ioannidis 2005

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Why most published research findings are false Aur´ elien Madouasse Context Introduction Modelling Framework Hypothesis testing Bias Multiple testing Comments Corollaries Conclusion Why most published research findings are false Article by John P. A. Ioannidis (2005) Aur´ elien Madouasse November 4, 2011

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Page 1: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Why most published research findings are falseArticle by John P. A. Ioannidis (2005)

Aurelien Madouasse

November 4, 2011

Page 2: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Plan

1 Context

2 Introduction

3 Modelling FrameworkHypothesis testingBiasMultiple testingComments

4 Corollaries

5 Conclusion

Page 3: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Context

• The author: John P.A. Ioannidis

• C.F. Rehnborg Chair in Disease Prevention at StanfordUniversity (US)

• Professor of Medicine and Director of the StanfordPrevention Research Center (US)

• Chaired the Department of Hygiene and Epidemiology atthe University of Ioannina School of Medicine (Greece)

• Has a 51 page CV

Page 4: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Context

• The author: John P.A. Ioannidis• C.F. Rehnborg Chair in Disease Prevention at Stanford

University (US)• Professor of Medicine and Director of the Stanford

Prevention Research Center (US)• Chaired the Department of Hygiene and Epidemiology at

the University of Ioannina School of Medicine (Greece)• Has a 51 page CV

Page 5: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Context

• The journal: PLoS Medicine

• Public Library of Science• Peer reviewed• Open Access• Publication fee: US$2900

Page 6: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Context

• The journal: PLoS Medicine• Public Library of Science• Peer reviewed• Open Access• Publication fee: US$2900

Page 7: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Context

• The article (Checked 2011-10-22)

• Views: 410,087• Citations:

• CrossRef: 312• PubMed Central: 118• Scopus: 579• Web of Science: 585

Page 8: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Context

• The article (Checked 2011-10-22)• Views: 410,087• Citations:

• CrossRef: 312• PubMed Central: 118• Scopus: 579• Web of Science: 585

Page 9: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Plan

1 Context

2 Introduction

3 Modelling FrameworkHypothesis testingBiasMultiple testingComments

4 Corollaries

5 Conclusion

Page 10: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Introduction

• Published research findings sometimes refuted bysubsequent evidence

• Increasing concern false findings may be the majority

• This should no be surprising

• Here is why . . .

Page 11: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Plan

1 Context

2 Introduction

3 Modelling FrameworkHypothesis testingBiasMultiple testingComments

4 Corollaries

5 Conclusion

Page 12: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis testing

• Consider a parameter measured in a population ofindividuals with a disease:

• Before treatment

• After treatment (Here assuming the treatment has an effect)

Some Parameter

Fre

quen

cy

Page 13: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis testing

• Consider a parameter measured in a population ofindividuals with a disease:

• Before treatment• After treatment (Here assuming the treatment has an effect)

Some Parameter

Fre

quen

cy

Page 14: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis Testing

• We want to know whether the treatment has an effect

• We make a hypothesis

• H0: The treatment has no effect

• We test our hypothesis

• We get a result

• If H0 were true, the probability of observing our datawould be . . .

• p(data|H0) = p − value

• We draw a conclusion

• If p(data|H0) > 0.05 we accept H0 → No effect• If p(data|H0) ≤ 0.05 we reject H0 → Effect

Page 15: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis Testing

• We want to know whether the treatment has an effect

• We make a hypothesis

• H0: The treatment has no effect

• We test our hypothesis

• We get a result

• If H0 were true, the probability of observing our datawould be . . .

• p(data|H0) = p − value

• We draw a conclusion

• If p(data|H0) > 0.05 we accept H0 → No effect• If p(data|H0) ≤ 0.05 we reject H0 → Effect

Page 16: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis Testing

• We want to know whether the treatment has an effect

• We make a hypothesis• H0: The treatment has no effect

• We test our hypothesis

• We get a result

• If H0 were true, the probability of observing our datawould be . . .

