Why did I start doing research during residency?Dr. Nelson LeeMBBS, MD, MRCP(UK), FRCP(Lond.), FRCP(Edin.), FIDSAProfessor, Division of Infectious DiseasesFaculty of Medicine and DentistryUniversity of Alberta

Disclosure• Relevant relationships with commercial entities

• consultancy work for Shionogi Ltd., Janssen Pharmaceuticals Inc., GlaxoSmithKline, AstraZeneca Hong Kong Ltd., Visterra Ltd., hVIVO Ltd., and Seqirus Inc.; support for investigator-initiated research from F. Hoffmann–La Roche; remunerated lecture for AstraZeneca Hong Kong Ltd., and Seqirus Inc.; support for travel to meetings from Sanofi-Aventis Hong Kong Ltd, MSD (Asia) Ltd., Pfizer Corporation Hong Kong Ltd., Gilead Sciences Hong Kong Ltd., and Janssen Pharmaceuticals Inc.

• Potential for conflicts of interest within this presentation• none

• Steps taken to review and mitigate potential bias• not applicable

By the end of this session, participants should be able to:1. Describe different strategies on time management, organization and team building to

accomplish efficient research.2. Enumerate different types of research projects that can be accomplished during

residency (basic science, microbiology lab, clinical research).

3. Apply some key questions to corner potential subject interests for research (i.e. interests, feasibility of the project, having the technical or statistical knowledge to complete the project).

4. Describe important characteristics of researchers/preceptors to work with to make projects feasible and list strategies to approach potential researches/preceptors.

Learning objectives

Personal journey

Review articles

Observational cohort study

10th March 2003

>138 HCWs, inpatients and students infected

Lee N et al. NEJM 2003Descriptive study; prognostic indicators

Outcome study (observational): 37 patients

Sung JY et al. Thorax 2004; Lee N, et al. J Clin Virol 2004; Lee N, Hui DS. Lancet 2012

[N >320]

Longitudinal progression & virokinetic studies

Hui DS et al. Radiology 2004; Wong KT et al. Radiology 2003, 2003

Peiris JS et al. Lancet2003. Lee N, Hui DS et al. J Clin Virol 2004 & Lancet 2012

Pneumonia extent &viral load peak at D10

RCT on corticosteroid treatment: harmful effects

Detects viraemiawithin 3.6 days (WHO endorsed)

Pathogenesis (e.g. complement activation), diagnosis, prognostication

prognostication

Chan PK, Emerg Inf Dis 2004; Ip M, Clin Infect Dis2004Combination of Upper/Lower respiratory, stool, and blood samples to optimize diagnosis

Clin Chem 2006

Clin Chem 2003

Week from onset

Posi

tivity

rat

e (%

)

SAR

S-C

oVR

NA

(cp/

mL)

“LRT > URT”

Pathogenesis and Immunology Studies

Viremicphase

Hyperimmunephase

Lung destruction phase

DAD & ARDS

SARS-CoV

Immune Evasion

non-SARS

Wong CK, Clin Exp Immu 2004; Tang NL, Clin Chem 2005; Wong RS, BMJ 2003; Tse GM, J Clin Patho 2004; Leung WK,Gastroenterology 2003; Peiris JSM, Nature Med 2004; Cameron MJ, J Virol 2007

(lymphopenia: CD4↓↓ CD8 ↓↓)(ineffective Type I IFN responses)

Cytokine storm

(lung and GI tract viral replic.)

Transmission and Infect. Control Studies

NEJM 2004

Clin Inf Dis 2005

Airborne transmission of influenza

Clin Infect Dis 2010

Computational fluid dynamics modeling

“International Young Investigator Award” Infectious Diseases Society of America (IDSA) conference, 2010

9 infected patients

distributed along airborne virus gradient

Outcome studies Virokinetic studies

Immunopathogenesis studies Descriptive cohort studies

Types of research

• Review articles• Case reports/series• Surveys • Observational studies

• retrospective, prospective• cross-sectional, longitudinal cohort• case control

• Intervention studies – clinical trials• Informatics and meta-analysis

Basic science & laboratory-based studies

Level of evidence (LOE)

Description

Level I

Evidence from a systematic review or meta-analysis of all relevant RCTs (randomized controlled trial) or evidence-based clinical practice guidelines based on systematic reviews of RCTs or three or more RCTs of good quality that have similar results.

