Alexa T. McCray
National Library of Medicine
Bethesda, Maryland
Scenario: Ellen is a 48 year old professional woman who lives and works in Hartford, Connecticut. She has four adult children and two grandchildren. She also has two aging parents who live nearby and who, though they have been active all their lives, are beginning to have health problems. Ellen's 75 year old mother has just come back from visiting her regular doctor who recommended that she undergo some testing for her frequent forgetfulness just to see if there is any cause for concern. She is somewhat distressed by this and calls her daughter to tell her about it. Ellen has a computer at home and regularly uses it to buy books, to make travel arrangements, and to follow the news on the Web. She decides to see if she can find anything that might be helpful by looking at her Internet provider's Health & Medicine section. Listed as a health resource is the National Library of Medicine at the National Institutes of Health. Ellen goes to the site where she finds, among other resources, the clinical studies information system. She searches on memory problems in the elderly and finds a new clinical research study that is looking for ways to slow or stop the onset of Alzheimer's disease. The study is supported by the National Institute on Aging and is being conducted at a large number of locations around the country, including nearby New Haven. People between the ages of 55 and 90 who have mild cognitive impairment (MCI) are eligible to participate in the trial. The study description links to further information about MCI, including how doctors diagnose this condition. Another link leads her to a site that has extensive information about Alzheimer's disease, including a listing of local resource centers.. Ellen prints out the information about the trial as well as the other information she has found and intends to take it with her when she visits her mother the next evening. She is thinking of suggesting that she accompany her mother to one of her next doctor's appointments so that they can together discuss the information she has found.
The study referred to in the scenario is a real clinical research study, but the scenario itself is fictitious. The clinical studies information system that is currently under development by the National Library of Medicine (NLM) at the National Institutes of Health (NIH) is being designed to provide the type of information illustrated in the scenario. The system will provide patients, families and members of the public easy access to information about clinical research studies, including information about which clinical trials are currently recruiting patients, where the trials are being conducted, what the design and purpose of the particular research study is, what the criteria are for participating, and in many cases, further information about the disease and treatment under study.
The Clinical Trial Process
Clinical trials are scientific studies conducted in human beings to evaluate the safety and effectiveness of new drugs, procedures, or other products that are used to treat, diagnose or prevent diseases. Clinical trials help investigators learn how different people respond to medications or other therapeutic approaches, and they may lead to new or improved treatments. Trials are conducted when there is no proven treatment for a specific disease or in order to test which of several treatments work best for a particular disease. Before testing a new treatment in people, researchers do animal and laboratory studies. This gives them an idea of both the positive and possibly negative effects of the treatment. If the treatment shows some promise during this preclinical phase, it may be considered for testing in humans.
Human testing proceeds in carefully controlled phases. Phase I trials are small studies designed to study safety and to begin to learn how the human body reacts to a treatment. Phase II trials are designed to evaluate the treatment in patients with a particular disease and to further study the short-term side effects and risks. Phase III trials are conducted on larger patient populations to gather the additional information needed to evaluate the overall benefit and risk of the treatment for a particular disease. Phase III trials usually compare the standard treatment for a disease with an experimental treatment. Generally, when standard and experimental treatments are being compared, patients are randomly assigned to either the standard treatment group (control group) or to one of the experimental treatment groups. In some cases, after a treatment is already available for general use, there may be Phase IV follow-up studies to determine additional information about its risks, benefits, and optimal use.
For each clinical trial, researchers prepare a detailed research plan, called a protocol, which describes the study, including the potential risks of participating, the specific procedures and tests that will be conducted, and the type of people who are eligible to participate. Eligibility criteria cover a variety of factors including the age, current medical condition, and medical history of potential participants.
Patients may want to participate in a clinical trial for a variety of reasons. Most often they are hopeful that the experimental treatment will help them. Researchers, though they cannot be sure of the value of a new treatment, conduct trials on treatments that they have some reason to believe will be successful. Patients who are enrolled in clinical trials often receive drugs or other therapies that are not yet available to the general public. Many patients who participate in clinical trials believe in the importance of medical research, and, after weighing the benefits and possible risks of participating in a trial, decide to participate because this allows them to contribute personally to a possible cure or better treatment for their disease. Before enrolling in a clinical trial, a patient is given a document, called an informed consent form, that outlines the purpose of the trial, as well as the potential risks of participating. Only after reading and signing this form, are patients officially enrolled in a clinical trial.
