Deborah J. Bowen

Design of the Women's Health Initiative clinical trial and observational study

The Womens Health Initiative (WHI) is a large and complex clinical investigation of strategies for the prevention and control of some of the most common causes of morbidity and mortality among postmenopausal women, including cancer, cardiovascular disease, and osteoporotic fractures. The WHI was initiated in 1992, with a planned completion date of 2007. Postmenopausal women ranging in age from 50 to 79 are enrolled at one of 40 WHI clinical centers nationwide into either a clinical trial (CT) that will include about 64,500 women or an observational study (OS) that will include about 100,000 women. The CT is designed to allow randomized controlled evaluation of three distinct interventions: a low-fat eating pattern, hypothesized to prevent breast cancer and colorectal cancer and, secondarily, coronary heart disease; hormone replacement therapy, hypothesized to reduce the risk of coronary heart disease and other cardiovascular diseases and, secondarily, to reduce the risk of hip and other fractures, with increased breast cancer risk as a possible adverse outcome; and calcium and vitamin D supplementation, hypothesized to prevent hip fractures and, secondarily, other fractures and colorectal cancer. Overall benefit-versus-risk assessment is a central focus in each of the three CT components. Women are screened for participation in one or both of the components--dietary modification (DM) or hormone replacement therapy (HRT)--of the CT, which will randomize 48,000 and 27,500 women, respectively. Women who prove to be ineligible for, or who are unwilling to enroll in, these CT components are invited to enroll in the OS. At their 1-year anniversary of randomization, CT women are invited to be further randomized into the calcium and vitamin D (CaD) trial component, which is projected to include 45,000 women. The average follow-up for women in either CT or OS is approximately 9 years. Concerted efforts are made to enroll women of racial and ethnic minority groups, with a target of 20% of overall enrollment in both the CT and OS. This article gives a brief description of the rationale for the interventions being studied in each of the CT components and for the inclusion of the OS component. Some detail is provided on specific study design choices, including eligibility criteria, recruitment strategy, and sample size, with attention to the partial factorial design of the CT. Some aspects of the CT monitoring approach are also outlined. The scientific and logistic complexity of the WHI implies particular leadership and management challenges. The WHI organization and committee structure employed to respond to these challenges is also briefly described.

How We Design Feasibility Studies

Public health is moving toward the goal of implementing evidence-based interventions. To accomplish this, there is a need to select, adapt, and evaluate intervention studies. Such selection relies, in part, on making judgments about the feasibility of possible interventions and determining whether comprehensive and multilevel evaluations are justified. There exist few published standards and guides to aid these judgments. This article describes the diverse types of feasibility studies conducted in the field of cancer prevention, using a group of recently funded grants from the National Cancer Institute. The grants were submitted in response to a request for applications proposing research to identify feasible interventions for increasing the utilization of the Cancer Information Service among underserved populations.

Lesbian, Gay, Bisexual, and Transgender Health: Findings and Concerns

Laura Dean, MEd,1 Ilan H. Meyer, PhD,1 Kevin Robinson, MHA, MSW,1 Randall L. Sell, ScD,1 Robert Sember, PhD,1 Vincent M.B. Silenzio, MPH, MD,1 Deborah J. Bowen, PhD,2 Judith Bradford, PhD,2 Esther Rothblum, PhD,2 Scout, MA,2 Jocelyn White, MD,2 Patricia Dunn, MSW, JD,3 Anne Lawrence, M.D., Ph.D.(c),4 Daniel Wolfe,1 Jessica Xavier,5 and With acknowledgment to Darren Carter, MD, Jennifer Pittman, and Ronald Tierney

The Women’s Health Initiative Memory Study (WHIMS): A Trial of the Effect of Estrogen Therapy in Preventing and Slowing the Progression of Dementia

Evidence from animal, human cross-sectional, case-control, and prospective studies indicate that hormone replacement therapy (HRT) is a promising treatment to delay the onset of symptoms of dementia. The Womens Health Initiative Memory Study (WHIMS) is the first double-masked, randomized, placebo-controlled, long-term clinical trial designed to test the hypothesis that HRT reduces the incidence of all-cause dementia in women aged 65 and older. WHIMS, an ancillary study to the Womens Health Initiative (WHI) funded by the National Institutes of Health, will recruit a subgroup of women aged 65 and older from among those enrolling in the HRT trial of the WHI. The WHI clinical centers and 10 affiliated satellites plan to enroll approximately 8300 women into WHIMS over a 2-year period. Participants will be followed annually for 6 years, receiving cognitive assessments via the Modified Mini-Mental State (3MS) Examination. Women who screen positively for cognitive impairment on the basis of an educational and age-adjusted 3MS cutpoint proceed to more extensive neuropsychological testing and neurologic evaluation. Each woman suspected to have dementia then undergoes a series of laboratory tests that confirm the clinical diagnosis and classify the type of dementia. WHIMS is designed to provide more than 80% statistical power to detect a 40% reduction in the rate of all-cause dementia, an effect that could have profound public health implications for older womens health and functioning.

