meta分析在生物医学领域的应用

Meta-Analysis and Bayesian Meta-Analysis of Phase III Randomized Controlled Trials-Bortezomib-Based Versus Non-bortezomib-Based Post-Transplantation Treatment in Multiple Myeloma Patients,刘小平 MS、邵亮 MD、刘尚勤MD武汉大学中南医院Colin K. He, PhD., MS,Multiple myeloma (MM),Multiple myeloma is the malignant counterpart of long-lived plasma cells with a strong tropism for bone and bone marrow.,Epidemiology of MM,Multiple myeloma is the second most frequent haematological malignancy with an age-adjusted incidence of six per 100 000 per year in the USA and Europe.The incidence of multiple myeloma is two to three times higher in African Americans, making it the most common haematological malignancy in this ethnic group,Clinical Presentations,Bone pain; lytic lesions on imaging; unexplained hypercalcemia; acute renal failuresystemic signs : fatigue, weakness, and weight loss; or increased total serum protein level,ent,Overall survival after diagnosis in patients with multiple myeloma,Post-transplantation therapy,Consolidation is short-term therapy administered to enhance the rate and depth of a previously obtained responseMaintenance therapy is given for an extended time, and the goal of maintenance therapy is the extension of response duration, and ultimately of PFS and overall survival (OS),Flow diagram of study selection,Funnel plots of overall response rate before and after the “trim and filled” method was applied,Meta-analysis of overall response rate after one hypothetical study was added to the integrated analysis,INSTALL RCMDRPLUGIN.EZR,http:/www.jichi.ac.jp/saitama-sct/SaitamaHP.files/statmedEN.html,Manuel,MANUEL,Fixed ModelDont check Conduct random,Meta-analysis of complete response or near complete response-Forrest and Accumulated Forest Plots,R Code for Accumulated Forest,R Code (Case Sensitivity):resCum- metacum(res, pooled=fixed) forest(resCum),Relative Risk/Risk Difference,Progression-free survival (PFS) -Forest and Accumulation Forest Plots,Overall survival (OS),Bayesian Meta-AnalysisOverall survival (OS),Log Scale Estimate Var 2.5% 50% 97.5%HR mu -0.25234945 0.09173044 -0.84746101 -0.2529008 0.3391747tausq 0.00000000 0.00000000 0.00000000 0.0000000 0.0000000Q 1.04716200 1.95187754 0.05964741 0.5053460 5.0288633Isq 0.05826869 0.02468276 0.00000000 0.0000000 0.6022958Sample size is not big. Is it reliable？Bayesian approach was apply by simulation (10,000)Result is Estimate Var 2.5% 50% 97.5%HR mu 0.7769732 1.096069 0.4285015 0.7765449 1.403789tausq 1.0000000 1.000000 1.0000000 1.0000000 1.000000Q 2.8495526 7.041897 1.0614622 1.6575589 152.759271Isq 1.0599998 1.024990 1.0000000 1.0000000 1.826307,All grade adverse events(AEs) during post-transplantation therapy,Bayesian Meta-Analysis Log Scale Estimate Var 2.5% 50% 97.5%OR mu 0.6321885 1.413086e+02 0.1488272 0.9403324 1.7374154tausq 739.6111083 2.884788e+06 0.0000000 0.0000000 0.0000000Q 2.6258743 2.002579e+00 1.6239331 2.0763028 6.7445221Isq 0.5512679 2.051132e-02 0.3842111 0.5183747 0.8517315 Estimate Var 2.5% 50% 97.5%OR mu 1.881724 2.341809e+61 1.160472 2.560833 5.682637tausq Inf Inf 1.000000 1.000000 1.000000Q 13.816649 7.408137e+00 5.073004 7.974929 849.393099Isq 1.735452 1.020723e+00 1.468455 1.679296 2.343702,Regular Meta-analysis was insignificant for All Grade Adverse Event, but Bayesian Meta-analysis was significant.,Meta-AnalysisGrade 3 or 4 adverse event,Bayesian Meta-Analysis Grade 3 or 4 adverse event,Log Scale Estimate Var 2.5% 50% 97.5%mu 0.5705096 0.27536991 -0.4517511 0.5679178 1.6058681tausq 0.0000000 0.00000000 0.0000000 0.0000000 0.0000000Q 3.6706504 1.99408881 2.6773026 3.1304453 7.7344376Isq 0.4043860 0.02065166 0.2529795 0.3611133 0.7414162Sample size is not big. Is it reliable？Bayesian approach was apply by simulation (10,000)Result is Estimate Var 2.5% 50% 97.5%mu 1.769168 1.317018 0.6365125 1.764589 4.982183tausq 1.000000 1.000000 1.0000000 1.000000 1.000000Q 39.277444 7.345507 14.5458047 22.884167 2285.722952Isq 1.498382 1.020866 1.2878568 1.434926 2.098906,MAIN RESULTS,Pooled ORs for the rates of overall response rate (ORR) and completes response and near complete response (CR/nCR) were 1.85 (95% CI: 1.29-2.64) and 1.75 (95% CI: 1.42-2.15), respectively. Pooled hazard ratio (HR) for PFS favored bortezomib-based therapy over non-bortezomib-based therapy (0.73, 95% CI: 0.67-0.81), while no statistically significant difference could be found between the two groups regarding the pooled HR for 3-year OS. Incidence rates of overall adverse event (AE) and grade 3 and 4 peripheral neuropathy (PN) were similar in the bortezomib-based groups and the non-bortezomib-based groups (p=0.12 and p=0.41, respectively). Meta Odd Ratio of all grade adverse events(AEs) is different from Bayesian Meta,CONCLUSIONS:,Bortezomib-based therapy after ASCT, with tolerable AEs, can obviously improve