From Uptake to Therapeutic Function in Engineered Exosome Delivery Systems.

Evidence-based medicine (EBM) has profoundly reshaped clinical and public health practice by privileging methodological rigor, reproducibility, and hierarchical grading of evidence.[] Within this architecture, systematic reviews and meta-analyses (SR-MA) are widely regarded as occupying the apex of the evidence pyramid because they synthesize findings across multiple primary studies to enhance statistical precision and generalizability.[] Over time, this methodological hierarchy has become embedded not only in clinical guideline development but also in funding decisions, academic promotion criteria, journal impact metrics, and global research prestige structures.[] The growth trajectory of SR-MA has been striking. Ioannidis documented that between 1986 and 2015, more than 266,000 meta-analyses and nearly 59,000 systematic reviews were indexed in PubMed, reflecting a growth rate exceeding 2,600%, compared with a 153% increase for overall publications.[] In certain years, systematic reviews have been published at a pace that rivals or even exceeds the production of new randomized controlled trials (RCTs).[] While the expansion of synthesis science reflects legitimate efforts to consolidate fragmented evidence, the scale and velocity of growth invite reflection on proportionality and research prioritization.[] These concerns assume particular relevance in low- and middle-income countries (LMICs), where research infrastructure, funding ecosystems, and academic incentives are evolving.[] In many settings, SR-MA are seen as efficient routes to publication requiring fewer resources than primary research; however, when synthesis dominates research portfolios, it raises opportunity costs by limiting original inquiry, translational experimentation, and contextual innovation.[]