Chapter 1

1. Chapter 1

3. Chapter 2

4. USA Dr Spock 1956 edition switches his recommendation to face down UK First study Suggests harm Systematic Review Published Second study Suggests harm Three further studies; two suggest harm Back to Sleep” Campaigns 1950 1960 1970 1980 1990 2000 2010 Dr Spock 1946 first edition recommends face up

5. UK Medicines Control Agency withdraws licence for eczema Evening primrose oil first suggested as possible treatment UK sales continue over the counter as “dietary supplement” 1980 1985 1990 1995 2000 2005 2010 Review of 10 published and 10 unpublished trials suppressed by theUK Department of Health First trial published in The Lancet Positive review published but excludes large negative trial English Health Technology Assessment programme publishes review of trials: no beneficial effects

6. Chapter 3

7. Fisher and others start large trials of less invasive surgery Halsted develops radical mastectomy Crile questions“more is better”in Life magazine Fisher trial and others reveal no survival advantage Radical mastectomyextended in various ways 20 year follow-ups confirm findings 1880 1900 1920 1940 1960 1980 2000 2020 Some clinicians, in professional circles, question need for radical surgery Rose Kushner publishes book on breast cancerexperiences

8. Chapter 4

9. Early detection Usual diagnosis Death No screening Screening Lead Time Death Ineffective screening Screening Lead Time Effective screening Death

10. Screening (early detection) Diagnosis (late detection) A B C no symptoms no symptoms symptoms no spread spread spread Growth and spread of cancer in heavy smokers

11. Chapter 5

12. On-going clinical uncertainty with risk of harm Lower leg plaster? No plaster? A Patient with broken ankle Decision Time New knowledge for better patient care in the future Treat within a randomized trial B

13. Chapter 6

14. 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.

15. A A B A B B A B B A B A A B Randomize days within a person Randomize eyes within a person Randomize communities within a region Randomize individuals within a group

16. Randomize Surgery Medical Die before surgery Dead Surgery Final outcome 6/6 alive 6/8 alive

17. Chapter 7

19. Death due to bleeding Risk Ratio (95% Confidence Interval) Continent A Continent B Continent C Other continents COMBINED Treatment Better Treatment Worse 0.6 0.7 0.8 0.9 1 1.1 0.5

20. Chapter 8

21. Chapter 12

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

23. 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.

24. Final Chapter

25. Waste at four stages of research 1 2 3 4 Questions relevant to clinicians and patients? Accessible full publication? Unbiased and usable report? Appropriate design and methods? Low priority questions addressed Important outcomes not assessed Clinicians and patients not involved in setting research agendas Over half of studies never published in full Biased under-reporting of studies with disappointing results 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 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 Research Waste