证据质量升级的最常见原因是效应量大。当方法学严谨的观察性研究表明风险至少降低或增加2倍时，GRADE建议考虑将证据质量升高1级；当风险至少降低或增加5倍时，考虑将证据质量升高2级。当存在剂量-反应关系，或所有合理的混杂、偏倚会降低明显的治疗效应，或混杂、偏倚使得结果无效为假效应时，系统评价作者和指南制定者也可考虑升高证据质量。其他考虑因素包括起效迅速、潜在的疾病（状态）趋势以及间接证据。
Objective To evaluate the role of systematic lymphadenectomy (SL) vs. unsystematic lymphadenectomy (USL) for improving overall survival (OS) in epithelial ovarian cancer (EOC). Methods The databases such as PubMed, EMbase, The Cochrane Library, Evidence-Based Medicine Reviews (EBMR), CBM, CNKI and VIP were searched between January 1, 1995 and December 31, 2010, the randomized controlled trials (RCTs) and observational studies on SL vs. USL in treating EOC were included. Based on Cochrane handbook, the data were extracted, the methodological quality was assessed, and then meta-analyses were conducted by using RevMan 5.0 software. Results The total 13 studies involving 22 796 patients were included, including 5 420 patients in the SL group, and the other 17 376 patients in the USL group. Two of the 13 studies were RCTs, and the other 11 were observational studies (including 2 studies retrieved from SEER data). The analyses on 2 RCTs showed that compared with USL, a) SL could not improve 5-PFS (OR=0.70, 95%CI 0.40 to 1.22, P=0.21) in early-stage EOC (FIGO I to II), but it did improve 5-PFS (OR=0.62, 95%CI 0.40 to 0.96, P=0.03) in advanced-stage EOC (FIGO III to IV); b) SL could not improve 5-OS in both early-stage EOC (OR=0.84; 95%CI 0.44 to1.58, P=0.58) and advanced-stage EOC (OR=0.93, 95%CI 0.64 to 1.37, P=0.73); and c) SL could not improve 5-OS in both early-stage (OR=0.84, 95%CI 0.44 to 1.58, P=0.58) and advanced-stage (OR=0.93, 95%CI 0.64 to 1.37, P=0.73) of EOC patients who had optimal tumor dubulking surgery. The analyses on observational studies showed that compared with USL, a) SL could not improve 5-PFS in both early-stage EOC (OR=0.38, 95%CI 0.08 to 1.74, P=0.21) and advanced-stage (OR=2.88, 95%CI 0.95 to 8.72, P=0.06) EOC; b) Whether SEER impacts were excluded or not, SL did improve 5-OS in both early-stage EOC (OR=0.54, 95%CI 0.46 to 0.63, Plt;0.000 01) and advanced-stage (OR=0.47, 95%CI 0.43 to 0.52, Plt;0.000 01) EOC; and c) For EOC patients who had optimal tumor dubulking surgery, SL could not improve 5-OS in early-stage (OR=0.32, 95% CI 0.02 to 6.19, P=0.45), but it did improve 5-OS in advanced-stage (OR=0.53, 95%CI 0.32 to 0.88, P=0.01). Conclusion These findings suggest that maybe SL can improve 5-PFS and 5-OS in EOC. However, the efficacy of SL on 5-PFS and 5-OS is still undetermined, so more relevant studies are required for further investigating the role of SL in EOC.
The necessity and methods of systematic review or Meta-analysis of observational studies were introduced. The difference between the systematic review or Meta-analysis of observational studies and randomized controlled trials was also described.
ObjectiveTo assess whether pre-operative use of infliximab (IFX) will increase the risk of post-operative infectious complications in patients with inflammatory bowel disease (IBD). MethodsPubmed, Web of Science, CBM, CNKI and Wanfang database were searched for all the trials that investigated the effects of infliximab on postoperative infectious complication rates in patients with IBD between January 1990 and April 2013. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted data and assessed the quality of the included studies. Then, meta-analysis was performed using RevMan 5.1 software. ResultsTotally, 14 cohort studies were finally included in the review. There was no significant difference on infectious complications [RR=0.99, 95%CI (0.47, 2.07), P=0.97] between IFX groups and control groups with ulcerative colitis. The same results were found in patients with Crohn's disease on infectious complications [RR=1.32, 95%CI (0.87, 1.98), P=0.19]. ConclusionPre-operative infliximab use is safe and does not increase the risk of post-operative infectious complications in patients with IBD.