• p(data|H0) = p − value

• We draw a conclusion

• If p(data|H0) > 0.05 we accept H0 → No effect• If p(data|H0) ≤ 0.05 we reject H0 → Effect

Page 17: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis Testing

• We want to know whether the treatment has an effect

• We make a hypothesis• H0: The treatment has no effect

• We test our hypothesis

• We get a result

• If H0 were true, the probability of observing our datawould be . . .

• p(data|H0) = p − value

• We draw a conclusion

• If p(data|H0) > 0.05 we accept H0 → No effect• If p(data|H0) ≤ 0.05 we reject H0 → Effect

Page 18: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis Testing

• We want to know whether the treatment has an effect

• We make a hypothesis• H0: The treatment has no effect

• We test our hypothesis

• We get a result

• If H0 were true, the probability of observing our datawould be . . .

• p(data|H0) = p − value

• We draw a conclusion

• If p(data|H0) > 0.05 we accept H0 → No effect• If p(data|H0) ≤ 0.05 we reject H0 → Effect

Page 19: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis Testing

• We want to know whether the treatment has an effect

• We make a hypothesis• H0: The treatment has no effect

• We test our hypothesis

• We get a result• If H0 were true, the probability of observing our data

would be . . .

• p(data|H0) = p − value

• We draw a conclusion

• If p(data|H0) > 0.05 we accept H0 → No effect• If p(data|H0) ≤ 0.05 we reject H0 → Effect

Page 20: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis Testing

• We want to know whether the treatment has an effect

• We make a hypothesis• H0: The treatment has no effect

• We test our hypothesis

• We get a result• If H0 were true, the probability of observing our data

would be . . .• p(data|H0) = p − value

• We draw a conclusion

• If p(data|H0) > 0.05 we accept H0 → No effect• If p(data|H0) ≤ 0.05 we reject H0 → Effect

Page 21: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis Testing

• We want to know whether the treatment has an effect

• We make a hypothesis• H0: The treatment has no effect

• We test our hypothesis

• We get a result• If H0 were true, the probability of observing our data

would be . . .• p(data|H0) = p − value

• We draw a conclusion

• If p(data|H0) > 0.05 we accept H0 → No effect• If p(data|H0) ≤ 0.05 we reject H0 → Effect

Page 22: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis Testing

• We want to know whether the treatment has an effect

• We make a hypothesis• H0: The treatment has no effect

• We test our hypothesis

• We get a result• If H0 were true, the probability of observing our data

would be . . .• p(data|H0) = p − value

• We draw a conclusion• If p(data|H0) > 0.05 we accept H0 → No effect

• If p(data|H0) ≤ 0.05 we reject H0 → Effect

Page 23: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis Testing

• We want to know whether the treatment has an effect

• We make a hypothesis• H0: The treatment has no effect

• We test our hypothesis

• We get a result• If H0 were true, the probability of observing our data

would be . . .• p(data|H0) = p − value

• We draw a conclusion• If p(data|H0) > 0.05 we accept H0 → No effect• If p(data|H0) ≤ 0.05 we reject H0 → Effect

Page 24: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis Testing

• This framework assumes that we accept to be wrong . . .

sometimes

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

• α = probability of declaring a relationship when there isnone - Type I error

• β = probability of finding no relationship when there isone - Type II error

• 1− β = probability of finding a relationship when there isone - Power

Page 25: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis Testing

• This framework assumes that we accept to be wrong . . .

sometimes

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

• α = probability of declaring a relationship when there isnone - Type I error

• β = probability of finding no relationship when there isone - Type II error

• 1− β = probability of finding a relationship when there isone - Power

Page 26: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis Testing

• This framework assumes that we accept to be wrong . . .

sometimes

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

• α = probability of declaring a relationship when there isnone - Type I error

• β = probability of finding no relationship when there isone - Type II error

• 1− β = probability of finding a relationship when there isone - Power

Page 27: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis Testing

• This framework assumes that we accept to be wrong . . .

