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American Thoracic Society&Turkish Thoracic Society

Methods in Epidemiologic, Clinical & Operations Research

(MECOR)

Level 2 Course Syllabus

Çeşme, Turkey

November 6, 2017 – November 11, 2017

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ACKNOWLEDGMENTS

The American Thoracic Society is the primary sponsor of the 2017 MECOR Course in

İzmir, Turkey. Additional support has come from the Turkish Thoracic Society. Our

sincere thanks to all who have shared the vision and support this program.

The American Thoracic Society acknowledges and gratefully thanks Dr.ÖzgeYılmaz

and SibelKarakurt, country course directors of MECOR Turkey 2017 and their

colleagues who assisted in its organization.

2016 ATS MECOR Course Staff

A. Sonia Buist, ATS MECOR Program Director

Fran Du Melle - Senior Director International Programs and Activities, American Thoracic Society

American Thoracic Society, 25 Broadway, New York, NY 10004 USA

E-mail: fdumelle@thoracic.org

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Table of Contents

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Acknowledgments 2 Introduction 4 Competencies 5 Course Outline 6-8 Protocol Outline 9 Course Faculty 10-14 Schedule 15

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Faculty Damon Scales Neill Adhikari Sibel Kıran ÖzgeYılmaz Teaching Assistants: Ülkü Aka Aktürk Welcome to Level 2! This course is an extension of what you learned in Level 1, but it will also introduce you to many new topics. The course is taught in a very interactive fashion – the lectures will be short and we expect you to ask and answer questions during all of the sessions. The course has 4 major goals:

(1) To build on the principles of clinical research and epidemiology you learned in the introductory course,

(2) To provide you with additional tools to critically appraise the literature using principles of clinical epidemiology,

(3) To discuss your clinical research proposal using a scholarly approach (4) To enhance your research communication skills.

In addition to the large group sessions, there will be various types of smaller group sessions:

Design Groups Meet: you will have time to work on your personal research project – you should at least bring one or two ideas for projects to work on at the course. The instructors will work with you in small groups to make improve your proposals. Design Groups Present: You will present your work in progress and get feedback from your colleagues. Discuss Paper: Your group will have 30 min to discuss the questions posed, then faculty will join for another 30 min to help with the discussion. If there is an article that you find interesting that covers the diagnosis, prognosis, therapy, or surveys of attitudes in pulmonary or critical care medicine, bring it along and we can consider using it to teach from at one of the sessions.

What you need to do before you come to the course 1) Read the original articles Paper 1 through Paper 5, pay more attention to methodology and

results than to introduction and discussion. 2) Do the Homework for these sections – we will review these together so don’t worry if there

are questions you can’t answer. 3) Send us the research question or questions that you will be working on during Level 2.

Please send this in a word document to Damon (damon.scales@sunnybrook.ca) and Ozge (oyilmaz_76@hotmail.com) as soon as possible before the course starts.

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Level 2 Competencies

Research Design Describe the basis of clinical epidemiology as an approach to diagnosis, prognosis, and treatment of disease.

Describe the application of study design to clinical studies

Research Question Apply and adapt epidemiologic questions to clinical and health services problems

Population Selection Develop feasible & valid approaches to population sampling

Measurement Procedures

Describe the balancebetween precision& accuracy in measurement Design and pre-test a study questionnaire.

Quality Control Describe effective approaches to monitoring quality of data gathering and data entry

Ethics & Informed Consent

Describe current standards of ethical treatment of human subjects Describe the role of Internal Review Boards.

Descriptive Statistics Apply descriptive statistics to characterize study populations.

Measures of Association Recognize and calculate common measures of association used in clinical research.

Sources of Error Describe the concepts of bias, confounding chance; type I and II errors, reliability, validity, accuracy and precision Identify and describe possible sources of error when critically appraising the literature.

Sample Size and Power Calculate the sample size for diverse types of research questions using standardized methods.

Multivariate Analysis Describe the underlying paradigm of statistical inference and statistical models. Select the appropriate statistical model for a specific research question.

Reading a scientific paper

Critically appraise of randomized controlled trial, a survey study, a prognosis study and a diagnostic study using standardized methodology.

