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Junior faculty are
able to start careers and make contributions most rapidly when
they can join in and draw on existing databases and biological
specimens to make contributions earlier than would be possible
if they depended on building, conducting and then analyzing their
own independent research programs. Using existing data and biological
specimens allows junior faculty to build the experience, expertise
and preliminary data that form the essential building blocks of
successful research plans and grant proposals that will be the
foundation of their independent research careers.
Here is a partial list
and brief description of these resources that are most directly
relevant to Chronic Diseases in Women.
The following databases
are relevant to all the interdisciplinary research areas in women’s
health and provide a rich source of research material for secondary
analysis.
This is a 4-center
longitudinal study of the distribution and development over time
of risk factors for CHD in a bi-racial population of African American
and white men and women who were 18-30 years old at CARDIA’s first
examination in 1984. Since then, the cohort has been re-examined
every two years, with collection of a rich dataset of information
on biological markers, behaviors and lifestyle characteristics,
usually obtained at multiple time points. Through Dr. Sidney,
these data would be available to address a number of questions
related to development of chronic disease risk factors in white
and black women.
Clinical and Administrative
Databases – these databases currently include the membership file
(providing demographic data and enrollment information useful
for creating sampling frames and conducting prospective analyses),
hospital discharge data (with principal and secondary diagnoses
and procedures) for both KP hospitals and outside hospital utilization;
pharmacy utilization (including medications, dosing instructions
and refills) for the >90% of members with a pharmacy benefit;
laboratory database (which includes both inpatient and outpatient
laboratory tests with results); an outpatient diagnosis database
with ICD-9 based diagnostic codes; and detailed utilization datasets,
which record all elements of healthcare utilization (visits, diagnostic
tests) and their costs. All of these databases use the same, unique
patient identifier, making linkage between datasets and over time
straightforward. Together, they have allowed the relatively inexpensive
and rapid study of a host of clinical and health services questions
often with unparalleled statistical power, even when restricted
to women subjects only.
DOR investigators
have also built many specialized registries and research datasets.
Some of these are the time-limited products of funded research
studies and others, such as the cancer registry, the diabetes
registry, and the HIV registry, have become an ongoing part of
the DOR research infrastructure. For access to any KP dataset,
a trainee would have to develop a relationship with the appropriate
DOR mentor with agreement on the research questions to be studied.
Originally funded by
the National Center for Health Services Research in the mid-1960s,
the DOR built a database of more than 1 million multiphasic health
checkups on more than half a million members over a 24 year period
from 1960-84. This remarkable database, which includes extensive
questionnaire information as well as a host of clinical measures
(lipids, glucose tolerance tests, liver and thyroid function tests,
complete blood counts, chest X-rays, electrocardiograms, and mammograms),
is an excellent resource for cross-sectional investigations or
as the basis for constructing well-defined cohorts that can be
followed subsequently for events such as cancer, stroke, heart
disease, hip fracture, or neurodegenerative diseases associated
with aging. Retention remains at approximately 50% for 20 years
or more following the baseline examination.
MORTLINK is the Division
of Research’s probability linkage system to the State of California’s
death certificates. It is based on the software known as CAMLIS,
which conducts probability matches based on known demographic
and personal identifiers. However, DOR investigators improved
the matching algorithms by adding information available on Kaiser
members that would not be available statewide, such as the location
of their usual source of medical care. This dataset is refreshed
annually and provides a highly sensitive system for identifying
out-of-hospital deaths in Kaiser Permanente members.
SWAN is a large, multi-site,
community-based longitudinal study of the menopause, funded primarily
by the National Institute of Aging. The purpose of SWAN is to
understand the biological process of perimenopause and how that
process is shaped by cultural, social and behavior factors in
women of diverse ethnicities. The SWAN cohort, recruited in 1996-97
from defined sampling frames at seven clinical centers throughout
the United States, consists of 3,305 African-American, Caucasian,
Chinese, Hispanic, and Japanese initially premenopausal women,
ages 42-52 at baseline. Cohort participants complete baseline
and annual follow-up examinations consisting of questionnaires,
(medical and reproductive history, demographics, lifestyle behaviors,
dietary intake and psychosocial factors), physiological measures
(body size, blood pressure), collection of biological specimens
(blood, timed to the menstrual cycle, and urine), and bone density/body
composition scans. Women are followed between examinations with
monthly menstrual calendars and a subset collect first morning
urine daily and complete a daily symptom diary for one complete
menstrual cycle a year. This dataset provides an opportunity to
address a variety of questions related to women's aging and the
development of chronic disease in collaboration with other study
investigators.
