Supported by a grant from the National Institute on Aging, National Institutes of Health (Grant No....

Supported by a grant from the National Institute on Aging, National Institutes of Health (Grant No. 5P30AG012857)

CCBAR Supported by the National Institutes of Health (P30 AG012857)

NSHAP Supported by the National Institutes of Health (5R01AG021487) including: National Institute on Aging

Office of Research on Women's Health Office of AIDS Research

Office of Behavioral and Social Sciences Research

Natalia Gavrilova, Ph.D.

Stacy Tessler Lindau, MD, MAPP

Biomarkers in Population-Based Aging and Longevity Research


Goals: Foster interdisciplinary research

community Establish means of exchanging rapidly

evolving ideas related to biomarker collection in population-based health research

Translation to clinical, remote, understudied areas


Why?

Need for move from interdisciplinary data COLLECTION to integrated data ANALYSIS

Barriers Models/methods Rules of academe Reviewers/editors


Why?

Growing emphasis on value of interdisciplinary health research NIH Roadmap Initiative NAS report

Overcome barriers of unidisciplinary health research Concern for health disparities Response bias in clinical setting Self-report in social science research


What is needed?

Methods and models for analytic integration

Streamlining data collection Advances in instruments Minimally invasive techniques Best practices Concern for ethical issues Central coordination?


Outline

NSHAP study as an example of a population-based study collecting biomarkers

Theoretical Foundations for Integrated Health Research

CCBAR website


Introduction to:


http://www.icpsr.umich.edu/NACDA/

Public Dataset


NSHAP Collaborators

Co-Investigators Linda Waite, PI Ed Laumann Wendy Levinson Martha McClintock Stacy Tessler Lindau Colm

O’Muircheartaigh Phil Schumm

NORC Team Stephen Smith and

many others

Collaborators David Friedman Thomas Hummel Jeanne Jordan Johan Lundstrom Thomas McDade

Ethics Consultant John Lantos

Outstanding Research Associates and Staff


Affiliated Investigators and Labs

LAB SPECIMENS

ASHA Test results

Lundstrom, Sweden Olfaction

Hummel, Germany Gustation

Magee Women’s Hospital, Jeanne Jordon

Vaginal Swabs, OrasureTM

McClintock Lab, Univ. Chicago

Vaginal Cytology

McDade Lab, Northwestern Univ.

Blood Spots

Salimetrics Saliva

USDTL* Urine


Corporate Contributions and Grants

Item Company/Contact Information

Smell pens Martha McClintock, Institute for Mind and Biology at the University of Chicago

OraSure collection device Orasure Technologies

Digital scales Sunbeam Corporation

Blood pressure monitors A & D Lifesource

Vision charts David Freidman, Wilmer Eye Institute at the Johns Hopkins Bloomberg School of Public Health

Filter paper for blood spot collection

Schleicher & Schuell Bioscience

Blood pressure cuff (large size)

A & D Lifesource

OraSure Western Blot Kit Biomerieux Company

HPV kits Digene Laboratory

Boxes of swabs Digene Laboratory

2-point discriminators Richard Williams


Study Timeline

Funding: NIH / October, 2003

Pretest: September – December, 2004

Wave I Field Period: June 2005 – March 2006

Wave I Analysis: Began October, 2006

Supported by a grant from the National Institute on Aging, National Institutes of Health (Grant No. 5P30AG012857)He, W., Sengupta, M., Velkoff, V. A., DeBarros, K. A. (2005). 65+ In the United States: 2005. Current Population Reports: Special Studies, U. S. Census Bureau.


Lindau ST, Laumann EO, Levinson W, Waite LJ. Perspectives in Biology &

Medicine. (2003)

The Interactive

Biopsychosocial Model (IBM)


Conceptual Framework

TIME

Biological/ Physiological Mechanisms

Sexuality Health

Positive sexual relationships promote health and mitigate illness as people age.