sometimes

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

• α = probability of declaring a relationship when there isnone - Type I error

• β = probability of finding no relationship when there isone - Type II error

• 1− β = probability of finding a relationship when there isone - Power

Page 28: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis Testing

• This framework assumes that we accept to be wrong . . .

sometimes

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

• α = probability of declaring a relationship when there isnone - Type I error

• β = probability of finding no relationship when there isone - Type II error

• 1− β = probability of finding a relationship when there isone - Power

Page 29: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis Testing

• This framework assumes that we accept to be wrong . . .

sometimes

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

• α = probability of declaring a relationship when there isnone - Type I error

• β = probability of finding no relationship when there isone - Type II error

• 1− β = probability of finding a relationship when there isone - Power

Page 30: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Hypothesis Testing

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

• For a given hypothesis, whether we get it wrong dependson:

• Whether the hypothesis is true• The magnitude of the effect• The values we choose for α and β

Some Parameter

Fre

quen

cy

Some Parameter

Fre

quen

cy

Some Parameter

Fre

quen

cy

Page 31: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Modelling the Framework for FalsePositive Findings

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

Total p 1 − p

• Central point of the paper

• Consider a population of possible hypotheses• Among these hypotheses, a proportion p are True• Hypothesis testing can be seen as testing for a disease in

Epidemiology• 1− β is the sensitivity• 1− α is the specificity• We can define a positive predictive value

Page 32: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Modelling the Framework for FalsePositive Findings

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

Total p 1 − p

• Central point of the paper• Consider a population of possible hypotheses

• Among these hypotheses, a proportion p are True• Hypothesis testing can be seen as testing for a disease in

Epidemiology• 1− β is the sensitivity• 1− α is the specificity• We can define a positive predictive value

Page 33: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Modelling the Framework for FalsePositive Findings

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

Total p 1 − p

• Central point of the paper• Consider a population of possible hypotheses• Among these hypotheses, a proportion p are True

• Hypothesis testing can be seen as testing for a disease inEpidemiology

• 1− β is the sensitivity• 1− α is the specificity• We can define a positive predictive value

Page 34: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Modelling the Framework for FalsePositive Findings

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

Total p 1 − p

• Central point of the paper• Consider a population of possible hypotheses• Among these hypotheses, a proportion p are True• Hypothesis testing can be seen as testing for a disease in

Epidemiology

• 1− β is the sensitivity• 1− α is the specificity• We can define a positive predictive value

Page 35: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Modelling the Framework for FalsePositive Findings

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

Total p 1 − p

• Central point of the paper• Consider a population of possible hypotheses• Among these hypotheses, a proportion p are True• Hypothesis testing can be seen as testing for a disease in

Epidemiology• 1− β is the sensitivity

• 1− α is the specificity• We can define a positive predictive value

Page 36: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Modelling the Framework for FalsePositive Findings

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

Total p 1 − p

• Central point of the paper• Consider a population of possible hypotheses• Among these hypotheses, a proportion p are True• Hypothesis testing can be seen as testing for a disease in

Epidemiology• 1− β is the sensitivity• 1− α is the specificity

• We can define a positive predictive value

Page 37: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Modelling the Framework for FalsePositive Findings

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

Total p 1 − p

• Central point of the paper• Consider a population of possible hypotheses• Among these hypotheses, a proportion p are True• Hypothesis testing can be seen as testing for a disease in

Epidemiology• 1− β is the sensitivity• 1− α is the specificity• We can define a positive predictive value

Page 38: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Modelling the Framework for FalsePositive Findings

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

Total p 1 − p

• Positive predictive value

• Ioannidis uses R = p1−p

Page 39: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Modelling the Framework for FalsePositive Findings

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

Total p 1 − p

• Positive predictive value

PPV =p(1− β)

p(1− β) + (1− p)α

• Ioannidis uses R = p1−p

Page 40: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Modelling the Framework for FalsePositive Findings

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

Total p 1 − p

• Positive predictive value

• Ioannidis uses R = p1−p

PPV =R

1+R × (1− β)R

1+R × (1− β) + 11+R × α

Page 41: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Modelling the Framework for FalsePositive Findings

