Principles of Urologic Research& Evidence Based UrologyA Presentationby Farouk Ashraf Hammoud

First and foremost I would like to thank Allah for giving me the power to accomplish this work.I would also like to express my gratitude to my supervisors, Prof. Dr. Mohammed Shoeb, Dr. Tarek Osman, and Dr. Diaa Abdelftah, for their continuous supervision and irreplaceable guidance. Also Prof. Dr. Amr El Shorbagy and Prof. Dr. Khaled El Gamal, thank you for attending, I know I put you through some difficulties.Finally my deep thanks goes out to my family and friends for their constant support.

Brief History of Medicine

Ancient medicine: Based on superstition and medical theories

Renaissance period:(14th to 17th century)Revolutionary scientific changes

Medicine & Statistics Change Research

Archie Cochrane

Bradford Hill

First modern randomized clinical

Founding father of EBM

What is 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.

Conducting Research

Conducting ResearchThe EBM process can be summarized

by four steps: (1) Formulate a sensible, focused clinical question: PICOT (2) Search the medical literature for evidence related to the focused, clinical question. (3) Rate the quality of the available studies. (4) Apply the evidence to a particular patient or clinical situation.

PICOTP = Population.I = Intervention. C = Comparison. O = Outcome. T = Type of study. Choose the

best study design

PICOTP = 63 year old with BPH I = medical therapy C = surgery O = reducing lower urinary tract

symptoms T = in a randomized controlled

trial or systematic review of randomized controlled trials

Search for Evidence

Where to SearchSynthesized sources: textbooks,

guidelines

Selected sources: research that is filtered and published as database Ex. BMJ EBM

Bibliographic database of published journal articles. Ex. PubMed

Type Name URL Info

Database Cochrane Library http://www.thecochranelibrary.com Database of

systemic reviews

Medline/Pubmed http://www.pubmed.gov Major source of biomedical publications

EMBASE http://www.embase.com/ European equivalent of Medline

TRIP: Turning Research Into Practice

http://www.tripdatabase.com/ Searches E-Medicine, guidelines, & other evidence-based publications

Guidelines American Urological Association Guidelines

http://www.auanet.org/guidelines/ Practice guidelines for patient management and current standard of care

European Association of Urology/guidelines

http://www.uroweb.org/

Preappraised sources

Evidence-base Medicine http://ebm.bmj.com/ Provides structured abstract of articles selected from journals by an editorial board, plus criticalappraisal of the validity, importance, and applicability 

ACPJC: American College of Physicians Journal Club

http://www.acpjc.org

CENTRAL: Cochrane Central Register of Controlled Trials

http://www.mrw.interscience.wiley.com/cochrane/cochrane_clcentral_articles_fs.html

Non English studies included

Understanding Study Design

Types of Studies

Descriptive Studies

Observational Analytic Studies ◦Cross Sectional studies◦Case Control studies◦Cohort studies

Experimental Studies◦Randomized controlled trials

Descriptive•Case report•Case series•Survey

Analytic

Observational•Cross sectional•Case-control•Cohort studies

Experimental•Randomized controlled trials

Strength of evidence for causality between a risk factor and outcome

Hierarchy of Study Types

Descriptive Studies

Descriptive Studies

Surveys “How many men in the U.S. filled

Viagra prescriptions in 2004?”

Case reports or case series Sildanefil-associated serous macular

detachment.

Descriptive StudiesCannot establish causal relationships

Play an important role in generating hypotheses to be tested

Alerting physicians to a new disease◦ Squamous cell carcinoma in sexual partner of

Kaposi sarcoma patient. Lancet. 1982 Jan 30;1(8266):286.

◦ New outbreak of oral tumors, malignancies and infectious diseases strikes young male homosexuals. CDA J. 1982 Mar;10(3):39-42.

◦ AIDS in the "gay" areas of San Francisco. Lancet. 1983 Apr 23;1(8330):923-4.

Descriptive•Case report•Case series•Survey

Analytic

Observational•Cross sectional•Case-control•Cohort studies

Experimental•Randomized controlled trials

Strength of evidence for causality between a risk factor and outcome

Hierarchy of Study Types

Analytic Studies

Analytic Studies

Attempt to establish a link between a predictor/risk factor and an outcome

Cross Sectional Cohort Case Control

Cross Sectional Study

Cross Sectional Study: Structure

time

Outcome

Exposure

Cross Sectional Study:

Descriptive value:◦ How many medical students smoke cigarettes?◦ What is the age and sex distribution of medical

students who smoke cigarettes?

Analytic value:◦ Is there an association between regular

cigarette smoking and test scores among med students?

Cohort Study

Cohort Study: Structure

time

OutcomeExposure

• Prospective• Retrospective

Cohort Study: Strength Exposure variable was present

before outcome variableIncidence Multiple outcomes of a single

exposureRetrospective cohorts where

available are cheaper and quicker.Analyse predictors (risk factors)

thereby enabling calculation of relative risk.

