Using Evidence in the Real World

John Doe
Date

Outline

Evidence-Based Medicine Framework

Assessing Evidence: The Science of Critiquing Papers

Basic Medical Statistics

Insulin Analogues: Systematic Review

Economics: Additional Evidence

Blood Glucose Test Strips for Self-Monitoring of Blood

Glucose

Evidence-Based Medicine (EBM)

Evidence-based medicine

is the conscientious, explicit

and judicious use of current
best evidence in making
decisions about the care of
individual patients.
-Dr. David Sackett

EBM movement
began in the early 1990s
Clinician preference, opinions
and experience and habits
opinion based model
EBM supported by enhanced
education, dissemination of
information
EBM endorsed by government
agencies, private sector
organizations and academic
institutions
Internet public drive for
information

Sackett DL, et al. BMJ. 1996 Jan 13;312(7023):71-2.

EBM Critique and Response

Criticisms of EBM
Cost-cutting measure
Cookbook medicine
Evidence for EBM
Uncertainty

Evidence-based
medicine is the
integration of the best
research with clinical
expertise and patient
values.

Context
Dr. David Sackett

Sackett DL, et al. BMJ. 1996 Jan 13;312(7023):71-2.

Evidence-Based Medicine (contd)

Clinical
Trials

Best
Evidence

Professional
Judgement

Systematic
Reviews

Experience

EBM
Clinical
Expertise

Patient
Values
Religious and Moral Beliefs
Preferences and Rights

Hierarchy of Evidence
Best Possible
Evidence

Guyatt G, Rennie D, eds. Users' guides to the medical literature:

a manual for evidence-based clinical practice. Chicago: AMA Press; 2002.

Why EBM? A Case Example

A Diabetes Educator has a few patients started on
sitagliptin, a DPP-4 (dipeptidyl peptidase 4) inhibitor
She notes very large improvements in A1C in these
patients
She wants to recommend that this medication be added to
the formulary

Why EBM? A Case Example (contd)

Choudhry NK,et al. Just a spoonful of medicine helps the sugar go down: Improving the management
of type 2 diabetes [Internet]. Boston (MA): Alosa Foundation; 2009.
Vinik A. Clin Ther. 2007; 29:1236-53.
Amori RE, et al. JAMA. 2007; 298: 194-206; Bolen S, et al. Ann of Int Med. 2007; 147: 386-99.

Why EBM? A Case Example (contd)

Comparative Efficacy, Safety and Cost of Oral Hypoglycemic Agents

Choudhry NK,et al. Just a spoonful of medicine helps the sugar go down: Improving the
management of type 2 diabetes [Internet]. Boston (MA): Alosa Foundation; 2009.

Canadian Agency for Drugs and

Technologies in Health
Independent, not-for-profit
organization
Not a part of government
Funded by Health Canada, the
provinces and territories
CADTH Programs

Assess drugs and health

technologies

Conduct drug reviews and

provide formulary listing
recommendations

Identify and promote evidencebased, clinical and costeffectiveness information on

optimal drug therapy

CADTH supports informed

decisions by providing
impartial, evidence-based
research and advice on drugs
and other health technologies

Assessing Evidence:
The Science of Critiquing Papers
What is the study about?
Was the study design reasonable?
Was the comparator appropriate?
How was the outcome measured?
Were patients randomized?
Was the randomization concealed?
Were patients analyzed in the groups to which they were
randomized?
Was follow-up complete?

Basic Statistics
Control Event Rate

(CER)

Treatment Event Rate

(TER)

Relative Risk (RR)

= TER / CER

Relative Risk Reduction (RRR)

= (1-RR) x 100%

Absolute Risk Reduction (ARR)

= CER TER

Number Needed to Treat (NNT)

= 1/ARR

Number Needed to Harm (NNH) = 1/ARI

An Example: Hypoglycemia
RCT of 20 patients comparing a new diabetes treatment
(drug A) vs. the control
Risk of experiencing hypoglycemia:
Drug A: 2 out of 10 pts
Risk = 2/10 = 0.2 or 20%
Control: 4 out of 10 pts
Risk = 4/10 = 0.4 or 40%
Relative Risk (RR) = risk in Drug A / risk in Control = 0.2/0.4 = 0.5

proportion of people having the event in the treatment

group compared to the control group

Examining ARR, RRR, and NNT

Event Rate

RRR

ARR

NNT

1% vs. 2%

50%

1%

100

10% vs. 20%

50%

10%

10

40% vs. 80%

50%

40%

2.5

(Treatment vs. Placebo)

