How to Write Introduction Section? Dr. Gholamreza Khalili Department of Epidemiology & Biostatistics School of public health Tehran University of Medical Sciences

Introduction Before you begin, answer the basic questions: What do I have to say? Is it worth saying? What is the right format? What is the audience? What is the right journal?

Introduction General, concise description of problem background to the work previous research Where that work is deficient how your research will be better State the hypothesis About 3 to 4 paragraphs

Paragraph1: Paragraph2: Paragraph3: What we know Paragraph2: What we don’t know ? Paragraph3: Why we did this study 4

Introduction Existing state of knowledge Gaps in knowledge which research will fill. State what you Intend to do & the purpose of article Give pertinent references Summarize the rationale for study or observation Define specialized terms or abbreviations you want to use

Inverted pyramid The structure should funnel down from a broad perspective to a specific aim Oxidative stress plays an important role in.... When LDL particles are oxidized ... Antioxidants are important... ...Paraoxonase...

Introduction Don’t make it a review article Don not include methods, results and discussion Don’t put down every all previous studies & their data gaps Don’t explain pathophysiology irrelevant to your study

Introduction Tell why you have undertaken the study Clarify what your work adds Follow the best advice Keep it short Make sure you are aware of earlier studies Tell about importance of your study Don’t baffle your readers Give the study design Think about using journalistic tricks

Introduction To write an effective introduction you must: Know your audience Keep it short Tell readers why you have done the study Explain why it is important Convince readers that it is better than others Try to hook them!

Types of study designs Dr. Gholamreza Khalili Department of Epidemiology & Biostatistics School of public health Tehran University of Medical Sciences

Types of Studies Descriptive Studies Observational Analytic Studies Cross Sectional studies Ecologic studies Case Control studies Cohort studies Experimental Studies Randomized controlled trials

Hierarchy of Study Types Analytic Descriptive Case report Case series Survey Observational Cross sectional Ecologic Case-control Cohort studies Experimental Randomized controlled trials Field Trials Community Trials Strength of evidence for causality between a risk factor and outcome

Descriptive studies Getting a “lay of the land” Surveys (NHIS, MCBS) Describing a novel phenomena Case reports or case series

Descriptive studies Cannot establish causal relationships Still play an important role in describing trends and generating hypotheses about novel associations The start of HIV/AIDS research 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.

Analytic Studies Attempt to establish a causal link between a predictor/risk factor and an outcome. You are doing an analytic study if you have any of the following words in your research question: greater than, less than, causes, leads to, compared with, more likely than, associated with, related to, similar to, correlated with

Hierarchy of Study Types Analytic Descriptive Case report Case series Survey Observational Cross sectional Ecologic Case-control Cohort studies Experimental Randomized controlled trials Field Trials Community Trials Strength of evidence for causality between a risk factor and outcome

Research Question Is the regular consumption of Red Bull associated with improved academic performance among U.S. medical students?

Background Alford C, Cox H, Wescott R. The effects of red bull energy drink on human performance and mood. Amino Acids. 2001;21(2):139-50. Warburton DM, Bersellini E, Sweeney E. An evaluation of a caffeinated taurine drink on mood, memory and information processing in healthy volunteers without caffeine abstinence. Psychopharmacology (Berl). 2001 Nov;158(3):322-8. Seidl R, Peyrl A, Nicham R, Hauser E. A taurine and caffeine-containing drink stimulates cognitive performance and well-being. Amino Acids. 2000;19(3-4):635-42. Horne JA, Reyner LA. Beneficial effects of an "energy drink" given to sleepy drivers. Amino Acids. 2001;20(1):83-9. Kennedy DO, Scholey AB. A glucose-caffeine 'energy drink' ameliorates subjective and performancedeficits during prolonged cognitive demand. Appetite. 2004 Jun;42(3):331-3.

Great idea, but how do you get started…. Interesting, novel, and relevant, but… You only have 25,000 dollars to start investigating this question. What is feasible?

Study Design #1 Cross-sectional study of UCSF medical students taking USMLE Step 2 Questionnaire administered when registering for USMLE 2 Primary predictor: self-report of >3 cans Red Bull per week for the previous year Covariates: Age, sex, undergraduate university, place of birth Outcome: Score on USMLE Step 2

Cross-sectional study: structure Red Bull consumption USMLE Score time

Cross-sectional Study: Descriptive value: How many UCSF medical students drink Red Bull? What is the age and sex distribution of UCSF medical students who drink Red Bull? Analytic value: Is there an association between regular Red Bull consumption and test scores among UCSF med students?

