observational study designs kirsten bibbins-domingo, phd, md associate professor of medicine and of...

Observational study designs

Kirsten Bibbins-Domingo PhD MDAssociate Professor of Medicine and of Epidemiology and BiostatisticsUniversity of California San Francisco

Objectives

To understand the difference between descriptive and analytic observational studies

To identify the strengths and weakness of different designs and apply different study designs to the same research question

To recognize types of study designs in the literature

Descriptive vs Analytic

Risk factors

Descriptive Questions

What proportion of patients in the GMC at SFGH have diabetes

What is the average age of patients with diabetes in the GMC at SFGH

Diabetes

Analytic QuestionsIs raceethnicity associated with diabetes among GMC patients

Is excessive consumption of sugar-sweetened beverages associated with diabetes among GMC patients

Analytic Studies Attempt to establish a causal link between

a predictorrisk factor and an outcome

You are doing an analytic study if you have any of the following words in your research question causes leads to compared with more likely

than associated with related to similar to correlated with greater than less than

Predictor(risk factor)

Outcome(disease)

Hierarchy of Study Types

DescriptivebullCase reportbullCase seriesbullSurvey

Analytic

ObservationalbullCross sectionalbullCase-controlbullCohort studies

ExperimentalbullRandomized controlled trials

Strength of evidence for causality between a risk factor and outcome

Measures of association

Disease

Yes No

Risk Facto

r

Yes A B

No C D

Risk ratio (relative risk)

AA + B

CC + D

Heart failure is a clinical syndrome

bull Heart unable to fill andor eject blood effectively

bull Results in chronic or episodic symptoms ndash Dyspnea fatigue

decreased functional capacity fluid overload

bull High rates of mortalityndash Sudden death or pump

failure

Research Question

Among patients seen in general medicine practice who

is at risk for heart failure

Great idea but how do you get startedhellip

Observations in clinical practice

Moving from descriptive to analytic studies

What is feasible

Study Design 1 Cross-sectional study

National Health and Nutrition Exam Survey (NHANES)

Outcome ldquohave you been told by a doctor that you have heart failurerdquo

Multiple possible predictors (demographic behavioral other CV risk factors)

Research question Is blood pressure elevation associated with heart failure risk

Cross-sectional study structure

time

Heart failure

Demographic factors (sex race SES)Behavioral (smoking alcohol drugs)

Biological factors (HTN Hx MI CKD DM)


Outcome(disease)

Cross-sectional Study Pluses

+ Prevalence

+ FastInexpensive - no waiting

+ No loss to follow up

+ Associations can be studied

Many well-known cross-sectional studies AAMC California Health Interview Survey (NHIS CHIS) National Hospital Discharge Survey

Cross-sectional study minuses

time

- Cannot determine causality

Heart failure

Chronic Kidney Disease


- Cannot study rare outcomes

- Cannot determine incidence

What if you are interested in the rare outcome

Heart failure in adults before age 50


Heart failure in children

ANSWER A Case-Control study

Study Design 2 A case-control study

Cases Adults with premature heart failure (18-50 years) General medicine vs cardiology UCSF vs community practice

Controls Adults 18-50 without heart failure Who are the appropriate controls

Potential predictors based on questionnaire demographic behavioral co-morbid risk factors

Research question Is blood pressure elevation early in adulthood associated with heart failure before age 50

Case control studies

Investigator works ldquobackwardrdquo (from outcome to predictor)

Sample chosen on the basis of outcome (cases) plus comparison group (controls)


Outcome(disease)

Case-control study structure

time

CASESAdults with

Heart failure that developsbefore age 50

CONTROLS

Adults (18-50) without heart failure

RISK FACTORS

DemographicBehavioralBiologicalGenetic

present


Cannot yield estimates of incidence or prevalence of disease in the population (why)

Odds Ratio is statistics


Disease

Yes No

Risk factor

Yes A B

No C D

Odds ratioA BCD

Alsohellip

A DC B

Case-control Study pluses

+ Rare outcomeLong 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

Case-control - ldquothe house redrdquo 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 134 per gm increase in absorbency)

Led to ldquoRELYrdquo brand tampons being taken off the market

Where are we

Preliminary results from our cross-sectional and case-control study suggest that black race hypertension and chronic kidney disease are associated with premature heart failure

Whatrsquos missing - strengthening evidence for a causal link between risk factors and heart failure

Use results from our previous studies to apply for funding for a prospective cohort study

Study design 3 Prospective cohort study

CARDIA study Prospective cohort study 5000 (MW blackwhite lowhigh SES) Age 18-30 at enrollment Followed 20 years Exam visits years 0 2 5 7 10 15 20

Outcome Incident heart failure

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 Nursesrsquo Health Study Physiciansrsquo Health Study Olmsted County Minnesota


Outcome(disease)

time

The present The future

Premature heart failure

Everyone else

Prospective cohort study structure

Incidence of heart failure before age 50 in black and white adults

Hypertension early in life is a risk factor for heart failure before age 50 among blacks

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

Studies of Medical Tests

Causality often irrelevant Not enough to show that test result

is associated with disease status or outcome

Need to estimate parameters (eg sensitivity and specificity) describing test performance

