Download Understanding Medical Controversies: When Evidence and Theory

Understanding Medical Controversies:
When Evidence and Theory Collide
Tom Tape, MD, FACP
October, 2013
Kansas Chapter ACP Meeting
Questions to consider…
 How do we know whether what we are
doing for the patient is right or wrong?
 Where do our “standards of practice”
come from?
Example: Bloodletting
 Based on the prevalent ideas about disease:
 Humoral imbalance (plethoras)
 Tainted blood
Example: Vitamin C for Scurvy
 Based on empirical evidence
from a clinical trial of
treatment with various acids:
 In 1747, James Lind tried 6
treatments on 12 sailors with
scurvy.
 Only the 2 getting citric acids
improved.
The Philosophy of Truth…
 There is more than one way to evaluate the
truth of a proposition.
 CoHerence: It is true because it makes
sense.
 It is logical
 It conforms to our theory
 CoRRespondence: It is true because it is
empirically correct.
 It is supported by evidence
Coherence reasoning guides research
and clinical judgment
 Coherence drives much of modern
biomedical research:
 First identify the cause of a disease, then design a
rational therapy.
 Coherence-based reasoning seems to
“explain” the cause of disease:
 Peptic ulcers attributed to stress and acid.
 Tension headaches attributed to muscle spasm.
Correspondence criteria support
Epidemiological studies & Clinical trials
 For example: Framingham heart study
 Epidemiological risk factors of Cardiac
disease
 Hypertension, cholesterol, diabetes, smoking, etc.
 Risk factors are correspondence-based without
effort to understand why they cause disease.
Kannel WB, et al. Factors of risk in the development of coronary heart disease-six year
follow-up experience; the Framingham study. Ann Intern Med. 1961;55:33-50.
Evidence-based Medicine (EBM)
 EBM became widely known in the 1990s.
 Largely correspondence-based:
 Conscientious, explicit and judicious use of current
best evidence from systematic research to make
decisions about the care of individual patients.
 De-emphasized intuition, unsystematic clinical
experience, and pathophysiologic rationale.
 EBM polarized the medical profession.
Sackett DL, et al. Evidence based medicine:
what it is and what it isn’t. BMJ 1996;312:71-2.
A current medical controversy
Atrial fibrillation:
How should it be
managed?
From: Frye WB. Tracing Atrial Fibrillation –
100 years. New Engl J Med.
2007;255:1412-1414.C
Atrial fibrillation (AF):
Key concepts of coherence model
• Chaotic electrical
activity in atria.
• Irregular and
often rapid
ventricular
response.
• Loss of atrial
contraction.
From:Zimetbaum P. Amiodarone for atrial fibrillation. New Engl J Med. 2007;236:935-41.
Until very recently, the modern management
of AF was based on coherence:
 Rhythm control strategy:
 Restore normal sinus rhythm with electrical cardioversion
and/or antiarrhymic medications.
 Coherence rationale:
 Slow, regular rhythm optimizes pumping action.
 Contracting atria help fill ventricles.
Correspondence Approach to AF
 Observation that patients seem to tolerate slow
AF with few or no symptoms.
 Hypothesis that control of heart rate might be
good enough treatment for AF
 Rate control strategy:
 Slow the ventricular response by giving drugs that
block conduction from the atria to the ventricles.
AFFIRM Trial (2002)
 4060 patients randomized to either:
 Rhythm control strategy
 Rate control strategy
 Outcomes measured:
 Death
 Hospitalizations
 Adverse drug effects
 AFFIRM Investigators. A comparison of rate control and
rhythm control in patients with atrial fibrillation. New Engl J
Med. 2002;347: 1825-1833.
AFFIRM Trial Results
 Rhythm control no better than rate
control.
 Higher mortality trend with rhythm control.
 More hospitalizations with rhythm control.
 Many more adverse effects with rhythm control.
Authors conclude:
– “None of the presumed benefits of rhythm control …were confirmed in this
study.”
Reaction to the AFFIRM Trial
 Accompanying editorial:
 “An attempt to restore sinus rhythm is still appropriate,
although it can no longer be deemed imperative.”
 Skeptics cite “design flaws” in AFFIRM; many
continue to favor rhythm control.
 But…five subsequent correspondence trials also show
detrimental effects of rhythm control.
Cardiologists cling to coherence
“Nature has equipped the human heart with a complex
electrical system for the purpose of coordinated
propulsion of blood under a variety of physiologic
conditions. Considerable effort is expended by the
heart to maintain sinus rhythm. Cardiac
electrophysiologists…are frustrated by the conundrum
that atrial fibrillation is associated with increased
morbidity and mortality, yet attempts to prove that a
strategy to maintain nature’s rhythm has a favorable
effect on patients have been met with one setback after
another.”
