RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 51

CONTENTS

FOREWORD i

Ruth L. Kirschstein, M.D.

Deputy Director, National Institutes of Health

PREFACE iii

Vivian W. Pinn, M.D.

Associate Director for Research on Women’s Health

National Institutes of Health

INTRODUCTION v

Shiriki R. Kumanyika, Ph.D., M.P.H.

Lewis H. Kuller, M.D., Dr.P.H.

PREPARED REMARKS OF CONGRESSWOMAN LOUISE M. SLAUGHTER (D-NY)

TO THE OFFICE OF RESEARCH ON WOMEN’S HEALTH SCIENTIFIC MEETING vii

Recruitment and Retention of Women in Clinical Studies

Exclusion of Women

Women’s Health Equity Act

Women’s Health—A Movement

Women in Health Care Reform

Conclusion

CHAPTER 1: OVERVIEW OF RECRUITMENT AND RETENTION ISSUES 1

Shiriki R. Kumanyika, Ph.D., M.P.H.

Lewis H. Kuller, M.D., Dr.P.H.

CHAPTER 2: DESIGN AND IMPLEMENTATION ISSUES IN CLINICAL STUDIES 3

Carol K. Redmond, Sc.D.

Julie E. Buring, Sc.D.

Introduction

Key Design and Implementation Issues

Summary and Recommendations

CHAPTER 3: INVESTIGATOR AND INSTITUTIONAL ISSUES IN THE

RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 7

Maureen M. Henderson, M.D., D.P.H.

Marion M. Lee, Ph.D., M.P.H.

Introduction

An Overview of Clinical Studies

Key Investigator and Institutional Issues

Benefits and Risks to Investigators in Conducting Clinical Studies

Summary and Recommendations

CHAPTER 4: PARTICIPANT AND COMMUNITY ISSUES IN THE

RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 17

Barry D. Kaufman, D.M.D.

Helen Rodriguez-Trias, M.D.

Introduction

Key Issues

Summary and Recommendations
CHAPTER 5: CURRENT EXPERIENCES IN WOMEN’S HEALTH RESEARCH 25

Lewis H. Kuller, M.D., Dr.P.H.

Introduction

Recruitment Strategies

Retention Strategies

Other Examples of Successful Clinical Studies Involving Women

Summary

CHAPTER 6: CONCLUSIONS AND RECOMMENDATIONS 29

Summary List of Recommendations

APPENDICES 33

Appendix I 35 Task Force Roster

Appendix II 39

Public Hearing Summary

Appendix III 61

Agenda

Appendix IV 67

Speakers

Appendix V 73

Observers

Appendix VI 93

Legal and Ethical Issues

Appendix VII 99

Lesbians in Health Research
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 41

FOREWORD Recruitment and Retention

of Women in Clinical Studies

I

nterest in women’s health issues has existed for a long

time but has only gained prominence and momentum

in the last decade. In 1983, I chaired the newly established

Public Health Service (PHS) Task Force on Women’s Health

Issues. This task force examined women’s health issues

across the lifespan, particularly in the context of sociological changes experienced by our Nation during the

late 20th century.

One of the most important recommendations that

emerged from the task force’s report Women’s Health Report

of the Public Health Service Task Force on Women’s Health

Issues was that biomedical and behavioral research should

be expanded to ensure emphasis on conditions and diseases

unique to, or more prevalent in, women of all ages. As a

first step toward implementing this recommendation, the

National Institutes of Health (NIH) developed and published a policy statement urging grant and contract applicants to include women in clinical research.

Although the policy was implemented, concerns

were expressed by many, including members of Congress,

about whether efforts to enhance the participation of

women and minorities as research subjects were being

taken seriously by the scientific community in general

and by NIH in particular.

As a result of these concerns, in 1989, the General

Accounting Office (GAO) was asked by Congress to review

the NIH inclusion policy,1

 specifically compliance by grant

applicants and policy monitoring and implementation by

the NIH. A major finding of the GAO’s June 1990 report

was that more uniform implementation and monitoring

of the inclusion policy were needed.

Following publication of the GAO report, the NIH

issued a revised, strengthened policy on the inclusion

of women and minorities in clinical research. The policy

stated that no funding would be awarded to applicants

who do not show adequate representation of women in

planned clinical research unless compelling justification

was provided. NIH began to apply this new policy to

research contracts and to clinical research conducted

in intramural and extramural programs.

The release of the PHS Task Force on Women’s Health

Issues report and the establishment and strengthening of

the NIH inclusion policy provided a unique opportunity

for the U.S. Department of Health and Human Services

(DHHS) to reassess its policies and focus attention on the

health of American women. This opportunity was realized

i
42

when the Office of Research on Women’s Health (ORWH)

was created on September 10, 1990. I was honored to

serve as its first acting director. One of the office’s primary

objectives was to reinforce the implementation of the

NIH policy, and, perhaps more importantly, to change

the culture surrounding the development and review of

clinical trials.

On June 10, 1993, the focus on issues related to

women’s health was firmly established in law with the

passage of the National Institutes of Health Revitalization

Act of 1993.2 Its provisions include the statutory establishment of the ORWH; an Advisory Committee on Research

on Women’s Health, which is to advise the ORWH on

appropriate research activities to be undertaken by the

NIH; and a statutory mandate for the inclusion of women

and minorities as subjects in clinical research funded by

the NIH.

 The passage of this legislation underscored continuing

congressional concern about research on women’s health

issues and congressional support of the ORWH’s research

and policy activities and the NIH’s demonstrated leadership

in this area.

Although many in the scientific community have

strongly embraced the need for expanded study populations, barriers to the full inclusion of women and minorities

in clinical research remain. Recruitment and Retention of

Women in Clinical Studies takes a focused and thorough look

at these issues. It identifies barriers to recruitment and

retention and offers concrete and viable recommendations.

The discussions and recommendations are based on the

experience of numerous nationally recognized experts from

diverse fields. This report is invaluable to the scientific

community, industry, academia, Congress, advocacy

groups, and the public. It demonstrates NIH’s firm commitment to improving the health of American women and,

thus, the health of the Nation.

Ruth L. Kirschstein, M.D.

Deputy Director

National Institutes of Health

Former Acting Director of the Office

of Research on Women’s Health

References

1. 59 FR 14508 (as republished March 28, 1994). NIH

Guidelines on the Inclusion of Women and Minorities

as Subjects in Clinical Research.

2. NIH Revitalization Act of 1993. P.L. 103-43. Approved

June 10, 1993.

ii
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 43

PREFACE

Attention to the inclusion of women in clinical researchhas become a far-reaching priority for members of

Congress, the scientific community, and women’s advocacy

groups. It is also central to the mandate for the Office

of Research on Women’s Health (ORWH) at the National

Institutes of Health (NIH) and its commitment to improving the health of women and minorities.

The ORWH’s mandate is to give the NIH a central

focus on women’s health issues and to establish a science

base that will permit reliable diagnoses, effective treatment, and preventive strategies for women.

The major objectives of the ORWH are to:

 Develop an integrated strategy for increased research

into diseases, disorders, and conditions that are unique

to, more prevalent among, or more serious in women

or for which there are different risk factors or interventions for women than for men.

 Ensure that women are appropriately represented in

biomedical and biobehavioral research studies, especially in clinical trials that are supported by the NIH.

 Direct initiatives to increase the number of women

who participate in biomedical research careers.

The second objective, which is among the highest

of the ORWH’s priorities, addresses the participation

of women in study populations, especially clinical trials. Women cannot expect to gain equitably from new advances

in therapy and interventions if they are not included in

the clinical trials that assess safety and efficacy.

The current NIH policy on the inclusion of women

and minorities in study populations clearly states that

women shall be included in clinical studies in numbers

proportional to the prevalence among women of the

condition under study. To monitor compliance with

this policy, the ORWH instituted a tracking system and

is beginning to analyze the results from the system’s

first year of implementation.

In addition, the ORWH has examined why women

are all too often excluded from research. Two of the most

commonly stated reasons for this exclusion are the legal

and ethical issues surrounding potential exposure and

risk to a fetus and the difficulty of recruiting women into

studies. Regardless of whether this exclusion is an act of

discrimination or of protection, it must be rectified immediately. In addition, most developing therapeutic modalities, biotechnological advances, preventive interventions,

or predictors of health or disease outcome will, by necessity, not only be applicable to men. They must also be

iii
44

applicable to a wide spectrum of women, including

those who are pregnant, of childbearing potential, elderly,

lesbian, of diverse racial or ethnic origin, of varied socioeconomic status, from rural areas, from inner cities, or

homeless. Therefore, it is imperative that we know and

understand the potential effects of diagnostic efforts,

treatment, and prevention in these populations and not

just infer their applicability to women based on studies

conducted in men.

The NIH is now in the process of establishing guidelines to implement recent congressional mandates for

the inclusion of women and minorities in NIH-funded

research. The NIH, in conjunction with the Institute

of Medicine (IOM), is addressing the legal and ethical

implications that investigators and administrators face

as they attempt to include more women in clinical studies

while keeping women’s health and the health of any

potential fetus at the forefront of research considerations.

There is also the need to recruit and retain women in

clinical studies if we are to fill in the gaps in our knowledge

of women’s health. To assist in this endeavor, the ORWH

formed a Task Force on the Recruitment and Retention of

Women in Clinical Studies, which held two meetings

during 1993: a public hearing in March and a scientific

meeting in July. We were honored to have Congresswoman

Louise Slaughter as our keynote speaker for the scientific

meeting; her perceptive and thought-provoking remarks

are included in this report.

In presenting Recruitment and Retention of Women in

Clinical Studies,which is a summary and synthesis of the

two meetings, I wish especially to thank Dr. Shiriki R.

Kumanyika and Dr. Lewis H. Kuller, who served as

cochairs of the task force; the other members of the task

force; and those who provided testimony at the public

hearing. The time, experience, and expertise given by

these individuals and by the other participants in the

meetings are clearly reflected in this report. Their contributions will be of invaluable assistance as the NIH

continues its efforts toward meeting the goal of full

inclusion of women and minorities in clinical research.

Vivian W. Pinn, M.D.

Associate Director for Research

on Women’s Health

National Institutes of Health

iv
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 45

I

n order to explore the issue of the participation of

women and minorities in clinical research and to develop

strategies for promoting the full inclusion of these groups,

the Office of Research on Women’s Health (ORWH) at the

National Institutes of Health (NIH) formed the Task Force

on the Recruitment and Retention of Women in Clinical

Studies. The task force held a public hearing in Bethesda,

Maryland, on March 29-30, 1993. Thirty-nine individuals

and organizations presented testimony at the hearing; an

additional 19 individuals and organizations submitted

written testimony. These testimonies addressed the social,

economic, and health experiences of many women in this

country; the need for including women in clinical studies;

and the barriers to women’s participation.

The information gathered by the task force at the public

hearing was used to plan a scientific meeting that was held

on July 12-13, 1993, in Bethesda, Maryland. The objectives

of this meeting were to generate recommendations for

action, develop strategies for fostering the participation of

women and minorities in clinical research, and highlight

successful instances for recruitment and retention of

women and minorities into research studies.

Participants in the scientific meeting discussed these

issues in a series of panel sessions, corresponding to the

topics covered in chapters 1, 2, 3, and 4 of this report.

Each panel session was led by two comoderators. Statements and presentations made by individuals and representatives of national organizations during the scientific

meeting clearly supported the view that a much broader

inclusion of women in clinical research studies is necessary.

Perhaps even more important, these statements and

presentations showed that this goal is, indeed, attainable.

Recruitment and Retention of Women in Clinical Studies

presents a summary and synthesis of results from the

public hearing and the scientific meeting. It is organized

into chapters, each of which considers a key aspect of the

issue of recruitment and retention of women in clinical

studies. Chapter 1 presents an overview of historical

issues in women’s health and women’s participation in

clinical research. Chapter 2 looks at study design and

implementation issues and how they affect the participation of women and minorities in clinical studies.

Chapter 3 explores some of the major investigator and

institutional issues that hamper the inclusion of women

and minorities in clinical research. Chapter 4 examines

the inclusion issue from the viewpoint of the participants

INTRODUCTION

v
46

and the community and looks at such areas as beliefs

and attitudes, appropriate communications channels,

and logistical barriers to participation. Chapter 5 highlights some success stories: studies in which women

and minorities have been effectively recruited and

retained and which have resulted in the formation of

strong partnerships between the sponsoring research

institution and the community. Finally, chapter 6 presents some overall conclusions and a summary list of

the recommendations presented in chapters 2, 3, and 4.

Shiriki R. Kumanyika, Ph.D., M.P.H.

Lewis H. Kuller, M.D., Dr.P.H.

vi
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 47

REMARKS

Representative Louise M. Slaughter (D-NY)

PRESENTED AT

THE OFFICE OF RESEARCH

ON WOMEN’S HEALTH

SCIENTIFIC MEETING ON

RECRUITMENT AND RETENTION

OF WOMEN IN CLINICAL STUDIES

I

t is an honor to be with you this morning. The last

time I addressed a scientific meeting of the National

Institutes of Health was April 1992. We were launching

a new, comprehensive initiative by the institutes to consider the lingering health effects of exposure to the pregnancy drug DES. As the author of legislation signed into

law to authorize this expanded research and public health

education program, I was honored to meet the men and

women scientists like yourself, who had dedicated their

careers and their very lives to finding answers to the

difficult questions of diethylstilbestrol (DES) mothers,

sons, and daughters: What has DES done to my body?

Will I get cancer? If I do, can I survive?

The questions that you pursue—in the laboratory, in

the treatment room, and in conferences like these—are

fundamental quality-of-life issues and critical life-or-death

questions. It is the noblest of pursuits because biomedical

research holds the promise to change lives and save lives.

It is simply unfair then, and perhaps even unethical, that

until now such promise did not equally apply to female lives.

Exclusion of Women

I

n 1986, the NIH adopted a policy requiring the inclusion of women in clinical trials, but a 1990 study by the

General Accounting Office (GAO) found that the policy

was not enforced, leaving women still excluded from the

bulk of government-sponsored medical research. You

probably know the list even better than I: the diabetes

study, the aspirin-a-day study on heart disease, diet pill

studies, and studies on the role of iron in cardiovascular

disease—all performed primarily on white males. No

matter that women are the primary consumers of diet

pills and iron supplements or that women and minorities

are three times more likely to have diabetes. No matter

that heart disease is the number one killer of women.

And, no matter that women pay at least one-half of the

Nation’s tax dollars, the same tax dollars that pay for

NIH research.

It has been almost three decades since the Civil

Rights Act of 1964 began tearing at the notion that

women couldn’t hold certain jobs because, surely, we

were handicapped by our hormones and menstrual

periods. But medical science didn’t follow suit. Menstrual cycles and irregular hormone levels were blamed

for data too difficult to analyze, becoming a convenient

excuse to ignore female subjects in many cases.

vii
48

But, when it comes to biology, we know that men and

women are not created equal. We have different chemistries, different average body weights, different organs.

It only stands to reason, then, that we would require

different treatments, different dosages, and different

means of prevention. But not enough research has been

done to figure out just what those differences are. This is

changing, obviously, or we wouldn’t be here today. A new

law signed by President Clinton, the National Institutes of

Health Revitalization Act of 1993, requires that women be

included in clinical studies for purposes of gender analysis.

Women’s Health Equity Act

Perhaps the 1990 GAO report started it all. It wasthe culmination of a year-long study requested by

the Congressional Caucus for Women’s Issues in order to

determine the extent to which women have been left out

of federally funded research. The caucus is made up of

all the women in the House of Representatives; at that

time, we numbered only 29—just over 6 percent of the

House. We may be small in numbers, but we make a lot

of noise and wear bright colors to stand out among the

navy and gray pinstripes. Well, let me tell you, we made

an awful lot of noise about women’s health that year in

the 102nd Congress.

We introduced an omnibus Women’s Health Equity

Act, an unprecedented package of 22 separate bills

designed to improve the status of women’s health in

the areas of research, services, and prevention. Among

the provisions of this mammoth legislation were: the

establishment and permanent authorization of the Office

of Research on Women’s Health (which has convened this

important meeting); the statutory requirement that women

and minorities must be included in NIH clinical studies,

where appropriate; the establishment of research centers on

osteoporosis, contraception, and infertility; and necessary

funding increases for research into the diseases that claim

unacceptable numbers of female lives, like breast, ovarian,

and cervical cancers.

We also authorized an expansion of existing studies

on conditions like lung cancer, heart disease, and acquired

immune deficiency syndrome (AIDS) so that researchers

could look specifically at gender differences in risks,

symptoms, and treatment protocols.

Even before the reinforcements arrived in the 103rd

Congress—22 new women were elected to Congress last

November—we made some remarkable progress in passing

certain elements of the Women’s Health Equity Act. We

enacted legislation establishing a $25 million program to

prevent infertility through screening and treatment of

chlamydia and other sexually transmitted diseases.

We also passed legislation setting Federal standards

for mammography facilities.

Many of the remaining provisions of the Women’s

Health Equity Act were included in the NIH bill that

was vetoed by President Bush because his administration

opposed lifting the ban on fetal tissue research and objected

to the women’s health section of the bill as “unnecessary.”

Thankfully, President Clinton made the NIH bill, and

especially its critical improvements of women’s health

research, one of his first legislative priorities. It was signed

on June 10, 1993, in a White House ceremony befitting

such historic legislation.

Much remains to be done in the area of women’s health,

and this year we will again introduce an omnibus Women’s

Health Equity Act. It will address, among other issues:

women and AIDS, women and alcoholism, lupus, RU486

research, pharmaceutical interactions and testing, teen

pregnancy, and menopause. And, as a caucus, the women

in Congress have already met with Mrs. Clinton and

testified before the Ways and Means Committee in order

to make sure that women’s special medical needs are

included in national health care reform.

Women’s Health—A Movement

How did we get to where we are today? Nineteenninety-two was popularly billed as the “Year of the

Woman,” but what confluence of political, social, and

economic factors conspired to make it so? How did

women’s health become almost a movement, a revolution?

When Anita Hill showed the Nation how absurdly

out-of-touch a nearly all-white-male Congress is with the

American woman, American women started looking into

all the other areas of public policy where their interests

were being neglected, including employment, education,

criminal justice, and health care. An analysis of Government funding spent for cancer research revealed that

relatively little was being spent on “female” cancers like

ovarian, breast, and cervical cancers. It was appalling

to learn that we have a blood test for the early detection

of prostate cancer, and yet we have no way to detect

ovarian cancer until it has become a death sentence.

As a member of the House Budget Committee, I worked

with the Breast Cancer Coalition in the 102nd Congress

viii
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 49

to secure an ambitious increase in breast cancer research

funding of $300 million. In the budget resolution, I

included that funding goal for breast cancer on top of

$200 million in additional increases for women’s health

research. It was the first time women’s health was specifically designated in the budget resolution, and as one of

only two women on the Budget Committee that year, I

believe it was probably the first time the words breast

and cervix were spoken in the budget hearing room.

In the Budget Committee of the 102nd Congress, I

began a debate that continues today, especially as resources

become more and more scarce. It simply makes no sense

to me that we can spend $3.8 billion on “Star Wars” against

a nonexistent enemy and yet struggle for a $300 million

appropriation to combat breast cancer—a very real enemy

that kills at least 46,000 American women in a single year.

 But the debate is not only one of ordering priorities like

defense over health care or education over criminal justice.

It is also a commonsense debate about how a small investment in biomedical research and prevention can yield

substantial savings in medical expenses. Until recently,

however, we neglected that investment by letting the

NIH budget stagnate; by refusing Medicare and Medicaid coverage for services like screening mammograms,

Pap smears, and vaccines; and by allowing private health

insurance companies to deny such coverage as well.

We’ve paid for this neglect. We’ve paid heavily.

We spend $289 billion on hospital services each year.

We spend another $142 billion on physician services.

And we spend $61 billion each year on prescription

drugs and other medical nondurables.

But all this money, in sums too great even to comprehend, has not bought us, as a population, good health.

Our health care system, the most expensive in the world,

has failed us.

Women in Health Care Reform

By failing to guarantee access to preventive healthservices, our current health care system has allowed

the death toll for breast cancer to rise to epidemic proportions. By failing to provide lifesaving vaccines to

adults and children, our current system has allowed

the incidence of rubella and measles to increase fivefold

since 1987. Over the past 3 years, we’ve sent 54,000

Americans to hospitals with measles, watching more

than 100 of those adults and children die from this

entirely preventable disease.

And, until we ensure coverage for a full range of primary and preventive reproductive health care services—

including family planning and contraception—we can

do nothing to reduce the appallingly high rates of teen

pregnancy, infant mortality, and babies born drug addicted

or infected with HIV, all of which ultimately impose costly

burdens not only on our health care system but also on

our schools, our housing programs, our criminal justice

system, and the national economy in general.

National health care reform is one of the most difficult and complicated issues that the 103rd Congress will

address, but, essentially, the current debate comes down

to compassion versus cost savings. One side argues that

health care is a right and that quality-of-life considerations

must be the guiding force of reform. The other side insists

that controlling runaway health costs must be our primary

objective. I submit to you, and I think you will agree, that

both objectives can be achieved through a commitment to

preventive health and the biomedical research that leads

to more effective means of prevention.

If we can successfully shift the primary mission of

health care away from curing sickness to understanding

sickness and maintaining wellness, we will simultaneously

realize both a dramatic increase in quality of life and

meaningful savings in health care expenditures.

Our experience with breast cancer provides a compelling example. A mammogram is a simple X ray that costs

under $100 per screening. Without the $100 investment

in a screening mammogram, breast tumors are not likely

to be identified until they have grown to the size of a

marble or even a Ping-Pong ball. At this point, the tumor

is not only more deadly, it is more expensive. Treatment

costs for advanced-stage breast cancer soar to an average

of $84,000 per patient—all because the opportunity for

early detection was missed.

As chair of the Women’s Caucus Task Force on

Women’s Health, I’m working to make sure that any

new plan for health care in the United States adopts

biomedical research and prevention as its primary

emphases. We have both the know-how for cuttingedge research and the technology for prevention and

early detection. It’s unforgivable that we haven’t yet been

completely successful in transferring what we’ve learned

in the laboratories to what we practice in the doctor’s

offices. Such is the drum I beat for this Congress, as

we undertake national health care reform.

ix
50

Conclusion

We must have a system that includes fundamentalprimary and preventive services, especially those

unique to women because, unless the women of this

country are healthy, we offer no hope of healthy children.

And, let’s face it, when we consider that women make up

the fastest growing segment of the labor force and that

women are starting up their own businesses at a rate at

least four times greater than that of men, we realize that

we cannot afford to rest the Nation’s economic future on

the stooped shoulders of women crippled by osteoporosis

or weakened by breast cancer. I say to the women in the

audience: Ladies, we are more than 100 million strong—

more than 50 percent of the Nation’s population. If we are

not healthy enough to do the Nation’s grocery shopping,

raise the Nation’s children, manage the Nation’s business,

educate the Nation’s youth, clean up the Nation’s forests

and oceans, and make the Nation’s laws, I don’t know what

kind of future the Nation can expect. The women’s health

movement is not a passing fad, it is truly a revolution for

the 1990’s and the 21st century.

x
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 1

OVERVIEW OF

RECRUITMENT

AND RETENTION

ISSUES

Shiriki Kumanyika, Ph.D., M.P.H.

Lewis H. Kuller, M.D., Dr.P.H.

CHAPTER 1

Until well into the 20th century, there was very littleexamination of the health of American women beyond

reproductive issues. A review of the medical and scientific

literature of the late 1800’s and early 1900’s shows that,

although women may have suffered from other ailments,

the medical and scientific attention that was paid to women

centered around questions of hormones, reproduction,

and childbearing.1

 A number of reasons can be cited to

explain this situation. The medical community’s ability to

define completely the range and nature of women’s health

problems was limited by the absence of measurement and

documentation systems or by the need to rely on systems

still in formative stages. The state-of-the-science did not

allow for significant collection and recording of data on

Americans’ overall health and was particularly lacking in

the areas of women’s, and especially minority women’s,

health care issues. Other reasons for the insufficient

attention to women’s health included restrictive social

conventions that gave rise to discrimination, biases,

and stereotypes and resulted in a diminished status

for women and their roles in family and society.

It was not until this century that medical research

into women’s health care issues began to expand beyond

gynecological and reproductive health. With increases

in funding, especially Government funding, and rapid

technological development, the ability to conduct scientific

research in many areas affecting the health of women

and men increased markedly.1

A major development in the conduct of scientific

research on humans came about with the use of randomized clinical trials and other types of human clinical studies

beginning in the 1940’s and 1950’s. Information gained

from these studies led to an enhanced understanding of

the causal factors in and optimum treatments for a broad

range of diseases, particularly chronic diseases.

As investigators began to rely more heavily on clinical

studies, two issues in study designs became crucially

important. The first was cost, particularly in the cases

of studies that required large sample populations and

many years to complete. The second issue was complexity.

Investigators felt that the best studies were simple in design

and involved the fewest number of variables. Involving

women in clinical studies was viewed as not only increasing

the complexity of the study design because investigators

would have to take into account hormonal fluctuations

and other gender-based differences but also as increasing

the costs due to increased sample sizes, particularly in

studies where the disease-event rate might be lower

in women than in men (e.g., coronary heart disease).
2 OVERVIEW OF RECRUITMENT AND RETENTION ISSUES

In addition to these factors, other concerns contributed

to the underrepresentation and even exclusion of women

from clinical studies. The tragic discoveries of the immediate or delayed teratogenic effects of certain drugs such as

diethylstilbestrol (DES) and thalidomide led the Food and

Drug Administration (FDA) to develop more stringent

policies on the inclusion of women of childbearing

potential in Phase I and early Phase II clinical studies.1

During the last decade, a number of forces have come

together to begin to change the situation with respect to

research on women’s health. The demographic, environmental, and societal changes that are occurring in the

United States are fostering collaboration between health

researchers from all disciplines and the public to promote

health and well-being. Increasingly large segments of the

American public are informed about, aware of, and committed to participating in biomedical research efforts.

The American public is also exercising its prerogative to

request, and at times demand, greater accountability for

expenditures of their tax dollars in biomedical research.

Women’s health and AIDS are but two examples of issues

in which consumer activism is playing an increasing

and constructive part in developing the research and

treatment agenda at the Federal, state, and local levels.

A visible result of these changes was the June 10, 1993,

signing of the National Institutes of Health Revitalization

Act of 1993 by President Clinton. This act statutorily

requires that women and minorities be included in

research that is supported by Federal funds.

Since its inception in September 1990, the ORWH

has been the focal point for women’s health research

policy development funded by the NIH and for the

creation of mechanisms to promote and monitor the

inclusion of women and minorities in clinical studies.

The ORWH shares the leadership for this latter responsibility with the Office of Research on Minority Health,

the Office of Extramural Research, and the Office of

Intramural Research, all of which are under the auspices

of the Office of Director of the NIH.

A major focus of the ORWH’s work, in collaboration

with the administrators and staff of NIH’s 24 constituent

institutes, centers, divisions, and offices, is to support

scientific endeavors that will provide data necessary to

improve the health and quality of life of American women.

The forging of such partnerships has created a heightened

awareness of women’s health issues and a fuller recognition

of women’s health as a priority in the research activities of

the NIH and the broader scientific community.

Reference

1. LaRosa JH, Pinn VW. Gender bias in biomedical

research. J Am Med Wom Assoc 1993;48(5):145-51.
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 3

DESIGN AND

IMPLEMENTATION

ISSUES IN CLINICAL

STUDIES

Carol K. Redmond, Sc.D.

Julie E. Buring, Sc.D.

Introduction

CHAPTER 2

The primary goal of any clinical study should be toprovide either a definite positive result on which

individual clinical decisionmaking and public health

recommendations can be reliably based or an informative

null result that will safely permit the rechanneling of

research and resources into more promising areas.

Including women and minorities in clinical studies

may introduce special scientific and logistical issues,

while concurrently creating opportunities for identifying

and addressing new areas of research. Investigators can

address these issues through the creation and development

of innovative designs, and they may identify cost-effective

options by considering alternative strategies for the study

design. The unique strength of a well-designed and

conducted study involving women and minorities is

its ability to provide information of direct benefit to

these populations, enabling health professionals from

many disciplines to make better informed judgments

about treatment and care. In addition, results from such

studies can enable policymakers at all levels to improve

the overall health of Americans.

Conducting a clinical study that provides an analysis

of whether the interventions or variables studied are

efficacious and safe for the specific groups of interest

requires a strong commitment to maintaining the scientific integrity of the study. Such a commitment is crucial

in every aspect of the study’s design, conduct, analysis,

and interpretation. A clinical study that is not properly

designed and implemented can provide misleading or

incorrect information that may, in fact, prove more detrimental than having no information at all. Any issues or

factors that could threaten the validity of a study must

be identified and addressed in the study design.

Scientific investigators have a special responsibility

to consider and carefully monitor the balance between

validity and the ability to generalize research findings

and analyses. The heterogeneity of study populations has

historically been thought to ensure that research findings

can be generalized to other groups. On the other hand,

the validity of study results, that is, the assurance that

the exposure or intervention itself is responsible for the

observed effects, is enhanced by studying homogeneous

populations to eliminate differences among the groups

that might lead to spurious results. It is crucially important

to recognize that the first requirement for generalizing a

study result is that it be valid—an invalid result simply

cannot be generalized to any group. The need for scientific
4

validity must be balanced against the need for heterogeneity of subjects so that results can be generalized

to the broadest possible population.

Key design and implementation issues of particularimportance in relation to the inclusion of women or

minority women in clinical studies are discussed below.

Although many of these issues may be applicable for all

clinical study populations, studies specifically targeting

women or minorities may differ in specification of the

research questions, and special study design and implementation approaches are often necessary to ensure

adequate recruitment and retention of these groups

in study cohorts. At the same time, investigators must

ensure that the data obtained on these groups are valid.

Therefore, it is crucial to consider how characteristics of

study participants relate to the design, conduct, analysis,

and interpretation of the study. These considerations

are important to consider in addition to the traditional

scientific issues.

THE RESEARCH QUESTION

The composition of the study population is directlyrelated to the question being addressed in a scientific

study because disease incidence, prevalence, and mortality—

as well as associations of risk factors with disease occurrence—

may differ by gender and across different racial and ethnic

groups. For example, African-American, Hispanic, and

Native American women have been shown to have higher

rates of diabetes, hypertension, and obesity than Caucasian

women, and associations of varying magnitudes of these

conditions with mortality are observed across race and

ethnicity.1,2,3 Different approaches to interventions or

treatments are sometimes needed by different groups.