Although if it isnrsquot you can stop

Studies of Diagnostic Test Accuracy for Prevalent Disease

Predictor = Test ResultOutcome = Disease status as

determined by Gold Standard

Designs

bullCase-control (sample separately from disease positive and disease negative groups)

bullCross-sectional (sample from the whole population of interest)

bullDouble-cohort-like sampling (sample separately from test-positive and test-negative groups)

Studies of Dx Tests

Importance of Sampling Scheme

If sampling separately from Disease+ and Diseasendash groups (case-control sampling) cannot calculate prevalence positive predictive value or negative predictive value

Dx Test Case-Control Sampling

Disease +Sampled

Separately

Disease ndashSampled

Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease

Sensitivity = a(a + c) Specificity = d(b + d)

Dx Test Cross-sectional Sampling

PPV = a(a + b)

NPV = d(c + d)

Prevalence = (a + c)N

Disease + Disease - Total

Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives

Total a + cTotal With

Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N

Studies of Prognostic Tests for Incident Outcomes

Predictor = Test ResultDevelopment of outcome or time to

development of outcome

Design Cohort study



Analytic




A study type of every budget purpose and research question

NAME THAT STUDY DESIGN

Abstracts from the New England Journal of Medicine

Plasma Natriuretic Peptide Levels and the Risk of Cardiovascular Events and Death

Thomas J Wang MD Martin G Larson ScD Daniel Levy MD Emelia J Benjamin MD Eric P Leip MS Torbjorn Omland MD Philip A Wolf MD and Ramachandran S Vasan

MDBackground The natriuretic peptides are counterregulatory hormones involved in volume homeostasis and

cardiovascular remodeling The prognostic significance of plasma natriuretic peptide levels in apparently asymptomatic persons has not been established

Methods We prospectively studied 3346 persons without heart failure Using proportional-hazards regression we examined the relations of plasma B-type natriuretic peptide and N-terminal prondashatrial natriuretic peptide to the risk of death from any cause a first major cardiovascular event heart failure atrial fibrillation stroke or transient ischemic attack and coronary heart disease

Results During a mean follow-up of 52 years 119 participants died and 79 had a first cardiovascular event After adjustment for cardiovascular risk factors each increment of 1 SD in log B-type natriuretic peptide levels was associated with a 27 percent increase in the risk of death (P=0009) a 28 percent increase in the risk of a first cardiovascular event (P=003) a 77 percent increase in the risk of heart failure (Plt0001) a 66 percent

increase in the risk of atrial fibrillation (Plt0001) and a 53 percent increase in the risk of stroke or transient ischemic attack (P=0002) Peptide levels were not significantly associated with the risk of coronary heart disease events B-type natriuretic peptide values above the 80th percentile (200 pg per milliliter for men and 233 pg per milliliter for women) were associated with multivariable-adjusted hazard ratios of 162 for death

(P=002) 176 for a first major cardiovascular event (P=003) 191 for atrial fibrillation (P=002) 199 for stroke or transient ischemic attack (P=002) and 307 for heart failure (P=0002) Similar results were obtained for N-terminal prondashatrial natriuretic peptide

Conclusions In this community-based sample plasma natriuretic peptide levels predicted the risk of death and cardiovascular events after adjustment for traditional risk factors Excess risk was apparent at natriuretic peptide levels well below current thresholds used to diagnose heart failure N Eng J Med 2004 350655-663

Needlestick Injuries among Surgeons in TrainingMartin A Makary MD MPH Ali Al-Attar MD PhD Christine G Holzmueller BA J

Bryan Sexton PhD Dora Syin BS Marta M Gilson PhD Mark S Sulkowski MD and Peter J Pronovost MD PhD

Background Surgeons in training are at high risk for needlestick injuries The reporting of such injuries is a critical step in initiating early prophylaxis or treatment Methods We surveyed surgeons in training at 17 medical centers about previous needlestick injuries Survey items inquired about whether the most recent injury was reported to an employee health service or involved a high-risk patient (ie one with a history of infection with human immunodeficiency virus hepatitis B or hepatitis C or injection-drug use) we also asked about the perceived cause of the injury and the surrounding circumstances

Results The overall response rate was 95 Of 699 respondents 582 (83) had had a needlestick injury during training the mean number of needlestick injuries during residency increased according to the postgraduate year (PGY) PGY-1 15 injuries PGY-2 37 PGY-3 41 PGY-4 53 and PGY-5 77 By their final year of training 99 of residents had had a needlestick injury for 53 the injury had involved a high-risk patient Of the most recent injuries 297 of 578 (51) were not reported to an employee health service and 15 of 91 of those involving high-risk patients (16) were not reported Lack of time was the most common reason given for not reporting such injuries among 126 of 297 respondents (42) If someone other than the respondent knew about an unreported injury that person was most frequently the attending physician (51) and least frequently a significant other (13)

Conclusions Needlestick injuries are common among surgeons in training and are often not reported Improved prevention and reporting strategies are needed to increase occupational safety for surgical providers (N Eng J Med 2007 3562693-2699)

