1. Epidemiologic Studies of Cancer, Diabetes & Its Treatments: Opportunities from Canada Jeffrey A. Johnson University of Alberta Edmonton, Canada Cancer & Diabetes Epidemiology Consortium June 14, 2010

2. Canadian Team University of Alberta, Edmonton Jeff Johnson Samantha Bowker Yutaka Yasui University of British Columbia, Vancouver, BC Carlo Marra

3. Welcome to Canada! ~ 10 million km 2 / ~3.9 million mi 2 population: ~34 million (2009) 10 provinces, 3 territories Health care is a national philosophy, but a P/T mandate 13 ‘health care systems’ All residents have publically funded insurance for ‘medically necessary’ health services (Canada Health Act) Physician and Hospital services Drug coverage varies (products, policy, population) Providers send ‘bill’ to Health Ministry Each resident has Personal Health Number

4. Health Care & Data Canadian Context Publically Funded, Privately Delivered Prescriber Amt Dispensed DIN Unique ID Mortality Health Services Demographic Data Unique ID HospitalPhysician Insurance Registry Age Gender Location of Residence Status Aboriginal Co-Morbidities /Procedures DM Status Incident/Prev DM Status Incident/Prev Co-Morbidities /Procedures Drug ICD-9-CM or ICD-10CA ICD-9-CM Vital Statistics COD

5. Year of Database Initiation ProvinceHospitalPhysicianDrugs Alberta197319731994 (seniors) BC198519851997 (All) Manitoba197019701994 (All) New Brunswick197319891990 (Seniors) Nova Scotia197319911975 (Seniors) Ontario196319891994 (Seniors) Prince Edward Island19841989 -- Quebec198319861981 (Seniors) Saskatchewan197019711975 (All)

6. Case Definition of DM with Large Admin Databases Case/Cohort Ascertainment  Identifying diabetes in admin data A.National Diabetes Surveillance System Case Def’n 2 physician visits for DM (ICD-9 250) in 2 year period or 1 hospitalization for DM (ICD-10CA E10-E14) B.Antidiabetic Drug Use - e.g., new users of oral antidiabetic agents

7. 0.50.91.01.3 Adjusted* HR: Reduced Risk Increased Risk Diabetes Treatments & Cancer Mortality Bowker et al., Diabetes Care, 2006 Retrospective Cohort Study Saskatchewan, Canada, 1991-1999 1.82.0 Sulfonylurea Monotherapy 1.30 Time fixed Cox regression analysis Metformin use as the reference group Insulin add-on as covariate Insulin Added 1.90 *age, sex, Chronic Disease Score

8. Diabetes Treatments & Cancer Mortality Retrospective Cohort Study Saskatchewan, Canada, 1991-1999 Time varying Cox regression analysis SU Monotherapy as the reference group Insulin add-on dose-risk gradient Bowker SL et al., Diabetologia, 2010 0.40.60.81 Adjusted HR: Reduced Risk Increased Risk Metformin Use No Insulin Ever (ref) < 3 Rx/year 3 to 11 Rx/year ≥ 12 Rx/year 0.80 2.22 6.40 1.52.04.06.0 3.33

9. Established in 1871 ~ 945,000 km 2 / ~ 365,000 mi 2 population: ~ 4.5 million (2010) Diabetes prevalence 1 : 4.9% (~ 200,0000) in 2006-07 Diabetes Incidence (2006-07) 1 : 5.0 per 1000 (~ 20,000 cases/yr) Cancer Incidence 2007 (per 100,000) 2 : Crude, all cancers, all ages: 532 (M) 452 (F) Age-std, all cancers, all ages: 438(M) 336(F) British Columbia 1 National Diabetes Surveillance System, PHAC 2 BC Cancer Agency

11. BC Cancer Agency MaleFemale

12. BC - DM & Cancer Cohort Study X X X X 11 yrs 8.5 yrs 4 yrs Subjects may be ‘censored’ due to: - death - leaving province - Dec. 31, 2007 199720022007 Washout CancerDM Index Period DM: NDSS case def’n non DM: sex, aboriginal match Follow-up Period 1995

