feb refresher katie 2010-1 - dalhousie university · dbp 115-1291 antihypertensives death, stroke,...

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Evidence Based Medicine, Family Physicians, and

Knowledge Translation (KATIE)

David Gardner PharmD, MSc Michael Allen MD

Dalhousie Refresher February 2010

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Disclosure

David Gardner Michael Allen Research/ development projects:

Department of Health, NS NSHRF Pfizer

Department of Health, NS Health Canada

Honouraria (expert/ speaker):

AstraZeneca Canadian Pharmacists

Association Mental Health

Commission of Canada

Canadian Optimal Medication Prescribing and Utilization Service (COMPUS)

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Objectives

•  Introduce the KATIE program

•  Raise your awareness about the importance of understanding basic terms that express therapeutic effects

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A Pervasive Concern

Continuing Medical Education often fails to lead to practice change.

Weinert et al Curr Opin Crit Care 2008

Green & Seifert. J Am Board Fam Pract 2005

Awareness

Acceptance

Adop2on

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The KATIE Program … because sometimes knowledge needs a translator

Objective

To narrow the knowledge-to-action gap by improving the effectiveness of continuing education and related activities .

The KATIE Program prioritizes the learner’s role in achieving this objective.

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Knowledge Translation has gone from country peasant to royalty

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Knowledge Translation a.k.a Knowledge-to-Action

Research Phase I-IV

Information dissemination

Information filtering and synthesis

Knowledge exchange

Action planning

Action implementation

Action evaluation

Service providers

individuals

clinics

departments

organizations

Policy makers

Adm

inistrators

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Knowledge Translation a.k.a Knowledge-to-Action

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The KATIE Program … because sometimes knowledge needs a translator

Method

Social marketing to effect a change in learning culture

Targets:

Learners

Presenters/CME developers

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Less of … More of …

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Less of …

More of …

Can you use this in your prac2ce? How?

More of …

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What the KATIE Program IS

•  A transformational influence that: –  Supports physicians and pharmacists in

making the most of their learning activities –  Promotes presenters and learners to focus

on appraising and applying new information

•  To be used in any learning situation –  Conference –  Evening presentation –  One-on-one meetings –  Readings

•  Enduring 14

What the KATIE Program is NOT

•  NOT a certification or approval program of CME content or speakers

•  NOT an activity that occurs only in formal learning settings

•  NOT a course in critical appraisal •  NOT a course in statistics This is a KATIE

approved program

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KATIE is a Collaborative Program

Drug Evaluation Unit

O’HALLORAN DESIGN

JOHN SHAW

GRAPHIC DESIGN

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KATIE Program Components and Activities

1.  The KATIE Card The appraisal/apply KT aid and reminder

2.  Katie on the 52 Crosstown The unorthodox critical appraisal teaching series

3.  KATIE @ CME Programs: •  An enduring presence of simple messages,

reminder icons

4.  KATIE for speakers 5.  www.katie.dal.ca

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To enhance CE learning and meaningful dialogue: –  learners –  presenters

An knowledge-to-action aid and reminder: –  Emphasis on

•  Critical appraisal (… should …) •  Application (… how …)

CE Programs: –  Copies available –  Content integrated

Aid for presenters 18

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Who

Outcomes

Numbers

Compared to

Believability

Chance

Follow Up

Drop-‐Outs

Risks

Missing

Worth

Str. of Evidence

Big Picture

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Mr. Edwards learns about Torturing Numbers

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The KATIE Program THEMES & ICONS

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When you see this image, what thoughts come to mind?

Marketing 101

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Marketing 101

Performance

Safety

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Marketing 101

Butt of jokes

Jokes

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What about these?

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Marketing 101

Woman with butterfly

Appraise Apply

Don’t know? Just ask

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Program developers:

Michael Allen

David Gardner

Tanya Hill

Pam McLean-‐Veysey

Andrea Murphy

Glenn Rodrigues

Corinne Tobin 28

Feedback

•  Visit our booth •  Complete the Refresher’s

evaluation •  Participate in upcoming surveys,

focus groups, or workshops

February Refresher Focus Group: Friday, 7:00 – 8:15 Workshop: Friday, 10:30 – 12:00

Over to you Mike …

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Epidemiology

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Risk

•  Risk is the probability of an event or outcome occurring, e.g., – Death – Myocardial infarction – Stroke – Healing of ulcers

