar safety risks in participants with excessive daytime sleepiness associated with obstructive sleep apnea. Ronnebaum S, Bron M, Patel D, etal. Indirect treatment comparison of solriamfetol, modafinil, and armodafinil for excessive daytime sleepiness in obstructive sleep apnea. J Clin Sleep Med. 2021;17(12):2543-2555.

Calcitonin Gene-Related Peptide Monoclonal Antibodies Versus Botulinum Neurotoxin a in the Preventive Treatment of Chronic Migraine: An Adjusted Indirect Treatment Comparison Meta-Analysis.

Purpose: Calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are new agents approved by the US Food and Drug Administration for preventive treatment of chronic migraine. Comparison between CGRPmAbs and previously approved Botulinum neurotoxin A (BoNT-A) will inform optimal preventive treatment of chronic migraine, but head-to-head trials are lacking. We therefore aimed to perform adjusted indirect comparison between CGRPmAbs and BoNT-A through a meta-analysis. Methods: OVID MEDLINE, EMBASE and the Cochrane central register of controlled trials, clinical registries, and government websites were searched from inception to September 2019. Randomized controlled trials comparing CGRPmAbs or BoNT-A with placebo in the preventive treatment of chronic migraine were included. The primary outcomes were headache days and migraine days measured at week 12. Data were synthesized by using a frequentist approach; and the treatments were ranked by P-score. Results: We included 10 trials (n = 4,678) after screening 1049 candidates. Six trials were with low risk of bias. Fremanezumab had an effect similar to BoNT-A in the reduction of headache days at week 12 (standard mean difference [SMD] 0.08, 95%CI -0.55 to -0.7). Galcanezumab reduced more migraine days than BoNT-A at week 12 (SMD, -0.94, 95%CI −1.24 to −0.63); fremanezumab showed similar findings (SMD, −0.55, 95%CI −0.85 to −0.24). Galcanezumab and fremanezumab had better effect in mitigating headache impact at week 12. CGRPmAbs and BoNT-A had similar adverse event rate. Conclusion: CGRPmAbs and BoNT-A had similar effect in the preventive treatment of chronic migraine. BoNT-A might be preferentially selected owing to its cost-effectiveness profiles. Further studies with direct comparison of the two treatments are warranted.

Comparison of Treatments for Nonmetastatic Castration-Resistant Prostate Cancer: Matching-Adjusted Indirect Comparison and Network Meta-Analysis.

For nonmetastatic castration-resistant prostate cancer (nmCRPC), 3 drugs under patent protection-apalutamide, enzalutamide, and darolutamide-were approved based on randomized, placebo-controlled trials; 1 drug with generic availability, abiraterone acetate, showed efficacy in a single-arm trial and is commonly prescribed. Lacking head-to-head trials, the optimal treatment for nmCRPC is unknown, despite widely varied treatment costs. We compared the efficacy and safety of nmCRPC treatments. We searched bibliographic databases, regulatory documents, and trial registries for nmCRPC trials. We included published results and, when available, original data. We performed matching-adjusted indirect comparison and network meta-analysis and compared treatments regarding metastasis-free survival, overall survival, and serious adverse events. We analyzed 5 trials with 4360 participants. Compared with placebo, abiraterone acetate engendered the lowest hazard of metastasis and death (hazard ratio [HR] = 0.22, 95% credible interval [CrI] = 0.12-0.41), followed by apalutamide (HR = 0.28, 95% CrI = 0.23-0.34), enzalutamide (HR = 0.30, 95% CrI = 0.25-0.36), and darolutamide (HR = 0.41, 95% CrI = 0.34-0.49); darolutamide led to the lowest hazard of death (HR = 0.69, 95% CrI = 0.53-0.90), followed by enzalutamide (HR = 0.73, 95% CrI = 0.61-0.87) and apalutamide (HR = 0.75, 95% CrI = 0.59-0.95); darolutamide resulted in the lowest odds of serious adverse events (odds ratio [OR] = 1.32, 95% CrI = 1.02-1.70), followed by enzalutamide (OR =1.43, 95% CrI = 1.08-1.89), apalutamide (OR = 1.58, 95% CrI = 1.23-2.03), and abiraterone acetate (OR = 1.94, 95% CrI = 1.17-3.22). For nmCRPC, darolutamide offered optimal efficacy and safety among approved drugs, and abiraterone acetate may offer comparable metastasis-free survival benefit with cost savings from generic availability. Future research is needed to more fully examine the benefit of abiraterone acetate.

