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Women and Clinical Trials

Fall/Winter 1997

A note from The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

What is a clinical trial? A clinical trial refers to any experiment that involves an investigational drug or medical device and one or more human subjects.

Clinical trials are conducted to determine the new drugs' efficacy and its safety profile prior to submission to the U.S. Food and Drug Administration (FDA) for final approval to be licensed and made commercially available (available by prescription).

Clinical trials are also done to compare drugs which may already be approved, looking at a different way to dose the medication or potential drug interactions with other medications.

Clinical trials provide evidence as to whether or not a new therapy or other interventions are efficacious. When the new therapy is used in a well-controlled clinical practice setting, it may or may not have the efficacy expected in the clinical trial. (This is sometimes called assessing the drug in the "real world")

The reasons for these differences are numerous and can include compliance, tolerance, drug interactions, differences in patient population and other factors. Clinical trials for a particular treatment are carried out in phases. First to show the safety of the treatment and later to test its effectiveness, while still collecting information on the safety profile.

# of Subjects
& Time Frame

Phase I
Clinical Trial

Determining the safety profile and side effect profile at the highest dose tolerated Small number of participants; lasting days to weeks

Phase II
Clinical Trial

Determining whether the treatment is effective and determining the safety profile; testing different doses of medication to find the best one Small number of participants; lasting days to several weeks

Phase III
Clinical Trial

Testing the effectiveness and continuing with safety profile Large number of participants; lasting months to years

Phase IV
Clinical Trial

After FDA approval, collecting more information on the safety profile Commercially available.

Federal Regulations

The regulatory process (the way drugs are approved) has changed in the last several years as a result of public pressure. The FDA's cautious approach to the licensure of new drugs stems from the 1962 disaster with thalidomide. In the late 1950s and early 1960s, an estimated 10,000 women in 46 countries took the sedative in their first trimester and later gave birth to babies with missing or stunted limbs.

But the urgency of the AIDS epidemic has changed the position of regulators from extreme caution to active participation and record speed in approving drugs. Zidovudine (AZT) was approved after only one controlled trial in 282 patients, because early and dramatic differences were seen between the two study arms. The FDA has taken a more active role in the early planning and conduct of clinical trials and is now allowing implementation of expanded access programs for unlicensed drugs.

Many in the AIDS activist community held heated debates with FDA officials, arguing that patients with terminal disease and no effective treatment had the right to waive their rights as human subjects to become involved in an investigational drug trial. In response to continued pressure, in 1987 the FDA softened its position and issued regulations that allowed widespread distribution of investigational drugs for therapeutic purposes, providing the disease is serious or life-threatening.


Clinical trials are based on a set of rules called a protocol. The protocol describes which types of patients may participate in the clinical trial, describes schedules of tests and procedures, drugs, and dosages; and defines the length of the study. Each patient participating in a clinical trial must agree to be treated by the rules of the protocol. In most protocols, the protocol teams look for patients who are alike in their medical conditions. Patients can gain access to treatment and drugs that are not available commercially and they have the opportunity to contribute to humankind.

The FDA has developed the concept of "Good Clinical Practices" (GCPs). This concept was designed with input from researchers, legal specialists and the pharmaceutical industry. These regulations are available through the FDA and provide guidelines for essentially all aspects of conducting a well-designed and well controlled clinical study. The regulations and guidelines concerning GCPs are detailed. The Code of Federal Regulations, under the section entitled "Protection of Human Subjects and Responsibilities of Sponsors and Investigators" describes in detail the regulations set forth by the FDA regarding the testing drugs in humans.


The Code of Federal Regulations (Title 45, "Public Welfare," of the Department of Health and Human Services National Institute of Health, Office for Protection from Research Risks, dated August 19, 1991) defines policies designed to ensure human subjects involved in clinical research trials are protected, their rights are preserved, confidentiality is maintained and human dignity remains intact.

Institutional Review Board

The FDA requires that an independent Institutional Review Board (IRB) review and have authority to approve, required modifications in or disapprove all research activities covered by the IRB regulations. An IRB is required to ensure that appropriate safeguards exist to protect the rights and welfare of research subjects. In fulfilling these responsibilities, an IRB is expected to review all of the research documents and activities that bear directly on the rights of and welfare of the subjects of proposed research, including any advertisements for subject recruitment.