RRR = relative risk reduction; ARR = absolute risk reduction; NNT = number needed to treat

Benefit and Risk

Pioglitazone vs. placebo for type 2 diabetes and macrovascular events
Outcomesatmean34.5months

Pioglitazone

Placebo

RRR(95%CI)

NNT(95%CI)
NotSignificant

PrimaryCompositeendpoint*

20%

22%

9.2%(0.9to18)

MainSecondaryCompositeEndpoint**

12%

14%

15%(1.9to26)

49(27to407)

Anyseriousadverseevent

46%

48%

4.6%(1.1to9.9)

NotSignificant

RRI(95%CI)

NNH(95%CI)

HeartFailure

11%

8%

40%(22to60)

23(16to38)

*Deathfromanycause,nonfatalmyocardialinfarction,stroke,acutecoronarysyndrome,legamputation,
coronaryrevascularisation,orrevascularisationoftheleg.
**Deathfromanycause,nonfatalmyocardialinfarction,orstroke.

RRR = relative risk reduction; NNT = number needed to treat; RRI = relative risk increase; NNH = number
needed to harm

Dormandy JA, et al. Lancet. 2005; 336: 1279-1289.

Isley W. ACP J Club. 2006; 142(2): 34.

Statistical vs. Clinical Significance:

Using A1C as an Example
Mean

Statistically significant
and clinically relevant

A1c

Confidence
interval
Fig 1: A point estimate

+0.7

Clinical relevance

Not statistically
significant

Statistical significance

Not statistically
significant
Statistical insignificance
(line = 0 for no absolute
differences, or line = 1 for no
relative differences)
Statistical significance

-0.7

Clinical relevance

CADTH. Optimal Therapy Report. 2009;3(6).

EBM in Action: Basal Insulin

Insulin

Onset of
action

Peak

Duration

5-8 h

Up to 18 h

Human Insulin
Intermediate-acting
(NPH, N)

1-3 h

Long-Acting Insulin Analogues (LAIA)

Glargine (Glar)
(Lantus)

90 min

No peak

24 h

Detemir (Det)
(Levemir)

90 min

No peak

16-24 h

CDA. Can J Diabetes 2008;32(suppl 1):i-S201.

Hirsch IB. N Engl J Med. 2005;352:174-83.
Triplitt C. U.S. Pharmacist. 2007;32:10-16.

EBM in Action: Bolus Insulin

Insulin

Onset of
action
Human Insulin

Peak

Duration

Short-acting
30-60 min
2-3 h
6.5 h
(Regular, Toronto)
Rapid-Acting Insulin Analogues (RAIA)
Lispro (Lis)
10-15 min
1-2 hours
3-5 h
(Humalog)
Aspart (Asp)
10-15 min
1-2 hours
3-5h
(NovoRapid)

CDA. Can J Diabetes 2008;32(suppl 1):i-S201.

Hirsch IB. N Engl J Med. 2005;352:174-83.
Triplitt C. U.S. Pharmacist. 2007;32:10-16.

Criteria in Choosing the Most

Appropriate Insulin
Adverse Effects

Efficacy

A1C, FBG, 2hPPG

Overall hypoglycemia

Prevention of chronic complications

Nocturnal hypoglycemia

Severe hypoglycemia

Weight gain

Coronary artery disease,

peripheral artery disease,
cerebrovascular disease
Retinopathy, nephropathy &
neuropathy
Gastroparesis, infections &
skin changes

Cost

Individual patient

Society

Quality of Life
A1C = hemoglobin A1C; FBG = fasting blood glucose; 2hPPG = 2-h postprandial glucose

Additional Statistical Terms

Weighted Mean Difference (WMD)

A method used to combine measures where the mean, standard

deviation and sample size in each group are known. The weight
given to each study is determined by the precision of its
estimate of effect.

Risk Ratio (RR)

The ratio of the absolute risk of a disease among the exposed

group to the absolute risk of the disease among the unexposed
group.

Rate Ratio

The ratio of the person-time incidence rate in the exposed group

to the person-time incidence rate in the unexposed group.

RAIA vs. HI in Adults with Type 2

Diabetes: A1C
Favors human
0.8
0.6

Lispro

WMD(%

0.4

Aspart

0.2
0.06
0.03
0.12

0
0.2

0.04
0.09
0.21

0.4
0.6
0.8

Favors analog

ILis vs. HI, 11 trials; 3,093 pts

IAsp vs. HI, 6 trials; 1031 pts

HI = regular human insulin; IAsp = insulin aspart; ILis = insulin lispro; RAIA = rapid-acting insulin analogue
Singh SR, et al. CMAJ. 2009;180(4):385-97.

