Introduction to the
Institute for Clinical Evaluative Sciences (ICES)
and ICES expansion site, ICES@Western
November 7, 2012
CPAH/RDC Statistics and Data Series at Western
Amit Garg, Director ICES@Western
Theresa Hands, Privacy Officer
Salimah Shariff, Lead Epidemiologist
Enhancing the effectiveness of health care
for Ontarians through research
2
Outline
• Who are we?
• What does ICES do?
• What does ICES@Western offer?
• Where is ICES@Western located?
• When will ICES@Western be operational?
• How does ICES do it?
Enhancing the effectiveness of health care
for Ontarians through research
3
Who are we?
ICES
• Independent, non-profit organization
• Conducts research that contributes to:
 effectiveness,
quality, equity and efficiency of
health care and health services in Ontario
Enhancing the effectiveness of health care
for Ontarians through research
4
Who are we?
Network of Health Services Research Centres
Opened 2012
Enhancing the effectiveness of health care
for Ontarians through research
5
What does ICES do?
ICES goals
•
•
•
Carry out population-based health services research
that is relevant to clinical practice and health policy
development
Document province-wide patterns and trends in
health care delivery
Develop and share evidence to inform decisionmaking by policy makers, managers, clinicians,
planners and consumers
Enhancing the effectiveness of health care
for Ontarians through research
6
What does ICES do?
ICES goals
•
•
Promote linkages among health services
researchers and decision-makers
Train researchers and promote a wider
understanding of epidemiology and health services
research
Enhancing the effectiveness of health care
for Ontarians through research
7
What does ICES do?
Examples of ICES studies
• Some of these you may have heard of….