First-Trimester Use of Selective Serotonin-Reuptake Inhibitors and the Risk of Birth Defects

Carol Louik ScD Angela E Lin MD Martha M Werler ScD Sonia Hernaacutendez-Diacuteaz MD ScD and Allen A Mitchell MD

Background The risk of birth defects after antenatal exposure to selective serotonin-reuptake inhibitors (SSRIs) remains controversial

Methods We assessed associations between first-trimester maternal use of SSRIs and the risk of birth defects among 9849 infants with and 5860 infants without birth defects participating in the Slone Epidemiology Center Birth Defects Study

Results In analyses of defects previously associated with SSRI use (involving 42 comparisons) overall use of SSRIs was not associated with significantly increased risks of craniosynostosis (115 subjects 2 exposed to SSRIs odds ratio 08 95 confidence interval [CI] 02 to 35) omphalocele (127 subjects 3 exposed odds ratio 14 95 CI 04 to 45) or heart defects overall (3724 subjects 100 exposed odds ratio 12 95 CI 09 to 16) Analyses of the associations between individual SSRIs and specific defects showed significant associations between the use of sertraline and omphalocele (odds ratio 57 95 CI 16 to 207 3 exposed subjects) and septal defects (odds ratio 20 95 CI 12 to 40 13 exposed subjects) and between the use of paroxetine and right ventricular outflow tract obstruction defects (odds ratio 33 95 CI 13 to 88 6 exposed subjects) The risks were not appreciably or significantly increased for other defects or other SSRIs or non-SSRI antidepressants Exploratory analyses involving 66 comparisons showed possible associations of paroxetine and sertraline with other specific defects

Conclusions Our findings do not show that there are significantly increased risks of craniosynostosis omphalocele or heart defects associated with SSRI use overall They suggest that individual SSRIs may confer increased risks for some specific defects but it should be recognized that the specific defects implicated are rare and the absolute risks are small (N Eng J Med 20073562675-83)

THE ROLE OF BLACK AND HISPANIC PHYSICIANS IN PROVIDING HEALTH CARE FOR UNDERSERVED POPULATIONS

MIRIAM KOMAROMY MD KEVIN GRUMBACH MD MICHAEL DRAKE MD KAREN VRANIZAN MA NICOLE LURIE MD MSPH DENNIS KEANE MPH AND ANDREW B BINDMAN MD

Background Patients who are members of minority groups may be more likely than others to consult physicians of the same race or ethnic group but little is known about the relation between patientsrsquo race or ethnic group and the supply of physicians or the likelihood that minority-group physicians will care for poor or black and Hispanic patients

Methods We analyzed data on physiciansrsquo practice locations and the racial and ethnic makeup and socioeconomic status of communities in California in 1990 We also surveyed 718 primary care physicians from 51 California communities in 1993 to examine the relation between the physiciansrsquo race or ethnic group and the characteristics of the patients they served

Results Communities with high proportions of black and Hispanic residents were four times as likely as others to have a shortage of physicians regardless of community income Black physicians practiced in areas where the percentage of black residents was nearly five times as high on average as in areas where other physicians practiced Hispanic physicians practiced in areas where the percentage of Hispanic residents was twice as high as in areas where other physicians practiced After we controlled for the racial and ethnic makeup of the community black physicians cared for significantly more black patients (absolute difference 25 percentage points P lt0001) and Hispanic physicians for significantly more Hispanic patients (absolute difference 21 percentage points Plt0001) than did other physicians Black physicians cared for more patients covered by Medicaid (Plt0001) and Hispanic physicians for more uninsured patients (P=003) than did other physicians

ConclusionsBlack and Hispanic physicians have a unique and important role in caring for poor black and Hispanic patients in California Dismantling affirmative action programs as is currently proposed may threaten health care for both poor people and members of minoritygroups (N Engl J Med 19963341305-10)

Effect of Cigar Smoking on the Risk of Cardiovascular Disease Chronic Obstructive Pulmonary Disease and Cancer in Men

Carlos Iribarren MD MPH PhD Irene S Tekawa MA Stephen Sidney MD MPH and Gary D Friedman MD

Background The sale of cigars in the United States has been increasing since 1993 Cigar smoking is a known risk factor for certain cancers and for chronic obstructive pulmonary disease (COPD) However unlike the relation between cigarette smoking and cardiovascular disease the association between cigar smoking and cardiovascular disease has not been clearly established

Methods We performed a cohort study among 17774 men 30 to 85 years of age at base line (from 1964 through 1973) who were enrolled in the Kaiser Permanente health plan and who reported that they had never smoked cigarettes and did not currently smoke a pipe Those who smoked cigars (1546 men) and those who did not (16228) were followed from 1971 through the end of 1995 for a first hospitalization for or death from a major cardiovascular disease or COPD and through the end of 1996 for a diagnosis of cancer

Results In multivariate analyses cigar smokers as compared with nonsmokers were at higher risk for coronary heart disease (relative risk 127 95 percent confidence interval 112 to 145) COPD (relative risk 145 95 percent confidence interval 110 to 191) and cancers of the upper aerodigestive tract