LAIA vs. NPH in Adults with Type 2

Diabetes: A1C
Favors human
0.8

Glargine
Detemir

0.6
0.49

WMD(%

0.4

0.38
0.28

0.2
0
0.2

0.22
0.13
0.03

0.07

0.04
0.05
0.13

w/o orals

0.1
0.18

0.4
0.6

Favors analog

with orals

0.8

IGlar vs.NPH (w/OAD), 9 trials; 3,397 pts

IDet vs. NPH (w/OAD), 3 trials; 1159 pts

with bolus
IGlar vs. NPH (w/o OADs), 1 trial; 518 pts
IDet vs.NPH (w/IAsp), 1 trial; 505 pts

IDet = insulin detemir; IGlar = insulin galrgine; LAIA = long-acting insulin analogue; NPH = neutral protamine Hagedorn

Singh SR, et al. CMAJ. 2009;180(4):385-97.

LAIA vs. HI in Adults: Weight Gain

Type 2 Diabetes
IGlar vs NPH

0.18 kg (95% CI: -0.11, 0.47)

IDet vs NPH

-0.96 kg (95% CI: -1.69, -0.23)*

* statistically significant
HI = human insulin; IGlar = insulin glargine; IDet = insulin detemir; LAIA = long-acting insulin analogue;
NPH = Neutral Protamine Hagedorn

CADTH. Optimal Therapy Report. 2008;2(1).

Hypoglycemia
Fear of Hypoglycemia
Blood Glucose < 4 mmol/L
Mild
-

Moderate
-

Tremor, palpitations, sweating & excessive hunger. Able to

self-treat.
Headache, irritability, paresthesias, decreased attentiveness,
mood changes. May be able to self treat.

Severe
-

Unresponsiveness, unconsciousness, seizure or coma.

Unable to self treat, requires assistance.
Nocturnal
- Symptoms at night (2400-0600h), 50% symptomatic, memory
impairment, warning signs inhibited

CDA. Can J Diabetes. 2008;32(suppl 1):i-S201.

CADTH. Optimal Therapy Report. 2008;2(1).

RAIA vs. HI in Adults with Type 2

Diabetes: Hypoglycemia
4.00

3.73

3.50

RiskRatio

3.00
2.50

Severe

Nocturnal

2.37

2.00
1.50

1.63

1.53

0.71

0.65

1.36

1.00
0.50

0.43

0.00

0.08

0.39
0.11

ILis vs. HI, 2 trials; 1622 pts

IAsp versus HI, 1 trial; 121 pts

0.28

ILis vs. HI, 1 trial; 178 pts

IAsp versus HI, 1 trial; 93 pts

HI = regular human insulin; IAsp = insulin aspart; ILis= insulin lispro

Singh SR, et al. CMAJ. 2009;180(4):385-97.

LAIA vs. NPH in Adults with Type 2

Diabetes Using OADs: Hypoglycemia
1.60
1.40

1.48

20.01

Severe

Nocturnal

RiskRatio

1.20
1.00
0.91
0.80
0.60

0.75
0.66

0.68
0.56
0.47

0.40
0.29

0.31

0.20
0.00

IGlar vs.NPH (w/OAD), 7 trials; 2866 pts

IDet vs. NPH (w/OAD), 2 trials; 808 pts

0.53

0.03

IGlar vs.NPH (w/OAD), 7 trials; 2532 pts

IDet vs. NPH (w/OAD), 2 trials; 808 pts

IDet = insulin detemir; IGlar = insulin glargine; NPH = neutral protamine Hagedorn; OAD = oral antidiabetes drug

Singh SR, et al. CMAJ. 2009;180(4):385-97.

Expanding Evidence
Evidence
Efficacy
Effectiveness
Economics
Efficiency
Ethics
Equity

Summary of Insulin Analogues

Cameron C, et al. CMAJ. 2009; 180(4): 400-7.

Costs of Insulin Products

10.00

AverageWholesalePrice($)permL

9.00
8.00
7.00
6.00
5.00
4.00
3.00
2.00
1.00
0.00

HumanInsulins
RapidActingInsulinAnalogues

LongActingInsulinAnalogues
PorkInsulins

McKessonCanada,MaximumWholesaleUnitPrice AverageofCanadianJurisdictions,March2008.
*Prices may vary locally and may change over time.

