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 Slide 2 Canadian Team University of Alberta, Edmonton Jeff
Johnson Samantha Bowker Yutaka Yasui University of British
Columbia, Vancouver, BC Carlo Marra Slide 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 Slide 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 Slide 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) Slide 6
Case Definition of DM with Large Admin Databases Case/Cohort
Ascertainment Identifying diabetes in admin data A.National
Diabetes Surveillance System Case Defn 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 Slide 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 Slide 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 Slide 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 Slide 10 Slide 11 BC Cancer Agency
MaleFemale Slide 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 defn non DM: sex, aboriginal match
Follow-up Period 1995 Slide 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 Slide 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 Slide 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 Slide 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 Slide
17 BC - DM & Cancer Cohort Study Slide 18 Thank you for your
attention Slide 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 Slide 20 BC Cancer Agency MaleFemale
Slide 21 Validity of DM Case Defn 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
*Youdens index = (Sens + Spec) - 1