Closure Techniques in Carotid Endarterectomy: Tracing the “Invisible” - Indirect Evidence from Randomised Controlled Trials with a Network Meta-analysis

According to the 2017 clinical practice guidelines of the European Society for Vascular Surgery on the management of atherosclerotic carotid and vertebral artery disease, “Eversion endarterectomy is recommended over routine primary arteriotomy closure”, whereas “The choice between eversion or patched endarterectomy should be left to the discretion of the operating surgeon”.1Naylor A.R. Ricco J.B. de Borst G.J. Debus S. de Haro J. Halliday A. et al.Editor's Choice – management of atherosclerotic carotid and vertebral artery disease: 2017 clinical practice guidelines of the European Society for Vascular Surgery (ESVS).Eur J Vasc Endovasc Surg. 2018; 55: 3-81Abstract Full Text Full Text PDF PubMed Scopus (491) Google Scholar The guidelines also conclude that “There is no evidence that patch type influences outcome”.1Naylor A.R. Ricco J.B. de Borst G.J. Debus S. de Haro J. Halliday A. et al.Editor's Choice – management of atherosclerotic carotid and vertebral artery disease: 2017 clinical practice guidelines of the European Society for Vascular Surgery (ESVS).Eur J Vasc Endovasc Surg. 2018; 55: 3-81Abstract Full Text Full Text PDF PubMed Scopus (491) Google Scholar The study by Lazarides et al. represents a step forward, discriminating between the various patch types and concluding that eversion endarterectomy and patching with bovine pericardium or polytetrafluoroethylene (PTFE) are associated with a similarly low 30 day stroke and death rate, while primary closure and Dacron, vein, or polyurethane patches perform statistically significantly worse.2Lazarides M.K. Christaina E. Argyriou C. Georgakarakos E. Tripsianis G. Georgiadis G. Network meta-analysis of carotid endarterectomy closure techniques.Eur J Vasc Endovasc Surg. 2021; 61: 181-190Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Eversion endarterectomy was also found to be associated with the lowest rate of restenosis compared with all other methods of arterial closure after carotid endarterectomy (CEA). Lazarides et al. have reached these conclusions using a novel and sophisticated methodological approach, called network meta-analysis, and should be commended for this high quality and resource demanding work. This method allows the combination of direct evidence from head to head studies, but additionally extends the analysis to incorporate indirect comparisons across trials based on a common comparator, using the effect estimates of the direct comparisons.3Salanti G. Indirect and mixed-treatment comparison, network, or multiple-treatments meta-analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool.Res Synth Methods. 2012; 3: 80-97Crossref PubMed Google Scholar In this way not only does it give the full picture instead of making pairwise comparisons, but it also ranks the various treatment modalities using summary outputs. In the study by Lazarides et al., eversion endarterectomy ranked first with respect to both 30 day stroke/death and late restenosis rates, followed by PTFE and bovine pericardium patch, although readers should be aware that a high probability of being the best does not necessarily mean a large difference in clinical outcomes.2Lazarides M.K. Christaina E. Argyriou C. Georgakarakos E. Tripsianis G. Georgiadis G. Network meta-analysis of carotid endarterectomy closure techniques.Eur J Vasc Endovasc Surg. 2021; 61: 181-190Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar The evidence provided by Lazarides et al. looks robust enough, as the authors have reported evaluation of the transitivity assumption, implying that it was equally likely that any patient could have been given any of the treatments in the randomised controlled trials network. Moreover, the comparison adjusted funnel plots did not reveal any evidence of asymmetry, with no significant publication bias, thus increasing the validity of the results. However, heterogeneity in definitions among the included studies did not allow the authors to evaluate other than 30 day stroke/death and late restenosis outcomes, while the effect of other covariates could not be assessed in a meta-regression analysis. By updating and promoting the use of universal reporting standards in future studies, we might be able to further focus on modelling multiple outcomes, account for the effect of confounding factors, and draw more conclusions about the optimal closure technique during carotid endarterectomy. Editor's Choice – Network Meta-Analysis of Carotid Endarterectomy Closure TechniquesEuropean Journal of Vascular and Endovascular SurgeryVol. 61Issue 2PreviewThere is discordance between reviews comparing eversion endarterectomy (EvE) with conventional carotid endarterectomy (CEA) mostly because under this term various “closure” techniques are included, from direct closure to a wide spectrum of patches with different materials. Full-Text PDF

A Systematic Review of the Clinical Efficacy of Treatments in Relapsed or Refractory Diffuse Large B Cell Lymphoma.

