Transcript Evidence Based Medicine - University of South Alabama

EVIDENCE BASED MEDICINE
Clista Clanton, MSLS, AHIP
June 22 & 23, 2010
Today’s topics
 What is EBM?
 Why is it important?
 Complementary/Alternative medicine
 Developing the “well built” clinical question
 Searching for evidence
 Evaluating the evidence
What is evidence based medicine (EBM)?
 “the conscientious, explicit and judicious use of
current best evidence in making decisions about
the care of individual patients.”
 The integration of individual clinical expertise with the best
available external clinical evidence from systematic research.
 Initially proposed by Dr. David Sackett and colleagues at McMasters
University in Ontario, Canada.
Sackett DL, et al. Evidence-Based Medicine: What it is and what it isn’t. BMJ 1996; 312:71-2.
Adapted from: Sackett D.L., Rosenberg M.C., Gray J.A., Haynes R.B., Richardson W.S. (1996).
Evidence based medicine: what it is and what it isn't. BMJ, 312, 71-72.
Paradigm shift

Unsystematic observations from clinical experience are a valid way of building and
maintaining one's knowledge about patient prognosis, the value of diagnostic tests,
and the efficacy of treatment.

The study and understanding of basic mechanisms of disease and pathophysiologic
principles is a sufficient guide for clinical practice.

A combination of thorough traditional medical training and common sense is sufficient
to evaluate new tests and treatment.

Content expertise and clinical experience are a sufficient base from which to generate
valid guidelines for clinical practice.

To sort out clinical problems, physicians can reflect on their own clinical experience,
reflect on the underlying biology, go to a textbook, or ask a local expert.

The "Introduction" and "Discussion" sections of a paper could be considered an
appropriate way of gaining the relevant information from a current journal.
Centre for Health Evidence. Evidence-based medicine: A new approach to teaching the practice of medicine. Available
at http://www.cche.net/usersguides/ebm.asp#7
New Paradigm
 Clinical experience, and the development of
clinical instincts are crucial and necessary parts of
becoming a competent physician. At the same
time, systematic attempts to record observations
in a reproducible and unbiased fashion markedly
increase the confidence one can have in
knowledge about patient prognosis, the value of
diagnostic tests, and the efficacy of treatment. In
the absence of systematic observation one must
be cautious in the interpretation of information
derived from clinical experience and intuition, for it
may at times be misleading.
Centre for Health Evidence. Evidence-based medicine: A new approach to teaching the practice of medicine. Available at
http://www.cche.net/usersguides/ebm.asp#7.
New Paradigm

The study and understanding of basic mechanisms of disease are necessary but
insufficient guides for clinical practice. The rationales for diagnosis and treatment which
follow from basic pathophysiologic principles may in fact be incorrect, leading to
inaccurate predictions about the performance of diagnostic tests and the efficacy of
treatments.
 Understanding certain rules of evidence is necessary to correctly interpret literature on
causation, prognosis, diagnostic tests, and treatment strategy.
 Clinicians should regularly consult the original literature in solving clinical problems and
providing optimal patient care.

Clinicians should be able to critically appraise the "Methods" and "Results" sections of
journal articles.
Centre for Health Evidence. Evidence-based medicine: A new approach to teaching the practice of medicine.
Available at http://www.cche.net/usersguides/ebm.asp#7.
What is EBM?
 “Evidenced-based medicine is the concept of formalizing the
scientific approach to the practice of medicine for identification
of “evidence” to support our clinical decisions. It requires an
understanding of critical appraisal and the basic epidemiologic
principles of study design, point estimates, relative risk, odds
ratios, confidence intervals, bias, and confounding. By using this
information, clinicians can categorize evidence, assess causality,
and make evidence-based recommendations. Evidence-based
medicine allows analysis of complicated material so that we can
make the best possible clinical decisions for the populations we
serve.”
Williams JK. Understanding evidence-based medicine: a primer. Am J Obstet Gynecol 2001:185-275-278.
Why is EBM important?
 New types of evidence are being generated
which can create changes in the way patients are
treated


How much is actually being applied to patient care?
Although evidence is needed on a daily basis, usually
physicians don’t get it.
1.
lack of time
2.
out-of-date textbooks, and
3.
the disorganization of the up-to-date journals6
Covell DG, Uman GC, Manning PR: Information needs in office practice: Are they being met? Ann Intern Med 1985;103:596-9.
Why is EBM important?
 Up-to-date knowledge and clinical performance can
deteriorate with time
 There is a statistically and clinically significant negative correlation between
a physician’s knowledge of up to date care and the years that have elapsed
since graduation from medical school.