Quantitative differences, or differences in the magnitude

of the benefits and risks may often exist, but even qualitative differences, in which different groups respond to the

intervention or treatment in an opposite manner, are

sometimes observed.

DESIGN AND STUDY METHODOLOGY

Many factors regarding methodology must be considered when planning a clinical study that includes

women, minorities, or those from diverse socioeconomic

strata as participants. For example, the need for keeping

a study concise must be weighed against the desire for

collecting as much data as possible, which could require a

more complicated study. A concise study does not overtax

participants with unnecessary tests and allows straightforward inference and interpretation. On the other hand,

studies of diverse populations may require more complex

assessments to achieve a similar level of validity within

each subgroup. Furthermore, in a more complex study

investigators may collect a large amount of data that can

be used to address a number of research questions from

one study rather than attempting to study the same population repeatedly. Collecting the required amount of data

is also important because certain types of clinical studies,

as a result of their high cost, can be conducted only once.

Another consideration when deciding on study methodology is how to balance design features that are necessary

to ensure the validity of a trial with issues that could create

barriers to participation. Using a double-blind study design

and incorporating a placebo into a trial may be necessary

for controlling bias and thus assessing subjective outcomes

and side effects. Also, random allocation is critical because

it is the only strategy that can achieve control of both

known and unknown confounding variables. However,

these and other design features may create barriers to the

participation of low-income women, for example, because

they may view study participation as a means to obtain

otherwise unavailable health care services. Some women

may fear being randomly assigned to a group and not

knowing if they are receiving an intervention. These fears

may arise legitimately from the sometimes unfortunate

history of women and minority populations as participants

in research studies. However, because these design features

may be essential to preserve the validity of the study, special

educational efforts may be required so that incorporating

these features does not create barriers to participation

and, ultimately, to the study’s success.

SAMPLE SIZE

The issue of adequate sample size is another criticallyimportant aspect of study design that is affected by

the nature of the study population. If the sample size is

inadequate to answer the question posed, investigators

run the risk of obtaining an informative null result, that

is, a finding that is not statistically significant because the

study did not have adequate power to detect an effect even

if one were, in fact, present. Such results can be scientifically very harmful; they are likely to be misinterpreted

as indicating no effect, when, in fact, the effect simply

could not be detected.

The exact sample size needed will depend directly

on the particular question. For example, a study in which

the investigators’ goal is to evaluate efficacy or side effects

separately for women and men or for different ethnic

groups would require a substantially larger sample than a

study that simply includes all genders and ethnic groups

as study participants and evaluates the overall data.

Key Design and Implementation Issues
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 5

Larger sample sizes of women may often be required

in comparison with sample sizes of men for several reasons. Increased variability attributable to cyclic hormonal

fluctuations or other physiologic gender-based differences

decreases the statistical power associated with a given

sample size. Larger sample sizes or a longer followup time

may also be required for studies with women than for

comparable studies with men because certain outcomes

of interest occur at a lower rate in women than in men.

For example, the baseline rate of cardiovascular disease

by age 60 in women is approximately one-third of that

in men. Thus, the Physician’s Health Study required a

sample size of 22,000 men older than age 40 to detect

a benefit of aspirin in the prevention of heart disease

whereas the Women’s Health Study required 40,000

women older than age 45 to detect the same result.4

Similarly, differences in disease prevalence among different

racial and ethnic groups must be accounted for when

determining sample size. In addition, when there is reason

to expect racial or ethnic variation in biological or clinical

responses, samples of minority women must be adequate

to detect benefit and risk patterns that may be different

from those in white women. The resultant increased

sample size in studies involving women and minorities

can increase the total cost of a study, which makes it

critical that each research question and each study

be as valid and efficiently implemented as possible.

METHODS OF RECRUITMENT AND RETENTION

Some of the potential barriers to recruitment andretention of women in clinical studies are unique. For

example, women in general may have special economic

or logistical barriers such as transportation or child-care

difficulties that may prevent them from participating in

a clinical study. Women from low socioeconomic groups

or from rural areas may have additional economic or

logistical barriers that do not necessarily apply to higher

income or urban women. For any study that is to include

these groups, investigators will have to make a substantial

commitment to address these and other issues or barriers

in every aspect of its design and conduct. The principal

investigator or other collaborators may want to invite

primary care physicians, whose practices often contain

the target populations, to planning meetings to request

their input regarding protocol design. Successful recruitment and retention can be enhanced by involving female

research staff similar in race and ethnicity to the participants in the planning and conduct of the study and by

designing recruitment materials and documents that

are comprehensible and culturally sensitive.

In an effort to reduce barriers to recruitment, investigators may want to consider offering evening and weekend

hours and providing child care, meals, and transportation.

For further discussion on potential barriers to recruitment

and how to overcome them see chapter 4: Participant and

Community Issues in the Recruitment and Retention of

Women in Clinical Studies.

When designing a clinical study, investigators mustconsider a number of issues, including the need to

maintain the highest standards of scientific integrity and

the balance between validity of findings and the ability

to generalize research results to the relevant population

groups. Key design issues include having a study population appropriate for the research question, various design

and measurement issues, sample size, and recruitment

and retention methods. Consideration of these issues

results in a number of recommendations designed to:

 Determine gender representation in clinical studies

based on the research question to be addressed and

the base rates of the illness by sex or by rates of

morbidity or mortality for the illness by sex.

 Incorporate extra visits and flexible scheduling

needed by women into the study design.

 Increase support for studies into the issue of

hormonal and other biologically driven, genderbased differences to determine the impact of these

differences on drug and treatment responses.

 Conduct research on the social and psychological

barriers to women’s participation in clinical studies.

 Include the participant’s own health care provider in

the study, if possible, so that the bonding achieved in this

relationship can be carried over to the research setting.

 Encourage meta-analyses and/or pooled analyses

on existing data sets of women and minorities that

are too small to be analyzed individually in an economical fashion.

 Ensure that all aspects of a study, from its planning

through its execution, are sensitive to the cultural,

linguistic, socioeconomic, and logistical characteristics

of the populations studied. For example, this should

include involving women and minorities in designing

the research, in preparing study materials, and in

interacting with participants in a culturally and

linguistically sensitive manner.

Summary and Recommendations
6

References

1. Gillum RF, Grant CT. Coronary heart disease in

black populations. II. Risk factors. Am Heart J

1982;104:852-64.

2. Ernst ND, Harlan WR. Obesity and cardiovascular

disease in minority populations. Am J Clin Nutr

1991;53:15075-16015.

3. Hanis CJ et al. Diabetes among Mexican Americans

in Starr County, Texas. Am J Epidemiol 1983;118:

659-72.

4. Buring JE, Hennekens CH. In press. A randomized

trial of cardiovascular disease in women: an

investigator’s view. Ann Epidemiol 1994;4:111-14.
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 7

Introduction

CHAPTER 3

Although involving women in study populationspresents many challenges for the institutions and

investigators, the benefits to society of including them

outweigh the associated costs.1 However, the appropriate

level of inclusion of women in clinical studies can only

be achieved if investigators and their sponsoring institutions incorporate female participants’ needs and concerns into their research planning decisions and work

in partnership with women and men in the communities

from which study populations are recruited. This should

occur during the study design and planning phase, during

outreach and recruitment efforts, and, most importantly,

during the study itself. To be successful, these efforts

must specifically address the barriers that prevent the

recruitment and retention of women—especially rural,

low-income, and minority women—in clinical studies.

Before discussing the main issues faced by investigatorsand institutions in the recruitment and retention of

women in clinical studies, it is useful to review the primary

types of studies that exist and the concerns the patients and

public have about these studies. Most clinical biomedical

research takes place in the following general formats:

randomized clinical or treatment trials, prevention trials,

nonrandomized treatment trials, and observational studies.

Each format presents investigators with different study

design and implementation issues.

THE RANDOMIZED CLINICAL TRIAL

Treatment Trials

The prospective randomized study is the foundation ofclinical research;1,2 it involves a considerable investment

of time and money as well as patient and investigator

efforts. With proper stratification, randomization can

achieve an excellent balance between groups on variables

that might otherwise introduce bias. The principal advantage

of randomization is that it protects against the probability

that a difference between comparison groups will be

observed and declared significant when, in fact, the interventions or treatments being compared are equivalent and

INVESTIGATOR AND

INSTITUTIONAL

ISSUES IN THE

RECRUITMENT

AND RETENTION

OF WOMEN IN

CLINICAL STUDIES

Maureen M. Henderson, M.D., D.P.H.

Marion M. Lee, Ph.D., M.P.H. An Overview of Clinical Studies
8

the observed differences are due only to chance. Assuming

adequate sample size, the randomized trial also protects

against a conclusion that two interventions or treatments

are equivalent when, in fact, one is superior. Randomized

studies tend to reduce and even eliminate biased conclusions that might occur because of subjective factors that

may influence research results, for example, patients want

to get better and investigators want successful results, or

patients or investigators may believe one treatment is

superior to another.3

Perhaps the most serious potential objections to randomized studies center around ethical issues,4,5,6,7 for example,

the decision to withhold treatment from a control group

or to give a possibly inferior treatment to one group. The

random allocation of patients in a well-designed clinical

study is more ethical than trying out a new therapy in

an unscientific manner or basing treatment on clinical

impressions or past experience.1 It has been argued that

researchers have an obligation to use their judgment and

recommend the “best” therapy, no matter how tentative or

inconclusive the data on which that judgment is based.8

However, problems arise when there is both uncertainty

about the value of a new therapy and doubt regarding

the efficacy of standard treatment.

The researcher involved in a randomized study makes

a scientifically valid judgment that the best therapy is not

known. Many physicians, however, have difficulty admitting to the patient or convincing the patient that they do

not know what the best available therapy is. A leading

cause for failure to enter a patient in a clinical study, when

an appropriate study is available, is physician choice.9

If certain types of patients are systematically excluded,

this can result in selection bias and reduce the ability

to generalize research results even when the study is

internally valid.10

The attitudes of patients and the public in general

toward clinical studies have been evaluated by Cassileth,

et al. in a survey of 295 subjects.11 Most respondents, 71

percent, believed that patients should serve as research

subjects and that such patients make an important contribution to society. However, a substantial minority, 29

percent, disapproved of patients serving as research

subjects, and 36 percent thought that patients receiving

treatment recommended by their physician received better

care. Of interest is that 70 percent of respondents thought

that their doctors knew privately which of the investigational treatments was best. Ganz’ summary of the concerns

of patients and the public regarding clinical studies is

shown in table 1.12

TABLE 1—CONCERNS OF PATIENTS AND THE PUBLIC

 Do patients entered into clinical studies receive the

best medical care?

 If physicians would not agree to participate in a clinical

study, should patients be expected to participate?

 How can patients (and their physicians) be assured

that clinical studies are well designed and will answer

important questions?

 Can better methods be developed to inform patients

about treatment options?

 How can patients obtain more information about

survival, treatment, toxicity, and quality-of-life

before considering participation in a clinical study?

 Is disease-free survival an acceptable outcome

measure for clinical studies?

SOURCE: Ganz P. Clinical trials: concerns of the patient and the public.

Cancer 1990;65:2394-99.

For human subjects who volunteer to participate

in clinical studies, the ultimate protection against the

conduct of an unethical study is an intelligent, informed,

conscientious, compassionate, and responsible investigator.13

Institutional review mechanisms or elaborately designed

consent forms14 are not foolproof means for avoiding

ethical problems. Four community models have been

established to make it possible for patients who are

treated in smaller communities to be included in

national clinical trial protocols.15

 The Medical System—Participation Model. In this model,

researchers bring health care professionals practicing

in the community into the research network. One

mechanism for attracting participants is to have local

physicians enroll women in studies and follow them to

detect possible side effects from an experimental drug.

 The Medical System—Referral Model. In this model,

representatives of the research organization ask local

practicing professionals to recruit patients and refer

them to a central network. In this case, the investigators

and support staff work totally within established

research organizations.

 The General Community—Direct Model. In this model,

the central research organization appeals directly to

community residents, often using familiar media sources.

 General Community—Indirect Model. In this model,

representatives of the research organization mobilize

institutions to serve as intermediaries between community residents and their organization. For example,
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 9

a network of outpatient clinic facilities might be used to

attract patients of a specific ethnic group. These clinics

perform the research with the sponsoring institution

acting as the partner with monitoring responsibilities.

Considerable organizational expertise is required

for mobilizing community members, leaders, and

representatives of institutions to participate directly

in research. This approach implies that there is a

preexisting infrastructure for identifying community

leaders and mobilizing community resources.

PREVENTION TRIALS

The factors motivating an individual to participate ina disease prevention study such as a chemoprevention

study for breast or prostate cancer include the following:

 Feelings of altruism that the study may ultimately

help someone else.

 An individual’s perceived risk of developing

the disease.

 The severity of the disease to be prevented.

 Personal or cultural attitudes toward the disease to

be prevented (e.g., a fatalistic attitude toward cancer).

 The perceived efficacy of the proposed intervention.

 The perceived risk of the intervention.

 An understanding of randomization and the nature

of controlled, especially placebo-controlled, studies.

 An understanding that there may be no personal

gain, only a gain in medical knowledge.

Another motivating issue that is similar to those for

treatment studies is trust in the investigator that she

or he will not place the subject at unnecessary risk.

The issue of perceived risk is exceedingly important

to prevention studies. If an individual feels that she or

he is at minimal or no risk for the development of a

given disease, there is no motivation for participation

in a prevention study. Currently, there is no established

instrument to measure perceived risk, but attempts are

being made to identify one.16,17 An individual’s perceived

risk of cancer, for example, is dependent on her or his

experiences with cancer in family, friends, and acquaintances as well as on her or his understanding of cancer

risk factors. Women who are at low risk but perceive

themselves to be at high risk often volunteer for clinical

trials, whereas women who are at high risk but perceive

themselves to be at low risk do not volunteer. Because

prevention studies involve healthy individuals who are

at risk but have not yet developed the disease in question,

the proposed intervention must be essentially devoid of

side effects. This situation differs markedly from the situation

of an individual being treated for a life-threatening disease

who is willing to tolerate undesirable and prolonged side

effects. For the research subject on a prevention study to

be compliant with long-term treatment and followup, she

or he should experience only minor, if any, side effects.

Trust in the investigator is a major issue in any clinical

study and lack of trust is a potential barrier to participation.18 The issue of trust is dependent upon the subject’s

prior experience with health care providers and the

reputation of the investigator or institution performing

the study. Long-lasting recollections and concerns, especially among African Americans, regarding the Tuskegee

syphilis study19 in which appropriate treatment for the

disease was withheld from the African-American men

participating in the study should not be underestimated.

These concerns and how they can be addressed by

investigators and institutions can be clustered into the

following issue categories presented in the next section.

To be successful, the investigator and the sponsoring

institution must be sensitive to all of these issues and

work closely to establish a partnership with the subject

and her or his supportive care system. Attempts to use

the models described above are now being used to

recruit healthy participants into prevention trials.

NONRANDOMIZED TREATMENT TRIALS

Although the principal aim of treatment studies isresearch, they also promote improved patient care

and contribute to the professional education of health care

providers.20 Well-designed treatment studies, in general,

offer more than just state-of-the-art care; they are the best

available treatment. The public, in general, is currently

more aware of the value of treatment studies than of other

types of studies. Cancer patients, in particular, are seeking

physicians and medical institutions that participate in

National Cancer Institute (NCI)-approved clinical studies.

The factors motivating an individual to participate in a

treatment study are complex. Individuals with advanced,

life-threatening diseases such as cancer and AIDS are, as

a rule, highly motivated to participate in clinical studies

because cutting-edge treatment offers them greater hope

of benefit than standard treatment. As noted by one

researcher, “The miserable have no other medicine . . .

only hope.”21 This knowledge places an even greater

responsibility on the investigator who may be interacting

with a potentially vulnerable class of patients. These

patients often wish to try all options in an attempt to

hold on until a “cure” is found.22
10

Kardinal and Cupper evaluated 50 patients with advanced

cancer who were being treated in NCI-approved clinical

studies23 and found that there were three primary factors

motivating them to participate:

 Hope that the new treatment offered a better chance

for control of their disease.

 Altruistic feelings that, even if the treatment does not

help them, it might ultimately help others. As stated

by a young man with acute leukemia, “I’m glad to be

on it. I have to be . . . for the men coming after me.”

 Trust that the physician would not have recommended

an investigational therapy unless she or he thought it

would help. It is this issue of trust that places enormous

responsibility on the physician investigator.24

Kardinal and Cupper also noted that some patients

with advanced cancer feel trapped by a lack of therapeutic

alternatives. Some of their views are summarized in the

following statements: “What option do I have?” “I know

what I have and I can’t shake it.” “There is a chance that

this might really help.” However, by participating in a study

even people who feel trapped show improved morale and

an increased sense of purpose. Because patients with

AIDS or cancer are forced to confront a number of issues,

including their own mortality, that are not applicable to

individuals with less-immediate life-threatening diseases,25

their rights and welfare must be especially safeguarded.

OBSERVATIONAL STUDIES

Observational studies differ in several importantrespects from other types of clinical studies, but

they have provided many unique and valuable insights

into the causes and development of major diseases. For

example, one of the major contributions of the Multiple

Risk Factor Intervention Trial (MRFIT) was the development of stable estimates of relative and absolute risk for

coronary heart disease in men based on their levels of

serum cholesterol. These estimates, which have been

critically important in formulating national guidelines

on cholesterol-lowering measures, were not based on

data generated during the MRFIT trial itself but on

observational data generated on the large group of

men screened for participation in MRFIT.

In observational studies, a nonrandomized population

is followed for a period of time. Baseline and followup

physical examinations are conducted and laboratory

samples taken. The data generated permit researchers to

identify and test hypotheses with regard to the etiology

and development of disease, to develop estimates of

comparative risk among population subgroups, and

to refine and improve the objectives and design of

other types of clinical studies.

Many of the strengths of observational studies lie in

the ways that they can complement other types of clinical

studies. For example, only a small number of intervention

arms are possible in randomized, controlled studies. Results

from such studies will not yield direct information on other

interventions that are similar to, but not the same as, the

interventions studied. An observational study, on the other

hand, can collect a broad base of data that may shed light

on a range of interventions.

Major randomized clinical studies require that many

potential participants be screened in order to recruit the

targeted number of actual participants. This group can

provide a population for an observational study at a

relatively modest additional cost. This is the case for

the NIH’s Women’s Health Initiative, which plans to

enroll 63,000 women in a randomized clinical study

and an additional 100,000 women in a complementary

observational study.

The significant size of the population enrolled in this

observational study will also allow researchers to collect

data across a spectrum of racial and ethnic minority groups,

thus increasing the chances of identifying and understanding disease risk factors in individual minority groups.

For many individuals, an observational study provides

an opportunity to participate in an ongoing and potentially

valuable research effort without having to undergo potentially undesirable treatments or interventions. Other

individuals may be able to participate in an observational

study even though they are ineligible for participation in

a prevention or treatment study.

COST AND INSURANCE ISSUES

The high costs of conducting clinical studies may renderany additional costs associated with the inclusion of

women or minorities in clinical studies excessive in the

perceptions of many investigators or research administrators. These high costs are inherent in the nature of the

research and are increasing due to current research trends.

Clinical investigators have responsibilities associated

with research in humans that do not apply to either the

work effort or budget of basic science studies; these

responsibilities exist whether participants are ill or healthy.

Increasingly, studies involving humans are designed to

measure incremental benefit, or the additional benefits of

a “new” treatment over the benefits of the best current

available treatment. These additional benefits may be

minor and are more often related to functioning and

quality-of-life than to survival. As the increments of

Key Investigator and Institutional Issues
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 11

improvement become smaller, increasing numbers of

investigators are turning their attention to research on

primary prevention of disease and its preclinical detection

and management. In the areas of preclinical detection

and management, large numbers of participants are

needed to measure success, which leads to an increase

in the numbers of multicenter, randomized studies.

An additional cost factor faced by investigators and

their institutions in including women in clinical research

is the lack of insurance to cover untoward events that

may affect study subjects. Historically, the costs of the

side effects of therapeutic studies have been paid for by

third-party, personal, organizational, or study-specific

liability insurance arrangements. Liability associated with

primary prevention studies has been traditionally covered

either by specifically designated public funds, as a direct

research cost or as a specifically insured research cost.

As clinical scientists have begun to solicit individuals

who are not their clients to volunteer as study subjects,

designating who will pay the costs of therapeutic and

primary prevention studies has become more difficult.

As a result, many subjects may be deterred from participating because they have no assurance that treatment for

possible costly side effects will be covered. Furthermore,

the lack of insurance coverage for participants may

make researchers and their institutions, already lacking

adequate resources, liable for the costs of researchassociated side effects.

Even for treatment studies in which costs could

potentially be covered under routine patient care and for

studies in which treatment is considered experimental,

costs may not be reimbursable. This factor may lead to

marked underrepresentation of low-income women in

clinical studies. Thus, in some cases, patients who wish

to enroll in studies of lifesaving treatments cannot afford

to participate unless investigators can cover their costs.

STUDY DESIGN AND RESEARCH STAFFING ISSUES

I

n designing studies to include female participants,

researchers should carefully analyze the goals and

purposes of the study to identify gender-specific issues.

Once researchers identify these issues, they should develop

solutions applicable to a broad range of subject needs and

situations. Employing women in visible, key positions

during the strategic planning process helps to ensure

that these solutions will be viable; it can also serve as

an aide to recruitment.

Because of the large number of subjects required, most

randomized studies of major diseases require multicenter

and multidisciplinary collaboration. The attention given to

the selection and recruitment of collaborating centers and

investigators is critical, as is the careful definition of the

number and qualifications of eligible subjects. The experience of research centers and whether they have adequate

systems for participant data collection and management

are important considerations in the assessment of community resources. The evaluation of these factors also

helps to determine whether the research design should be

centralized and carried out from a single research facility

or decentralized and carried out in community centers.

The success of some networks designed to bring community hospitals and clinics, their health care professionals,

and their patients into cancer chemotherapeutic studies

has led to their involvement in chemoprevention preclinical

detection and management studies. These networks have

been required to join with a research center and have

usually chosen to link-up with one or more designated

groups of institutions committed to multicenter studies.

There has been a serious effort to include cancer prevention and control research in these networks. For this reason,

researchers should consider addressing not only existing

networks but also newly created or ad hoc alliances among

existing networks, institutions within those networks, or

outside organizations.

ISSUES RELATED TO INSTITUTIONAL

REVIEW BOARDS AND THE PERSPECTIVES

OF POTENTIAL STUDY PARTICIPANTS

I

n 1973, NIH established an Office for the Protection

from Research Risks, which mandated Institutional

Review Boards (IRBs) in each institution receiving Federal

research funding.26 The primary purpose of these IRBs

is to ensure that researchers are aware of the rights and

well-being of study subjects in clinical research projects.

Among the few initial rules promulgated by the IRBs was

the mandate requiring that the research designs include

an “equitable selection of subjects.”

 Members of IRBs review research protocols before

granting funds to researchers. The boards require that

investigators provide justification for single-gender

selection and for populations selected. However, it

is not until the annual or interim project review that

the board actually learns the composition of the study

population; this procedure limits the ability of an IRB

to ensure a balanced study population before research

begins. Despite recent efforts of IRBs to encourage

diversity in study populations, researchers tend to

choose subjects from the most convenient subject

population. If asked to account for a lack of diversity,

they often indicate that the effort made to recruit other

than mostly middle-class male subjects was unsuccessful.

In addition to the responsibility for ensuring the

appropriate diversity among study subjects, IRBs are

also charged with establishing a communication framework to answer participants’ questions about the studies.
12

Although answering questions on potential side effects in

ways that study participants can understand may require

extra effort from investigators, the benefits of this in terms

of enhanced trust and cooperation from participants are

unmistakable in general and may be particularly salient

for women in groups heretofore excluded from research,

less trusting of researchers, or less experienced with the

research environment.

At times, investigators may be responsible for screening

individuals whose participation may not be in their own

best interest or in the interest of the study. For example,

an individual may perceive herself or himself to be at

high risk for a disease and consider volunteering for a

study when, in fact, the information obtained does not

indicate that she or he faces such risk. This is often the

case among young women who volunteer to participate

in breast cancer studies. Investigators may be tempted to

enroll these individuals because they are anxious to participate and will comply with study requirements. However,

investigators must not capitalize on these individuals’

perceptions of personal risk but should decide whether

such participation makes a valid contribution to the study.27

ISSUES RELATED TO RECRUITMENT AND

RETENTION OF WOMEN IN CLINICAL STUDIES

A lthough experience from studies such as the NationalHeart, Lung, and Blood Institute’s (NHLBI’s) Pawtucket

Heart Health Program (PHHP) shows that, in general,

women, including older women, are responsive study

participants,28 a majority of clinical investigators are

inexperienced in the use of strategies to recruit patients

who do not present through the usual channels, particularly women of diverse racial and ethnic groups and

socioeconomic strata.

Most urban universities have not yet fully reached

minority communities to educate them on the personal

and societal benefits of participating in clinical research.

Time-consuming and costly targeted recruitment strategies

often have to be added to population- or network-based

recruitment to ensure that diverse populations are reached.

Recruitment yields in special populations may be less than

the 3 to 15 percent reported in clinical studies and the

1 to 2 percent reported in primary prevention studies.29

This means that 85 percent or more of the researchers’

community recruitment activities are nonproductive;

unfortunately, such nonproductive activity is not

usually budgeted.

Each special population requires a recruitment strategy

customized to its characteristics and concerns. The more

customized the targeted strategies, the more additional

resources have to be planned and budgeted. Time commitments required from staff also increase markedly when

targeted recruitment strategies are used. In the case of

identifying high-risk women, additional staff time is

needed to review pathology records. Additional outreach

recruiters may also be required when researchers who

have limited familiarity with the cultures or languages

of ethnically diverse populations are attempting to

recruit those populations for a clinical research study.

Effective recruitment may also require the development

of partnerships between research organizations and their

target groups. The ability to develop partnerships is central

to the successful planning of the recruitment and retention

of women in clinical prevention studies. There are two

basic types of partnerships:

 Partnerships With Individuals. Forming partnerships

with individuals or volunteers who help to recruit

additional women into studies is a cost-effective way

to increase participation rates.30 The volunteers’ awareness and knowledge of the cultural environment can

provide credibility and access for the research team.

Because they are often members of targeted social

networks, volunteers help foster local awareness while

acting as full-time agents for information dissemination.

This partnership also helps promote study retention

and institutionalization of programs after funding ends.

 Partnerships With Organizations. Partnerships with

representatives or agents of organizations may be more

difficult to foster than partnerships with individuals.

Organizations must be approached carefully through

gatekeepers or decisionmakers. The goals and needs

of the organization must always be respected and

accountability criteria such as profit, reputation,

and prestige openly discussed.

The Columbia River Clinical Community Oncology

Program in Portland, Oregon, provides one example of

the successful recruitment and retention of women in

clinical studies using partnerships and networks. The

program involves members of the Urban League and

the American Cancer Society Underserved Committee.

Researchers in the program have formed a liaison with

the AIDS Research Network and the National Black

Leadership Initiative. Women’s church groups in the

African-American community also have been contacted.

Contact with these groups has led to the development

of a list of community leaders; leaders who appear on

several lists are considered as potential research recruitment agents. Recent activities using leaders from the

community have helped to identify battered women

as potential participants in cancer research.

Establishing an advisory committee or coalition comprised of a wide range of groups to participate in the

initial planning of the study and to function as an integral

component of the study as it develops is an important

component in successful recruitment and retention of

special populations. The committees or coalitions are
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 13

able to assist with study design and act as endorsers.

The coalition should be comprised of a wide range of

organizations and their representatives, including public

agencies, health care providers, senior citizens’ groups,

worksite managers, families, and spiritual and/or religious

organizations. There are many other possible sources

for participants as well; for example, social clubs may

provide investigators with access to women of differing

ethnic backgrounds; professional organizations provide

access to women in health-related, education, business,

or other fields; housing or tenant associations provide

access to specific neighborhoods, subsidized populations,

or elderly persons. Finally, voluntary and professional

organizations such as the National Cancer Society, the

American Heart Association, the American Psychological

Association, the National Medical Association, and many

others can be essential in forming a coalition.

Study visibility is one of the most reliable indicators

of what the level of participation will be. Large-scale,

low-budget public relations campaigns reach community

members, especially those who have no affiliation with

community organizations, in the environments they

frequent the most. Efforts to reach the public in these

different environments may include, for example, placing

posters in a grocery store or public service announcements

on the television or radio. Learning about a study through a

familiar information source may lend credibility to a project.

Benefits and Risks to Investigators

in Conducting Clinical Studies

I

nvolving women in clinical studies can augment the

career development and general benefits that accrue

from involvement in clinical research for the investigator

and her or his institution. There may be special incentives

for involving women in clinical trials until the historical

underrepresentation of women and the relative neglect

of the disorders affecting them has been rectified. Furthermore, some sectors of the public perceive clinical research

as producing great social benefit and this positive perception carries over to sponsoring institutions.

No specific risks, except the historical concerns regarding research with women of childbearing potential, apply

to clinical studies that include female subjects. However,

all clinical investigators assume general risks. Perhaps the

greatest risk to investigators and their sponsoring institutions is that their research will not answer important

questions. Thus, researchers must avoid any distraction

from the pursuit of high-quality research, including the

temptation to conduct easily fundable research or research

with less than optimum designs. Inappropriate specification of a study design, with respect to addressing gender

and diversity issues, would fall into this category. The lack

of insurance coverage for the untoward events affecting

clinical study subjects, discussed earlier in this chapter,

is another major risk for investigators and institutions.

Finally, the additional burdens placed on researchers

in clinical settings as opposed to basic research settings

may be regarded as a risk. For example, investigators are

required to provide detailed explanations of research

protocols, risks, and benefits to participants. They must

also respond to unanticipated health-related and personal

events in participants’ lives. Meeting these demands

reduces productivity and places clinical investigators

at a special risk in the academic environment.