IntroductionNovel treatment options are needed to improve outcomes in transplant-ineligible relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). This systematic literature review evaluated clinical evidence on treatments for patients with R/R DLBCL ineligible for, or relapsed following, stem cell transplantation.MethodsWe assessed the feasibility of conducting an indirect treatment comparison (ITC) or network meta-analysis (NMA) to evaluate the relative efficacy and safety of polatuzumab vedotin in combination with bendamustine + rituximab versus other relevant treatments.ResultsThirty-seven studies were identified, of which 20 were eligible [seven randomized, controlled trials (RCTs); 13 observational/single-arm trials]. Due to a lack of RCTs, an ITC/NMA summary of the relative efficacy and safety of the treatment options was not possible. Only two of the seven RCTs had positive outcomes.ConclusionsThese findings highlight the paucity of published RCTs to establish the comparative efficacy of treatments for transplant-ineligible R/R DLBCL and lack of standard of care in this setting.Electronic Supplementary MaterialThe online version of this article (10.1007/s12325-020-01507-7) contains supplementary material, which is available to authorized users.

Major bleeding risk with non-vitamin K antagonist oral anticoagulant vs. aspirin in heart failure: network meta-analysis.

AimsRelative bleeding risks of different antithrombotic agents in heart failure (HF) patients is an important consideration in treatment decision making, making detailed comparative analysis desirable. The aim of this study was to conduct a network meta‐analysis to investigate the major bleeding risk for individual novel oral anticoagulants (NOACs) vs. aspirin among patients with HF.Methods and resultsWe searched Pubmed, EMBASE, Cochrane Collaboration Central Register of Controlled Clinical Trials, and Clinicaltrials.gov from 1966 to November 2019 to identify relevant randomized clinical trials. Studies comparing individual NOACs vs. aspirin were analysed using direct study‐level meta‐analysis. Studies comparing aspirin to warfarin and NOACs to warfarin were then additionally added using network (direct and indirect) study‐level meta‐analysis. Primary endpoint was major bleeding. Final analysis included nine trials with 34 367 participants, including one direct comparison trial (apixaban vs. aspirin) and eight indirect comparison trials against the shared warfarin comparator (four aspirin trials and one trial each of apixaban, dabigatran, rivaroxaban, and edoxaban). For apixaban, network meta‐analysis combing direct and indirect comparison showed that major bleeding risk might not be different between apixaban and aspirin (odds ratio, 1.18 [95% confidence interval, 0.38 to 3.65]) in HF patients. In contrast, indirect‐comparison meta‐analysis showed dabigatran, rivaroxaban, and edoxaban compared with aspirin might be associated with a higher risk of major bleeding in HF patients.ConclusionsIn network meta‐analysis, apixaban might be associated with a comparable risk of major bleeding compared with aspirin in patients with HF, while other NOACs might be associated with a higher risk. However, such results were not strongly convincing because of lack of direct comparison in an original trial and small sample size of trials and participants. A clinical trial directly comparing apixaban vs. aspirin in patients with HF and sinus rhythm may be worth undertaking.

Causal inference and adjustment for reference-arm risk in indirect treatment comparison meta-analysis.

Aim: To illustrate that bias associated with indirect treatment comparison and network meta-analyses can be reduced by adjusting for outcomes on common reference arms. Materials & methods: Approaches to adjusting for reference-arm effects are presented within a causal inference framework. Bayesian and Frequentist approaches are applied to three real data examples. Results: Reference-arm adjustment can significantly impact estimated treatment differences, improve model fit and align indirectly estimated treatment effects with those observed in randomized trials. Reference-arm adjustment can possibly reverse the direction of estimated treatment effects. Conclusion: Accumulating theoretical and empirical evidence underscores the importance of adjusting for reference-arm outcomes in indirect treatment comparison and network meta-analyses to make full use of data and reduce the risk of bias in estimated treatments effects.

“One more time”: why replicating some syntheses of evidence relevant to COVID-19 makes sense

• Given the urgent need for credible answers to high-priority questions about the health and social impacts of COVID-19, many systematic reviewers seek to contribute their skills and expertise. • Rather than embarking on unnecessary, duplicate reviews, we encourage the evidence synthesis community to prioritise purposeful replication of systematic reviews of evidence relevant to COVID-19. • We explain why replication of systematic reviews is important, how to carry out a replication, and when to consider replication of reviews.