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Risk

•  Risk is the probability of an event or outcome occurring

•  Probability is number between 0 and 1 or a percentage 0.4 or 40%

•  Risk sometimes referred to as event rate

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Risk

•  Event occurs in 400 out of 1000 persons •  Risk = 400/1000 = 0.4 or 40% •  In a randomized controlled trial

Relative risk = risk in study group / risk in placebo group

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Relative Risk

•  Risk in study group / risk in placebo group – Drug disease in 100 / 1000 people

•  Risk = 0.1 or 10%

– Placebo disease in 400 / 1000 people •  Risk = 0.4 or 40%

•  Relative risk = 0.1 / 0.4 = 0.25 or 25% •  Relative risk reduction =

– 1 minus relative risk – 1 minus 0.25 = 0.75 or 75%

Efficacy or Percent of events prevented

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Absolute Risk Reduction

•  Relative risk = Risk in study group / risk in placebo group

•  Relative risk reduction = 1 minus relative risk (percent of events prevented)

•  Absolute risk reduction = Risk in study group minus risk in placebo group

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Relative vs absolute values

•  Drug disease in 100 / 1000 people = 10% •  PBO disease in 400 / 1000 people = 40%

•  Relative risk = 10/40 = 0.25 or 25% •  Relative risk reduction = 1 – 0.25 = 75%

•  Absolute risk reduction = 40% - 10% = 30% •  Number needed to treat = 1/ARR = 1/0.3 = 3.3

Risk

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•  Drug disease in 10 / 1000 people = 1% •  PBO disease in 40 / 1000 people = 4%

•  Relative risk = 1/4 = 0.25 or 25% •  Relative risk reduction = 1 – 0.25 = 75%

•  Absolute risk reduction = 4% - 1% = 3% •  Number needed to treat = 1/ARR = 1/0.03 = 33

Risk

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PBO Drug RRR ARR NNT

400 40%

100 10% 75% 30% 3.3

40 4%

10 1% 75% 3% 33

Events / percent

1000 patients in placebo and drug group

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Number Needed to Treat - NNT

•  The number of patients who need to be treated to prevent one bad outcome. –  If NNT is 10

•  Have to treat 10 patients in order to prevent 1 bad outcome OR

•  1 in 10 people will benefit

•  Important to know the period of time. •  Generally, should not extrapolate beyond

period of the study 40

Number Needed to Treat

•  What’s a good NNT? •  Depends

– Severity of outcome – Cost of the drug – Adverse effects of the drug – Duration of therapy

•  Ideal is NNT = 1

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Number Needed to Treat

Condition Intervention Events prevented Time NNT

DBP 115-1291 Antihypertensives Death, stroke, MI 1.5 yrs 8

DBP 90-1091 Antihypertensives Death, stroke, MI 5.5 yrs 128

Mild to mod Donepezil vs PBO No functional 1 yr 7

Alzheimers1 decline

Dyslipidemia Statins CHD death or MI 5 yrs 57 primary prvn2

1 Evidence-based Medicine 3rd Edition 2005

2 Dalhousie Academic Detailing Service 2005

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•  Number needed to treat - NNT – The inverse of the absolute risk reduction –  If ARR = 10% NNT = 1 / 0.1 = 10 –  If ARR = 1.0% NNT = 1 / 0.01 = 100

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Relative •  Odds ratios – OR •  Hazard ratios – HR •  Relative risk – RR •  Relative risk

reduction – RRR

Absolute •  Absolute risk

reduction – ARR •  Number needed to

treat – NNT

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95% confidence interval

•  A range of values within which we can be 95% sure that the true value lies

•  Corresponds to a p-value of 0.05 but provides estimate of precision

•  For ratios (odds ratio, hazard ratio, rel risk) –  If the CI includes 1, result is not statistically

significant

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•  For ratios –  If the CI includes 1, result is not statistically

significant •  Relative risk of MI = 0.80; 95% CI 0.65 to 1.1 Not sig •  Relative risk of MI = 0.80; 95% CI 0.65 to 0.90 Sig

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•  Wide confidence interval –  Indicates wide variation in result

– Less confident in result

– Often a result of small sample size

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Think about this RCT …

•  Outcomes: non-fatal myocardial infarction and death from coronary heart disease

•  Subjects: No history of coronary heart disease (primary prevention).

•  Duration: 3.3 years •  N: 5100 patients in the control and 5100 patients in the drug

group •  The patient characteristics are:

–  80% male –  mean age = 63 yrs. –  mean blood pressure = 164/95

ASCOT Lancet 2003;361:1149-58

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1.  The drug led to a 36% decrease in the incidence of non-fatal MI and CHD death (relative risk reduction).