Traditional continuing medical education programs have
not been shown to improve clinical performance

Systematic reviews of the relevant randomized trials have shown that
traditional, instructional CME fails to modify clinical performance and is
ineffective in improving the health outcomes of patients.
Ramsey PG, Carline JD, Inui TS et al: Changes over time in the knowledge base of practicing internists. JAMA 1991;266:1103-7.
Davis DA, Thompson MA, Oxman AD, Haynes RB: Changing physician performance. A systematic review of the effect of continuing
medical education strategies. JAMA 1995;274:700-5.
Why is EBM important?
 Knowledge translation –
increasing the uptake of
the best available evidence
into practice – has always
been a challenge
 Scurvy: use of citrus was
proven to prevent and cure
scurvy in 1754, but it was
almost 50 years after the data
was published before lemon
juice was added to British
ships
The James Lind Library. Available from
http://www.jameslindlibrary.org/. Accessed 26 June 2008.
Table 1. Lind’s study on scurvy:1747
Additive to diet (n=2
in each group
Observed
effect
Quart of cider
Minor
improvement
Unspecified elixir
t.d.s
No change
Seawater
No change
Garlic, mustard and
horseradish
No change
Spoonfuls of vinegar
No change
Two oranges and a
lemon
Dramatic
recovery
Why is EBM important?

Chloride of lime: In 1846 Ignatz Semmelweis attributed puerperal fever to an infection carried by
obstetricians. Despite reducing maternal mortality from 18 to 1.2% by hand-washing in chloride
of lime, his findings were rejected by the medical society of Vienna. It would take until the 1890’s
before it was accepted that microorganisms can cause disease.
Table 2. Mortality rates and characteristic of obstetrics clinics in Vienna 1784-1859
Period
Characteristics of period
No.
deliveries
No.
maternal
deaths
Maternal
deaths/1000
deliveries
17841822
No routine post-mortems
71,395
897
12.5
18231838
Routine post-mortems
65,035
3,745
57.6
18391847
Clinic arrangements changed
First clinic: doctors and students
Second clinic: midwives
20,204
17,791
1,989
691
90.2
33.8
18481859
Hand-washing introduced
First clinic
Second clinic
47,938
40,770
1,712
1,248
35.7
30.6
EBM processes can help with
dissemination and adoption
Role of literature searching
 Can improve the treatment of medical inpatients, even those
already receiving evidence-based treatment.

Random sample of 146 inpatients cared for by 33 internal medicine
attending physicians.

After physicians committed to a specific diagnosis and treatment plan, investigators
performed standardized literature searches and provided the search results to the
attending physicians.

Attending physicians changed treatment for 23 (18%) of the 130 eligible patients as a
result of the literature searches.
Lucas BP, Evans AT, et al. The impact of evidence on physician’s inpatient treatment decisions. J Gen Intern Med 2004;19:402-409.
Complementary/Alternative Medicine
 Complementary and alternative medicine is a group of diverse
medical and health care systems, practices, and products that are
not presently considered to be part of conventional medicine.

While some scientific evidence exists regarding some CAM
therapies, for most there are key questions that are yet to be
answered through well-designed scientific studies--such as:

Are these therapies safe?

Do these therapies work for the diseases or medical conditions for which
they are used?
National Center for Complementary and Alternative Medicine. Understanding complementary and alternative medicine. Available at:
http://nccam.nih.gov/health/.
Are Complimentary and Alternative
Medicine Interchangeable Terms?
 Complementary medicine is used together with conventional
medicine. Example: Using aromatherapy to help lessen a
patient's discomfort following surgery.

Alternative medicine is used in place of conventional medicine.
Example: When Suzanne Somers rejected chemotherapy in
favor of a drug called Iscador (uses extracts of Mistletoe) to treat
her breast cancer.
National Center for Complementary and Alternative Medicine. Understanding complementary and alternative medicine. Available
at: http://nccam.nih.gov/health/.
Family: Woman Died After Choosing Herbal
Medicine Over Cancer Surgery
Studies estimate that 60 percent of cancer
patients try unconventional remedies and
about 40 percent take vitamin or dietary
supplements
None has turned out to be a cure, although some show promise for
easing symptoms. Touch therapies, mind-body approaches and
acupuncture may reduce stress and relieve pain, nausea, dry
mouth and possibly hot flashes, and are recommended by many
top cancer experts. A recent study found that ginger capsules
eased nausea if started days before chemotherapy.
One quarter of supplements tested by an independent company
over the last decade have had some sort of problem. Some
contained contaminants. Others had contents that did not match
label claims. Some had ingredients that exceeded safe limits. Some
contained real drugs masquerading as natural supplements.
$2.5 billion spent, no alternative cures found
Big, government-funded studies show most work no better than placebos
The Associated Press
updated 11:15 a.m. CT, Wed., June 10, 2009
BETHESDA, Md. - Ten years ago the government set out to test herbal and
other alternative health remedies to find the ones that work. After spending
$2.5 billion, the disappointing answer seems to be that almost none of them
do.
Echinacea for colds. Ginkgo biloba for memory. Glucosamine and chondroitin
for arthritis. Black cohosh for menopausal hot flashes. Saw palmetto for
prostate problems. Shark cartilage for cancer. All proved no better than
dummy pills in big studies funded by the National Center for Complementary
and Alternative Medicine. The lone exception: ginger capsules may help
chemotherapy nausea.
As for therapies, acupuncture has been shown to help certain conditions, and
yoga, massage, meditation and other relaxation methods may relieve
symptoms like pain, anxiety and fatigue.
Major Types of Complementary and
Alternative Medicine
 Alternative medicine systems: Built upon complete systems of
theory and practice. Examples: homeopathic medicine,
naturopathic medicine, traditional Chinese medicine, Ayurveda.

