Cross Sectional Red Bull
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Transcript of 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
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
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
Cross-sectional study: minuses
time
- Cannot determine causality
•ACE inhibitor use and hospitalization rates among those with heart failure
•Heart failure patients with a documented DNR status and mortality
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: 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.
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
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
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
A study type of every budget, purpose and research question