13. BC - DM & Cancer Cohort Study Table. Baseline characteristics of the diabetes and controls cohorts (1997-2006) Diabetes cohort (N=306,210)Control cohort (N=292,782) Baseline characteristicsn% n% Sex Male162,90153.2%155,39853.1% Female142,58346.6%137,38446.9% Age, years 30-4031,43710.3%31,54510.8% 40-5055,89418.3%55,55219.0% 50-6069,23722.6%67,53323.1% 60-7072,51923.7%68,97623.6% 70+77,12325.2%69,17623.6% Mean (SD)59.3 (14.2)58.7 (14.1) Socioeconomic status (in 1997) 1 st quintile64,79821.2%57,24819.6% 2 nd quintile59,15519.3%55,31118.9% 3 rd quintile52,76517.2%55,37318.9% 4 th quintile49,61516.2%56,42119.3% 5 th quintile43,53414.2%59,34520.3% Missing7,6132.5%9,0843.1% First-nations / ethnicity Yes

14. BC - DM & Cancer Cohort Study Table. Cancer and mortality incidence by diabetes index date First neoplasm (any site)Deaths (any cause) Follow-up Incidence rate Cohor tindex dateN(years)n%(/1000PY) n% Incident Diabetes 1997-200198,838 559,7618,2688.4%14.815,35515.5%27.4 199720,128 145,5852,12510.6%14.64,41821.9%30.3 199819,216 125,0971,8689.7%14.93,46118.0%27.7 199919,674 112,3901,6338.3%14.52,98415.2%26.6 200019,402 94,6281,3817.1%14.62,44412.6%25.8 200120,418 82,0621,2616.2%15.42,04810.0%25.0 2002-200693,468 149,3232,7292.9%18.34,7915.1%32.1 Controls* None 1994- 2001292,782 2,423,29130,97210.6%12.8 42,55514.5%17.6

15. BC - DM & Cancer Cohort Study Table. First cancer incident rates by site for incident diabetes and controls cohorts Incident diabetes (N=192,306)Control cohort (N=292,782) Incidence rate First cancer site n%(/1000PY) n% IRR Any 10,9975.7%15.530,97210.6%12.8 1.21 Colo-rectal 1,4020.7%2.03,6281.2%1.5 1.32 Pancreas 5370.3%0.86250.2%0.3 2.94 Lung 1,3570.7%1.94,1071.4%1.7 1.13 Breast 1,0290.5%1.53,3551.1%1.4 1.05 Cervical/Endometrial 3850.2%0.59040.3%0.4 1.46 Prostate 1,5100.8%2.15,4441.9%2.2 0.95 Thyroid 710.0%0.1 1590.1%0.1 1.53 * 709,085 and 2,423,291 years follow-up in the incident diabetes and controls cohorts

16. Pharmacologic Agents in BC Formulary StatusDuration Data for Study Metformin ✔ (Open) 1980s ✔ Sulfonylureas ✔ (Open) 1980s ✔ Glitazones ✔ rosiglitazone ✔ (Spec Auth) 2005 ✔ ?? pioglitazone ✔ (Spec Auth) 2005 ✔ ?? Insulins Human ✔ (Open) 1980s ✔ Long-acting Analogs glargine ✔ (Spec Auth) 08/2007 ✗ detemir ✗ -- ✗ GLP-1 therapies ✗ -- ✗ BC - DM & Cancer Cohort Study Source: http://www.health.gov.bc.ca/pharmacare

17. BC - DM & Cancer Cohort Study

18. Thank you for your attention…

19. Advantages of BC Admin Dataset : - Population-based data (minimize selection bias) - Linkable databases on PHN - BC Cancer Agency data is rich - Efficient use of available data - Large populations/samples - Historic data Disadvantages of BC Admin Dataset : - Accuracy of diagnostic codes / billing data - Incomplete information on potential confounders - e.g., lifestyle behaviours; clinical data - Limited use of new agents of interest (i.e., glargine, GLP-1) Epidemiologic Studies with Large BC Admin Databases

20. BC Cancer Agency MaleFemale

21. Validity of DM Case Def’n in Large Admin Databases Author ‘Gold’ standard Sens % Spec % PPV %kappa Youden Index* MBRobinson, 1997 Self- Report 75.597.872.40.720.73 NSLeBlanc, 1998 Self- report 62.799.4.. 0.62 PEIVan Til, 2001Diabetes registry 89.296.662.20.710.86 ONHux 2002Physician charts 86.097.080.00.800.83 MBLix 2006CCHS 2001 79.599.387.90.820.79 *Youden’s index = (Sens + Spec) - 1