Evidence based medicine - limitations, and benefits in integrative medicine

1. Challenges with
Evidence in Integrative
Medicine

2. o "Keep an open mind – but not so
open that your brain falls out."
o - attributed to Richard Feynman, Carl
Sagan, and others

3. Parachute use to prevent death and major trauma
related to gravitational challenge: systematic
review of randomised controlled trials
o Objectives To determine whether parachutes are
effective in preventing major trauma related to
gravitational challenge.
o Design Systematic review of randomised
controlled trials.
o Data sources: Medline, Web of Science, Embase,
and the Cochrane Library databases; appropriate
internet sites and citation lists. BMJ. 2003 Dec 20;
327(7429): 1459–1461.

4. o Study selection: Studies showing the effects of
using a parachute during free fall.
o Main outcome measure Death or major trauma,
defined as an injury severity score > 15.
o Results We were unable to identify any
randomised controlled trials of parachute
intervention.

5. o Conclusions As with many interventions
intended to prevent ill health, the
effectiveness of parachutes has not been
subjected to rigorous evaluation by using
randomised controlled trials. Advocates of
evidence based medicine have criticised the
adoption of interventions evaluated by using
only observational data. We think that
everyone might benefit if the most radical
protagonists of evidence based medicine
organised and participated in a double blind,
randomised, placebo controlled, crossover
trial of the parachute.

6. Challenges with EBM in
Integrative Medicine
o Research Funding
o Remedies we choose
o Individualized Treatments
o “Placebo” vs. Context effects
o Complex illness and complex treatments
o The usual suspects:
Publication bias, etc.

7. Research Funding
o Almost 75% of U.S. clinical trials in
medicine are paid for by private companies
Bodenheimer, T. 2000. Uneasy alliance: Clinical investigators and the
pharmaceutical industry. New England Journal of Medicine 342:1539-1544.
o Research that will not occur
o Bioidentical Hormone Therapy
o Kitchen Herbalism
o Etc.

8. Challenges with EBM in
Integrative Medicine
o Research Funding
o Remedies we choose
o Individualized Treatments
o “Placebo” vs. Context effects
o Complex illness and complex treatments
o The usual suspects:
Publication bias, etc.

9. Remedies we Choose
o Plant medicine heterogeneity
o Any good herbalist will tell you that a plant
should be harvested in a particular season,
location, etc.
o Portion of plant used
 Leaves vs roots vs flowers
o How plant is extracted –
 Solvent – water vs ethanol vs scary things
 Heat
 Not extracted at all in some products

10. Standardized extracts
o Standardized extracts – standardized to 1 or
two plant components
o Questions whether the standardization is to the
“active ingredient”
o Questionable practices in “standardization”
 Spiking with one ingredient rather than
concentrating the whole plant extract

11. Quality of herbal and supplement
products on the market
o Ginseng Am J Clin Nutr. 2001 Jun;73(6):1101-6.
o Red Yeast Rice Extract J Alt Comp Med. 2001 Apr;7(2):133-9.
o Total monacolin content varied from 0% to
0.58% w/w and only 1 of 9 preparations had the
full complement of 10 monacolin compounds.
o Citrinin was found at measurable
concentrations in 7 of the 9 preparations
o Consumerlab.com

12. Challenges with EBM in
Integrative Medicine
o Research Funding
o Remedies we choose
o Individualized Treatments
o “Placebo” vs. Context effects
o Complex illness and complex treatments
o The usual suspects:
Publication bias, etc.

13. Individualized Treatments
o Many traditional systems (Ayurveda,
Acupuncture, Homeopathy) consider
individual constitution, not just diagnosis
when formulating treatments
o RCT’s looking at the overall approach may
show benefit whereas RCT’s of particular
remedies/points do not
o Challenges in using this data as a
practitioner (my own example learning
acupuncture)

14. Challenges with EBM in
Integrative Medicine
o Research Funding
o Remedies we choose
o Individualized Treatments
o “Placebo” vs. Context effects
o Complex illness and complex treatments
o The usual suspects:
Publication bias, etc.

15. Placebo ≠ Ineffective
Effect size between placebo and untreated control. In three-arm trials: direct
comparison between placebo and untreated control within the three trials
that included placebo and untreated control, In all trials: indirect comparison
between all placebo (n = 193) and all untreated control (n = 14) from different
trials. Zhang, W et al. Ann Rheum Dis 2008;67:1716-1723

16. Placebo, or Context Effects
o Placebo benefits vary by
o Culture: 0-100% Moerman, D. E. 2000 Cultural variations in the placebo
effect: ulcers, anxiety, and blood pressure. Med. Anthropol. Q. 14, 51–72.
o Expectation – better drug response in trials with
active comparator than placebo
o Invasiveness – surgical placebo
o Distance of travel to obtain – “pilgrimage effect”
o Color and number of pills
o Etc.

