c1109 evidence in real world final e

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

• Context

“Evidence-based medicine is the

integration of the best research with clinical expertise and patient

values.”

Dr. David Sackett

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

Patient Values

Best Evidence

Clinical Expertise

• Professional Judgement

• Experience

EBM

• Religious and Moral Beliefs

• Preferences and Rights

• Clinical Trials

• Systematic Reviews

Evidence-Based Medicine (cont’d)

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 (cont’d)

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 (cont’d)

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

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

• 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 evidence-based, clinical and cost-effectiveness information on optimal drug therapy

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

= 1/ARR

= 1/ARI

Number Needed to Treat (NNT)

Number Needed to Harm (NNH)

= CER – TERAbsolute Risk Reduction (ARR)

= (1-RR) x 100%Relative Risk Reduction (RRR)

= TER / CERRelative Risk (RR)

(TER)Treatment Event Rate

(CER)Control Event Rate

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 RateEvent Rate(Treatment vs. Placebo)(Treatment vs. Placebo)

RRRRRR ARRARR NNTNNT

1% vs. 2% 50% 1% 100

10% vs. 20% 50% 10% 10

40% vs. 80% 50% 40% 2.5

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

Outcomes at mean 34.5 months Pioglitazone Placebo RRR (95% CI) NNT (95% CI)

Primary Composite endpoint* 20% 22% 9.2% (‐0.9 to 18) Not Significant

Main Secondary Composite Endpoint** 12% 14% 15% (1.9 to 26) 49 (27 to 407)

Any serious adverse event 46% 48% 4.6% (‐1.1 to 9.9) Not Significant

RRI (95% CI) NNH (95% CI)

Heart Failure 11% 8% 40% (22 to 60) 23 (16 to 38)

* Death from any cause, non‐fatal myocardial infarction, stroke, acute coronary syndrome, leg amputation,

coronary revascularisation, or revascularisation of the leg.** Death from any cause, non‐fatal myocardial infarction, or stroke.

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

Statistical significance

Statistical significanceClinical relevance

Clinical relevance

Statistically significantand clinically relevant

Statistical insignificance(line = 0 for no absolute differences, or line = 1 for norelative differences)

Not statistically significant

Confidenceinterval

Mean

Fig 1: A point estimate

Not statisticallysignificant

+0.7

-0.7

A1c

0

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

EBM in Action: Basal Insulin

InsulinOnset of action

Peak Duration

Human Insulin

Intermediate-acting (NPH, N)

1-3 h 5-8 h Up to 18 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

InsulinOnset of action

Peak Duration

Human Insulin

Short-acting (Regular, Toronto)

30-60 min 2-3 h 6.5 h

Rapid-Acting Insulin Analogues (RAIA)

Lispro (Lis) (Humalog®)

10-15 min 1-2 hours 3-5 h

Aspart (Asp) (NovoRapid®)

10-15 min 1-2 hours 3-5h

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

Efficacy

• A1C, FBG, 2hPPG

• Prevention of chronic complications

Coronary artery disease, peripheral artery disease, cerebrovascular disease

Retinopathy, nephropathy & neuropathy

Gastroparesis, infections & skin changes

Quality of Life

Adverse Effects

• Overall hypoglycemia

• Nocturnal hypoglycemia

• Severe hypoglycemia

• Weight gain

Cost

• Individual patient

• Society

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.

‐0.03‐0.09‐0.12‐0.21

0.06 0.04

‐0.8

‐0.6

‐0.4

‐0.2

0

0.2

0.4

0.6

0.8

WMD (%

RAIA vs. HI in Adults with Type 2 Diabetes: A1C

IAsp vs. HI, 6 trials; 1031 pts ILis vs. HI, 11 trials; 3,093 pts

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

HI = regular human insulin; IAsp = insulin aspart; ILis = insulin lispro; RAIA = rapid-acting insulin analogue

Favors human

Favors analog

Lispro Aspart

‐0.05

0.28

0.13 0.1

‐0.13

0.07

‐0.18

0.04

0.49

0.22

0.38

0.03

‐0.8

‐0.6

‐0.4

‐0.2

0

0.2

0.4

0.6

0.8

WMD (%

LAIA vs. NPH in Adults with Type 2 Diabetes: A1C


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

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

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

Favors analog

Favors human

DetemirGlargine

with orals with bolus

w/o orals

LAIA vs. HI in Adults: Weight Gain

HI = human insulin; IGlar = insulin glargine; IDet = insulin detemir; LAIA = long-acting insulin analogue;

NPH = Neutral Protamine Hagedorn

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


Hypoglycemia Fear of HypoglycemiaBlood Glucose < 4 mmol/L• Mild

- Tremor, palpitations, sweating & excessive hunger. Able to self-treat.