INTERACTIVE BIOPSYCHOSOCIAL MODEL

HYPOTHESIS:


Integrated Health Research

Health Social

Factors

Biological / Physiologic

al Mechanisms

TIME

Social Factors

Biological / Physiologic

al Mechanisms


Interview 3,005 community-residing adults ages 57-85

Population-based sample, minority over-sampling

75.5% weighted response rate 120-minute in-home interview

Questionnaire Biomarker collection

Leave-behind questionnaire

NSHAP Design Overview


Men Women(n=1455) (n=1550)

AGE 57-64 43.6 39.2 65-74 35.0 34.8 75-85 21.4 26.0RACE/ETHNICITY White 80.6 80.3 African-American 9.2 10.7 Latino 7.0 6.7 Other 3.2 2.2RELATIONSHIP STATUS Married 77.9 55.5 Other intimate relationship 7.4 5.5 No relationship 14.7 39.0SELF-RATED HEALTH Poor/Fair 25.5 24.2 Good 27.5 31.5 Very good/Excellent 47.0 44.3

Est. Pop. Distributions (%)

slindau

print notes


Medical Physical Health Medications, vitamins,

nutritional supplements Mental Health Caregiving HIV

Women’s Health Ob/gyn history, care Hysterectomy,

oophorectomy Vaginitis, STDs Incontinence

Demographics Basic Background

Information Marriage Employment and

Finances Religion

Social Networks Social Support Activities, Engagement Intimate relationships,

sexual partnerships Physical Contact

Domains of Inquiry


NSHAP Biomeasures Blood: hgb, HgbA1c, CRP, EBV

Saliva: estradiol, testosterone, progesterone, DHEA, cotinine

Vaginal Swabs: BV, yeast, HPV, cytology

Anthropometrics: ht, wt, waist

Physiological: BP, HR and regularity

Sensory: olfaction, taste, vision, touch

Physical: gait, balance


NSHAP Biomeasures Cooperation

Measure Eligible

Respondents Cooperating Respondents

Cooperation Rate*

Height 2,977 2,930 98.6% Weight 2,977 2,927 98.4% Blood pressure 3,004 2,950 98.4% Touch 1,502 1,474 98.4% Smell 3,004 2,943 98.3% Waist circumference 3,004 2,916 97.2% Distance vision 1,505 1,441 96.0% Taste 3,004 2,867 95.9% Get up and go 1,485 1,377 93.6% Saliva 3,004 2,721 90.8% Oral fluid for HIV test 972 865 89.2% Blood spots 2,493 2,105 85.0% Vaginal swabs 1,550 1,028 67.6% * Person-level weights are adjusted for non-response by age and urbanicity.


Principles of Minimal Invasiveness

Compelling rationale: high value to individual health, population health or scientific discovery

In-home collection is feasible

Cognitively simple

Can be self-administered or implemented by single data collector during a single visit

Affordable

Low risk to participant and data collector

Low physical and psychological burden

Minimal interference with participant’s daily routine

Logistically simple process for transport from home to laboratory

Validity with acceptable reliability, precision and accuracy

Lindau ST and McDade TW. 2006. Minimally-Invasive and Innovative Methods for Biomeasure Collection in Population-Based Research. National Academies and Committee on Population Workshop. Under Review.


Applying Biomeasures in NSHAP

Uses of Biomeasures

Population-Based Sample

Clinic-Based Sample

To detect and monitor risk for disease, pre-disease, disease, mortality OR to quantify and monitor function

++ ++

To recruit or exclude people from study

- ++

To determine efficacy of intervention

-- ++

To determine effectiveness of intervention

++ +

To identify biological correlates or mechanisms of social/environmental conditions

