Vinay Prassad, hematólogo-oncólogo y profesor de Medicina en la Oregon Health and Sciences University. Ponencia presentada en el marco de la jornada Cómo revertir prácticas clínicas de escaso valor organizada por la Societat Catalana de Gestió Sanitària el 18 de mayo de 2018.

1. Medical Reversals
Why 40% of What We Do Is Wrong
Vinay Prasad, MD MPH
Assistant Professor of Medicine
Division of Hematology-Oncology
Department of Public Health and Preventive Medicine
Senior Scholar in the Center for Ethics
Oregon Health & Science University

2. Disclosure
Funding:
@VinayPrasadMD

3. Disclosure
• Some of this talk is controversial.
• It is not my purpose to disparage any
particular practice
• Broad patterns of medical progress/
innovation/ evidence (& hijacked) and
missteps in medicine

4. What is Medical Reversal?
Often in medicine new practices replace older ones.

5. What is Medical Reversal?
H2 → PPI

6. What is Medical Reversal?
MOMP → MOPP → ABVD

7. What is Medical Reversal?
Streptokinase → TPA → PCA BM stent → drug eluting

8. What is Medical Reversal?
Many other times, something we had been doing is
found to be no better or worse than a prior or lesser
standard of care (including doing nothing)

9. What is Medical Reversal?
Routine use of Swan Ganz for monitoring ICU patients

10. What is Medical Reversal?
Routine HT for post-menopausal women

11. What is Medical Reversal?
Routine PCA for stable angina

12. What is Medical Reversal?
Much more like this….

13. Definition of Medical Reversal
A large, well done study; typically RCT (with better
blinding/controls/ power/ endpoints aka less bias);
contradicts current medical practice

14. Similar to other concepts
• No-value or low-value care
• De-adopt failed practices
• Contradicted or refuted
practices
• Slow med

15. Talk Outline
• Select examples of reversal
• Frequency estimates
• Harms
• Origins
• Solutions
• Objections
• What will EBM look like in the age of
recognition of Medical Reversal

16. Talk Outline
• Select examples of reversal
• Frequency estimates
• Harms
• Origins
• Solutions
• Objections
• What will EBM look like in the age of
recognition of Medical Reversal

18. Though common practice, ASTRAL
showed no benefit for stenting
over optimal medical
management for RAS
NEJM 2009

19. Steroid injection for spinal stenosis

20. Steroid injection for spinal stenosis

22. Talk Outline
• Select examples of reversal
• Frequency estimates
• Harms
• Origins
• Solutions
• Objections
• What will EBM look like in the age of
recognition of Medical Reversal

23. Our own estimate

24. How often does it happen?

25. How often does it happen?

26. How often does it happen?

27. How often does it happen?
We detail all 146 Reversals in the
Supplementary Appendix

28. Reversals include:
• Medications… Procedures… Devices…
Surgeries… Screening tests… OTC
medications… Vitamins… Supplements…
Treatment algorithms (P2y12 testing)
…Diagnostic instruments (Swan Ganz)…
Systems interventions… Quality and
performance measures
• In short, every corner of health care

29. Talk Outline
• Select examples of reversal
• Frequency estimates
• Harms
• Origins
• Solutions
• Objections
• What will EBM look like in the age of
recognition of Medical Reversal

30. What are the harms of reversal?
Harms are threefold:
1. People who undergo the practice during the
years it fell in favor

31. What are the harms of reversal?
Harms are threefold:
2. People who undergo the practice during the
lag time before it falls out of favor
Ten years of inertia

32. What are the harms of reversal?

33. What are the harms of reversal?
Harms are threefold:
3. Loss of trust in medical system
Mammography

34. Talk Outline
• Select examples of reversal
• Frequency estimates
• Harms
• Origins
• Solutions
• Objections
• What will EBM look like in the age of
recognition of Medical Reversal

35. Why does Reversal happen?
• We adopted something based on inadequate
& biased studies
(w/o definitive trials ongoing or forthcoming)