Summary and Recommendations

Each of the major approaches used in biomedicalresearch—randomized clinical or treatment trials

and nonrandomized treatment studies, prevention trials,

and observational studies—presents a different set of

study design and implementation challenges. Other issues

considered in this chapter cut across all types of clinical

research. These issues include cost and insurance reimbursement, research study staffing, and collaborative

networking, IRBs and the perspectives of potential study

participants, and recruitment and retention strategies.

Recommendations related to these issues are to:

 Resolve the issue of lack of insurance coverage

for treatment of incidental medical conditions

and research-associated side effects to promote

the inclusion of women in clinical studies.

 Analyze the goals and purposes of clinical studies

to identify issues of particular relevance to women.

 Include women in the strategic planning process and

employ them in visible, key positions, whenever possible.

 Plan and establish infrastructure to support both

multicenter and community-based disease treatment

and prevention studies, and use current exploratory

models to develop estimates of the dimensions, performance, and utility of proposed future networks.

 Make efforts to capture, analyze, and evaluate information on the process of establishing and maintaining

research partnerships.

 Expand the role of IRBs to encompass research funded

by non-Federal agencies and the ongoing process of

research.
14

 Involve IRBs in the early design phases of research to

ensure that there is an equitable blend of study subjects.

 Ensure that all participants’ questions about the study

and possible side effects of treatment are answered

fully and comprehensibly; avoid even subtle intimidation of study participants.

 Develop cost-effective recruitment approaches that

combine strategies targeted toward involving women

as a group as well as women of a particular race, socioeconomic status, age, risk profile, or geographic location.

 Encourage partnerships and networks, which are

excellent methods for recruitment of diverse female

populations, and disseminate information about successful recruitment strategies such as screening, counseling,

and referral events (SCOREs), which were developed for

the Pawtucket Heart Health Program.31,32

References

1. Byar DP, Simon RM, Friedeward WT, Schlesselman JJ,

DeMets DL, Ellenberg JH, Gail MH, Ware JH. Randomized clinical trials: perspectives on some recent ideas.

N Engl J Med 1976;295(2):74-80.

2. Green SB. Randomized clinical trials: design and

analysis. Semin Oncol 1981;8(4):417-23.

3. Ederer F. Patient bias, investigator bias and the doublemasked procedure in clinical trials. Am J Med

1975;58(3):295-99.

4. Spodlick DH. The randomized controlled clinical trial:

scientific and ethical bases. Am J Med 1982;73:420-25.

5. Schafer A. The ethics of the randomized clinical trial.

N Engl J Med 1982;307(12):719-24.

6. Rosner F. The ethics of randomized clinical trials.

Am J Med 1981;82:283-90.

7. Wikler D. Ethical considerations in randomized

clinical trials. Semin Oncol 1981;8(4):437-41.

8. Passamini E. Clinical trials—are they ethical?

N Engl J Med 1991;324(22):1589-91.

9. Hunter CP, Frelick RW, Feldman AR, Bavier AR,

Dunlap WH, Ford L, Henson D, Macfarlane D,

Smart CR, Yancik R, et al. Selection factors in clinical

trials: results from the community clinical oncology

program physician’s patient log. Cancer Treat Rep

1987;71(6): 559-65.

10. Antman K, Amato D, Wood W, Corson J, Suit H,

Proppe K, Carey R, Greeberger J, Wilson R, Frei III E.

Selection bias in clinical trials. J Clin Oncol

1985;3(8):1142-47.

11. Cassileth BR, Lusk EJ, Miller DS, Hurwitz S. Attitudes

toward clinical trials among patients and the public.

JAMA 1982;248(8):968-70.

12. Ganz P. Clinical trials: concerns of the patient and

the public. Cancer 1990;65:2394-99.

13. Lidz CW, Meisel A, Osterweis M, Holden JL, Marx JH,

Munetz MR. Barriers to informed consent. Ann Intern

Med 1983;99:539-43.

14. Beecher HK. Ethics and clinical research. N Engl J

Med 1966;274(24):1354-60.

15. Winn R. Outreach planning and designing and

implementing clinical research. Presented at the

Scientific Meeting on Recruitment and Retention

of Women In Clinical Studies, Bethesda, Maryland,

July 12-13, 1993.

16. Wittes RE, Friedman MA, Simon R. Some thoughts

on the future of clinical trials in cancer. Cancer Treat

Rep 1986;70(2):241-50.

17. Lipsett MB. On the nature and ethics of phase I

clinical trials of cancer chemotherapies. JAMA

1982;248(8):941-42.

18. Markman M. The ethical dilemma of phase I

clinical trials. CA 1986;36(6):367-69.

19. Kardinal CG, Cupper HT. Hope, consent, and

clinical research. Forum on medicine 1978;48-49.

20. Micetich KC, Thomasma DC. The ethics of patient

requests in experimental medicine. CA 1984;

34(2):118-20.

21. Kardinal CG, Strand B. Confrontation with cancer:

historical and existential aspects. In: Gross SC, Garb S,

eds. Cancer treatment and research in humanistic perspective: Springer Publishing Company, 1985;173-75.

22. Stromborg M. Evaluating cancer risk. In: Baird S,

McCorkle R, Grant M, eds. Cancer nursing, a

comprehensive textbook. Philadelphia: W.B.

Sanders Co., 1991;155-89.

23. Cohen R, Stromborg M. Risk assessment and

cancer risk factors. In: Grunwald S, Frogge M,

Yarbro C, Goodman M, eds. Cancer nursing.

2nd ed. 1990;103-18.

24. Bateman M, Kardinal CG, Lifsey D, Gralla RJ,

Washington A, Scroggins T, Allen S. Barriers to

minority recruitment: implications for chemoprevention trials. Proceedings of the American Society

of Clinical Oncology 12:169 (Abstract 472), 1993.

25. Des Jarlais DC, Stepherson B. History, ethics, and

politics in AIDS prevention research. Am J Public

Health 1991;81(11):1393-94.

26. McCarthy, CR. Federal protections for human research

subjects: historical perspective. J Clin Res Drug Dev

1987;1:131-41.
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 15

27. Taplin S, Anderman C, Grothaus L. Breast cancer

risk and participation in mammographic screening.

Am J Public Health 1989;79:1494-98.

28. Assaf AR, Lapane KL, Lasater TM, Carleton RA. New

perspectives on the gender gap: women try harder, but

are less successful at CVD risk reduction. Memorial

Hospital of RI, Pawtucket, RI, Brown University,

Providence RI. Abstract. Circulation 1994; 89(2):2.

Article submitted for publication.

29. Personal communication of Dr. Henderson.

30. Elder JP, McKenna C, Lazieh M, Ferreira A,

Lasater TM, Carleton RA. The use of volunteers

in mass screening for high blood pressure. Am J

Prev Med 1986;2(5):268-72.

31. Lasater TM, Lefebvre RC, Carleton RA. The Pawtucket

Heart Health Program: IV. Community level programming for heart health. RI Med J 1988;71:31-34.

32. Lasater T, Abrams D, Artz L, Beaudin P, Caberera L,

Elder J, Ferreira A, Knisley P, Peterson G, Rodrigues A,

et al. Lay volunteer delivery of community-based

cardiovascular risk factor modification programs: the

Pawtucket experiment. In: Matarazzo, JD, et al., eds.

Behavioral health: a handbook of health enhancement

and disease prevention: New York: John Wiley and

Sons, Inc. 1984;1166-70.
16
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 17

PARTICIPANT

AND COMMUNITY

ISSUES IN THE

RECRUITMENT

AND RETENTION

OF WOMEN IN

CLINICAL STUDIES

Barry D. Kaufman, D.M.D.

Helen Rodriguez-Trias, M.D.

Introduction

CHAPTER 4

Federal and state governments, researchers, and institutions have expressed an increasing interest in recruiting

women into clinical studies. However, the road to meeting

that goal is paved with challenges. The needs, attitudes,

and beliefs of women, including minority women and

women from low socioeconomic strata, must be examined

if they are to be effectively recruited and retained for

clinical research. Studies have suggested that the underrepresentation of women in clinical studies is probably

related to multiple factors.1 Access to health care, mistrust

of the medical system, language barriers, cultural beliefs,

and even transportation and child care are all issues that

must be addressed to ensure that women are able and

willing to participate in clinical studies.2 These cultural,

social, and economic voids may serve as barriers between

research organizations and the patient populations they

are intended to serve.

The studies that have been most successful in recruiting and retaining women have used a variety of strategies.

Examples of some of these successful recruitment strategies

are described in chapter 5: Current Experiences in Women’s

Health Research. Community partnerships, spiritual and

religious leaders, and support networks can all play a role

in reaching women of heterogenous backgrounds, lifestyles,

and occupations. In addition, the media, through public

service announcements, health programs, and printed

materials, can do much to establish trust relationships

and inform women about health issues.

ISSUES IN THE BELIEFS AND ATTITUDES OF WOMEN

Understanding perceptions, beliefs, and attitudes iscritical if women from specific populations targeted

for study are to be successfully recruited. Misinformation,

suspicion, or distrust among potential study participants

regarding clinical studies, the medical profession, and

research team members can greatly diminish the success

of patient enrollment efforts.

Though the body of research on patient attitudes is

still limited, the existence of such reservations about

participation in clinical studies in certain populations

has been suggested by the findings of several studies

conducted in the United States and Europe.2

 The patients

who most readily elect to participate in clinical studies

Key Issues
18

may not always come from the populations most in need

of study. Actual study participants tend to be young and

well educated.2

Participants’ opinions about the quality of study design

and confidence in those conducting the research can be

important determinants of enrollment and retention. The

history of women’s medical treatment has also influenced

their perceptions of the health care establishment and

of the long-term safety of some treatments. Reports of

medical treatments with adverse effects, for example,

therapies with thalidomide and DES, have also diminished many women’s trust in the research community.

The experiences of members of minority communities,

who may not have adequate access to or availability of

affordable services because they lack or have insufficient

health insurance, only reinforce such perceptions. For

example, the Tuskeegee3

 experiment, conducted on poor,

rural black men, is the basis for mistrust of research

within this group in particular.

This sense of mistrust has been aggravated by women’s

perceptions of a male medical establishment that is insensitive to their needs and concerns.4

 Such perceptions may

be hard to dispel when clinical studies are designed and

conducted primarily by white males. Historically, only a

small percentage of health and research team personnel

have been minorities and women.

Another factor limiting the willingness of many women

to participate in a clinical study may be a lack of knowledge

about health and disease issues and about clinical studies in

general. Denial of the presence and dangers of a suspected

illness can compound a reluctance to participate; this is a

problem experienced by many women of diverse backgrounds. Other barriers, for example, a sense of fatalism

or of yielding to inevitable external forces, may be more

characteristic of certain populations or socioeconomic

groups. Researchers have found this to be prevalent, for

example, among Hispanics, and it can prevent the entry

of Hispanic women into clinical trials.5 In addition, when

the husband is the sole decisionmaker it is also less likely

that the woman in the family will participate in a clinical

trial. Lastly, concerns about confidentiality can impede

the enrollment of many women. For example, women

may fear that their human immunodeficiency virus (HIV)

status will become known to family or friends if they

participate in a clinical trial.

A number of strategies have been explored to overcome

the reluctance felt by many women to participate in clinical

studies. In the African-American community, for example,

researchers have found church-based outreach programs

effective in building strong, long-lasting relationships

that have created trust. Among those who attend AfricanAmerican churches, 85 percent are women at midlife or

older.6 Church-based outreach programs are exemplified

by the joint programs of the Congress of National Black

Churches (CNBC) for health-related education in conjunction with research institutions. The CNBC has successfully

collaborated with George Washington University and

Howard University in developing education programs

for the African-American community in the metropolitan

Washington, D.C., area, including programs on lipid

research, heart disease in women, and health issues for

youth and families.6

 Similar advantages can be gained

by hiring influential members of the study population

to recruit participants. We recommend that the following

steps be taken:

 Nurture positive attitudes and beliefs by establishing

and maintaining, whenever possible, one-on-one

relationships that foster trust and respect between

research staff and study participants.

 Include women in clinical trial staffs, particularly

women of the same ethnic or racial origins as those in

the study population, to the greatest extent possible.

 Promote joint decisionmaking and informed consent

to the maximum extent possible so that participants

are empowered to become active participants in their

own treatment.

 Encourage interactions and facilitate the establishment of educational and support networks between

former and current study participants to help support

positive attitudes.

ISSUES IN SOCIOECONOMIC STATUS

Frequently, the effects of low income correlate stronglywith a disproportionate burden of disease. In many

populations, lower income levels are often accompanied

by lower levels of education, literacy, and employment.

Substandard housing and environments threatened by

violence and substance abuse are also common among

members of lower socioeconomic groups.

Women of low socioeconomic strata, particularly those

who serve as caregivers, have extremely limited time and

financial resources to invest in clinical study participation.

Child care and food costs associated with participation in

a study as well as an inability or unwillingness to take

time off from a job can preclude their enrollment. The

mobile lifestyles of other populations, for example, migrant

workers and the homeless, present additional barriers to

participation. Principal investigators who are unfamiliar

with these lifestyles must make special efforts to understand these barriers and overcome them if these groups

are to be successfully recruited and retained. We recommend that the following steps be taken:

 Make participation in clinical studies possible for

women, regardless of their ability to pay. The use
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 19

of financial incentives, without creating an undue

influence, is an appropriate recruitment tool.

 Adapt program designs that overcome the barriers to

women’s participation, particularly minority women

and women from low socioeconomic strata. Examples

of such actions include maintaining extended and

flexible study clinic hours, providing transportation

and child care, and developing study materials that

are culturally and linguistically appropriate.

ISSUES IN INFORMATION DISSEMINATION

AND COMMUNICATIONS

Clinical study designers and staff face great challengesin communicating a basic understanding and awareness of particular research opportunities. As mentioned

above, educational, economic, and geographic factors can

weigh heavily on the abilities of individuals in target populations to receive and understand the necessary information.

Physician referrals are a crucial element in the successful

recruitment of a study population, but many physicians

and other health care providers, including women and

minority health care providers, are either unaware of

clinical trials or do not adequately encourage qualified

patients to participate in research projects.

For many populations, limited language skills can affect

communication and outreach efforts of clinical programs.

Researchers and others who develop communication

strategies must take careful account of target populations’

primary language or dialects, use of slang, and literacy

levels. Alternative learning styles must also be accommodated. Since their first use in 1975 by the NHLBI for its

Coronary Primary Preventive Trial (CPPT),7

 media-based

recruitment campaigns with specially designed communications and education strategies have proven to be a costeffective method for recruiting subjects for clinical trials.

The “Cuidando Su Salud” radio program on Radio

Borinquen (WILC-AM 90) in the metropolitan Washington,

D.C., area provides an example of effective media outreach

to minority populations. The program, produced by Elmer

E. Huerta, M.D., M.P.H., targets Spanish-speaking audiences

with messages and discussions about current health topics,

including screening for cancer and AIDS and tobacco

use prevention messages; the program also reassures the

audience about the confidentiality of their enrollment in

preventive health programs. The daily program reaches

an estimated audience of 75,000 people. Since it began

in 1989, it has had a measurable impact on the number

of women seeking local services for mammograms and

Pap smears.

For certain populations, which are geographically

isolated or experience high rates of poverty, mass media

alone may not always be effective. For these populations,

distributing flyers through Federal aid programs, for

example, Food Stamps or Social Security, can help.

In one example, the Hawaiian study Malama Na Wahine

Hapai: Caring for Pregnant Women8

, interpersonal communications were the key elements for patient recruitment.

The Changing Asthma Through Social Support program

of the St. Louis Neighborhood Asthma Coalition1

 relied

on trained neighborhood residents who gave asthma

management presentations and served as case workers for

children enrolled in the program. The program enrolled

300 children in study neighborhoods and another 300

in comparable control neighborhoods. Initial enrollment

was primarily accomplished through personal contacts

with the participants’ mothers, based on information

received from emergency room and asthma clinic records.

We recommend that the following steps be taken:

 Plan carefully, select communications channels judiciously, and pretest thoroughly before launching

recruitment efforts. Followup is also essential and

should include solicitation of feedback and evaluation

of program effectiveness.

 Rely on multiple channels for communications and

outreach to health professionals from many disciplines

to assist in the recruitment of study populations.

 Develop media outreach strategies with spokespersons

who can serve as role models and emphasize ethnically

targeted messages, when appropriate.

 Use informal communication networks to promote

enrollment and compliance with clinical protocols.

 In all outreach efforts, adapt the language of science

to the needs of patient groups. Make efforts to accommodate alternative ways of learning, including the

use of low-literacy materials.

ISSUES IN ACCESS TO SERVICES

As discussed above, the responsibilities frequentlyassumed by women as caregivers and providers for

children, spouses, and parents leave little time or room

for participation in clinical trials. Often, practical and

logistical problems can present the greatest barriers.

For example, women with disabilities may have great

difficulty in accessing basic health care services, much

less a specialized clinical research study.

Geographic isolation can result in limited awareness

of available services and clinical study opportunities. In

rural settings, lack of transportation and distantly located

research centers can present the greatest barriers to both

recruitment and retention, particularly for women from

low socioeconomic strata.

Barriers to research opportunities can also reflect poor

access to health care. The lack of a primary care provider

or other source of health care and/or a lack of health
20

insurance are major reasons for poor health care. A survey

whose findings were recently issued by the Commonwealth

Fund of New York found that more than one-third of the

women surveyed said they lacked basic, preventive services

during the past year, largely because of high costs and

gaps in insurance.9

 Among women who have some form

of insurance, exclusions of coverage for clinical studies

are common and create a financial barrier to enrollment.

Some populations face additional barriers in accessing

health services, including clinical trials, because of differential treatment. Lesbian women, for example, have traditionally experienced misunderstanding and even hostility on

the part of health care providers, particularly in communities in which this type of life style is unfamiliar.10 Studies

have also shown that perceptions of differential treatment

held by lesbian women have led them to fear receiving

inferior care because of their sexual orientation. With

respect to clinical studies, fears about confidentiality

breaches, unequal treatment, and biases by study staff

can seriously impede enrollment of lesbian women,

particularly as they grow older.

Finally, lack of U.S. citizenship, fear of confidentiality

breaches with respect to immigration status, and possible

deportation are important barriers for immigrant groups.

We recommend that the following steps be taken:

 Conduct community consultation and proper staff

training to accommodate the special needs of study

populations when designing clinical studies.

 Provide access to health research programs and

facilities for women to the fullest extent possible,

including transportation services.

 Enhance participant retention by developing flexible

schedules at study sites, providing alternative service

delivery such as the use of at-home examinations,

offering complete medical insurance coverage for

study participation, and providing day-care services.

 Establish and use role models and advisory boards

from the community to help direct programs. Use

community confidants to help engender a sense

of trust and guarantee of confidentiality.

ISSUES IN COMMUNITY RELATIONSHIPS

A central element in nearly every barrier to recruitmentand retention of participants in clinical studies,

particularly recruitment and retention of minority women

and women from low socioeconomic strata, is the nature

of the relationship between research institutions and the

communities whose populations they target for clinical

study participation. In the absence of common goals or a

shared recognition of the unique needs of the community,

clinical studies cannot successfully coexist with a community. The development of partnerships with concerned

members and representatives of communities is a critical

element for successful recruitment and retention. These

partnerships must be based on a foundation of trust and

mutual respect among the research institution, community

leaders, and study candidates.

Effective partnerships not only engender broad community support and successful study participation but

also result in a number of additional, tangible benefits

to all concerned. Such partnerships foster strong personal

relationships between study subjects and clinical staff that

ensure good patient retention and compliance with study

protocols. In the words of one cancer patient, “I still

consider my research nurse to be one of my best friends.

There is a definite need for continuity in the health care

profession to bring about a feeling of trust.”11 The partnerships also help ensure that study protocols and recruitment

methods are culturally sensitive. Studies benefit from hiring

program staff who reflect the ethnic and racial composition

of the populations being studied, but benefits accrue

beyond the core study staff to participating volunteers and

community staff who gain marketable skills and training.

Finally, the broad community support and participation

that result from successful partnerships can also produce

beneficial secondary effects such as greater community

interest in the sciences, stable employment opportunities,

and greater community activism. We recommend that

the following steps be taken:

 Capitalize on the success of community partnerships

in meeting recruitment and retention goals by initiating the partnerships early in the planning process.

 Identify representatives of broad-based groups,

including spiritual, religious, and business leaders,

to participate in partnerships with the research

institution.

 Use research team members with similar racial,

 ethnic, and language backgrounds as the potential

study participants. Whenever possible employ women

and minorities as principal investigators and educators

to help inspire a greater sense of trust among female

study participants.

 Address sensitivity to gender, racial, and ethnic issues

during research training. Stress the importance of

developing mutual confidence between study participants and research staff and the importance of patient

responsibility and decisionmaking skills.

 Inform patients of findings of the protocol to the

fullest extent possible by openly discussing the treatments and their implications.
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 21

ISSUES IN SOCIAL SUPPORT SYSTEMS

The availability of social support systems such as group

counseling or the use of confidants positively influences

health behavior outcomes for all patients. Studies have

linked the availability of “confidants” to individuals

undergoing stress as an important factorin reducing

depression.12 Other studies have suggested a possible

link between social support and certain measures of

immune response and the improvement of health status.12

Traditional methods of designing and conducting

studies have not always recognized the importance of

social support systems as communications channels and

as important mechanisms for the health and support of

patients. For women in particular, the integration of social

support systems into study design may be an important

element in successful recruitment and retention. These

social support systems may play an especially important

role in helping women to cope with treatment-related

stress that occurs during a study. In studies on smoking

cessation, for example, researchers have found women to

be more attuned to and better able to use social support

than men.12 In a randomized study of 66 female and male

smokers, investigators found that women were more

responsive to clinic therapy that stressed social support.13

Adequate social support may also be of greater importance

for certain populations of women who traditionally rely

on networks of extended relatives and informal networks,

including church- and neighborhood-based groups. We

recommend that the following steps be taken:

 Incorporate formal and informal sources of social

support into the design and conduct of studies by

developing cooperation between clinical study

programs and communities.

 Work with existing community structures such as

church groups that can help make patients aware of

clinical studies and help them cope with treatments

once the study is initiated. Informal networks can

be accessed through formal community structures.

ISSUES OF DATA AVAILABILITY AND

TARGETING OF SPECIAL POPULATIONS

Medical interventions in certain populations arehindered by a lack of knowledge about the incidence and prevalence of disease and about health service

utilization. For example, studies on Native Americans

can present a challenge because health data in general,

and especially for some tribal groups, do not exist or are

limited. These challenges are compounded when formal

health services are undeveloped within tribal communities,

particularly in rural areas.

Lesbian women also present a challenge to investigators.

Historically, lesbians have been alienated from health care

systems because of negative or hostile attitudes expressed

by providers.10 Consequently, there are inadequate data

about this population, although some of the data do

suggest that there may be important differences in several

health parameters between lesbians and heterosexual

women. Efforts to identify and/or recruit lesbians for

participation in clinical studies require specially crafted

research tools. We recommend that the following steps

be taken:

 Make the best use of all available community sources

of data when studying poorly documented populations.

 Include information on cultural, racial, and behavioral

characteristics when defining special populations.

 Make the fullest use of clinics, advisory boards, and

other resources that serve a target special population;

they have the ability to provide needed data about

that group and can provide assistance in recruiting

study participants.

Summary and Recommendations

I

n order to successfully recruit and retain women in

clinical studies, particularly minority women and

women from low socioeconomic strata, investigators and

staff must examine and understand the needs, attitudes,

and beliefs that raise barriers to participation. Sensitivity

to the constraints placed on women by poverty, family

responsibilities, experience with the health care system,

language limitations, and limited access to health care

services must be a hallmark of efforts to recruit and

retain women. We recommend that the following

efforts be made:

 Nurture positive attitudes and beliefs by establishing

and maintaining, whenever possible, one-on-one

relationships that foster mutual trust and respect

between research staff and study participants.

 Include women in clinical trial staffs, particularly

women of the same ethnic or racial origins as those in

the study population, to the greatest extent possible.

 Promote joint decisionmaking and informed consent

to the maximum extent possible so that participants

are empowered to become active participants in their

own treatment.

 Encourage interactions and facilitate the establishment

of educational and support networks between former

and current study participants to help support positive

attitudes.
22

 Make participation in clinical studies possible for

women, regardless of their ability to pay. The use

of financial incentives, without creating an undue

influence, is an appropriate recruitment tool.

 Adapt program designs to overcome the barriers to

women’s participation, particularly minority women

and women from low socioeconomic strata. Examples

of such actions include maintaining extended and

flexible study clinic hours, providing transportation

and child care, and developing study materials that

are culturally and linguistically appropriate.

 Plan carefully, select communications channels judiciously, and pretest thoroughly before launching

recruitment efforts. Followup is also essential and

should include solicitation of feedback and evaluation

of program effectiveness.

 Rely on multiple channels for communications and

outreach to health professionals from many disciplines

to assist in recruitment of study populations.

 Develop media outreach strategies with spokespersons

who can serve as role models and emphasize ethnically

targeted messages, when appropriate.

 Use informal communication networks to promote

enrollment and compliance with clinical protocols.

 In all outreach efforts, adapt the language of science

to the needs of patient groups. Make efforts to accommodate alternative ways of learning, including the use

of low-literacy materials.

 Conduct community consultation and proper staff

training to accommodate the special needs of study

populations of clinical studies.

 Provide access to health research programs and facilities

for women to the fullest extent possible, including

transportation services.

 In order to enhance participant retention, develop

flexible schedules at study sites, provide alternative

service delivery such as the use of at-home examinations, complete medical insurance coverage for study

participation, and day-care services.

 Establish and use role models and advisory boards

from the community to help direct programs. Use

community confidants to help engender a sense of

trust and guarantee of confidentiality.

 Capitalize on the potential success of community

partnerships in meeting recruitment and retention

goals by initiating the partnerships early in the

planning process.

 Identify representatives of broad-based groups,

including spiritual, religious, and business leaders,

to participate in partnerships with the research

institution.

 Use research team members with similar racial,

ethnic, and language backgrounds as the potential

study participants. Whenever possible, use women

and minorities as principal investigators and educators

to help inspire a greater sense of trust among female

study participants.

 Address sensitivity to gender, racial, and ethnic issues

during research training. Stress the importance of

developing mutual confidence between study participants and research staff. The importance of patient

responsibility and decisionmaking skills should also

be stressed.

 Inform patients of findings of the protocol, to the

fullest extent possible, by openly discussing the treatments and their implications.

 Incorporate formal and informal sources of social

support into the design and conduct of studies by

developing cooperation between clinical study

programs and communities.

 Work with existing community structures such as

church groups that can help make patients aware of

clinical studies and help them cope with treatments

once the study is initiated. Informal networks can

be accessed through formal community structures.

 Make the best use of all available community sources

of data when studying poorly documented populations.

 Include information on cultural, racial, and behavioral

characteristics when defining special populations.

 Make the fullest use of clinics, advisory boards, and

other resources that serve a target special population;

they have the ability to provide needed data about

that group and can provide assistance in recruiting

study participants.
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 23

References

1. Ganz P. Participants expectations and needs. Paper

presented at the Scientific Meeting on Recruitment

and Retention of Women in Clinical Studies, Bethesda,

Maryland, July 12-13, 1993.

2. Summary of Public Hearing on Recruitment and

Retention of Women in Clinical Studies, National

Institutes of Health Office of Research on Women’s

Health (ORWH), Bethesda, Maryland, March

29-30, 1993.

3. Des Jarlais DC, Stepherson B. History, ethics, and

politics in AIDS prevention research. Am J Public

Health 1991;81(11):1393-94

4. Summary of Public Hearing on Recruitment and

Retention of Women in Clinical Studies, National

Institutes of Health Office of Research on Women’s

Health (ORWH), Bethesda, Maryland, March 29-30,

1993, p. 5.

5. Perez-Stable EJ, Sabogal F, Otero-Sabogal R, Hiatt RA,

McPhee SJ. Misconceptions about cancer among

Latinos and Anglos. JAMA 1992;3219-23.

6. Crawford VA. Participant and community issues on

recruitment and retention in clinical studies. Paper

presented at the Scientific Meeting on Recruitment

and Retention of Women in Clinical Studies,

Bethesda, Maryland, July 12-13, 1993.

7. Lipid Research Clinics Program. The lipid research

clinics primary prevention trial results: reduction

in incidence of coronary heart disease. JAMA

1984;251:351-64.

8. Affonso D. Patient needs and expectations. Paper

presented at the Scientific Meeting on Recruitment

and Retention of Women in Clinical Studies, Bethesda,

Maryland, July 12-13, 1993.

9. Rich S. One-third of women in survey lack preventive

health service. Washington Post, July 15, 1993, p. A6.

10. O’Hanlan K. Lesbians in health research. Paper presented at the Scientific Meeting on Recruitment and

Retention of Women in Clinical Studies, Bethesda,

Maryland, July 12-13, 1993.

11. Brown BS. Paper presented at Scientific Meeting on

Recruitment and Retention of Women in Clinical

Studies, Bethesda, Maryland, July 12-13, 1993.

12. Fisher EB. Community organizations and social

support among African-American women. Paper

presented at the Scientific Meeting on Recruitment

and Retention in Clinical Studies, Bethesda, Maryland,

July 12-13, 1993.

13. Fisher EB, Jr., Rehberg HR, Beaupre PM, et al. Gender

differences in response to social support in smoking

cessation. Association for Advancement of Behavior

Therapy, New York, November 1991.
24
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 25

CURRENT

EXPERIENCES

IN WOMEN’S

HEALTH

RESEARCH

Lewis H. Kuller, M.D., Dr.P.H.

Introduction

CHAPTER 5

As the previous chapters have illustrated, investigatorsand women face many issues and barriers in their

efforts to promote the full inclusion of women in clinical

research. Current experiences in women’s health research,

several of which are described in this chapter, have not

only demonstrated the challenges involved but also have

provided valuable information about successful strategies

for recruiting and retaining various segments of the female

population, including minorities, older women, poor

women, lesbians, and women with disabilities. These

studies have shown that, although many successful recruitment and retention principles apply to women and men,

there are special considerations that apply to women in

general and to certain populations of women in particular.

Thus, experience suggests that recruitment techniques

must be tailored not only to the study’s design, but also

to the targeted study population.

