THE EFFECT DIRECTION SHOULD BE TAKEN INTO ACCOUNT WHEN ASSESSING SMALL-STUDY EFFECTS

Objective: Studies with statistically significant results are frequently more likely to be published than those with non-significant results. This phenomenon leads to publication bias or small-study effects and can seriously affect the validity of the conclusion from systematic reviews and meta-analyses. Small-study effects typically appear in a specific direction, depending on whether the outcome of interest is beneficial or harmful, but this direction is rarely taken into account in conventional methods. Methods: We propose to use directional tests to assess potential small-study effects. The tests are built on a one-sided testing framework based on the existing Egger's regression test. We performed simulation studies to compare the proposed one-sided regression tests, conventional two-sided regression tests, as well as two other competitive methods (Begg's rank test and the trim-and-fill method). Their performance was measured by type I error rates and statistical power. Three real-world meta-analyses on measurements of infrabony periodontal defects were also used to examine the various methods’ performance. Results: Based on simulation studies, the one-sided tests could have considerably higher statistical power than competing methods, particularly their two-sided counterparts. Their type I error rates were generally controlled well. In the case study of the three real-world meta-analyses, by accounting for the favored direction of effects, the one-sided tests could rule out potential false-positive conclusions about small-study effects. They also are more powerful in assessing small-study effects than the conventional two-sided tests when true small-study effects likely exist. Conclusion: We recommend researchers incorporate the potential favored direction of effects into the assessment of small-study effects.