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

Total p 1 − p

• Positive predictive value

• Ioannidis uses R = p1−p

PPV =R(1− β)

R(1− β) + α

Page 42: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Bias

• Among the studies that should have been reported asnegative

• A proportion u are reported as positive because of bias

TruthTrue relationship No relationship

Trial

Relationship 1 − β αNo relationship β 1 − α

Total p 1 − p

Page 43: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Bias

• Among the studies that should have been reported asnegative

• A proportion u are reported as positive because of bias

TruthTrue relationship No relationship

Trial

Relationship 1 − β + uβ α + u(1 − α)No relationship (1 − u)β (1 − u)(1 − α)

Total p 1 − p

Page 44: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Bias

TruthTrue relationship No relationship

Trial

Relationship 1 − β + uβ α + u(1 − α)No relationship (1 − u)β (1 − u)(1 − α)

Total p 1 − p

• Positive predictive value

• Ioannidis uses R = p1−p

Page 45: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Bias

TruthTrue relationship No relationship

Trial

Relationship 1 − β + uβ α + u(1 − α)No relationship (1 − u)β (1 − u)(1 − α)

Total p 1 − p

• Positive predictive value

PPV =p(1− β + uβ)

p(1− β + uβ) + (1− p)(α + u(1− α))

• Ioannidis uses R = p1−p

Page 46: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Bias

TruthTrue relationship No relationship

Trial

Relationship 1 − β + uβ α + u(1 − α)No relationship (1 − u)β (1 − u)(1 − α)

Total p 1 − p

• Positive predictive value

• Ioannidis uses R = p1−p

PPV =R(1− β) + uβR

R + α− βR + u − uα + uβR

Page 47: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Bias

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

u = 0.05u = 0.2u = 0.5u = 0.8

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

u = 0.05u = 0.2u = 0.5u = 0.8

Power = 0.8

Page 48: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Bias

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

u = 0.05u = 0.2u = 0.5u = 0.8

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

u = 0.05u = 0.2u = 0.5u = 0.8

Power = 0.5

Page 49: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Bias

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

u = 0.05u = 0.2u = 0.5u = 0.8

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

u = 0.05u = 0.2u = 0.5u = 0.8

Power = 0.2

Page 50: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Testing by Several IndependentTeams

• Increases the probability of a positive finding . . . by chance

• Positive findings more likely to be published

• Association with publication bias?

• Positive findings more likely to receive attention

• Probability of at least one positive finding:

1 - probability of negative findings only

TruthTrue relationship No relationship

Trial

Relationship 1 − βn 1 − (1 − α)n

No relationship βn (1 − α)n

Page 51: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Testing by Several IndependentTeams

• Increases the probability of a positive finding . . . by chance

• Positive findings more likely to be published• Association with publication bias?

• Positive findings more likely to receive attention

• Probability of at least one positive finding:

1 - probability of negative findings only

TruthTrue relationship No relationship

Trial

Relationship 1 − βn 1 − (1 − α)n

No relationship βn (1 − α)n

Page 52: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Testing by Several IndependentTeams

• Increases the probability of a positive finding . . . by chance

• Positive findings more likely to be published• Association with publication bias?

• Positive findings more likely to receive attention

• Probability of at least one positive finding:

1 - probability of negative findings only

TruthTrue relationship No relationship

Trial

Relationship 1 − βn 1 − (1 − α)n

No relationship βn (1 − α)n

Page 53: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Testing by Several IndependentTeams

• Increases the probability of a positive finding . . . by chance

• Positive findings more likely to be published• Association with publication bias?

• Positive findings more likely to receive attention

• Probability of at least one positive finding:

1 - probability of negative findings only

TruthTrue relationship No relationship

Trial

Relationship 1 − βn 1 − (1 − α)n

No relationship βn (1 − α)n

Page 54: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Testing by Several IndependentTeams

• Increases the probability of a positive finding . . . by chance

• Positive findings more likely to be published• Association with publication bias?