Mind-body interventions: Uses a variety of techniques designed
to enhance the mind's capacity to affect bodily function and
symptoms. Some techniques that were considered CAM in the
past have become mainstream (patient support groups and
cognitive-behavioral therapy). Other mind-body techniques are
still considered CAM, including meditation, prayer, mental
healing, and therapies that use creative outlets such as art,
music, or dance.
National Center for Complementary and Alternative Medicine. Understanding complementary and alternative medicine. Available
at: http://nccam.nih.gov/health/.
Major Types of Complementary and
Alternative Medicine cont.
 Biologically Based Therapies: Use substances
found in nature (herbs, foods, and vitamins).
Example: shark cartilage to treat cancer.

Examples of dietary supplements that have been
incorporated into mainstream medicine:

Folic acid to prevent birth defects

Regimen of vitamins and zinc to slow the progression age-related
macular degeneration (AMD).
National Center for Complementary and Alternative Medicine. Understanding complementary and alternative medicine. Available
at: http://nccam.nih.gov/health/.
Major Types of Complementary and
Alternative Medicine cont.
 Manipulative or Body-Based Methods: Based on manipulation
and/or movement of one or more parts of the body. Examples:
chiropractic or osteopathic manipulation, massage.

Energy Therapies: Involve the use of energy fields.

Biofield therapies: intended to affect energy fields that purportedly
surround and penetrate the human body (the existence of such fields has
not yet been scientifically proven). Examples: qi gong, Reiki, Therapeutic
Touch.