Mortality among Patients Admitted to Hospitals on
Weekends as Compared with Weekdays (NEJM, 2001)
Cyclo-oxygenase-2 inhibitors versus non-selective nonsteroidal anti-inflammatory drugs and congestive heart
failure outcomes in elderly patients: a population-based
cohort study (Lancet, 2004)
Unwalkable neighborhoods, poverty, and the risk of
diabetes among recent immigrants to Canada compared
with long-term residents (Diabetes Care, 2012)
Enhancing the effectiveness of health care
for Ontarians through research
ICES Ontario, Canada
linked database characteristics
Cost: if had to collect data same data prospectively or
through medical chart review very expensive.
Question
Do kidney
donors
compared to
non donor
controls of
similar health
have a higher risk of
major cardiovascular
events
when followed
for years after
donation?
Garg AX et al. BMJ 2012
We conducted a retrospective,
population-based, matched cohort
study that used large Ontario, Canada
population-based healthcare
databases
Ontario Residents
Restriction: Excluded any Ontario
resident with a medical condition before
their index date that could preclude
donation:
i.e. population
kidney disease, DM, HTN, Cancer,
Randomly assigned an index date to entire Ontario
(using same distribution of index dates in donors)CVD, pulmonary dx, liver dx, SLE,
chronic infections, HIV
This provided on average of 11 years of medicalFrom
records
for baseline
assessment,
9.6 million
Ontarians
this resulted in
with 99% of people having at least two years ofexclusion
baselineof
data
forofreview
85%
adults (15% remained)
Healthy Non-Donors
Living Kidney Donors
1992-2009
- Manual review of all charts
Match each donor to 10 non-donors
Date of nephrectomy
(controls)
AgeNon-Donors
(±2 years), Sex
referred to asIndex
index
date
Date health
(±6 months)
of similar
as donors
(start time ofIncome
follow-up)
and Residential Status
Some Baseline Characteristics
Living Kidney Donors
Non-Donors
(N = 2028)
(N = 20,280)
Age at Index Date, Years (IQR)
43 (34-50)
43 (34-50)
Age Last Follow-Up, Years (IQR)
50 (42-58)
50 (42-58)
60%
60%
6.8 (0.5 to 18)
6.5 (0.1 to 18)
15,176
147,332
Women
Follow-Up, years (range)
Follow-up, total-person years
Validated codes were used
Major cardiovascular event (death censored)
Good precision in the estimate
No difference between the groups
Donors:
1.3%; 1.7 events per 1000 person years
Non-donors: 1.4%; 2.0 events per 1000 person years
Hazard ratio 0.85, 95% CI 0.57 to 1.27
Population database strengths
• Large population-based assessment
• Databases allow for rigorous selection of non-donor controls
• F/u up to 18 years, minimal loss to follow-up. (<6% emigrated)
• CV events based on accurate and reliable codes (no recall bias)
• Cost of this study $ vs. prospective study $$$$$$
Population database limitations
• Association vs. causation. Unmeasured confounding
• Some data not available:
body mass index, blood pressure values, creatinine, cause of death
2) Hepatocytes
Statin Metabolism
CYP3A4 Metabolized Statins
Atorvastatin, simvastatin, lovastatin
2%
40%
2% Systemic Availability
1) Enterocytes - Small Intestine
100%
40%
Statin Metabolism + CYP3A4 inhibitor
2) Hepatocytes
CYP3A4 Metabolized Statins
+
Clarithromycin
/
erythromycin
Clarithromycin or Erythromycin
40%
inhibits CYP3A4 40% Systemic Availability
80%
1) Enterocytes - Small Intestine
Azithromycin a macrolide
antibiotic used for similar
indications does not100%
inhibit
CYP3A4
80%
Population Based Study of Older statin users
with new outpatient co-prescriptions
Can’t ethically
randomize
Question:
30 severe
days
a patient to a potentially
adverse
interaction.
Clarithro drug-drug
/
Hospitalization with
Erythro
rhabdomyolysis
(n ~ 75,000)
Hospitalization with AKI
Azithro
(data in subpopulation)
Would be required to intervene
All cause mortality
to
atcompared
time knew
about+worrisome
AKI based on serum
creatinine
prescription.
(n ~ 68,000)
Patel A et al. (under review) 2012
Baseline Characteristics by co-prescription
Clarithromycin
n=72,591
Erythromycin
n = 3,267
total n = 75,858
Azithromycin
n = 68,478
74 (SD 6)
74 (SD 6)
40,130 (53%)
36,323 (53%)
Cerebrovascular disease
3,189 (4%)
2,765 (4%)
Peripheral vascular disease
2,101 (3%)
1,844 (3%)
Coronary artery disease
39,908 (53%)
36,950 (54%)
Congestive heart failure
12,652 (17%)
11,776 (17%)
Systemic malignancy
21,875 (29%)
19,955 (29%)
Demographics
Age, years
Women
Co-morbidities
Clarithromycin
n=72,591
Erythromycin
n = 3,267
total n = 75,858
Azithromycin
n = 68,478
Atorvastatin
55,027 (73%)
50,111 (73%)
Simvastatin
18,421 (24%)
16,369 (24%)
2,410 (3%)
1,998 (3%)
High dose statin
30,296 (40%)
27,550 (40%)
Low dose statin
45,562 (60%)
40,928 (60%)
Oral hypoglycemic or insulin
20,367 (27%)
17,819 (26%)
Beta-blockers
29,318 (39%)
27,008 (39%)
7,941 (11%)
7,206 (11%)
18,521 (24%)
16,982 (25%)
3,307 (4%)
2,992 (4%)
Non-potassium sparing diuretics
26,901 (36%)
24,720 (36%)
NSAIDs (excluding aspirin)
16,516 (22%)
14,797 (21%)
ACE inhibitor or ARB
49,017 (65%)
44,323 (65%)
Statin Characteristics
Lovastatin
Medication use in preceding year
Verapamil or diltiazem
Use of other calcium channel blockers
Potassium sparing diuretics
Clarithromycin
n=2,334
Erythromycin
n = 93
total n = 2,427
Azithromycin
n = 1,488
serum creatinine, µmol/L
90 (76-108)
90 (76-108)
eGFR mL/min/1.73 m2
66 (51-80)
65 (51-79)
≥ 90 mL/min/1.73m2
170 (7%)
109 (7%)
60-89 mL/min/1.73m2
1294 (53%)
782 (53%)
45-59 mL/min/1.73m2
564 (23%)
331 (22%)
30-44 mL/min/1.73m2
281 (11%)
199 (13%)
118 (5%)
67 (5%)
Renal Function
eGFR category
< 30 mL/min/1.73m2
Results
Number of Events (%)
Clarithromycin/
Erythromycin
n=75,858
Azithromycin
n=68,478
Adjusted
Relative Risk
(95% CI)
Rhabdomyolysis
24 (0.03%)
10 (0.01%)
2.17 (1.03 to 4.52)
Acute kidney
injury
347 (0.46%)
176 (0.26%)
1.78 (1.52 to 2.19)
Mortality
529 (0.70%)
306 (0.45%)
1.56 (1.37 to 1.82)
Number needed to harm (death) 1 in 400
Subpopulation with Lab Values
Number of Events (%)
Acute kidney injury
(AKIN stage 1)
Clarithromycin/
Erythromycin
Azithromycin
n=2,427
n=1,488
47 (1.94%)
10 (0.67%)
Relative Risk
(95% CI)
2.92 (1.47 to 5.79)
Number needed to harm (AKI) 1 in 80
Patel A et al. (under review) 2012
Strengths
 First population based study
looking at outcomes of this
drug-drug interaction.
 Consistent with
pharmacokinetic and case
report data.
 Large number of patients.
 Near identical baseline
characteristics table for both
groups.
Limitations
 Associations, therefore not
causal.
 Unable to analyze by specific
statin type.
 Analysis restricted to older
adults.
25
How does ICES do it?
Key to ICES research
•
•
Ability to anonymously link population-based
health information on an individual patient basis
Linked data allows researchers to obtain a more
comprehensive view of specific health care
issues
Enhancing the effectiveness of health care
for Ontarians through research
26
Ms. Theresa Hands
Privacy Officer, ICES@Western
Enhancing the effectiveness of health care
for Ontarians through research
27
How does ICES do it?
How health data is generated
•
•
•
Patient enters hospital to receive care
Person sees physician for a consult
Elderly person lives in nursing home
CONSENT
• Given to the institution / caregiver only
• Can be explicit or implicit
• Use data for care, or for improving future care
Enhancing the effectiveness of health care
for Ontarians through research
28
How does ICES do it?
How health data is generated
• Patient enters clinical study
• Person fills out survey
EXPLICIT CONSENT
• to use data for specified purpose
Enhancing the effectiveness of health care
for Ontarians through research
29
How does ICES do it?
Ontario Privacy Law: PHIPA (2004)
• Personal Health Information Protection Act
• No use of Personal Health Information
(PHI) without consent
Enhancing the effectiveness of health care
for Ontarians through research
30
How does ICES do it?
So… how can we do our work?
EXCEPTION: “Prescribed Entities”
• 4 of these in Ontario