(relative risk 202 95 percent confidence interval 101 to 406) and lung (relative risk 214 95 percent confidence interval 112 to 411) with evidence of dosendashresponse effects There appeared to be a synergistic relation between cigar smoking and alcohol consumption with respect to the risk of oropharyngeal cancers and cancers of the upper aerodigestive tract

Conclusions Independently of other risk factors regular cigar smoking can increase the risk of coronary heart disease COPD and cancers of the upper aerodigestive tract and lung (N Eng J Med 1999 3401773-1780)

CLINICAL AND NEURORADIOGRAPHIC MANIFESTATIONS OF EASTERN EQUINE ENCEPHALITIS

ROBERT L DERESIEWICZ MD SCOTT J THALER MD LIANGGE HSU MD AND AMIR A ZAMANI MD

Background Eastern equine encephalitis occurs principally along the east and Gulf coasts of the United States Recognition of the neuroradiographic manifestations of eastern equine encephalitis could hasten the diagnosis of the illness and speed the response to index cases

Methods We reviewed all cases of eastern equine encephalitis reported in the United States between 1988 and 1994 The records of 36 patients were studied along with 57 computed tomographic (CT) scans and 23 magnetic resonance imaging (MRI) scan from 33 patients

Results The mortality rate was 36 percent and 35 percent of the survivors were moderately or severely disabled Neuroradiographic abnormalities were common and best visualized by MRI Among the patients for whom MRI scans were available the results were abnormal for all eight comatose patients as well as for all three noncomatose patients who subsequently became comatose The CT results were abnormal in 21 of 32 patients with readable scans The abnormal findings included focal lesions in the basal ganglia (found in 71 percent of patients on MRI and in 56 percent on CT) thalami (found in 71 percent on MRI and in 25 percent on CT) and brain stem (found in 43 percent on MRI and in 9 percent on CT) Cortical lesions meningeal enhancement and periventricular white-matter changes were less common The presence of large radiographic lesions did not predict a poor outcome but either high cerebrospinal fluid white-cell counts or severe hyponatremia did

Conclusions Eastern equine encephalitis produces focal radiographic signs The characteristic early involvement of the basal ganglia and thalami distinguishes this illness from herpes simplex encephalitis MRI is a sensitive technique to identify the characteristic early radiographic manifestations of this viral encephalitis (N Engl J Med 19973361867-74)

Helicobacter pylori Infection and Gastric LymphomaJulie Parsonnet Svein Hansen Larissa Rodriguez Arnold B Gelb Roger A Warnke Egil

Jellum Norman Orentreich Joseph H Vogelman and Gary D Friedman

Background Helicobacter pylori infection is a risk factor for gastric adenocarcinoma We examined whether this infection is also a risk factor for primary gastric non-Hodgkins lymphoma

Methods This __________________________ involved two large cohorts (230593 participants) Serum had been collected from cohort members and stored and all subjects were followed for cancer Thirty-three patients with gastric non-Hodgkins lymphoma were identified and each was matched to four controls according to cohort age sex and date of serum collection For comparison 31 patients with nongastric non-Hodgkins lymphoma from one of the cohorts were evaluated each of whom had been previously matched to 2 controls Pathological reports and specimens were reviewed to confirm the histologic type of the tumor Serum samples from all subjects were tested for H pylori IgG by an

enzyme-linked immunosorbent assay

Results Thirty-three cases of gastric non-Hodgkins lymphoma occurred a median of 14 years after serum collection Patients with gastric lymphoma were significantly more likely than matched controls to have evidence of previous H pylori infection (matched odds ratio 63 95 percent confidence interval 20 to 199) The results were similar in both cohorts Among the 31 patients with nongastric lymphoma a median of six years had elapsed between serum collection and the development of disease No

association was found between nongastric non-Hodgkins lymphoma and previous H pylori infection (matched odds ratio 12 95 percent confidence interval 05 to 30)

Conclusions Non-Hodgkins lymphoma affecting the stomach but not other sites is associated with previous H pylori infection A causative role for the organism is plausible but remains unproved (N Eng J Med 1994 3301267-1271)

Adherence to a Mediterranean Diet and Survival in a Greek Population

Antonia Trichopoulou MD Tina Costacou PhD Christina Bamia PhD and Dimitrios Trichopoulos MD

Background Adherence to a Mediterranean diet may improve longevity but relevant data are limited

Methods We conducted a _______________________________ involving 22043 adults in Greece who completed an extensive validated food-frequency questionnaire at base line Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean-diet scale that incorporated the salient characteristics of this diet (range of scores 0 to 9 with higher scores indicating greater adherence) We used proportional-hazards regression to assess the relation between adherence to the Mediterranean diet and total mortality as well as mortality due to coronary heart disease and mortality due to cancer with adjustment for age sex body-mass index physical-activity level and other potential confounders