Evidence-Based-Medicine

Describe roles and methods of systematic review, meta-analysis

Protocol Develop a research protocol outline.

Communication Participate during interactive lectures given by the faculty. Discuss the original articles with your designated discussion group. Present a research protocol using a power-point format and in English.

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Course Outline

1) Elements of a research proposal This module will orient you to the basic

elements of well written research proposal

- Research question

- Hypotheses - Study design

- Study population

- Variables and measurements - Sample size

- Data analysis - Limitations

- Implications

2) Feasible study designs for limited funds Good research is not necessarily expensive – in this module you

will learn how to get the most out of the lease expensive study designs and methods.

- Surveys

- Chart review

- Secondary data analyses of existing databases

3) Diagnosis This module will take the student through the concepts necessary to understand how diagnostic

tests are evaluated and how information about test performance is applied at the bedside. Read the attached

article and homework for this section.

- How accurate is this test? All around the 2x2 table: sensitivity, specificity, accuracy, predictive values.

ROCand its area as single overall measure of test discrimination.

- If doctors think in terms of predictive values, why are tests reported as sensitivity and specificity?

- From information to decisions: how accurate a test needs to be depends on the decision.

- Evaluating studies of diagnostic tests

- Generalizability expertise and experience of test setting

spectrum bias

- Chance with particular reference to the confidence interval around zero and 100%

- How to evaluate tests when there is no criterion standard or when continuous results are provided. Categorical results: kappa and measures of inter-observer variability.

Continuousresults: Bland-Altman plots.

4) Prognosis Making prognoses is an important and difficult clinical task. This module will teach you the basic

concepts behind prognostication, how to use prognostic data, and the pitfalls of prognostic studies. Read the

attached article and homework for this section.

- Many different types of prognostic information available to clinicians: Disease staging (cancer)

Risk models (APACHE)

Clinical prediction rules

- Differences between clinical prognosis and risk adjustment.

- What is the role of confounding and causal inference in studies of prognosis? Differences between multivariate modeling when the goal is generate an unbiased estimate of one of the

coefficients (that is, when the goal is determine the unconfounded “effect” of the exposure) versus multivariate

modeling for prediction when the goal is a model that is accurate (calibration and/or discrimination) and

generalizable.

- Identifying relevant prognostic variables.

- Generalizability - a key factor in assessing the use of prognostic data.

- Expressing prognosis

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Rates, relative rates, hazards and hazard ratios.

Median survival

Probability of event

5) Assessing attitudes and behaviors Understanding patients and clinician’s knowledge, attitudes, and behavior

is an important area of research. Read the attached article and homework for this section.

- Survey design and validation

- Existing instruments versus developing your own

- Available population versus target population

- Response rates and bias

- Limitations of cross-sectional data and associations

6) Therapy Ultimately, questions about therapy are questions about causation. Does the treatment causethe

improved outcome? Causality is hard to prove and this module will teach you how to think about studies

about treatment. Read the attached article and homework for this section.

- Inference from randomized experiment What is the purpose of randomization?

Reducing confounding to chance.

The purpose of Table 1. Do the P values in Table 1 mean anything?

What is the purpose of blinding? To reduce bias.

Do randomization and blinding serve any role in enhancing generalizability?

What are the limitations of experiments? Efficacy and Effectiveness

- Inference from observational studies What are the advantages of observational studies in evaluating medical treatments?

Potential for confounding - particularly confounding by indication.

Advanced techniques for addressing confounding in observational studies of medical treatments.

Confounder scores

Propensity scores

Instrumental variables

- Expressing the effect of a therapy Relative risk

Risk reduction

Attributable risk, Number Needed to Treat

- Identifying relevant prognostic variables.

- Generalizability - a key factor in assessing the use of prognostic data.

- Expressing prognosis Rates, relative rates, hazards and hazard ratios.