Expanded Access

The most recent change in drug trial regulation has occurred with the expanded access, or parallel track programs. This allows patients with HIV infection to obtain certain drugs that have not yet been approved by the FDA. The idea is to provide access to treatment for people with no other treatment options and who do not meet protocol criteria to enroll in trials of the drug.

The expanded assess to drugs through the pharmaceutical companies can often operate concurrently with the clinical trial and serves two purposes: It helps the patient obtain medication that may be desperately needed, and maintains the integrity of trials by reducing the incentive to enroll appropriate subjects as a way of obtaining treatment. It is a humane response to the legitimate demands of a disease-affected community-waiting for the full approval of a drug is no option in the face of certain death from a consistently fatal disease.

Informed Consent

Ethical issues arise in the relationship between the clinician and the patient, including problems of confidentiality, informed consent and respect for patient autonomy. Although some evidence suggests that regulations for human experimentation based on informed consent were recognized as early as the 19th century, the Nuremberg code of 1947 is generally regarded as the first document to set a standard for ethical regulations in human experimentation based on informed consent.

The issue of ethics with respect to medical experimentation in Germany during the 1930s and 1940s was a crucial part of the Nuremberg trials and related trials of doctors and public health official. Those involved in the horrible crimes against humankind attempted to excuse themselves by arguing that there were no explicit rules governing medical research on human beings in Germany during the period, and that research practices in Germany were not different from those in Allied countries.

From the Nuremberg trials, ten principles to guide physicians, physician assistants and nurse practitioners who are investigators in an experiments with human subjects took shape. These principles included a : "voluntary consent form" written at a reading level that the average person can understand.

The treatment consent protects the patient's right to privacy and confidentiality, and helps to determine liability and responsibility to prevent abuse of people in various experiments. Consent to treat has become an important part of clinical trials, private practice, public practices and hospitalization, along with the "Patient's Bill of Rights".

The Patient's Bill of Rights

Before Participating in the Study,
patients must be informed about the following:
  • The nature and purpose of the study.

  • The procedures in the study and any drug or device to be used.

  • The discomforts and risks to be expected from the study.

  • The benefits to be expected from the study

  • Alternative procedures, drugs or devices that might be helpful, and their risks and benefits.

  • The availability of medical treatment, should complications occur.

  • The opportunity to ask questions about the study or the procedure.

  • The opportunity to withdraw at any time without affecting the patient's future care at the institution.

  • A copy of the written consent form for the study.

  • The opportunity to consent freely to the study without the use of coercion.

  • A statement regarding liability for physical injury, if applicable.

Women and Trials

Until the early 1990's women were generally not included in early phase clinical trials because of a potential risk of pregnancy and a possible dangerous effect on the fetus. (Exclusion criteria often read: "no pregnant women and no non-pregnant women".)

Because of pressure exerted by activism, the FDA revised their clinical guidelines to allow the enrollment of women into clinical trials. Small numbers of women began to enroll into most HIV clinical trials adhering to strict regulations of using two methods of birth control. (less than 6-8% of total number of enrollees were women.)

During 1994-95 women finally were allowed to enroll into phase I clinical trials, phase I clinical trials very little information is known about the drug being studied. To date, women still only account for less than 10% of the total enrollment into clinical trials and very few clinical trials are designed strictly for female enrollment.

Year of the Woman

1997 has been the year of the woman, where more than six clinical trials have been designed just for women. Many questions still remain specifically about women, such questions as does body weight or composition make a difference in medication dosing? Do women metabolize drugs differently or can certain drugs be more beneficial for women? Why do many HIV+ women have difficulty with their periods.

The only way we will get answers to these questions is if women actively participate in clinical trial. Waiting for the answers to come from studies conducted primarily in men may not be the best approach.


Clinical trials can provide answers to questions that will set the standard of care for the future and women are an important component to formulating an appropriate and complete answer. Many clinical trials, in many different phases of study are available for women to participate in, take the time to look around and see if there is a study that is right for you. There are many ways to get more information on clinical trials. Check out the list of studies available in HIV/AIDS magazines or consult your medical provider, your treatment advocate or call the USC Clinical Trials Unit at 213.343.8288.

The Future

Be a part of molding the future of care for HIV infected women and men. Get involved and join a study.

The content of this article was extracted from "Navigating Through Clinical Trials" published in Advance for Physician Assistants, 9/97. Vol. 5, No. 9.

A note from The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

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This article was provided by Women Alive. It is a part of the publication Women Alive Newsletter.
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