2.  The drug decreased the rate of non-fatal MI and CHD death from 3.0% to 1.9%, an absolute risk reduction of 1.1%.

3.  You would have to treat 94 patients for 3.3 years to prevent one non-fatal MI or a death from CHD (number needed to treat).

4.  The 95% confidence intervals around the previous result (ie, treat 94 patients for 3.3 years to avoid one non-fatal MI or CHD death) are 60 and 215.

5.  At the end of 3.3 years, 97.0% of patients who don't take the drug will remain free of a cardiac event and 98.1% of patients who take the drug will remain free of a cardiac event (inverse absolute RR).

What is your interpretation of the following results? How likely might you be to prescribe the drug based on each one?

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Patients not having MI or dying - Placebo

Patients having MI or CHD death

Patients NOT having MI or CHD death

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Patients not having MI or dying - Drug

Patients having MI or CHD death

Patients NOT having MI or CHD death

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36% relative risk reduction in non-fatal MI and fatal

CHD

Absolute risk reduction 1.1% in non-fatal MI and

fatal CHD NNT=94 (60 to 215)

ASCOT Lancet 2003

48% relative risk reduction in stroke

95% CI 11% to 69%

Absolute risk reduction 1.3% in

stroke NNT 77 (42 to 424)

CARDS Lancet 2004

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Shingles Prevention Study – Results

Outcome Event rate

Placebo Zostavax

Herpes zoster 3.3% 1.6%

PH neuralgia 0.42% 0.14%

RRR ARR

51% 1.7%

66% 0.3%

Time (Yrs)

NNT 95% CI

4 yrs 59 50 – 72

4 yrs 363 263 – 587

Lyle NEJM 2007;357:1799-1809

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Atorvastatin: primary prevention

Outcome Event rate

Placebo Atorv

CHD Death Non-fatal MI 3.0% 1.9%

Stroke 2.8% 1.5%

RRR ARR

35% 1.1%

46% 1.3%

Time (Yrs)

NNT 95% CI

3.3 yrs 94 60-215

3.9 yrs 77 42 – 424

ASCOT Lancet 2003; CARDS Lancet 2004 54

Atorvastatin: primary prevention

Outcome Event rate

Placebo Atorv

CHD Death Non-fatal MI 3.0% 1.9%

Stroke 2.8% 1.5%

RRR ARR

35% 1.1%

46% 1.3%

Time (Yrs)

NNT 95% CI

3.3 yrs 94 60-215

3.9 yrs 77 42 – 424

Outcome (Conditions being studied)

Percent of people in

placebo and drug group having the outcome

Relative risk reduction

(Efficacy or percent of

cases prevented)

Absolute risk

reduction (Event rate in placebo

minus event rate

drug)

Number needed to treat

(Number of people we

must treat to prevent one

outcome event)

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Shingles Prevention Study – Results

Outcome Event rate

Placebo Zostavax

Herpes zoster 3.3% 1.6%

PH neuralgia 0.42% 0.14%

RRR ARR

51% 1.7%

66% 0.3%

Time (Yrs)

NNT 95% CI

3.1 yrs 59 50 – 72

3.1 yrs 363 263 – 587

Lyle NEJM 2007;357:1799-1809

Outcome (Conditions being studied)

Percent of people in

placebo and drug group having the outcome

Relative risk reduction

(Efficacy or percent of

cases prevented)

Absolute risk

reduction (Event rate in placebo

minus event rate

drug)

Number needed to treat

(Number of people we

must treat to prevent one

outcome event)

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ARBs - Reductions in HF Hospitalizations

Pfeffer MA et al. Lancet 2003;363:759-66. Cohn JN et al. N Engl J Med 2001;345:1667-75.

Event rate 24% vs 20% - Hosps RRR 18% ARR 4% NNT 23 (14 – 41) 3.5 yrs

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Questions to ask

•  Is that relative risk reduction or absolute risk reduction?

•  What is the number needed to treat? – Over what period of time?

•  What are the 95% confidence intervals?

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More information

•  http://www.cebm.utoronto.ca/

•  http://cme.medicine.dal.ca/EBM.htm PPT templates and Excel calculator

•  Workshop Friday at 1030

Questions?

feb refresher katie 2010-1 - dalhousie university · dbp 115-1291 antihypertensives death, stroke,...

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