Cross-sectional Study: Pluses + Prevalence (not incidence) + Fast/Inexpensive - no waiting! + No loss to follow up + Associations can be studied

Measures of association Risk ratio (relative risk) A A + B C C + D Disease Yes No Risk Factor A B C D

Cross-sectional study: minuses - Cannot determine causality Red Bull consumption USMLE Score time

Cross-sectional study: minuses - Cannot determine causality ACE inhibitor use and hospitalization rates among those with heart failure time

Cross-sectional study: minuses - Cannot determine causality - Cannot study rare outcomes

What if you are interested in the rare outcome? The association between regular Red Bull consumption and… A perfect score on the USMLE – Step 2 Graduating top 1% of the medical school class Acceptance into a highly selective residency ANSWER: A Case-Control study

Study Design #2 A case-control study Cases: med students accepted to residency in “highly selective specialty X”. Controls: med students who applied but were not accepted. Predictor: self-reported regular Red Bull consumption Additional covariates (age, sex, medical school, undergraduate institution)

Case control studies Investigator works “backward” (from outcome to predictor) Sample chosen on the basis of outcome (cases), plus comparison group (controls)

Study multiple exposures in a Case-control Study B Exposed to A Not Exposed Disease No Disease

Case-control study structure present ACTUAL CASES students who matched in “highly selective specialty X” Red Bull consumption YES Red Bull consumption NO ACTUAL CONTROLS students who failed to match in “highly selective specialty X” time

Case control studies Determines the strength of the association between each predictor variable and the presence or absence of disease Cannot yield estimates of incidence or prevalence of disease in the population (why?) Odds Ratio is statistics

Case-control Study: pluses + Rare outcome/Long latent period + Inexpensive and efficient: may be only feasible option + Establishes association (Odds ratio) + Useful for generating hypotheses (multiple risk factors can be explored)

Case-control study-minuses Causality still difficult to establish Selection bias (appropriate controls) Recall bias: sampling (retrospective) Cannot tell about incidence or prevalence

Where are we? Preliminary results from our cross-sectional and case-control study suggest an association between Red Bull consumption and improved academic performance among medical students What’s missing? - strengthening evidence for a causal link between Red Bull consumption and academic performance Use results from our previous studies to apply for funding for a prospective cohort study!

Study design #3 Prospective cohort study of UCSF medical students Class of 2009 All entering medical students surveyed regarding consumption and variety of other potential covariates Survey updated annually to record changes in Red Bull consumption Outcomes: USMLE Step 1 score, USMLE Step 2 score, match in first choice residency

Cohort studies A cohort (follow-up, longitudinal) study is a comparative, observational study in which subjects are grouped by their exposure status, i.e., whether or not the subject was exposed to a suspected risk factor The subjects, exposed and unexposed to the risk factor, are followed forward in time to determine if one or more new outcomes (diseases) occur Subjects should not have outcome variable on entry The rates of disease incidence among the exposed and unexposed groups are determined and compared.

Study multiple outcomes in a cohort Study Exposed Not Exposed C B Develop Disease A Do not

Elements of a cohort study Selection of sample from population Measures predictor variables in sample Follow population for period of time Measure outcome variable Famous cohort studies Framingham Nurses’ Health Study Physicians’ Health Study Olmsted County, Minnesota

Prospective cohort study structure The present The future Top USMLE scorers Everyone else time

Strengths of cohort studies Know that predictor variable was present before outcome variable occurred (some evidence of causality) Directly measure incidence of a disease outcome Can study multiple outcomes of a single exposure (RR is measure of association)

Weaknesses of cohort studies Expensive and inefficient for studying rare outcomes Often need long follow-up period or a very large population Loss to follow-up can affect validity of findings

Other types of cohort studies Retrospective cohort Identification of cohort, measurement of predictor variables, follow-up and measurement of outcomes have all occurred in the past Much less costly than prospective cohorts Investigator has minimal control over study design

Other types of cohort studies Nested case-control study Case-control study embedded in a cohort study Controls are drawn randomly from study sample Case cohort Study

Hierarchy of Study Types Analytic Descriptive Case report Case series Survey Observational Cross sectional Ecologic Case-control Cohort studies Experimental Randomized controlled trials Field Trials Community Trials Strength of evidence for causality between a risk factor and outcome