++ --

++ = Very well suited -- = Poorly suited


Applying Biomeasures in NSHAP

Uses of Biomeasures


Clinic-Based Sample


RISK: Genital HPV Tobacco use

ObesityFUNCTION: Mucosal

integritySex hormone metabolism

++


- ++


-- ++


Future public health interventions:

e.g. smoking cessation, HPV vaccine, new hearing devices

+


HypertensionImpaired Glucose

MetabolismRestricted Mobility

--



Disciplinary Use of Biomeasures

Uses of Biomeasures


Clinic-Based Sample


RISK: Genital HPV Tobacco use

ObesityFUNCTION: Mucosal

integritySex hormone metabolism

++


- ++


-- ++


Future public health interventions:

e.g. smoking cessation, HPV vaccine, new hearing devices

+


HypertensionImpaired Glucose

MetabolismRestricted Mobility

--


EPIDEMIOLOGY

BIODEMOGRAPHY/ANTHROPOLOGY

BIO

ME

DIC

INE

EPIDEMIOLOGY


McClintock Laboratory(Cytology)

Jordan Clinical LabMagee Women’s Hospital(Bacterial, HPV Analysis)

McDade Lab Northwestern(Blood Spot

Analysis)

Salimetrics(Saliva

Analysis)

“Laboratory Without Walls”

UC Cytopathology(Cytology)

NSHAP Biomeasures


Sex hormone assays

Salivary Biomeasures

Estradiol Progesterone DHEA Testosterone

Cotinine


Salivary Sex Hormones (preliminary analysis)

log(progesterone)

Freq

uen

cy

log(estradiol)

Freq

uen

cy

log(testosterone)

Freq

uen

cy

Units: pg/ml


Nicotine metabolite Objective marker of tobacco exposure,

including second-hand Non-invasive collection method (vs.

serum cotinine)

Salivary Cotinine


10 ng 15 ng 34 ng 10% M

103 ng 30% M

344 ng M

Nonsmoker Passive

Occasiona

lRegular

0

.05

.1

.15

.2

Fract

ion

-5 0 5 10log(Cotinine)

M = mean cotinine among female who report current smoking

Bar on left corresponds to cotinine below level of detection

Cut-points based on distribution among smokersClassification of Smoking Status by Cotinine Level in Females

Distribution of Salivary Cotinine

slindau

print notes


C-Reactive Protein (CRP)

Epstein-Barr Virus (EBV) Antibody Titers

Dried Blood Spots

Thanks, Thom and McDade Lab Staff!


Demographic Variables: Age

Race/Ethnicity

Education

Insurance Status

Self-Report Measures

slindau

print notes


Social/Sexuality Variables: Spousal/other intimate partner status

Cohabitation

Lifetime sex partners

Sex partners in last 12 months

Frequency of sex in last 12 months

Frequency of vaginal intercourse

Condom use



Health Measures: Obstetric/Gynecologic history

Number of pregnancies Duration since last menstrual period Hysterectomy

Physical health Overall health Co-morbidities

Health behaviors Tobacco use Pap smear, pelvic exam history

Cancer



Challenges


Additional HPV testing considered

“future use”

Genotyping of Hybrid Capture 2

negative specimens

Consent for additional genotyping?

Commercial availability of genotyping

assays (experimental vs. FDA-

approved)

Human Subjects Issues in Data Analysis


First enrollment

March 2006

Specimens collected and sent to lab

When does a When does a study end?study end?

July, 2005

Last enrollment

Initial storage (pre-assay)

Interim storage (post-assay)

Continued storage (post-assay)

Storage for Storage for future use?future use?

Destruction?Destruction?

Specimen Storage


More Information on Biomarkers is Available at the

CCBAR website

http://biomarkers.uchicago.edu/


CCBAR Website Objectives Central resource for collecting,

monitoring, and disseminating the most recent developments

Virtual research collaborative, establishing a means of exchanging rapidly evolving ideas related to all aspects of biomarker collection in population-based research

Educate public about integrated population-based health research


Website Components

CCBAR

Research and Scientific Resources

Workshop Proceedings

Studies Collecting Biomarkers in Population Settings

Centers, Labs and Industry

Grants and Funding Opportunities


Studies Collecting Biomarkers in Population

Settings

Local, regional, national and international studies and investigators involved in population-based health research involving collection of biological and physical measures.


Web-based search of studies collecting specific biomarkers


Studies collecting C-reactive protein


Questions?

Supported by a grant from the National Institute on Aging, National Institutes of Health (Grant No....

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