Pediatric Oncology Group of Ontario (POGO)
Cancer Care Ontario (CCO)
Canadian Institute for Health Information (CIHI)
Institute for Clinical Evaluative Sciences (ICES)
Enhancing the effectiveness of health care
for Ontarians through research
31
How does ICES do it?
Privacy
•
•
•
ICES is a prescribed entity under PHIPA 2004 (s. 45[1]
and O. Reg 329/04 section 18[1] ): Disclosure for
planning and management of the health system
Health information custodians may disclose personal
health information (PHI) to ICES for the purposes of:
Analysis and compiling statistical information related to




managing the health system
allocation of resources
evaluation and monitoring
planning for all or part of the health system
Enhancing the effectiveness of health care
for Ontarians through research
32
How does ICES do it?
Prescribed Entities
•
•
Have policies, practices and procedures in place to
protect the privacy interests of the individuals and
the capacity to make sure it is kept securely
The Ontario Information and Privacy
Commissioner (IPC) has reviewed and approved
these policies, practices and procedures
•
The review / approval is renewed every three years
•
VERY big deal!
Enhancing the effectiveness of health care
for Ontarians through research
33
Dr. Salimah Shariff
Lead Epidemiologist, ICES@Western
Enhancing the effectiveness of health care
for Ontarians through research
34
How does ICES do it?
Key to ICES research
•
Ability to anonymously link population-based
health information on an individual patient basis
Enhancing the effectiveness of health care
for Ontarians through research
35
How does ICES do it?
Data sources – Patient-level data
• Health Services Databases
“transactions” of health care utilization





Ontario Health Insurance Plan Claims (OHIP)
Discharge Abstracts for Inpatient Hospitalizations
(CIHI DAD)
Same Day Surgery (CIHI SDS)
National Ambulatory Care Reporting System (NACRS)
Ontario Drug Benefit Claims (ODB)
Enhancing the effectiveness of health care
for Ontarians through research
36
How does ICES do it?
Data sources – Patient-level data
• Disease Cohorts/Registry Databases
Received from partner organization


Ontario Cancer Registry (OCR)
Canadian Organ Replacement Register (CORR)
ICES Derived Databases