Results During a median of 44 months of follow-up there were 275 deaths A higher degree of adherence to the Mediterranean diet was associated with a reduction in total mortality (adjusted

hazard ratio for death associated with a two-point increment in the Mediterranean-diet score 075 [95 percent confidence interval 064 to 087]) An inverse association with greater adherence to this diet was evident for both death due to coronary heart disease (adjusted hazard ratio 067 [95 percent confidence interval 047 to 094]) and death due to cancer (adjusted hazard ratio 076 [95 percent confidence interval 059 to 098]) Associations between individual food groups contributing to the Mediterranean-diet score and total mortality were generally not significant

Conclusions Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in total mortality (N Eng J Med 2003 3482599-2608)

WHAT CAN YOU LEARN FROM OBSERVATIONAL STUDIES

Spironolactone and heart failure

Spironolactone for heart failure

bull Patients with chronic heart failure have a high degree of morbidity and mortality

bull Spironolactone ndash an aldosterone antagonist is associated may improve survival

bull Significant side-effects including hyperkalemia

The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure Bertram Pitt MD Faiez Zannad MD Willem J Remme MD Robert

Cody MD Alain Castaigne MD Alfonso Perez MD Jolie Palensky MS Janet Wittes PhD for The Randomized Aldactone Evaluation Study Investigators (N Engl J Med 1999341709-17)

Background and Methods Aldosterone is important in the pathophysiology of heart failure In a double-blind study we enrolled 1663 patients who had severe heart failure and a left ventricular ejection fraction of no more than 35 percent and who were being treated with an angiotensin-convertingndashenzyme inhibitor a loop diuretic and in most cases digoxin A total of 822 patients were randomly assigned to receive 25 mg of spironolactone daily and 841 to receive placebo The primary end point was death from all causes

Results The trial was discontinued early after a mean follow-up period of 24 months because an interim analysis determined that spironolactone was efficacious There were 386 deaths in the placebo group (46 percent) and 284 in the spironolactone group (35 percent relative risk of death 070 95 percent confidence interval 060 to 082 Plt0001) This 30 percent reduction in the risk of death among patients in the spironolactone group was attributed to a lower risk of both death from progressive heart failure and sudden death from cardiac causes The frequency of hospitalization for worsening heart failure was 35 percent

lower in the spironolactone group than in the placebo group (relative risk of hospitalization 065 95 percent confidence interval 054 to 077 Plt0001) In addition patients who received spironolactone had a significant improvement in the symptoms of heart failure as assessed on the basis of the New York Heart Association functional class (Plt0001) Gynecomastia or breast pain was reported in 10 percent of men who were treated with spironolactone as compared with 1 percent of men in the placebo group (Plt0001) The incidence of serious hyperkalemia was minimal in both groups of patients

Conclusions Blockade of aldosterone receptors by spironolactone in addition to standard therapy substantially reduces the risk of both morbidity and death among patients with severe heart failure

Research questions

Among heart failure patients in clinical practice

1 Is spironolactone associated with lower mortality

2 What characteristics are associated with monitoring for hyperkalemia after initiation of spironolactone

3 Is spironolactone use associated with hyperkalemia

4 What characteristics are associated with receiving spironolactone

Usefulness of spironolactone in a specialized heart failure clinic Sligl W et al Am J Cardiol 2004 Aug 1594(4)443-7

Several case series published after the when prescribed to participants not in a trial and the appropriateness Randomized Aldactone Evaluation Study (RALES) have focused on the adverse effects of spironolactone of these prescribing practices however there is a paucity of data on potential benefits in patients not in a trial

Therefore we examined data from a prospective cohort study of 1037 patients with heart failure seen at the University of Alberta Heart Function Clinic

Median age was 69 years 66 were men 75 had systolic dysfunction and mean ejection fraction was 33 Only 40 of the 136 patients prescribed spironolactone had New York Heart Association class III or IV symptoms and lt25 fulfilled all of the RALES eligibility criteria Mean daily dose of spironolactone was 239 mg 25 of patients had spironolactone withdrawn after initiation mostly due to increases in potassium andor creatinine (9) gynecomastia (5) or dehydrationhyponatremia (6) Only 1 of our spironolactone-treated patients developed serum potassium gt6 mmolL Coxs proportional hazards analysis confirmed the association between use of spironolactone and increased survival rate (relative risk 009 95 confidence interval 002 to 039) even though 78 of our patients did not fulfill the RALES eligibility criteria

Thus although the complication rate was higher the benefits of spironolactone seen in RALES extended to participants not in a trial who were treated with similar doses and followed closely in a clinic specializing in heart failure

Laboratory evaluation of potassium and creatinine among ambulatory patients prescribed spironolactone are we monitoring for hyperkalemia

Raebel MA et al Ann Pharmacother 2007 Feb41(2)193-200

BACKGROUND Serum potassium and creatinine evaluation is recommended in patients prescribed spironolactone yet the proportion of ambulatory patients chronically dispensed spironolactone receiving evaluation is not well understood

OBJECTIVE To estimate the rate of potassium and creatinine evaluation and identify factors associated with conducting these tests among ambulatory patients dispensed spironolactone

METHODS A retrospective cohort study was designed to evaluate patients at 10 health maintenance organizations with ongoing spironolactone dispensing for one year (N = 2257) Potassium and creatinine evaluation were determined from administrative data Associations between patient characteristics and laboratory testing were assessed using logistic regression modeling