Recruitment Strategies

MULTIPLE MASS MEDIA OUTREACH

The collective experience gained through currentstudies demonstrates that the recruitment and retention of different types of women into clinical studies is

feasible when a wide variety of strategies is used. The

Postmenopausal Estrogen/Progestin (PEPI)1 study, for

example, demonstrated that large numbers of women

can be recruited for a clinical trial when a direct appeal

is made by multiple strategies, when the prevalence

of the target condition is high, and when eligibility

criteria are broad.

PEPI is a multicenter, double-masked, randomized,

placebo-controlled clinical study that compares the effects

of unopposed estrogen and three estrogen-progestin

combinations on multiple cardiovascular risk factors.

Participants must complete 10 clinic visits over 3 years

and undergo multiple procedures, including venipuncture,

bone-density measurements, electrocardiograms, mammograms, endometrial biopsies, and glucose-tolerance tests.

The PEPI study recruited 875 healthy, postmenopausal

women over a 56-week period, exceeding the goal of 840.

PEPI recruitment strategies included a wide variety of print

and broadcast media communications and communitybased approaches that appealed directly to the target
26

group. These strategies included publishing articles about

the study and the clinics in local newspapers, advertising

the study through mass mailings and radio and television

news media, and televising interviews with clinic staff and

physicians. Five of the seven clinics involved in the study

found that local newspaper articles about the study, mass

mailings, or television interviews were most efficacious.

While a national publicity campaign produced a low direct

yield, it did generate local media interest in the study. The

recruitment organization included a coordinator for each

clinic and central monitoring that provided regular and

frequent feedback about each clinic’s progress. Retention

through the screening process was also successful. Careful

telephone screening of approximately 8,400 women

resulted in 1 woman being randomly assigned to a study

group for every 10 calls made; for every 2 women among

the 1,466 who attended the initial screening visit 1 was

randomly assigned.

SINGLE MASS MEDIA OUTREACH: MASS MAILINGS

The Women’s Health Trial (WHT): Feasibility Study inMinority Populations2 successfully used mass mailings

to recruit minority women and women from diverse socioeconomic strata into a broader nutrition study called the

“Women’s Health Trial.”

The WHT is a cooperative effort among the NIH’s NCI

and NHLBI, the Fred Hutchinson Cancer Research Center in

Seattle, and several clinical centers, including the University of Alabama-Birmingham, Emory University in Atlanta,

and the University of Miami, Florida. The primary purpose

of the WHT was to determine the feasibility of recruiting

healthy, postmenopausal women, especially minorities,

into a year-long nutrition study. The selection of the

clinical centers was based on whether the center’s patients

included a significant minority population from which

participants could be recruited. Participants were recruited

using a mass mailing strategy and were then randomly

assigned into a high-fat or low-fat group.

Recruitment into the study was very successful, resulting in 934 participants. Recruitment of a significant

percentage of minority women was achieved: Birmingham

and Atlanta recruited 20 percent and 49 percent AfricanAmerican participants, respectively, and 30 percent of

recruits from Miami were Hispanic. Mass mailings resulted

in a 7 to 10 percent response rate, which was significantly

higher than expected.

ONE-ON-ONE HOME RECRUITMENT

The objective of the Cardiovascular Health Study(CHS)3 is to determine the risk factors for coronary

heart disease and stroke and the consequent disability

in men and women age 65 years or older. The study is

taking place in California, Maryland, North Carolina,

and Pennsylvania and will continue until 1999.

Successful recruitment of women age 65 years or older

was achieved by presenting information to them at their

homes. In addition to personal recruitment, the following

factors were found to enhance the enrollment of these

women in this study:

 Study legitimacy (and perceived legitimacy).

 Community physician approval.

 Interviewers who were middle-age or older.

 Interviewers who were gracious and assertive.

 Individualized attention to participants.

 Tokens of appreciation.

 Flexibility.

In all, 2,942 women have been recruited into the study,

compared with an expected enrollment of 3,000. Most are

married, high school graduates, and have an income in

excess of $16,000. Retention in the study has been excellent, with approximately 94 percent of women remaining

in the study after 4 years.

Another example of this successful recruitment strategy

is the Strong Heart Study,4

 a study of cardiovascular disease

in Native Americans that was begun in 1988 and is sponsored by the NHLBI in cooperation with Medlantic Research

Institute, University of Oklahoma, and Aberdeen Indian

Health Service. Investigators in this study faced the

challenge of a target study population that was widely

scattered over large rural areas5 in Arizona, Oklahoma,

North Dakota, and South Dakota. A frequent lack of

telephones or modern roads further complicated recruitment. To overcome these barriers, investigators relied

upon individuals who were hired from the study population to make personal visits to many tribal communities;

these individuals also assisted in conducting examinations

during the trial, which successfully studied a total of 4,559

patients over a 3-year span.

HOME STUDY PARTICIPATION

Currently in its baseline phase, the objective of theWomen’s Health and Aging Study (WHAS)3 is to

determine the major diseases and conditions responsible

for physical disabilities and changes in disabilities over

time in moderately-to-severely disabled women age 65

years or older. Potential participants had to experience

difficulty in two or more of the following areas:

 Mobility tasks.

 Upper extremity tasks.

 Instrumental activities of daily living.

 Self-care tasks.
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 27

In order to successfully recruit disabled women,

investigators designed the study so that examinations

and interviews were provided in the convenience and

privacy of the participants’ homes. In addition to home

study participation, the following factors were found to

enhance enrollment of disabled women in the WHAS:

 Outreach to physicians and family members.

 Appeal to generativity (participants will be helping

their daughters, granddaughters, and sisters).

 Interventions by interviewers (interviewers provide

support on issues facing participants such as distress

and depression).

Fifty disabled women have been enrolled in the study

to date. Sixty-six percent of the participants are white,

have at least an eighth-grade education but have not

received a high school diploma, and most rate their

health as fair or poor. There is a higher percentage of

participants in this study with chronic conditions as compared with the Cardiovascular Health Study participants.

Retention Strategies

Most of the studies cited in the chapter have reportedthat retention is not as severe a problem as recruitment. However, many of the logistical and financial barriers

described in previous chapters also contribute to low rates

of retention. The continued provision of assistance in child

care, transportation, insurance coverage, and other areas

is essential if participants are to complete the study. In

addition, the development of close, personal relationships

between staff and study participants also seems to play an

important role in retention.5 Minorities and people of low

socioeconomic strata often have many problems in addition

to the condition being studied, for example, homelessness,

unemployment, marital problems, or financial problems.

Differences in ethnic values and cultural attributes can

also have an effect on retention. An attitude of caring and

assistance on the part of investigators and staff may keep

participants returning to the facility not only to participate

in the study but also for the personal and social contacts.

Sensitivity on the part of study staff toward the unique

needs and attitudes of all women and a willingness to

accommodate those needs appears to be a hallmark of

effective recruitment and retention. It is not enough to

recruit women into clinical studies; it is critical that

researchers help women be successful study participants.

In the NHLBI’s Pawtucket Heart Health Program (PHHP)

study, for example, even though women made more

attempts than men to change their risk factor behaviors,

the men were more successful. The PHHP researchers

discovered that by accommodating women’s needs female

participants could be successful. For example, female

participants in the PHHP who needed to lose more than

50 pounds told investigators that they felt uncomfortable

meeting with thinner women in weight loss groups. At their

request, a weight loss group was established for them and

has been extremely popular and successful.

Other Examples of Successful Clinical

Studies Involving Women

Malama Na Wahine Hapai: Caring for PregnantWomen.6 In this Hawaiian study, begun in 1990 and

conducted by Emory University in collaboration with the

State of Hawaii Department of Health, researchers use radio

and cable TV public service announcements and special

sections in a local newspaper, among other resources, to

recruit for their clinical study. In addition, study investigators establish relationships with leaders of prominent

businesses and community service organizations to promote study enrollment; these partnerships have helped

to ensure that study protocols and recruitment methods

are culturally sensitive. Using such partnerships, personto-person communications, and the media, the study

continues to maintain exceptionally successful recruitment and retention.

Another distinguishing attribute of this study is that

researchers actively integrate and honor study participants’

choices involving cultural and ethnic healing. By consulting

indigenous scholars and inviting them to serve as project

counselors and consultants, researchers are able to work

in harmony with the participants by respecting their longstanding cultural beliefs and have successfully garnered

the trust of the study population.

Heart, Body and Soul, Inc.7

 This east Baltimore,

Maryland, community-based study has faced a number

of significant issues in recruitment, retention, and study

design. The community is one in which 75 percent of

residents’ income is allocated to housing, and 14 percent

of all eligible adults are unemployed. For many of these

people, attention to health issues, including enrollments

in clinical studies, is secondary to basic human needs, for

example, adequate housing, nutrition, and protection from

violence. Substance abuse and the effects of crime have

also had a devastating influence on individuals, blocking

their ability to even consider clinical trial participation.

In addition to these issues, the study designers had to

overcome a history of strained relations between The Johns

Hopkins Medical Institutions, which was the host medical

institution, and the surrounding community. Among the

obstacles was a sense of mistrust based on community
28

experiences in the institution’s emergency room and other

treatment facilities. One of the sponsors of Heart, Body,

and Soul, the Clergy United for Renewal in East Baltimore

(CURE), was instrumental in building bridges between

study sponsors and the community where 65 percent of

the population attends church. With leadership roles and

responsibilities equally vested in the community and the

sponsor, strategies were developed and implemented that

maximized local acceptance of the program.

 Today, Heart, Body, and Soul operates three centers with

more than 300 trained volunteers and 32 staff members.

Neighborhood health workers provide prevention, health

education, monitoring, referral, followup, and support

services. Regular screening services are offered and rapidaccess clinics are available for immediate referral into

specialized treatment centers.

Summary

Anumber of clinical research projects have demonstrated that improved recruitment and retention can

be achieved. Many of the recommendations suggested in

earlier chapters—increased sensitivity to cultural and

ethnic attributes of individuals and communities, greater

attention to the financial and logistical barriers faced by

potential participants, increased attention to inclusion

issues during study design and staffing phases—were put

to successful use in the studies highlighted in this report.

References

1. Miller V. The recruitment experience in PEPI. Paper

presented at the Scientific Meeting on the Recruitment

and Retention of Women in Clinical Studies, Bethesda,

Maryland, July 12-13, 1993.

2. Hall WD. Women’s health trial: feasibility study in

minority populations. Paper presented at the Scientific Meeting on the Recruitment and Retention of

Women in Clinical Studies, Bethesda, Maryland,

July 12-13, 1993.

3. Fried L. Recruitment and retention of older women

to longitudinal observational studies: the experience

of the cardiovascular health study and the women’s

health and aging study. Paper presented at the Scientific Meeting on the Recruitment and Retention of

Women in Clinical Studies, Bethesda, Maryland,

July 12-13, 1993.

4. Howard BV. The Strong Heart Study: a study of cardiovascular disease in American Indians, recruitment and

retention. Paper presented at the Scientific Meeting on

the Recruitment and Retention of Women in Clinical

Studies, Bethesda, Maryland, July 12-13, 1993.

5. El-Sadir W, Capps L. The challenge of minority

recruitment in clinical trials for AIDS. JAMA

1992;267(7):954-57.

6. Affonso D. Patient needs and expectations. Paper

presented at the Scientific Meeting on the Recruitment

and Retention of Women in Clinical Studies, Bethesda,

Maryland, July 12-13, 1993.

7. Becker DM, Tuggle MB. Forming effective community

partnerships: the health care system and community

perspectives. Paper presented at the Scientific Meeting

on the Recruitment and Retention of Women in Clinical

Studies, Bethesda, Maryland, July 12-13, 1993.
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 29

CONCLUSIONS

AND

RECOMMENDATIONS

Lewis H. Kuller, M.D., Dr.P.H.

CHAPTER 6

I

t is clear from the information contained in this document

that if women, especially minority or low-income or rural

women, are to be successfully recruited into clinical trials,

new approaches to the conduct of clinical research must

be substituted for the traditional practices that have created

the barriers currently associated with clinical studies.

These new approaches may constitute more than a procedural change for clinical research institutions. Along

with the medical establishment as a whole, these institutions must undergo true, fundamental changes in their

prevailing culture.

Clinical research can no longer be carried out in isolation

from the broader needs and interests of the communities

in which it is conducted. For women in particular, partnerships must evolve that promote mutual trust and respect.

Study protocols must appeal to and support women and be

implemented in full consideration of the cultural traditions

and obstacles faced by women of diverse racial and ethnic

backgrounds and socioeconomic strata.

Current experiences in health research demonstrate that

recruitment of various groups of women can be successful

if the study designs are properly tailored and if appropriate

recruitment strategies are used. The research project and

benefits of participation need to be explained clearly and

in a culturally appropriate manner to all potential participants. Mass media strategies can be effective; more personal

approaches, for example, home visits and recruitment

through clinics and personal physicians, can also be very

effective. Retention of participants in studies requires

equally diligent attention to the needs of the participants.

At the same time, regardless of the design features and

implementation methods that are chosen for a study, it

is critical that investigators uphold high standards of

scientific integrity so that all data obtained are valid and

applicable to a larger population. Recognizing issues

related to women and minorities in clinical studies and

incorporating the recommendations for addressing those

issues into study design and implementation will help to

provide clinical data that may fill the research gaps on

women’s health issues.

Efforts to fully include women, minorities, and those

from diverse socioeconomic strata in clinical research

have been ongoing for some years and will continue

to flourish. Future reviews of ongoing research efforts

will provide additional “lessons learned” and will guide

researchers toward even more effective means of recruiting and retaining study participants.
30

 Expand the role of IRB’s to encompass research

funded by non-Federal agencies and the ongoing

process of research.

 Involve IRB’s in the early design phases of research to

ensure that there is an equitable blend of study subjects.

 Ensure that all participants’ questions about the study

and possible side effects of treatment are answered fully

and comprehensibly; avoid even subtle intimidation

of study participants.

 Develop cost-effective recruitment approaches that

combine strategies aimed at involving women as a

group and also women of a particular race, socioeconomic status, age, risk profile, or geographic location.

 Encourage partnerships and networks, which are

excellent methods for recruitment of diverse female

populations, and disseminate information about

successful recruitment strategies such as screening,

counseling, and referral events (SCOREs), which were

developed for the Pawtucket Heart Health Program.

 Nurture positive attitudes and beliefs by establishing

and maintaining, whenever possible, one-on-one

relationships that foster mutual trust and respect

between research staff and study participants.

 Include women in clinical trial staffs, particularly

women of the same ethnic or racial origins as those in

the study population to the greatest extent possible.

 Promote joint decisionmaking and informed consent

to the maximum extent possible so that participants

are empowered to become active participants in their

own treatment.

 Encourage interactions and facilitate the establishment of educational and support networks between

former and current study participants to help support

positive attitudes.

 Make participation in clinical studies possible for

women, regardless of their ability to pay. The use

of financial incentives, without creating an undue

influence, is an appropriate recruitment tool.

 Adapt program designs that overcome the barriers to

women’s participation, particularly minority women

and women from low socioeconomic strata. Examples

of such actions include maintaining extended and

flexible study clinic hours, providing transportation

and child care, and developing study materials that

are culturally and linguistically appropriate.

Summary List of Recommendations

 Determine gender representation in clinical studies

based on the research question to be addressed and

the base rates of the illness by sex or by rates of

morbidity or mortality for the illness by sex.

 Incorporate extra visits and flexible scheduling needed

by women into the study design.

 Increase support for studies into the issue of hormonal

and other biologically driven, gender-based differences

to determine the impact of these differences on drug

and treatment responses.

 Conduct research on the social and psychological

barriers to women’s participation in clinical studies.

 Include the participant’s own health care provider

in the study, if possible, so that the bonding achieved

in this relationship can be carried over to the

research setting.

 Encourage meta-analyses and/or pooled analyses

on existing data sets of women and minorities that

are too small to be analyzed individually in an

economical fashion.

 Ensure that all aspects of a study, from its planning

through its execution, are sensitive to the cultural,

linguistic, socioeconomic, and logistical characteristics

of the populations studied. For example, this should

include involving women and minorities in designing

the research, in preparing study materials, and in

interacting with participants in a culturally and

linguistically sensitive manner.

 Resolve the issue of lack of insurance coverage

for treatment of incidental medical conditions

and research-associated side effects to promote

the inclusion of women in clinical trials.

 Analyze the goals and purposes of clinical studies

to identify issues of particular relevance to women.

 Include women in the strategic planning process

and use them in visible, key positions in the study,

whenever possible.

 Plan and establish infrastructure to support both

multicenter and community-based disease treatment

and prevention studies, and use current exploratory

models to develop estimates of the dimensions, performance, and utility of proposed future networks.

 Make efforts to gather, analyze, and evaluate information concerning the process of establishing and

maintaining research partnerships.
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 31

 Plan carefully, select communications channels judiciously, and pretest thoroughly before launching

recruitment efforts. Followup is also essential and

should include solicitation of feedback and evaluation

of program effectiveness.

 Rely on multiple channels for communications and

outreach to health professionals from many disciplines

to assist in recruitment of study populations.

 Develop media outreach strategies with spokespersons

who can serve as role models and emphasize ethnically

targeted messages, when appropriate.

 Use informal communication networks to promote

enrollment and compliance with clinical protocols.

 In all outreach efforts, adapt the language of science

to the needs of patient groups. Make efforts to accommodate alternative ways of learning, including the

use of low-literacy materials.

 Conduct community consultation and proper staff

training so as to accommodate the special needs of

study populations when designing clinical studies.

 Provide access to health research programs and facilities

for women to the fullest extent possible, including

transportation services.

 In order to enhance participant retention, develop

flexible schedules at study sites, provide alternative

service delivery such as the use of at-home examinations, complete medical insurance coverage for study

participation, and day-care services.

 Establish and use role models and advisory boards

from the community to help direct programs. Use

community confidants to help engender a sense

of trust and guarantee of confidentiality.

 Capitalize on the potential success of community

partnerships in meeting recruitment and retention

goals by initiating the partnerships early in the

planning process.

 Identify representatives of broad-based groups,

including spiritual, religious, and business leaders,

to participate in partnerships with the research

institution.

 Use research team members with similar racial, ethnic,

and language backgrounds as the potential study

participants. Whenever possible, use women and

minorities as principal investigators and educators

to help inspire a greater sense of trust among female

study participants.

 Address sensitivity to gender, racial, and ethnic issues

during research training. Stress the importance of

developing mutual confidence between study participants and research staff. The importance of patient

responsibility and patient decision- making skills

should also be stressed.

 Inform patients of findings of the protocol, to

the fullest extent possible, by openly discussing

the treatment and its implications.

 Incorporate formal and informal sources of social

support into the design and conduct of studies by

developing cooperation between clinical study

programs and communities.

 Work with existing community structures such as

church groups that can help make patients aware of

clinical studies and help them cope with treatments

once the study is initiated. Informal networks can

be accessed through formal community structures.

 Make the best use of all available community sources

of data when studying poorly documented populations.

 Include information on cultural, racial, and behavioral

characteristics when defining special populations.

 Make the fullest use of clinics, advisory boards, and

other resources that serve a target special population;

they have the ability to provide needed data about

that group and can provide assistance in recruiting

study participants.
32
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 33

THE OFFICE OF RESEARCH

ON WOMEN’S HEALTH

NATIONAL INSTITUTES OF HEALTH

Appendices
34
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 35

Appendix I

THE OFFICE OF RESEARCH

ON WOMEN’S HEALTH

NATIONAL INSTITUTES OF HEALTH

SCIENTIFIC MEETING:

RECRUITMENT

AND RETENTION

OF WOMEN IN

CLINICAL STUDIES

TASK FORCE

ROSTER

HOLIDAY INN BETHESDA

BETHESDA, MARYLAND

JULY 12-13, 1993
36
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 37

TASK FORCE

ROSTER

Appendix I

Co-Chairs

Lewis H. Kuller, M.D., Dr.P.H.*

Professor and Chairperson

Department of Epidemiology

University of Pittsburgh

Graduate School of Public Health

Pittsburgh, Pennsylvania

Shiriki Kumanyika, Ph.D., M.P.H., R.D.*

Professor and Associate Director for Epidemiology

Center for Biostatistics and Epidemiology

Pennsylvania State University College of Medicine

Hershey, Pennsylvania

Julie E. Buring, Sc.D.*

Associate Professor of Ambulatory Care and Prevention

Harvard Medical School

Associate Epidemiologist

Brigham and Women’s Hospital

Boston, Massachusetts

Janette L. Cupp, M.D.*

General Surgeon

Gallup Indian Medical Center

Indian Health Service

Gallup, New Mexico

Wafaa El-Sadr, M.D., M.P.H.*

Director

Division of Infectious Diseases

Harlem Hospital

New York, New York

Andrea Foote, Ph.D.

Associate Research Scientist

Institute of Labor and Industrial Relations

University of Michigan

Ann Arbor, Michigan

Ellen R. Gritz, Ph.D.*

Professor and Chair

Department of Behavioral Science

M.D. Anderson Cancer Center

The University of Texas

Houston, Texas

Task Force Members
38

Maureen M. Henderson, M.D., D.P.H.*

Head

Cancer Prevention Research Program

Fred Hutchinson Cancer Research Center

Professor of Epidemiology and Medicine

University of Washington

Seattle, Washington

Carl G. Kardinal, M.D.*

Principal Investigator

Ochsner CCOP

Associate Director

Ochsner Cancer Institute

Alton Ochsner Medical Foundation

New Orleans, Louisiana

Barry D. Kaufman, D.M.D.*

Health Broadcaster/Analyst

CBS Radio Medical News Network

Wilmette, Illinois

Marion M. Lee, Ph.D., M.P.H.*

Assistant Professor

Department of Epidemiology and Biostatistics

University of California at San Francisco

 School of Medicine

San Francisco, California

Andrew S. Levey, M.D.

Director

Nephrology Clinical Research Center

Division of Nephrology

New England Medical Center

Boston, Massachusetts

Manuel R. Modiano, M.D.*

Director

Clinical Research

Cancer Care Center of Southern Arizona

Tucson, Arizona

Jonathan D. Moreno, Ph.D.*

Professor and Director

Humanities in Medicine

State University of New York Health

 Science Center at Brooklyn

Brooklyn, New York

Carol K. Redmond, Sc.D.*

Professor and Chairperson

Department of Biostatistics

Graduate School of Public Health

University of Pittsburgh

Pittsburgh, Pennsylvania

Barbara K. Rimer, Dr.P.H.*

Director

Cancer Prevention, Detection, and Control Research

Duke University Medical Center

Durham, North Carolina

Helen Rodriguez-Trias, M.D.*

Pediatrician/Consultant

President

American Public Health Association

Brookdale, California

Karen Rothenberg, J.D., M.P.A.*

Professor of Law

Director

Law and Health Care Program

University of Maryland

 School of Law

Baltimore, Maryland

Julia R. Scott, R.N.*

Director

Public Education/Policy Office

National Black Women’s Health Project

Washington, D.C.

Diane B. Stoy, Ed.D., R.N.*

Operations Director

Lipid Research Clinic

George Washington University

 Medical Center

Washington, D.C.

*Task Force Members in attendance at the Scientific Meeting.
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 39

Appendix II

THE OFFICE OF RESEARCH

ON WOMEN’S HEALTH

NATIONAL INSTITUTES OF HEALTH

PUBLIC HEARING

ON THE

RECRUITMENT

AND RETENTION

OF WOMEN IN

CLINICAL STUDIES

SUMMARY

BETHESDA HOLIDAY INN

BETHESDA, MARYLAND

MARCH 29–30, 1993
40
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 41

Appendix II—Contents

FOREWORD 43

INTRODUCTION 45

OPENING REMARKS 46

Vivian W. Pinn, M.D., Director, Office of Research on Women’s Health

National Institutes of Health

REMARKS 47

Antonia C. Novello, M.D., M.P.H., Surgeon General, Public Health Service

U.S. Department of Health and Human Services

REMARKS 48

Dianne Murphy, M.D., Assistant Director for Medical Affairs, Division of Anti-Viral Drug Products

Center for Drug Evaluation and Research, Food and Drug Administration

U.S. Department of Health and Human Services

SUMMARY OF ISSUES AND RECOMMENDATIONS 50

ISSUES AND RECOMMENDATIONS 52

ISSUE 1: Regulatory and Legal Issues

ISSUE 2: Cost and Insurance Issues

ISSUE 3: Study Design and Research Staffing Issues

ISSUE 4: Perspectives of Potential Study Subjects

ISSUE 5: Special Concerns for Recruiting Low-Income and Minority Women

PARTICIPANTS 59
42
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 43

Appendix II

FOREWORD The Office of Research on Women’s Health (ORWH)

was established within the Office of the Director of

the National Institutes of Health (NIH) in September

1990. It was charged with the critical objectives of giving a central NIH focus to women’s health issues and

of establishing a science base that will yield reliable

diagnoses as well as effective treatment and prevention

strategies for women.

The Office of Research on Women’s Health recognizes

the enormous actual and potential contributions of women

to the advancement of science, not only as full members

of the scientific and research communities but also as

participants in the clinical research process. We applaud

recent efforts to increase the inclusion of women in clinical

research studies but are concerned about the continuing

underrepresentation of women in these trials.

It has become increasingly clear that we cannot continue

to assume that risk factors for diseases are the same for

women and men, nor can we assume that treatment and

prevention interventions suitable for men are also applicable to women. The exclusion of women from important

studies that examine lifestyle modifications, risk factor

reductions, and intervention strategies for preventing

morbidity and mortality from chronic diseases leaves

a gap in knowledge regarding what behavioral changes

are suitable and what interventions are appropriate in

diagnosing, treating, and preventing diseases in women.

What can be done to bring more women into clinical

research? How can we eliminate gaps in scientific knowledge resulting from the previous exclusion of women from

clinical studies? The Office of Research on Women’s Health

is looking to the scientific and educational communities

and to women’s advocates to provide us with assistance in

convincing the research establishment of the benefits of

having more women participate in clinical research studies

and formulating innovative strategies for overcoming the

barriers women experience when participating in studies.

We appreciate the participation of all who have contributed to this process.

Vivian W. Pinn, M.D.

Director

Office of Research on Women’s Health

National Institutes of Health
44
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 45

Appendix II

I

n recent years, the NIH, scientists, health care professionals, congressional representatives, women’s advocacy

groups, and the public have become increasingly aware

of the underrepresentation of women in clinical research.

This has led to a greater interest in the inclusion of women

in biobehavioral studies. Analysis of issues have contributed to enhanced efforts to recruit and retain women

of diverse racial and ethnic groups and socioeconomic

strata into clinical research.

To define and delineate barriers to the participation

of women in clinical studies, the ORWH held a public

hearing on March 29-30, 1993. In response to a Federal

Register notice dated March 4, 1993, 39 individuals and

representatives of organizations presented oral and submitted written testimony. An additional 19 submitted

only written testimony. The testimonies identified barriers

and offered recommendations related to the participation

of women in clinical research.

Recommendations presented at the public hearing are

being incorporated into the planning for the “Recruitment

and Retention of Women in Clinical Studies” scientific

meeting to be held July 12-13, 1993, in Bethesda,

Maryland. The objectives of the meeting are to:

 Generate innovative recommendations for action.

 Develop strategies for enhancing the participation

of women in clinical research and for improving

the design of research studies.

 Highlight successful strategies for recruiting and

retaining women in clinical studies.

This document summarizes testimony presented

at the public hearing. In some instances, statements are

paraphrased or synthesized to encompass several similar

recommendations. This summary groups issues and

recommendations into five main categories. The document represents the viewpoints of those who provided

testimony and does not necessarily represent the views

of the ORWH or the NIH.

The emphasis in the summary on the concerns of

women of diverse racial and ethnic groups and socioeconomic strata reflects the fact that one-third of the 58

testimony statements addressed issues of interest to this

population. Presenters described social, economic, and

health status factors of this population; the consequent

need to include them in clinical studies; and the significant barriers affecting their participation in the studies.

A reference number is printed in parentheses ( ) after

those statements in which data are presented. This number

refers to the number of the testimony as identified on pages

59 and 60. An attempt was made to state each recommendation only once, although it should be noted that many

of them were offered by multiple presenters.

INTRODUCTION
46

The NIH has implemented a strengthened and revitalized policy on the inclusion of women and minorities

in study populations.

The policy clearly states that adequate numbers of

women shall be included in clinical studies proportional

to prevalence among women of the condition under study.

NIH funding components will not fund or award grants

or contracts until the applicant provides sufficient information on the study population to ensure compliance

with the NIH policy on inclusion of women and minorities

in study populations.

We have further instituted a tracking system in order

to monitor compliance with this policy, and the results

are beginning to be analyzed for the first year of the

system’s implementation.

Why have women often been excluded from research?

Was their exclusion an act of discrimination or of protection? Some of the reasons stated for the exclusion

have been:

 Women’s cyclical hormonal changes may confound

research results.

 Study populations would be less homogeneous.

 Study costs would be higher if gender-specific

hypotheses or subgroup analyses are anticipated.

 Recruitment of women into studies is more difficult.

 Legal and ethical issues surround potential exposure

to a fetus.

However, because many treatments and modalities

will be used in pregnant women, women of childbearing

age, elderly women, women of diverse racial or ethnic

origin, and women of varied socioeconomic circumstances,

there is a need to know and understand potential effects

and/or effectiveness of diagnostic efforts, treatment, and

prevention in these populations and not just to infer their

application to women from studies in men.

Through a contract, NIH is working with the Institute

of Medicine (IOM) to address the legal and ethical implications of including more women in more clinical studies.

The NIH and the IOM are developing recommendations

to overcome some of the barriers investigators and administrators face in facilitating the applications of treatment for

women from studies in men through the system while

still keeping women’s health, and that of any potential

conceptus, at the forefront of their consideration.

If we are to fully address gaps in knowledge about women’s

health, we must succeed in our efforts to recruit and retain

women in clinical studies. To assist us in this endeavor, we

have formed a Planning Task Force on the Recruitment and

Retention of Women in Clinical Studies. The task force has

as its goals to:

Opening Remarks

PUBLIC HEARING

RECRUITMENT AND RETENTION

OF WOMEN IN CLINICAL STUDIES

29 MARCH 1993

Vivian W. Pinn, M.D., Director, Office of Research

on Women’s Health, National Institutes of Health

The Office of Research on Women’s Health (ORWH)was founded in September 1990 by Dr. William Raub,

then acting director of the NIH. The impetus for the

establishment of this office, within the Office of the

Director of NIH, was a recognition resulting from a

General Accounting Office (GAO) Report in June 1990

that the NIH had not fully implemented its 1986 policy

encouraging the inclusion of women in clinical research.

