eHeath supportive interventions have become essential complementary solutions in cancer care to enhance support at the distance between treatment sessions, with evidence of improving patient outcomes. This potential to impact clinically-relevant outcomes is a major determinant of success in any health intervention, influencing its funding, development, adoption and implementation in real-world practice. In the particular case of eHealth interventions, the complexity of evaluating effectiveness goes beyond the selection of intervention-sensitive outcomes that are both clinically- and person-relevant. The specificities of these complex health interventions related to the delivery context and the self-paced interaction, lead to many uncertainties such as, intervention’s dosage and exposure, that determine greatly an intervention’s effect. Therefore, equally important to determine the intervention’s effect, is understanding the factors leading to that effect. Such ambitions might challenge the implementation of the gold standard of randomized controlled trials to evaluate intervention’s effectiveness as there might be too many dimensions to be controlled. 

Departing from our experience as oncology nursing researchers involved in different eHealth interventions’ development and evaluation, we discuss these complexity dimensions in light of well-established methodological frameworks and guidance for complex interventions, towards a pragmatic approach to effectiveness study design of eHealth interventions.