RESULTS Serum creatinine and potassium were evaluated in 723 of patients during a 13 month period The likelihood of potassium and creatinine monitoring was greater among patients who were older (OR 128 95 CI 117 to 141 per decade of life) male (OR 125 95 CI 101 to 154) had diabetes (OR 163 95 CI 131 to 203) received concomitant therapy with angiotensin-converting enzyme inhibitorsangiotensin receptor blockers (OR 223 95 CI 174 to 287) potassium supplements (OR 196 95 CI 151 to 254) or digoxin (OR 210 95 CI 148 to 298) or had more outpatient visits (OR 131 95 CI 119 to 144) Among patients with heart failure (n = 790) factors associated with the incidence of laboratory testing were diabetes (OR 164 95 CI 114 to 234) outpatient visits (OR 120 95 CI 102 to 141) and digoxin therapy (OR 226 95 CI 138 to 369)

CONCLUSIONS Three-fourths of ambulatory patients dispensed spironolactone receive recommended laboratory evaluation with monitoring more likely to be completed in patients prescribed concomitant therapy with drugs that increase hyperkalemia risk older patients and those with diabetes

Clinical factors associated with hyperkalemia in patients with congestive heart failure F H Ramadan MD et al

Journal of Clinical Pharmacy and Therapeutics Volume 30 Issue 3 Pages 233 - 239

Objective To identify clinical factors associated with hyperkalemia on initial presentation in patients hospitalized for CHF

Design A casendashcontrol study

Setting Two university-affiliated tertiary-care hospitals

Subjects Using ICD-9 code for CHF CHF admissions with hyperkalemia on presentation (cases) were identified from a population of 938 non-dialysis-dependent CHF patients CHF admissions with normokalemia on presentation were used as controls Hyperkalemia was defined as serum K ge 5middot6 mmolL and normokalemia as serum K ge 3middot5 and le5middot5

Methods Data were collected on demographic characteristics clinical variables comorbidity and medication use Factors associated with hyperkalemia on initial presentation were examined

Results Mean age did not differ between cases [76 years standard deviation (SD) = 12] and controls (75 years SD = 12) (P = 0middot824) Mean potassium levels for cases and controls were 6middot2 mmolL (range 5middot6 to 8middot2) and 4middot3 mmolL respectively (P lt 0middot001) On multivariate analysis diabetes mellitus [odds ratio (OR) = 2middot42 95 confidence interval (CI) = 1middot04ndash5middot59] creatinine clearance lt40 mLmin (OR = 8middot36 CI = 2middot73ndash25middot56) use of spironolactone (OR = 4middot18 CI = 1middot27ndash13middot79) and use of ACE inhibitors (OR = 2middot55 CI = 1middot06ndash6middot13) were independently associated with hyperkalemia

Conclusions In CHF patients hyperkalemia on presentation is independently associated with diabetes creatinine clearance lt40 mLmin use of spironolactone and use of ACE inhibitors Recommendations for use of spironolactone and ACE inhibitors in CHF and the intensity of serum K monitoring need to be clarified to account for patients at higher risk for hyperkalemia

Adoption of spironolactone therapy for older patients with heart failure and left ventricular systolic dysfunction in the United States 1998-2001 Masoudi FA et al Circulation 2005

Jul 5112(1)39-47

BACKGROUND Concerns have been raised about the appropriateness of spironolactone use in some patients with heart failure We studied the adoption of spironolactone therapy after publication of the Randomized Aldactone Evaluation Study (RALES) in national cohorts of older patients hospitalized for heart failure

METHODS AND RESULTS This is a study of serial cross-sectional samples of Medicare beneficiaries gt or =65 years old discharged after hospitalization for the primary diagnosis of heart failure and with left ventricular systolic dysfunction The first sample was discharged before (April 1998 to March 1999 n=9758) and the second sample after (July 2000 to June 2001 n=9468) publication of RALES in September 1999 We assessed spironolactone prescriptions at hospital discharge in patient groups defined by enrollment criteria for the trial Using multivariable logistic regression we identified factors independently associated with prescriptions not meeting these criteria Spironolactone use increased gt7-fold (30 to 213 Plt00001) after RALES Of patients meeting enrollment criteria 241 received spironolactone as compared with 174 of those not meeting the criteria Of all prescriptions after RALES 309 were provided to patients not meeting enrollment criteria Spironolactone was prescribed to 228 of patients with a serum potassium value gt or =50 mmolL to 141 with a serum creatinine value gt or =25 mgdL and to 173 with severe renal dysfunction (estimated glomerular filtration rate lt30 mLmin(-1)173 m(-2)) In multivariable analyses factors associated with prescriptions not meeting enrollment criteria included advanced age noncardiovascular comorbidities discharge to skilled nursing facilities and care provided by physicians without board certification

CONCLUSIONS Spironolactone prescriptions increased markedly after the publication of RALES and many treated patients were at risk for hyperkalemia Simultaneously many patients who might have benefited were not treated These findings demonstrate the importance of balancing efforts to enhance use among appropriate patients and minimizing use in patients at risk for adverse events