• Moderate- 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

0.43 0.39

0.65

0.08 0.11

2.37

1.36

1.63

0.71

0.28

3.73

1.53

0.00

0.50

1.00

1.50

2.00

2.50

3.00

3.50

4.00

Risk Ratio

Severe Nocturnal

ILis vs. HI, 2 trials; 1622 pts

IAsp versus HI, 1 trial; 121 pts

ILis vs. HI, 1 trial; 178 pts

IAsp versus HI, 1 trial; 93 pts


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

LAIA vs. NPH in Adults with Type 2 Diabetes Using OADs: Hypoglycemia

0.660.75

0.56 0.53

0.29

0.47

1.48

0.68

0.31

0.03

0.91

0.00

0.20

0.40

0.60

0.80

1.00

1.20

1.40

1.60

Risk Ratio

20.01

Severe Nocturnal

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


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



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

Expanding Evidence

Evidence

Efficacy

Effectiveness

Economics

Efficiency

Ethics

Equity

Summary of Insulin Analogues

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

0.00

1.00

2.00

3.00

4.00

5.00

6.00

7.00

8.00

9.00

10.00

Average W

holesalePrice ($) per mL

Long Acting Insulin Analogues

Pork Insulins

Human Insulins

Rapid Acting Insulin Analogues

Costs of Insulin Products

McKesson Canada, Maximum Wholesale Unit Price – Average of Canadian Jurisdictions, March 2008.

*Prices may vary locally and may change over time.

Types of Economic Analyses

Analytic Method

Input (Cost) Consequences Primary Concern

Cost - benefit (CBA)

Monetary Monetary Maximal increment in benefit for limited

resources Cost-

effectiveness (CEA)

Monetary Clinical: life-year gained, % patients

reaching goal

Least costly way to achieve objective;

compare alternatives within 1 therapeutic

category Cost-utility

(CUA) Monetary Quality-adjusted

life-year (QALY) gained

Societal allocation; compare alternatives across therapeutic

categories Cost-

minimization (CMA)

Monetary Equal benefit ASSUMED

Efficiency (e.g., generic, therapeutic

substitution) Cost-of-illness Monetary Total cost

identification

Cost-Utility (CU) Analysis

• Incremental CU ratio

= Cost drug A - Cost drug B

QALY drug A - QALY drug B

= $20,000 - $16,000

2.6 QALYs - 2.0 QALYs

= $6,400 / QALY

Numerator

Denominator

Pharmacoeconomics

CLINICAL ECONOMIC

Safety

Workproductivity

Direct Medical Costs

Quality of Life

Bothersomeness,tolerability

HUMANISTIC

Satisfaction

Efficacy/Effectiveness

Resourcesconsumed

Sideeffects

Denominator – QALYs Gained

Perfect 1.0Health

Dead 0.0

Hea

lth-r

elat

edqu

ality

of

life

(Wei

ghts

)

Intervention Death 1Duration (years)

Death 2

2. WithProgram

ABQuality-Adjusted Life Years Gained

1. WithoutProgram

“A” + “B” represents the totalgain in quality and quantity of life. “A” is gained by improving quality, “B” is gained by extendinglife.

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

Morbidity

Mortality

Healthy

Denominator

Comparing Drugs

Improved clinical benefits (+)

Incr

ease

in

to

tal

cos

ts (

+)

O

Consider Cost-effectiveness

Consider Cost-effectiveness

Intervention A Better than status quo

?

?Intervention A Worse than status quo

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

Reduced clinical benefit (-)

Dec

reas

e in

to

tal

cos

ts(-

)

0

0

NE

SW

NW

SE

Difference in cost

Difference in effectiveness

Straight line from Origin represents ICUR

Understanding the Plane

ICUR = incremental cost-utility ratio

NE

SW

NW

SE

Difference in cost


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


ICUR = incremental cost-utility ratio


NE

SW

NW

SE

Difference in cost


If ICUR < WTP then should adopt

If ICUR > WTP then should not adopt

ICUR = incremental cost-utility ratio; WTP = willingness to pay

NE

SW

NW

SE

Uncertainty in Economic Analysis

NE

SW

NW

SE


NE

SW

NW

SE

WTP = Zero


WTP = willingness to pay


NE

SW

NW

SE

WTP = $50, 000 per QALY

QALY = quality-adjusted life-year; WTP = willingness to pay


NE

SW

NW

SE

WTP = $100 000 per QALY

QALY = quality-adjusted life-year; WTP = willingness to pay


NE

SW

NW

SE

WTP = ∞

WTP = willingness to pay


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 PlotIncremental 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

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 isno 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

Outcomes at 12 months

Self TestingSelf

MonitoringControl

Difference in mean change (95% CI)

‐0.14% ‐ 0.00% –0.14% (‐0.35 to 0.07)‐ ‐0.17% 0.00% –0.17% (‐0.37 to 0.03)

RRI (95% CI) NNH (95% CI)

22% ‐ 10% 123% (28 to 292) 9 (5 to 26)‐ 28% 10% 189% (70 to 396) 6 (4 to 10)

A1C

Hypoglycemic Episodes

Farmer A, et al. BMJ 2007;335:132.Waldron-Lynch F. ACP J Club. 2008; 148(1): 1.

