American Thoracic Society & Turkish Thoracic Society

Level 2 Course Syllabus

Methods in Epidemiologic, Clinical & Operations Research (MECOR)

- Cesmi, Turkey

Monday 17.November.2014 – Saturday 22.November.2014

1 ACKNOWLEDGMENTS

The American Thoracic Society is the primary sponsor of the 2014 MECOR Turkey Course in Cesme, Turkey

The Turkish Thoracic Society has provided the principle support for MECOR Turkey 2014.

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

The American Thoracic Society acknowledges and gratefully thanks Füsun Eyüboğlu, country coordinator of MECOR Turkey 2014 and her colleagues who assisted in its organization.

MECOR Turkey 2014 Course Staff

A. Sonia Buist, ATS MECOR Program Director Füsun Eyüboğlu, MECOR Turkey Country Course Director

Fran Du Melle, Sr. Director, International Activities, American Thoracic Society E-mail: [email protected]

“Improving global lung health through development of local, country and regional lung disease research capacity”

Table of Contents Page

2 Acknowledgments 2

Introduction 4

Competencies 5

Course Outline 6-8

Protocol Outline 9

Course Faculty 10-14

Schedule 15

3 Faculty

Damon Scales Tim Watkins Sibel Kiran Begum Ergan (TA) Refika Ersu (TA)

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 ([email protected]) as soon as possible before the course starts.

4 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 Describe the balance between precision & accuracy in measurement Procedures Design and pre-test a study questionnaire. Quality Control Describe effective approaches to monitoring quality of data gathering and data entry Ethics & Informed Describe current standards of ethical treatment of human subjects Consent 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 Critically appraise of randomized controlled trial, a survey study, a prognosis study paper and a diagnostic study using standardized methodology. Evidence-Based- Describe roles and methods of systematic review, meta-analysis Medicine 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.

5 Course Outline

6 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. ROC and 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. Continuous results: 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

7 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 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 cause the 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 med ical treatments. Confounder scores Propensity scores Instrumental variables

- Expressing the effect of a therapy 8 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

Protocol Outline

9 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)

LEVEL 2- Course Faculty

10 Damon C. Scales MD PhD Associate Professor 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: [email protected] [email protected]

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 Associate 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 (RCT). Most recently, 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 is now conducting (as PI) a stepped-wedge cluster RCT to improve the application of evidence-based neuroprognostication for cardiac arrest survivors (PremaTOR; funded by HSF) and also an individual patient RCT (as PI) of pre-hospital cooling by paramedics of cardiac arrest victims (ICE-PACS, funded by CIHR). He has taught MECOR courses since 2010 (Brazil, Columbia, Turkey, Indonesia).

11 Timothy R. Watkins, MD MSc Assistant Professor, Division of Pulmonary and Critical Care Medicine Assistant Member, Research Division Puget Sound Blood Centre

Harborview Medical Center Campus Box 359762 325 - 9th Avenue Seattle, WA 98104 [email protected]

Dr Timothy Watkins holds an undergraduate degree in Biology from Ohio University, a medical degree from Ohio State University and a Master’s degree in Public Health from the University of Washington.

Dr. Watkins performs clinically-oriented translational research, studying outcomes following critical illness and injury, examining specifically how blood product transfusions might contribute to adverse clinical outcomes. His research areas of interest include examining the clinical and biologic relationships between blood product transfusions and the development of lung injury, sepsis, and multiple organ failure. He is focusing on elements of blood product processing, storage, and even blood donor health-related factors in order to identify mechanisms to improve transfusion safety in critically ill and injured populations. These groups seem especially vulnerable to transfusion-associated complications.

12 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: [email protected]

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).

