Chapter 1

Chapter 2

Dr Spock 1956 editionswitches his recommendation

to face down USA

1950 1960 1970 1980 1990 2000 2010

Second study Suggests harm

First studySuggests harm

UK

Systematic Review Published

Three further studies; two suggest harm

Dr Spock 1946 first editionrecommends face up

Back to Sleep”Campaigns

1980 1985 1990 1995 2000 2005 2010

UK Medicines Control Agencywithdraws licence for eczema

First trialpublished in The Lancet

Positive review published but excludes largenegative trial

Review of 10 published and 10 unpublished

trials suppressed by theUK Department of Health

Evening primrose oilfirst suggested aspossible treatment

English Health Technology Assessment programme publishes review of trials: no beneficial effects

UK sales continue over the counter as “dietary supplement”

Chapter 3

1880 1900 1920 1940 1960 1980 2000 2020

Fisher and othersstart large trials of

less invasive surgery

Radical mastectomyextended in various

ways

Crile questions“more is better”in Life magazine

Rose Kushner publishes book on

breast cancerexperiences

Halsted develops radical mastectomy

Fisher trial and othersreveal no survival advantage

20 year follow-ups confirm findings

Some clinicians, in professional circles, question

need for radical surgery

Chapter 4

Early

detection

No screening Death

Ineffective screening DeathScreening

Lead Time

Usual

diagnosis

Effective screening DeathScreening

Lead Time

A B Cno symptoms no symptoms symptoms no spread spread spread

Growth and spread of cancer in heavy smokers

Screening (early detection) Diagnosis (late detection)

Chapter 5

Patient with broken

ankle

Lower leg plaster?

No plaster?

New knowledge for better patient care in the future

Treat within a randomized trial

On-going clinical uncertainty with risk of harm

Dec

isio

n Ti

me

A

B

Chapter 6

Concealing treatment allocation by telephone randomization

The patient’s condition fits the trial, and she

has consented. Which treatment pack should I

give her?

Yes doctor, your patient is eligible. She will be

allocated to treatment pack X32. After the trial we will tell you what treatment X32 was.

AAB B B

A

Randomize days within a person

Randomize individuals within a groupRandomize communities within a region

A B

A BB A

B A

Randomize eyes within a person

Randomize

Surgery Medical

SurgeryDead

Final outcome

6/6 alive 6/8 alive

Die beforesurgery

Chapter 7

Death due to bleeding

Other continents

Continent A

Continent B

Continent C

COMBINED

Risk Ratio (95% Confidence Interval)

Treatment WorseTreatment Better0.6 0.7 0.8 0.9 1 1.10.5

Chapter 8

Chapter 12

What will happen to 100 people like you in the next 10 years?

1. What would happen if I do nothing?

2. What treatments can you suggest?3.Which might be best for me?4. What are the likely benefits? Are

there any downsides for me?

So the tests confirm our diagnosis. We need

to decide the best course of action for

you.

Final Chapter

Nearly a third of trial interventions not sufficiently described

Over half of planned study outcomes not reported

Most new research not interpreted in the context of systematic assessment of other relevant evidence

Unbiased and usable report?

Research Waste

Waste at four stages of research

Low priority questions addressed

Important outcomes not assessed

Clinicians and patients not involved in setting research agendas

Questions relevant

to clinicians and patients?

Over half of studies designed without reference to systematic reviews of existing evidence

Over half of studies fail to take adequate steps to reduce biases, e.g. unconcealed treatment allocation

Appropriate design and methods?

Over half of studies never published in full

Biased under-reporting of studies with disappointing results

Accessible full publication?

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