Types of Economic Analyses

Analytic
Method
Cost - benefit
(CBA)

Input (Cost) Consequences

Monetary

Costeffectiveness
(CEA)

Monetary

Cost-utility
(CUA)

Monetary

Costminimization
(CMA)
Cost-of-illness

Monetary

Monetary

Primary Concern

Maximal increment
in benefit for limited
resources
Clinical: life-year Least costly way to
gained, %
achieve objective;
patients
compare alternatives
reaching goal
within 1 therapeutic
category
Quality-adjusted Societal allocation;
life-year (QALY) compare alternatives
gained
across therapeutic
categories
Efficiency (e.g.,
Equal benefit
generic, therapeutic
ASSUMED
substitution)
Monetary
Total cost
identification

Cost-Utility (CU) Analysis

Incremental CU ratio
Numerator

= Cost drug A - Cost drug B

QALY drug A - QALY drug B
Denominator

$20,000 - $16,000
2.6 QALYs - 2.0 QALYs

= $6,400 / QALY

Pharmacoeconomics

CLINICAL

Safety

ECONOMIC

Side
effects

Efficacy/
Effectiveness

HUMANISTIC
Satisfaction

Work
productivity

Resources
consumed

Direct Medical
Costs

Quality
of Life

Bothersomeness,
tolerability

Denominator QALYs Gained

1.0

Health-related
quality of life
(Weights)

Perfect
Health

Dead 0.0

A + B represents the total

gain in quality and quantity of
life. A is gained by improving
quality, B is gained by extending
life.

2. With
Program

A
Qu
alit
y-

B
Adj

1. Without
Program

Intervention

Death 1
Duration (years)

ust
ed

Life

Yea
r

Death 2

Drummond MF, et al. Methods for the economic evaluation of health care programmes. 3rd
ed. Oxford: Oxford University Press; 2005.

Denominator
Healthy

Morbidity

Mortality

sG

ain
ed

Intervention A
Worse than status quo

Decrease in
total costs(-)

Consider
Costeffectiveness

Increase in
total costs (+)

Comparing Drugs

Intervention A
Better than status quo

Consider
Costeffectiveness
Reduced clinical benefit (-)

Improved clinical benefits (+)

O = what intervention is compared to (e.g., status quo)

Understanding the Plane

NW

NE

Straight line
from Origin
represents
ICUR

Difference in cost

SW

ICUR = incremental cost-utility ratio

SE

Difference in
effectiveness

Understanding the Plane

Represents a
Societal
Willingness to
Pay (WTP) for
an additional
unit of outcome

Difference in cost
NW

NE

SW

SE

Difference in
effectiveness

ICUR = incremental cost-utility ratio

Understanding the Plane

If ICUR <
WTP then
should
adopt

Difference in cost
NW

NE

If ICUR >
WTP then
should not
adopt

SW

ICUR = incremental cost-utility ratio;

WTP = willingness to pay

SE

Difference in
effectiveness

Uncertainty in Economic Analysis

NW

NE

SW

SE

Uncertainty in Economic Analysis

NW

NE

SW

SE

Uncertainty in Economic Analysis

NW

NE

WTP = Zero

SW

SE

WTP = willingness to pay

Uncertainty in Economic Analysis

WTP = $50, 000 per
QALY
NW

NE

SW

SE

QALY = quality-adjusted life-year;

WTP = willingness to pay

Uncertainty in Economic Analysis

WTP = $100 000
per QALY
NW

NE

SW

SE

QALY = quality-adjusted life-year;

WTP = willingness to pay

Uncertainty in Economic Analysis

WTP =
NW

NE

SW

SE

WTP = willingness to pay

Uncertainty in Economic Analysis

CEAC = cost-effectiveness acceptability curve; QALY = quality-adjusted life-year;

WTP = willingness to pay

Willingness to Pay Thresholds

Criteria for Interpreting Cost-utility Ratios
_______________________________________________
Cost-utility Ratio

Interpretation

___________________________________________________________

Less than GDP per capita

Good value

>1X and <3X GDP per capita

Intermediate value

More then 3X GDP per capita

Cost prohibitive

_______________________________________________

Scatter Plot
Incremental cost-utility scatter plot of glargine vs. NPH in
patients with type 2 diabetes

ICER = incremental cost-effectiveness ratio; LE = life expectancy; NPH = neutral protamine Hagedorn; QALE = quality-adjusted life expectancy

CADTH. Optimal Therapy Report. 2008;2(4).