Ontario Diabetes Database (ODD)
Linkage of delivering mothers to their newborns
(MOMBABY)
Enhancing the effectiveness of health care
for Ontarians through research
37
How does ICES do it?
Data sources – Patient-level data
• Externally Linked Data Sources
 Chart
reviews
 Electronic medical records (ex. Cerner)
 Surveys
• Statistics Canada
(Canadian Community Health Survey - CCHS)
• Interviews, questionnaires
 Research
datasets
Enhancing the effectiveness of health care
for Ontarians through research
38
How does ICES do it?
Data sources – Patient-level data
• Patient-level data sources can be linked to
each other using unique patient identifiers
 ICES
Key Numbers (IKN)= Encrypted OHIP #
Enhancing the effectiveness of health care
for Ontarians through research
39
How does ICES do it?
Data sources – Supporting data
• Population and Demographic Data
 Registered
Persons Database files (RPDB)
 Population Estimates
 Canadian Census Profiles
 PCCF+ (StatsCan postal code conversion file)
 Citizenship and Immigration Canada
Enhancing the effectiveness of health care
for Ontarians through research
40
How does ICES do it?
Data sources – Supporting data
• Other Supporting Data Sources
 Care
providers (all physicians in Ontario)
 Facilities and Institutions
 Management Information System (MIS;
financial and statistical data for hospitals)
 Geographic conversion tables (LHIN, Census
Subdivisions, Counties, Residence codes, etc)
 Coding tables (ICD9, ICD10, CCP, CCI, OHIP)
Enhancing the effectiveness of health care
for Ontarians through research
41
How does ICES do it?
Linking datasets
•
All data sources can be linked at various levels
IKN
Health
care
facilities
Facility
Identifier
Patientlevel
Postal Code, LHIN
Population
&
Geography
Enhancing the effectiveness of health care
for Ontarians through research
RPDB
Physician
Identifier
Care
providers
42
What does ICES@Western offer?
Process for intaking ICES studies
1. Develop a research question
 Do we have the data you need?
2. Identify ICES Scientist
 Only ICES Scientists can access ICES data for
research
 Principal investigator or co-principal investigator must
be an ICES scientist
 Must participate fully in the research project
 Responsible party within ICES
Enhancing the effectiveness of health care
for Ontarians through research
43
What does ICES@Western offer?
Process for intaking ICES studies
3. Submit 1-page research proposal &
Privacy Impact Assessment (PIA)
 Reviewed by a lead Scientist
 PIA used to ensure privacy requirements at ICES
mandated by the “Personal Health Information
Protection Act” (PHIPA)
 Ensures that project conforms to ICES policies and
procedures
Enhancing the effectiveness of health care
for Ontarians through research
44
What does ICES@Western offer?
Process for intaking ICES studies
4. Submit Project Activation Worksheet (PAW)
 Required in order to activate the project
 Provide estimate of resources and time for project
(budget)
5. Request REB approval from Western
 Submit to Health Sciences REB, Delegated Review
Enhancing the effectiveness of health care
for Ontarians through research
45
What does ICES@Western offer?
Process for intaking ICES studies
6. Develop Dataset Creation Plan (DCP)





Study design
Data sources and data elements
Time-frames
Inclusion/Exclusion criteria
Variable definitions
•
•
•
Exposure
Outcomes
Other variables
 Analytic plan
 Output tables
Enhancing the effectiveness of health care
for Ontarians through research
46
What does ICES@Western offer?
Process for intaking ICES studies
7. Submit project for execution at ICES@Western
 Reviewed by lead epidemiologist/analyst
 Entered into the queue
 Analyst assigned
•
•
Only ICES staff and faculty have access to ICES data
holdings
Analysts are trained and have expertise in conducting
health administrative database research
Enhancing the effectiveness of health care
for Ontarians through research
47
What does ICES@Western offer?
Process for intaking ICES studies
8. Project commences
 Continuous communication with analyst & study
team
 May require modifications to DCP
9. Results provided
 Aggregate level
 Results with fewer than 6 individuals are reported as
“<=5”
10.Publish!
Enhancing the effectiveness of health care
for Ontarians through research
48
What does ICES@Western offer?
Things to consider
•
Cost

Cost recovery

Grant support letter
• Project must have grant (or other) money
• Staff time is billed to investigator
• Must be submitted at least 4 weeks prior to grant
submission deadline
•
Time

Projects vary in time depending on scope and
resources required
Enhancing the effectiveness of health care
for Ontarians through research
49
What does ICES@Western offer?
Services we can provide
•
Epidemiological


•
Biostatistical

•
Literature searches
Study design/methodology, DCP advice
Analytic design advice
Administrative



Grant support letters
REB submission
New data linkages
Enhancing the effectiveness of health care
for Ontarians through research
50
What does ICES@Western offer?
Services we can provide
•
Support for Graduate Student Training



Work closely with an analyst
Have limited access to data
Can perform own analyses
Enhancing the effectiveness of health care
for Ontarians through research
51
What does ICES@Western offer?
Services we can provide
•
Faculty Scholars Program




www.iceswestern.ca
Open to all Western Faculty
Training, mentorship, epidemiologic and analytic
support to help Scholars develop and complete a
minimum of one ICES study
Guidance on grant writing and manuscript preparation
Applications accepted until February 2013 for
program commencement in September 2013
Enhancing the effectiveness of health care
for Ontarians through research
52
When & Where
ICES@Western
•
When will we be operational?


•
January, 2013
Process for new projects can start NOW
Where are we located?


ELL-218 (within Pharmacy hallway)
Victoria Hospital, E-Tower, Lower Level
Enhancing the effectiveness of health care
for Ontarians through research
53
Contact Us
ICES@Western
•
Amit Garg, Director ICES@Western


•
Theresa Hands, Privacy Officer


•
amit.garg@lhsc.on.ca
519-685-8502
theresa.hands@lhsc.on.ca
519-685-8500 x56045
Salimah Shariff, Lead Epidemiologist


salimah.shariff@ices.on.ca
519-685-8500 x56555
Enhancing the effectiveness of health care
for Ontarians through research
54
Questions?
Enhancing the effectiveness of health care
for Ontarians through research
54 of XX