1. No category

Power analysis and sample size
calculation
Eirik Skogvoll, MD, PhD
Professor, Faculty of Medicine
Consultant, Dept. of Anaesthesiology and Emergency medicine
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The hypothesis test framework
Rosner tbl. 7.1
P (type II error)
Truth
Conclusion
H0 correct
1– α
α
H0 accepted
H0 rejected
P (type I error)
Power
Type I error: rejecting H0 if H0 is true
Type II error: accepting H0 if H0 is wrong
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H0 wrong
β
1–β
Hypothesis
A statement about one or more population parameters, e.g.
μ ≤3
μ1 = μ2
σ2 = 14
π = 0,4
π1 =π2
ψ =1
β1 = 0
ρ >0
(Expected value, or “true mean”)
(Two expected values)
(variance)
(probability of a “success”, in a binomial trial)
(two probabilities)
(odds ratio, from a contingency table)
(regression coefficient)
(correlation coefficient)
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The sample size is a compromise…
• Significance level
• Required or optimal power
• Available resources
– Money
– Time
– Practical issues of recruiting patients or subjects
• The problem under investigation
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Power
• The probability that some test will detect a difference, if it exists
• With low power, even large differences may go unnoticed:
Absence of evidence is not evidence of absence!
• Power is usually set to 0.8 – 0.9 (80-90 %)
• An infinitely small difference is impossible to detect
• The researcher must specify the smallest difference of (clinical) interest
• Power calculations requires knowledge of the background variability (usually
the standard deviation)
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Power or significance?
• We wish to reduce the probability of both a type I error (α) and a type II
error (β) , because…
– A small α means that it is diffcult to reject H0
– A small β means that it is easier to reject H0 (and accept H1)
– But minimizing α and β at the same time is complicated, because
α increases as β decreases, and vice versa
• Strategy:
– Keep α at a comfortable level (0.10, 0.05, 0.01);
the maximum ”acceptable” probability of making a type I error; i.e. rejecting H0
when it is true
– Then choose a test that minimizes β, i.e. maximizes power ( =1 - β).
Beware of H1: tests may have different properties!
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Power (Rosner 7.5)
One- sided alternative hypothesis
H0: μ = μ0
vs.
H1: μ = μ1 < μ0
H0 is rejected if zobs < zα and accepted if zobs ≥ zα .
The decision dose not depend on μ1 as long μ1 < μ0.
(Rosner Fig. 7.5)
Power, Pr (reject H0|H0 wrong) = 1 – Pr(type II error) = 1 – β, however,
depends on μ1.
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Rosner
Fig. 7.5
H1: μ = μ1 < μ0
9
vs.
H 0: μ = μ 0
⎛ σ2 ⎞
Under H1 , X ~ N ⎜⎜ μ1 , ⎟⎟
n ⎠
⎝
We reject H0 if the observed statistic z is less than critical value zα , i.e. if zobs < zα .
Using the corresponding value for X:
⎛
⎞
⎜ X −μ
⎟
σ ⎞
⎛
0
< zα ⎟ = Pr ⎜ X < μ0 + zα ⋅
Pr ( Z < zα ) = Pr ⎜
⎟
σ
n
⎝
⎠
⎜
⎟
⎜
⎟
n
⎝
⎠
(zα < 0)
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... remember that Z =
X − μ1
σ
⇔ X =Z⋅
σ
n
+ μ1
n
σ ⎞
σ ⎞
⎛
⎛ σ
+ μ1 < μ 0 + zα
thus, Power = P⎜ X < μ 0 + zα
⎟ = P⎜ Z
⎟
n⎠
n
n⎠
⎝
⎝
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σ ⎞
σ ⎞
⎛
⎛
zα
zα
⎟
⎜
⎟
⎜
μ
μ
μ
n ⎟ = P⎜ Z < 0 − μ1 +
n⎟
= P⎜ Z + 1 < 0 +
σ
σ
σ ⎟
σ
σ
σ ⎟
⎜
⎜
⎟
⎜
⎟
⎜
n ⎠
n
n
n ⎠
n
n
⎝
⎝
⎞
⎛
⎞
⎛
⎟
⎜
⎟
⎜
−
( μ 0 − μ1 )
μ
μ
μ
μ
−
⎛
⎞
0
1
0
1⎟
⎜
⎟
⎜
= P⎜ Z < zα +
⋅ n⎟
=P Z<
+ zα = P Z < zα +
σ
σ ⎟
⎜
⎟
⎜
σ
⎝
⎠
⎟
⎜
⎟
⎜
n
n
⎠
⎝
⎠
⎝
( μ 0 − μ1 )
⎛
⎞
= Φ⎜ zα +
⋅ n ⎟ ... because P(Z < z ) = Φ ( z ) ... table 3a
σ
⎝
⎠
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One-sided alternatives, in general:
H0: μ = μ0
vs.