• Positive findings more likely to receive attention

• Probability of at least one positive finding:

1 - probability of negative findings only

TruthTrue relationship No relationship

Trial

Relationship 1 − βn 1 − (1 − α)n

No relationship βn (1 − α)n

Page 55: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Testing by Several IndependentTeams

• Increases the probability of a positive finding . . . by chance

• Positive findings more likely to be published• Association with publication bias?

• Positive findings more likely to receive attention

• Probability of at least one positive finding:

1 - probability of negative findings only

TruthTrue relationship No relationship

Trial

Relationship 1 − βn 1 − (1 − α)n

No relationship βn (1 − α)n

Page 56: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Testing by Several IndependentTeams

TruthTrue relationship No relationship

Trial

Relationship 1 − βn 1 − (1 − α)n

No relationship βn (1 − α)n

Total p 1 − p

• Positive predictive value

• Ioannidis uses R = p1−p

Page 57: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Testing by Several IndependentTeams

TruthTrue relationship No relationship

Trial

Relationship 1 − βn 1 − (1 − α)n

No relationship βn (1 − α)n

Total p 1 − p

• Positive predictive value

PPV =p(1− βn)

p(1− βn) + (1− p)(1− (1− α)n)

• Ioannidis uses R = p1−p

Page 58: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Testing by Several IndependentTeams

TruthTrue relationship No relationship

Trial

Relationship 1 − βn 1 − (1 − α)n

No relationship βn (1 − α)n

Total p 1 − p

• Positive predictive value

• Ioannidis uses R = p1−p

PPV =R(1− βn)

R + 1− ((1− α)n + Rβn)

Page 59: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Testing by Several IndependentTeams

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

n = 1n = 5n = 10n = 50

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

n = 1n = 5n = 10n = 50

Power = 0.8

Page 60: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Testing by Several IndependentTeams

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

n = 1n = 5n = 10n = 50

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

n = 1n = 5n = 10n = 50

Power = 0.5

Page 61: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Testing by Several IndependentTeams

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

Pre−study odds

Pos

t−st

udy

prob

abili

ty (

PP

V)

n = 1n = 5n = 10n = 50

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

0.0 0.2 0.4 0.6 0.8 1.00.

00.

20.

40.

60.

81.

0

Pre−study probability

Pos

t−st

udy

prob

abili

ty (

PP

V)

n = 1n = 5n = 10n = 50

Power = 0.2

Page 62: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Comments on the framework

• The use of odds instead of probabilities makes the articlehard to follow

• Odds

• Max 1 on the plots i.e. p ≤ 0.5• Plausible values?

• It would be great if the framework could be formallyassessed for various scientific fields!

• Typical values for p and u in Veterinary Epidemiology???• Is it possible to design a study to estimate these???• Problem: Gold Standard

Page 63: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Comments on the framework

• The use of odds instead of probabilities makes the articlehard to follow

• Odds

• Max 1 on the plots i.e. p ≤ 0.5• Plausible values?

• It would be great if the framework could be formallyassessed for various scientific fields!

• Typical values for p and u in Veterinary Epidemiology???• Is it possible to design a study to estimate these???• Problem: Gold Standard

Page 64: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Comments on the framework

• The use of odds instead of probabilities makes the articlehard to follow

• Odds• Max 1 on the plots i.e. p ≤ 0.5

• Plausible values?

• It would be great if the framework could be formallyassessed for various scientific fields!

• Typical values for p and u in Veterinary Epidemiology???• Is it possible to design a study to estimate these???• Problem: Gold Standard

Page 65: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Comments on the framework

• The use of odds instead of probabilities makes the articlehard to follow

• Odds• Max 1 on the plots i.e. p ≤ 0.5• Plausible values?

• It would be great if the framework could be formallyassessed for various scientific fields!

• Typical values for p and u in Veterinary Epidemiology???• Is it possible to design a study to estimate these???• Problem: Gold Standard

Page 66: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Comments on the framework

• The use of odds instead of probabilities makes the articlehard to follow

• Odds• Max 1 on the plots i.e. p ≤ 0.5• Plausible values?

