Creating a Cohort of Cases – ICTR Workshop on Clinical Registries Josef Coresh, MD, PhD Professor of Epidemiology, Biostatistics & Medicine Johns Hopkins University Director, George W. Comstock Center for Public Health Research and Prevention Director, Cardiovascular Epidemiology Training Program
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Creating a Cohort of Cases – ICTR Workshop on Clinical Registries Josef Coresh, MD, PhD Professor of Epidemiology, Biostatistics & Medicine Johns Hopkins.
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Creating a Cohort of Cases – ICTR Workshop on
Clinical Registries
Josef Coresh, MD, PhDProfessor of Epidemiology, Biostatistics & Medicine Johns
Hopkins University Director, George W. Comstock Center for Public Health
Research and PreventionDirector, Cardiovascular Epidemiology Training Program
Outline• Cohort definition (see Gordis “Epidemiology” text for overview)
– Membership criteria (“Case” Definition in a clinical cohort of cases
– but remember that case series is a weak design)
- Considering Referral Pathway
- Considering Precohort Factors
• Data collection – Exposures, Treatments & outcomes (mostly covered by other lectures)
• Examples of different cohorts to illustrate ideas:
– ARIC
– CHOICE
– CLUE
• Discussion of planned cohorts by participants
Taxonomy of Designs
• Randomized Controlled Trial• Prospective Cohort Study
– Variations exist – non-concurrent (going
back to old records etc.)
• Case-Control Study• Cross-Sectional Study• Other Designs
– Quasi-Experimental
– Ecologic
– Case Report
The basic fighting unit was a cohort, composed of six centuries(480 men plus 6 centurions). The legion itself was composed of ten cohorts, and the first cohort had many extra men—the clerks, engineers, and other specialists who did not usually fight—and the senior centurion of the legion, the primipilus, or “number one javelin.”
pro·spec·tive Pronunciation: pr&-'spek-tiv also 'prä-", prO-',prä-'Function: adjectiveDate: circa 1699
1 : relating to or effective in the future2 a : likely to come about : EXPECTED <the prospective benefits of this law> b : likely to be or become <a prospective mother>
• Home visits• Mailed materials• Telephone Interview
• Medical Records• Administrative Data
– Medicare
– Medicaid
– Managed Care
– Veterans Admin
• Birth Records• Death Certificates• Specimen Bank
Challenges in Cohort Studies
• Possibly long duration• Possibly large sample size• Need to recruit people “at risk”• Drop outs, Deaths, Other losses• Concern about residual confounding• Multiple comparisons Type I error
How to Exploit Cohort Design When Time is Short & Money is Scarce
• Analyze existing data from another study• Piggy-back onto on-going study• Choose hospital-based cohort• Choose short-term outcome• Consider administrative data• Consider public-use data• Consider non-concurrent design
Examples – Food for Thought
Results Drift – Even in a “good” labSerum Creatinine Compared to the Mean of All Labs:
College of American Pathologists (CAP) Data
Coresh J et al. Am J Kid Dis 2002;39:920-929
-0.4
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0
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1/1/1992 1/1/1994 1/1/1996 1/1/1998 1/1/2000
Date
Ser
um C
reat
inin
e D
iffer
ence
, mg/
dl
White Sands - Mean of All Methods
Cleveland Clinic - Mean of All Methods
Average White Sands - Mean of All Methods
Average Cleveland Clinic - Mean of All Methods
Systematic Errors can be “corrected”
• NHANES 1988-1994 data can be “calibrated” to the cleveland clinic foundation (CCF) 2006 standardized serum creatinine assay using regression
01
23
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06 C
CF
Cre
atin
ine
from
sto
red
sam
ple
(mg/
dL)
0 1 2 3 4Uncalibrated NHANES III (mg/dL)
Uncalibrated NHANES III vs 2006 CCF with identity line
black lines are +/- 1.96*SDBland-Altman Plot for Creatinine
Selvin et al. Am J Kidney Dis. 2007; 50(6):918-26.
ARIC – Atherosclerosis Risk in Communities
• NHLBI cohort to study atherosclerosis
– Community based sample ages 45-64
– ~5 hour examination: interview, exam,
phlebotomy, carotid ultrasound (all standardized)• Baseline, 3, 6, 9 years … 25 years
– Annual telephone calls
– Chart abstraction of all hospitalizations
– Morbidity and Mortality Classification Committee
review of CHD outcomes
ARIC-NCSCalendar Year 1987-89 1990-92 1993-95 1996-99 2004-06 2011-13
Aim 1PrevalenceX
Stage 2 Eval2637
Aim 4
ARIC-NCS Study Design Overview
Exam 1 Exam 2 Exam 3 Exam 4Brain MRI
Aim 3
8,220+phone
Genetics – Aim 5
R – Retinal photography
Aim 2
X2,000**
Cognitive testing X X (n) 14,201 11,343
Brain MRI X1,134
X1,929
Stage 3MRI
** Includes 357 dementia,852 MCI, 791 normal; 547 with 2 previous brain MRIs•Numbers updated to reflect 2011 start + distant + no lower age limit
X X XX
X X XX
X X
X
RR
15,792 14,348 12,887 11,656 8220 examined more incl. phone
(n)
Median follow-up ,y 0 3 6 9 17 25
1,134
Vascular risk factors
Vascular markers
Age range,y 45-64 48-67 51-70 54-73 62-82 68-89
ARIC V5
Combined visit
XEcho-
cardiogram
X
ARIC – NCS: Aims1) estimate the prevalence of dementia/MCI by race and
sex in participants aged 70-89, 2) determine whether midlife vascular factors (risk factors
and markers of macrovascular and microvascular disease) predict dementia, MCI and cognitive change,
3) determine whether the associations between midlife vascular factors and dementia/MCI differ by dementia/MCI subtype defined clinically or by MRI signs,
4) identify cerebral markers associated with cognitive change, including progression of MRI ischemic burden and atrophy across 3 MRI scans spanning 17 years, and
5) identify genomic regions containing susceptibility loci for cognitive decline, using 106 SNPs spanning the genome.
