Table 2:
Bivariable and adjusted multivariable models: medication regimen factors and endocrine therapy initiation, discontinuation, adherence
| Initiation n=21,894 |
aDiscontinuation n=17,512 |
bAdherence n=17,512 |
|||||
|---|---|---|---|---|---|---|---|
| Parameter | Unadjusted HR (95% CI) |
Adjusted Multivariable HR (95% CI) |
Unadjusted HR (95% CI) |
Adjusted Multivariable HR (95% CI) |
Unadjusted Estimate (95% CI) |
Adjusted Multivariable Estimate (95% CI) |
|
| cIntercept | - | - | - | - | - | **0.773 (0.754, 0.793) | |
| MRCI-A Route Complexity | 2-4 | 0.99 (0.96-1.03) | *0.96 (0.93-0.99) | 1.01 (0.95-1.08) | 1.07 (1.00-1.14) | 0.004 (−0.002, 0.009) | 0.001 (−0.004, 0.007) |
| (ref= 0-1) | 5+ | 1.02 (0.98-1.07) | 1.00 (0.95-1.05) | 1.05 (0.95-1.15) | *1.12 (1.02-1.24) | **0.017 (0.009, 0.025) | **0.014 (0.006, 0.023) |
| Overall variable p value | 0.57 | 0.08 | 0.62 | 0.04 | <0.001 | 0.002 | |
| Combined Medication & Visit Score | 1-3 Meds | **1.30 (1.19-1.43) | **1.34 (1.19-1.50) | 0.87 (0.74-1.03) | *0.71 (0.56-0.89) | 0.005 (−0.011, 0.022) | *0.024 (0.005, 0.044) |
| (ref= No Meds) | 4+ Meds or 2+ Visits | **1.27 (1.18-1.37) | **1.36 (1.23-1.51) | **0.74 (0.65-0.84) | **0.56 (0.45-0.68) | *0.022 (0.009, 0.036) | **0.049 (0.032, 0.065) |
| 4+ Meds & 2+ Visits | **1.30 (1.22-1.40) | **1.47 (1.33-1.63) | **0.72 (0.64-0.81) | **0.48 (0.39-0.59) | **0.029 (0.016, 0.041) | **0.060 (0.043, 0.076) | |
| Overall variable p value | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | |
| Out-of-Pocket Medication Costs | $1 < $50 | **1.19 (1.13-1.26) | 0.98 (0.91-1.06) | **0.82 (0.74-0.92) | 1.17 (0.99-1.39) | 0.008 (−0.001, 0.017) | **−0.021 (−0.032, −0.009) |
| (ref= $0 < $1) | $50 < $500 | **1.17 (1.11-1.23) | 0.96 (0.89-1.03) | 0.93 (0.84-1.03) | *1.31 (1.11-1.55) | −0.007 (−0.016, 0.001) | **−0.042 (−0.053, −0.031) |
| $500+ | 1.03 (0.96-1.10) | *0.86 (0.79-0.94) | 0.92 (0.81-1.06) | *1.25 (1.03-1.51) | 0.000 (−0.012, 0.012) | **−0.037 (−0.050, −0.023) | |
| Overall variable p value | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | |
| Stage at Diagnosis | II | **1.13 (1.10-1.17) | **1.14 (1.10-1.18) | **0.81 (0.76-0.87) | **0.80 (0.75-0.85) | −0.001 (−0.007, 0.004) | −0.001 (−0.006, 0.005) |
| (ref= I) | III | *1.07 (1.01-1.13) | 1.04 (0.99-1.10) | **0.74 (0.65-0.84) | **0.72 (0.64-0.82) | *−0.016 (−0.027, −0.006) | *−0.014 (−0.024, −0.004) |
| IV | **1.50 (1.29-1.74) | **1.57 (1.36-1.82) | 1.24 (0.96-1.61) | 1.13 (0.87-1.47) | **−0.060 (−0.092, −0.029) | *−0.048 (−0.078, −0.017) | |
| Unknown | **0.82 (0.73-0.92) | *0.87 (0.77-0.97) | 0.87 (0.70-1.09) | 0.84 (0.67-1.05) | −0.006 (−0.025, 0.014) | −0.003 (−0.022, 0.017) | |
