Synthesizing evidence from the earliest studies to support decision-making: To what extent could the evidence be reliable?

In evidence-based practice, new topics generally only have a few studies available for synthesis. As a result, the evidence of such meta-analyses raised substantial concerns. We investigated the robustness of the evidence from these earliest studies. Real-world data from the Cochrane Database of Systematic Reviews (CDSR) were collected. We emulated meta-analyses with the earliest 1 to 10 studies through cumulative meta-analysis from eligible meta-analyses. The magnitude and the direction of meta-analyses with the earliest few studies were compared to the full meta-analyses. From the CDSR, we identified 20,227 meta-analyses of binary outcomes and 7683 meta-analyses of continuous outcomes. Under the tolerable difference of 20% on the magnitude of the effects, the convergence proportion ranged from 24.24% (earliest 1 study) to 77.45% (earliest 10 studies) for meta-analyses of few earliest studies with binary outcomes. For meta-analyses of continuous outcomes, the convergence proportion ranged from 13.86% to 56.52%. In terms of the direction of the effects, even when only three studies were available at the earliest stage, the majority had the same direction as full meta-analyses; Only 19% for binary outcomes and 12% for continuous outcomes changed the direction as further evidence accumulated. Synthesizing evidence from the earliest studies is feasible to support urgent decision-making, and in most cases, the decisions would be reasonable. Considering the potential uncertainties, it is essential to evaluate the confidence of the evidence of these meta-analyses and update the evidence when necessary.