[Methods for controlling and evaluating residual confounding in the association analysis of observational study with...

The observational research based on big data in healthcare has attracted increasing attention, with the control and evaluation of residual confounding being the critical issue that needs to be solved urgently. This review summarized the methods for statistical adjustment and sensitivity analysis of residual confounding in the association analysis with a multicenter database. Based on individual-level data, the residual confounding can be adjusted in each subcenter using methods such as regression discontinuity design, while the pooled estimate can be obtained as a weighted average. Based on the center-level results, the Bayesian Meta-analysis method can adjust the pooled estimates. The sensitivity analysis of residual confounding can also be carried out using center-level data to calculate the E-value, p^(q), T^(r, q) and G^r,q. The abovementioned methods should be selected reasonably according to the requirements for practical applications, advantages, and disadvantages. For example, the use of subcenter individual data for residual confounding adjustment usually needs strict study design and frequent coordination; the Bayesian Meta-analysis is based on some strong assumptions; the interpretation of the results in the sensitivity analysis, such as E-value requires professional judgment to assess the risk of residual confounding. Therefore, the methods for controlling and evaluating residual confounding in association analysis based on multicenter databases still need further development and improvement.