17. Embrace the placebo effect
o Listen and provide empathy and understanding
o Touch the patient
o Align beliefs congruent to your patient’s culture
o Use frequent dosing
o Apply therapies in a therapeutic setting
o Deliver therapies in a warm and caring way
o Deliver therapies with confidence and in a credible way
o Be invasive if at all indicated
o Etc.
o Wayne B Jonas Phil. Trans. R. Soc. B (2011) 366, 1896–1904;
o Motivational Interviewing Literatuure

18. Challenges with EBM in
Integrative Medicine
o Research Funding
o Remedies we choose
o Individualized Treatments
o “Placebo” vs. Context effects
o Complex illness and complex treatments
o The usual suspects:
Publication bias, etc.

19. Complex Chronic Illness
o Many illnesses are multifactorial
o “Silver bullet” Treatments may not be
available
o Thus RCT’s of single interventions are
disappointing
o Solutions:
o Study complex interventions
 Active treatment vs Waiting list controls
 Multiple placebo trials – see Teitelbaum CFS Volume3, Issue 4
(1995) issue of "The Journal of Musculoskeletal Pain".

20. Challenges with EBM in
Integrative Medicine
o Research Funding
o Remedies we choose
o Individualized Treatments
o “Placebo” vs. Context effects
o Complex illness and complex treatments
o The usual suspects:
Publication bias, etc.

21. Solutions
o Research techniques
o Effectiveness
o Using evidence in the clinical encounter

22. Research techniques
o Improve understanding and communication
about herbal or supplement characteristics
o Wait list controls
o Attention controls
o Support group vs. intervention group
o Multiple placebo vs. multiple active
treatment trial

23. Research techniques
o Improvements in sham treatment use in
research
o N of 1 trials with an individual patient
o Need someone to help administer this

24. Solutions
o Research techniques
o Effectiveness
o Using evidence in the clinical encounter

25. Effectiveness, or Rubber
Meets Road
o We like the approach in Rakel’s Textbook
of Integrative Medicine, with an added
consideration. . . .
o This is my filter for every intervention I
learn about:
o Efficacy
o Risk of Harm
o Accessibility for my patient population

26. Levels of Evidence
Grade A Based on consistent, good-quality, patient-oriented evidence (e.g.,
systematic review or meta-analysis showing benefit, Cochrane
Review with clear recommendation, high-quality patient-oriented
randomized controlled trial). Example: Acupuncture for nausea and
vomiting.
Grade B Based on inconsistent or limited-quality patient-oriented evidence.
Example: Ginger for osteoarthritis.
Grade C Based on consensus, usual practice, opinion, disease-oriented
evidence (e.g., study showing a reduction in blood sugar but no
studies in humans to show a benefit to those with diabetes).

27. Grading Potential Harm
Grade 3
(most
harm)
This therapy has the potential to result in death or permanent
disability. Example: Major surgery under general anesthesia or
carcinogenic effects of the botanical Aristolochia (birthwort).
Grade 2
(moderate
harm)
Grade 2 (moderate harm) This therapy has the potential to cause
reversible side effects or interact in a negative way with other
therapies. Example: Pharmaceutical or nutraceutical side effects.
Grade 1
(least
hearm)
This therapy poses little, if any, risk of harm. Examples: Eating
more vegetables, increasing exercise, elimination diets, encouraging
social connection.

28. Putting these together
Strengths of evidence vs. harm grading:
o Gives more credibility to therapies that have little
potential harm.
e.g. social support, reducing stress, and
enhancing spiritual connection
o Helps us honor our primary goal, which is to
“first, do no harm.”

29. Grading Accessibility
$$$ (Most
expense,
difficulty in
applying to
underserved
populations)
Requires expensive modalities not covered by Medicaid or other
insurers or inclusion of alternative practitioners with significant
political barriers to involvement in standard medical
settings. Example: IV nutrients or chelation, integration of non-
licensed health care providers in inpatient settings, or application of
therapies not culturally acceptable to patients, such as yoga therapy
for fundamentalist Christian patients or Acupuncture for Russian
patients
$$ (Moderate
expense/barriers
to care)
This therapy involves modalities with moderate expense or
infrastructure requirements, such as availability of a teaching kitchen
for dietary interventions, dietary supplements costing more than $15
per month
$ (Least
expense/barriers
to care)
This therapy involves inexpensive/widely accessible substances
which are acceptable to most patients, or which can be implemented
by primary care providers with minimal additional training e.g. nasal
saline for chronic sinusitis, strain-counterstrain for musculoskeletal
complaints, low-cost dietary supplements such as magnesium or
vitamin D for musculoskeletal pain, or homeopathic remedies for
PTSD.

30. Solutions
o Research techniques
o Effectiveness
o Using evidence in the clinical encounter

31. Evidence in the Exam Room
o Patients as active partners
o Empowerment – the intangible benefits of self-
efficacy gained by making the patient an active
participant in the decision about options for
care
o Helping patients to analyze the literature
o Levels of evidence, animal vs human trials, etc.
o The Numbers
 Absolute Risk Reduction
 Number needed to Treat