Model outcome	Risk ratio	95% CI	E-value	95% LCL
Physical function
TNDE	0.94	0.83 to 1.07	1.31	1.0
TNIE	0.84	0.78 to 0.90	1.68	1.47
Total effect	0.79	0.69 to 0.90	1.85	1.47

Fatigue
TNDE	0.92	0.809 to 1.038	1.407	1.0
TNIE	0.88	0.826 to 0.931	1.542	1.36
Total effect	0.80	0.707 to 0.912	1.797	1.42

Sleep disturbance
TNDE	0.91	0.798 to 1.034	1.434	1.0
TNIE	0.89	0.840 to 0.933	1.511	1.35
Total effect	0.81	0.708 to 0.914	1.792	1.42

Social roles
TNDE	0.96	0.848 to 1.084	1.255	1.0
TNIE	0.85	0.788 to 0.910	1.644	1.43
Total effect	0.81	0.712 to 0.925	1.767	1.38

LCL reported as minimum value of 1.0 for estimates that were not statistically significant.
LCL = lower confidence limit;
TNDE = total natural direct effect;
TNIE = total natural indirect effect

Table 4. Risk ratio and E-values for natural direct, natural indirect and total effects.