Measuring Relative Risk

Disease

Yes No

Risk Factor

Yes A B

No C D

Risk ratio (relative

risk) A A + B C C + D

Cohort Study: Weakness

Confounding variablesSelection bias Loss to follow up Recall bias

Case Control Study

Retrospective

time

OutcomeExposure

Case-Control Study

TARGET CONTROLSMales without prostate cancer

TARGET CASESMales with prostate cancer

Case-Control Study: Structure

time

ACTUAL CASESMales with prostate cancer confirmedby biopsy

ACTUAL CONTROLSMales admitted to hospital for non-neoplastic and non-hormone relateddisease

Dietary Zinc intakeYES

Dietary Zinc intakeNO

Case Control Study: Strength

• Simple, fast and inexpensive• Rare outcome & long latency

period• Determines the strength of

the association between each predictor variable and the presence or absence of disease

• Determines odds ratio

Case Control Study: Weakness

Can only look at one outcomeConfounding variablesBias is a major problem

◦Selection◦Recall

Hierarchy of Study Types

Descriptive•Case report•Case series•Survey

Analytic

Observational•Cross sectional•Case-control•Cohort studies

Experimental•Randomized controlled trials

Strength of evidence for causality between a risk factor and outcome

Randomized Controlled Trials

RCTs:Gold standard: Causality

Investigator controls the predictor variable (intervention or treatment)

Randomization: ◦The only way to avoid selection and

confounding bias

Randomization◦Simple◦Urn method◦Computer generated

Equal treatmentBlinding

◦Single◦Double◦Triple

Guarding against Bias: Design

Guarding against Bias: AnalysisSample size

Reporting effect size

Intention to treat principle

Sample SizeOptimal sample size

◦Type I Error: False positives < 5%P-value < 0.05

◦Type II Error: False negatives > 20%

Probability that H0 is rejectedLess than 1/20 = statistically

significant

P-value & CIConfidence Interval relates to P-

value◦Confidence level = 95%◦Confidence limits = Range

Wider CI reflects higher confidence level

◦ Ex. 99% CI when mean age CI = 25 and 29

Effect Size

The observed relationship between an intervention and an outcome is statistically expressed as an “estimate of effect” ◦Odds ratio (OR) or a ◦ Relative risk (RR)

True effect size lies within confidence interval

Intention-to-treat analysis:Including and analysing all

randomised patients according to their original treatment allocation, irrespective of whether they actually received or completed the treatment.

This preserves the unbiased comparison of treatment groups afforded by randomization.

RCTs: WeaknessExpensive Legnthy External validity

Systematic Review

Systematic ReviewAttempts to review all of the

relevant articles in the field

Uses study design based on the hierarchy of evidence◦Most use RCTs (gold standard)

Uses clearly defined parameters

Systematic ReviewAccurate and reliableReduces large quantities of

information into manageable sizeExternal validity is more

applicable than populations from single studies

Meta-analysis

Meta-analysisType of systematic review that

focuses on numerical results◦Uses statistics to integrate findings

Can detect small effects across a group of studies that individually lack statistical power to detect the effect

Common problem is heterogeneity of studies◦Noncompatibility

Rating Quality of Studies

Hierarchy of Evidence

Evidence Based Medicine

EBM

Level Therapy/Prognosis/Aetiology1a SR (with homogeneity) of RCTs

1b Individual RCT (with narrow Confidence Interval)

1c All or none case report/series2a SR (with homogeneity) of cohort studies

2b Cohort study

3a SR (with homogeneity) of case-control studies

3b Case-Control Study

4 Case-series

5 Expert opinion without explicit critical appraisal, or based on physiology, bench research or "first principles"

GRADE system: Grading of Recommendations Assessment, Development & Evaluation

EBM - What is it?

Clinical Expertise

Research Evidence

Patient Preferenc

es

Acquire the best evidence

Appraise the evidence

Applyevidence to patient care

Ask clinical questions

EBM Method

Ask Clinical Questions

Patient/Population Outcome

Intervention/Exposure

Comparison

In patients withBPH

does treatment

with alpha blocker

compared to surgery

decrease LUTS?

P I C O

Acquire the Best Evidence

Where do you find high-quality evidence?◦Textbook (print or online)◦Pre-appraised evidence

Best Evidence Clinical Evidence (Therapy only) Cochrane Collaboration (Therapy only) UpToDate

◦Medline or PubMed search: find and review articles

Appraise the Evidence

Are the results valid?

What are the results?

Can we apply the results to our patient?

Appraise the Evidence

Determine if evidence is unbiasedor flawed◦Critically appraise articles yourself◦Used a source that appraises trials for you Best Evidence Clinical Evidence Cochrane Library UpToDate

Apply the Evidence

Evidence must be applied to each individual patient◦Is your patient similar enough to those studied?

◦Do benefits outweigh harms?◦Cost◦What are your patient’s values and preferences?

Take Home Message Research is like riding a bicycle

◦ It needs practice

Research needs planning◦If you fail to plan, you plan to fail

Not all of us need to do research

◦ But all of us should practice EBM

Thank You