Bioelectromagnetic-based therapies: unconventional use of
electromagnetic fields, such as pulsed fields, magnetic fields, or alternatingcurrent or direct-current fields.
National Center for Complementary and Alternative Medicine. Understanding complementary and alternative medicine. Available
at: http://nccam.nih.gov/health/.
NCCAM
 National Center for Complementary and Alternative Medicine
 Part of NIH, established in 1998
 Dedicated to exploring complementary and alternative healing
practices in the context of rigorous science, training
complementary and alternative medicine (CAM) researchers,
and disseminating authoritative information to the public and
professionals.
 NCCAM Web site (nccam.nih.gov): publications, information for
researchers, frequently asked questions, and links to other CAMrelated resources.
Use of Alternative/Complementary Medicine
in the U.S.
 36% of U.S. adults aged 18 years and over use
some form of complementary and alternative
medicine.
 CAM use was greater among women; people with
higher education; those who had been hospitalized
within the past year; and former smokers,
compared to current smokers or those who had
never smoked.
Barnes P, Powell-Griner E, McFann K, Nahin R. CDC Advance Data Report #343. Complementary and Alternative Medicine
Use Among Adults: United States, 2002. May 27, 2004.
Developing clinical questions
“To get the right answer,
you must first ask the right question.”
Developing the clinical question
 Step 1: Formulate the clinical issue into a
searchable, answerable question.
 Step 2: Distinguish what type of question you
may have.
Background
Foreground
Experience with Condition
Background questions
 Background questions ask for general
information about a condition or thing.
 A question root (who, what, when, etc) combined
with a verb.
What microbial organisms can cause
community-acquired pneumonia?
Background questions are typically answered by textbooks.
Foreground questions
 Foreground questions ask for specific
knowledge about a specific patient with a
specific condition.
Is St. John’s Wort effective in relieving
the symptoms of post-partum
depression?
Foreground questions are typically answered by
databases that access the research literature
Developing the question
 Foreground questions usually have four
components.
P = Patient population
I = Intervention
C = Comparison
O = Outcome
PICO: Components of an answerable, searchable question
Patient population/disease
The patient population or disease of interest
- age
- gender
- ethnicity
- with certain disorder (e.g., hepatitis)
Intervention
The intervention or range of interventions of interest
- Exposure to disease
- Prognostic factor A
- Risk behavior (e.g., smoking)
Comparison
What you want to compare the intervention against
- No disease
- Placebo or no intervention/therapy
- Prognostic factor B
- Absence of risk factor (e.g., non-smoking)
Outcome
Outcome of interest
- Risk of disease
- Accuracy of diagnosis
- Rate of occurrence of adverse outcome (e.g., death)
Melnyk, B. M., & Fineout-Overholt, E. (2005). Evidence-based practice in nursing & healthcare : A guide to best practice. Philadelphia,
PA: Lippincott Williams & Wilkins.
In patient with
[Patient/
Problem]
does
or
affect
[Intervention] [Comparison, [Outcome]
if any]
In patients with chronic pain, does the use of progressive
muscle relaxation lead to a lessening of pain?
In patients with significant anterior or posterior vaginal
wall prolapse, do vaginal cones help?
In patients with moderate depression, is St. John’s Wort
vs. traditional SSRI’s effective in relieving symptoms
with fewer adverse effects?
Types of Questions
 Diagnosis: How to select a diagnostic test or how to interpret
the results of a particular test.
 Prognosis: What is the patient's likely course of disease, or how
to screen for or reduce risk.
 Therapy: Which treatment is the most effective, or what is an
effective treatment for a particular condition.
 Harm or Etiology: Are there harmful effects of a particular
treatment, or how these harmful effects can be avoided.
 Prevention: How can the patient's risk factors be adjusted to
help reduce the risk of disease?
 Cost: Looks at cost effectiveness, cost/benefit analysis.
Question Templates for Asking PICO Questions
Therapy
In __________________, what is the effect of ____________________ on
______________________ compared with __________________?
Etiology
Are ______________ who have _________________ at ________________
risk for/of ____________________ compared with _____________________
with/without ______________________?
Diagnosis or Diagnostic Test
Are (Is) _________________________ more accurate in diagnosing
________________ compared with ________________?
Prevention
For _________________ does the use of _______________ reduce the future risk of
________________ compared with _________________?
Prognosis
Does _______________ influence _________________ in patients who have
__________________?
Melnyk, B. M., & Fineout-Overholt, E. (2005). Evidence-based practice in nursing & healthcare : A guide to best practice. Philadelphia, PA: Lippincott Williams & Wilkins.
Medical literature
 Primary – original
 Secondary – reviews of
research
original research
 Experimental (an intervention
is made or variables are
manipulated)
 Randomized Control Trials
 Controlled trials
 Meta-analysis
 Observational (no
intervention or variables are
manipulated)
 Cohort studies
 Case-control studies
 Case reports
 Systematic reviews
 Practice guidelines
 Reviews
 Decision analysis
 Consensus reports
 Editorial, commentary
Case series/case reports
 Reports on treatment, etc. of individual
patients
Anbar RD, Savedoff AD. Treatment of binge eating with automatic word
processing and self-hypnosis: a case report.
Am J Clin Hypn. 2005 Oct-2006 Jan;48(2-3):191-8.
Binge eating frequently is related to emotional stress and mood problems. In this
report, we describe a 16-year-old boy who utilized automatic word processing
(AWP) and self-hypnosis techniques in treatment of his binge eating, and
associated anxiety, insomnia, migraine headaches, nausea, and stomachaches. He
was able to reduce his anxiety by gaining an understanding that it originated as a
result of fear of failure. He developed a new cognitive strategy through AWP, after
which his binge eating resolved and his other symptoms improved with the aid of
self-hypnosis. Thus, AWP may have helped achieve resolution of his binge eating
by uncovering the underlying psychological causes of his symptoms, and selfhypnosis may have given him a tool to implement a desired change in his behavior.
Case Control Studies
 Studies in which patients who already have a
specific condition are compared with people
who do not
 Rely on medical records and patient recall for
data collection
Hepatitis C; a retrospective study, literature review, and naturopathic
protocol. Milliman WB. Lamson DW. Brignall MS. Alternative Medicine
Review. 5(4):355-71, 2000 Aug.
The standard medical treatment of hepatitis C infection is only associated with
sustained efficacy in a minority of patients. Therefore, the search for other
treatments is of utmost importance. Several natural products and their
derivatives have demonstrated benefit in the treatment of hepatitis C and
other chronic liver conditions. Other herbal and nutritional supplements have
mechanisms of action that make them likely to be of benefit. This article
presents comprehensive protocol, including diet, lifestyle, and therapeutic
interventions. The authors performed a retrospective review of 41 consecutive
hepatitis C patients. Of the 14 patients with baseline and follow-up data who
had not undergone interferon therapy, seven had a greater than 25-percent
reduction in serum alanine aminotransferase (ALT) levels after at least one
month on the protocol. For all patients reviewed, the average reduction in ALT
was 35 U/L (p=0.026). These data appear to suggest that a conservative
approach using diet and lifestyle modification, along with safe and indicated
interventions, can be effective in the treatment of hepatitis C. Controlled trials
with serial liver biopsy and viral load data are necessary to confirm these
preliminary findings.
Cohort studies
 From a large population, follows patients who
have a specific condition or receive a
particular treatment over time and compared
with another group that has not been
affected by the condition or treatment
studies
Kristal AR, Littman AJ, Benitez D, White E.
Yoga practice is associated with attenuated weight gain in healthy, middle-aged men
and women. Altern Ther Health Med. 2005 Jul-Aug;11(4):28-33.