Level II Evidence obtained from at least one well-designed RCT (e.g. large multi-site RCT).

Level IIIEvidence obtained from well-designed controlled trials without randomization (i.e. quasi-experimental).

Level IV Evidence from well-designed case-control or cohort studies.

Level V Evidence from systematic reviews of descriptive and qualitative studies (meta-synthesis).

Level VI Evidence from a single descriptive or qualitative study.

Level VII Evidence from the opinion of authorities and/or reports of expert committees.

• Treatment Research generally involves an intervention…….

• Prevention Research looks for better ways to prevent disorders from developing or returning………

• Diagnostic Research refers to the practice of looking for better ways to identify a particular disorder or condition.

• Screening Research aims to find the best ways to detect certain disorders or health conditions.

• Quality of Life Research explores ways to improve comfort and the quality of life for individuals with a chronic illness.

• Genetic studies aim to improve the prediction of disorders by identifying and understanding how genes and illnesses……

• Epidemiological studies seek to identify the patterns, causes, and control of disorders in groups of people.

• Clinical trials: Phase I trials: Researchers test an experimental drug or treatment in a small group of people for the first time. The researchers evaluate the treatment’s safety, determine a safe dosage range, and identify side effects. Phase II trials: The experimental drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety. Phase III trials: The experimental study drug or treatment is given to large groups of people. Researchers confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely. Phase IV trials: Post-marketing studies, which are conducted after a treatment is approved for use by the FDA, provide additional information including the treatment or drug’s risks, benefits, and best use.

• Micro-organism (e.g. bacteria, viruses, mycobacteria, fungus, parasites)• Microbiota (e.g. GI, RT)• Host response / immunology (e.g. innate, adaptive)• Host-pathogen interactions (e.g. receptors, cell entry)• Clinical

• descriptive (e.g. novel infections)• analytical (e.g. risk factors, outcomes, diagnostics, treatment)• interventional (e.g. efficacy, effectiveness, safety)

• Public health (e.g. prevention strategies, vaccines)

• Any combinations of the above!

Types of research – ID & microbiology

Finding your interests: hot topics

WHO:

Finding your interests: hot topics• Antimicrobial resistance (AMR)• Emerging infections and

pandemic preparedness• Vector-borne infections• Blood-borne infections (e.g. HIV,

hepatitis) and STI• New diagnostics, point-of-care

tests (POCT)• Biomarkers

• Novel therapeutics (including host-target therapies)

• Novel vaccines• Immunopathogenesis and host-cell

interactions• Microbiome studies• Public health: transmission and

infection prevention• ………………

Know how: training aspects• epidemiology and biostatistics• types of studies and design• statistical analysis (e.g. SPSS, SAS)

• descriptive statistics• parametric and non-parametric tests• binomial logistic regression, and multivariate analysis• survival analysis• cox regression, and multivariate analysis

• writing skills• graphical presentation• inserting references• applying for ethics approval

Know how: training aspects• epidemiology and biostatistics• types of studies and design• statistical analysis (e.g. SPSS, SAS)

• descriptive statistics• parametric and non-parametric tests• binomial logistic regression, and multivariate analysis• survival analysis• cox regression, and multivariate analysis

• writing skills (Introduction, Methods, Results, Discussion)• drawing up tables and figures• inserting references• applying for ethics approval

Presentations / Publications

• poster and oral presentations in meetings and conferences• choosing your target journal(s) • journal impact factors• choosing the article type• formatting: journal style • tables & figures• defining authorship

Concept and design: Data acquisition: Laboratory analysis: Data analysis and interpretation: Drafting of article: Critical revision for important intellectual content:Final approval of article:

Journals: Infectious Diseases

Journals: Microbiology

Journals: General and Internal Medicine

Barriers to research

• Identify the barriers• Ways to overcome these barriers?

• Propose a research project• is it an impactful topic?• how would you design the study• identify the expertise you’ll require (“who to call”?)• your target journal?