As large as possible …
H1: μ = μ1
| μ0 − μ1 |
| μ0 − μ1 |
⎛
⎞
⎛
⎞
Power = Φ ⎜ zα +
⋅ n ⎟ = Φ ⎜ − z1−α +
⋅ n⎟
σ
σ
⎝
⎠
⎝
⎠
(Rosner, Eq. 7.19)
(remember that zα = – z1-α)
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Factors influencing power:
•
•
•
•
Power is reduced if α is reduced (zα becomes more negative)
Power increases with increasing |μ0 – μ1|
Power is reduced with increasing σ
Power is increased with increasing n
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Example (Rosner expl. 7.26)
Birth weight.
H0: μ0 = 120 oz, vs. H1: μ1 = 115 oz,
α = 0.05, σ = 24, n = 100.
Power = Pr(rejecting H0|H0 wrong) =
120 − 115
5 ⋅10
⎞
⎛
= Φ (0.438)
Φ⎜ z0.05 +
⋅ 100 ⎟ = Φ (−1.645 +
24
24
⎠
⎝
= Pr( Z < 0.438) = 0.66
→ Pr(type II error) = Pr(accept H0|H0 wrong) = β= 1– 0.669 = 0,331
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Example (Rosner expl. 7.29)
Birth weight.
H0: μ0 = 120 oz, vs. H1: μ1 = 110 oz,
α = 0.05, σ = 24, n = 100.
120 − 110
10 ⋅10 ⎞
⎞
⎛
⎛
Φ⎜ z0.05 +
⋅ 100 ⎟ = Φ⎜ − 1.645 +
⎟ = Φ (2.52)
24 ⎠
24
⎝
⎠
⎝
= Pr( Z < 2.52) = 0.99
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Power for a one sample test, two sided alternative (in general):
H0: μ = μ0
vs.
H1: μ = μ1 ≠ μ0
⎛
⎞
| μ0 − μ1 |
Power ≈ Φ ⎜ − z α +
⋅ n ⎟ (Rosner Eq. 7.21)
σ
⎝ 1− 2
⎠
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From Power to Sample size…
From Rosner Eq. 7.21 :
⎛
| μ 0 − μ1 | ⋅ n ⎞
⎟ = 1 − β ... now we set (" fix" ) 1 − β
Power = Φ⎜⎜ − z1−α / 2 +
⎟
σ
⎝
⎠
⎛ ⎛
| μ 0 − μ1 | ⋅ n ⎞ ⎞⎟
−1 ⎜
⎟ = Φ −1 (1 − β )
Φ Φ⎜⎜ − z1−α / 2 +
⎟⎟
⎜
σ
⎠⎠
⎝ ⎝
− z1−α / 2 +
| μ 0 − μ1 | ⋅ n
σ
= z1− β ⇔
⇔ μ 0 − μ1 ⋅ n = σ ⋅ (z1− β
| μ 0 − μ1 | ⋅ n
σ
= z1− β + z1−α / 2
σ ⋅ (z1− β + z1−α / 2 )
+ z1−α / 2 ) ⇔ n =
μ 0 − μ1
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Sample size for one sample test, two sided alternative:
H0: μ = μ0
vs.
H1: μ = μ1 ≠ μ0
σ 2 (z1− β + z1−α / 2 )2
n=
(Rosner Eq. 7.28)
2
(μ0 − μ1 )
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Two sample test: sample size (Rosner 8.10)
Given X1 ∼ N(μ1, σ21) and X2 ∼ N(μ2, σ22)
H0: μ1 = μ2 vs. H1: μ1 ≠ μ2 (two sided test),
significance level α, and Power 1 – β.