BACKGROUND: Yoga is promoted or weight maintenance, but there is little evidence of its
efficacy. OBJECTIVE: To examine whether yoga practice is associated with lower mean 10year weight gain after age 45. PARTICIPANTS: Participants included 15,550 adults, aged 53
to 57 years, recruited to the Vitamin and Lifestyle (VITAL) cohort study between 2000 and
2002. MEASUREMENTS: Physical activity (including yoga) during the past 10 years, diet,
height, and weight at recruitment and at ages 30 and 45. All measures were based on selfreporting, and past weight was retrospectively ascertained. METHODS: Multiple
regression analyses were used to examined covariate-adjusted associations between yoga
practice and weight change from age 45 to recruitment, and polychotomous logistic
regression was used to examine associations of yoga practice with the relative odds of
weight maintenance (within 5%) and weight loss (> 5%) compared to weight gain.
RESULTS: Yoga practice for four or more years was associated with a 3.1-lb lower weight
gain among normal weight (BMI < 25) participants [9.5 lbs versus 12.6 Ibs] and an 18.5-lb
lower weight gain among overweight participants [-5.0 lbs versus 13.5 Ibs] (both P for
trend <.001). Among overweight individuals, 4+ years of yoga practice was associated with
a relative odds of 1.85 (95% confidence interval [CI] 0.63-5.42) for weight maintenance
(within 5%) and 3.88 (95% Cl 1.30-9.88) for weight loss (> 5%) compared to weight gain (P
for trend .026 and .003, respectively). CONCLUSIONS: Regular yoga practice was
associated with attenuated weight gain, most strongly among individuals who were
overweight. Although causal inference from this observational study is not possible,
results are consistent with the hypothesis that regular yoga practice can benefit
individuals who wish to maintain or lose weight.
Randomized controlled trials
 Study effect of therapy on real patients
 Include methodologies that reduce the
potential for bias
 Intervention group vs control group
 Patients assigned in randomized fashion
 Blinded or non-blinded studies
Harikumar R, Raj M, Paul A, Harish K, Kumar SK, Sandesh K, Asharaf S, Thomas V.
Listening to music decreases need for sedative medication during colonoscopy: a
randomized, controlled trial. Indian J Gastroenterol. 2006 Jan-Feb;25(1):3-5.
BACKGROUND: Music played during endoscopic procedures may alleviate anxiety
and improve patient acceptance of the procedure. A prospective randomized,
controlled trial was undertaken to determine whether music decreases the
requirement for midazolam during colonoscopy and makes the procedure more
comfortable and acceptable. METHODS: Patients undergoing elective
colonoscopy between October 2003 and February 2004 were randomized to either
not listen to music (Group 1; n=40) or listen to music of their choice (Group 2;
n=38) during the procedure. All patients received intravenous midazolam on
demand in aliquots of 2 mg each. The dose of midazolam, duration of procedure,
recovery time, pain and discomfort scores and willingness to undergo a repeat
procedure using the same sedation protocol were compared. RESULTS: Patients
in Group 2 received significantly less midazolam than those in Group 1 (p=0.007).
The pain score was similar in the two groups, whereas discomfort score was lower
in Group 2 (p=0.001). Patients in the two groups were equally likely to be willing
for a repeat procedure. CONCLUSION: Listening to music during colonoscopy
helps reduce the dose of sedative medications and decreases discomfort
experienced during the procedure.
Systematic review
 Extensive literature search is conducted in
systematic fashion
 Only uses studies with sound methodology
 Studies are collected, reviewed, assessed and
the results summarized according to
predetermined criteria of the review question
Jepson RG, Mihaljevic L, Craig J. Cranberries for preventing urinary tract infections. The Cochrane Database of Systematic
Reviews 2004, Issue 2.
Background: Cranberries (particularly in the form of cranberry juice) have been used widely for several decades for the
prevention and treatment of urinary tract infections (UTIs). The aim of this review is to assess the effectiveness of
cranberries in preventing such infections.
Objectives: To assess the effectiveness of cranberry juice and other cranberry products in preventing UTIs in susceptible
populations.
Search strategy: Electronic databases and the Internet were searched using English and non English language terms;
companies involved with the promotion and distribution of cranberry preparations were contacted; reference lists of
review articles and relevant trials were searched…searched in February 2003.
Selection criteria: All randomised or quasi randomised controlled trials of cranberry juice/products for the prevention of
urinary tract infections in susceptible populations. Trials of men, women or children were included.
Data collection and analysis: Two reviewers independently assessed and extracted information. Information was
collected on methods, participants, interventions and outcomes (urinary tract infections (symptomatic and
asymptomatic), side effects and adherence to therapy). RR were calculated where appropriate, otherwise a narrative
synthesis was undertaken. Quality was assessed using the Cochrane criteria.
Main results: Seven trials met the inclusion criteria (four cross-over, three parallel group). The effectiveness of cranberry
juice (or cranberry-lingonberry juice) versus placebo juice or water was evaluated in six trials, and the effectiveness of
cranberries tablets versus placebo was evaluated in two trials (one study evaluated both juice and tablets). In two good
quality RCTs, cranberry products significantly reduced the incidence of UTIs at twelve months (RR 0.61 95% CI:0.40 to 0.91)
compared with placebo/control in women. One trial gave 7.5 g cranberry concentrate daily (in 50 ml), the other gave 1:30
concentrate given either in 250 ml juice or in tablet form. There was no significant difference in the incidence of UTIs
between cranberry juice versus cranberry capsules (RR 1.11 95% CI:0.49 to 2.50). Five trials were not included in the metaanalyses due to methodological flaws or lack of available data. However, only one reported a significant result for the
outcome of symptomatic UTIs. Side effects were common in all trials, and dropouts/withdrawals in several of the trials
were high.
Authors' conclusions: There is some evidence from two good quality RCTs that cranberry juice may decrease the number
of symptomatic UTIs over a 12 month period in women. If it is effective for other groups such as children and elderly men
and women is not clear. The large number of dropouts/withdrawals from some of the trials indicates that cranberry juice
may not be acceptable over long periods of time. In addition it is not clear what is the optimum dosage or method of
administration (e.g. juice or tablets). Further properly designed trials with relevant outcomes are needed.
Meta-analysis
 Examines a group of valid studies on a topic
 Combines results using accepted statistical
methodology to reach a consensus on the
overall results
Linde K, Berner M, Egger M, Mulrow C.
St John's wort for depression: meta-analysis of randomised controlled trials.
Br J Psychiatry. 2005 Feb;186:99-107.
BACKGROUND: Extracts of Hypericum perforatum (St John's wort) are widely
used to treat depression. Evidence for its efficacy has been criticised on
methodological grounds. AIMS: To update evidence from randomised trials
regarding the effectiveness of Hypericum extracts.
METHODS: We performed a systematic review and meta-analysis of 37 doubleblind randomised controlled trials that compared clinical effects of Hypericum
monopreparation with either placebo or a standard antidepressant in adults
with depressive disorders.
RESULTS: Larger placebo-controlled trials restricted to patients with major
depression showed only minor effects over placebo, while older and smaller
trials not restricted to patients with major depression showed marked effects.
Compared with standard antidepressants Hypericum extracts had similar
effects. CONCLUSIONS: Current evidence regarding Hypericum extracts is
inconsistent and confusing. In patients who meet criteria for major depression,
several recent placebo-controlled trials suggest that Hypericum has minimal
beneficial effects while other trials suggest that Hypericum and standard
antidepressants have similar beneficial effects.
Levels of evidence
 Level I: obtained from at least one properly