What distinguishes observational studies from experiments? Ability to control for confounding Confounder Predictor Outcome Examples: sex (men are more likely to drink red bull and men are more likely to match in neurosurgery) Undergraduate institution (students from northwest school are more likely to drink red bull and also more likely to score higher on USMLE)

But we measured all of the potential confounders……. In a prospective cohort study you can (maybe) measure all potential known confounders, but… You can’t control for unmeasured confounders

Study design # 4 Randomized controlled trial of daily Red Bull consumption among entering UCSF medical students Class 2009 Randomized to daily consumption of Red Bull vs. daily consumption of placebo Outcomes: USMLE Step 1 score, USMLE Step 2 score, match in first choice residency

Randomized controlled trials Investigator controls the predictor variable (intervention or treatment) Major advantage over observational studies is ability to demonstrate causality Randomization controls unmeasured confounding Only for mature research questions

Basic Trial Design Treatment Dx No Dx Control Dx No Dx Placebo Population Treatment Dx No Dx Randomization Sample Control Dx No Dx Placebo For example, select persons with high LDL-cholesterol from among patients presenting to the metabolic clinic at the SFVA and treat with lovastatin to see if this results in lower LDL cholesterol. Note can have an uncontrolled trial or time series design. These have no concurrent control group and can produce the wrong answer due to learning, regression to the mean or secular trends. Note, for example, that it is common to have a 30-50% improvement in depression scores, pain scores, hot flash scores. Can have a controlled trial without randomization. This addresses learning, regression to the mean and secular trends, but introduces the issue of baseline differences in the groups. This design is really no different from a double cohort study. Can have a randomized controlled trial without placebo (blinding). This allows (as will be discussed later) for co-intervention and biases outcome ascertainment. Also note that these three elements - treatment, randomization and blinding result in the major ethical concerns regarding randomized trials.

Steps in a randomized controlled trial Select participants Measure baseline variables Randomize Eliminates baseline confounding Types (simple, stratified, block)

Steps in a randomized controlled trial Blinding the intervention As important as randomization Follow subjects Measure outcome Clinically important measures Adverse events

Comparing Cohort Studies with Randomized Trials Interventional Study Observational Study Study group Study group Random Allocation No Allocation Cannot randomize people to receive a putatively harmful substance, such as a suspected carcinogen, the “exposure” in most randomized trials is a treatment or preventive measure Critical to interpreting study findings In a nonrandomized study, when we observe an association of an exposure with a disease, we are left with uncertainty as to whether the association may be a result of the fact that people were NOT randomized to the exposure; Perhaps it is not the exposure, but rather the factors that led people to be exposed, that are associated with the disease. E.g., If an increased risk of a disease is found in workers at a certain factory, and if workers at this factory tend to live in a certain area, the increased risk of disease could result from an exposure associated with their place of residence rather than with their occupation or place of work. Group A Group B Group A Group B

Hierarchy of Study Types Analytic Descriptive Case report Case series Survey Observational Cross sectional Ecologic Case-control Cohort studies Experimental Randomized controlled trials Field Trials Community Trials Strength of evidence for causality between a risk factor and outcome

How to Write Methods & Material Section? Dr. Gholamreza Khalili Department of Epidemiology & Biostatistics School of public health Tehran University of Medical Sciences

Methods Allows reader to judge the quality of the work Identifies weaknesses Allows repetition of the study State the study design & specifications

Methods WWWWWH (who, what, where, why, when & how?) Define variables Patient/Participants inclusion Dates Randomisation/Placebo/Blindness Ethics/consent Treatments Outcomes and endpoints Statistical methods & power

Check list for Methods Study design mentioned? Who, what, where, why, how, when? Inclusion/exclusion criteria? logical & chronological order? Measurements defined? justified? detailed? referenced?

Check list for Methods Sample size justified? Transformations and statistical analyses clear? New techniques validated properly? Could the reader reproduce your study from the details provided?