Family history of diabetes as a potential public health tool

Given the substantial morbidity and mortality associated with type 2 diabetes, it is important that public health seek ways to delay or prevent the onset of this condition. Risk factors for type 2 diabetes are well established and include underlying genetic susceptibility. Despite this knowledge, as well as significant advances in understanding the human genome, the prevalence of type 2 diabetes continues to rise at an alarming rate. Because type 2 diabetes is a complex condition involving a combination of genetic and environmental factors, DNA testing for susceptibility genes is not yet warranted. However, because family history reflects genetic susceptibility in addition to other factors, it may be a useful public health tool for disease prevention. When evaluating family history as a public health tool, several important issues need to be considered, including the analytic and clinical validity and the clinical utility of using family history as a screening tool. These issues as well as a review of the epidemiologic evidence evaluating family history as a risk factor will be reviewed.Overall, a family history approach appears to be a promising new public health tool to fight the growing epidemic of diabetes in the United States. Adequate levels of funding to further evaluate this approach and to develop appropriate tools should be made available for research activities focused on this important area.

Types of Alternative Medicine Used by Patients with Breast, Colon, or Prostate Cancer: Predictors, Motives, and Costs

OBJECTIVE Assess predictors and costs of various types of alternative medicine used by adult patients with cancer. DESIGN, LOCATION, SUBJECTS: Telephone survey of 356 patients with colon, breast, or prostate cancer identified from the population-based Cancer Surveillance System of western Washington. RESULTS Overall, 70.2% of patients used at least one type of alternative medicine, with 16.6% seeing alternative providers, 19.1% using mental/other therapy, and 64.6% taking dietary supplements. Compared to males, females were five times more likely to see an alternative provider and about twice as likely to use mental therapies or supplements (p < 0.05 for all). Older patients were less likely to use mental/other therapy. Higher education (but not income) was associated with use of all types of alternative medicine. Patients with multiple medical treatments were two times more likely to take dietary supplements compared to patients having only surgery (p < 0.01). Varying by the type of alternative therapy, 83%-97% of patients reported that they used alternative medicine for general health and well-being while 8% to 56% reported use for treatment of cancer. Almost all patients reported that the alternative therapy improved their well-being. Expenditures for alternative medicine averaged

Differences in Survival by Histologic Type of Pancreatic Cancer

68 per user per year, but ranged from

Pentostatin, cyclophosphamide, and rituximab regimen in older patients with chronic lymphocytic leukemia

4 to

Comorbid conditions and survival in unselected, newly diagnosed patients with chronic lymphocytic leukemia

14,659. CONCLUSIONS Given the high prevalence of use and that patients believed that alternative medicine improved their well-being, clinicians should show an open mind toward these treatment choices and encourage frank discussion. Familiarity and some knowledge regarding use of alternative medicine is important in cases where interactions between conventional and alternative medicine may occur. It is also important to identify potential patient needs for mental health support beyond conventional care and support patients who want to make healthful lifestyle changes. Longitudinal investigations are urgently needed to investigate associations of alternative medicine use with survival and quality of life in patients with cancer.

Future Health Applications of Genomics Priorities for Communication, Behavioral, and Social Sciences Research

Objective: Although pancreatic cancer has an extremely high case fatality rate, little is known about differences in mortality by histologic types. We examined median survival and risk of mortality for endocrine pancreatic tumors and two types of exocrine tumors, adenocarcinomas, and mucinous tumors. Method: This analysis included 35,276 pancreatic cancer cases reported to the nine population-based cancer registries participating in the Surveillance, Epidemiology, and End Results program from 1973 to 2000. Survival among cases with pancreatic adenocarcinomas, mucinous tumors, and endocrine tumors were compared using Kaplan-Meier plots. Comparative risks of mortality were evaluated using multivariate adjusted Cox regression models. Results: Endocrine pancreatic cancer cases had a median survival of 27 months compared with a median survival of 4 months for adenocarcinoma and mucinous tumor cases. Compared with adenocarcinoma cases, endocrine tumor cases had a 0.28-fold lower risk of mortality [95% confidence interval (95% CI), 0.26-0.30], and mucinous tumor cases had a 0.88-fold lower risk (95% CI, 0.84-0.91). These results were similar for men and women. Within histologic types, advanced tumor stage, older diagnosis age, surgery, and Black race were associated with increased risks of mortality, whereas female sex and more recent year of diagnosis were associated with decreased risks. Conclusion: This study confirms the clinical observation that patients with endocrine pancreatic cancer survive longer than patients with exocrine tumors. A better understanding of these differences could contribute to identifying the underlying causes of pancreatic cancer and to improving survival rates across all histologic types.