MRI – same day as Stage 2 for dementia + normals (for borderline cases MRI sampling depends on Stage 2)
(6.5 hours) (~3 hours) (~1 hour)
Home or LTC Abbreviated exam Abbreviated – done with Stage 1
No MRIs
Overview of ARIC Visit 5 + NCS Data Collection
* Only applies to sampled individuals – sampling fractions based on CF & ∆CF** Skip the neuro exam on most (all but n=50) normals
CHOICE CohortChoices for Healthy Outcomes in Caring for ESRD
• Study Design: national prospective cohort study (CHOICE; PI:Powe & Klag & specimen bank Coresh)
• Study Population: – 1026 incident outpatient dialysis patients
– Enrolled between 10/95 and 06/98 (DCI + St. Raph)
– Recruited within a median of 45 days from 1st dialysis (98% within 4 months)
– From 81 dialysis clinics in 19 States
– Age 18 years or older, English or Spanish speaker
– Provided informed consent
• Main research topics: Dose & ModalityOutcomes
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CHOICE Top Papers119 cited 2,110 by 2010 by (Fink N* AND (Coresh or Powe or Klag))
1. Association between cholesterol level and mortality in - Role of inflammation dialysis patients and malnutrition . Author(s): Liu YM, Coresh J, Eustace JA, et al. JAMA 2004 Times Cited: 209 2. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE study. Author(s): Longenecker JC, Coresh J, Powe NR, et al. JASN 2002 Times Cited: 180 3. The timing of specialist evaluation in chronic kidney disease and mortality Author(s): Kinchen KS, Sadler J, Fink N, et al. Ann Int Med 2002 Times Cited: 176 4. Validation of comorbid conditions on the end-stage renal disease medical evidence report: The CHOICE study. Author(s): Longenecker JC, Coresh J, Klag MJ, et al. JASN 2000 Times Cited: 141 5. Changes in serum calcium, phosphate, and PTH and the risk of death in incident dialysis patients: A longitudinal study. Author(s): Melamed ML, Eustace JA, Plantinga L, et al. Kidney Int 2006 Times Cited: 96
CHOICE Top Papers119 cited 2,110 by 2010 by (Fink N* AND (Coresh or Powe or Klag))
6. MYH9 is associated with nondiabetic end-stage renal disease in African Americans Author(s): Kao WHL, Klag MJ, Meoni LA, et al. Nature Genetics 2008 Times Cited: 93 7. Timing of nephrologist referral and arteriovenous access use: The CHOICE study Author(s): Astor BC, Eustace JA, Powe NR, et al. Am J Kidney Dise 2001 Times Cited: 92 8. Comparing the risk for death with peritoneal dialysis and hemodialysis in a national cohort of patients with chronic kidney disease Author(s): Jaar BG, Coresh J, Plantinga LC, et al. Ann Int Med 2005 Times Cited: 86 9. Type of vascular access and survival among incident hemodialysis patients: The choices for healthy outcomes in caring for ESRD (CHOICE) study Author(s): Astor BC, Eustace JA, Powe NR, et al. J Am Soc Nephrol 2005 Times Cited: 73 10. Comorbidity and other factors associated with modality selection in incident dialysis patients: The CHOICE Study Author(s): Miskulin DC, Meyer KB, Athienites NV, et al. J Am Soc Nephrol 2002 Times Cited: 72
Research Opportunities in Washington County: From shoe-leather epidemiology to genomics
Josef Coresh, MD, PhD Professor of Epidemiology, Biostatistics & Medicine Johns Hopkins UniversityDirector, George W. Comstock Center for Public Health Research and Prevention
Ana Navas-Acien, MD, PhDAssistant Professor, Environmental Health Sciences & Epidemiology Sleep
The CLUE Specimen Banks: A paradigm for long-term, population-basedstudies to evaluate cancer-related biomarkers
CLUE I (1974)N=26,147
Serum
Plasma WBC RBC
Follow-up for cancer outcomes through Washington County Cancer Registry (medical record/treatment info available)
Active follow-up of CLUE II cohort: questionnaires
Key advantages: • large, prospective• population-based• long term follow-up• specimens from multiple time points• specimens obtained prior to diagnosis• multiple health outcomes
(8297 also gave to CLUE I)
Odyssey
CLUE II (1989)N=32,894
Baseline questionnaire – FFQ included in CLUE II
1996, 1998, 2000, 2003, 2007
Number of Deaths from CLUE I and CLUE II Volunteersas of 6/30/2009