To the next level, in planta experiments in controlled environments, i.e., phytotron cabinets, growth chambers, greenhouses and screenhouses, can be carried out to test the efficacy of both active substances and agrochemicals on model pathosystems as well as obligate pathogens. In these experimental conditions, phytotoxicity and adverse effects on non-target plant species can also be evaluated. Overall, in vitro and in planta experiments (pre-open field studies) can be compared to in vitro/in vivo preclinical research of biomedical area, at the base of the evidence-based phytoiatry pyramid (Figure 2). Following this parallelism, multi-year open field trials, with positive (untreated) and negative (reference standard) controls, performed in a completely randomized design are at the top of the pyramid, providing the highest level of evidence on efficacy of plant protection products including fungicides, elicitors, plant activators, insecticides and herbicides. Figure 1: Pyramid of scientific evidence—Evidence-based medicine (EBM). In biomedical sciences, a pyramid represents the quality of scientific evidence; the base consists of pre-clinical research, with in vitro and in vivo experiments, which provides insights towards potential efficacy of a certain therapy. Clinical research represents a higher level of evidence, referring to in human studies; in this context, randomized controlled trials are methodologically the best current clinical studies. At the apex, updated systematic reviews and meta-analyses are considered the best available knowledge, suitable for clinicians to face decision-making (adapted from [PERSON] et al., 2015 [1]). Of course, to design and perform an open-field trial is complex, and a number of general principles should be followed. First, the concept of Good Plant Protection Practice (GPP) was defined by the European and Mediterranean Plant Protection Organization (EPPO), a specific set of recommendations including guidelines on decision-making for choice of active substances and formulations, dosage (and appropriate volume), number of applications, timing or frequency of applications, equipment and method of application [2]. In addition, EPPO provides a number of standards covering two application fields: phytosanitary measures and plant protection products. Main topics include analysis of efficacy evaluation trials, efficacy evaluation of plant protection products (PPPs), number of efficacy trials, minimum effective dose, principles of acceptable efficacy and dose expression for PPPs, to name a few [3]. In addition, we have to take into account that legislations on PPPs are demanding, lengthy and costly, especially in the EU where issues related to their assessment and evaluation trials are controlled by the regulation EC 1107/2009 placed on the market of PPPs. During the approval process, the steps concerning the registration of new PPPs are declined because they require multi-year field trials to prove the efficacy of a given PPP against a target pest (sensu lato) under different pedo-climatic situations ruling out any negative effect on non-target organisms. Not last, systematic reviews (and meta-analyses) are not used in phytoiatry/plant pathology research as a powerful tool to reach the highest level of evidence in a specific phytosanitary issue. Therefore, we believe that the plant protection sector can neither be apart from considering that different levels of scientific evidence actually exist nor disregard a modern evidence-based approach.