The UCSF CC specializes
in coordinating multicenter studies in women’s health, osteoporosis,
heart disease, and aging. Led by Dr.
Cummings, the UCSF CC coordinates large, multicenter cohort
studies and clinical trials. Scholars will have access to the
data sets and repositories of biological specimens for all of
these studies. Fellows and trainees are encouraged to use the
data for analysis and writing projects. For example, fellows in
our training programs have written 22 papers and presented over
50 abstracts from the Study of Osteoporotic (SOF) database alone.
These publications by trainees have addressed osteoporosis, breast
cancer, depression, dementia, and cardiovascular disease, and
many have been in high-impact journals.
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Study of Osteoporotic Fractures (SOF),
a prospective, pioneering study of osteoporosis and aging in
10,000 elderly women at four sites in the US, now in its 14th
year. SOF has a wealth of risk factor and clinical outcome data
that have been collected during the course of 6 biennial examinations.
This includes serial measurements of joint pain, functional
status, musculoskeletal examinations, lower extremity muscle
strength, bone density, fractures, medications, and stored serum,
urine and genetic samples. Since 1989, over 80 papers have been
published using SOF data.
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SOF Osteoarthritis Study,
the largest epidemiological study of radiographic hip OA in
the world. This study has data on prevalent radiographic hip
OA in over 8,000 elderly white women, and on incident radiographic
hip OA in over 6,000 of these women. There are also large databases
from this study of radiographic hand and spine OA (n = 1,500).
- Beijing
Osteoarthritis Study, the first population-based
prevalence study to collect data on osteoarthritis in an Asian
population and, because of its use of data from comparable Caucasian
populations, will permit an assessment of whether prevalence
in Chinese and Caucasians differs. The cohort is 2,500 Chinese
men and women 60 years and over in Beijing. Data collected includes
arthritis histories, examinations, knee, hip, and hand x-rays
and risk factors.
- Dynamics
of Health, Aging and Body Composition (Health ABC),
a ten year prospective cohort study of the causes of loss of
strength and decline in function among 3,000 elderly Caucasian
and African Americans at 2 sites in the US. The Heath ABC has
comprehensive data on all aspects of aging on its 3,000 participants,
including many state-of-art measurements of body composition.
- Women’s
Health Initiative (WHI), randomized trials of
estrogen therapy, low fat diet, calcium and vitamin D involving
40,000 postmenopausal women and an observational study of 100,000
women. The UCSF Coordinating Center serves as the bone densitometry
reading center for the WHI. The WHI has a very comprehensive
array of data on many aspects of women’s health and risk factors
and validated occurrence of many chronic diseases relevant to
our training program, including breast cancer, hip fractures,
dementia, incontinence, and heart disease. WHI also has a huge
library of biological specimens.
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Fracture Intervention Trial (FIT),
a trial of alendronate for fracture prevention in 6,400 women
at 11 centers in the US. The original X year trial has been
funded for an additional 5 years.
-
Multiple
Outcomes Studies of Raloxifene Evaluation (MORE),
a trial of raloxifene for prevention of fractures in 7,700 postmenopausal
women at 180 centers worldwide, and a recent extension of the
trial to examine breast cancer and heart disease outcomes.
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Heart
and Estrogen/progestin Replacement Study (HERS),
a trial of estrogen plus progestin for prevention of recurrent
coronary events in 2,700 postmenopausal women with heart disease
at 20 centers in the US, and a 3-year extension of the trial.
- The
Isoflavone Clover Extract (ICE) Menopause Study,
a double-blinded, randomized clinical trial of two red clover
extracts containing phytoestrogens in 270 postmenopausal women
experiencing clinically significant hot flashes at 3 clinical
centers in the US. The primary endpoint is a reduction in hot
flashes. Secondary endpoints include improvements in lipid profiles,
bone turnover markers, and several quality of life measures.
Women will be followed for 3 months after randomization.
- Ultra
Low-dose Transdermal Estrogen Replacement Assessment (ULTRA)
Trial, a randomized double-blinded, placebo controlled
trial evaluating the safety and efficacy of an ultra low dose
continuous estradiol transdermal patch in the prevention of
osteoporosis. This is a two-year, three-center trial that will
recruit 406 postmenopausal women who will be randomized to placebo
or an ultra low-dose estradiol patch. Outcomes include bone
mineral density, biochemical parameters of bone metabolism,
endometrial hyperplasia, uterine bleeding, urinary incontinence,
serum lipids, quality of life, cognitive function and general
safety parameters.