36. Why does Reversal happen?
• We adopted something based on inadequate
& biased studies
(w/o definitive trials ongoing or forthcoming)
– Pathophysiology alone
– Pathophysiology plus anecdotal evidence

37. Why does Reversal happen?
• We adopted something based on inadequate
& biased studies
(w/o definitive trials ongoing or forthcoming)
– Pathophysiology alone
– Pathophysiology plus anecdotal evidence
– Epidemiological evidence (with residual
confounding)
– Historical controlled evidence

38. Why does Reversal happen?
• We adopted something based on inadequate & biased studies
(w/o definitive trials ongoing or forthcoming)
– Pathophysiology alone
– Pathophysiology plus anecdotal evidence
– Epidemiological evidence (with residual confounding)
– Historical controlled evidence
– Randomized trials
• Inappropriate patients (too young/ non representative)
• Inappropriate dosing/ comparators/ concom. medications
• Single center
• Drug run periods
• Inappropriate endpoints (surrogates)
• Early termination
• Selective reporting/ publication bias
– Meta-analysis – based on caliber of included studies & completeness
Pragmatic

39. Sham controls needed
for subjective endpoints
• Meniscectomy for knee OA
• Debridement for knee OA
• RV pacing for HOCM
• Vertebroplasty
• Lumbar steroid injections
• PCA for stable angina (IMA ligation, Cobb)

43. • Y = Mortality
• X1 = Vitamin E exposure
• X2 = Age
• X3 = Sex
• X4 = Race

44. • Y = Mortality
• X1 = Vitamin E exposure
• X2 = Age
• X3 = Sex
• X4 = Race
• X5 = Income

45. • Y = Mortality
• X1 = Vitamin E exposure
• X2 = Age
• X3 = Sex
• X4 = Race
• X5 = Income
• X6 = Smoking

46. • Y = Mortality
• X1 = Vitamin E exposure
• X2 = Age
• X3 = Sex
• X4 = Income
• X5 = Smoking
• X6 = body mass index (BMI), hypertension,
diabetes, cholesterol, alcohol consumption,
education, family history of heart disease,
heart disease, any cancer, physical activity)
and race/ethnicity

47. • Many investigators with access to the data,
probing these relationships
• Each adjust for some set of covariates that
make sense to them
• What if you simulate the entire research
community?

49. Observational/ Epidemiology studies
can say anything
Hazard Ratio
Significance

51. Sacubitril
Valsartan 160 mg BID

52. Sacubitril
Valsartan 160 mg BID Enalapril 10mg BID

53. Drug run in periods
• Test a different
question: whether it
is better to stay on
Entresto or switch to
enalapril after
exposure to both
agents for unequal
time

54. The Media doesn’t help
Randomized trials
Observational trials

55. Talk Outline
• Select examples of reversal
• Frequency estimates
• Harms
• Origins
• Solutions
• Objections
• What will EBM look like in the age of
recognition of Medical Reversal

56. Solutions*
• New costly technologies that are being
introduced to health systems are ideal for
testing in RCTs

57. Solutions*
• We need to prioritize unproven medical
practice (Value of information) and run a
large, non-conflicted trials agenda

58. Solutions*
• Design and conduct of clinical trials should
move to third party agency

60. Talk Outline
• Select examples of reversal
• Frequency estimates
• Harms
• Origins
• Solutions
• Objections
• What will EBM look like in the age of
recognition of Medical Reversal

61. What about RCTs of parachutes?

62. What about RCTs of parachutes?
• Two limits of the analogy
1. A single clear etiology (BCR-ABL)
Trauma –
2. A huge effect size

63. Prior “parachutes” were no such thing

64. Most medical practices don’t have
large treatment effects

65. Some advances have been tested
without RCT

68. Final thought
• History has taught us that the arc of medicine
bends towards higher standards of evidence

69. Questions
Purpose of this talk is not to litigate any particular practice
But to speak broadly about patterns of medical progress and
missteps.
If you liked the talk, check out the book
@VinayPrasadMD