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Evidence Based Medicine
Cynthia Fraed, MD
Evidence based medicine (EBM) 1,2 arose from the need to critically assess the literature
available from research and apply it to real patient populations in clinical practices. It provides
the tools to question what is being presented and a systematic way to use them. The tools and
rules of EBM help physicians review medical information to assess its validity and veracity. It is
designed to give physicians in clinical practice the ability to critically review scientific
information and hold it accountable in a standardized way.
Journals have their own unique publication bias and usually publish positive outcomes. If a
paper proves a negative outcome it is much less likely to reach publication. EBM provides tools
to help discover biases like this.
The tools used in EBM are both qualitative and quantitative.
The qualitative tools include assessments of:
1. The quality of the journal. Where was the study done? What language was used? What
is the context of the study?
2. Who funded the study and did they pay to have it published? Was it peer reviewed?
3. What are the credentials of the author and are there any biases of the author with the
funding source?
4. The description of the population being considered and whether the results can be
generalized to the population being considered.
5. What is the study design? Is it an assessment and clear description of the clinical
research question at hand? Is it a meta-analysis of double blinded randomly controlled
trials (RCT) or is it an isolated case report?
The quantitative tools include inquiries of:
1. What are the basic statistical concepts related to study design? What is the size of the
study? What is the testing question and what end points are being measured? Is the
study large enough to have the statistical power to show the effect it claims?
2. What is the epidemiologic evidence such as incidence, prevalence, sensitivity, positive
and negative predictive value, number needed to treat, number needed to harm,
absolute risk reduction, and relative risk reduction?
3. Does the study provide a clear answer for the patients in the reader’s practice who are
like the study participants?
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Keeping in mind that the patient is the center of the decision, consider whether the study is
looking at patient oriented evidence that matters (POEMs) or disease oriented evidence (DOEs).
We now have the tools that evidence based medicine provides, but these tools are not always
used properly.
EXAMPLE #1 - The Women’s Health Initiative Study
An example of misuse of these concepts is the Women’s Health initiative (WHI) study3 and its
original media-based presentation. WHI has indeed had a profound impact on peri-menopausal
and postmenopausal women since the decision to halt one arm of the study made the nightly
news and newspapers in 2002. Women were terrorized with headlines showing that the
relative risk (RR) of breast cancer in women prescribed postmenopausal hormone replacement
therapy (Prempro) was increased by 26%. This translates to an absolute risk of 8 extra breast
cancers in 10,000 women in 1 year or 0.08% per year, invoking a significantly lower fear factor
than the headlines suggested.
As we apply EBM to WHI there are several issues with the way the results were manipulated. 4
1. The average age of a woman enrolled in the WHI study was 63 making them 12 – 15
years past the onset of menopause. Most (appx 74%) of these women had never
used hormone replacement. Much has been written about the window of
opportunity within the 3 – 4 years after a woman finishes menopause that may be
cardio-protective and cognitive-protective but this is a different population than the
one studied. The WHI women had the opportunity to have developed vascular
changes prior to the onset of the study.
2. The only “estrogen” used was Premarin which is a conjugated equine estrogen
product containing 50% estrone as well as estrogens unique to horses. How do these
horse estrogens (equilin and equilenin) attach to human estrogen receptors? This
group of estrogens was generalized to apply to all estrogen preparations and not
preparations containing just human estrogens (estradiol, estrone, estriol).
Additionally the only “progesterone” used in the trial was a progestin
(medroxyprogesterone acetate) which as shown in the PEPI trial 5 has a different
effect on lipids than micronized progesterone.
3. Once the women were randomized they were free to decide if the wished to
continue their assigned treatment or undergo diagnostic procedures. Forty-five
percent became unblended regarding their treatment group and this eliminated the
power of a randomized placebo-controlled study.
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4. Although the original study did calculate the absolute risk, the relative risk
percentages were released to the press and caused many women to stop their
hormonal therapy abruptly out of fear for their lives.
EXAMPLE #2: Breast Cancer Screening Guidelines
A different example of the use of EBM is found in looking at the interpretation of mammogram
guidelines drawn by different medical entities. There has been much controversy over the
guideline.

United States Preventive Services Task Force (USPSTF) 6
o Women Over the Age of 40: The USPSTF concludes that the current evidence is
insufficient to assess the additional benefits and harms of clinical breast
examination (CBE) beyond screening mammography in women 40 years or older.
o Women Before the Age of 50: The decision to start regular, biennial screening
mammography before the age of 50 years should be an individual one and take
patient context into account, including the patient's values regarding specific
benefits and harms.
o Women Age 50-74: The USPSTF recommends biennial screening mammography
for women 50-74 years.
o Women 75 Years and Older: The USPSTF concludes that the current evidence is
insufficient to assess the benefits and harms of screening mammography in
women 75 years and older.