Attention to the inclusion of women in clinical research

has escalated into a far-reaching priority not only for the

NIH but also for members of Congress, the wider scientific

community, and women’s advocacy groups.

The 1985 Report of the Public Health Service Task Force on

Women’s Health Issues stated: “Biomedical and behavioral

research should be expanded to ensure emphasis on

conditions and diseases unique to, or more prevalent in,

women in all age groups.” Yet, only recently has the full

implementation of this directive become a priority of the

medical and scientific communities. This directive is

central to the mandate for the Office of Research on

Women’s Health at NIH.

The ORWH has as its mandate to give NIH a central

focus on women’s health issues and to establish a science

base that will permit reliable diagnoses and effective

treatment and prevention strategies for women.

The major objectives of our office are:

 To develop an integrated strategy for increased research

into diseases, disorders, and conditions that are unique

to, more prevalent among, or more serious in women,

or for which there are different risk factors of interventions for women than for men.

 To ensure that women are appropriately represented

in biomedical and biobehavioral research studies,

especially clinical trials, that are supported by NIH.

 Direct initiatives to increase the number of women

who are participants in biomedical research careers.

The second objective, ensuring participation of women

in study populations, especially clinical trials, is one of

the highest initial priorities of our office. Women cannot

expect to gain equitably from new advances in therapy

and interventions if they are not included in the clinical

trials that assess safety and efficacy.
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 47

 Assess the experiences of clinical trial researchers,

practitioners, and women participants in the recruitment, retention, adherence, and compliance of women

in clinical research.

 Identify issues and barriers unique to the recruitment

and retention of women of all races and socioeconomic

strata involved in different types of studies, with a

particular emphasis on clinical trials.

 Review models and approaches that enhance the

participation of women in clinical research.

 Develop a summary report with recommendations for

improving access, participation, and retention of women

from all racial and ethnic groups and socioeconomic

strata in clinical research.

This public hearing has been convened to provide

guidance and assistance to address the inclusion of women

in clinical research through proven and improved methods

for the recruitment and retention of women in biomedical

and biobehavioral research and to eliminate barriers to

their inclusion.

Recommendations from this planning task force will

be submitted to the director of the National Institutes

of Health and made available to the scientific and lay

communities.

We appreciate your participation in this process, and

look forward to your recommendations and expertise.

PUBLIC HEARING

RECRUITMENT AND RETENTION

OF WOMEN IN CLINICAL STUDIES

29 MARCH 1993

Antonia C. Novello, M.D., M.P.H., Surgeon General, Public

Health Service, U.S. Department of Health and Human Services

We have made progress in the past few year, thanksto all the women in biomedical careers and the

activists who have insisted on equality, at least some

equality, for women in biomedical research. But

colleagues, we haven’t done enough.

The Women’s Health Initiative is a clinical trial whose

time has come. But other trials, equally important, aren’t

even on the “drawing boards,” and they are needed as well.

This country is far more diverse than we can imagine

and needs far more prevention and health care than what

we have now. Let’s not forget that this is a country of 250

million people, more than half of them women. More

than 15 percent of our population is African-American,

more than 9 percent Hispanic, 3 percent Asian Pacific

Islander, 1 percent Native American, and almost 1 in 5

of our citizens is under 12 years of age; and more than

1 in 10 is over age 65. We have to shape our research

and our thinking to meet these demographic realities;

otherwise, we will be practicing and planning in a vacuum.

I think we must guard against refighting old battles.

We have won the battle that women’s diseases must be

studied. We’ve whipped all the dead horses about clinical

trials, about aging, aspirin, beta carotene and the like—

trials well known to have excluded women. We have

embarrassed some scientists and some institutions and

raised consciousness of the neglect of women’s health

issues. Now we must polish our act and come up with

some new tactics and strategies for action.

We need to be in total command of the relevant facts.

And we must not be bought off by a few new clinical trials

or old ones being repackaged with new “women’s this or

that” names. We must really “get our act together,” and, for

that, this hearing is a welcome and well-planned first step.

We not only need to look at the diseases that ravage

and shorten the lives of women, but we must find how to

get women into clinical trials and look at the subgroups

most severely affected by diseases as well. We need to look

at HIV, AIDS, heart attacks, stroke, cancer—especially

breast, cervical, and lung cancer—osteoporosis and

Alzheimer’s disease. We need to monitor tuberculosis,

and we need to look at diseases such as diabetes.

And we need to do this soon.

Equally, we mustn’t forget alcoholism, drug addiction,

and depression as well as other mental illnesses. We are

going to need the maximum sophistication to see that

more women are added to ongoing as well as new trials.

We must also seriously reconsider whether simply adding

women to research protocols should be our number one

task as we move ahead under our mandate to equalize

women in research. This is especially important in cases

where the answers given by current research on men are

useful to women. In the search for parity and quality,

our credibility must always remain a top priority.

I won’t rehash the old clinical trials mentality, which

excluded women from studies. Ours is a new day. We are

learning in our clinical trials to address the complexities

of women, their shifting hormonal patterns, and their

needs. We have accepted that if medications or treatments

are to be used on women, they should be tested on women.

Look at the numbers: approximately 249,000 women

will die of cancer in 1993. About 365,000 women will

die of heart attacks and about 100,000 of stroke this year.

About 6.2 million women will suffer serious depression

in any given month.

But as important as all of those items are, we also know

that we need to help women who face multiple daily life

issues today to become part of the research mainstream.

No less important, women are going to need the best

research in diagnosis, treatment, and rehabilitation, and

they will need to be part of the planning system as well.
48

Research must address conditions such as low educational status, low expectations and self-esteem, substandard

living conditions, unemployment, risk-promoting lifestyles,

environmental and occupational toxic exposures, and

diminished access to prevention and screening. They

all must be part of the research protocol.

We know that poverty or affluence, access to medical

care or lack of it, access to information or lack of appropriate information makes a life and death difference for

women in some cases.

Let’s talk a minute about another issue and see how our

past endeavors sometimes come full cycle. Between 1948

and 1971, many pregnant women were given diethylstilbestrol (DES) in an attempt to prevent miscarriages and

preterm births, exposing an estimated 9 million children

in utero to DES. Now epidemiologic studies are being

conducted by NCI to determine the aftermath of the DES

exposure on the mothers and the children and to assess

the occurrence of cancer, genitourinary abnormalities,

and other diseases.

Are there other drugs or therapies being prescribed

for women, still unstudied and affecting women and their

children yet to be born? Are we still going to continue

to study women as mothers and not women as women?

Let’s make it a point to answer these questions.

At the same time, in our quest for biotechnology, let

us not forget for whom studies are intended. We need

to be utterly practical and realistic and never think that

“women” comprise a unified group. Social issues affect

women in devastating ways. The woman’s role in the

family, the pressures on her to maintain discretion and

confidentiality, the role she plays to safeguard culture,

her responsibilities for her children, her financial and

emotional dependence on a man or on herself—these

issues all enter into her ability to consider enrollment

in clinical trials and to use health care services at all.

Although there is a tremendous need for educating

women, there is also a tremendous need for educating

health care professionals regarding women’s concerns as

well. The examples that come to mind are gynecologic

infections such as candidiasis and pelvic inflammatory

disease and human papillomavirus, genital ulcers,

cervical dysplasias, and genital warts.

We all know that regarding HIV, women have been so

underdiagnosed that many first learned of their own HIV

infection when their children were diagnosed.

Let me talk to you now about clinical trials and AIDS.

As Surgeon General, I have seen the devastation of AIDS.

Today, most women with AIDS are either African-American

(53 percent) or Latino (21 percent). Between 30,000 to

40,000 African-American or Latino children will lose

both parents to AIDS between 1995 and the year 2000.

About 71 percent of the women diagnosed with AIDS

have been sexual partners of intravenous drug users

or have injected drugs themselves.

In the presence of such data, why is it that so many

people with AIDS have either been excluded or not

included in the services that do exist?

Allow me to tell you why. Women have told me that:

 Women are discriminated against because of their

childbearing potential.

 Women mistrust the system—after all, clinical trials

have been designed by men for men, and those men

have never “walked in the shoes” of a woman.

Women and their health care providers have told me that:

 Clinics are not open at the times women can go. They

are not found in the places women can reach. They are

on floors too high for the women who are sick to climb

stairs when there are no elevators. And the clinics are

tended by people they can’t understand.

 Women are requested to pay too many visits, without

any consideration for the transportation costs involved

and the respite and child care needed. Food is not

available in the clinics. Who will feed their children?

 There is no “one-stop shopping”—care for the woman,

her children, and husband all in one place. Family

unity is disregarded in the presence of HIV infection.

 Too much blood is drawn without apparent coordination among laboratories. Are people guinea pigs?

 There are no facilities for their children at these

clinics—no place for them to play, to be cared for,

or to feel welcome.

 Too much medication is being prescribed without

explanation or understanding of what 28 pills a day

can do to a woman’s life, to a woman’s time.

 There is a fear that the side effects of hunger are

being confused with the side effects caused by the

medication itself.

 There is lack not only of language sensitivity but

of cultural sensitivity as well.

 No explanation is given about why participation in

clinical trials is important for the entire family and

not only as a cure for the mother. Families need to

be considered as a whole.

 They fear upsetting their mates, they fear abandonment

by the community.
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 49

 They fear being thrown out of a clinical trial if side

effects become evident. Where do they go next? Will

they be given AZT again? Who will place them back

on routine care?

 There is a lack of adequate communication about

contraceptives. What might be adequate contraception

in some communities may be inadequate contraception

for some others, especially where “the rhythm method”

is employed but no one acknowledges or asks about

it. Any discussion of this issue must be linguistically

and culturally sensitive. If contraception is needed as

part of a clinical trial, who will provide for this, and

who will pay?

 Women, in some cultures, must have permission

from their husbands in order to participate in a

clinical trial. In the absence of this approval, they

are unable to comply.

 There are no caseworkers outside of the clinic to

explain why the trial is important in a sensitive,

simple human way early on in the recruiting process.

In addition to addressing these problems, women have

recommended that:

 Once information about clinical trials is available

(and is linguistically and culturally appropriate),

that information can then be widely disseminated.

 The care of children is linked to the care of women

and linked to the care of the family. This reality

must dictate the nature of the clinical trial and

how it is administered.

Obviously, we need to know more about the biology

of pregnant women with HIV and more about how the

unborn child is affected by anti-retroviral drugs. It may

make researchers feel more comfortable to exclude pregnant women from clinical trials, but, at the same time, it

may rob women and children of important therapeutics.

We need rapid progress on tests to determine if a child

is infected and vaccines to protect the baby as well as

the mother.

Currently, when information about HIV-related

clinical trials is needed (both federally and non-federally

funded), people are instructed to call the AIDS Clinical

Trials Information Service. The HIV/AIDS clinical trials

are usually listed by “adult” and “children.” Much searching is needed to find out how many trials enroll women.

I think in all clinical trials, not just AIDS trials, we have

to press the research community to make this information easily and readily available to all of us.

In addition, the concepts of safer sex have been

predicated on partners with equality. I ask you, how

many women can interrogate partners about their sexual

histories or sexual patterns today and then make purely

intellectual decisions about how, when, and if sex should

occur? I think we’ve been highly unrealistic here, and

unintentionally, we have been setting women up. The

woman’s role in making such decisions depends on her

value to her partner, their relationship, her value to her

family, her value to her culture, and her value to her

community, among other complex, mitigating factors.

We cannot continue to ask women to make decisions

that rob them of their emotional and financial security.

We still have a great deal of work to do in the area of

safer sexual practices.

We need to consider all the socioeconomic, legal,

and ethical issues that impinge on the health status of

women. But we should recognize what a woman can do

versus what we want her to do. Approaches should be

more sensitive to her culture and to her realities, not

only to our protocols.

We must not forget that poverty is associated with

a high degree of insecurity in our society; it simply limits

one’s options and ability to plan. Being poor may mean

that you don’t have a telephone to call for information,

or you don’t have the level of education to understand

clinical procedures or the very concept of a clinical trial.

Let’s meet women in the middle. Let’s stop making

them feel uncommunicative or uncaring. We must

start giving poverty some respect and give women

back their dignity.

Finally, I would like to correct a very pervasive idea.

I often hear that poor people won’t comply with medical

protocols or clinical trials. Maybe they can’t comply—

not that they won’t, but they can’t. Maybe they can’t afford

the bus fare, don’t have a baby sitter, can’t miss work, can’t

pay for drugs or checkups. Can’t. Not that they won’t.

The time has come to end the fractionation of women.

It is time to tear down the barriers and open wide the

doors. We need an end to any self-limiting attitudes

and an insistent appreciation of women’s worth.

As we move ahead to that point, we must monitor

the process and participate in the outcome. But most

importantly, we must remember that any successful

effort to improve women’s health will have to include

women as equal partners in the development of policies

pertaining to them and to their families.

Thank you.
50

PUBLIC HEARING

RECRUITMENT AND RETENTION

OF WOMEN IN CLINICAL STUDIES

29 MARCH 1993

Dianne Murphy, M.D., Assistant Director for Medical

Affairs, Division of Anti-Viral Drug Products, Center

for Drug Evaluation and Research, Food and Drug

Administration, U.S. Department of Health and

Human Services

I

am Dr. Dianne Murphy, Assistant Director for

Medical Affairs in the Division of Anti-Viral Drug

Products, at the Center for Drug Evaluation and Research,

Food and Drug Administration (FDA).

I am here today representing Dr. David Kessler, Commissioner of Food and Drugs; Dr. Ruth Merkatz, the

Commissioner’s Special Assistant for Women’s Health;

and the FDA Working Group on Women in Clinical Trials.

Like our colleagues at NIH, we at the FDA have been

concerned about the issues surrounding the inclusion of

women in clinical trials.

During the past several years, a number of events

have helped to focus attention on women’s health issues.

To name just a few, a Public Health Service (PHS) task

force established in 1985 concluded that women were

disadvantaged both in terms of health care and access to

biomedical and behavioral research. The PHS task force

recommended that steps be taken to address the overall

health needs of women—from bench to bedside. In the

1980’s and early 1990’s, the Congressional Women’s

Caucus was formed on the Hill, the Women’s Health

Equity Act was introduced in the U.S. Congress, an

increasing focus on women’s health occurred at NIH,

and advocacy organizations made their influence felt in

promoting a national women’s health research agenda.

Over the past decade at FDA, there have been many

internal discussions and analyses focused on the appropriate inclusion of women in clinical trials. In addition,

we have sought guidance and input externally by cosponsoring or participating in a number of scientific conferences

to examine relevant issues: the Institute of Medicine’s

(IOM) March 1991 planning meeting on the inclusion

of women in clinical trials, the Institute of Medicine’s

Drug Forum on Women and Drug Development in June

1992, and the Food and Drug Law Institute’s Workshop

on Women in Clinical Trials of FDA-Regulated Products

in October 1992.

Two important concepts have evolved from these

scientific and ethical discussions: (1) those involved in

drug development should include appropriate representation of women in their clinical studies, and the new drug

applications that emerge from these clinical studies should

include analyses of potential gender differences; and

(2) the FDA’s 16-year general exclusion of women of

“childbearing potential” from the earliest phases of

clinical trials may no longer be appropriate.

Over the past year, the FDA has been working in

an intensive, focused manner to develop new guidance

designed to expand the number of women of childbearing

potential in clinical trials of new drugs and biologics.

As you know, underlying the exclusion of women

of childbearing potential was a desire to minimize

unnecessary risk to a fetus in the event that a female

subject became pregnant during exposure to an investigational agent. As we speak today in 1993, protecting a

fetus from unanticipated exposure to potentially harmful

drugs remains a principle of paramount importance in

designing clinical trials. However, it is also important

to consider the potential scientific benefits of including

women of childbearing potential in earlier phases of

clinical trials. Identifying important gender differences

during the early phases of clinical studies may facilitate

the appropriate design of critical later studies which, in

turn, can further clinical understanding of the appropriate

use of drugs in women. It should also be noted that we

now have available a number of options to utilize in

preventing and in quickly and accurately diagnosing

pregnancy. These technical advances can be put to use

in providing assurance that we are not unknowingly

exposing fetuses to experimental therapies.

As Dr. Kessler has said, “In the past, medical research

has focused on males and all too frequently women have

been included as an afterthought. Eliminating these

barriers is the right thing to do.”

The FDA hopes the changes in the guidance concerning women during the conduct of clinical trials will

contribute to our knowledge and understanding of the

optimal use of therapeutic agents in women.

I would like to thank Dr. Vivian Pinn and Dr. Judith

LaRosa for providing the FDA with an opportunity to

participate in opening what, I am sure, will be an interesting and exciting couple of days of hearings. I look forward

to the proceedings.

SUMMARY OF ISSUES AND RECOMMENDATIONS

Currently, women constitute approximately 51 percentof the U.S. population. On average, women also live

7.5 years longer than men. The elderly population—those

over age 65—is growing rapidly, and, among those, the

group over age 85 is growing the most rapidly. Women

are the majority of this population, and they are more

likely to spend their later years with multiple chronic

health conditions.(55)
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 51

Heart disease alone exacts an enormous toll in women,

equivalent in scope to the toll in men.

 More than 244,000 women die of heart attacks each

year and more than 90,000 die from stroke. Coronary

heart disease and stroke rank first and third as causes

of death for middle-age and older women. With each

decade of life, the death rate from coronary heart

disease increases threefold to fourfold.(54)

Many other diseases also place a heavy burden of death

and disability on women.

 Rheumatoid arthritis affects women three times as

frequently as men.(52)

 Systemic lupus erythematosus occurs nine times

more often in women than in men.(52)

 It is estimated that 2.6 million women live with

breast cancer—1 million of whom are aware of their

disease—1.6 million of whom are not yet diagnosed.

It is estimated that in 1993 there will be 185,000

newly diagnosed cases and 46,000 deaths.(33)

 Osteoporosis affects one-third to one-half of all

women after menopause.(52)

 At least 80 percent of the patients with scleroderma

are women.(52)

 Genital herpes or human papilloma virus infections

affect 15 to 20 million women.(56)

Perhaps, not surprisingly, women rely much more

heavily on the medical system than do men. Approximately two-thirds of all visits to doctors and pharmacists

are made by women,(44) and studies document greater

health-seeking behavior in general by women as compared with men.(33)

In the search for greater understanding of the etiology,

diagnosis, treatment, and prevention of disease, numerous

clinical research studies have been undertaken using

human subjects. Yet, women have traditionally been

underrepresented or excluded from many clinical studies.

This exclusion has been made despite some clear evidence

of gender-based differences in the progress of disease and

the response to treatments.

 Many psychiatric disorders, including depression,

schizophrenia, many personality disorders, and

attention deficit hyperactive disorder, have different

prevalence rates and courses in women and men.(1)

 Women and men differ in their vulnerability to

important medication side effects.(1)

 Behavioral interventions designed to decrease high-risk

activities (smoking or HIV infection) differ between

women and men, for example, the interventions do

not seem to work as well for women as for men.(1)

 HIV infection may present differently in women and

men; the challenges of living day-to-day with HIV

also appear to be different for women and men.(45)

Considerably more information is required on how

women’s different hormonal and physiological characteristics influence the progress of disease and the response to

treatments. This makes application of research findings

to the general population that have been derived solely

from males questionable, at best.

Several reasons have been given for excluding women

from studies,(26) including:

 Concerns about fetal safety preclude recruitment of

women with reproductive potential.

 Hormonal changes associated with the menstrual

cycle and other physiologic differences between

women and men create major methodological

problems in data collection and analysis.

 Women are difficult to recruit for studies and,

once recruited, are more difficult to retain for

the length of the study.

This has resulted in a situation in which gender-related

factors are often used as reasons for excluding women

from research populations. On the other hand, genderrelated factors are ignored when health interventions

derived from studies of men are generalized to the

entire population.(42)

In recent years, this situation has gradually begun

to change in large measure because of:

 A revised NIH policy, issued in 1990, that requires

applicants for clinical research grants to include

women in study populations unless there is a

“clear, compelling rationale” for their exclusion.

 A growing body of evidence showing that women

have been systematically underrepresented in clinical

research (e.g., the 1990 GAO report) and that they,

in fact, do not refuse to participate in or drop

out of studies in greater numbers than men.(31,59)

 A growing appreciation by the scientific community

of the need to recruit and retain women in clinical

studies, particularly low-income and minority women.

Despite this changing environment, steps still need to

be taken to achieve parity between women and men in

clinical studies. During the public hearing, the issues

involved in recruiting and retaining women fell into

five major areas:

 Regulatory and legal issues.

 Cost and insurance issues.

 Study design and research staffing issues.
52

 Issues related to the perspectives of potential

study subjects.

 Issues related to recruiting and retaining low-income

and minority women.

Numerous recommendations were made in the areas

listed below:

 Recommendations about changes to NIH policies

to require inclusion of women in studies; changes in

incentives for drug manufacturers were also suggested.

 Recommendations regarding changes in health insurance policies so that participation in research protocols

is covered.

 Recommendations regarding the design of research

protocols and materials, advancement of women and

minorities in clinical research positions, and staffing

of research studies with personnel who are bilingual

and culturally sensitive.

 Recommendations regarding the needs, concerns,

and characteristics of female study participants.

There was also a recognition that efforts to recruit anxd

retain women in clinical research will result in greatly

increased cost(40) because of the need for:

 Much larger sample sizes.

 Extended, more flexible research facility hours.

 Provision of child care, transportation, and

appropriate incentives.

 Training and staffing of multiethnic research teams.

 Greater consultation and coordination with local

communities in the design and implementation of

clinical studies.

ISSUE 1

REGULATORY AND LEGAL ISSUES

Barriers(18)

Key players who decide what role women areto have in any given clinical study include:

 Study sponsors  Research institutions

 Federal regulators  Women’s advocates

 Potential female subjects  Public officials

 Investigators

Some groups have used specific concerns as a basis for

their policies regarding exclusion of premenopausal women

in clinical research. Two of these concerns focus on:

 Possible harm to a fetus caused by the experimental

treatment or drug.

 Possible harm to a female subject’s reproductive

potential.

In 1991, NIH issued strengthened guidelines on the

“Inclusion of Minorities and Women in Study Populations.” Although these guidelines strongly encourage

applicants for research grants to include women, they

list several permissible justifications for excluding them.

Among these justifications is a provision stating that:

“. . . the experimental procedures/treatments present

unacceptable risks for women of child-bearing age.”

By not defining an “unacceptable risk,” the guidelines

allow a trial sponsor to cite any uncertainty about the

treatment or drug’s effect on fertility as meeting the

exclusion justification.

Other barriers thought to be presented by drug manufacturers who, in some instances, determine that costs

associated with including women in clinical trials

outweigh any perceived benefits include:

 Liability for in utero injuries is a real possibility.

The consent form a women signs waiving the right

to sue for any injuries suffered applies only to herself,

not to any fetus conceived during the study.

 Manufacturers’ legal liability can be reduced if fertile

women are excluded from clinical trials, if the drugs

are not actively marketed to them, and if warning

labels are carried, even though the manufacturer

knows that the drug will eventually be used by

some pregnant women.

Recommendations

A number of people presenting testimony praised NIH

for its recent steps in encouraging the recruitment of

women in clinical studies and for its formation of the

ORWH. They also made recommendations for changing

the regulatory and legal climate to one that even more

strongly favors the inclusion of fertile women:

 Emphasize early, extensive contraception counseling

with women of childbearing potential who participate

in studies.(36)

 Encourage use of superior methods of contraception

and use endocrine measures to detect very early

pregnancy.(36)

 Recruit study participants from the very large pool

of premenopausal women for whom pregnancy is

impossible or highly unlikely: celibate or homosexual

women or those who have undergone tubal ligation

or hysterectomy.(36)

Issues and Recommendations
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 53

 Change the incentive structure for manufacturers

by decreasing the threats posed by suits based on

in utero injuries and by increasing the incentives

for including fertile women.(18)

 Increase the number of women in leadership positions such as principal investigators of clinical trials,

members of grant review committees, and members of

conference planning and invitation committees.(28,35)

 Continue to promote the advancement of women

in biomedical careers.(57)

The following recommendations were directed toward

the Congress, the NIH, and the ORWH:

 Congress should pass proposed legislation that

would codify NIH’s policy on including women and

minorities. This legislation would also require specific

guidelines under which the inclusion of women is

inappropriate.(18)

 NIH’s current guidelines should be strengthened by

a requirement that researchers detail strategies for

recruiting and retaining women as part of the grant

proposal.(18)

 NIH should award “bonus points” to proposals that

suggest particularly effective or creative strategies

for recruiting and retaining women.(39)

 Increase efforts to attract and fund research proposals

of qualified female researchers.(35)

ISSUE 2

COST AND INSURANCE ISSUES

Barriers

Financial constraints pose a significant barrier to theparticipation of many women in clinical studies,

particularly those brought about by the current system

of health insurance.

 Virtually all third-party payers and health maintenance

organizations (HMO’s) include a clause in insurance

contracts that excludes coverage for all costs associated

with “experimental treatments.”(24)

 Medicare regulations also contain this exclusion.(24)

 Depending on state guidelines, Medicaid regulations

may also contain this exclusion.(24)

 A recent Gallup survey indicated that, of those

oncologists who refer patients to clinical trials,

29 percent said that lack of reimbursement posed

a significant barrier to patients’ participation.(29)

If an individual participates in a clinical study, the

usual procedure is for the sponsor to cover the costs

of data collection and the drug or treatment being tested.

However, patients are responsible for hospital and laboratory fees and doctor services associated with the study.

The results of this policy indicate the following:(24)

 Patients have limited access to important, sometimes

life-saving treatments, even though they may cost less

than standard treatments.

 Patients do not participate in trials unless they can

afford the costs and are willing to pay them. This

cuts out an enormous pool of lower income potential

study subjects.

 Oncologists sometimes alter their choice of therapy

in response to these reimbursement constraints.

 Patients are reluctant to appeal the decision when

access to treatment is denied; many doctors do not

know how to assist patients with an appeal.

Recommendations

A number of participants at the hearing were concerned

about this issue and offered specific recommendations:

 Cover subjects’ costs associated with participation

in a clinical trial.(24,33,39)

 Clinical studies should meet the following criteria

if expenses are to be covered:(29)

– The treatment under study is therapeutic.

– The treatment is a part of a trial approved by NIH,

an NIH cooperative group, the FDA, Department

of Veterans Affairs (VA), or a “qualified nongovernmental entity.”

– The proposed therapy is reviewed and approved

by a qualified Institutional Review Board (IRB).

– The facility is adequate and personnel are qualified.

– There is no available noninvestigational therapy

that is superior to the protocol treatment.

– Available data suggest that the treatment will be

as efficacious as noninvestigational therapy.

 The President’s Health Care Reform Task Force should

consider this issue and include some form of coverage

in the minimum health care benefits package for all

Americans.(24)

 The NIH and professional medical associations should

produce guidelines for clinicians on supporting their

medical decisions to third-party payers.(24)

 All NIH-sponsored clinical trials should require the

designation of an individual to assist patients with

insurance preapproval and appeal processes.(24)
54

ISSUE 3

STUDY DESIGN AND RESEARCH STAFFING ISSUES

Barriers

Cyclic hormonal fluctuations and other physiologicgender-based differences create significant challenges

in the design and execution of clinical studies. Measurements often need to be timed carefully during the subject’s

menstrual cycle, and, therefore, women may need to be

seen for extra visits or may require frequent rescheduling

because of unpredictable menstrual cycles. This has a

number of repercussions for the design and budgeting

of clinical studies, including:

 Increased financial and personnel costs.

 Need for larger sample sizes to account for the

increased variability of data.

 A lack of comparability with data from previous

studies that have included only male subjects.

Also at issue is the design and development of recruitment materials and documents related to the study protocols and design. Research protocols, consent forms, and

other materials that are “incomprehensible, harsh, and

culturally insensitive”,(12) as they often are, effectively

preclude the participation of many women, particularly

minority women.

A further barrier to participation is posed by the

staffing of clinical study teams because many women

mistrust and feel intimidated by clinical research staff

because of differences in gender, race, ethnicity, education, and socioeconomic background.

Recommendations

A number of recommendations were made at the public

hearing on the subject of study design and staffing:

 Increase support for studies into the issue of hormonal

and gender-based differences in order to determine

the nature and extent of these differences on drug

and treatment responses. The results of these studies

could assist in the design of future studies.(14,42)

 Conduct research on the social and psychological

barriers to women’s participation in clinical studies.(34)

 Determine gender representation in clinical studies

based on the base rates of the illness by sex or by rates

of morbidity or mortality for the illness by sex.(36)

 Encourage meta-analyses and/or pooled analyses on

existing data sets of women and minorities that are too

small to be analyzed individually in an economical

fashion.(53)

 Include women in the process of writing of proposals,

research protocols, consent forms, and materials to be

used with patients.(12)

 Include groups or individuals who represent the

study population in planning the study in order

to ensure a mutually acceptable research design.(9)

 Include, if possible, the subject’s own doctor in the

study so that the bonding achieved in the regular

doctor-patient relationship can be carried over to

the research setting as well.(6)

 Design clinical studies to accommodate the menstrual

and hormonal cycles of subjects by including the

need for extra visits and flexible scheduling in the

protocol.(26)

 Increase the numbers of clinical research staff—at

both the junior and senior level—who are similar

to the study population in demographics and

ethnicity.(43)

 Ensure that the staff members who work with study

populations are bilingual and bicultural, if necessary.(10,30)

 Encourage the full participation of junior research

staff members, who are currently more likely to

be the bilingual and bicultural staff members, in

the planning and execution of clinical studies.(17)

 Ensure that staff is sensitive to the concerns, questions,

and fears of female study subjects.(30,32,35,38,43)

ISSUE 4

PERSPECTIVES OF POTENTIAL STUDY SUBJECTS

Barriers

Anumber of general barriers to the participation ofwomen in clinical studies exist. These have to do

primarily with the level of awareness and understanding

that women have about the medical system and how it

works. They can be characterized as follows:

 Women are often unaware of planned clinical trials

or their eligibility to participate.(33,34)

 Many women encounter a “gatekeeper” mentality

from their physicians, in which they are not given

information about a condition, therapy, or clinical

study because it is deemed “too complex” or

“unnecessary.”(34)

 When women are told about clinical trials, many

hesitate because they fear the unknown, are concerned about being a “guinea pig” in an “experimental” treatment, or feel that participation means

that the physician is making a “last ditch effort” for

the patient.(24)

Frequently, the heart of the issue is a fundamental

difference in approach to medical care and clinical

research held by researchers and female subjects;(6)

the researchers’ main interest is in the disease process
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 55

or drug under study, whereas the female subjects’ concerns

are with overall patient care and personal, sympathetic

relationships with the personnel on the research team.

