## 3 Methodology
### Causal Links between RF-EMF Exposure Level and Duration and Potential Health Effects  
The methods for evaluating and integrating the evidence on environment and health topics are transitioning from an \"expert-based narrative\" to a \"systematic\" review. SRs of aetiological studies are regarded as the best-practice method for evaluating evidence used in decision-making [34]. Complexity is an inherent feature of environmental health hazard and risk assessments, and methodological advances in all evidence streams relevant to hazard/risk assessments (toxicology, epidemiology, and exposure science) are increasing the challenges for evidence assessment and integration. **Umbrella review of human cancer hazards from exposure to near-field and far-field sources of RF-EMF:** WHO is undertaking an updated assessment of health hazards from exposure to RF-EMF, including 10 systematic reviews of experimental and observational studies on six major topics (cancer, adverse reproductive outcomes, cognitive impairment, symptoms, oxidative stress, and heat-related effects) [35]. There have already been published detailed systematic review protocols for the effect of RF-EMF on different topics,such as [36; 37], which will be considered in NextGEM for setting out research questions and methodology. Cancer is the most relevant potential hazard of RF-EMF at exposure levels below current international guidelines. If RF-EMF exposure increased the risk of cancer, this would have serious public health consequences and require population-level preventive strategies, including a revision of the threshold-based limitation principle currently applied to non-ionizing exposure in the radiofrequency range [38]. Neoplastic diseases are also the most investigated potential adverse effect of prolonged exposure to RF-EMF from mobile communication, accounting for about 56% of all related epidemiological studies (n = 327) up to 2021, as indexed in the specialized literature database EMF-Portal ([[https://www.EMF-portal.org/en](https://www.EMF-portal.org/en)]([https://www.EMF-portal.org/en](https://www.EMF-portal.org/en)) (accessed on 1 March 2023)). NextGEM's consortium includes cutting-edge methodological and subject-matter expertise in umbrella reviews and meta-analyses required for a critical summary of findings from SRs of epidemiological studies on the potential carcinogenicity of RF-EMF [23], and will focus on this outcome. NextGEM will compile the available evidence on RF-EMF and cancer risk in humans by performing an umbrella review of relevant narrative or quantitative reviews published in the last decade. Umbrella reviews, defined as the systematic collection and evaluation of information taken from multiple systematic reviews and meta-analyses, have the potential to provide the highest quality of evidence, graded according to the criteria described by [PERSON] [39]. **Development and validation of a Risk Assessment model to assist evidence-informed decision making on RF-EMF exposure:** The basic existing assessments of risks associated with RF-EMF exposure need to be improved, and this is a capital objective of NextGEM. To this aim, relevant data from an exposure assessment, in vitro and in vivo experiments, the level of evidence resulting from the umbrella reviews of human observational studies, the evidence pertaining to experimental studies of carcinogenic effects of RF-EMF in animal and cells models, and the results of the human observational studies conducted within NextGEM will be integrated. Common exposure protocols will be defined at the early stages of this project to ensure the harmonized data collection required for a robust risk assessment. Based on stakeholder (industry, insurers, regulators, and consumers) input, requirements for output information criteria will be identified.