Plasma Natriuretic Peptide Levels and the Risk of Cardiovascular Events and Death Thomas J Wang MD Martin G Larson ScD Daniel Levy MD Emelia J Benjamin MD Eric P Leip MS Torbjorn Omland MD Philip A Wolf MD and Ramachandran S Vasan MD

Needlestick Injuries among Surgeons in Training Martin A Makary MD MPH Ali Al-Attar MD PhD Christine G Holzmueller BA J Bryan Sexton PhD Dora Syin BS Marta M Gilson PhD Mark S Sulkowski MD and Peter J Pronovost MD PhD

First-Trimester Use of Selective Serotonin-Reuptake Inhibitors and the Risk of Birth Defects Carol Louik ScD Angela E Lin MD Martha M Werler ScD Sonia Hernaacutendez-Diacuteaz MD ScD and Allen A Mitchell MD

THE ROLE OF BLACK AND HISPANIC PHYSICIANS IN PROVIDING HEALTH CARE FOR UNDERSERVED POPULATIONS MIRIAM KOMAROMY MD KEVIN GRUMBACH MD MICHAEL DRAKE MD KAREN VRANIZAN MA NICOLE LURIE MD MSPH DENNIS KEANE MPH AND ANDREW B BINDMAN MD

Effect of Cigar Smoking on the Risk of Cardiovascular Disease Chronic Obstructive Pulmonary Disease and Cancer in Men Carlos Iribarren MD MPH PhD Irene S Tekawa MA Stephen Sidney MD MPH and Gary D Friedman MD

CLINICAL AND NEURORADIOGRAPHIC MANIFESTATIONS OF EASTERN EQUINE ENCEPHALITIS ROBERT L DERESIEWICZ MD SCOTT J THALER MD LIANGGE HSU MD AND AMIR A ZAMANI MD

Helicobacter pylori Infection and Gastric Lymphoma Julie Parsonnet Svein Hansen Larissa Rodriguez Arnold B Gelb Roger A Warnke Egil Jellum Norman Orentreich Joseph H Vogelman and Gary D Friedman

Adherence to a Mediterranean Diet and Survival in a Greek Population Antonia Trichopoulou MD Tina Costacou PhD Christina Bamia PhD and Dimitrios Trichopoulos MD

Slide 49

What can you learn from observational studies


The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure Bertram Pitt MD Faiez Zannad MD Willem J Remme MD Robert Cody MD Alain Castaigne MD Alfonso Perez MD Jolie Palensky MS Janet Wittes PhD for The Randomized Aldactone Evaluation Study Investigators (N Engl J Med 1999341709-17)

Research questions


Laboratory evaluation of potassium and creatinine among ambulatory patients prescribed spironolactone are we monitoring for hyperkalemia Raebel MA et al Ann Pharmacother 2007 Feb41(2)193-200

Clinical factors associated with hyperkalemia in patients with congestive heart failure F H Ramadan MD et al Journal of Clinical Pharmacy and Therapeutics Volume 30 Issue 3 Pages 233 - 239

Adoption of spironolactone therapy for older patients with heart failure and left ventricular systolic dysfunction in the United States 1998-2001 Masoudi FA et al Circulation 2005 Jul 5112(1)39-47

Objectives

To understand the difference between descriptive and analytic observational studies

To identify the strengths and weakness of different designs and apply different study designs to the same research question

To recognize types of study designs in the literature


Risk factors




Diabetes








Outcome(disease)



Analytic





Disease

Yes No

Risk Facto

r

Yes A B

No C D


AA + B

CC + D






failure

Research Question






What is feasible







time

Heart failure




Outcome(disease)


+ Prevalence






time


Heart failure



















Outcome(disease)


time

CASESAdults with


CONTROLS


RISK FACTORS


present





Disease

Yes No

Risk factor

Yes A B

No C D

Odds ratioA BCD

Alsohellip

A DC B



















Where are we











Outcome(disease)

time



Everyone else
















design









Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions






Risk factors




Diabetes








Outcome(disease)



Analytic





Disease

Yes No

Risk Facto

r

Yes A B

No C D


AA + B

CC + D






failure

Research Question






What is feasible







time

Heart failure




Outcome(disease)


+ Prevalence






time


Heart failure



















Outcome(disease)


time

CASESAdults with


CONTROLS


RISK FACTORS


present





Disease

Yes No

Risk factor

Yes A B

No C D

Odds ratioA BCD

Alsohellip

A DC B



















Where are we











Outcome(disease)

time



Everyone else
















design









Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions










Outcome(disease)



Analytic





Disease

Yes No

Risk Facto

r

Yes A B

No C D


AA + B

CC + D






failure

Research Question






What is feasible







time

Heart failure




Outcome(disease)


+ Prevalence






time


Heart failure



















Outcome(disease)


time

CASESAdults with


CONTROLS


RISK FACTORS


present





Disease

Yes No

Risk factor

Yes A B

No C D

Odds ratioA BCD

Alsohellip

A DC B



















Where are we











Outcome(disease)

time



Everyone else
















design









Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions







Analytic





Disease

Yes No

Risk Facto

r

Yes A B

No C D


AA + B

CC + D






failure

Research Question






What is feasible







time

Heart failure




Outcome(disease)