(σ 12 + σ 22 )( z
n=
1−
α
+ z1− β ) 2
2
( μ2 − μ1 )
2
…. in each group (Rosner Eq. 8.26)
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Rules of thumb
Lehr’s ”quick” equations for two-sample comparison:
• 80 % power, α = 0.05 (two sided), Δ = standardized difference,
m = no. in each group:
m = 16/Δ2
• 90 % power, α = 0.05 (two sided), Δ = standardized difference,
m = no. in each group
m = 21/Δ2
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The standardized difference
Machin et al. ”Sample size tables for Clinical studies” 3.ed, 2009
Altman 1991 (figure 15.2)
Need to specify the ”standardized difference”:
Δ=
| μ 2 − μ1 |
σ
… the least, clinically important difference expressed as standard
deviations. May vary 0,1 – 1,0, where Δ= 0,1 – 0,2 constitutes a ”small”
difference, while Δ = 0,8 is ”large”.
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What is the background variability (”noise”)?
•
•
•
From other studies
Pilot data
From the range of possible values (”quick and dirty”):
Range
SD ≈
4
•
This results stems from the basic properties of the Normal (Gaussian) distribution,
in which approx. 95 % of the population are found within ± 2SD of the mean
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Example
• 80 % power, α = 0.05 (two sided), Δ = standardised difference = 0.5
m = 16/Δ2 = 16/0.25 = 4*16 = 64
Total sample size = 64*2 = 128
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Nomogram
(Altman 1991)
(total sample size)
Standardised
difference
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Example
80 % power, α = 0.05
(two sided), Δ = 0.5
N (total) = 125
(total sample size)
Standardised
difference
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Factors influencing power (1-ß)
•
•
•
•
Power decreases if α is reduced (zα becomes more negative)
Power increases with increasing |μ0 – μ1|
Power decreases with increasing σ
Power increases with increasing sample size ”n”
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Factors leading to increased sample size (n)
•
•
•
•
Large standard deviation
Strict requirement for α (low level, 0.01- 0.02)
Strict requirement for power (1 – β) (high level: 0.90-0.95)
Low absolute difference between parameters under H1 and H0 (|μ1 – μ0|)
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Confidence intervals
• Most journals want CI’s reported along with (or instead of) p-values
• The expected length of a confidence interval is determined by the sample
size:
l = 2·tn-1,1-α/2·s/√n
…where
t=
relevant quantile of the t distribution with n-1 degrees of freedom
s = sample standard deviation
n = no. of observations
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How to make efficient use of your subjects
• Re-use subjects if possible, using a repeated measurements design.
Intra-subject variance will be reduced, as each subject acts as his own
control.
• Enter more than one experimental factor, using a factorial design. Each
subject counts twice (or thrice…) !
• Refine your measurement methods to reduce residual error
• Never, never, never…! dichotomize a continuous outcome variable to a
binary one (i.e. 1 or 0) ! This has the largest variance.
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Software for sample size calculations
• Machin et al. ”Sample Size Software for Clinical studies” 3.ed, 2009 -- but
you need to set dot (.) as decimal separator /
• Sample Power
• R
• StatExact (for special procedures)
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References
•
•
•
•
•
•
•
•
Eide, DM. Design av dyreforsøk (kap. 28) i A. Smith: Kompendium i forsøksdyrlære.
http://oslovet.veths.no/dokument.aspx?dokument=262 (2007)
Mead R. The Design of Experiments. Statistical Principles for Practical Applications.
Cambridge: Cambridge Univ. Press; 1990
Altman DG. Practical statistics for medical research. London: Chapman & Hall; 1991.
Altman DG, Bland JM. Absence of evidence is not evidence of absence. BMJ. 1995
Aug 19;311(7003):485.
Rosner B. Fundamentals of Biostatistics. Belmont, CA: Duxbury Thomson
Brooks/Cole; 2005.
Schulz KF, Grimes DA. Sample size calculations in randomised trials: mandatory and
mystical. Lancet. 2005 Apr 9-15;365(9467):1348-53.
Bland JM. The tyranny of power: is there a better way to calculate sample size? BMJ.
2009 October 6, 2009;339(oct06_3):b3985-.
Machin D, Campbell M, Tan SB, Tan SH. Sample Size Tables for Clinical Studies. 3
ed. Oxford: Wiley-Blackwell; 2009.
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