controlled randomized trial, considered the gold
standard of evidence.
Level II-1:derived from controlled trials without
randomization.
Level II-2: well-designed cohort or case-control
studies.
Level II-3: includes studies with external control
groups or ecological studies.
Level III evidence is derived from reports of
expert committees, not because it is weaker than
levels I or II, but because it is often difficult to
ascertain the scientific origin of the committee
opinion.
Evidence Pyramid
Meta-analysis
Systematic Review
Randomized Controlled Trial
Cohort Studies
Case Control Studies
Case Series/Case Reports
Animal Research
Type of Question
Suggested Best Type of Study
Therapy
RCT > cohort > case control > case series
Diagnosis
Prospective, blind comparison to gold
standard
Etiology / Harm
RCT > cohort > case control > case series
Prognosis
Cohort study > case control > case series
Prevention
RCT > cohort study > case control > case
series
Clinical Exam
Prospective, blind comparison to gold
standard
Cost
Economic analysis
Questions of therapy, etiology and prevention which can best be
answered by RCT can also be answered by a meta-analysis or
systematic review.
In patient with
[Patient/
Problem]
does
or
affect
[Intervention] [Comparison, [Outcome]
if any]
Question:
In adult with acute maxillary sinusitis, does a 3-day
course of trimethoprim-sulfamethoxazole yield the
same cure rates as a 10-day course, with fewer
adverse effects and costs?
Type of question:
Therapy
Type of study:
RCT>cohort>case control> case
series
A 42-year old woman presented at the emergency room of the hospital
complaining of muscle pain and tiredness. She was found to have
hyperventilation and weakness of four limbs, with muscle power of grade 5
( )/5. All her symptoms gradually subsided over the next few hours. History
revealed she was taking maqianzi', a herbal remedy, for neck pain. Could
this herbal supplement have caused her problems?
In patient with
[Patient/ Problem]
does
[Intervention]
or
[Comparison, if
any]
affect
[Outcome]
Question:
In an adult woman, does maqianzi cause muscle pain and tiredness?
Type of question:
Etiology
Type of study:
RCT>cohort>case control> case series
A middle-age male patient has heard that onions and garlic help protective against
cancer and cardiovascular disease? He has a family history of cancer and is thinking
of taking them to help protect him.
In patient with
[Patient/ Problem]
does
[Intervention]
or
[Comparison, if
any]
affect
[Outcome]
Question:
In an adult with family history of lung cancer will onions or garlic act as a
preventive agent?
Type of question:
Prevention
Type of study:
RCT>cohort>case control> case series
You have heard that kidney yin deficiency is a valid tool to diagnose
postmenopausal women with vasomotor symptoms. You need to
find further information on this test.
In patient with
[Patient/ Problem]
does
[Intervention]
or
[Comparison, if
any]
affect
[Outcome]
Question:
In a postmenopausal woman is kidney yin deficiency as effective as
standard tools in diagnosis of vasomotor symptoms?
Type of question:
Diagnosis
Type of study:
Prospective blind comparison to gold standard
Systems
Computerized
decision support
Summaries
Dynamed, UptoDate
Clinical Evidence, EBM guidelines
Adapted from
Haynes (2001)
Synopses
TRIP
ACP Journal Club
Syntheses
Cochrane Systematic Reviews,
DARE
Studies
PubMed, CINAHL, Scopus
Haynes RB. Of studies, summaries, synopses, and systems: the “5S" evolution of services for finding current best evidence. ACP Journal
Club. 2001;134: A11–13.
If an original study is your best
option…….
Original Studies
IMRAD format
 Introduction: why the authors decided to
conduct the research.
 Methods: how they conducted the research
and analyzed their results.
 Results: what was found.
And
 Discussion: what the authors think the results
mean.
PP-ICONS
 Problem
 Patient or population
 Intervention
 Comparison
 Outcome
 Number of subjects
 Statistics
Flaherty, Robert J. A simple method for evaluating the clinical literature. Fam Prac Mgt, May 2004;47-52. Available online at
http://www.aafp.org/fpm/20040500/47asim.html.
Scenario
 You just saw a nine-year old patient with
common warts on her hands. She is an ideal
candidate for cryotherapy. Her mother has
heard about treating warts with duct tape
and wants to know if you would recommend
this treatment.
Clinical question
 What is your clinical question?
 PICO: Patient, Intervention/Comparison,
Outcome
“In children with warts, is duct tape as
effective as cryotherapy in eliminating
the wart?
Search
 After you have your clinical question, search the
appropriate databases:
 Dynamed, PIER, UpToDate, Cochrane, Clinical
Evidence, Essential Evidence Plus
 PubMed
 Focht DR 3rd, Spicer C, Fairchok MP.
The efficacy of duct tape vs cryotherapy in the
treatment of verruca vulgaris (the common
wart). Arch Pediatr Adolesc Med. 2002
Oct;156(10):971-4.
Abstract

