Use of Joinpoint Regression to Define Phases of Care From Diagnosis of Metastases Until Death in Patients With Advanced Melanoma

Transcription

1 Use of Joinpoint Regression to Define Phases of Care From Diagnosis of Metastases Until Death in Patients With Advanced Melanoma Sasikiran Nunna, MS 1 Anna D. Coutinho, B.Pharm, PhD 2 Michael Eaddy, PharmD, PhD 2 Pamela Landsman-Blumberg, MPH, DrPH 2 1 University of Mississippi, University, MS, USA 2 Xcenda LLC, Palm Harbor, FL, USA

2 Disclosures This study was funded by Bristol-Myers Squibb. Sasikiran Nunna was a summer intern at Xcenda and primary analyst at the time the study was conducted. Anna Coutinho, Pamela Landsman-Blumberg, and Michael Eaddy are employees of Xcenda, which received research funds from Bristol-Myers Squibb in connection with conducting this study. Acknowledgements The authors would like to acknowledge Tony Okoro and Manan Shah from Bristol-Myers Squibb for their support and review of the analyses. 2

3 Presentation Outline Background Study Objective Methodology Results Limitations Discussion and Conclusion Accessing Joinpoint Trend Analysis Software 3

4 Background Utilization of healthcare services and costs among cancer patients are often estimated by the phase of care 1 initial, interim, and terminal Diagnosis of cancer/metastases Death proxy date Initial Phase Primary course of therapy and adjuvant therapy Interim Phase Treatment of complications from initial therapy and recurrence prevention Terminal Phase Includes end-oflife care and palliative care services 1. Brown ML, Riley GF, Schussler N, Etzioni R. Estimating health care costs related to cancer treatment from SEER-Medicare data. Med Care. 2002;40(8):IV

5 Background Phases of care vary with the type of cancer and the stage of diagnosis No consistent basis to define duration of phases of care Diagnosis of cancer/metastases Death proxy date Breast cancer patients 1 Dx of cancer Initial Interim Terminal 5 months after diagnosis 12 months prior to death Pancreatic cancer patients 2 Dx of cancer 12 months prior to death Metastatic colorectal cancer patients 3 Dx of metastases 3 months after diagnosis 3 months prior to death 1. Brown ML, Riley GF, Schussler N, Etzioni R. Estimating health care costs related to cancer treatment from SEER-Medicare data. Med Care. 2002;40(8):IV Chang S, Long SR, Kutikova L, Bowman L, Crown WH, Lyman GH. Burden of pancreatic cancer and disease progression: economic analysis in the US. Oncology. 2006;70(1): Paramore LC, Thomas SK, Knopf KB, Cragin LS, Fraeman KH. Estimating costs of care for patients with newly diagnosed metastatic colorectal cancer. Clin Colorectal Cancer. 2006;6(1):

6 Study Objective Establish data-driven phases of care to enable estimation of healthcare costs in patients with advanced melanoma who died Diagnosis of metastases Duration (?) Duration (?) Duration (?) Death proxy date Initial Phase Interim Phase Terminal Phase 6

7 Methodology Study Design A retrospective cohort study using the IMS LifeLink PharMetrics Plus Database during the period of Jan 1, 2009 Sep 30, 2014 Death was identified using a proxy from claims data All-cause costs were assessed from diagnosis of metastases to death Population Advanced melanoma patients with evidence of death during the period of Jan 1, 2010 Sep 30, 2014 Aged 18 years or older at death Continuously enrolled in health plan from diagnosis of metastases to death 7

8 Methodology Analysis Approach The analysis was performed using Joinpoint Regression - A piece-wise linear regression used to identify the best-fitting points (Joinpoints) where statistically significant changes in the trend of monthly costs occur 1 - Software developed by the National Cancer Institute 2 originally to analyze the trends of cancer-related incidence, prevalence, mortality, and survival 1. Kim HJ, Fay MP, Feuer EJ, Midthune DN. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med. 2000;19: (correction: 2001;20:655). 2. Joinpoint Regression Program, Version April 2015; Statistical Methodology and Applications Branch, Surveillance Research Program, National Cancer Institute. 8