13 Begum Ergan, MD Director of Critical Care Unit Dokuz Eylul University, Department of Pulmonary and Critical Care, İzmir, Turkey e- mail: [email protected]

Dr. Ergan received her medical degree from Hacettepe University School of Medicine, Ankara, Turkey. After completing her residency in the Department of Chest Diseases in the same hospital, she did started the critical care fellowship programme between 2006 and 2010. In 2009 she visited Harvard Medical School Brigham and Womens Hospital Lung Transplant Unit for 6 months. She was then assigned to Diskapi Yildirim Beyazit Education and Research Hospital, as part of her obligatory duty for Turkish Ministry of Health, where she took an active role in establishment of the medical intensive care unit in that hospital. After finishing her obligatory work for Turkish Ministry of Health in May 2014, she started working in intensive care unit of Dokuz Eylul University Pulmonary and Critical Care Department. Her research interests include critical care, chronic respiratory failure, end-stage COPD and noninvasive ventilation. Her non-medical interests include travelling and jogging. She has participated in MECOR since 2008.

14 Refika Ersu, MD Professor of Pediatrics Division of Pediatric Pulmonology Marmara University Istanbul-Turkey E-mail: [email protected]

Dr. Ersu obtained her MD from the University of Istanbul. She then completed her residency in Pediatrics at Marmara University. She worked as a research fellow in Pediatric Respiratory Division at Royal Brompton Hospital for a year. She then worked as a pediatric pulmonology fellow at Childrens Hospital Los Angeles in California between 1998 and 2001. She is a Professor of Pediatrics at Marmara University and is also the Director of Pediatric Sleep Laboratory.

Her research interests are sleep disordered breathing in children including obstructive sleep apnea, sleep disordered breathing in children with chronic lung disease and cystic fibrosis. She is an active member of the Pediatric Respiratory Physiology and Sleep group in Pediatrics Section in European Respiratory Society. She also works in the Educational Committee of American Thoracic Society Sleep and Respiratory Neurobiology Assembly.

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

Module 1 Welcome and Introductions Daily Review Quiz Daily Review Quiz Daily Review Quiz Final Review Quiz Design groups (08:30- (08:00-09:00) present 09:00) Selecting a Good Research Question (Sonia; 09:00- 09:30) (09:00 – Overview of study designs. Diagnosis Prognosis (Tim) Data Management Design Groups Meet 10:30) SOPs, Registration, (Tim) ROC Review – Bewick and Collection Reporting of Results Hulley Ch 12 Prognosis (Begum) (Damon; 09:30-10:30) ROC Review Bewick Paper (P4) (Refika) Hulley Ch 1 Diagnosis Handout Treatment Diagnosis A and B Morning Break Module 2 Developing your research Paper (P1): Approaches to confounding: Survival analysis Learning from your Design groups (10:45- proposal (Sibel) Hulley Ch 2 Bias, Confounding, matching, stratification, (Damon) own mistakes: present 12:45) Chance (Damon) randomization, and models Survival Review – instructors present (Damon) Bewick their biggest research Hulley Ch 9 Survival - Stolberg mistakes (ALL) Multivariate analysis review - Katz Building your research Quick Review: Basic Paper (P2) Diagnosis: Design Groups Meet Design Groups Meet proposal: measuring Statistics p values and (Tim) variables (Outcome, bivariate statistics Exposure, Covariates) (Tim) (Refika or Begum) Hulley Ch 3 and 4 Stat Reviews 1-5 Lunch Module 3 Bias, confounding, chance Sample Size and Power Assessing attitudes and Paper (P5): Design groups meet (13:45- (Damon) (Damon) behavior- (Sibel) Survey (Sibel) 15:45) Hulley Ch 9 Hulley Ch 6 Survey Review - Burns Power Calculations

Treatment (Refika) Paper (P3) Prognosis (Tim) Design groups meet Hulley Ch 10 OR Design Groups Meet Therapy A and B Afternoon Break Module 4 Design Groups Meet: Design Groups Meet: Design Groups Meet: Design Groups Meet Design groups meet (16:00- Elaborate your question and Define your statistical 18:00) study design. Clarify your analysis and calculate subjects and variables. your sample size