CEAC Diagrams for Insulin Analogues

Cameron C, et al. CMAJ. 2009; 180(4): 400-7.

Insulin Analogue Overview

For routine use in most patients with type 2 diabetes, regular

and NPH insulins are safe and effective

For routine use in most patients with type 2 diabetes, there is
no clear clinical advantage to using insulin analogues as first-line
agents
Although the evidence is limited and inconsistent, patients who
are experiencing significant hypoglycemia while taking human
insulin may benefit from insulin analogues.
Assess individual needs in choosing an insulin
Type of diabetes
Efficacy, adverse effects, cost, quality of life

Testing Blood Glucose

Self-testing with blood glucose meter vs. self monitoring vs. no use
of a meter (control) in patients with type 2 diabetes not on insulin
Outcomesat12
months
A1C
Hypoglycemic
Episodes

0.14%

Self
Monitoring

0.17%

22%

28%

SelfTesting

Control
0.00%
0.00%
10%
10%

Differenceinmean
change(95%CI)
0.14%(0.35to0.07)
0.17%(0.37to0.03)
RRI(95%CI)
123%(28to292)
189%(70to396)

A1C = hemoglobin A1C; CI = confidence interval; NNH = number needed to harm; RRI = Relative Risk Increase

Farmer A, et al. BMJ 2007;335:132.

Waldron-Lynch F. ACP J Club. 2008; 148(1): 1.

NNH(95%CI)
9(5to26)
6(4to10)

Blood Glucose Testing

Blood glucose test strips (BGTS) in top 5 classes of agents in
total drug expenditure and exceed the costs of all oral
antidiabetes drugs combined.
Estimated that > 50% of expenditure on BGTS are in patients
that are not using insulin
Paradoxically there has been very little study of blood glucose
monitoring in adults with type 2 diabetes who are not using
insulin
Despite this high level of expenditure the systematic review
identified only 9 RCTs and 15 observational studies of BGTS
in patients with type 2 diabetes

CADTH. Optimal Therapy Report. 2009;3(4).

Systematic Review - Results

Systematic review suggests that self monitoring of blood glucose

resulted in a slightly lower A1C {-0.25 (95% CI -0.36 to -0.15)} than
no monitoring in adults with type 2 diabetes not on insulin

CADTH. Optimal Therapy Report. 2009;3(2).

Blood Glucose Test Strips Economic

Evaluation
Patients with Non-Insulin Treated Type 2 Diabetes Mellitus
No SMBG

SMBG

Difference
Between SMBG
and No SMBG

7.298

7.322

0.02385

$27,997

$30,708

$2,711

Quality-adjusted life-years gained*

Total direct costs [C$]*

Incremental cost per QALY gained (ICUR)*

$113,643

ICUR = incremental cost-utility ratio; QALY = quality-adjusted life-year; SMBG = self-monitoring of blood glucose.
*Discounted at 5% per year.
Cost in $C per incremental quality-adjusted life-year gained.

CADTH. Optimal Therapy Report. 2009;3(3).

Sensitivity Analysis
ICUR (C$/QALY)
Reference Case

$113,643/QALY

Lower limit of 95% CI for WMD in A1C from 7 RCTs ( A1C = -0.39%)

$77,706/QALY

Upper limit of 95% CI for WMD in A1C from 7 RCTs ( A1C = -0.15%)

$189,376/QALY

Price per test strip reduced by 25% (C$0.55/strip)

$86,129/QALY

Price per test strip reduced by 50% (C$0.36/strip)

$58,615/QALY

Price per test strip reduced by 75% (C$0.18/strip)

$31,101/QALY

History of diabetes-related complications reflective of patients in DICE study and

Canadian diabetes atlases

$89,656/QALY

SMBG <1/day, ( A1C = -0.20%; frequency = 0.77 SMBG/day)

$81,654/QALY

SMBG 1-2/day, ( A1C = -0.26%; frequency = 1.46 SMBG/day)

$122,416/QALY

SMBG >2/day, ( A1C = -0.47%; frequency = 3.5 SMBG/day)

$169,120/QALY

Baseline A1C< 8.0% (WMD in A1C%=0.16%, Baseline A1C = 7.5%)

$213,503/QALY

Baseline A1C, 8.0 to 10.5% (WMD in A1C% = 0.30%, Baseline A1C = 8.7%)

$94,443/QALY

Patients using OAD(s)

$91,724/QALY

Patients using diet only therapy

$292,144/QALY

A1C = hemoglobin A1C; CI = confidence interval; ICUR = incremental cost-utility ratio;

OAD = oral antidiabetes drug; QALY = quality-adjusted life-year; RCT = randomized controlled trial;
SMBG = self-monitoring of blood glucose; WMD = weighted mean difference

CADTH. Optimal Therapy Report. 2009;3(3).

