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. 2021 Dec 30;23(4):1115–1132. doi: 10.1093/biostatistics/kxab049

Fig. 1.

Fig. 1.

Illustration of Assumption 3 and its distinction compared to the monotonicity assumption using seven hypothetical units. Units Inline graphic and Inline graphic are allowed under both assumptions, Assumption 3 and monotonicity. For unit Inline graphic, APOE expedites both AD and death, but in a way that AD remains before death. For unit 2, APOE impedes AD but expedites death. Nevertheless, unit 2 would live long enough under APOE for AD to occur. Similar protective effect occurs for unit Inline graphic, however, this unit violates monotonicity at time Inline graphic (as an example). Unit Inline graphic also violates monotonicity (at Inline graphic and Inline graphic) but not Assumption 3. Unit Inline graphic does not suffer from AD under any APOE value, hence it is allowed by Assumption 3 but it does violate monotonicity (at Inline graphic and Inline graphic) as AD carries a protective effect against death. Unit Inline graphic violates Assumption 3 but not monotonicity. Arguably, for this unit the APOE effect on death is so strong the unit would have died under APOE before getting the chance to have AD. Finally, unit Inline graphic violates both assumptions.