ObjectiveTo evaluate the association between H2RA and the risk of hip fracture by performing a meta-analysis. MethodsWe searched CNKI, PubMed and EMbase from inception to September 19th 2016, to collect case-control studies or cohort studies reporting the risk of hip fracture with H2RA. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed using Stata 13 software. ResultsEleven studies involving 206 276 hip fracture cases were included. The result of meta-analysis showed that patients receiving H2RA therapy had approximately 1.12 times the risk of developing hip fracture compared with nonusers (OR=1.12 95%CI 1.02 to 1.24, P=0.022). Subgroup analyses by interval time indicated that the risk appeared greater with the continuous users (OR=1.11, 95%CI 1.01 to 1.24, P=0.039) whereas the discontinuous users was not significantly associated with hip fracture risk. ConclusionH2RA therapy may be associated with an increased risk of hip fracture. For patients with intermittent medication, the side effect may disappear by discontinuation of PPI use for at least 30 days, but the study did not find time-effect relationship or dose-effect relationship. Considering the limitations of this study, more rigorous clinical trials evaluating the potential side-effect of H2RA are needed.
Compared with traditional clinical trials, the real-world studies set higher requirements on the authenticity (reality), applicability, and timeliness of the evidence obtained. In this paper, we brought up a hypothesis that creating synergies between observational and experimental studies may meet these requirements. And then it was discussed in three aspects including providing evidence, research design and execution. In addition, data analysis facilitated generating efficient and robust evidence which was in support of decision making. Finally, some enlightenment may be offered for Traditional Chinese Medicine evaluation methods based on the synergies of both study types.
The level of evidence in randomized controlled studies is high. However, it cannot be widely applied due to its high cost, external authenticity, ethics and other reasons. The traditional observational studies reduce the internal authenticity due to various confounding factors, and the level of evidence is low. Regression discontinuity design (RDD) is a design that observes and compares outcome of object around the threshold under practical clinical conditions. Its capability to adjust confounding factors is second only to that of randomized control studies. It can be used in cases where the intervention (or exposure) is directly related to the value of a continuous variable. For instance, whether an HIV patient needs antiretroviral treatment mainly depends on whether the CD4 cell count is lower than 200/μL. Because the measurement of continuous variables has random error, whether intervention is given near the threshold or is close to random, the baseline of patients in the intervention group and non-intervention group near the threshold should be balanced and comparable. Based on this assumption, the causal effect of intervention (or exposure) and outcome can be estimated by comparing the outcomes of populations near the threshold. RDD is mainly applicable to the study of classification outcomes in medicine, among which two-stage least square method, likelihood ratio based estimation method and Bayesian method are more commonly used model estimation methods. However, the application conditions of RDD and the requirement of sample size limit its extensive application in medicine. With the improvement of data accessibility and the development of real world research, RDD will be more widely used in clinical research.
Observational studies based on real-world data are providing increasing amount of evidence for evaluating therapeutic outcomes, which is important for timely decision-making. Although time and costs for data collection could be saved using real-world data, it is significantly more complex to design real world researches with lower risk of bias. In order to enhance the validity of causal inference and to reduce potential risk of bias in real world studies, the Working Group of China Real world data and studies Alliance (China REAL) has formulated recommendations for designing observational studies to evaluate therapeutic outcomes based on real-world data. This guidance introduces design types commonly used in real world research; recommends key elements to consider in observational studies, including sample selection, specifying and allocating exposures, defining study entry and endpoints, and pre-designing statistical analysis protocols; and summarizes potential biases and corresponding control measures in real-world studies. These recommendations introduces key elements in designing observational studies using real-world data, for the purpose of improving the validity of causal inference. However, the application scope of these recommendations may be limited and warrant constant improvement.
Propensity score methods belong to an analytical approach by incorporating the measured covariates and mimicking randomization to enhance the comparability between groups, hence reducing the impact of potential confounding in observational studies. Propensity score methods have been increasingly used in observational studies. This paper illustrates the principle and the methods based on the propensity score, in combination with its application in observational studies. It also compares results from propensity score methods with those from multivariable regression and randomized controlled trials. It was found that currently there has been a lack of recommendations for the selection of propensity score methods. Differences may exist when comparing results from propensity score methods with findings from typical regression analyses and randomized controlled trials.
Objective To systematically review the association between periodontal disease during pregnancy and the risk of gestational diabetes mellitus (GDM). Methods PubMed, Web of Science, CBM and CNKI databases were electronically searched to collect studies on periodontal disease and GDM from inception to October 23, 2021. Two researchers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed using RevMan 5.4 software. Results A total of 11 studies were included, involving 2 910 pregnant women. The results of meta-analysis showed that pregnant women with periodontal disease during pregnancy reported more GDM than normal pregnant women (OR=1.81, 95%CI 1.31 to 2.50, P=0.000 3). Conclusion The current evidence suggests that there is a positive association between periodontal disease during pregnancy and the risk of GDM. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.