Recommendations

 Promote public education efforts about clinical trials

that address patient fears and target appropriate

literacy levels.(24)

 Foster open discussion between care providers and

patients so that the patient learns about the possibilities

of participating in a trial and concerns, questions, and

fears are allayed.(6)

 Maintain a full and open discussion of the study purpose and plan so as to find a middle ground between

the researchers’ and the subjects’ objectives. Researchers

should design a study in such a way that the subjects

are truly cared for, not just studied.(6)

 Encourage closer relationships among local health care

providers, universities, and research centers, particularly

in minority communities, so that primary patient care

and clinical research can be more closely integrated (i.e.,

the cancer care and research model) and information

about clinical trials can be disseminated.(29)

The following recommendations were directed to NIH

and the ORWH:

 NIH should maintain a register of ongoing clinical

trials that would be accessible to practitioners and

the public.(33)

 Research, including focus group studies, on barriers

to participation and strategies for overcoming such

barriers should be funded.(34,59)

 Methods for tracking and monitoring enrollment

and retention of women in clinical trials should be

funded.(14)

 The ORWH should convene a task force to study the

adaptation for medical schools of the American Medical

Women’s Association’s Advanced Curriculum on Women’s

Health to assist physicians in providing a more sensitive

and appropriate approach to women’s unique health

problems.(46)

ISSUE 5

SPECIAL CONCERNS FOR RECRUITING

LOW-INCOME AND MINORITY WOMEN

Barriers

L ow-income and minority women constitute a keypopulation of concern in the recruitment and retention of women in clinical research, not only because they

have traditionally been excluded but also because of their

high rates and high risk of major diseases such as heart

disease, cancer, HIV/AIDS, sexually transmitted diseases

(STD’s), tuberculosis (TB), and others.(10,17)

 The majority of women with AIDS are African-American

(53%) or Hispanic (21%).(14)

 Through perinatal transmission, AIDS is the leading

cause of death among Hispanic children and the second

leading cause for African-American children.(17)

 Rates of coronary heart disease and stroke are substantially higher in African-American women than

in white women.(54)

This key population includes diverse groups such

as African-Americans, Hispanics, Asian Pacific Islanders,

and Native Americans.(16) The socialization of some

segments of these populations is not geared to the acceptance of traditional medical care or participation in

clinical trials and, therefore, poses a special challenge

to the research community.(38)

Some Hispanic women, in particular, constitute a

high-risk group because of their social, economic, and

citizenship status; their heavy responsibilities as the

social, psychological, and financial support for their

families; and their high-stress, urban lives.(22) Although

there is a dearth of data about the health status of

Hispanics, particularly about the distinct subgroups

within this population, a number of facts are known:

 Hispanics are the fastest growing population in

the United States today.(22,30)

 The Hispanic population will double in the next

30 years.(30)

 Hispanics are a young population with a median

age of 26.2 years.(43)

 Hispanics are the least likely population group

to have health insurance coverage.(43*)

 Hispanics experience very high rates of poverty

and school dropout.(22)

 Teenage Hispanic women have the highest fertility

rate in the Nation.(17,19)

 Hispanics experience very high rates of sexually

transmitted diseases, HIV infection, and chronic

diseases such as diabetes and hypertension.(17,19)

A second distinct population of special concern is

migrant farmworkers:(15)

 There are 3.5 to 5 million women, men, and children

who work as migrant and seasonal farmworkers.

 The bulk of these workers—85 percent—are ethnic

minorities. Most are Hispanic, but there are also

Jamaicans, African-Americans, and Haitians.
56

 Many experience English literacy and fluency

difficulties. A 1989 study reported that 9 out of 10

migrant workers in Wisconsin reported Spanish as

their primary language, one-half spoke no English,

and 1 out of 4 had not completed the fifth grade

(a measure of functional literacy).

 A significant number experience stringent working

conditions, inadequate housing, and poor nutrition.

 A 1989 study reported the median family income

of migrant and seasonal farm workers to be $7,330,

supporting an average of 5.2 persons per family.

 They live an extremely mobile lifestyle and therefore

have limited access to affordable health care, comprehensive health insurance, and other social support

services.

 They have the highest infectious disease rate in the

United States, high rates of chronic disease, and their

risk of HIV infection is 10 times the national average.

 A recent Centers for Disease Control and Prevention

(CDC) study indicated that as many as 44 percent of

migrant farmworkers test positive on TB skin tests.

There are multiple barriers to recruiting and retaining

poor women of color to clinical studies. The barriers

are economic, cultural, social, and psychological.(32)

These women:

 Lack awareness about available studies.(10)

 Often do not understand the purpose of a proposed clinical study or what benefits might result

to them personally or to their community from

their participation.(5)

 Mistrust researchers and the medical establishment

in general because of the gaps in gender, ethnicity,

and social and educational backgrounds.(30,32)

 Are reluctant to be used as subjects of experiments.(30)

 Have significant logistical problems—lack of child

care, lack of transportation, and lack of flexibility

about schedules.(10,30)

 Frequently live isolated lives in rural areas.(10)

 Lack the financial ability to pay for treatments

associated with a clinical study.(10)

 Are reluctant to join a study because they deny a

suspected illness or are concerned about issues of

confidentiality.(21)

Some Hispanic women experience a number of

additional barriers:

 They may be reluctant to participate in a situation

where they have to give personal information because

of concerns about immigration authorities.(30)

 They have different beliefs about medicine and

follow folk medicine practices.(45*)

 They may need to receive the permission of a male

partner or father in order to participate.(32)

 For Hispanic migrant farmworkers in particular,

a mobile lifestyle makes participation difficult.

For these individuals, “anything that interferes

with work is to be avoided.”(15)

Recommendations

Numerous recommendations were made about ways

to encourage the participation and retention of lowincome and minority women in clinical studies.

 Use culturally sensitive/bilingual outreach workers

to work with appropriate community groups (e.g.,

churches, social service agencies, communitybased organizations, and local businesses) to discuss

potential studies, and to identify and recruit study

subjects.(4,10,17,38,41,43)

 Involve representatives of the study populations in

planning the study so as to ensure mutually acceptable decisionmaking.(10,12,43)

 Design bilingual, culturally sensitive data collection

materials, information materials, consent forms,

and research methods. These should be concise,

at an appropriate reading level, and written in

the subjects’ first language.(30)

 Ensure that study subjects understand the purpose

of the study and understand the benefit to them

personally and to their community. Help them

to develop a pride of ownership in the study.(10)

 Include minorities and women in both senior and

junior positions on the research team.(17,43)

 Develop specific ethnic and socioeconomic status

indicators to identify accurately Hispanic women,

especially distinct Hispanic subpopulations.(14,19)

 Increase the career opportunities for female and

minority scientists.(30)

 Ensure that study personnel who work with subjects

are bicultural/bilingual and sensitive to subjects’

concerns and fears. A mutual relationship of trust,

respect, and honesty is crucial.(30,32,38,43)

 As the study is implemented, ensure that the subjects’

sense of their importance to the study and their

personal worth is continually reinforced.(32)

 Provide transportation; child care; and expanded,

flexible scheduling of visits to research sites.(21)

 Combine elements of the study in one site to increase

convenience for subjects.(10,21)
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 57

 Conduct aspects of the study in the community itself,

for example, in the church social hall, community

health care center, or migrant camp.(15)

 Provide culturally sensitive and appropriate incentives

for participation.(4,30)

 Provide financial coverage for participation in the

study.(24,41)

 Develop partnerships among communities, their

representatives, and research centers.(22)

 Recruit the family, not just the individual, to

participate.

 Build on the stronger concern that many of these

subjects have for their children’s health rather than

for their own. If their children are enrolled in a

study, they may be more likely to participate in

one themselves.(21)

 Provide followup to participants and their community

once the study is completed by sharing the results

and benefits.(22,43)

It is also recommended that NIH fund a practicebased research infrastructure in migrant and community

health centers as an avenue for recruitment and retention

of farmworkers and other women of color in clinical

studies.(15)
58
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 59

Appendix II

PARTICIPANTS SPEAKERS

Vivian W. Pinn, M.D.

Director

Office of Research on Women’s Health

Antonia C. Novello, M.D., M.P.H.

Surgeon General, Public Health Service

Dianne Murphy, M.D., F.A.A.P.

Assistant Director for Medical Affairs

Food and Drug Administration

Shiriki K. Kumanyika, Ph.D.

Associate Professor and Associate Director

 for Epidemiology

Pennsylvania State University

College of Medicine

PRESENTED TESTIMONY

1 Nada Logan Stotland, M.D., American Psychiatric

Association 2 Randy E. Stevens, M.D., Clinical Assistant Professor

Division of Radiation Oncology, New York University

Medical Center 3 Ciro V. Sumaya, M.D., M.P.H.T.M., San Antonio

Hispanic, Health Initiative 4 Paula S. Gomez, Executive Director, Brownsville

Community Health Center 5 Amelie G. Ramirez, Dr.Ph.H., South Texas Health

Research Center 6 Mohammed A. Bey, M.D., Tulane/LSU AIDS Clinical

Trials Unit 7 Geraldine Schechter, M.D., Chief of Hematology

Washington Veterans Affairs Medical Center 9 Wesley Segawa, President, Advisory Board

Malama Na Wahine Hapai Project 10 Lee Lee Doyle, M.A., Ph.D., Associate Dean for

Continuing Education and Professor of Obstetrics

and Gynecology, University of Arkansas for

Medical Sciences 11 Edith S. Lisansky Gomberg, Ph.D., Professor

of Psychology, University of Michigan School

of Medicine Alcohol Research Center 12 Dyanne Affonso, Ph.D., R.N., Professor, School

of Nursing, University of California at San Francisco 14 Iris L. Long, Ph.D., AIDS Coalition To Unleash

Power (ACT-UP) 15 Ed Zuroweste, M.D., Board Chair, Migrant

Clinicians Network 16 Linda Devore, B.S., M.A., President, American

Association of Dental Schools
60

17 John F. Alderete, Ph.D., Professor, Department

of Microbiology, The University of Texas, Health

Science Center at San Antonio 18 Michelle Oberman, Ph.D., Professor, Chicago

Bar Association’s Alliance for Women 19 Ruth E. Zambrana, Ph.D., M.S.W., University of

California at Los Angeles School of Social Welfare 20 Lynne C. Hartmann, M.D., Consultant, Medical

Oncology, Mayo Clinic, North Central Cancer

Treatment Groups 21 Rebecca Clark, M.D., Maternal Child Director,

HIV Outpatient Clinic, Charity Hospital of

New Orleans 22 Maria Teresa Pizarro, M.S.W., M.S., Counselor,

Rape Victim Services Program, Community

Counseling Centers of Chicago 23 Margaret Jensvold, M.D., Director, Institute

for Research on Women’s Health 24 Kimberly Calder, M.P.S., Director of Public Policy,

Cancer Care, Inc. 25 Shirley Buttrick, Ph.D., University of Illinois at

Chicago Center for Research on Women and Gender 26 Susan Johnson, M.D., American College of

Obstetricians and Gynecologists 27 Martha Cortes, D.D.S., Representative/Member,

Hispanic Dental Association 28 Barbara Brookmyer, Legislative Affairs Director,

American Medical Student Association 29 Stacey Beckhardt, Director, Government Relations,

American Society of Clinical Oncology 30 John D. Rugh, Ph.D., Professor and Director

of Research, Dental School, The University

of Texas Health Science Center at San Antonio 31 Maria Bustillo, M.D., Board Member, Society for

the Advancement of Women’s Health Research 32 Jennifer Wild, Ed.D., Evaluation Researcher,

NOVA Research Company 33 Kay Dickersin, Research Task Force Cochair,

National Breast Cancer Coalition 34 Susan Persons, M.A., Associate Director of

Governmental Relations, Consortium of Social

Science Associations 35 Catherine J. Didion, Executive Director, Association

for Women in Science 36 Jean A. Hamilton, M.D., American Medical Women’s

Association 37 Joyce Korvick, M.D., Medical Officer, National

Institute of Allergy and Infectious Diseases,

AIDS Clinical Trials Group 38 Sandra W. Wearins, Health Educator, Baltimore

American Indian Center 39 Cindy Pearson, Program Director, National

Women’s Health Network

40 Naomi K. Fukagawa, M.D., PH.D., The

Rockefeller University Hospital, NIH General

Clinical Research Centers 41 Barbara Brown, Virginia Breast Cancer Foundation 42 Palma E. Formica, M.D., Member, Board of Trustees,

American Medical Association 43 Aida L. Giachello, Ph.D., Assistant Professor,

The University of Illinois at Chicago, Jane Addams

College of Social Work

SUBMITTED TESTIMONY

44 Robert M. Elenbaas, Pharm.D., F.C.C.P, Executive

Director, American College of Clinical Pharmacy 45 Karolynn Siegel, Ph.D., Memorial Sloan-Kettering

Cancer Center 46 Lila A. Wallis, M.D., F.A.C.P., Clinical Professor

of Medicine, National Council on Women’s Health 47 Elaine K. Harris, Executive Director, Sjogren’s

Syndrome Foundation Inc. 48 Linda G. Phillips, M.D., President, Division of

Plastic Surgery, Association of Women Surgeons 49 Nancy L. Day, Ph.D., Associate Professor of

Psychiatry, Western Psychiatric Institute and Clinic 50 Mary Kay Richter, President, National Alliance

for Oral Health 51 Donald Abrams, M.D., Chairman, Community

Consortium 52 Amanda Spitler, Government Affairs Representative,

American College of Rheumatology 53 Judith C. Woodward, The Society of Behavioral

Medicine 54 Edward Cooper, M.D., President, American

Heart Association 55 Amy Pryluck, Executive Director, National

Women’s Health Resource Center 56 Susan Calvert Finn, Ph.D., R.D., President,

Division of Government Affairs, The American

Dietetic Association 57 Cynthia M. Shewan, Ph.D., Director, American

Speech—Language-Hearing Association 58 Reverend William Burden, Ph.D., St. Augustine

College 59 American Psychological Association
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 61

Appendix III

THE OFFICE OF RESEARCH

ON WOMEN’S HEALTH

NATIONAL INSTITUTES OF HEALTH

SCIENTIFIC MEETING:

RECRUITMENT

AND RETENTION

OF WOMEN IN

CLINICAL STUDIES

AGENDA

HOLIDAY INN BETHESDA

BETHESDA, MARYLAND

JULY 12-13, 1993
62
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 63

Appendix III

AGENDA Monday, July 12

8:30 a.m.

Introduction of Acting Director of the National

Institutes of Health

Vivian W. Pinn, M.D.

Director, ORWH

8:35 a.m.

Opening Remarks

Ruth L. Kirschstein, M.D.

Acting Director, NIH

8:50 a.m.

Overview of the Office of Research on Women’s

Health and Conference Statement

Vivian W. Pinn, M.D.

Director, ORWH

PLENARY SESSION

9:10 a.m.

Overview Statement

Moderator

Shiriki R. Kumanyika, Ph.D., M.P.H.

Pennsylvania State University College of Medicine

Task Force Cochair

9:20 a.m.

Gender Bias in Women’s Health Research

Jeri A. Sechzer, M.A., Ph.D.

Pace University

9:40 a.m.

Break

10:00 a.m.

Women’s Health Research Legislative and Public

Policy Update

Congresswoman Louise M. Slaughter

(D-NY)

10:30 a.m.

Advocacy and Women’s Health Research

Leslie R. Wolfe, Ph.D.

Center for Women Policy Studies
64

10:45 a.m.

Ethical and Legal Issues

Karen H. Rothenberg, J.D., M.P.A.

University of Maryland School of Law

11:00 a.m.

Summary of ORWH Public Hearing on Recruitment

and Retention of Women in Clinical Studies

Shiriki R. Kumanyika, Ph.D., M.P.H.

Pennsylvania State University College of Medicine

Task Force Cochair

11:15 a.m.

Discussion

12:00 p.m.

Lunch

PANEL I:

DESIGN AND IMPLEMENTATION ISSUES IN CLINICAL STUDIES

1:30 p.m.

Overview Statement

Moderators

Carol K. Redmond, Sc.D.

University of Pittsburgh

Task Force Member

Julie E. Buring, Sc.D.

Harvard Medical School

Task Force Member

1:45 p.m.

Getting the Job Done in Treatment and Prevention

Clinical Trials

 AIDS Treatment and Prevention Research

Melanie A. Thompson, M.D.

AIDS Research Consortium of Atlanta

 Cancer Research in Community Settings

Harry E. Hynes, M.D., Ph.D.

Cancer Center of Kansas

2:15 p.m.

Prevention Studies

 Unique Issues for Risk Factor Assessments in Women

John M. Flack, M.D., M.P.H.

University of Minnesota Hospital and Clinic

 Research Considerations Across Diseases and Conditions

Donna Kritz-Silverstein, Ph.D.

University of California at San Diego

2:55 p.m.

Discussion

3:15 p.m.

Break

3:30 p.m.

Prevention Studies (continued)

 Behavioral Modification Studies

Maureen M. Henderson, M.D., D.P.H.

University of Washington

 Cancer Screening

Dinah K. Pearson, M.H.A.

University of Missouri - Columbia

 Contributions of Observational Evidence:

Nurses’ Health Study

Charles H. Hennekens, M.D., Dr.P.H.

Harvard Medical School

4:30 p.m.

Discussion

5:00 p.m.

Closing Remarks

Vivian W. Pinn, M.D.

Director, ORWH

5:10 p.m.

Recess
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 65

Tuesday, July 13

PANEL II:

PARTICIPANT AND COMMUNITY ISSUES IN RECRUITMENT

AND RETENTION IN CLINICAL STUDIES

8:00 a.m.

Remarks: Food and Drug Administration

Ruth B. Merkatz, Ph.D., R.N.

Food and Drug Administration

8:10 a.m.

Overview Statement

Moderators

Barry D. Kaufman, D.M.D.

CBS Radio/Medical News Network

Task Force Member

Helen Rodriguez-Trias, M.D.

American Public Health Association

Task Force Member

8:15 a.m.

Participants’ Expectations and Needs

Dyanne D. Affonso, Ph.D., F.A.A.N.

University of California at San Francisco

Patricia A. Ganz, M.D.

University of California at Los Angeles Schools

 of Medicine and Public Health

8:45 a.m.

Community Partnerships in Research

Vanella A. Crawford, M.S.W., L.C.S.W.

The Vanella Group

Edwin B. Fisher, Jr., Ph.D.

Washington University School of Medicine

Diane M. Becker, Sc.D., M.P.H.

The Johns Hopkins Center for Health Promotion

Reverend Melvin B. Tuggle

Heart, Body, and Soul, Inc.

Barbara V. Howard, Ph.D.

Medlantic Research Institute

9:55 a.m.

Discussion

10:15 a.m.

Break

10:30 a.m.

Recruitment and Retention of Special Populations

Barbara S. Brown, M.Ed.

Goochland Elementary School

Goochland, Virginia

Elmer E. Huerta, M.D., M.P.H.

National Cancer Institute, NIH

Lee Lee Doyle, M.A., Ph.D.

University of Arkansas for Medical Sciences

 College of Medicine

Katherine A. O’Hanlan, M.D.

Stanford University Medical Center

11:10 a.m.

Decisionmaking Process

John C. Fletcher, Ph.D.

University of Virginia School of Medicine

11:25 a.m.

Discussion

12:00 noon

Lunch

PANEL III:

INVESTIGATOR AND INSTITUTIONAL ISSUES IN

RECRUITMENT AND RETENTION IN CLINICAL STUDIES

1:15 p.m.

Overview Statement

Moderators

Maureen M. Henderson, M.D., D.P.H.

University of Washington

Task Force Member

Marion M. Lee, Ph.D., M.P.H.

University of California at San Francisco

Task Force Member

1:20 p.m.

Outreach Planning in Designing and Implementing

Clinical Research

Rodger J. Winn, M.D.

University of Texas M.D. Anderson

 Cancer Center

Annlouise R. Assaf, M.S., Ph.D.

Memorial Hospital of Rhode Island
66

1:50 p.m.

Benefits and Risks to Investigators and Institutions

in Conducting Clinical Studies

William R. Hazzard, M.D.

Bowman Gray School of Medicine

 of Wake Forest University

2:05 p.m.

Office for Protection From Research Risks (OPRR)

and Institutional Review Board (IRB) Issues

Paula Knudson

The University of Texas Health Science

 Center at Houston

2:20 p.m.

Discussion

PANEL IV:

CURRENT EXPERIENCES IN WOMEN’S HEALTH RESEARCH

2:45 p.m.

Overview Statement

Moderator

Lewis H. Kuller, M.D., Dr.P.H.

University of Pittsburgh

Task Force Cochair

2:50 p.m.

Women’s Health Feasibility Study

W. Dallas Hall, M.D.

Emory University School of Medicine

3:05 p.m.

Postmenopausal Estrogen/Progestin Intervention (PEPI) Study

Valery T. Miller, M.D.

George Washington Medical Center

3:20 p.m.

Cardiovascular Health Study (CHS) and Women in

Aging Study

Linda P. Fried, M.D., M.P.H.

The Johns Hopkins Health Institutions

3:35 p.m.

Discussion

CLOSING SESSION

4:00 p.m.

Concluding Remarks

Vivian W. Pinn, M.D.

Director, ORWH

4:15 p.m.

Adjourn
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 67

Appendix IV

THE OFFICE OF RESEARCH

ON WOMEN’S HEALTH

NATIONAL INSTITUTES OF HEALTH

SCIENTIFIC MEETING:

RECRUITMENT

AND RETENTION

OF WOMEN IN

CLINICAL STUDIES

SPEAKERS

HOLIDAY INN BETHESDA

BETHESDA, MARYLAND

JULY 12-13, 1993
68
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 69

Appendix IV

SPEAKERS Dyanne D. Affonso, Ph.D., F.A.A.N.

Professor

University of California at San Francisco

DFHCN N411Y

San Francisco, CA 94143

Annlouise R. Assaf, M.S., Ph.D.

Principal Investigator

Women’s Health Initiative

Memorial Hospital of Rhode Island

111 Brewster Street

Pawtucket, RI 02860

Diane M. Becker, Sc.D., M.P.H.

Director

The Johns Hopkins Center for Health Promotion

1830 East Monument Street, Room 8025

Baltimore, MD 21205

Barbara S. Brown, M.Ed.

Principal

Goochland Elementary School

3150 River Road West

Goochland, VA 23063

Vanella A. Crawford, M.S.W., L.C.S.W.

President/CEO

The Vanella Group

c/o 1109 Michigan Avenue, N.E.

P.O. Box 29472

Washington, D.C. 20017

Lee Lee Doyle, M.A., Ph.D.

Professor

Obstetrics and Gynecology

Associate Dean for CME and Faculty Development

Department of Obstetrics and Gynecology

University of Arkansas for Medical

Sciences College of Medicine

Slot 518

4301 West Markham

Little Rock, AR 72205

Edwin B. Fisher, Jr., Ph.D.

Professor of Psychology

Director

Center for Health Behavior Research

Washington University School of Medicine

33 South Euclid, 2nd Floor

St. Louis, MO 63108
70

John M. Flack, M.D., M.P.H.

Assistant Professor of Medicine and Epidemiology

University of Minnesota Hospital and Clinic

Department of General Internal Medicine

Box 741 UMHC

420 Delaware Street, S.E.

Minneapolis, MN 55455

John C. Fletcher, Ph.D.

Professor of Biomedical Ethics

University of Virginia School of Medicine

Box 348 HSC

Charlottesville, VA 22908

Linda P. Fried, M.D., M.P.H.

Associate Professor

Medicine and Epidemiology

The Johns Hopkins Health Institutions

Carnegie 296, Johns Hopkins Hospital

600 North Wolfe Street

Baltimore, MD 21205

Patricia A. Ganz, M.D.

Director

UCLA Division of Cancer Prevention and Control

Professor

University of California at Los Angeles Schools

of Medicine and Public Health

Suite 711

1100 Glendon Avenue

Los Angeles, CA 90024

W. Dallas Hall, M.D.

Professor of Medicine

Emory University School of Medicine

69 Butler Street

Atlanta, GA 30303

William R. Hazzard, M.D.

Professor and Chairman

Department of Internal Medicine

Bowman Gray School of Medicine

of Wake Forest University

Medical Center Boulevard

Winston-Salem, NC 27157-1052

Maureen M. Henderson, M.D., D.P.H.

Head

Cancer Prevention Research Program

Fred Hutchinson Cancer Research Center

Professor of Epidemiology and Medicine

University of Washington

1124 Columbia Street, MP-702

Seattle, WA 98104

Charles H. Hennekens, M.D., Dr.P.H.

Professor of Medicine and Ambulatory Care

and Prevention

Harvard Medical School

Chief

Division of Preventive Medicine

Brigham and Women’s Hospital

900 Commonwealth Avenue, East

Boston, MA 02215

Barbara V. Howard, Ph.D.

President

Medlantic Research Institute

108 Irving Street, N.W.

Washington, D.C. 20010

Elmer E. Huerta, M.D., M.P.H.

Cancer Prevention Fellow

National Cancer Institute

National Institutes of Health

Executive Plaza North, Room 233

Bethesda, MD 20892

Harry E. Hynes, M.D., Ph.D.

Principal Investigator

Wichita Community Clinical Oncology Program

Cancer Center of Kansas

Suite 403

818 North Emporia

Wichita, KS 67214

Ruth L. Kirschstein, M.D.

Acting Director

National Institutes of Health

Building 1, Room 126

Bethesda, MD 20892

Paula Knudson

Executive Coordinator

Office of Research Support Committees

The University of Texas Health Science Center at Houston

P.O. Box 20036

Houston, TX 77006

Donna Kritz-Silverstein, Ph.D.

Assistant Adjunct Professor

Department of Family and Preventive Medicine

University of California at San Diego

9500 Gilman Drive, 0631-C

La Jolla, CA 92093-0631
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 71

Shiriki R. Kumanyika, Ph.D., M.P.H., R.D.

Professor and Associate Director for Epidemiology

Center for Biostatistics and Epidemiology

Pennsylvania State University

College of Medicine

P.O. Box 850

500 University Drive

Hershey, PA 17033

Ruth B. Merkatz, Ph.D., R.N.

Special Assistant to the Commissioner

Women’s Health Issues

Food and Drug Administration

5600 Fishers Lane, Room 1462 (HFI)

Rockville, MD 20857

Valery T. Miller, M.D.

Associate Professor of Medicine

George Washington Medical Center

Medical Director

Lipid Research Clinic

Suite 500

908 New Hampshire Avenue, N.W.

Washington, D.C. 20037

Katherine A. O’Hanlan, M.D.

GYN Cancer Service, A-344

Stanford University Medical Center

Stanford, CA 94305-5317

Dinah K. Pearson, M.H.A.

Associate Director

Health Services Management Group

University of Missouri - Columbia

324 Clark Hall

Columbia, MO 65211

Vivian W. Pinn, M.D.

Director

Office of Research on Women’s Health

Office of the Director

National Institutes of Health

Bethesda, MD 20892

Karen H. Rothenberg, J.D., M.P.A.

Professor of Law

Director

Law and Health Care Program

University of Maryland

School of Law

500 West Baltimore Street

Baltimore, MD 21201

Jeri A. Sechzer, Ph.D., M.A.

Research Professor

Department of Psychology

Pace University

Pace Plaza

New York, NY 10038

Congresswoman Louise M. Slaughter

(D-NY)

421 Rayburn House Office Building

Washington, D.C. 20515

Melanie A. Thompson, M.D.

Principal Investigator

AIDS Research Consortium of Atlanta

Suite 220

131 Ponce de Leon Avenue, N.E.

Atlanta, GA 30308

Reverend Melvin B. Tuggle

Chairman

Heart, Body, and Soul, Inc.

1131 Gorsuch Avenue

Baltimore, MD 21218

Rodger J. Winn, M.D.

Director

M.D. Anderson Cancer Center

University of Texas

1515 Holcombe Boulevard

Box 501

Houston, TX 77030

Leslie R. Wolfe, Ph.D.

Executive Director

Center for Women Policy Studies

Suite 508

2000 P Street, N.W.

Washington, D.C. 20036
72
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 73

Appendix V

THE OFFICE OF RESEARCH

ON WOMEN’S HEALTH

NATIONAL INSTITUTES OF HEALTH

SCIENTIFIC MEETING:

RECRUITMENT

AND RETENTION

OF WOMEN IN

CLINICAL STUDIES

OBSERVERS

HOLIDAY INN BETHESDA

BETHESDA, MARYLAND

JULY 12-13, 1993
74
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 75

Appendix V

OBSERVERS Diane Aiken, M.A.

Assurance Coordinator

National Institutes of Health

Building 31, Room 5B63

Bethesda, MD 20892

Alisa Alma, M.S.

Program Analyst

Office of Disease Prevention and Health Promotion

Office of the Assistant Secretary for Health

U.S. Department of Health and Human Services

Switzer Building, Room 2132

330 C Street, S.W.

Washington, D.C. 20201

Diane Mane Amalfitano, D.O.

Diplomate of A.O.B.G.P.

Annandale Women’s Center

2839 Duke Street

Alexandria, VA 22314

Margaret Anderson, M.A.

Research Analyst

Department of Professional Affairs

American Public Health Association

1015 Fifteenth Street, N.W.

Washington, D.C. 20005

Beth Ansel, Ph.D.

Program Administrator

Division of Communication Sciences and Disorders

National Institute on Deafness and Communication

Disorders

National Institutes of Health

Executive Plaza South, Room 400C

Rockville, MD 20852

Rhona S. Applebaum, Ph.D.

Director of Scientific Affairs

Distilled Spirits Council of the United States

Suite 900

1250 Eye Street, N.W.

Washington, D.C. 20005-3998

Linda Arviso-Miller

Management Program Analyst

Indian Health Service

U.S. Department of Health and Human Services

Parklawn Building, Room 6-40

Rockville, MD 20857
76

Warren K. Ashe, Ph.D.