-
PTH-Alendronate Trial,
a randomized double-blinded, placebo controlled trial testing
the efficacy of combining two powerful anti-osteoporosis drugs
(PTH and alendronate) that exhibit very different mechanisms
of action. The trial includes 240 postmenopausal women at 4
clinical centers followed for two years. The primary endpoints
are changes in BMD at several sites and changes in biochemical
markers.
The following databases
focus on special populations or disease conditions and will provide
research material to one or more of the research clusters in women’s
health.
Ten large physician
groups in California were recruited to participate in this cross-sectional
mailed survey of primary care physicians and their adult, managed
care patients. The patient survey was conducted in the fall of
1997, the physician survey in the spring of 1998. Participating
physician groups included three independent practice associations,
3 integrated medical groups, and 4 integrated groups affiliated
exculsively with one large group model HMO.
The patient survey
included items investigating 3 main areas of interest: 1) patient
attitudes toward the first contact and coordinating role of their
primary care physicians, 2) patient ratings of their primary care
physicians, 3)patient perceptions of barriers to specialty referrals.
The adjusted response rate for the patient survey was 71% (8395/11853).
The physician questionnaire
assessed physician demographics;satisfaction with the medical
group and with the availability and quality of specialty consultation;
physician perception of the use of referral guidelines and prior
authorization with their group; understanding of sources of income
(% of income from direct salary, fixed capitation, fee-for-service,
incentives or performance pay, and other); the basis for incentive
pay (quality of care, patient satisfaction, costs of care, use
of referrals, use of diagnostic tests and use of hospital services;
and perceptions of the strength of several influences on referral
decisions.
The Minimum Uniform
Data Set (MUDS) was established in 1985 and has been refined and
updated on a regular basis. The MUDS is currently one of the largest
data sets on persons with dementia with information on approximately
12,000 patients. Part 1 of the MUDS includes baseline patient
demographic, service utilization, clinical and neuropsychological
data as well as ARCC program operations data. Part 2 consists
of re-evaluation data that is collected on a subset of ARCC patients
on a yearly basis.
This is a prospective
study of a large random sample of untreated and treated problem
drinkers, with a large proportion of women (N=695, N=425 over
age 40), in Contra Costa County, CA directed by Dr. Connie Weisner.
Untreated subjects were drawn from the general population and
treated subjects are representative admissions from public, Kaiser,
and other private alcohol treatment programs. This longitudinal
study includes in-person interviews with subjects at baseline,
and at 1, 3, 5, and 7 years. The main focus of the study is on
the role that individual, treatment, and extra-treatment factors
have in an individual’s trajectory of alcohol and drug problems.
The study is designed for separate analysis of women. It includes
numerous measures of psychiatric, alcohol, and drug disorders,
as well as treatment access, social networks, and health services
measures of contacts with health and mental health, criminal justice,
and welfare agencies.
Dr. Habel is currently
building a cohort of approximately 1,200 Kaiser Permanente members
diagnosed with ductal carcinoma in situ (DCIS) of the breast between
1990 and 1997. These women will be followed through 2004 for disease
recurrence and new primary breast cancer. Data on mammographic
features, diagnosis, treatment, and tumor and patient characteristics
are being collected from mammograms, medical records, and pathology
reports. The aim of the study is to examine the association between
mammographic features and prognosis. Several ancillary projects
could be conducted with this cohort, such as a study to examine
quality of life issues among women with DCIS.
This a prospective
clinical examination study of cardiovascular disease risk factors
directed by Dr. Selby. Gary Friedman, MD was the study’s P.I for
the first examination which was conducted performed in 1977-78.
Twelve years later, DOR secured a second RO1 to recruit and re-examine
the same cohort. 711 women (82% of the original cohort) completed
follow-up exams. 4% of the cohort had died (all deaths were ascertained),
and an additional 84 women (9.6% of the cohort) completed health
history questionnaires. This unique dataset contains phenotypic
information on a large number of CHD risk factors in women. Twin
analyses (both heritability analyses and matched co-twin designs)
have been used to study genetic and environmental influences on
risk factors. DNA was also collected and stored at the second
exam. This database resides at DOR.
RAS is a multi-center,
prospective study of the possible role of insulin resistance as
a risk factor for atherosclerosis in middle-aged men and women.