| Overall variable p value | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 | 0.003 | |
| Race | Asian | *1.11 (1.04-1.20) | *1.11 (1.03-1.19) | *0.81 (0.69-0.94) | *0.82 (0.70-0.95) | *0.015 (0.004, 0.026) | 0.010 (−0.002, 0.021) |
| (ref= White) | Black | 0.99 (0.93-1.05) | 0.95 (0.89-1.01) | **0.72 (0.63-0.83) | **0.74 (0.64-0.86) | *−0.012 (−0.023, −0.001) | *−0.015 (−0.026, −0.004) |
| Other | 1.02 (0.85-1.22) | 0.98 (0.82-1.17) | 0.87 (0.59-1.29) | 0.91 (0.61-1.35) | −0.033 (−0.067, 0.001) | *−0.039 (−0.073, −0.005) | |
| Overall variable p value | 0.03 | 0.01 | <0.001 | <0.001 | 0.001 | 0.002 | |
|
Ethnicity (ref= Non-Hispanic) |
Hispanic | 1.03 (0.97-1.10) | 0.99 (0.93-1.06) | *0.80 (0.69-0.92) | *0.82 (0.71-0.95) | −0.004 (−0.015, 0.007) | −0.008 (−0.019, 0.003) |
| Age at Diagnosis | 75-84 | **0.91 (0.88-0.94) | **0.92 (0.89-0.95) | **1.24 (1.16-1.32) | **1.27 (1.19-1.35) | −0.003 (−0.008, 0.002) | −0.003 (−0.008, 0.003) |
| (ref= 68-74) | 85-94 | **0.64 (0.60-0.67) | **0.65 (0.61-0.68) | **1.50 (1.36-1.65) | **1.57 (1.42-1.73) | *0.010 (0.001, 0.018) | *0.012 (0.004, 0.020) |
| 95+ | **0.44 (0.33-0.59) | **0.45 (0.34-0.60) | *2.33 (1.40-3.87) | **2.68 (1.61-4.48) | −0.036 (−0.099, 0.027) | −0.026 (−0.091, 0.039) | |
| Overall variable p value | <0.001 | <0.001 | <0.001 | <0.001 | 0.03 | 0.01 | |
|
Adjusted NCI Comorbidity Score (6-month time varying) |
0.99 (0.99-1.00) | 1.00 (0.99-1.01) | 1.01 (0.99-1.02) | 1.01 (1.00-1.03) | **0.005 (0.004, 0.006) | −0.001 (−0.002, 0.000) | |
| Function-related Indicators | 1 | 0.98 (0.94-1.02) | 1.00 (0.96-1.03) | 1.06 (0.99-1.14) | 1.03 (0.96-1.11) | *−0.010 (−0.017, −0.004) | **−0.011 (−0.017, −0.005) |
| (ref= 0) | 2 | **0.87 (0.82-0.92) | **0.91 (0.86-0.96) | *1.19 (1.07-1.31) | *1.13 (1.01-1.26) | −0.003 (−0.012, 0.006) | −0.005 (−0.014, 0.005) |
| 3+ | **0.91 (0.86-0.96) | 0.97 (0.91-1.03) | 1.02 (0.91-1.14) | 0.92 (0.81-1.05) | 0.005 (−0.004, 0.014) | 0.003 (−0.007, 0.013) | |
| Overall variable p value | <0.001 | 0.01 | 0.009 | 0.04 | 0.004 | 0.002 | |
| Bipolar and Psychotic Disorder | *0.90 (0.84-0.96) | *0.92 (0.86-0.98) | 1.13 (0.99-1.28) | 1.12 (0.98-1.28) | 0.001 (−0.010, 0.013) | −0.002 (−0.013, 0.010) | |
| Anxiety Disorder | 1.00 (0.95-1.05) | 0.99 (0.94-1.05) | **1.24 (1.13-1.37) | **1.23 (1.11-1.36) | −0.004 (−0.013, 0.005) | −0.007 (−0.016, 0.003) | |
| Dementia Disorder | **0.82 (0.76-0.88) | *0.89 (0.82-0.97) | 1.09 (0.94-1.28) | 1.02 (0.86-1.20) | 0.008 (−0.005, 0.021) | 0.005 (−0.009, 0.018) | |
| Substance Use Disorder | 1.00 (0.93-1.07) | 0.98 (0.91-1.05) | **1.41 (1.24-1.61) | **1.44 (1.26-1.64) | **−0.026 (−0.040, −0.012) | **−0.024 (−0.038, −0.010) | |