Assistant Dean for Research

Howard University College of Medicine

520 W Street, N.W.

Washington, D.C. 20059

Alison Aubrey

National Women’s Health Network

1325 G Street, N.W.

Washington, D.C. 20005

Marie Bass

Principal

Bass and Howes, Inc.

Suite 801

1601 Connecticut Avenue, N.W.

Washington, D.C. 20009

Anne R. Bavier, M.N., F.A.A.N.

Women’s Health Coordinator

Agency for Health Care Policy and Research

2101 East Jefferson Street

Rockville, MD 20895

Sarah Begus, Ph.D.

Senior Research Associate

Center for Women Policy Studies

2000 P Street, N.W.

Washington, D.C. 20036

Yvette J. Benjamin

Consultant

108 Pembrooke View Lane

Gaithersburg, MD 20877

Karin Bierstein, J.D., M.P.H.

Washington Counsel

Department of Issues Management

American Medical Association

1101 Vermont Avenue, N.W.

Washington, D.C. 20008

Maggie Bierwirth

Senior Legislative Assistant for

Representative Sam Gejdenson

2416 Rayburn House Office Building

Washington, D.C. 20515

Mary G. Bonk, R.N.

Complications of Gynecologic

Surgery Women’s Support Group

225 Glencourtney Drive, N.E.

Atlanta, GA 30328

Louisa Borio, C.R.N.P.

Clinical Director for Ambulatory Nursing

Obstetrics and Gynecology Department

Hospital of the University of Pennsylvania

3400 Spruce Street

Philadelphia, PA 19104-4283

S. Lori Brown, Ph.D.

Epidemiology Fellow

Epidemiology, Demography, and Biometry Program

National Institute on Aging

National Institutes of Health

Gateway Building, Room 3C309

Bethesda, MD 20892

Shirley V. Brown

Editor

Gerontology News

The Gerontological Society of America

Suite 350

1275 K Street, N.W.

Washington, D.C. 20005-4006

Ruth Bulger, Ph.D.

Institute of Medicine

Division on Health Sciences Policy

National Academy of Science

2101 Constitution Avenue, N.W.

Washington, D.C. 20418

Linda Burhansstipanov, M.S.P.H., Dr.P.H., CHES

Program Director

Native American Cancer Control

Special Populations Branch

National Cancer Institute

National Institutes of Health

Executive Plaza North, Room 240

Bethesda, MD 20892

Carlos E. Caban, Ph.D., M.P.H.

Policy Officer

Extramural Programs

National Institutes of Health

Building 31, Room 5B31

Bethesda, MD 20892

Virginia S. Cain, Ph.D.

National Institute of Child Health

and Human Development

National Institutes of Health

Executive Plaza North, Room 8B13

Bethesda, MD 20892
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 77

Faye Calhoun, D.P.A., M.S.

Deputy Chief for Review

Division of Research Grants

National Institutes of Health

Westwood Building, Room 340

Bethesda, MD 20892

Martha Ann Carey, Ph.D.

Nurse Scientist Administrator

National Center for Nursing Research

National Institutes of Health

Westwood Building, Room 754

Bethesda, MD 20814

Christine Carter, Ph.D., M.P.H.

Senior Epidemiologist

The EMMES Corporation

Suite 214

11325 Seven Locks Road

Potomac, MD 20854

Donna H. Carter

Management Intern

National Heart, Lung, and Blood Institute

National Institutes of Health

Building 31, Room 5A29

Bethesda, MD 20892

Olivia Carter-Pokras, M.H.S.

Public Health Analyst

Office of Minority Health

Office of the Assistant Secretary for Health

U.S. Department of Health and Human Services

Rockwall Building, Room 1102

5515 Security Lane

Rockville, MD 20852

Nelvis Castro-Morales

Coordinator

Hispanic Education Program

Office of Cancer Communications

National Cancer Institute

National Institutes of Health

Building 31, Room 4B43

Bethesda, MD 20892

Jennifer Chambers

Co-Chair

Women and AIDS Coalition

Suite 201

105 9th Street, S.E.

Washington, D.C. 20003

Kenneth Chance, D.D.S.

Director

Health Policy Program

Office of Research

The Joint Center for Political and Economic Studies

Suite 1100

1090 Vermont Avenue, N.W.

Washington, D.C. 20005-4961

Vivian T. Chen, M.A., M.S.W., Sc.D.

Acting Director

Office of Minority and Women’s Health

Bureau of Primary Health Care

Parklawn Building, Room 8A41

Rockville, MD 20857

Aïda A. Chohayeb, D.D.S., M.S.D., F.A.C.D., F.I.C.D.

Professor

Howard University College of Dentistry

American Association of Women Dentists

600 W Street, N.W.

Washington, D.C. 20059

Michaele C. Christian, M.D.

Head

Developmental Chemotherapy Section

Investigational Drug Branch

Cancer Therapy Evaluation Program

Division of Cancer Treatment

National Cancer Institute

National Institutes of Health

6130 Executive Boulevard, Room 731B

Rockville, MD 20852

Mary T. Chunko, M.A.

Special Assistant for Communications

Division of Communications

Office of the Director

National Institutes of Health

Building 1, Room 257

Bethesda, MD 20892

Katie Clarke

Legislative Assistant on Women’s Issues

for Representative Bernard Sanders

213 Cannon House Office Building

Washington, D.C. 20515
78

Anne Claysmith

Health Specialist

Division of Acquired Immunodeficiency Syndrome

Office of the Director

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Solar Building, Room 2A22

Bethesda, MD 20892

Lucretia B. Coffer

Federal Women’s Program Manager

Division of Equal Opportunity

Office of the Director

National Institutes of Health

Building 31, Room 2B-40

Bethesda, MD 20892

Lois Ann Colaianni

Associate Director

Library Operations

National Library of Medicine

National Institutes of Health

Building 38, Room 2W04A

Bethesda, MD 20894

Linda Cook

Chief

Office of Information and Legislation

National Institute of Nursing Research

National Institutes of Health

Building 31, Room 5B13

Bethesda, MD 20854

Verna S. Cook, Ph.D.

Research Analyst

Administration on Aging

Department of Health and Human Services/OS

Cohen Building, Room 4747

330 Independence Avenue, S.W.

Washington, D.C. 20201

Judith A. Cooper, Ph.D.

Deputy Director

Division of Communication Sciences and Disorders

National Institute on Deafness and Other

Communication Disorders

National Institutes of Health

Executive Plaza South, Room 400-B

Rockville, MD 20892

Martha Cortes, D.D.S.

Chairperson

Latin American Cultural Center

(Educational)

Hispanic Dental Association

745 5th Avenue

New York, NY 10151

Sharon Courtney

Legislative Assistant for Representative John Murtha

2423 Rayburn House Office Building

Washington, D.C. 20009

Legislative Assistant for Representative Donald Payne

417 Cannon House Office Building

Washington, D.C. 20215

Nancy B. Cummings, M.D.

Associate Director

Research and Assessment

National Institute of Diabetes and Digestive

and Kidney Diseases

National Institutes of Health

Westwood Building, Room 627

Bethesda, MD 20892

Dorynne Czechowicz, M.D.

Associate Director for Medical and Professional Affairs

Division of Clinical Research

National Institute on Drug Abuse

National Institutes of Health

Parklawn Building, Room 10A-12

Rockville, MD 20857

Mary Ann Danello, Ph.D.

Director

Office of Scientific and Trade Affairs

Food and Drug Administration

Parklawn Building, Room 15-61

Rockville, MD 20857

Deborah Dauphinais, M.D.

Coordinator for Women’s Mental Health Research

National Institute of Mental Health

National Institutes of Health

Parklawn Building, Room 17C-14

Rockville, MD 20857

Helen C. Davies, Ph.D.

Associate Dean of Students

Professor of Microbiology

Department of Microbiology

University of Pennsylvania School of Medicine

Suite 100, Stemmler

Philadelphia, PA 19104-6087

Deborah Davis

Office of Research on Women’s Health

Office of the Director

National Institutes of Health

Bethesda, MD 20892
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 79

Yede Dennis, D.D.S.

General and Hospital Dentistry

New Jersey Dental School

110 Bergen Street, Room D803

Newark, NJ 07103

Teresa DePiñeres

Government Affairs Intern

American Medical Women’s Association

Suite 400

801 North Fairfax Street

Alexandria, VA 22314

Judy M. Destouet, M.D.

Chief of Mammography

Department of Radiology

Copeland, Hyman, and Shackman

1700 Reisterstown Road

Baltimore, MD 21208

Catherine Didion

Executive Director

Association for Women in Science

Suite 820

1522 K Street, N.W.

Washington, D.C. 20005

Agnes Donahue, D.D.S., M.Sc.D., M.P.H.

Director

Office on Women’s Health

Department of Health and Human Services

200 Independence Avenue, S.W.

Washington, D.C. 20201

Marie A. Dray, M.B.A.

Senior Director

Regulatory Agency Relations

Merck Research Laboratories

Suite 125

5615 Fishers Lane

Rockville, MD 20852

Anne Driscoll

Researcher

Fox, Bennett & Turner

Suite 1100

750 17th Street, N.W.

Washington, D.C. 20007

Debra Egan, M.P.H.

Health Program Specialist

Clinical Trials Branch

National Heart, Lung, and Blood Institute

National Institutes of Health

Federal Building, Room 5C-10

Bethesda, MD 20892

Elaine M. Eklund, M.S.

Associate Director

American Association of University Affiliated Programs

Suite 410

8630 Fenton Street

Silver Spring, MD 20707

Gary B. Ellis, Ph.D.

Director

Office of Protection from Research Risks

National Institutes of Health

Building 31, Room 5B63

Bethesda, MD 20892

Patricia M. Erickson, M.A.

Health Systems Specialist

Indian Health Service

Tucson Program Area

7900 South J. Stock Road

Tucson, AZ 85746

Odom Fanning

Correspondent

Internal Medicine World Report

9206 Bulls Run Parkway

Bethesda, MD 20817

Coralie Farlee, Ph.D.

Assistant Director for International

Legislation and Advisory Activities

Fogarty International Center

National Institutes of Health

389 O Street, S.W.

Washington, D.C. 20024

Erin Foley

National Women’s Health Network

1325 G Street, N.W.

Washington, D.C. 20005

Leslie G. Ford, M.D.

Chief

Community Oncology and Rehabilitation Branch

National Cancer Institute

National Institutes of Health

Executive Plaza North, Room 300

Bethesda, MD 20892

Zylphia L. Ford, M.P.H.

Project Coordinator

Center for Research on Women and Gender

University of Illinois at Chicago

Mail Code 980, Room 207

1640 West Roosevelt Road

Chicago, IL 60608
80

Jean L. Fourcroy, M.D., Ph.D.

Medical Officer (Urology)

Food and Drug Administration

5600 Fishers Lane

Rockville, MD 20857

Judith E. Fradkin, M.D.

Chief

Endocrinology and Metabolic Diseases Programs Branch

National Institute of Diabetes and Digestive and

Kidney Diseases

National Institutes of Health

Westwood Building, Room 621

Bethesda, MD 20892

Julia B. Freeman, Ph.D.

Centers Director

Director for Research on Women’s and Minorities’ Health

National Institute of Arthritis and Musculoskeletal

and Skin Diseases

National Institutes of Health

Westwood Building, Room 403

Bethesda, MD 20892

Richard K. Fuller, M.D.

Director

Division of Clinical and Prevention Research

National Institute on Alcohol Abuse and Alcoholism

National Institutes of Health

Parklawn Building, Room 14C-10

Rockville, MD 20857

Fumiko Furukawa, R.N.

Clinical Trials Branch

Division of Epidemiology and Clinical Applications

National Heart, Lung, and Blood Institute

National Institutes of Health

Federal Building, Room 5C10

Bethesda, MD 20892

Barbara Gaffney

Deputy Associate Administrator for Policy Coordination

Health Resources and Services Administration

Parklawn Building, Room 14A-12

Rockville, MD 20857

Dorothy B. Gaither, M.D.

Obstetrics and Gynecology

Annandale Women’s Center

2839 Duke Street

Alexandria, VA 22314

Mikella Gallagher

Research Assistant

Fox, Bennett & Turner

Suite 1100

750 17th Street, N.W.

Washington, D.C. 20006

Sheryle J. Gallant, Ph.D.

Associate Professor

Medical Psychology

U.S. Uniformed Health Services

4301 Jones Bridge Road

Bethesda, MD 20814-4799

Rekha Garg, M.D.

Medical Officer

Clinical Trials Branch

National Heart, Lung, and Blood Institute

National Institutes of Health

Federal Building, Room 5C-10

Bethesda, MD 20892

Emily M. Gause

Planning Officer

Office of Science Policy and Program Planning

National Institute of Mental Health

National Institutes of Health

Parklawn Building, Room 17C-26

Rockville, MD 20857

Frederick K. Goodwin, M.D.

Director

National Institute of Mental Health

National Institutes of Health

Parklawn Building, Room 17-99

Rockville, MD 20895

Enoch Gordis, M.D.

Director

National Institute on Alcohol Abuse and Alcoholism

National Institutes of Health

Parklawn Building, Room 16-105

Rockville, MD 20857

Harriet Gordon, M.D.

Medical Officer

General Clinical Research Centers Program

National Center for Research Resources

National Institutes of Health

Westwood Building, Room 10A-03

Bethesda, MD 20892
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 81

Karen Gordon, M.P.H.

Director of Health Education

Princeton University Health Services

Princeton, NJ 08544

Laverne M. Green, M.H.A.

Clinical Nurse Specialist

Bureau of Primary Health Care

5600 Fishers Lane, Room 9-12

Rockville, MD 20856

Phyllis Greenberger, M.S.W.

Executive Director

Society for the Advancement of Women’s Health Research

Suite 600

1920 L Street, N.W.

Washington, D.C. 20036

Theresa Greene-Reed, M.D., M.P.H.

Historian

National Medical Association

1012 10th Street, N.W.

Washington, D.C. 20001

Laura Greer

Intern

Healthy Mothers, Healthy Babies

409 12th Street, S.W.

Washington, D.C. 20024

Jeane Ann Grisso, M.D., M.Sc.

Associate Professor of Medicine

Center for Clinical Epidemiology and Biostatistics

University of Pennsylvania

317R NEB/6095

420 Service Drive

Philadelphia, PA 19104

Denise M. Hagan, M.A.

Research Nurse Coordinator

Department of OB/GYN Reproductive Endocrinology

Wayne State University

Hutzel Hospital

University Center for Women’s Medicine

Suite 320

28800 Ryan Road

Warren, MI 48092

Cynthia Hall

Legislative Director for Representative Connie Morella

223 Cannon House Office Building

Washington, D.C. 20515

Eleanor Hanna, Ph.D.

Special Expert

Division of Biometry and Epidemiology

National Institute on Alcohol Abuse and Alcoholism

National Institutes of Health

Parklawn Building, Room 14C-26

Rockville, MD 20857

Anne E. Hardman

Technical Information Specialist

National Institute on Aging

National Institutes of Health

Building 31, Room 5C-05

Bethesda, MD 20892

William R. Harlan, M.D.

Associate Director

Office of Disease Prevention

Office of the Director

National Institutes of Health

Building 1, Room 260

Bethesda, MD 20892

Susan B. Harris, J.D.

Washington Representative

Department of Public Affairs

National MS Society

Suite 405

236 Massachusetts Avenue, N.E.

Washington, D.C. 20002

Suzanne G. Haynes, Ph.D.

Chief

Health Education Section

National Cancer Institute

Project Officer

Women’s Health Initiative

National Institutes of Health

Executive Plaza North, Room 241

Bethesda, MD 20892

Janyce N. Hedetniemi, M.S.

Chief

Office of Program Analysis and Evaluation

National Institute of General

Medical Sciences

National Institutes of Health

Westwood Building, Room 819

Bethesda, MD 20892
82

Janet B. Henrich, M.D.

Special Assistant

Center for Population Research

National Institute of Child

Health and Human Development

National Institutes of Health

6100 Executive Boulevard, Room 8B07

Bethesda, MD 20892

Susan Herbert, M.A.

Clinical Trials Specialist

MDD

National Institute on Drug Abuse

National Institutes of Health

5600 Fishers Lane, Room 11A55

Rockville, MD 20857

Stephen P. Heyse, M.D., M.P.H.

Director

Office of Prevention, Epidemiology, and

Clinical Applications

National Institute of Arthritis and Musculoskeletal

and Skin Diseases

National Institutes of Health

Building 31, Room 4C13

Bethesda, MD 20892

Euthymia D. Hibbs, Ph.D.

Head

Psychosocial Treatment Research

Child and Adolescent Disorders Research Branch

Division of Clinical and Treatment Research

National Institute of Mental Health

National Institutes of Health

Parklawn Building, Room 18C-17

Rockville, MD 20857

Jeanne E. Hicks, M.D.

Deputy Chief

Rehabilitation Medicine

Warren Grant Magnuson Clinical Center

National Institutes of Health

Building 10, Room 6S235

Bethesda, MD 20892

Shaun Hill

Public Policy Liaison

Administration Department

National Medical Association

1012 10th Street, N.W.

Washington, D.C. 20001

Jacqueline A. Horton, Sc.D.

Associate Director

Department of Research and Technology Assessment

American College of Obstetricians and Gynecologists

409 12th Street, S.W.

Washington, D.C. 20024-2188

Anne Houser, M.S.

Director

Division of Legislative Liaison and Analysis

Office of Legislative and Policy Analysis

National Institutes of Health

Building 1, Room 244

Bethesda, MD 20892

Sandra N. Howard

Health Policy Analyst

Office of the Assistant Secretary for Planning

and Evaluation

U.S. Department of Health and Human Services

Hubert H. Humphrey Building, Room 442E

200 Independence Avenue, S.W.

Washington, D.C. 20201

Carrie P. Hunter, M.D.

Special Assistant to the Director

Office of Research on Women’s Health

Office of the Director

National Institutes of Health

Federal Building, Room 6A09

Bethesda, MD 20892

Norman Hymowitz, Ph.D.

Clinical Professor

Co-Principal Investigator

Women’s Health Initiative, Newark Center

Department of Psychiatry

New Jersey Medical School

Adm-C, Room 1430

30 Bergen Street

Newark, NJ 07107

Caroline Isber

Senior Program Analyst for Legislation and Special Projects

Office of Research on Women’s Health

Office of the Director

National Institutes of Health

Bethesda, MD 20892

Debbie Jackson, M.A.

Health Policy Analyst

Division of Medicine

5600 Fishers Lane, Room 4C-18

Rockville, MD 20857
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 83

Donna M. Jermain, Pharm.D.

Clinical Pharmacist/Assistant Professor

Pharmacy/Psychiatry Department

Scott White Hospital

Texas A & M University

2401 South 31st Street

Temple, TX 76508

Joanne Johnson

Assistant Chief

New York Hospital

Cornell Burn Center

American Burn Association

525 East 68th Street

Box 142

New York, NY 10021

Karen A. Johnson, M.D., Ph.D.

Program Director

Community Oncology and Rehabilitation Branch

National Cancer Institute

National Institutes of Health

Executive Plaza North, Room 300

Bethesda, MD 20892

Tamara Lewis Johnson, M.B.A., M.P.H.

Public Health Analyst

Policy Assistance Division

Bureau of Primary Health Care

Health Resources and Services Administration

5600 Fishers Lane

Rockville, MD 20857

Antony W. Kalm

Research Assistant

Fox, Bennett & Turner

Suite 1100

750 17th Street, N.W.

Washington, D.C. 20006

Julie Kaneshiro

Management Intern

Office for Protection from Research Risks

National Institutes of Health

Building 31, Room 5B63

Bethesda, MD 20892

Mark Kapiloff

Associate Publisher

Sentinel Newspapers

P.O. Box 1272

Rockville, MD 20849

Linda Karacoloff, M.S.

Associate Director

American Physical Therapy Association

1111 North Fairfax Street

Alexandria, VA 22314

Kimberly Kasberg

Research Associate

Institute of Medicine

2101 Constitution Avenue, N.W.

Washington, D.C. 20418

Terri Kendrix

Administrative Officer

Office of Research on Women’s Health

Office of the Director

National Institutes of Health

Bethesda, MD 20892

Lydia Kenlaw

Management Intern

Deputy Director for Management

National Institutes of Health

Bethesda, MD 20892

Karen Kiang

National Women’s Health Network

1325 G Street, N.W.

Washington, D.C. 20005

Kristin G. King

Legislative Assistant for Representative James Moran

430 Cannon House Office Building

Washington, D.C. 20515

Thomas Kirk, M.S.S.W.

Director

Patient and Family Services

Alzheimer’s Association, National Headquarters

Suite 1000

919 North Michigan Avenue

Chicago, IL 60611-1676

Kurt Kleiner, M.S.

702 Glastone Avenue, #1

Baltimore, MD 21210

Mary C. Knipmeyer, Ph.D.

Acting Associate Administrator for Women’s Services

Substance Abuse and Mental Health Administration

U.S. Department of Health and Human Services

Parklawn Building, Room 13-99

Rockville, MD 20857
84

Joy Koenig, M.D., M.S.

Associate Regional Health Administrator

U.S. Public Health Service-Region I

JFK Federal Building, Room 1826

Boston, MA 02203

Annette Kornblum, M.S.

Medical Writer

P.O. Box 53323

Washington, D.C. 20009

Natalie Kurinij, Ph.D.

Health Science Administrator

National Eye Institute

National Institutes of Health

Executive Plaza South, Room 350

Bethesda, MD 20892

Lynne Lackey, Ph.D.

Senior Policy Analyst

Office of the Assistant Secretary for Health

U.S. Department of Health and Human Services

Hubert H. Humphrey Building, Room 740G

200 Independence Avenue, S.W.

Washington, D.C. 20201

Jean A. Langlois, Ph.D.

Epidemiologist

Epidemiology, Demography, and Biometry Program

National Institute on Aging

National Institutes of Health

Gateway Building, Room 3C309

Bethesda, MD 20892

Judith H. LaRosa, Ph.D.

Deputy Director

Office of Research on Women’s Health

Office of the Director

National Institutes of Health

Bethesda, MD 20892

Elizabeth Lawton

Public Policy Grants Coordinator

American Foundation for AIDS Research

Suite 802

1828 L Street, N.W.

Washington, D.C. 20010

Meryl S. LeBoff, M.D.

Director

Skeletal Health and Osteoporosis Clinic

Brigham and Women’s Hospital

Endocrine-Hypertension Division/

Internal Medicine Department

Harvard Medical School

221 Longwood Avenue

Boston, MA 02115

Barbara Lewis

Clinical Research Nurse

Medical-Oncology Department

Georgetown University Medical Center

3800 Reservoir Road, N.W.

Washington, D.C. 20007

Margaret R. Light, R.N., M.S.N.

Nurse Practitioner

Annandale Women’s Center

2839 Duke Street

Alexandria, VA 22314

Marian Limacher, M.D.

Associate Professor of Medicine

Division of Cardiology

Department of Medicine

Box 100277 JHMHC

University of Florida

Gainesville, FL 32610

Melody Lin, Ph.D.

Director

Human Subject Protection

National Institutes of Health

Building 31, Room 5B59

Bethesda, MD 20892

Lance A. Liotta, M.D., Ph.D.

Deputy Director

Intramural Research

National Institutes of Health

Building 1, Room 114

Bethesda, MD 20892

Barbara Marzetta Liu, S.M.

Scientific Program Specialist

National Heart, Lung,and Blood Institute

National Institutes of Health

Building 31, Room 5A03

Bethesda, MD 20892
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 85

Martha Man

Intern

National Women’s Health Network

1325 G Street, N.W.

Washington, D.C. 20005

Gilda Marques, M.B.A., M.D.

Medical Officer

National Institute of Neurological

Disorders and Stroke (NINDS)

National Institutes of Health

Building 31, Room 8A-03

Bethesda, MD 20895

Joy A. Marshall, R.N.

Annandale Women’s Center

Cygma Health Center

Metro Medical Centers

Suite 508

5990 Richmond Highway

Alexandria, VA 22303

Margaret S. Mason, M.S., Ph.D.(c)

Director

Center for Minority Health

Office of Community Relations

Department of Health and Mental Hygiene

201 West Preston Street, Room 504

Baltimore, MD 21201

Margaret Mattson, Ph.D.

Health Scientist Administrator

Division of Clinical and Prevention Research

National Institute on Alcohol Abuse and Alcoholism

National Institutes of Health

Parklawn Building, Room 14C-20

Rockville, MD 20857

Marsha Lakes Matyas, Ph.D.

Education Officer

American Physiological Society

9650 Rockville Pike

Bethesda, MD 20814-3991

Mary S. McCabe

Clinical Trials Specialist

Cancer Therapy Evaluation Program

National Cancer Institute

National Institutes of Health

Executive Plaza North, Room 715

Bethesda, MD 20892

Tricia McCauley

Alliance Coordinator

National Alliance for Oral Health c/o AADS

1625 Massachusetts Avenue, N.W.

Washington, D.C. 20036

Eileen McGrath, J.D.

Executive Director

American Medical Women’s Association

Suite 400

801 North Fairfax Street

Alexandria, VA 22314

Jean McKay, M.L.S.

Program Analyst

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Executive Plaza North, Room 2A21

Bethesda, MD 20892

Irma Mebane-Sims, Ph.D.

Epidemiologist

Lipid Metabolism Atherogenesis Branch

National Heart, Lung, and Blood Institute

National Institutes of Health

Federal Building, Room 401

Bethesda, MD 20892

Diana Medina

Medical Student

Educational Affairs/Hispanic Center of Excellence

New Jersey Medical School

185 South Orange Avenue, MSB C-661

Newark, NJ 07103

Vijaya L. Melnick, Ph.D.

Director

Center for Applied Research and Urban Policy

University of the District of Columbia

4200 Connecticut Avenue, N.W.

Washington, D.C. 20008

Cristina L. Monroe

Office of Research on Women’s Health

Office of the Director

National Institutes of Health

Bethesda, MD 20892

Ann Montgomery, R.N., M.A.

Clinical Research Specialist

MDD

National Institute on Drug Abuse

National Institutes of Health

5600 Fishers Lane, Room 11A55

Rockville, MD 20857
86

Elizabeth Clark Moore, M.S., R.Ph.

Coordinator

Research and Development Agreements

Regulatory Affairs Branch

National Cancer Institute

National Institutes of Health

Executive Plaza North, Suite 718

Bethesda, MD 20892

Karen Y. Morita, M.P.A.

American Foundation for AIDS Research

Suite 802

1828 L Street, N.W.

Washington, D.C. 20010

Nancy Moss, Ph.D.

Expert Sociologist

National Institute of Child Health and

Human Development

National Institutes of Health

Bethesda, MD 20892

Frances M. Murphy, M.D., M.P.H.

Assistant Chief

Neurology Service

Veterans Administration Medical Center

50 Irving Street, N.W.

Washington, D.C. 20422

Jalil H. Mutakabbir

NIH Black Employment Manager

Office of Equal Opportunity

Office of the Director

National Institutes of Health

Building 31, Room 2B40

Bethesda, MD 20892

Ralph F. Naunton, M.D.

Director

Division of Communication Sciences and Disorders

National Institute on Deafness and Other

Communication Disorders

National Institutes of Health

Executive Plaza South, Room 400C

Rockville, MD 20852

Susan Nemeth, Ph.D.

Senior Manager

Regulatory Affairs

Schering Plough Research Institute

2000 Galloping Hill Road

Kenilworth, NJ 07208

Ruth Newjack-Raymer, R.D.H., M.P.H.

Public Health Researcher

Epidemiology and Oral Disease Prevention Program

National Institute of Dental Research

National Institutes of Health

Westwood Building, Room 538

Bethesda, MD 20892

Margaret A. Nosek, Ph.D.

Associate Professor

Physical Medicine and Rehabilitation

Baylor College of Medicine

Suite 1000

2323 South Shepherd Drive

Houston, TX 77019

K.C. Pani, M.D., M.S., F.A.C.P.

International Consultant

Medical and Tropical Diseases

6509 Greentree Road

Bethesda, MD 20817

301-365-5870

Kathryn Peek, Ph.D.

Director

Research Training

Department of Academic Affairs

University of Texas Medical School at Houston

Suite G024

6431 Fannin

Houston, TX 77030

Susan Persons, M.A.

Associate Director for Government Affairs

Consortium of Social Science Associations

Suite 836

1522 K Street, N.W.

Washington, D.C. 20005

Anne Petruska

The Blue Sheet

Suite 1

5550 Friendship Boulevard

Chevy Chase, MD 20815

Pamela Phillips, M.H.S.

Information Specialist

The EMMES Corporation

Suite 214

11325 Seven Locks Road

Potomac, MD 20854
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 87

Vivian W. Pinn, M.D.

Director

Office of Research on Women’s Health

Co-Director

Women’s Health Initiative

Office of the Director

National Institutes of Health

Bethesda, MD 20892

Ellyn J. Pollack, M.A., APR

Public Affairs Specialist

Office of Research on Women’s Health

Office of the Director

National Institutes of Health

Bethesda, MD 20892

Joan Porter, D.P.A.

Office of the Director

Office of Protection from Research Risks

National Institutes of Health

Building 31, Room 5B59

Bethesda, MD 20892

Kimberly Queen

Health and Human Resource Specialist

AIDS Program

West Virginia Bureau of Public Health

1422 Washington Street, East

Charleston, WV 25301

Jennifer L. Reck

Jacobs Institute of Women’s Health

409 12th Street, S.W.

Washington, D.C. 20024-2188

Stephanie Roberts

Office of Planning, Evaluation, and Communications

National Institute of Dental Research

National Institutes of Health

Building 31, Room 2C34

Bethesda, MD 20892

Jessica Roth

Legislative Correspondent for Senator Bill Bradley

731 Hart Senate Office Building

Washington, D.C. 20510

Jean P. Rowan, M.D.

Senior Director

Endocrine Department

Parke-Davis

2800 Plymouth Road

Ann Arbor, MI 48105

Joyce Rudick

Senior Program Analyst

Office of Research on Women’s Health

Office of the Director

National Institutes of Health

Bethesda, MD 20892

Cathy Russell, J.D.

Assistant Director

Division of Government Relations

American Psychiatric Association

1400 K Street, N.W.

Washington, D.C. 20005

Sally J. Rynne, M.A.

President

Women’s Healthcare Consultants

Suite 700

500 Davis Street

Evanston, IL 60201

Patricia Salomon, M.D.