Median survival

Probability of event

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Protocol Outline

Title: Clear and descriptive Research Question:

One sentence concisely stating your question

Significance: One to several paragraphs indicating why the question is important Study Design: Cross-sectional vs. case-control, vs. cohort, etc. Participants: Entry and exclusion criteria: Recruitment strategy: Variables: Outcome (dependent variable, response variable): Exposure (risk factor, independent variable, predictor, explanatory variable, treatment): Potential confounders: Method of data collection and quality control: E.g., questionnaire, medical record review, etc. Statistical issues: Hypothesis: Sample size and power: Limitations Funding Implications (Adapted from Hulley et al.: Designing Clinical Research: An Epidemiologic Approach, Appendix 1.1, page 15)

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LEVEL 2- Course Faculty Damon C. Scales MD PhD AssociateProfessor Interdepartmental Division of Critical Care Medicine University of Toronto Department of Critical Care Medicine Sunnybrook Health Sciences Centre 2075 Bayview Avenue, Room D108, Toronto, ON Canada M4N 3M5 E-mail: damon.scales@sunnybrook.ca Damon.scales@gmail.com

Dr. Scales obtained his MD from the University of Toronto (UofT,1997). He then completed residencies in Internal Medicine and Critical Care Medicine (CCM) and a PhD in Clinical Epidemiology. He is an Assistant Professor of Medicine (UofT) and an Intensivist at Sunnybrook HSC. He is also the Program Director of the UofT Adult CCM Residency program.

His research evaluates interventions and system-factors that influence outcomes of critically ill patients. He has also conducted several large quality improvement randomized trials (RCTs). He was the co-Principal Investigator of the SPARC (Strategies in Post Arrest Resuscitation Care) stepped-wedge cluster RCT to improve the use of therapeutic hypothermia in cardiac arrest survivors (funded by CIHR & Heart and Stroke Foundation (HSF)). He was also the PI of a stepped-wedge cluster RCT to improve the application of evidence-based neuroprognostication for cardiac arrest survivors (PremaTOR; funded by CIHR and HSF) and also an individual patient RCT (as PI) of prehospital cooling by paramedics of cardiac arrest victims (ICE-PACS, funded by CIHR). Most recently, he has been funded (CIHR) to conduct a large RCT of prehospital identification and treatment of sepsis, and a large RCT of airway management strategies for brain-injured patients who are weaned but remain intubated and mechanically ventilated because of a decreased level of consciousness. He has taught MECOR courses since 2010 (Brazil, Columbia, Turkey, Indonesia).

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Neill Adhikari, MDCM, M.Sc Sunnybrook Health Sciences Centre 2075 Bayview Ave., Room D1 08 Toronto, ON M4N 3M5 Phone: 416-480-4522 Email: neill.adhikari@sunnybrook.ca

DrAdhikari is an intensivist at Sunnybrook Health Sciences Centre and Lecturer in the Interdepartmental Division of Critical Care at the University of Toronto. He is the Physician lead, Cardiovascular Intensive Care Unit, Sunnybrook Health Sciences Centre and the Director of Research for the Department of Critical Care Medicine. Dr. Adhikari received his medical degree from McGill University and then completed residency training in Internal Medicine (McGill) and Respirology and Critical Care Medicine (Manitoba and Toronto). He subsequently obtained a MSc in Heath Research Methodology from McMaster University. His research interests include critical care delivery in low-resource settings, renal replacement therapy in the ICU, and meta-analysis methods.

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Dr. ÖZGE YILMAZ, MD

Celal Bayar University Medical Faculty

Department of Pediatric Allergy and Pulmonology

Manisa, Turkey

E-mail: oyilmaz_76@hotmail.com

Phone: +90-533-3690131

Dr. ÖzgeYılmaz is currently Associate professor of Pediatrics in Celal Bayar University Medical Faculty, Department of Pediatric Allergy and Pulmonology. She graduated from Hacettepe University Medical Faculty in 2001 and completed her Pediatric residency and fellowship in Pediatric Allergy in 2007 and 2011 respectively. She was a student in the first three levels of MECOR courses between 2008 and 2011 in Turkey and she finished the Global MECOR course in 2011. She has worked as a teaching assistant in MECOR for two years and since 2014 she is working as a faculty. She is the chair of Experimental Research Assembly of Turkish Thoracic Society and a member of School committee. She is currently the co-chair of the Pediatric Assembly international relations committee of American Thoracic Society and a member of the planning committee of the same assembly. Moreover, she is a member of European Respiratory Society and European Academy of Allergy and Clinical Immunology. Her work focuses on pathophysiological aspects and developmental origins of pediatric asthma and wheezing in children as well as psychosocial aspects of these diseases.