| Home Rurality | Metro | **0.82 (0.74-0.91) | **0.84 (0.76-0.92) | 1.21 (0.99-1.49) | 1.22 (0.99-1.50) | **−0.032 (−0.046, −0.018) | **−0.032 (−0.045, −0.018) |
| (ref= Rural) | Non-metro | *0.84 (0.76-0.93) | *0.86 (0.77-0.95) | 1.15 (0.92-1.42) | 1.15 (0.93-1.43) | *−0.022 (−0.037, −0.006) | *−0.020 (−0.035, −0.006) |
| Unknown | 1.59 (0.40-6.26) | 1.54 (0.38-6.20) | 3.38 (0.47-24.26) | 3.33 (0.46-23.97) | −0.046 (−0.162, 0.071) | −0.040 (−0.143, 0.064) | |
| Overall variable p value | <0.001 | 0.003 | 0.11 | 0.11 | <0.001 | <0.001 | |
| Year of Diagnosis | 2008 | 0.99 (0.93-1.06) | 0.98 (0.92-1.04) | 0.95 (0.86-1.05) | 0.95 (0.86-1.06) | 0.002 (−0.009, 0.014) | 0.002 (−0.009, 0.013) |
| (ref= 2007) | 2009 | 1.01 (0.95-1.08) | 1.01 (0.94-1.07) | 0.91 (0.82-1.00) | 0.91 (0.82-1.00) | **0.021 (0.010, 0.032) | **0.023 (0.012, 0.033) |
| 2010 | **1.13 (1.06-1.20) | *1.10 (1.04-1.18) | *0.86 (0.77-0.97) | *0.86 (0.77-0.96) | **0.049 (0.038, 0.059) | **0.058 (0.048, 0.069) | |
| 2011 | **1.18 (1.10-1.25) | **1.16 (1.09-1.23) | 0.91 (0.81-1.02) | 0.91 (0.81-1.02) | **0.049 (0.038, 0.059) | **0.069 (0.059, 0.080) | |
| 2012 | **1.17 (1.10-1.25) | **1.15 (1.09-1.22) | 0.92 (0.82-1.05) | 0.92 (0.81-1.04) | **0.048 (0.037, 0.058) | **0.084 (0.073, 0.094) | |
| 2013 | **1.21 (1.14-1.29) | **1.18 (1.11-1.26) | 0.94 (0.82-1.08) | 0.93 (0.81-1.06) | **0.024 (0.012, 0.035) | **0.082 (0.071, 0.094) | |
| Overall variable p value | <0.001 | <0.001 | 0.24 | 0.22 | <0.001 | <0.001 | |
| cYear of Endocrine Therapy Use | 2 | - | - | - | - | **0.061 (0.057, 0.065) | **0.067 (0.063, 0.071) |
| (ref= 1) | 3 | - | - | - | - | **0.079 (0.074, 0.084) | **0.089 (0.084, 0.094) |
| 4 | - | - | - | - | **0.100 (0.095, 0.106) | **0.119 (0.113, 0.125) | |
| 5 | - | - | - | - | **0.102 (0.095, 0.109) <0.001 | **0.131 (0.123, 0.139) | |
| Overall variable p value | - | - | - | - | <0.001 | <0.001 | |
P value *<0.05, **<0.001, 95% confidence interval. Overall variable p value calculated for categorical variables with 3 or more strata. “Combined Medication & Visit” variable created from each variable’s significant response levels in separate adjusted models (Appendix 2).
a,b
Follow-up began the day of endocrine therapy initiation, concluding at censoring or a maximum five years of endocrine therapy use. Discontinuation was assessed in Cox regression.
a
Discontinuation analysis censored after five years continuous use.
b
Adherence measured with the proportion of days covered (PDC), for patients with one or more years of observation with over half of this time outside hospitals and skilled nursing facilities. Estimate of 0.01 corresponds to 1%.
c
Applicable to adherence only.