Methods What subjects/patients/animals/specimens techniques were used? Reason for selecting the experimental design of the study. Statistical methods used for analysis The section should be called "Material and Methods” only if inanimate specimens have been used. (continue)

Methods Patient / Animals / Specimens Numbers How are they grouped Criteria Informed consent obtained

Techniques Give enough details for readers to assess the validity of the results, and repeat the study If standard techniques is used, give appropriate reference, any modifications should be clearly explained If drug trial, clear description of trial

CONSORT Statement CONSORT stands for Consolidated Standards of Reporting Trials. It is developed by the CONSORT Group to alleviate the problems arising from inadequate reporting of randomized controlled trials (RCTs). The website: http://www.consort-statement.org

Methods Study design Participants Ethical approval Sample size Questionnaires Interventions Clinical assessments Statistical methods

What to include in the methods section (1) How the study was designed: Keep the description brief Say how randomization was done Use names to identify parts of study sequence

What to include in the methods section (2) How the study was carried out: How the participants were recruited and chosen Give reasons for excluding participants Consider mentioning ethical features Give accurate details of materials used Give exact drug dosages Give exact form of treatments

What to include in the methods section (3) How the data were analysed: Use a P value to disprove the null hypothesis Give an estimate of power of the study Give the exact tests used for statistical analysis

How to Write Abstract Section? Dr. Gholamreza Khalili Department of Epidemiology & Biostatistics School of public health Tehran University of Medical Sciences

The Abstract The function of the abstract is to provide an overview of the paper. The overview should present the main story and a few essential details of the paper for readers who read only the abstract and should serve as both a clear preview and a clear, accurate recapitulation of the main story for readers who read the paper. Thus, the abstract should make sense both when read alone and when read with the paper .

Abstract Summarizes the major findings in the broad context of the work Consists of two or three sentences of topic introduction Selected results (not all but the most important) Concludes with implications of work

Abstracts The abstract should be neither vague and general on the one hand nor fussily detailed on the other. It should be specific and selective.

Abstracts the question that was asked, The abstract of a paper should state concisely: the question that was asked, what was done to answer the question, what was found that answers the question, and the answer to the question.

Abstracts Most journals limit the length of the abstract (usually to 250 words or less) “Uniform Requirements for Manuscripts Submitted to Biomedical Journals” For un-structured abstracts, limit the abstract to 150 words or less. If no limit is stated, make your abstract no longer than the abstracts in recent issues of the journal.

In summary: The abstract should provide an overview of the main story and a few essential -details. The abstract should be clear both to readers who read the paper and to readers who do not read the paper.

Abstract Writing Write the abstract as one paragraph. Use the techniques of continuity to make the paragraph flow. Use signals to indicate the parts of the abstract: Signal what you found by "We found that" or something similar.

Abstract Writing Signal the answer by "We conclude that" or "Thus" or something similar. Signal implications by "We suggest that" or something similar. The question and what was done can usually be written in one sentence in “the form "To determine X, we. ..." If the question and what was done are in separate sentences, use signals such as "We asked whether. .." (question) and "To answer this question, we. .." (what was done).

Abstract Writing Use present tense verbs for the question and the answer. Use past tense verbs to state what was done and what was found. Be careful not to omit the question, not to state the question vaguely, and not to state an implication instead of the answer .

Abstract Writing To ensure that the question is specific rather than vague, check the question against the answer: use the same key terms for the independent and dependent variables; keep the same point of view; and, to anticipate the answer , use the same verb in the question as in the answer . If you give a p value, also give data (for example, mean(SD) and the sample size (n).

Abstract Writing Write short sentences. Use simple words. Avoid jargon. Avoid abbreviations. Keep the abstract short. Omit less important information (experimental preparation, confirmatory results, comparisons with previous results, data for less important variables, definitions, background, implications).

Abstract Writing Omit details [unnecessary details of methods, exact data (give percent change), p values, "significantly"]. Avoid repetition (use a category term in what was done and name the variables in what was found; state "mean ::t SD" only once). Use active voice instead of passive voice.

Abstract Writing Omit unnecessary words (use "Thus" instead of "We conclude that"; use an adjective or an apostrophe instead of an "of' phrase: for example, "ductal rings" instead of "rings of ductus arteriosus," "rings' sensitivity" instead of "sensitivity of the rings"; but do not omit "a," "an," or "the" when they are necessary). Exceptions If the journal to which you are submitting a paper requests a different form for the abstract, follow the requested form.

Keywords Select terms that you would look up to find your own paper and that would attract the readers you hope to reach. Select current, specific terms, preferably medical subject headings (MeSH), that name important topics in your paper . Use phrases as well as single words. If the journal asks you to supply only terms that are not in the title of the paper, do so If necessary, include a term as an indexing term even if the term does not appear in your paper .

Check list for Abstract Background, methods, results, discussion? Key features mentioned? Anything that does not appear in full text? Results in words? Conclusion: justified? objective? Meaningful interpretation Follows the guidelines