American cancer society (ACS) 7
o Women age 40-44 should have the choice to start annual breast cancer
screening with mammograms if they wish to do so. The risks of screening as well
as the potential benefits should be considered.
o Women age 45-54 should get mammograms every year.
o Women age 55 and older should switch to mammograms every 2 years, or have
the choice to continue yearly screening.
o Screening should continue as long as a woman is in good health and is expected
to live 10 more years or longer.

American College of Radiology (ACR) 8
o All women of average risk should have annual breast imaging beginning at the
age of 40 years.
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
American Congress of Obstetricians and Gynecologists (ACOG)9
o All women over the age of 40 should have mammography annually.
In this clinical situation, the use of “evidence” leaves us with conflicting guidelines from a
number of experts. This means that we are left to make the best decision possible with our
patient as a partner. Evidence alone is insufficient.
An important premise of practicing medicine is “primum non nocere” – first do not harm. The
basis of “practicing” medicine is observation, investigation and inductive reasoning. Using
evidence based medicine to dissect the usefulness of a study is but one tool. Seeing patterns
develop by taking a history, performing a physical exam and obtaining laboratory evaluation,
leads to an understanding of why the patient is having problems and helps direct us to find
ways to help them return to improved health. Ultimately, the discussion with the patient about
the evidence in the context of their life and from their perspective, lead us to an individual plan
for a specific patient in a partnership on a healing path.
REFERENCES
1
Belsey J. What is evidence-based medicine? 2nd edition. Hayward Medical Communications. 2009. Available at
http://www.medicine.ox.ac.uk/bandolier/painres/download/whatis/ebm.pdf. Accessed 7.24.2016.
2
Evidence-Based Medicine Working Group (November 1992). "Evidence-based medicine. A new approach to
teaching the practice of medicine". JAMA 268 (17): 2420–5.
3
Writing Group for the Women’s Health Initiative Investigators. Risks and Benefits of Estrogen Plus Progestin in
Healthy Postmenopausal Women: Principal Results From the Women’s Health Initiative Randomized Controlled
Trial. JAMA. 2002;288(3):321-333.
4
Clark JH. A critique of Women’s Health initiative Studies (2002-2006). Nucl recept Signal. 2006; 4:3023.
Available at https://www.nursa.org/NRS/nrs04023.pdf. Accessed 7.24.2016.
5
Langer, R. D. 2008. Postmenopausal Estrogen/Progestin Intervention Trial (PEPI). Wiley Encyclopedia of Clinical
Trials. 1–10. Available at http://onlinelibrary.wiley.com/doi/10.1002/9780471462422.eoct399/abstract. Accessed
7.24.2016.
6
Breast Cancer Screening. United States Preventive Services Task Force. Available at:
http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/breast-cancer-screening.
Accessed 7.24.2016.
7
Oeffinger KC, Fontham ETH, Etzioni R, Herzig A, Michaelson JS, Shih YT, Walter LC, Church TR, Flowers CR,
LaMonte SJ, Wolf A, DeSantis C, Lortet-Tieulent J, Andrews K, Manassaram-Baptiste D, Saslow D, Smith RA, Brawley
OW, Wender R. Breast Cancer Screening for Women at Average Risk: 2015 Guideline Update From the American
Cancer Society. JAMA. 2015:314(15):1599-1614.
8
Lee CH, Dershaw DD, Kopans D, Evans P, Monsees B, Monticciolo D, Brenner RJ, Bassett L, Berg W, Feig S,
Hendrick E, Mendelson E, D’Orsi C, Sickles E, Burhene LW. Breast Cancer Screening with Imaging:
Recommendations from the Society of Breast Imaging and the ACR on the Use of Mammography, Breast MRI,
Breast Ultrasound, and Other Technologies for the Detection of Clinically Occult Breast Cancer, JACR January 2010
Vol 7 Issue 1 pp. 18-27.
9
Breast Cancer Screening. American Congress of Obstetricians and Gynecologists Practice Bulletein. Number 122,
August 2011. Available at
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http://www.acog.org/Resources_And_Publications/Practice_Bulletins/Committee_on_Practice_Bulletins_Gynecol
ogy/Breast_Cancer_Screening. Accessed 7.24.2016.
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