Table 3 Four-way decomposition of relationship between COC, excessive polypharmacy, and DDI.

	2011		2012		2013		2014		2015		2016		2017
	β^a,b	p	β	p	β	p	β	p	β	p	β	p	β	p
Mediator at 0
Total excess RR	− 0.570	< 0.001	− 0.581	< 0.001	− 0.586	< 0.001	− 0.606	< 0.001	− 0.623	< 0.001	− 0.616	< 0.001	− 0.625	< 0.001
Excess RR due to controlled direct effect	0.001	0.767	− 0.002	0.635	− 0.001	0.794	− 0.011	0.002	− 0.010	0.004	− 0.015	< 0.001	− 0.019	< 0.001
Excess RR due to reference interaction	− 0.437	< 0.001	− 0.449	< 0.001	− 0.444	< 0.001	− 0.453	< 0.001	− 0.475	< 0.001	− 0.462	< 0.001	− 0.466	< 0.001
Excess RR due to mediated interaction	0.127	< 0.001	0.130	< 0.001	0.139	< 0.001	0.145	< 0.001	0.156	< 0.001	0.151	< 0.001	0.157	< 0.001
Excess RR due to pure indirect effect	− 0.261	< 0.001	− 0.261	< 0.001	− 0.280	< 0.001	− 0.287	< 0.001	− 0.294	< 0.001	− 0.290	< 0.001	− 0.297	< 0.001
Mediator at 1
Total excess RR	− 0.570	< 0.001	− 0.581	< 0.001	− 0.586	< 0.001	− 0.606	< 0.001	− 0.623	< 0.001	− 0.616	< 0.001	− 0.625	< 0.001
Excess RR due to controlled direct effect	− 0.590	< 0.001	− 0.600	< 0.001	− 0.600	< 0.001	− 0.615	< 0.001	− 0.639	< 0.001	− 0.620	< 0.001	− 0.625	< 0.001
Excess RR due to reference interaction	0.154	< 0.001	0.150	< 0.001	0.155	< 0.001	0.152	< 0.001	0.154	< 0.001	0.144	< 0.001	0.140	< 0.001
Excess RR due to mediated interaction	0.127	< 0.001	0.130	< 0.001	0.139	< 0.001	0.145	< 0.001	0.156	< 0.001	0.151	< 0.001	0.157	< 0.001
Excess RR due to pure indirect effect	− 0.261	< 0.001	− 0.261	< 0.001	− 0.280	< 0.001	− 0.287	< 0.001	− 0.294	< 0.001	− 0.290	< 0.001	− 0.297	< 0.001

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