Living network meta-analysis was feasible when considering the pace of evidence generation.

OBJECTIVES: The aim of the study was to assess the feasibility of living network meta-analysis (NMA) taking into account the pace of evidence generation across different medical areas. STUDY DESIGN AND SETTING: We performed a systematic review to identify published NMAs. For each NMA, we calculated the cumulative number of new trials. To assess the feasibility of living NMA, we considered different update frequencies (4, 6, and 12 months), then evaluated the number of new trials to be included at each update in the NMA and the workload percentage for an update relative to the initial NMA. RESULTS: We identified 77 NMAs covering 17 different medical areas; 60 (78%) had fewer than four new trials included per year, on average, and 5 (7%) had more than seven trials. With an update frequency of 4, 6, and 12 months, the median number of new trials to be included in the NMA was 0 (interquartile range, 0-1), 1 (0-2), and 2 (1-4), respectively, with mean of 4%, 5%, and 11% workload per update, respectively. CONCLUSION: The workload associated with updating a living NMA represents about one-tenth of the initial workload; therefore, living NMA is manageable.

Comparative efficacy and safety of second-line treatments for advanced non-small cell lung cancer with wild-type or unknown status for epidermal growth factor receptor: a systematic review and network meta-analysis.

BACKGROUND: Docetaxel, pemetrexed, erlotinib, and gefitinib are recommended as second-line treatment for advanced non-small cell lung cancer (NSCLC) with wild-type or unknown status for epidermal growth factor receptor (EGFR). However, the number of published randomized clinical trials (RCTs) on this topic is increasing. Our objective was to assess the comparative effectiveness and tolerability of all second-line treatments for advanced NSCLC with wild-type or unknown status for EGFR by a systematic review and network meta-analysis. METHODS: MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and the US Food and Drug Administration website, as well as other sources, were searched for available reports up to June 6, 2017. Two reviewers independently selected published and unpublished reports of RCTs comparing any second-line treatments, extracted data and assessed the risk of bias of all included trials. We performed a Bayesian network meta-analysis. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included objective response (ObR), the number of serious adverse events, and quality of life. RESULTS: We included 102 RCTs involving 36,058 patients (62% male, median age 61 years, 81% with stage IV cancer, 80% smokers, and 92% with performance status 0-1). We revealed a differential reporting of outcomes between efficacy and safety outcomes. Half of the trials reported safety outcomes and less than 20% quality of life. For OS, nivolumab was more effective than docetaxel (hazard ratio (HR) 0.69, 95% credible interval (CrI) 0.56-0.83), pemetrexed (0.67, 0.52-0.83), erlotinib (0.68, 0.53-0.86), and gefitinib (0.66, 0.53-0.83). Pembrolizumab, atezolizumab, and pemetrexed plus erlotinib were also significantly more effective than docetaxel, pemetrexed, erlotinib, and gefitinib. For PFS, erlotinib plus cabozantinib was more effective than docetaxel (HR 0.39, 95% CrI 0.18-0.84), pemetrexed (0.38, 0.18-0.82), erlotinib (0.37, 0.18-0.78), and gefitinib (0.38, 0.18-0.82). Cabozantinib and pemetrexed plus erlotinib were also significantly more effective than the four recommended treatments. For ObR, no treatment was significantly more effective. The effectiveness of the four recommended treatments was similar and they were ranked among the 25 less-effective treatments. For safety, evidence is insufficient to draw certain conclusions. CONCLUSIONS: Nivolumab, pembrolizumab, atezolizumab, and pemetrexed plus erlotinib may be the most effective second-line treatments for NSCLC in terms of OS. The four recommended treatments seem to have relatively poor performance. However, the impact on life expectancy of immunotherapy versus other treatments should be further explored by future analyses, and more trials comparing the novel treatments are needed to reduce uncertainty in these results. TRIAL REGISTRATION: Registration number: PROSPERO ( CRD42015017592 ).

Uncertainty in Treatment Rankings: Reanalysis of Network Meta-analyses of Randomized Trials.

BACKGROUND: Ranking of interventions is one of the most appealing elements of network meta-analysis. There is, however, little evidence about the reliability of these rankings. PURPOSE: To empirically evaluate the extent of uncertainty in intervention rankings from network meta-analysis. DATA SOURCES: Two previous systematic reviews that involved searches of the Cochrane Library, MEDLINE, and Embase up to July 2012 for articles that included networks of at least 3 interventions. STUDY SELECTION: 58 network meta-analyses involving 1308 randomized trials and 404 interventions with available aggregated outcome data. DATA ANALYSIS: Each network was analyzed with a Bayesian approach. For each intervention, the surface under the cumulative ranking curve (SUCRA) and its 95% credible interval (95% CrI) were estimated. Through use of the SUCRA values, the interventions were then rank-ordered between 0% (worst) and 100% (best). DATA SYNTHESIS: The median width of the 95% CrIs of the SUCRA was 65% (first to third quartile, 38% to 80%). In 28% of networks, there was a 50% or greater probability that the best-ranked treatment was actually not the best. No evidence showed a difference between the best-ranked intervention and the second and third best-ranked interventions in 90% and 71% of comparisons, respectively. In 39 networks with 6 or more interventions, the median probability that 1 of the top 2 interventions was among the bottom 2 was 35% (first to third quartile, 14% to 59%). LIMITATION: This analysis did not consider such factors as the risk of bias within trials or small-study effects that may affect the reliability of rankings. CONCLUSION: Treatment rankings derived from network meta-analyses have a substantial degree of imprecision. Authors and readers should interpret such rankings with great caution. PRIMARY FUNDING SOURCE: Cochrane France.