OBJECTIVE: To determine if application of duct tape is as effective as cryotherapy in the
treatment of common warts.
DESIGN: A prospective, randomized controlled trial with 2 treatment arms for warts in
children.
SETTING: The general pediatric and adolescent clinics at a military medical center.
PATIENTS: A total of 61 patients (age range, 3-22 years) were enrolled in the study from
October 31, 2000, to July 25, 2001; 51 patients completed the study and were available for
analysis.
INTERVENTION: Patients were randomized using computer-generated codes to receive
either cryotherapy (liquid nitrogen applied to each wart for 10 seconds every 2-3 weeks) for
a maximum of 6 treatments or duct tape occlusion (applied directly to the wart) for a
maximum of 2 months. Patients had their warts measured at baseline and with return
visits.
MAIN OUTCOME MEASURE: Complete resolution of the wart being studied.

RESULTS: Of the 51 patients completing the study, 26 (51%) were treated with duct tape,
and 25 (49%) were treated with cryotherapy. Twenty-two patients (85%) in the duct tape
arm vs 15 patients (60%) enrolled in the cryotherapy arm had complete resolution of their
warts (P =.05 by chi(2) analysis). The majority of warts that responded to either therapy did
so within the first month of treatment.
CONCLUSION: Duct tape occlusion therapy was significantly more effective than
cryotherapy for treatment of the common wart.
Problem (PP-ICONS)
 What is the clinical condition that was studied
in the article?
OBJECTIVE: To determine if application of
duct tape is as effective as cryotherapy in the
treatment of common warts.
 The problem studied should be sufficiently
similar to your clinical problem, or the results
will not be relevant.
Patient or Population (PP-ICONS)
 Is the study group similar to your patient or
practice?
SETTING: The general pediatric and
adolescent clinics at a military medical center.
PATIENTS: A total of 61 patients (age range,
3-22 years)
 If the patients in the study are not similar to
your patient (older, sicker, different gender or
more clinically complicated), the results may
not be relevant.
Intervention (PP-ICONS)
 Is the intervention the same as what you are
looking for?
 Could be a diagnostic test or a treatment
The patient’s mother has heard about
treating warts with duct tape and wants to
know if you would recommend this
treatment.
Comparison (PP-ICONS)
 The comparison is what the treatment is
tested against.
 Could be a different diagnostic test, another
therapy, placebo, or no treatment at all.
INTERVENTION: Patients were randomized using
computer-generated codes to receive either
cryotherapy (liquid nitrogen applied to each wart for
10 seconds every 2-3 weeks) for a maximum of 6
treatments or duct tape occlusion (applied directly to
the wart) for a maximum of 2 months.
Outcome (PP-ICONS)
 Disease-oriented outcomes (DOEs): usually
reflect changes in physiologic parameters.
 It has long been assumed that improving the
physiologic parameters of a disease will result in a
better outcome, but this is not always true.
 Patient-oriented evidence that matters (POEMs):
look at outcomes such as morbidity, mortality
and cost.
 Therefore, DOEs are interesting but of
questionable relevance, whereas POEMs are very
interesting and very relevant.
MAIN OUTCOME MEASURE: Complete resolution of
the wart being studied.
Number (PP-ICONS)
 Number of subjects in the study is crucial in
whether accurate statistics can be generated
from the data.
 Too few patients may not be enough to show that a
difference really exists between intervention and
comparison groups (power of a study).
 Many studies contain <100 subjects, which is usually
inadequate to provide reliable statistics.
 Good rule of thumb – 400 subjects needed.
51 patients completed the study
Krejcie RV, Morgan DW. Determining sample size for research activities. Educational and Psychological Measurements. 1970;30:607-610.
Statistics (PP-ICONS)
 Relative risk reduction (RRR): the percent
reduction in events in the treated group
compared to the control group event rate.
 Not a good way to compare outcomes
 Amplifies small differences and makes insignificant findings
appear significant
 Doesn’t reflect the baseline risk of the outcome event
 Can make weak results look good, therefore
 Popular and will be reported in almost every journal article
 Ignore – it can mislead you
RRR would be (85 percent – 60 percent/60 percent x 100 = 42 percent
I.e. 42 percent more effective than cryotherapy in treating warts
Statistics (PP-ICONS)
 Absolute risk reduction (ARR): the difference
in the outcome event rate between the
control group and the experimental group.
ARR for the wart study is the outcome event rate
(complete resolution of warts) for duct tape (85
percent) minus the outcome event rate for
cryotherapy (60 percent) = 25 percent
 A better statistic to evaluate outcome, as it
does not amplify small differences, but shows
the true difference between the experimental
and control interventions.
Statistics (PP-ICONS)
 Number needed to treat (NNT): number of patients who
must be treated to prevent one adverse outcome OR the
number of patients who must be treated for one patient
to benefit
 Single most clinically useful statistic
 Easy to calculate, simply the inverse of the ARR.
For the wart study, the NNT is 1/25 percent = 1/0.25 = 4
4 patients need to be treated with duct tape for one to
benefit more than if treated by cryotherapy
 The lower the NNT, the better. For primary therapies, an NNT
of 10 or less is good, with less than 5 being very good.
 For preventive interventions, the NNT will be higher. An NNT
for prevention of less than 20 might be particularly good.
Intention to Treat Analysis

