ObjectivesTo systematically evaluate the effects of second-generation ALK-inhibitors: Ceritinib and Alectinib on ALK+ NSCLC patients.MethodsPubMed, EMbase, The Cochrane Library, WanFang Data, ClinicalTrials.gov and VIP databases were systematically searched for clinical trials containing treatment of two principal second-generation ALK-inhibitors for ALK (+) NSCLC patients from inception to December 31st, 2017. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias included in the studies. Stata 12.0 software was used for meta-analysis.ResultsEleven studies were included. Meta-analysis showed that the ORR of all was 57% (95%CI 0.48 to 0.66, P<0.001). The ORR of patients with Crizotinib-resistance was 51% (95%CI 0.44 to 0.57,P<0.001). The IDCR of patients who had brain metastases was 78% (95%CI 0.71 to 0.86,P<0.001).ConclusionsThe second-generation ALK-inhibitors has effect on ALK (+) NSCLC. Due to limitation of the included studies, more larger sample studies are required to verify above conclusions.
Objective To form the list of methodological quality evaluation and explanation for the selection of objective performance criteria in single arm trial, and initially construct a methodological guiding tool for the selection and evaluation of target value, so as far to provide a research basis for improving the system of single-arm trial quality evaluation by objective performance criteria method. Methods Combining the bias risk assessment method of observational study, interventional trails, domestic and foreign policy documents, and systematically collecting the common bias and evaluation key points, preliminarily proposing the list of methodological quality evaluation and explanation for the selection of objective performance criteria in single-arm trial, via two rounds of expert consensus voting using nominal group method, finally formulating the list based on the voting results and expert opinions. Results Through two rounds of discussion, sorting, comprehensive expert opinions, we improved the corresponding items in the list and finally formed the list of methodological quality evaluation and explanation for the selection of objective performance criteria in single-arm trial, which included four areas: authority, traceability, comparability, and reliability, including 10 items. The entries in each field considered both design and implementation throughout the clinical trial. Conclusion The methodology list developed in this study provides methodological guidance for the selection of objective performance criteria and quality evaluation, and provides a solid theoretical basis for the establishment of a complete methodological system of quality evaluation for objective performance criteria single arm trails.
Randomised controlled trials are often difficult to conduct for rare diseases, the treatment of life-threatening and serious diseases with no effective treatment options, and single-arm clinical trials are one of the most common choices. However, single-arm clinical trials lack a control group, making it difficult to determine whether the observed treatment effects stem from the drug itself or are influenced by natural disease progression, placebo effects, or selection bias. In recent years, with the continuous accumulation of real-world data, it is possible to use real-world data to construct an external control for single-arm clinical trials. However, it is necessary to carefully consider how to select appropriate external control data to enhance the credibility of the results. Based on the existing studies and relevant laws and regulations in China and abroad, this study expounds the key considerations of using real-world data to construct the external control of single-arm clinical trials on the source data from the perspective of external control setting model, reference intervention selection, data source, and so on. This study could provide references for relevant researchers to conduct similar studies.