Just over half the cohort is female. The cohort consists of 1600
African American, Hispanic, and non-Hispanic Whites who were age
45-69 years in 1992. By design, approximately one third of the
cohort had type 2 diabetes at the first exam; one third had impaired
glucose tolerance; and a third had normal glucose tolerance. Two
clinical examinations have been conducted. At each, a frequently
sampled intravenous glucose tolerance test was conducted to measure
insulin resistance. B-mode carotid ultrasound, as well as a host
of cardiovascular disease risk factors were collected at each
examination and both plasma and DNA are stored. Annual follow-up
and review for atherosclerotic events is conducted in this cohort.
Dr. Selby is the chair of this study’s P&P committee. Nationally,
a number of research fellows, doctoral and pre-doctoral candidates
have participated in analyses and as first authors of manuscripts
from this study.
Dr. Weisner directs
this randomized study comparing integrated medical and chemical
dependency treatment with treatment as usual (N=795). It includes
a large epidemiological dataset of health and mental health conditions.
It also includes a sample for comparative analysis matched on
age, gender, and length of enrollment in the Kaiser health plan
drawn from the same catchment area. It is designed for separate
analysis of women.
In collaboration with
the California Tumor Registry and the Northern California Cancer
Center, the DOR maintains a comprehensive registry of all members
diagnosed at a KP facility with cancer. This registry includes
the 8 facilities in the SEER registry catchment area. For these
sites, comprehensive data are available since 1973. For the remaining
sites within the Northern California region, the California Tumor
Registry began collecting data comparable to those of SEER in
1991. Thus, we obtain clinical, staging and initial treatment
data on each incident case of cancer in a KP member. This registry
has served as the sampling frame for large numbers of NCI-funded
cohort and case-control studies, including several that involved
subsequent collection of biological specimens. Because of its
size, the registry lends itself to the study of rare cancers (e.g.
colorectal cancers occurring before age 35) as well as common
neoplasms.
The DOR has maintained
a registry of all HIV infected members since 1985. Its patient
identification algorithms have changed over the years in association
with changes to the CDC’s definitions of AIDS and HIV-infection.
An annual report is prepared and limited use has been made of
the dataset for outcomes research.
The Kaiser Permanente
(KP) Diabetes Registry contains information on essentially all
diabetic members, or more than 100,000 current members. Complete
clinical information (inpatient and outpatients diagnoses, laboratory
tests with results, pharmacy records including dosages, outpatient
diagnostic tests, and visit records to all specialties, and unit-level
costs of care) are incorporated on an annual basis into the registry
database. In addition the population has been (and can be surveyed)
and has yielded response rates of 70% by mailed survey, raised
to 85% with Computer-Assisted Telephone Interview (CATI) follow-up
of non-responders. The purpose of the KP Diabetes Registry is
to facilitate high-quality, longitudinal epidemiololgic and health
services research.
This is an observational
cohort of 3000 women recently diagnosed with early stage breast
cancer directed by Dr. Caan. The primary aim of the study is to
examine behavioral factors relating to quality of life and disease
recurrence in breast cancer survivors. Behavioral and medical
risk factors including diet, physical activity, vitamin, mineral
and herbal supplementation, extensive psychosocial measures, co-morbid
conditions, anthropometric measures and other health habits such
as smoking, alcohol and caffeine use will be ascertained twice
during the five -year follow-up period. Endpoints of recurrence,
hospitalization and death will be ascertained every six months.
This dataset will provide extensive opportunities for Scholars
to pursue ancillary studies and secondary data analyses.
This is a randomized
trial of women with breast cancer assigned to one of two 12-week
interventions (a Life Issues Support Group, which represents a
standard group support/therapy model; and an Integrated Intensive
Support Program, in which women practice yoga, meditation, movement,
art, imagery, and engage in psychospiritual exploration. The women
are followed for at least one year for psychological and medical
outcomes.
This is a randomized,
placebo-controlled trial to examine the effect of the herbal product,
Longevity Treasure, on memory, sexual function and Qi. Longevity
Treasure is an herbal mixture widely used in China that is believed
to have life-prolonging effects. It is also purported to increase
Qi as well as memory, energy, and sexual function. The trial takes
place in Beijing and will enroll 240 patients. In addition to
studying the effect of the herbal product, the trial allow interesting
comparisons between traditional Chinese measure of health (Qi,
as measured by tongue and pulse examination) and Western measure
of quality of life. This project is the model for many future
projects in the area of alternative medicine in collaboration
with scientists at the Peking Union Medical College.