Attrition: Were patients lost to follow-up, and if so, why?
Intention to treat: subjects are analyzed according to
the categories into which they were originally
randomized.
– Benefits of a treatment are more difficult to demonstrate
with intention-to-treat analysis.
– Helps to mitigate differences by including subjects who are
unlikely to have experienced benefit from the intervention.
Six patients from cryotherapy group and 4 patients from the duct tape
group were lost to follow-up (16% of patients).
Worst case scenario: 6 cryotherapy patients had wart resolution and the 4
duct tape patients had residual wart.
Wart resolution would then be: duct tape 78% and cryotherapy 68% (95%
CI, -17 to 28) – therefore not a statistically significant difference between
the two treatments.
Christakis DA, Lehmann HP. Is duct tape occlusion therapy as effective as cryotherapy for the treatment of the common wart? Arch Pediatr Adolesc Med, Oct 2002; vol.
156; 975-977.
Best Type of Study for Your Question
Type of Question
Suggested Best Type of Study
Therapy
RCT > cohort > case control > case series
Diagnosis
Prospective, blind comparison to gold standard
Etiology / Harm
RCT > cohort > case control > case series
Prognosis
Cohort study > case control > case series
Prevention
RCT > cohort study > case control > case series
Clinical Exam
Prospective, blind comparison to gold standard
Cost
Economic analysis
Questions of therapy, etiology and prevention which can best be answered
by RCT can also be answered by a meta-analysis or systematic review.
Assignment





Identify a clinical problem with a patient
Formulate a clinical question using PICO
Search the literature for appropriate article(s)
Evaluate the article(s)
Complete the online assignment within two weeks after
date of lecture.
 http://bl.southalabama.edu/library/?q=ebmrotationsassignment