cross sectional red bull

Dr. Legiran, M.Kes

Types of Studies

Descriptive Studies Observational Analytic Studies

Cross Sectional studies Case Control studies Cohort studies

Experimental Studies Randomized controlled trials

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

Descriptive studies Descriptive studies are weak because they

make no attempt to link cause and effect and therefore no causal association can be determined

Descriptive studies however, are often the first step to a well designed epidemiological study

They allow the investigator to define a good hypothesis which can then be tested using a better design

Descriptive studies Getting a “lay of the land”

Surveys (NHIS, MCBS) “How many men in the U.S. filled Viagra

prescriptions in 2004?”

Describing a novel phenomena Case reports or case series

Viagra-associated serous macular detachment.

Sildenafil-associated nonarteritic anterior ischemic optic neuropathy.

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



Analytic




Research QuestionIs the regular consumption of Red Bull associated with improved academic

performance among U.S. medical students?

Rationale “functional drink” designed for periods of

mental and physical exertion. performance, concentration, memory,

reaction time, vigilance, and emotional balance

Taurine + glucuronolactone + caffeine

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

time

USMLE Score

Red Bull consumption

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? Univariate Multivariate (controlling for “confounders”)

Other cross-sectional surveys: AAMC California Health Interview Survey (NHIS, CHIS) National Health and Nutrition Exam Survey (NHANES)

Cross-sectional Study: Pluses

+ Prevalence (not incidence)

+ Fast/Inexpensive - no waiting!

+ No loss to follow up

+ Associations can be studied

Measures of associationDisease

Yes No

Risk Facto

r

Yes A B

No C D

Risk ratio (relative risk)

AA + B

CC + D

Cross-sectional study: minuses

time

- Cannot determine causality

USMLE Score

Red Bull consumption


time


•ACE inhibitor use and hospitalization rates among those with heart failure

•Heart failure patients with a documented DNR status and mortality



- 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: 4th year med students accepted to

residency in “highly selective specialty X”. Controls: 4th year 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)

Case-control study structure

time

TARGET CASESMedical students accepted to highly selective residencies

ACTUAL CASES4th year UCSF students who matched in “highly

selective specialty X”

TARGET CONTROLSAll unsuccessful applicants to highly

selective residency programs

ACTUAL CONTROLS4th year students who failed to match in “highly selective

specialty X”

Red Bull consumptionYES

Red Bull consumptionNO

present

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)- Caffeine and Pancreatic cancer in the GI clinic

- Recall bias: sampling (retrospective)- Abortion and risk of breast cancer in Sweden

- Cannot tell about incidence or prevalence- Studies of diagnostic tests:

- Sensitivity, specificity- Positive predictive value, negative predictive value

Measures of associationDisease

Yes No

TestYes A B

No C D

Sensitivity = A/A+C

Specificity = D/B+D

PPV = A/A+B

NPV = D/C+D

Case-control - “the house red” Rely tampons and toxic shock syndrome:

High rates of toxic shock syndrome in menstruating women Suspected OCPs or meds for PMS Cases: 180 women with TSS in 6 geographic areas Controls: 180 female friends of these patients and 180

females in the same telephone code Tampon associated with TSS (OR = 29!) Super absorbency associated with TSS (OR 1.34 per gm

increase in absorbency) Led to “RELY” brand tampons being taken off the market.

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 beverage 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• No new subjects allowed in after initial recruitment

• The rates of disease incidence among the exposed and unexposed groups are determined and compared.

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

time

The present The future

Top USMLE scorers

Everyone else

Prospective cohort study structure

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 HERS vs. WHI

Often need long follow-up period or a very large population CARDIA

Loss to follow-up can affect validity of findings Framingham

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

Double cohort Used to compare two separate cohorts with

different levels of exposure to predictor variable (e.g., occupational groups)

What type of study is this? Among individuals with coronary disease, what is the

association between baseline levels of B-type natriuretic peptide and subsequent risk of heart failure?

Among individuals presenting to heart failure clinic, what is the association between self-reported symptoms and risk of hospitalization for heart failure?

Using data from HERS (RCT of HRT in women with coronary disease): Determine the risk factors for developing incident heart

failure among women without heart failure at baseline. Determine whether HRT is associated with mortality

among women with heart failure. Determine genetic markers for development of heart

failure among black women in HERS.



Analytic




What distinguishes observational studies from experiments? Ability to control for confounding

Predictor Outcome

Confounder

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 onUSMLE)

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 unanticipated or 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

Population

Sample

Treatment Dx No Dx

Control Dx No DxPlacebo

Randomization

Steps in a randomized controlled trial1. Select participants

high-risk for outcome (high incidence) Likely to benefit and not be harmed Likely to adhere

2. Measure baseline variables3. Randomize

Eliminates baseline confounding Types (simple, stratified, block)

Steps in a randomized controlled trial4. Blinding the intervention

As important as randomization Eliminates

co intervention biased outcome ascertainment biased measurement of outcome

5. Follow subjects Adherence to protocol Lost to follow up

6. Measure outcome Clinically important measures Adverse events

What is Blinding? Single blind - participants are not

aware of treatment group Double blind - both participants

and investigators unaware Triple blind - various meanings

persons who perform tests outcome adjudicators safety monitoring group

Why blind?: Co interventions Unintended effective interventions

participants use other therapy or change behavior

study staff, medical providers, family or friends treat participants differently

Nondifferential - decreases power Differential - causes bias

Why blind?: Biased Outcome Ascertainment or adjudication

If group assignment is known participants may report symptoms or outcomes

differently physicians or investigators may elicit symptoms

or outcomes differently Study staff or adjudicators may classify similar

events differently in treatment groups

Problematic with “soft” outcomes investigator judgement participant reported symptoms, scales

Analysis of randomized controlled trial Analyzed like cohort study with RR Intention to treat analysis

Most conservative interpretation Include all persons assigned to

intervention group (including those who did not get treatment or dropped out)

Subgroup analysis Groups identified pre-randomization

High Quality Randomized Trials Tamper-proof randomization Blinding of participants, study

staff, lab staff, outcome ascertainment and adjudication

Adherence to study intervention and protocol

Complete follow-up



Analytic




A study type of every budget, purpose and research question

cross sectional red bull

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