Cain ME. Rhythm control in atrial fibrillation—one setback after another.
New Engl J Med. 2008;258-2725-7
A Recent Example: Vitamin D
 Annual High-Dose Oral Vitamin D and Falls and
Fractures in Older Women
 Sanders, KM et al. JAMA. May 12, 2010 303:1815-22
 Hypothesis: Vitamin D supports bone health.
 Randomized 2256 women 70 years & older to
receive high dose vitamin D or placebo for 3-5
years.
 Fall rate and fracture rate were increased in the
women taking vitamin D.
An editorial questions the findings
 “The biological plausibility of these findings
remains speculative.”
 “…vitamin D may improve physical performance,
reduce chronic pain, and improve mood in older
adults. Such benefits may have led to increased
mobility and opportunity for falls…”
 “Another plausible explanation is that
supplemental [vitamin D] may have decreased the
rate of wintertime infections.”

Dawson-Hughes B & Harris SS. High-dose vitamin D supplementation: Too much of a good thing?
JAMA May 12, 2010 303:1861
Another Recent Example: FEAST Study
 Mortality after Fluid Bolus in African
Children with Severe Infection
 K. Maitland et al. NEJM 2011;364:2483-95.
 Premise: “Rapid, early fluid resuscitation
in patients with shock, a therapy that is
aimed at the correction of hemodynamic
abnormalities, is one component of goaldriven emergency care guidelines.”
Fluid Expansion as Supportive Therapy
 Random allocation of 3170 children to (1)
Albumin bolus, (2) Saline bolus, or (3) No
bolus
Albumin Bolus
Saline Bolus
No Bolus
Death at 48 hrs (%)
10.6
10.5
7.3
Death at 4 wks (%)
12.2
12.0
8.7
 “The results of this study challenge the
importance of bolus resuscitation as a
lifesaving intervention…for children with
shock….”
Editorial comment regarding FEAST
 “The results of the FEAST trial…make it imperative
that we reappraise the fundamentals.”
 “We can only speculate on the mechanisms…”
 Interruption of catecholamine-mediated host defense responses by
rapid increase in plasma volume.
 Exacerbation of capillary leak in patients who are susceptible to
intracranial hypertension or pulmonary edema.
 “Fluid resuscitation is such a fundamental
intervention in acute medicine that these results
indicate that further high-quality research is
urgently required to define appropriate practice….”
 J. Myburgh. NEJM 2011;364:2543-2544
Physicians lack insight about the
coherence – correspondence distinction.
 Coherence and correspondence are not
part of the medical vocabulary.
 Physicians using the two different approaches don’t
understand why their viewpoints differ.
 When the two approaches produce
conflicting results, coherence often
becomes the favored strategy.
Reversal of Accepted Medical Practices
 146 Contradicted Medical Practices
identified in a 10-year review of NEJM.
 Antibiotic treatment of asymptomatic bactiuria in
diabetic women.
 Allergen-impermeable bed covers for asthma
 PCI for stable CAD
 Intensive glucose lowering in Type 2 diabetes
 Revascularization for renal artery stenosis
 Prasad V, et al. A Decade of Reversal: An Analysis of 146
Contradicted Medical Practices. Mayo Clin Proc. 2013;88:790-8
Why do we cling to coherence?
 Much of modern medical research is
coherence-based.
 Coherence-based theories and
correspondence-based evidence are often
concordant.
 We are drawn to explanations that “make
sense.”
Paying attention to conflict can
advance the field in surprising ways.
 Coherence approach to new drug development:
“Rational drug design”
 Sildenefil designed to relax smooth muscle in blood vessels in hopes
of lowering blood pressure.
 Correspondence trials found little effect on BP.
 But, subjects did not wish to surrender their supply of unused study
drug!
 Further coherence-based work has radically
changed our understanding of Erectile
Dysfunction.
Kling J. Modern Drug Discovery. 1998:1:31-8.
Other examples
 Liberal vs. Restrictive transfusion policy
 Role of erythropoietin in anemia therapy
 Low fat vs. low carb diets for obesity
 Empiric antibiotics in various settings
 Routine pre-operative testing
 High dose chemo with BMT for Breast Ca
 HDL risk factor reduction for CAD
 Ezetimibe to reduce CAD events
 Treatment of PVCs in heart disease patients
 Evaluation and Treatment of Low back pain
 Intensive glucose lowering in Type 2 diabetes
 Periodic wellness visit
Summary points
 Coherence / correspondence terms
are essentially unknown to medical
professionals.
 Controversies in the field often
involve a coherence vs.
correspondence debate.
 Understanding and applying both
approaches can both reduce
controversy and advance the field.