Associate Bureau Director for Clinical Affairs

Bureau of Primary Health Care

Health Resources and Services Administration

U.S. Public Health Service

5600 Fishers Lane, Room 9-12

Rockville, MD 20856

Ruth Sanchez-Way, Ph.D.

Director

Division of Community Prevention and Training

CSAP and Associate Administrator for Minority Concerns

Substance Abuse and Mental Health Administration

5600 Fishers Lane

Rockwall II Building, Room 9D18

Rockville, MD 20857

Alberta H. Sandel

Secretary to the Director

Office of Research on Women’s Health

Office of the Director

National Institutes of Health

Bethesda, MD 20892

Donna Savage, M.Ed.

Projects Coordinator

Sharon Sloane Enterprises

7th Floor

6116 Executive Boulevard

Rockville, MD 20852
88

Iris J. Schneider

Assistant Director

Program Operations and Planning

National Cancer Institute

National Institutes of Health

Building 31, Room 11A48

Bethesda, MD 20892

Johanna Schneider

Senior Advisor for Media Relations

Office of the Director

National Institutes of Health

Building 1, Room 338

Bethesda, MD 20892

Eleanor B. Schron, M.S., R.N.

Public Health Analyst

Clinical Trials Branch

Division of Epidemiology and Clinical Applications

National Heart, Lung, and Blood Institute

National Institutes of Health

Federal Building, Room 5C10

Bethesda, MD 20892

Ellen Seely, M.D.

Director of Clinical Research

Endocrine Hypertension Division

Brigham and Women’s Hospital

221 Longwood Avenue

Boston, MA 02115

Valerie P. Setlow, Ph.D.

Director

Division of Health Sciences Policy

Institute of Medicine

National Academy of Sciences

2101 Constitution Avenue, N.W.

Washington, D.C. 20418

Belinda Seto, Ph.D.

Assistant for Minority Health Issues to the Associate

Director for Research on Minority Health

Office of Research on Minority Health

Office of the Director

National Institutes of Health

Building 1, Room 255

Bethesda, MD 20892

Sherry Sherman, Ph.D.

Director

Osteoporosis Program

National Institute on Aging

National Institutes of Health

Gateway Building, Suite 3E327

Bethesda, MD 20892

John D. Siegfried, M.D.

Associate Vice President of Medical Affairs

Pharmaceutical Manufacturing Association

Suite 900

1100 15th Street, N.W.

Washington, D.C. 20006

Eleanor M. Simonsick, Ph.D.

Epidemiologist

Epidemiology, Demography, and Biometry Program

National Institute on Aging

National Institutes of Health

Gateway Building, Room 3C309

Bethesda, MD 20892

Sonia Skarlatos, Ph.D.

Health Scientist Administrator

National Heart, Lung, and Blood Institute

National Institutes of Health

Federal Building, Room 4A08

Bethesda, MD 20892

Linda C. Skidmore, M.Ed.

Study Director

Committee on Women in Science and Engineering

National Research Council

Room TJ 2011

2101 Constitution Avenue, N.W.

Washington, D.C. 20418

Lana R. Skirboll, Ph.D.

Director

Office of Science Policy and Program Planning

National Institute of Mental Health

National Institutes of Health

Parklawn Building, Room 17C-26

Rockville, MD 20857

Sharon Sloane, M.A.

President

Sharon Sloane Enterprises

7th Floor

6116 Executive Boulevard

Rockville, MD 20852

Rochelle Small, Ph.D.

Program Administrator

Division of Communication

Sciences and Disorders

National Institute on Deafness and Other

Communication Disorders

National Institutes of Health

Executive Plaza South, Room 400C

Rockville, MD 20852
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 89

Ruthann M. Smejkal, Ph.D.

Health Science Administrator

Office of Research Management

Walter Reed Army Institute of Research

Washington, D.C. 20307-5100

Sonya K. Sobrian, Ph.D.

Associate Professor of Pharmacology

Department of Pharmacology

Howard University College of Medicine

520 W Street, N.W.

Washington, D.C. 20059

Barbara C. Sonies, M.S., Ph.D.

Chief

Speech Language Pathology Section

Department of Rehabilitation Medicine

Warren Grant Magnuson Clinical Center

National Institutes of Health

Building 10, Room 6S235

Bethesda, MD 20892

Maria Soto-Greene, M.D.

Associate Professor of Clinical Medicine

Director

Hispanic Center of Excellence

New Jersey Medical School

185 South Orange Avenue, MSB C-661

Newark, NJ 07103

Christine G. Spain, M.A.

Director

Research Planning and Special Projects

President’s Council on Physical

Fitness and Sports

Suite 250

701 Pennsylvania Avenue, N.W.

Washington, D.C. 20004

Amanda L. Spitler

Government Affairs Representative

American College of Rheumatology

Suite 800

2011 Pennsylvania Avenue, N.W.

Washington, D.C. 20006-1808

Martha Staller

American Physical Therapy Association

1111 North Fairfax Street

Alexandria, VA 22306

Julie Steele, M.P.H., CHES

Patient Education Specialist

Patient Education Section

Office of Cancer Communications

National Cancer Institute

National Institutes of Health

Building 31, Room 4B43

Bethesda, MD 20852

Randy E. Stevens, M.D.

Assistant Professor of Radiology

Department of Radiation Oncology

New York University Medical Center

566 First Avenue, Room HC107

New York, NY 10016

Joyce Stichman, M.S.

Vice President

Academic Administration

Memorial Sloan-Kettering Cancer Center

1275 York Avenue

New York, NY 10021

Irene Stith-Coleman, Ph.D.

Head

Biomedical Policy Section

Science Policy Research Division

Congressional Research Service

Library of Congress

101 Independence Avenue, S.E.

Room LM413

Washington, D.C. 20540

Peggy Stotz

Project Coordinator

Coalition on Alcohol and Drug Dependent Women

and Their Children

Suite 926

1511 K Street, N.W.

Washington, D.C. 20005

Jennifer Sutton, M.S.

Staff Associate

Division of Biomedical Research

Association of American Medical Colleges

2450 N Street, N.W.

Washington, D.C. 20015
90

Betty Tai, Ph.D.

Clinical Pharmacologist

Medications Development Division

National Institute of Drug Abuse

National Institutes of Health

Parklawn Building, Room 11A-55

Rockville, MD 20816

Holly Taylor, M.P.H.

Special Assistant to the Director

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Building 31, Room 7A-04

Bethesda, MD 20892

Julie Taylor

Policy Analyst

American Society of Clinical Oncology

Suite 1100

750 17th Street, N.W.

Washington, D.C. 20006

Marilou E. Taylor, J.D.(c)

Department of Regulatory Affairs

DuPont Merck Pharmaceutical Company

Barley Mill Plaza, P27-2372

4301 Lancaster Avenue

Wilmington, DE 19880-0024

Maria C. Teehan

Legislative Staff Assistant for Representative

Robert A. Underwood

507 Cannon House Office Building

Washington, D.C. 20515

Rosemary Torres, J.D., B.S.N.

Special Assistant to the Director

Office of Research on Women’s Health

Office of the Director

National Institutes of Health

Bethesda, MD 20892

Nina M. Trocky, R.N.

PLCO Study Coordinator

Georgetown University Medical Center

Lombardi Cancer Center

3800 Reservoir Road, N.W.

Washington, D.C. 20007

Marilyn Tuttleman, M.S.

Statistician

National Institute of Arthritis and Musculoskeletal

and Skin Diseases

National Institutes of Health

Building 31, Room 4C13

Bethesda, MD 20892

Artrice Valentine-Bader, Ph.D.

Health Science Administrator

#1 Whisperwood Court

Rockville, MD 20852

Sheila Walsh

Washington Blade

1408 U Street, N.W.

Washington, D.C. 20009

E. Lea Watson, D.M.D., M.A.

Geriatric Dental Fellow

Center for Aging

UMDNJ-SOM

301 South Central Plaza

Cherry Hill, NJ 08084

Marilyn Weiner

President

Education Department

Screenscope, Inc.

4330 Yuma Street, N.W.

Washington, D.C. 20016

Beth Weinhouse, M.S.

Ballantine Publishing

103 Virginia Street

Oxford, MS 38655

Wendy Wertheimer

Program Planning Officer

Office of AIDS Research

Office of the Director

National Institutes of Health

Building 1, Room 201

Bethesda, MD 20892

Susan Wescott

Health Specialist

Division of AIDS

National Institute of Allergy and Infectious Diseases

National Institutes of Health

6003 Executive Boulevard, Room 2B02

Rockville, MD 20892
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 91

Nola Whitfield, M.Ed.

Program Analyst

National Institute of Diabetes and Digestive

and Kidney Diseases

National Institutes of Health

Building 31, Room 9A07

Bethesda, MD 20892

Ethel James Williams, M.S.S.W.

Board of Directors

Black Women’s Agenda, Inc.

Suite N720

1301 Delaware Avenue, S.W.

Washington, D.C. 20024

Susan S. Wise

Program Analyst

National Institute of Dental Research

National Institutes of Health

Building 31, Room 2C34

Bethesda, MD 20892

Pamela M. Witcher, Ph.D.

Research Instructor

Psycho-Oncology Research Program

Department of Psychiatry

Georgetown University Medical Center

3800 Reservoir Road, N.W.

Washington, D.C. 20007-2197

Susan F. Wood, Ph.D.

Science Advisor

Congressional Caucus for Women’s Issues

2471 Rayburn House Office Building

Washington, D.C. 20515

Christina Wowk, M.S., M.T.(ASCP), Ph.D.(c)

Nutrition Science Department

Pennsylvania State University

4903 Edgemoor Lane

Bethesda, MD 20814

Arnette Wright, R.N.

Women and Minority Health Leaders

Division of Programs for Special Populations

Bureau of Primary Health Care

Health Resources and Services Administration

U.S. Public Health Service

5600 Fishers Lane, Room 9-12

Rockville, MD 20856

Deborah A. Zarin, M.D.

Associate Director

Office of Research

American Psychiatric Association

1400 K Street, N.W.

Washington, D.C. 20005

Troy Zimmerman

Washington Representative

Arthritis Foundation

426 C Street, N.E.

Washington, D.C. 20002

Veva H. Zimmerman, M.D.

Associate Dean

Office of the Dean

New York University School of Medicine

550 First Avenue

New York, NY 10016
92
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 93

Appendix VI

THE OFFICE OF RESEARCH

ON WOMEN’S HEALTH

NATIONAL INSTITUTES OF HEALTH

SCIENTIFIC MEETING:

RECRUITMENT

AND RETENTION

OF WOMEN IN

CLINICAL STUDIES

LEGAL AND

ETHICAL ISSUES

HOLIDAY INN BETHESDA

BETHESDA, MARYLAND

JULY 12-13, 1993
94
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 95

Legal Considerations

Federal Statutes, Regulations, Guidelines

and Policies

The applicable federal human subjects regulations,guidelines and policies are: the Department of Health

and Human Services (DHHS) protection of human subject regulations,1

 the December 1990 NIH Memorandum

(containing the NIH policy for inclusion of women and

minorities in study populations), and the NIH Revitalization Act.2

 The NIH Revitalization Act requires the inclusion

of women and minorities in clinical research trials where

appropriate. They may be excluded if inclusion would be

inappropriate with respect to the health of the subjects,

the purpose of the research, or other such circumstances

as the Secretary (DHHS) may designate. Regulations are

currently being written to implement this act. The 1977

FDA Guidelines (“General Considerations for the Clinical

Evaluation of Drugs”) are currently being significantly

revised to recognize that women should be included

in clinical trials, although FDA policy with respect to

pregnant women is still to be developed. It should be

further noted that it was anticipated that these 1977

guidelines would be re-reviewed approximately every

18 to 24 months and that no such timely re-review had

been made until this past year. The NIH Memorandum

and FDA Guidelines are not regulations, but rather guidelines and policies. All have problems of ambiguity.

For example, subpart B of the HHS regulations

(which has not been changed since 1975) requires

partner consent (absent a few exceptions) when research

on pregnant women is for the benefit of the fetus, but not

when research is for the “health needs of the mother.”

Such terminology is not defined.

The NIH policy concerning the inclusion of minorities

and women in study populations, described in the 1990

NIH Memorandum, also has ambiguous provisions. The

policy specifically allows exclusion of women from study

populations on the basis of a “clear, compelling rationale.”

An example of such a rationale is that the study presents

an “unacceptable risk for women of childbearing age.”

Again, this terminology is not defined. Information

from NIH on the justifications deemed acceptable in

practice is needed.

Appendix VI

LEGAL AND

ETHICAL ISSUES

Karen H. Rothenberg, J.D., M.P.A.

Director, Law & Health Care Program

University of Maryland School of Law
96

Liability for exclusion of women may potentially be

greater than liability exposure for inclusion. Current

policies stipulate that greater numbers of women be

“guinea pigs” during the marketing phase of drugs than

the numbers required by policies governing the numbers

of women included in phase I trials or when only small

numbers of subjects would be exposed to risk. This issue

came to the forefront as a result of the controversy surrounding the use of women in AIDS trials. If women

are not included in clinical trials, there may be greater

liability exposure, since we now know that there may

be foreseeable risks to women if drugs are not pre-market

tested on them. If the failure to inform study participants

of foreseeable risks reaches the level of reckless indifference, punitive damages as well as compensatory damages

may be awarded to an injured plaintiff.

Constitutional Issues

A possible constitutional issue has arisen as a resultof a recent Supreme Court case, Johnson Controls.

This was a case brought under Title VII, a Federal law

concerning unlawful employment practices. The company,

Johnson Controls, had a policy that excluded all women

of childbearing age from jobs in the company’s battery

factory, where there would be potential lead exposure.

The Supreme Court determined that this was a violation

of Title VII. The company had argued that it was concerned

with fetal protection and the prevention of possible lawsuits

by affected offspring. One Supreme Court justice wrote

that, if in fact, the company knew what the risks were and

acted appropriately in sharing them with the woman, and

the woman knew what they were and agreed to continue

to work, it would be highly unlikely—although not a

guarantee—that a court would ever find the company

negligent. This is because negligence means falling below

the accepted standard at a point in time; negligence does

not mean being perfect or being an insurer.

Johnson Controls is not a perfect analogy to the exclusion

of women from clinical trials because having a right to a

job is not the same as having a right to be in a clinical trial.

The underlying argument and the public policy, however,

may be applicable: that is, are we prepared, as a matter of

fairness, to exclude women from the benefits of clinical

trials just because they are in their reproductive years? It is

reasonable to conclude that the exclusion of fertile women

does have the effect of denying women as a class an equal

opportunity to benefit from government funded research.3

Common Law: Tort Liability

There are two basic relevant tort principles: strictliability and negligence. Under the principle of

strict liability, if you have an unreasonably dangerous

product or activity and it causes injury, you can be liable

for that injury even without proof of fault. (Proof of

causation, however, is required.) Comment k to Section

402A of the Restatement (Second) of Torts [a compilation

listing general rules of torts] specifies that the principle

of strict liability will not generally be applied with respect

to a drug or vaccine if there is a warning of the drug or

vaccine’s known and foreseeable side effects. The issue

arises if it is possible to give informed consent in the

situation where there are no data applicable to women

of childbearing potential in any of the phase 1 or early

phase II clinical trials.

Under the principle of negligence, a plaintiff must

show that the defendant owed the plaintiff a duty of care,

the defendant breached that duty (often a battle of plaintiff

and defense experts), the plaintiff was injured, and the

defendant’s breach of the standard of care was the cause

of injury. Causation is difficult for the plaintiff to prove.

Often, those who are in clinical trials are not healthy,

making it even more difficult to prove that a particular

drug caused an injury. Perhaps there are not more of these

types of cases because causation is difficult to prove, or

because informed consent has been adequate.

Notwithstanding sufficient informed consent, a difficult

question arises about the mother’s ability or the potential

mother’s ability to waive a right of a future child injured

to bring a lawsuit against a researcher. To date, there is

no case law on point.

In any case, the concern for liability exposure is out

of proportion to the reality. Based on reported cases, the

liability threat in the area of clinical research has been

basically nil. One of the few cases involving clinical

research was against the University of Chicago and concerned the testing of DES on pregnant women. The gist

of the action was that the class of pregnant women were

not told that they were a part of a double blind experiment to determine the effectiveness of DES in preventing

miscarriage. The focus of the class action for battery was

that the plaintiffs did not give consent to be a part of the

experiment and did not have knowledge of the experiment. The court held that the battery claim was proper

and the case was settled.
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 97

Areas of Potential Inquiry

 Do the current HHS regulations, together with the NIH

Memorandum’s guidelines and FDA guidelines, need to

be clarified to specify under what circumstances, if any,

it is appropriate to exclude women?

 Is liability, in fact, greater for exclusion than inclusion?

Manufacturers cannot hide behind a “myth of liability”

for inclusion of women in clinical research.

 What are the constitutional limitations following Johnson

Controls? Is there an equal protection argument, that is,

are we treating men and women differently without a

reason (whether rational or higher level of scrutiny)?

Why they are being treated differently? Why are women

of childbearing years being treated differently from

other women? Why are pregnant women being

treated differently from non-pregnant women,

and how do we justify these distinctions?

Ethical Considerations4

The three ethical principles highlighted in the worksof the National Commission for the Protection of

Human Subjects are beneficence, respect for persons

(including autonomy), and justice.

Beneficence refers to the obligation of researchers

to provide a favorable risk-benefit ratio to their subjects.

For both female and male subjects, there is a risk related

to their future reproductive health. For future children,

there is a risk of harm (of being born with birth defects).

When women are excluded as a class from research, all

women are at risk from a lack of information about their

health needs.

The principle of respect for persons refers primarily

to informed consent issues (and also to recruitment,

retention, and “compliance” issues). Informed consent

has many factors to be considered, including a subject’s

capacity to give informed consent, the quality of information given, and the voluntariness of consent granted.

Compliance issues, in this context, relate to the difficulty

women may have in continuing to adhere to the behavior

required by the study: namely, not getting pregnant

during the course of a clinical trial.

The principle of justice dictates that the burdens and

benefits of research be distributed equitably. The burdens

of human subject research should not fall unduly on one

class or group of persons, and no class of persons should

be denied the right to participate as research subjects.

Recent feminist conceptions of justice consider the past

oppression and exclusion of women from the benefits of

research and the need to consider affirmative action for

their inclusion.

The ethic of care may also have application to this area.

The paradigm of the mother/child relationship and the

need for a contextual understanding of a woman’s concern

for others, including her offspring, should support a strong

ethical foundation for trusting the judgment of women to

decide whether to participate in clinical research.

References

1. 45 CFR, pt. 6, esp. subpt. B.

2. HR4, S1.

3. Alta Charo R. Presentation to the Committee on the

Legal and Ethical Issues Relating to the Inclusion of

Women in Clinical Studies. Bethesda, Maryland,

March 24, 1993.

4. Presentation to the Committee on the Legal and

Ethical Issues Relating to the Inclusion of Women

in Clinical Studies. Bethesda, Maryland, December 2,

1992, and March 24, 1993.
98
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 99

Appendix VII

THE OFFICE OF RESEARCH

ON WOMEN’S HEALTH

NATIONAL INSTITUTES OF HEALTH

SCIENTIFIC MEETING:

RECRUITMENT

AND RETENTION

OF WOMEN IN

CLINICAL STUDIES

LESBIANS IN

HEALTH RESEARCH

HOLIDAY INN BETHESDA

BETHESDA, MARYLAND

JULY 12-13, 1993
100
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 101

Overview: Why Study or Stratify?

DEMOGRAPHICS NOT KNOWN

A comparison of data from three lesbian healthsurveys (National, n = 1,925,1 Los Angeles, n = 330,2

and Michigan, n = 1,6813), a lesbian and gay drug

use survey4 and three national surveys (the National

Health Interview Survey,5 the National Health Study

on Drug Abuse6 and the National Health and Nutrition

Examination Survey7) suggests that there are important

epidemiologic differences between lesbians and heterosexual women.

 Lesbians may smoke more.1,5

 Lesbians may be more likely to use/abuse alcohol.4,6

 Lesbians may have higher body mass index.1,7

 Lesbians definitely have higher oligoparity,

nulliparity rates.1,2,3,8

 Lesbians may obtain fewer screening exams.3,5,9

For example:

– blood pressure – breast exam

– pap smear – mammogram

– stool blood

 Lesbians may have lower rates of self-care.1,5

For example:

– breast self exam

– skin exam

– other (present to M.D. for spotting, pain)

If the above demographic is correct, in comparrison

to all women, lesbians would then have a higher risk/

morbidity/mortality from:

 Breast Cancer

 Lung Cancer

 Ovarian Cancer

 Endometrial Cancer

 Colon Cancer

 Cervical Cancer

 Heart Disease and Stroke.

What is needed is a single large epidemiologic study

which will confirm or negate the above suggestions. The

Women’s Health Initiative (n = 160,000) can provide this

in the baseline questionnaire.

Appendix VII

LESBIANS

IN HEALTH

RESEARCH

Katherine A. O’Hanlan, M.D.

Associate Director

Gynecologic Cancer Section

Stanford University
102

ACADEMIC RESEARCH STANDARDS

Blending data from two distinct populations swaysresults for all and renders the smaller population

invisible, potentially leading to inappropriate testing,

incorrect diagnosis, and ineffective therapy. Screening

programs may not be targeted to the population at

greatest risk.

STATED OBJECTIVES OF THE OFFICE OF

RESEARCH ON WOMEN’S HEALTH

Public Hearing Summary Draft, May 27, 1993: Thesestandards, originally written to apply to all women,

should, in addition, be specifically applied to lesbians.

For example:

1. “Research into diseases, disorders, conditions unique

to or more prevalent in [lesbian] women.”

Lesbians are a marginalized group that does not readily

or regularly access the health care system. Historically,

lesbians have been alienated from the health care system

by health care providers’ hostile attitudes toward them.

Ample documentation exists describing discriminatory

attitudes by physicians,10 nursing personnel11 and

medical students.12 All of the survey data1,2,3,12 confirm

that lesbians perceive this and subsequently access the

health care system less often, frequently with fear that

they are receiving inferior care because of hatred for

homosexuals.13,14

2. “To ensure that [lesbian] women are appropriately

represented in biomedical and biobehavioral research

studies and clinical trials suggested by NIH”.

3. “Direct initiatives to increase the numbers of [lesbian]

women who are participants in biomedical research

careers.”

4. “[Lesbian] women cannot expect to gain equitably

from new advances in therapy and interventions

if they are not included in the clinical trials that

ascertain safety and efficacy.”

Defining Lesbians in Socio-Political Constructs

for Epidemiologic/Demographic Profile

HOUSEHOLD ENUMERATION STUDY

The only way to generate a true demographic profile is

to classify dwellings by occupants and pick randomly

among those households with single or double female

occupancy as the National Census 1990 and the National

Health Interview Survey describe for their studies.

 This technique locates the broad diversity of lesbians

and includes marginalized lesbians, those who are not

“out,” have low income, are illiterate, or are women of

color. It is more expensive, but provides the sensitivity

and human contact necessary for accuracy, and most

importantly will confirm whether data are applicable

to the general population.

DEFINING BY BEHAVIOR

A woman whose sexual behavior ranges from exclusivesexual experience with women to bisexuality, and may

include situational experience with males. For example:

In general, if and when you are sexual, do you have

sex with:

a) men

b) women

c) both

d) neither.

 Requires no labels.

 Most women ARE very comfortable answering this.

 Is an objective question which can be seen as appropriate and non-threatening in a scientific health

questionnaire.

 Misses the socio-cultural identity and support

systems which impact behavior.

 Probably more accurate for demographic profile.

DEFINING BY IDENTITY

A woman whose erotic desire, emotional, social andaffectional orientation are toward other women may

be defined as lesbian. Most of these women are raised as

heterosexuals, repressing their feelings towards other girls

in childhood, until coming to reckon with these feelings

at some later age. Some have never had sex with males;

some have married and borne children; some are situationally sexual with males due to economics, cultural factors

or sexual desire, and may or may not culturally identify as

lesbians. For example:

In general, do you identify yourself as:

a) heterosexual

b) bisexual

c) lesbian, gay, homosexual

d) don’t know, none of the above.

 Requires an individual to categorize herself by

self-concept.

 May be inaccurate over time.

 Terms not used by all (some lesbians will not use

this term for themselves).
RECRUITMENT AND RETENTION OF WOMEN IN CLINICAL STUDIES 103

 Some women identify more with race/ethnic group

and not so strongly by sexual orientation.

IDENTITY VERSUS BEHAVIOR—TENTATIVE CONCLUSIONS

Both questions are important and should be includedin all studies to generate data until such profiles

have been delineated which show important differences.

Behavior questions should be in a behavior section: for

instance, in the first half of a questionnaire, separate from

an identity question in the self-conceptual section, or at

the end of the questionnaire.

Behavioral questions are always more important in

the medical exam and should always be included in any

survey as a minimum investigation into this area. It is

recommended that the research team write a behavioral

question that reflects an understanding of the population

to whom the survey will be administered.

Recruitment of Lesbians into Health Research

SAFETY ISSUES

Some lesbians, fearing for their job, their reputation, ortheir safety elect to hide their orientation and require

anonymity. It is important to reassure them of the reasonable limits of research confidentiality. Show a willingness

to share results with subjects and reassure them that lesbians have been involved in the writing of the project and

analysis of data. Include “out” lesbians in all staff and

research levels.

LOGISTICS

 Clinical research staff should include lesbians, lesbians

of color, and reflect the lesbian community in general.

 Recruitment efforts in the general lesbian community

should include:

– Advertisements in lesbian newspapers, organizations, bookstores, clinics, metropolitan community

churches. Expect lesbian-specific posters to be

stolen; it is necessary to replace them frequently.

– Obtaining endorsements of advertisements by lesbian

community leaders, lesbian clinics, or lesbian-friendly

health care providers.

– Informants, that is, members of the community with

whom a personal relationship is established and who

allow their names to be used in recruiting, can serve

as potential interviewers and give feedback on

instrument.

– Use of lesbian clinics as sites.

– Establishment of a local lesbian advisory committee

for further advice.

 Issues in recruiting lesbians of color:

– Some suggest recruiting first only lesbians of color.

It is often recommended that the goal should be

greater than or equal to 50% people of color.

“Especially invited” does not work.

– Sending posters to ethnic/race organizations.

– Reassuring people of color of the benefits to

them and their community of this research.

Don’t “rip off” data.

– Use of informants and attendance at meetings

with people of color to describe research.

 Recruitment of low-income lesbians should include:

– Advertisements specifically for low-income lesbians.

Place posters in government assistance offices,

methadone clinics, homeless shelters, soup

kitchens, grocery stores, emergency rooms.

– Pay incentives and/or free lab tests.

Retention

Important issues include:

 Ensuring continuity of clinic staff, female staff, staff

sensitive to lesbian issues, comfortable with lesbians.

 Continuing to reassure participants that their

community will benefit from the research.

 Showing appreciation for their commitment to

research progress.

 Keeping in contact with substance abusers, lowincome women, and HIV positive women, all of

whom may need more frequent contact.

 Providing ongoing pay for appointments.

Instrument

USE GENDER NEUTRAL TERMS

“Partner,” not “husband.” Use neutral pronouns or“he/she” and “her/him.”
104

CULTURALLY SENSITIVE

All questions with respect to race/ethnicity/lesbianorientation must be framed in a culturally sensitive

way. A culturally sensitive instrument can encourage

collaboration with lesbians, people of color, researchers

in areas of race/ethnicity and sexual orientation. Obesity

is a controversial issue for lesbians; rather than ask about

it, simply calculate body mass index from measured

height and weight.

QUESTIONNAIRE FORMAT

The interviews should be conducted preferably by afemale interviewer, face-to-face, to maximize information from lesbians of low income and lesbians of color.

References

1. National Lesbian Health Care Survey. Conducted by

Judith Bradford, Ph.D., Caitlin Ryan, M.S.W., National

Gay and Lesbian Health Foundation, November, 1987.

Prepared by Survey Research Laboratory, VCU. Funded

by: NIMH, Ms. Foundation, Chicago Resource Center.

1,925 respondents from all 50 states, ages 17-80.

2. Lesbian Health Needs Assessment. Prepared for the

Los Angeles Gay and Lesbian Community Services

Center, April, 1992. Conducted by Lynn Warchafsky,

M.A. 330 respondents from the Los Angeles area,

ages 16-59, average 34 years.

3. Michigan Lesbian Health Survey: A Report to the

Michigan Organization for Human Rights and the

Michigan Department of Public Health. D. Bybee,

Ph.D., March, 1990. 7,500 questionnaires: 54%

mailed, 20% concerts, 13% business or bars, 2%

churches, 11% handed to individuals. 1,681 returned.

4. Skinner WF, Otis MD. Trilogy Project: Research in

the Lesbian and Gay Community, 14th National

Lesbian and Gay Health Conference, Los Angeles,

CA, July 1992.

5. National Health Interview Survey, 1985.

6. National Health Study on Drug Abuse, 1992.

7. National Health and Nutrition Examination Survey,

1976-80.

8. Deevy S. Older Lesbian Women: An Invisible

Minority. J Geron Nurs, 1990;16:35-39.

9. Robertson P, Schacter J. Failure to Identify Venereal

Disease in a Lesbian Population. Sex Trans Dis

April-June 1982; Pp. 75-76.

10. Mathews, WC, Booth, MW, Turner, JD et al. Physicians’

Attitudes Toward Homosexuality - Survey of a California County Medical Society. West J Med;1986;144:106.

11. Randall J. Nurs Educ;1989;28(7):302.

12. Kelly JA, St. Lawrence JS, Smith, S Jr., et al. Medical

Students’ Attitudes Toward AIDS and Homosexual

Patients, J Med Educ;1987;62:549.

13. Johnson SR, Smith EM, Guenther SM. Comparison of

Gynecologic Health Care Problems Between Lesbian

and Bisexual Women. J Reprod Med;1987;32: 805-11.

14. Stevens, PE, Hall, JM. Images. J Nurs Scholarship;1988;

20 (2): 69-73; Stigma, Health Beliefs and Experiences

with Health Care in Lesbians. J Nurs Scholarship;1988;20:5.

15. Johnson SR, Guenther SM, Laube DW, Keetel WC.

Factors Influencing Lesbian Gynecologic Care. Ann J

Obstet Gynecol;1981; 140:20.