This is a randomized
study comparing two chemical dependency interventions (intensity
of substance abuse treatment) at Kaiser, and following patients
for 7 years. The studies were designed for sub-group analysis
by gender of treatment retention and outcome, as well as analysis
of cost-effectiveness, cost-offset, and cost-benefit. This is
particularly relevant because women, who represent a minority
among substance abuse treatment program clients, may have differing
clinical presentations and underlying problems, as well as differing
treatment outcomes compared with men. The study design also allowed
for follow-up of large samples of "self-selected" patients
for methodological analyses on efficacy and effectiveness research.
National surveys of
the adult U.S. general population conducted every five years since
1969 include large samples of women (ranging from 1,250 – 6,000).
Coordinated with these trends surveys are also several longitudinal
surveys. The data comparable across these epidemiologic studies
include alcohol and drug use patterns and problems; health and
mental health conditions and status; attitudes and norms toward
alcohol and drug use and treatment.
This is a large database
coordinated by Dr. Hal Barron at Genentech that provides a unique
opportunity to evaluate the practice patterns involved in the
care of patients with myocardial infarction (MI). The clinical
centers enrolled in NRMI represent a cross-section of the acute-care
hospitals across the United States that treat patients with MI,
and participating hospitals are expected to enroll all consecutive
MI patients. The database enrolls approximately 15,000 patients
per month.
The National Health
and Nutrition Examination Survey (NHANES) was established in 1971
to collect the kinds of health data best obtained by direct physical
examinations and physiological and biochemical measurements. NHANES
is the cornerstone of the National Monitoring and Related Research
Program, providing data needed for nutrition monitoring, food
fortification policy, establishing dietary guidelines, and assessing
government programs and initiatives such as Healthy People 2000
and 2010 objectives of DHHS.
This was a cohort study
comparing adult primary care practice patterns, resource utilization
and medical outcomes during 1994 between Kaiser family practitioners,
general internists, and board certified internal medicine subspecialists.
For this study "subspecialists" including endocrinology,
rheumatology, pulmonary medicine, and infectious disease, because
these physicians are not heavily involved in performing procedures
and do carry substantial primary care caseloads in several medical
centers.
Practice patterns included
visit frequency, continuity of care, referral patterns (to medicine
subspecialties and nonmedicine specialties), laboratory, pharmacy
and x-ray utilization measurements, prevention practices, and
appropriateness of care measures. Costs of care, both disease-specific
and for patients populations, were calculated. Medical outcomes
included hospital and emergency room visits (both total and for
subgroups of "avoidable" admissions and visits). These
measures were determined using the Kaiser Permanent administrative
databases.
Additionally, a cross-sectional
patient survey (74% response rate or 10205 survey respondents)
measured patient reports of physician performance on primary care
measures of coordination, comprehensiveness, and accessibility
of care, preventive care procedures, and health promotion. Additional
items measured patient satisfaction and health values and beliefs.
The study database includes all data from both the automated databases
and the patient survey database.
The Raloxifene
Use for the Heart (RUTH) is a 5-year trial of the effect of raloxifene
on coronary disease and breast cancer risk among 10,000 women
at high risk for coronary disease. RUTH will take place at 159
centers worldwide, and is funded by Eli Lilly. As a member of
the Executive Committee that planned and monitors the trial, Dr.
Grady has authority to request ancillary studies and analyses.
The SF Mammography
Registry is a population-based, computerized database containing
demographic, clinical and risk factor information, mammographic
interpretations and cancer outcomes on a cohort of women obtaining
mammograms in San Francisco. The registry contains information
on 178,887 women and 361,884 mammograms, and is expected to increase
to 210,000 women and 800,000 mammograms within 5 years. The database
is a valuable resource for addressing issues related to mammography
performance, for identifying factors that optimize the quality
of mammography, for biologic studies of screen-detected compared
with other cancers, for developing clinical guidelines, and for
future studies of emergent screening technologies and clinical
interventions to improve screening outcomes.
The Women's Interagency
HIV Study (WIHS), a multicenter, prospective study, was established
in August, 1993 to carry out comprehensive investigations the
clinical, laboratory and psychosocial aspects of HIV infections
in women. The UCSF site, one of seven across the country, is led
by Dr. Ruth Greenblatt. A total of 2641 women (2066 HIV positive
and 575 negative), 80% of minority background, were enrolled and
continue to be followed. The flexible design of WIHS allows researchers
to include sub-studies and modify goals to reflect new knowledge
and state-of-the art methodology. WIHS's repository specimens
and blood, CVL, urine and saliva and comprehensive data from ongoing
semiannual visits provide a unique opportunity to investigate
HIV/AIDS in a diverse cohort of women.
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