Epidemiologic Studies of Cancer, Diabetes & Its

Treatments:Opportunities from Canada

Jeffrey A. JohnsonUniversity of Alberta

Edmonton, Canada

Cancer & Diabetes

EpidemiologyConsortium

June 14, 2010

Canadian Team

University of Alberta, Edmonton

Jeff Johnson Samantha Bowker Yutaka Yasui

University of British Columbia, Vancouver, BC

Carlo Marra

Welcome to Canada!~ 10 million km2 / ~3.9 million mi2

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

Health Care & DataCanadian ContextPublically Funded, Privately Delivered

Prescriber

Amt Dispensed

DIN

Unique ID

Mortality

Demographic Data

Hospital PhysicianInsurance Registry

Age

Gender

Location of Residence

Status Aboriginal

Co-Morbidities/Procedures

DM StatusIncident/Prev

DM StatusIncident/Prev

Co-Morbidities/Procedures

Drug

ICD-9-CMor

ICD-10CA

ICD-9-CMVital StatisticsCOD

Year of Database Initiation

Province Hospital Physician Drugs

Alberta 1973 1973 1994 (seniors)

BC 1985 1985 1997 (All)

Manitoba 1970 1970 1994 (All)

New Brunswick 1973 1989 1990 (Seniors)

Nova Scotia 1973 1991 1975 (Seniors)

Ontario 1963 1989 1994 (Seniors)

Prince Edward Island 1984 1989 --Quebec 1983 1986 1981 (Seniors)

Saskatchewan 1970 1971 1975 (All)

Case Definition of DMwith 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 periodor

1 hospitalization for DM (ICD-10CA E10-E14)

B. Antidiabetic Drug Use

- e.g., new users of oral antidiabetic agents

0.5 0.9 1.0 1.3Adjusted* HR:

Reduced Risk Increased Risk

Diabetes Treatments& Cancer Mortality

Bowker et al., Diabetes Care, 2006

Retrospective Cohort StudySaskatchewan, Canada, 1991-1999

1.8 2.0

Sulfonylurea Monotherapy1.30

• Time fixed Cox regression analysis

• Metformin use as the reference group

• Insulin add-on as covariate

Insulin Added1.90

*age, sex, Chronic Disease Score

Diabetes Treatments& Cancer MortalityRetrospective 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

0.4 0.6 0.8 1Adjusted 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

1.5 2.0 4.0 6.0

3.33

British Columbia

1 National Diabetes Surveillance System, PHAC2 BC Cancer Agency

BC Cancer Agency

Male Female

BC - DM & Cancer Cohort Study

X

X

X

X

11 yrs

8.5 yrs

8.5 yrs

4 yrs

Subjects may be ‘censored’ due to:- death- leaving province- Dec. 31, 2007

1997 2002 2007

WashoutCancer DM

Index PeriodDM: NDSS case def’nnon DM: sex,

aboriginal match

Follow-up Period

1995

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 characteristics n % n %Sex

Male 162,901 53.2% 155,398 53.1%Female 142,583 46.6% 137,384 46.9%

Age, years30-40 31,437 10.3% 31,545 10.8%40-50 55,894 18.3% 55,552 19.0%50-60 69,237 22.6% 67,533 23.1%60-70 72,519 23.7% 68,976 23.6%70+ 77,123 25.2% 69,176 23.6%Mean (SD) 59.3 (14.2) 58.7 (14.1)

Socioeconomic status (in 1997)

1st quintile 64,798 21.2% 57,248 19.6%2nd quintile 59,155 19.3% 55,311 18.9%3rd quintile 52,765 17.2% 55,373 18.9%4th quintile 49,615 16.2% 56,421 19.3%5th quintile 43,534 14.2% 59,345 20.3%Missing 7,613 2.5% 9,084 3.1%

First-nations / ethnicityYes

BC - DM & Cancer Cohort Study

Table. Cancer and mortality incidence by diabetes index date First neoplasm (any site) Deaths (any cause)

Follow-upIncidence

rateIncidence

rateCohort index date N (years) n % (/1000PY) n % (/1000PY)Incident Diabetes

1997-2001 98,838 559,761 8,268 8.4% 14.8 15,355 15.5% 27.41997 20,128 145,585 2,125 10.6% 14.6 4,418 21.9% 30.31998 19,216 125,097 1,868 9.7% 14.9 3,461 18.0% 27.71999 19,674 112,390 1,633 8.3% 14.5 2,984 15.2% 26.62000 19,402 94,628 1,381 7.1% 14.6 2,444 12.6% 25.82001 20,418 82,062 1,261 6.2% 15.4 2,048 10.0% 25.0

2002-2006 93,468 149,323 2,729 2.9% 18.3 4,791 5.1% 32.1Controls*

None 1994-2001 292,782 2,423,291 30,972 10.6% 12.8 42,555 14.5% 17.6

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

rateIncidence

rate

First cancer site n % (/1000PY) n % (/1000PY) IRRAny 10,997 5.7% 15.5 30,972 10.6% 12.8 1.21

Colo-rectal 1,402 0.7% 2.0 3,628 1.2% 1.5 1.32Pancreas 537 0.3% 0.8 625 0.2% 0.3 2.94Lung 1,357 0.7% 1.9 4,107 1.4% 1.7 1.13Breast 1,029 0.5% 1.5 3,355 1.1% 1.4 1.05Cervical/Endometrial 385 0.2% 0.5 904 0.3% 0.4 1.46Prostate 1,510 0.8% 2.1 5,444 1.9% 2.2 0.95Thyroid 71 0.0% 0.1 159 0.1% 0.1 1.53

* 709,085 and 2,423,291 years follow-up in the incident diabetes and controls cohorts

Pharmacologic Agents in BCFormulary

Status DurationData 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

BC - DM & Cancer Cohort Study

Thank you for your

attention…

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 Studieswith Large BC Admin

Databases

BC Cancer Agency

Male Female

Validity of DM Case Def’nin Large Admin

Databases

Author‘Gold’

standardSens

%Spec

%PPV

% kappaYoudenIndex*

MB Robinson, 1997

Self-Report

75.5 97.8 72.4 0.72 0.73

NS LeBlanc, 1998

Self-report

62.7 99.4 .. .. 0.62

PEI Van Til, 2001 Diabetes registry

89.2 96.6 62.2 0.71 0.86

ON Hux 2002 Physician charts

86.0 97.0 80.0 0.80 0.83

MB Lix 2006 CCHS 2001

79.5 99.3 87.9 0.82 0.79

*Youden’s index = (Sens + Spec) - 1