+ Prevalence






time


Heart failure



















Outcome(disease)


time

CASESAdults with


CONTROLS


RISK FACTORS


present





Disease

Yes No

Risk factor

Yes A B

No C D

Odds ratioA BCD

Alsohellip

A DC B



















Where are we











Outcome(disease)

time



Everyone else
















design









Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions






Disease

Yes No

Risk Facto

r

Yes A B

No C D


AA + B

CC + D






failure

Research Question






What is feasible







time

Heart failure




Outcome(disease)


+ Prevalence






time


Heart failure



















Outcome(disease)


time

CASESAdults with


CONTROLS


RISK FACTORS


present





Disease

Yes No

Risk factor

Yes A B

No C D

Odds ratioA BCD

Alsohellip

A DC B



















Where are we











Outcome(disease)

time



Everyone else
















design









Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions










failure

Research Question






What is feasible







time

Heart failure




Outcome(disease)


+ Prevalence






time


Heart failure



















Outcome(disease)


time

CASESAdults with


CONTROLS


RISK FACTORS


present





Disease

Yes No

Risk factor

Yes A B

No C D

Odds ratioA BCD

Alsohellip

A DC B



















Where are we











Outcome(disease)

time



Everyone else
















design









Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions





Research Question






What is feasible







time

Heart failure




Outcome(disease)


+ Prevalence






time


Heart failure



















Outcome(disease)


time

CASESAdults with


CONTROLS


RISK FACTORS


present





Disease

Yes No

Risk factor

Yes A B

No C D

Odds ratioA BCD

Alsohellip

A DC B



















Where are we











Outcome(disease)

time



Everyone else
















design









Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions








What is feasible







time

Heart failure




Outcome(disease)


+ Prevalence






time


Heart failure



















Outcome(disease)


time

CASESAdults with


CONTROLS


RISK FACTORS


present





Disease

Yes No

Risk factor

Yes A B

No C D

Odds ratioA BCD

Alsohellip

A DC B



















Where are we











Outcome(disease)

time



Everyone else
















design









Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions











time

Heart failure




Outcome(disease)


+ Prevalence






time


Heart failure



















Outcome(disease)


time

CASESAdults with


CONTROLS


RISK FACTORS


present





Disease

Yes No

Risk factor

Yes A B

No C D

Odds ratioA BCD

Alsohellip

A DC B



















Where are we











Outcome(disease)

time



Everyone else
















design









Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions






+ Prevalence






time


Heart failure



















Outcome(disease)


time

CASESAdults with


CONTROLS


RISK FACTORS


present





Disease

Yes No

Risk factor

Yes A B

No C D

Odds ratioA BCD

Alsohellip

A DC B



















Where are we











Outcome(disease)

time



Everyone else
















design









Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions






time


Heart failure



















Outcome(disease)


time

CASESAdults with


CONTROLS


RISK FACTORS


present





Disease

Yes No

Risk factor

Yes A B

No C D

Odds ratioA BCD

Alsohellip

A DC B



















Where are we











Outcome(disease)

time



Everyone else
















design









Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions






















Outcome(disease)


time

CASESAdults with


CONTROLS


RISK FACTORS


present





Disease

Yes No

Risk factor

Yes A B

No C D

Odds ratioA BCD

Alsohellip

A DC B



















Where are we











Outcome(disease)

time



Everyone else
















design









Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions






time

CASESAdults with


CONTROLS


RISK FACTORS


present





Disease

Yes No

Risk factor

Yes A B

No C D

Odds ratioA BCD

Alsohellip

A DC B



















Where are we











Outcome(disease)

time



Everyone else
















design









Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions









Disease

Yes No

Risk factor

Yes A B

No C D

Odds ratioA BCD

Alsohellip

A DC B



















Where are we











Outcome(disease)

time



Everyone else
















design









Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions























Where are we











Outcome(disease)

time



Everyone else
















design









Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions












Outcome(disease)

time



Everyone else
















design









Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions





time



Everyone else
















design









Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions



















design









Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions













Designs




Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions





Studies of Dx Tests




Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions






Disease +Sampled

Separately


Separately

Test +a

True Positives

bFalse Positives

Test -c

False Negatives

dTrue Negatives

Totala + c

Total With Disease

b + dTotal Without

Disease



PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions






PPV = a(a + b)

NPV = d(c + d)



Test +

aTrue

Positives

bFalse

Positives

a + bTotal

Positives

Test -

cFalse

Negatives

dTrue

Negatives

c + dTotal

Negatives


Disease

b + dTotal

WithoutDisease

a + b + c + d

Total N




Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions








Design Cohort study



Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions







Analytic









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions









































































Research questions




























Jul 5112(1)39-47













Slide 49




Research questions



























Jul 5112(1)39-47













Slide 49




Research questions





observational study designs kirsten bibbins-domingo, phd, md associate professor of medicine and of...

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