9 Methodology Joinpoint Models Model 1: Initial Phase (costs modeled forward) Diagnosis of metastases Death proxy Cost Month 1 Cost Month 2 Cost Month 3 Model 2: Terminal Phase (costs modeled backward) Diagnosis of metastases Death proxy 9 Cost Month 3 Cost Month 2 Cost Month 1

10 Methodology Joinpoint Models Dependent variable - All-cause healthcare costs (log transformed) - Cost per patient per month (eg, cost_month 1, cost_month 2, ) Independent variable - Time (in monthly intervals from diagnosis of metastases to death) A heteroskedastic, uncorrelated error model was used - Heteroskedasticity (Breusch-Pagan / Cook-Weisberg test) - Autocorrelation (Breusch-Godfrey LM test) 10

11 Methodology Joinpoint Selection A sequential algorithm-based method called Grid Search to identify best fit of the data - 1 to a max of 3 Joinpoints were specified for each model - Bonferroni correction for the overall significance-level testing of Joinpoints 1 1. Kim HJ, Fay MP, Feuer EJ, Midthune DN. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med. 2000;19: (correction: 2001;20:655). 11

12 Results A total of 1,671 advanced melanoma patients met the study criteria Characteristics of Advanced Melanoma Patients Total (N=1,671) Age in years, mean (SD) 61.2 (12.6) Males, n (%) 1,092 (65.4%) Charlson comorbidity index, mean (SD) 2.5 (2.6) Time from diagnosis of metastases to death (in days), mean (SD) 383 (349) Time from diagnosis of metastases to death (in days), n (%) Less than 6 months 578 (34.6%) 6 months 1 year 422 (25.3%) 1 2 years 419 (25.1%) 2 3 years 169 (10.1%) 3 4 years 62 (3.7%) More than 4 years 21 (1.3%) 12

13 Results Initial Phase 1-Joinpoint model identified as best fit with Grid Search method A statistically significant and sharp decline in monthly cost trend at month 5 (monthly percent change [95% CI] = -13.0% [-16.9%, -8.8%]) Duration of initial phase = 5 months from diagnosis of metastases Average All-cause Costs ($) Modeling Costs Forward Months (post-diagnosis of metastasis) 13

14 Results Terminal Phase 3-Joinpoint model identified as best fit with Grid Search method A statistically significant and sharp decline in monthly cost trend at month 5 (monthly percent change [95% CI] = -14.0% [-17.6%, -10.2%]) Duration of terminal phase = 5 months prior to death Average All-cause Costs ($) Modeling Costs Backwards Months (prior to diagnosis) 14

15 Results Costs by Phase of Care Terminal phase costs were higher followed by initial and then interim costs Costs following diagnosis of metastases until death in melanoma followed a U-shape distribution which was similar to cost distributions from diagnosis of (any) cancer until death 1 Monthly Costs (mean, SD) Initial (N=1,167) Interim (N=810) Terminal (N=1,671) $11,852 (14,804) $8,868 (12,756) $17,746 (21,335) 1. Brown ML, Riley GF, Schussler N, Etzioni R. Estimating health care costs related to cancer treatment from SEER-Medicare data. Med Care. 2002;40(8):IV

16 Limitations Lack of death data to confirm if patient died, and may under-estimate terminal phase costs if patient is misclassified as having died Claims-based algorithm to identify death used hospitalization and ER visits in the last month before last claim date or end of enrollment may overinflate costs in the terminal phase. The diagnoses of metastases was done using a claims-based algorithm in the absence of clinical data. 16

17 Discussion and Conclusion Healthcare costs provide a basis to establish phases of care in patients with advanced melanoma In this metastatic melanoma population, the optimal duration of the initial and terminal phases of care was 5 months immediately after diagnosis of metastases and prior to death, respectively This data-supported approach using Joinpoint Regression should be complemented with clinical judgment to identify the appropriate duration of phases of care for reporting costs from diagnosis of metastases to death 17

18 Accessing Joinpoint Trend Analysis Software Desktop version has a graphical user interface and is for interactive use Command-line version is for use in a batch mode or called from other software, such as SAS or R Contact for Presentation Sasikiran Nunna, MS: snunna@go.olemiss.edu Anna D. Coutinho, B.Pharm, PhD: anna.coutinho@xcenda.com Slides available on the ISPOR Scientific Presentation Database: 18

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