Scientific research publications have grown at an astonishing rate overall, and for systematic reviews (SRs) in particular. A study on the epidemiology of SRs found that about 2500 SRs were published in Medline in 2004, 1 and grew to about 8000 SRs a year when replicated a decade later. 2 SRs combine evidence from primary research and stand at the top of the hierarchy of evidence, especially when meta-analyses are possible. SRs and other forms of knowledge synthesis (e.g., scoping reviews, rapid reviews, realist reviews, evidence maps) 3 are a key source of synthesised evidence for informing the decision-making of clinicians as well as other health stakeholders (e.g., public health authorities, health planners, health managers, and policy-makers). [4][5][6][7][8][9] To do so, the family of SRs help identify, characterise, integrate, and synthesise the array of primary research findings within a topic or research question that otherwise end-users cannot keep up with or combine for themselves.However, SRs are only valid if they are rigorous and transparent, to be trustable. With this regard, methodological assessments of SRs and other forms of knowledge synthesis continue to show that conduct and reporting gaps remain a commonplace, albeit improved over time. 2,[10][11][12][13][14] For example, studies continue to find low compliance rates with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses 15 ) reporting guidelines, 2,13 as well as selective reporting. [10][11][12] In a remarkable example, a study comparing the published SRs with the prospectively registered study protocol has found that a third of SRs did not specify or change the primary outcome, that is, a major review protocol deviation that raises multiple questions on the issues of transparency. 10 On the negative side, one can expect worse deviation rates for the conjunct of SRs which did not take the step towards increased transparency of prospectively registering their review protocols. Just the fact that one has no means to really seize the magnitude of the problem for the non-registered reviews is a major problem in itself -for the sake rigour, transparency, and trust in SRs. On the positive side, SRs with a prospective register for example, enable peer-reviewers and editors in identifying SR deviations from the final report to the planned procedures. Editors or reviewers can then ask authors for the due report of that deviation and its rationale, being able to appraise the reported deviations accordingly. Otherwise, there are no means for deviations, due or undue, to be traced. Of note, sometimes protocol deviations are justifiable or even desirable in the face of evolving circumstances, but here transparency and trust are paramount, that is, not omitting or concealing deviations, providing the rationale for the deviations, and providing the means for the deviations to be traced, reported, and appraised.When study protocols are prospectively registered, deviations can be identified, prevented, or addressed. Due deviation...