School Cancer of Epidemiology something Group FACULTY OF OTHER MEDICINE AND HEALTH Investigation of relative survival from colorectal cancer between NHS organisations Katie Harris k.harris@leeds.ac.uk
Background Survival from colorectal cancer in UK is poor Increasing demand for NHS to publish data on clinical outcomes to inform patient choice Cancer survival rates are an effective representation of quality of health care performance Health status of an individual maybe determined by factors operating at a higher level
Aim To assess variation between Hospital Trusts in survival for colorectal cancer patients
Data National Cancer Data Repository All patients diagnosed in England with colorectal cancer between 1998 and 2008 319797 Allocated to a Trust 292131 150 NHS trusts (547-4585 patients) Stage missing for 25% of patients Complete data for 218713 patients Variables: Survival, Demographics, Treatment
What to do about missingness? Why are data missing? Options: Only use complete cases Missing data indicator Replace missing value with mean value Distributing all cases with unknown stage proportionally to the known stages Imputation Is data missing at random?
Multiple Imputation Multiple imputation model includes: Stage Imputed Deprivation score Imputed Age at diagnosis Sex Vital status (Alive/ Dead) Cancer site Year of diagnosis Survival time Admission type Procedure type Charlson comorbidity index Trust work load Trust Network Missing at random observed values are predictive of missing values Survival data outcome and survival time must be imputed Clustering Trust modelled as fixed effect Five imputations and five iterations Software: mice in R
Imputation Results Stage 1 2 3 4 9 Before Imputation (All) 9% 25% 26% 15% 25% Before Imputation (Staged only) 12% 34% 34% 20% After Imputation 12% 31% 31% 26%
0.8 1.0 Exploration of data 0.0 0.2 0.4 Survival 0.6 Survival Curves by NHS Trust 0 1000 2000 Days 3000 4000
Statistical Modelling Aim: to examine differences in cancer survival between Trusts Data from population-based cancer registries Cause of death? Multiple patients nested within multiple hospitals Adjust for casemix Separate models for colon and rectal cancer Colon 206180 patients (391 3203 Trust range) Rectal 85919 patients (148 1385 Trust range)
Relative Survival Regression framework Generalised Linear Mixed Effects Model with Poisson errors Individual level data Five year survival Complete approach Software: lme4 in R
Model specification Outcome: Alive or dead (censoring inidcator) Offset: log Survival time Link function: log Error distribution: Poisson Hierarchy: Trust Explanatory variables: Stage, Sex, Age, Deprivation, Admission, Procedure, Charlson Model specification in R: glmer (Outcome ~ 1 + (1 Trust) + offset(log(survtime)), family = Poisson)
Fixed effect coefficients Rectal Cancer C20 Colon Cancer C18 C19 Fixed effects Original Pooled Original Pooled Stage 2 1.19 1.19 1.10 1.11 Stage 3 1.53 1.57 1.63 1.65 Stage 4 3.55 3.48 4.41 4.41 Sex (F) 0.94 0.95 0.98 1.00 Dep 2 1.03 1.03 1.04 1.05 Dep 3 1.06 1.07 1.07 1.09 Dep 4 1.09 1.09 1.11 1.13 Dep 5 1.14 1.15 1.15 1.17 Age 1.02 1.02 1.02 1.02 Admission (Emergency) 1.57 1.66 1.52 1.55 Proc LE 1.26 1.25 1.18 1.08 Proc NS 1.76 1.98 2.07 2.41 Proc palliative 2.23 2.24 2.42 2.48 Charlson 1 1.23 1.26 1.21 1.23 Charlson 2 1.38 1.41 1.43 1.43 Charlson 3+ 1.64 1.54 1.80 1.70
