Differential vulnerability and susceptibility: how to make use of recent development in our understanding of mediation and interaction to tackle health inequalities

The overall effect of an exposure on an outcome, in the presence of a mediator with which the exposure may interact, can be decomposed into 4 components: (1) the effect of the exposure in the absence of the mediator, (2) the interactive effect when the mediator is left to what it would be in the absence of exposure, (3) a mediated interaction, and (4) a pure mediated effect. These 4 components, respectively, correspond to the portion of the effect that is due to neither mediation nor interaction, to just interaction (but not mediation), to both mediation and interaction, and to just mediation (but not interaction). This 4-way decomposition unites methods that attribute effects to interactions and methods that assess mediation. Certain combinations of these 4 components correspond to measures for mediation, whereas other combinations correspond to measures of interaction previously proposed in the literature. Prior decompositions in the literature are in essence special cases of this 4-way decomposition. The 4-way decomposition can be carried out using standard statistical models, and software is provided to estimate each of the 4 components. The 4-way decomposition provides maximum insight into how much of an effect is mediated, how much is due to interaction, how much is due to both mediation and interaction together, and how much is due to neither.

Despite broad agreement that the vulnerable have a claim to special protection, defining vulnerable persons or populations has proved more difficult than we would like. This is a theoretical as well as a practical problem, as it hinders both convincing justifications for this claim and the practical application of required protections. In this paper, I review consent-based, harm-based, and comprehensive definitions of vulnerability in healthcare and research with human subjects. Although current definitions are subject to critique, their underlying assumptions may be complementary. I propose that we should define vulnerability in research and healthcare as an identifiably increased likelihood of incurring additional or greater wrong. In order to identify the vulnerable, as well as the type of protection that they need, this definition requires that we start from the sorts of wrongs likely to occur and from identifiable increments in the likelihood, or to the likely degree, that these wrongs will occur. It is limited but appropriately so, as it only applies to special protection, not to any protection to which we have a valid claim. Using this definition would clarify that the normative force of claims for special protection does not rest with vulnerability itself, but with pre-existing claims when these are more likely to be denied. Such a clarification could help those who carry responsibility for the protection of vulnerable populations, such as Institutional Review Boards, to define the sort of protection required in a more targeted and effective manner.