The document discusses the benefits and risks of using case reports to draw inferences about the effects of medical interventions, noting that while case reports can provide useful information, conclusions drawn from them without controls could be incorrect. It also references debates around the appropriate role and hierarchy of evidence from randomized controlled trials and case reports. A variety of specific historical case reports and studies are cited relating to topics like bloodletting, thyroidectomy, and anti-arrhythmic drugs.

1. The benefits and risks of case reports Iain Chalmers Editor, James Lind Library www.jameslindlibrary.org “Celebrating case reports, the stories in health care” Royal College of Physicians 15 May 2009

2. “ To reinvigorate medicine and provide a useful information tool for clinicians and patients .”

3. Bastian, Glasziou and Chalmers (Submitted).

4. Cases and case series without formal controls for drawing inferences about the effects of interventions

5. "Our main wish, from which all others stem, is that RCTs be taken off their pedestal, their exalted position at the top of an artificial evidence hierarchy, that all forms of evidence be appreciated for what they can offer .” Jadad AR, Enkin MW. Randomized controlled trials: questions, answers and musings. Oxford: Blackwell Publishing , 2007, quoted with approval by Richard Smith in his introductory editorial in Cases Journal.

6. BMJ 2007;334:349-351.

8. Case 25. Instruction for a dislocation of his mandible. Edwin Smith Surgical Papyrus, IX 2-6. C. 1550 BCE.

9. “ If you examine a man having a dislocation in his mandible and you find his mouth open and his mouth does not close for him, you then place your finger[s] [? thumb] on the back of the two rami of the mandible inside his mouth, your two claws [groups of fingers] under his chin, you cause them [i.e. the two mandibles] to fall so they lie in their [correct] place!”

10. Cooper A (1801). Farther observations on the effects which take place from the destruction of the Membrana Tympani of the ear; with an account of the operation for the removal of a particular species of deafness. Philosophical Transactions of the Royal Society, Part 1:435-451. Four case reports of tympanotomy in deaf patients, with immediate restoration of hearing.

11. Liebreich O (1869). Chloral, a new hypnotic and anesthetic. Berliner Klinische Wochenschrift 6:325-327. “In all these cases the sleep produced by this substance was normal, and began sometimes only 5 minutes after administration.”

12. Maclagan T (1876). The treatment of acute rheumatism by salicin. Lancet 1:342-43 & 383-84.

14. 1676

17. Before thyroidectomy for goitre: Kocher’s patient (at rear) with her sister

18. Nine years after thyroidectomy: Kocher’s patient (on the left, with her sister) had stopped growing and become cretinoid.

21. BMJ 2007;334:349-351.

22. The danger of incorrect inferences about the effects of treatments when prognosis is variable and the association between intervention and outcome is not dramatic?

23. Tom Jefferson. More cases, doctor? Yes please! Cases Journal 2008;1:38 “Think of the practical benefits [of establishing a casebank]. What if we could access the case book of William Osler…? How many lessons would we learn or relearn?”

24. William Osler (1849-1919) pictured in 1902

25. “ Pneumonia is one of the diseases in which a timely venesection [bleeding] may save life … In a full-blooded, healthy man with a high fever and bounding pulse the abstraction of from twenty to thirty ounces of blood is in every way beneficial ”.

26. Alexander Lesassier Hamilton (1787-1839)

28. Controlled trial by 3 army surgeons to assess the effects of bloodletting in 366 sick soldiers during the Peninsular War “It had been so arranged, that this number was admitted, alternately , in such a manner that each of us had one third of the whole. The sick were indiscriminately received , and were attended as nearly as possible with the same care and accommodated with the same comforts …

29. “ Neither Mr. Anderson nor I ever once employed the lancet. He lost two, I four cases [mortality 2.5%]; whilst out of the other third [treated with bloodletting by the third surgeon] thirty five patients died.” [mortality 28.7%]

30. Your informed patient choice! Osler’s case reports, or Hamilton’s controlled trial? The choice remains fundamentally the same today.

31. Sheridan DJ, Crawford L, Rawlins MD, Julian DG. Antiarrhythmic action of lignocaine in early myocardial infarction . Lancet 1977;1:824-5. “…In nine patients with acute myocardial infarction, 100 mg of lignocaine was administered intravenously and 300 mg into the deltoid muscle.… A marked reduction in the occurrence of ventricular ectopic beats was observed… No serious side-effects were noted .”

32. At the peak of their use in the late 1980s, it has been estimated that anti-arrhythmic drugs were causing – every year in the USA - comparable numbers of deaths to the total number of Americans who died in the Vietnam war. Moore 1995.

33. “ To reinvigorate medicine and provide a useful information tool for clinicians and patients .”

34. "Our main wish, from which all others stem, is that RCTs be taken off their pedestal, their exalted position at the top of an artificial evidence hierarchy, that all forms of evidence be appreciated for what they can offer .” Jadad AR, Enkin MW. Randomized controlled trials: questions, answers and musings. Oxford: Blackwell Publishing , 2007, quoted with approval by Richard Smith in his introductory editorial in Cases Journal.

38. Venning GR (1982). Validity of anecdotal reports of suspected adverse drug reactions: the problem of false alarms. BMJ 284:249-254.

39. “ Impressions [based on cases without formal controls] about the effects of care are sometimes right, and sometimes wrong. … I wish the new Cases Journal well; but if indeed it does wish to support the counterrevolution called for by Enkin and Jadad, I hope it will follow the methodological lead set by Geoffrey Venning quarter of a century ago. The Journal should establish a prospective cohort study now to assess the extent to which its case reports about purported treatment effects lead to reliable evidence about ways of improving the care of patients.” Chalmers I (2008). ?still somewhere in Cases Journal ’s cyberspace

40. Lancet 2008;372:2023-2030.