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Level 2 Teaching Assistants Dr. Ülkü Aka Aktürk

Sibel Kiran, MD PhD Associate Professor, Public Health Institute of Hacettepe

University of Ankara

Professional Social network: tr.linkedin.com/pub/sibel-

kiran/29/34/67a/

e- mail: sibelkiran@gmail.com

Sibel Kiran graduated from Dokuz Eylul University School of Medicine in 1996. She received her PhD in

Occupational Health from the Public Health Department as a residence of Dokuz Eylul University Health

Science Institute in 2003. Between 2003-Ocober 2013 she had worked in Public Health Department and

Health Science Institute of Bulent Ecevit University (former Zonguldak Karaelmas University). Currently,

she is working as an Associate Professor at the Public Health Institute of Hacettepe University of Ankara.

She is certified as Occupational physician, Occupational physician trainer, ILO pneumoconiosis reader, sleep

medicine physician, problem based learning and tutors’ trainer, Basic Occupational Health Services Trainer

of Health care Workers', and for advanced epidemiology, mental health education and management in

occupational medicine.

She is a Member of ICOH and three scientific committees of ICOH, Society of Public Health Specialists,

Occupational Health Study Group, Turkish Thoracic Society scientific advancement committee, Turkish

Sleep Society epidemiologic advisory board, Cancer coordination board and Training of trainers commission

of Bulent Ecevit University

She is currently involved in occupational epidemiological studies on sleep, shift work, health care workers

and exposure assessment.

She has been teaching MECOR courses since 2011 (Turkey).

Photo

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Day 1 Day 2 Day 3 Day 4 Day 5 Day 6

Module 1

(08:30-

09:00)

Welcome and Introductions

(08:00-09:00)

Daily Review Quiz Daily Review Quiz Daily Review Quiz Final Review Quiz Design groups

present

(09:00 –

10:30)

Selecting a Good Research

Question (Sonia)

Diagnosis (Ozge)

HulleyCh 12

ROC Review Bewick

Diagnosis Handout

Diagnosis A and B

Prognosis(Neill)

ROC Review – Bewick

Prognosis

Ethics session

(combined with

other levels)

Design Groups Meet

Morning Break Module 2

(10:45-

12:00)

Overview of study designs.

SOPs, Registration, Reporting

of Results (Damon)

HulleyCh 1

Paper (P1):

Bias, Confounding,

Chance

Approaches to confounding:

matching, stratification,

randomization, and models

(Damon)

HulleyCh 9

Multivariate analysis review -

Katz

Data Management

and Collection

(Sibel )

Paper (P4)

Treatment

Learning from your

own mistakes:

instructors present

their biggest research

mistakes (ALL)

Design groups

present

Bias, confounding, chance

(Damon)

HulleyCh 9

Quick Review: Basic

Statistics p values and

bivariate

statistics(Neill)

Stat Reviews 1-5

Paper (P2) Diagnosis:

Design Groups Meet Design Groups Meet

Lunch Module 3

(13:00-

15:30)

Developing your research

proposalHulleyCh 2 (Neill)

Sample Size and

Power(Damon)

HulleyCh 6

Power Calculations

Assessing attitudes and

behavior (Neill)

Survey Review - Burns

Survival

analysis(Damon)

Survival Review –

Bewick

Survival - Stolberg

Design groups meet

Building your research

proposal: measuring

variables(Neill)

(Outcome, Exposure,

Covariates)

HulleyCh 3 and 4

Treatment (Sibel)

HulleyCh 10

Therapy A and B

Paper (P3) Prognosis

OR Design Groups Meet

Design groups meet

Afternoon Break Module 4

(16:00-

17:30)

Design Groups Meet:

Elaborate your question and

study design. Clarify your

subjects and variables.

Design Groups Meet:

Define your statistical

analysis and calculate

your sample size

Design Groups Meet: Design Groups Meet Design groups meet