Cost-effectiveness Acceptability Curve

Type 2 Diabetes Price of Strips
Reference case; price= $ 0.73

100%

75% price decrease, $ 0.18

50% price decrease, $ 0.36

90%

25% price decrease, $ 0.55

Probability that SMBG is cost-effective

P rice o f lo w co st alternative o n Ontario fo rmulary ($ 0.40)

A lternative price o n o ther fo rmularies ($ 0.81)

80%
70%
60%
50%
40%
30%
20%
10%
0%
$0

$25,000

$50,000

$75,000

$100,000

$125,000

$150,000

Willingness to pay per quality-adjusted life year gained

CADTH. Optimal Therapy Report. 2009;3(3).

Cost-effectiveness Acceptability Curve

Type 2 Diabetes Testing Frequency
100%

P robability that S M BG is cost-effective

90%

Reference Case
<1 SMBG per day

80%

1 to 2 SMBG per day

70%

>2 SMBG per day

60%
50%
40%
30%
20%
10%
0%
$0

$25,000

$50,000

$75,000

$100,000

Willingness to pay per QALY gained

CADTH. Optimal Therapy Report. 2009;3(3).

$125,000

$150,000

Potential Impact

Opportunity Cost
The value of opportunity forgone, as a result of engaging resources in an activity
A reduction in utilization from 9 strips/week (current use in Ontario) to 1-2 strips/week
for patients not using insulin.
Potential cost savings of $150 million
Are there alternative uses for this $150 million?
* This estimate is based on 2006 data from eight publicly funded drug plans in Canada (BC, MB, NL, NIHB, NS,
ON, QC, SK) plus data from 67% of privately funded drug plans that submitted data to Brogan Inc. Some patients
in the dataset could not be classified by province or territory, therefore the estimate is understated.

Conclusions

SMBG is associated with a modest reduction in

hemoglobin A1C in patients with type 2 diabetes
not treated with insulin

Routine use of self-monitoring of blood glucose in patients with type

2 diabetes who are not on insulin and without hypoglycemia is not
necessary

Based on available information, daily SMBG is associated with

unfavourable cost-effectiveness estimates in this group

There is an opportunity cost at a societal and individual level to

expenditure on blood glucose strips

A reduction in the price of test strips and/or testing frequency would

improve the cost-effectiveness

References
Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2
diabetes: systematic review and meta-analysis. JAMA. 2007 Jul 11;298(2):194206.
Bolen S, Feldman L, Vassy J, Wilson L, Yeh HC, Marinopoulos S, et al. Systematic
review: comparative effectiveness and safety of oral medications for type 2
diabetes mellitus. Ann Intern Med. 2007 Jul 16;147(6):386-99. Available from:
http://www.annals.org/cgi/reprint/147/6/386.pdf
Cameron CG, Bennett HA. Cost-effectiveness of insulin analogues for diabetes
mellitus. CMAJ. 2009 Feb 17;180(4):400-7.
Canadian Agency for Drugs and Technologies in Health. An economic evaluation
of insulin analogues for the treatment of patients with type 1 and type 2
diabetes mellitus in Canada [Internet]. Ottawa: The Agency; 2008. (Optimal
therapy report; vol. 2 no. 4) [cited 2008 Apr 11]. Available from:
http://cadth.ca/media/compus/reports/compus_Economic_IA_Report.pdf
Canadian Agency for Drugs and Technologies in Health. Current utilization of
blood glucose test strips in Canada [Internet]. Ottawa: The Agency; 2009 Mar.
(Optimal therapy report; vol. 3 no. 4) [cited 2009 Mar 31]. Available from:
http://www.cadth.ca/media/pdf/compus_CU_Report-BGTS.pdf

References
Canadian Agency for Drugs and Technologies in Health. Long-acting insulin
analogues for the treatment of diabetes mellitus: meta-analyses of clinical
outcomes [Internet]. Ottawa: The Agency; 2008 Mar. (Optimal therapy report;
vol. 2 no. 1) [cited 2008 Apr 9]. Available from:
http://cadth.ca/media/compus/reports/compus_Long-Acting-Insulin-AnalogsReport_Clinical-Outcomes.pdf

Canadian Agency for Drugs and Technologies in Health. Optimal therapy

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