Diagnostic accuracy of cardiac MRI, FDG-PET, and myocardial biopsy for the diagnosis of cardiac sarcoidosis: a protocol for a systematic review and meta-analysis

BackgroundCS constitutes a rare but potentially underdiagnosed and fatal disease. Its diagnosis remains difficult owing to the infrequent and indistinguishable symptoms and the lack of formal diagnostic criteria dependent upon the diagnostic techniques used. Early diagnosis and treatment, however, may help to counter its poor prognosis.We aim to characterize and compare the diagnostic accuracy of cardiac MRI, FDG-PET and myocardial biopsy for the diagnosis of cardiac sarcoidosis and to advance and compare methods for complex diagnostic test accuracy reviews and meta-analysis.MethodsFollowing a systematic review on DTA studies on the aforementioned topic, a four-part approach to meta-analysis will be used: (1) direct comparison of index tests with clinical reference standard, (2) indirect comparison of index tests with clinical reference standard, (3) addition of an alternative test to that indirect comparison (4) and Bayesian meta-analysis using results of part 3 as informative prior for comparisons analogous to part 1 and 2.DiscussionThe most widely recognized diagnostic algorithm for cardiac sarcoidosis is considered out of date, as it precedes the introduction of imaging techniques in diagnostic pathways. These novel imaging techniques, like CMR and FDG-PET scan, have emerged as promising diagnostic tools which may fill the current diagnostic gap. Thus, a systematic review and evaluation of CS diagnosis are much needed. Such an attempt is anticipated to alter the current diagnostic guidelines for CS by shedding more light on the role of sophisticated imaging techniques on prompt CS therapy and follow-up.Trial registrationPROSPERO, CRD42019047126

Application of computed tomography, positron emission tomography-computed tomography, magnetic resonance imaging, endobronchial ultrasound, and mediastinoscopy in the diagnosis of mediastinal lymph node staging of non-small-cell lung cancer: A protocol for a systematic review.

Background:Ruling out distant metastases, non-small cell lung cancer (NSCLC)treatment depends on the results of mediastinal node staging (N staging). Several diagnostic methods play central roles in mediastinal N staging. This study is intended to evaluate the existing diagnostic methods and report quality, and to search for the best method for staging mediastinal lymph nodes.Methods:We searched PubMed, Embase, and the Cochrane Library to identify relevant studies, including randomized controlled trials and retrospective studies. These studies report the application of computed tomography, positron emission tomography-computed tomography, magnetic resonance imaging, endobronchial ultrasound, and mediastinoscopy in the diagnosis of mediastinal lymph node staging of NSCLC. The quality of the literature was assessed using the Quality Assessment of Diagnostic Accuracy Study 2. The true positive, false positive, true negative, and false negative of each study was extracted. The corresponding sensitivity, specificity, and other indicators were calculated and the Summary Receiver Operating curve was established. Then, head-to-head and indirect comparison meta-analyses will be conducted.Results:The results of this study will be published in a peer-reviewed journal.Conclusion:This study will provide basis for mediastinal lymph node staging of non-small cell lung cancer.PROSPERO registration number:CRD42019145667

Histamine2-Receptor Antagonists, Proton Pump Inhibitors, or Potassium-Competitive Acid Blockers Preventing Delayed Bleeding After Endoscopic Submucosal Dissection: A Meta-Analysis.

Background: Endoscopic submucosal dissection (ESD) was commonly used for en bloc resection in gastric cancer and adenoma with the risk of delayed bleeding after ESD. We conducted a direct and indirect comparison meta-analysis to evaluate the best choice in preventing post-ESD bleeding among proton pump inhibitors (PPIs), histamine2-receptor antagonists (H2RAs), and the most widely used potassium-competitive acid blocker, vonoprazan. Methods: The Pubmed, Cochrane Library, and Embase were searched for randomized trials. We pooled odds ratios (OR) for preventing post-ESD bleeding using meta-analysis. Results: Sixteen randomized trials met the inclusion criteria including 2,062 patients. Direct comparisons showed slightly significant efficacy in PPIs rather than H2RAs in preventing post-ESD bleeding [OR: 1.83; 95% confidence interval (CI): 1.10 to 3.05] and vonoprazan was better than PPIs (OR: 0.46; 95% CI: 0.25 to 0.86). The adjusted indirect comparison indicated vonoprazan was superior to H2RAs (OR: 0.30, 95% CI: 0.12 to 0.74). In subgroup analysis, PPIs had similar efficacy as H2RAs in 4 weeks, while PPIs were better than H2RAs in 8 weeks’ treatment (OR: 1.91; 95% CI: 1.08 to 3.40). The superiority of vonoprazan than PPIs was more significant in combination therapy (OR: 0.18; 95% CI: 0.04 to 0.69). There was a significant difference in vonoprazan for 8 weeks of medication (OR: 0.44; 95% CI: 0.21 to 0.92). Conclusions: The effects of vonoprazan is better than PPIs than H2RAs in preventing bleeding after ESD. When vonoprazan combined with mucosal protective antiulcer drug in treatment or used in 8 weeks of medication, the efficacy may be even better.