• It would be great if the framework could be formallyassessed for various scientific fields!

• Typical values for p and u in Veterinary Epidemiology???• Is it possible to design a study to estimate these???• Problem: Gold Standard

Page 67: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Comments on the framework

• The use of odds instead of probabilities makes the articlehard to follow

• Odds• Max 1 on the plots i.e. p ≤ 0.5• Plausible values?

• It would be great if the framework could be formallyassessed for various scientific fields!

• Typical values for p and u in Veterinary Epidemiology???

• Is it possible to design a study to estimate these???• Problem: Gold Standard

Page 68: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Comments on the framework

• The use of odds instead of probabilities makes the articlehard to follow

• Odds• Max 1 on the plots i.e. p ≤ 0.5• Plausible values?

• It would be great if the framework could be formallyassessed for various scientific fields!

• Typical values for p and u in Veterinary Epidemiology???• Is it possible to design a study to estimate these???

• Problem: Gold Standard

Page 69: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Comments on the framework

• The use of odds instead of probabilities makes the articlehard to follow

• Odds• Max 1 on the plots i.e. p ≤ 0.5• Plausible values?

• It would be great if the framework could be formallyassessed for various scientific fields!

• Typical values for p and u in Veterinary Epidemiology???• Is it possible to design a study to estimate these???• Problem: Gold Standard

Page 70: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Comments on the framework

• Link between magnitude of the effect, α, β and samplesize

• Trade off between α and β• Smaller effects require bigger samples

Some Parameter

Fre

quen

cy

Some Parameter

Fre

quen

cy

Some Parameter

Fre

quen

cy

Page 71: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Comments on the framework

• Link between magnitude of the effect, α, β and samplesize

• Trade off between α and β

• Smaller effects require bigger samples

Some Parameter

Fre

quen

cy

Some Parameter

Fre

quen

cy

Some Parameter

Fre

quen

cy

Page 72: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Comments on the framework

• Link between magnitude of the effect, α, β and samplesize

• Trade off between α and β• Smaller effects require bigger samples

Some Parameter

Fre

quen

cy

Some Parameter

Fre

quen

cy

Some Parameter

Fre

quen

cy

Page 73: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Comments on the framework

• The corollaries follow from the proposed model

Page 74: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Plan

1 Context

2 Introduction

3 Modelling FrameworkHypothesis testingBiasMultiple testingComments

4 Corollaries

5 Conclusion

Page 75: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Corollary 1

The smaller the studies conducted in a scientific field, theless likely the research findings are to be true

Page 76: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Corollary 2

The smaller the effect sizes in a scientific field, the lesslikely the research findings are to be true

Page 77: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Corollary 3

The greater the number and the lesser the selection oftested relationships in a scientific field, the less likely theresearch findings are to be true

Page 78: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Corollary 4

The greater the flexibility in designs, definitions, outcomesand analytical modes in a scientific field, the less likely theresearch findings are to be true

Page 79: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Corollary 5

The greater the financial and other interests and prejudicesin a scientific field, the less likely the research findings areto be true

Page 80: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Corollary 6

The hotter a scientific field (with more scientific teamsinvolved), the less likely the research findings are to be true

Page 81: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

Plan

1 Context

2 Introduction

3 Modelling FrameworkHypothesis testingBiasMultiple testingComments

4 Corollaries

5 Conclusion

Page 82: Ioannidis 2005

Why mostpublishedresearch

findings arefalse

AurelienMadouasse

Context

Introduction

ModellingFramework

Hypothesistesting

Bias

Multiple testing

Comments

Corollaries

Conclusion

How can we improve the situation?

• Cannot draw firm conclusions based on a single positiveresult

• It is possible to test for something until we find what wewant!

• And this is more likely to receive attention

• Selecting research questions• Avoid marketing driven questions• Importance of pre study odds

• Increase power• Larger samples

• For research questions with high pre-study odds• To test major concepts rather than narrow specific

questions

• Research standards