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

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


Systematic Review - Results

• Systematic review suggests that self monitoring of blood glucoseresulted 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


Blood Glucose Test Strips Economic Evaluation

No SMBG SMBG Difference Between SMBG and No SMBG

Quality-adjusted life-years gained* 7.298 7.322 0.02385

Total direct costs [C$]* $27,997 $30,708 $2,711

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.

Patients with Non-Insulin Treated Type 2 Diabetes Mellitus


Sensitivity AnalysisICUR (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



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


Cost-effectiveness Acceptability Curve Type 2 Diabetes – Price of Strips

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

$0 $25,000 $50,000 $75,000 $100,000 $125,000 $150,000

Willingness to pay per quality-adjusted life year gained

Pro

bab

ilit

y th

at S

MB

G i

s co

st-e

ffec

tive

Reference case; price= $0.73

75% price decrease, $0.18



Price of low cost alternative on Ontario fo rmulary ($0.40)

Alternative price on o ther formularies ($0.81)


0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

$0 $25,000 $50,000 $75,000 $100,000 $125,000 $150,000

Willingness to pay per QALY gained

Pro

bab

ilit

y th

at S

MB

G i

s co

st-e

ffec

tive

Reference Case

<1 SMBG per day

1 to 2 SMBG per day

>2 SMBG per day

Cost-effectiveness Acceptability Curve Type 2 Diabetes – Testing Frequency


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):194-206.

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-Analogs-Report_Clinical-Outcomes.pdf

Canadian Agency for Drugs and Technologies in Health. Optimal therapy recommendations for the prescribing and use of blood glucose test strips [Internet]. Ottawa: The Agency; 2009 Jul. [cited 2009 Jul 31]. (Optimal therapy report; vol. 3 no. 6). Available from: http://www.cadth.ca/media/pdf/compus_BGTS_OT_Rec_e.pdf

Canadian Diabetes Association 2008 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes [Internet]. 2008 [cited 2009 Mar 20];32(suppl 1):i-S201. Available from: http://www.diabetes.ca/files/cpg2008/cpg-2008.pdf

Choudhry NK, Fischer MA, Jackowski L, Shrank WH. Just a spoonful of medicine helps the sugar go down: Improving the management of type 2 diabetes[Internet]. Boston (MA): Alosa Foundation; 2009 [cited 2010 Jan 20]. Available from: http://www.rxfacts.org/pdf/Diabetes.ev.doc.UPDATED.2009.03.06.pdf

References

Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspectivepioglitAzone Clinical Trial in macroVascular Events): a randomised controlled trial. Lancet. 2005;366(9493):1279-89.

Drummond MF, Sculpher MJ, Torrance GW, O'Brien BJ, Stoddart GL. Methods for the economic evaluation of health care programmes. 3rd ed. Oxford: Oxford University Press; 2005.

Farmer A, Wade A, Goyder E, Yudkin P, French D, Craven A, et al. Impact of self monitoring of blood glucose in the management of patients with non-insulin treated diabetes: open parallel group randomised trial. BMJ. 2007 Jul 21;335(7611):132.

Guyatt G, Rennie D, eds. Users' guides to the medical literature: a manual for evidence-based clinical practice. Chicago: AMA Press; 2002.

Hirsch IB. Insulin analogues. N Engl J Med. 2005;352(2):174-83.

References

Isley WL. Pioglitazone did not reduce a composite endpoint of macrovascularcomplications and increased risk for heart failure in type 2 diabetes with macrovascular disease. ACP J Club. 2006 Mar;144(2):34.

Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence based medicine: what it is and what it isn't. BMJ. 1996 Jan 13;312(7023):71-2.

Singh SR, Ahmad F, Lal A, Yu C, Bai Z, Bennett H. Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis. CMAJ.2009 Feb 17;180(4):385-97.

Triplitt C. How to initiate, titrate, and intensify insulin treatment in type 2 diabetes. US Pharm. 2007 [cited 2009 Feb 2];32(10):10-6. Available from: http://www.uspharmacist.com/content/t/diabetes/c/10215/

Vinik A. Advancing therapy in type 2 diabetes mellitus with early, comprehensive progression from oral agents to insulin therapy. Clin Ther. 2007;29 Spec No:1236-53.

Waldron-Lynch F, Dinneen S. Self-monitoring of blood glucose did not improve glycemic control in patients with type 2 diabetes not treated with insulin. ACP J Club. 2008 Jan;148(1):1.

c1109 evidence in real world final e

Documents

evidencebased research

spoonful of medicine

model ebm

responsecriticisms of

formularywhy ebm

diabetes internet

clinical practice

care of individual patients