Chapter 1

Chapter 2

Dr Spock 1956 edition switches his recommendation to face down USA Second study Suggests harm First study Suggests harm UK Systematic Review Published Three further studies; two suggest harm Dr Spock 1946 first edition recommends face up Back to Sleep” Campaigns

UK Medicines Control Agency withdraws licence for eczema First trial published in The Lancet Positive review published but excludes large negative trial Review of 10 published and 10 unpublished trials suppressed by the UK Department of Health Evening primrose oil first suggested as possible treatment English Health Technology Assessment programme publishes review of trials: no beneficial effects UK sales continue over the counter as “dietary supplement”

Chapter 3

Fisher and others start large trials of less invasive surgery Radical mastectomy extended in various ways Crile questions “more is better” in Life magazine Rose Kushner publishes book on breast cancer experiences Halsted develops radical mastectomy Fisher trial and others reveal 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 Death Screening Lead Time Usual diagnosis Effective screening Death Screening Lead Time

A B C no 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 Decision Time 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.

A ABBB A Randomize days within a person Randomize individuals within a groupRandomize communities within a region A B B A Randomize eyes within a person

Randomize SurgeryMedical Surgery Dead Final outcome 6/6 alive6/8 alive Die before surgery

Chapter 7

Death due to bleeding Other continents Continent A Continent B Continent C COMBINED Risk Ratio (95% Confidence Interval) Treatment WorseTreatment Better

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?