Literature Appraisal Effectiveness of Therapy. Measures of treatment effect Statistical significance...

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Literature AppraisalLiterature Appraisal

Effectiveness of TherapyEffectiveness of Therapy

Measures of treatment effect

• Statistical significance• Odds ratio• Relative risk• Absolute risk reduction• Number needed to treat

Measures of treatment effect

Outcome (death)

Yes No

Control a b

Experiment c d

200

Total

200100

100

Total in each group

200100

100

25

Die

10

Total in each group

After 1 year

200100

100

25 (75)

Die

10 (90)

(Survive)Total in each group

+

+

After 1 year

Risk & Relative Risk

200100

100

25 (75)

Die

10 (90)

(Survive) Risk? (a proportion)

What is the Total in each group

+

+

After 1 year

200100

100

25 (75)

Die

10 (90)

(Survive) RiskTotal in each group

+

+

After 1 year

200100

100

25 (75)

Die

10 (90)

(Survive) RiskTotal in each group

+

+

After 1 year

200100

100

25 (75)

Die

10 (90)

(Survive) RiskTotal in each group

+

+

After 1 year

200100

100

25 (75)

Die

10 (90)

(Survive) Risk

0.2525%

+

+

After 1 year

200100

100

25 (75)

Die

10 (90)

(Survive) Risk

0.25 25%

+

+

After 1 year

200100

100

25 (75)

Die

10 (90)

(Survive) Risk

0.25 25%

0.110%+

+

200100

100

25 (75)

Die

10 (90)

(Survive) Risk

0.25 25%

0.1 10%+

+

200100

100

25 (75)

Die

10 (90)

(Survive) Risk

Risk ratio or Relative risk (RR) =

+

+ 0.25 25%

0.1 10%

200100

100

25 (75)

Die

10 (90)

(Survive) Risk

Risk ratio or Relative risk (RR) =

+

+ 0.25 25%

0.1 10%

200100

100

25 (75)

Die

10 (90)

(Survive) Risk

Risk ratio or Relative risk (RR) =

2.5

+

+ 0.25 25%

0.1 10%

Odds & Odds Ratio

Odds

• The ratio between the amounts staked by parties in a bet, based on the expected probability either way.

• The balance of advantage or superiority.

200100

100

25 (75)

Die

10 (90)

(Survive) Risk

0.25

0.1

Odds?What about

+

+

200100

100

25 (75)

Die

(90)

(Survive) Risk

0.25

0.1

Odds

10 +

+

200100

100

25 (75)

Die

(90)

(Survive) Risk

0.25

0.1

Odds

10

1to3

+

+

200100

100

25 (75)

Die

10 (90)

(Survive) Risk

0.25

0.1

Odds

1to3

+

+

200100

100

25 (75)

Die

10 (90)

(Survive) Risk

0.25

0.1

Odds

1to3

1to9+

+

200100

100

25 (75)

Die

10 (90)

(Survive) Risk

0.25

0.1

Odds

1to3

1to9+

+

200100

100

25 (75)

Die

10 (90)

(Survive) Risk

0.25

0.1

Odds

1to3

1to9

Odds Ratio (O.R.) =

+

+

200100

100

25 (75)

Die

10 (90)

(Survive) Risk

0.25

0.1

Odds

1to3

1to9

Odds Ratio (O.R.) =

+

+

200100

100

25 (75)

Die

10 (90)

(Survive) Risk

0.25

0.1

Odds

1to3

1to9

Odds Ratio (O.R.) =

+

+

3

200100

100

25 (75)

Die

10 (90)

(Survive) Risk

0.25

0.1

Odds

1to3

1to9

3

Odds Ratio (O.R.) =

+

+

Risk ratio or Relative risk (RR) =

2.5

Measures of treatment effect influence clinicians decisions

• Clinicians:– more inclined to treat if the results are

presented as relative risk

– less inclined to treat if the results are presented as absolute risk reduction

Forrow et al. Am J Med 1992;92:121

• Control group event rate (CER) = Deaths / Controls

• Experiment group event rate (EER)

= Deaths / Treated

Absolute risk reduction (difference)

ARR = CER - EER

Absolute Risk Reduction

200100

100

25

Die

10

Risk

0.25 25%

0.110%

Absolute Risk Reduction

(ARR) =

CER

EER

200100

100

25

Die

10

Risk

0.2525%

0.110%

Absolute Risk Reduction

(ARR) =0.15 15%

Number Needed to Treat

NNT

Clinical value of measures of treatment effect

Number Needed To Treat• The odds ratio etc. not easy to understand,

especially for patients.

• The number needed to treat (NNT) to prevent an adverse event is a more clinically relevant measure of the consequences of treatment

Sackett DL. EBM 1996; 1: 164-6

Sinclair JC. J Clin Epidemiol 1994; 47: 881-9

Number Need to Treat (NNT)

Out of 100 patients treated 10 died compared to 25 in the placebo group

and 15 extra survived.

Therefore:

To get 1 more patient to survive, 6.7 (100/15) have to be treated.

100/15

1/ 0.15

NNT = 1/ ARR

200100

100

25

Die

10

Risk

0.2525%

0.110%

Absolute Risk Reduction (ARR) =

0.1515%

NNT=1/ARR=1/0.15=

6.7

Q.E.D.

MAGPIEOf the patients treated (5015) 40 fitted compared to 96 in the placebo group (5055)

In % Mg 0.8% vs Placebo 1.9%

Therefore: ARR 1.8 – 0.8 = 1.1% (11 per 1000)

To get 1 more patient to survive, 91 (100/1.1) have to be treated. = NNT