Results Significant cluster variation No notable difference in fixed and random coefficients from complete case analysis and imputed models Imputation reduces standard errors of coefficients All fixed effects significant with narrow 95% CI Rectal cancer has slightly better survival Excess deaths = 45% for Rectal Cancer Excess deaths = 52% for Colon Cancer
Identifying Outlying Trusts Convert survival data into a summary value Excess hazard ratio for each Trust Trusts that are beyond limits of normal variation Options: Confidence interval Caterpillar plot Funnel plot (Intercept) 142 134 127 125 116 62 94 17 42 34 93 81 18 43 132 100 140 111 136 141 145 79 39 32 16 70 97 78 55 90 53 33 80 77 60 83 68 91 65 61 75 31 41 96 63 1 144 10 663 51 54 82 126 103 130 131 105 106 128 110 29 99 86 20 15 64 85 48 74 19 71 13 25 35 21 47 14 44 23 114 112 123 129 121 149 102 108 73 45 37 69 72 26 22 75 135 137 150 120 124 139 36 38 40 59 52 118 115 114 122 87 113 146 1439 28 148 104 13 8 119 46 27 98 30 89 56 147 133 107 67 24 109 50 57 58 88 12 117 92 76 2 101 84 95-0.3-0.2-0.1 0.0 0.1 0.2
Funnel plots Established technique To identify Trusts that have excess hazard of death higher (above) or lower (below) than the risk of death from cancer in all trusts combined Plot excess hazard ratio against work load of Trust 95% and 99% control limits Software: funnelcompar in Stata
Rectal Cancer 1.4 Trust 1.2 125 127 1.8 95.6 0 500 1000 1500 Trust patient number C20
Colon Cancer 1.4 Trust 1.2 93 125 1.8 84 147.6 95 500 1000 1500 2000 2500 3000 Trust patient number C18 C19
Conclusions High quality source of data Relative survival models and funnel plots are effective methods for assessing Trust disparities in cancer survival Significant variation in survival of colorectal cancer patients exists between hospital Trusts in England Possible inequalities in the level of care between Trusts Outlying Trusts to be notified of results
Any Questions?
Acknowledgments Eva Morris Paul Finan Philip Quirke James Thomas Louise Whitehouse John Wilkinson
Rectal Model with 95%CI Fixed effects Original 95% CI Pooled 95% CI Stage 2 1.19 (1.16,1.21) 1.19 (1.16, 1.21) Stage 3 1.53 (1.50,1.57) 1.57 (1.54, 1.59) Stage 4 3.55 (3.46,3.63) 3.48 (3.42, 3.55) Sex (F) 0.94 (0.92,0.95) 0.95 (0.94, 0.96) Dep 2 1.03 (1.00,1.05) 1.03 (1.01, 1.05) Dep 3 1.06 (1.04,1.08) 1.07 (1.05, 1.09) Dep 4 1.09 (1.06,1.11) 1.09 (1.07, 1.11) Dep 5 1.14 (1.11,1.16) 1.15 (1.13, 1.17) Age 1.02 (1.02,1.02) 1.02 (1.02, 1.02) Admission (Emergency) 1.57 (1.52,1.62) 1.66 (1.61, 1.71) Proc LE 1.26 (1.21,1.30) 1.25 (1.22, 1.28) Proc NS 1.76 (1.73,1.80) 1.98 (1.95, 2.01) Proc palliative 2.23 (2.16,2.30) 2.24 (2.19, 2.29) Charlson 1 1.23 (1.20,1.26) 1.26 (1.23, 1.28) Charlson 2 1.38 (1.32,1.44) 1.41 (1.37, 1.45) Charlson 3+ 1.64 (1.55,1.74) 1.54 (1.49, 1.61)
Colon Model with 95% CI Fixed effects Original 95% CI Pooled 95% CI Stage 2 1.10 (1.08, 1.12) 1.11 (1.09,1.13) Stage 3 1.63 (1.60, 1.65) 1.65 (1.62,1.67) Stage 4 4.41 (4.33, 4.49) 4.41 (4.34,4.48) Sex (F) 0.98 (0.97, 0.99) 0.99 (0.99,1.00) Dep 2 1.04 (1.02, 1.05) 1.05 (1.04,1.06) Dep 3 1.07 (1.06, 1.08) 1.09 (1.08,1.10) Dep 4 1.11 (1.09, 1.12) 1.13 (1.12,1.15) Dep 5 1.15 (1.13, 1.16) 1.17 (1.16,1.18) Age 1.02 (1.02, 1.02) 1.02 (1.02,1.02) Admission (Emergency) 1.52 (1.51, 1.54) 1.55 (1.53,1.56) Proc LE 1.18 (1.14, 1.23) 1.08 (1.05,1.11) Proc NS 2.07 (2.04, 2.09) 2.41 (2.38,2.43) Proc palliative 2.42 (2.36, 2.48) 2.48 (2.44,2.53) Charlson 1 1.21 (1.20, 1.22) 1.23 (1.21,1.24) Charlson 2 1.43 (1.40, 1.45) 1.43 (1.41,1.45) Charlson 3+ 1.80 (1.75,1.84) 1.70 (1.66,1.73)