Legislative Initiative
Partly because of intense interest in clinical trials by AIDS patients who were eager to have access to the latest treatments, even if these were still in the experimental stages, the Health Omnibus Programs Extension (HOPE) Act was passed in 1988. One outcome of that legislation was the development of an extensive database of AIDS clinical trials information (currently available at http://www.actis.org/).
Almost ten years later, in the fall of 1997, Congress passed legislation which, among other things, requires the Department of Health and Human Services, through the NIH, to establish a registry of clinical trials for both federally and privately funded trials "of experimental treatments for serious or life-threatening diseases and conditions", thereby broadening the public's access to information about clinical trials to a broad range of diseases. (Section 113, Information Program on Clinical Trials for Serious or Life-threatening diseases, Food and Drug Administration Modernization Act of 1997, Public Law 105-115, 105th Congress.) According to the legislation, the database should, for each trial, contain the purpose of the trial, eligibility criteria for participation, the location of the trial sites, and a point of contact for those wanting to enroll in the trial. The data should be in a form that is readily understood by members of the public. The legislation also notes that the database may include information pertaining to the results of clinical trials. In passing this legislation, Congress wanted to ensure that people have a central, easily accessible source of information for clinical trials no matter where the trials are being conducted, what the particular drugs or diseases under study are, or who is sponsoring the trials.
The Clinical Studies System
The clinical studies system currently under development at the NLM is being designed to be a comprehensive resource about clinical trials that will not only help patients find trials that might be of interest to them, but also provide additional information that might be useful. Some of the characteristics and planned capabilities of the system are outlined below. The system is being designed to:
Basic information for clinical trial in the database will include the name of the sponsoring institution, the title of the study, a brief summary of the purpose of the research study, a description of both the inclusion and exclusion criteria for participation, and whether the trial is currently recruiting patients. Also included will be information about the study type, e.g., whether it is a treatment, diagnosis, or prevention study; information about the phase of the study; about the disease or condition under study, and about the particular treatment or intervention under study. Interventions may be drugs, or vaccines, or certain kinds of procedures. Contact and location information will also be included for each trial.
In many cases a particular trial is conducted at a single university hospital or other health care institution. In other cases the trial is a multi-center trial where the same research study is being carried out in many places. The memory impairment study mentioned in the scenario, for example, is taking place at over sixty locations around the country. The information listed for each trial should allow patients and their doctors to evaluate whether it would be worthwhile to consider participation in a particular trial.
The system will be freely available over the World Wide Web, and patients and others will be able to search and browse the system in a variety of ways. They may choose to browse the system by looking, for example, at a list of disease names, and then narrow this down by looking at a map that shows the locations where trials for these diseases are currently being conducted. Alternatively, they may prefer to interact with the system by entering a word or a phrase that the system searches across the entire database.
For example, if a social worker who works with HIV positive children in Chicago has heard that the drug saquinavir is being tested in children with HIV infection, she might do a simple search for "saquinavir" in the database. She would find about fifty clinical trials currently studying this drug. This may be too much to look at, so she may decide to do a more focused search using the system's "fill-in-the-blanks" mode. She would fill in the investigational drug slot with "saquinavir", the disease slot with "HIV infection", the age range slot with "children", and the slot for preferred location with "Chicago, Illinois". This would find a current Phase II trial in HIV-infected children that is assessing the tolerance, safety, and effectiveness of saquinavir given in combination with other drugs. The trial is supported by NIH's National Institute of Allergy and Infectious Diseases and has as one of its over 30 locations Children's Memorial Hospital in Illinois.
The clinical studies system, as it is being designed, will be linked to the online medical literature and other related health resources. For example, in the scenario above, the clinical trial that Ellen found was directly "hot-linked" to further information about the condition as well as to the sponsoring institution, in this case, NIH's National Institute on Aging. Additional links allow Ellen to find information on aging, including resource and support groups in her area. If a study has been completed and the investigators have published the results of their research, then it may be possible to link to NLM's MEDLINE database which contains almost 10 million references to articles in some 4,000 journals in the health sciences. NIH has many other online sources of health information, including dictionaries, reviews of recent research results, and other educational materials. Links to these resources may be helpful to patients and others who would like to get a better understanding of what is involved in a clinical trial, what the standard therapy for a particular disease is, or even to better understand the disease itself.
The first version of the planned clinical studies information system, which is being developed in close collaboration with all NIH Institutes, will provide access to NIH sponsored studies and is expected to be available by the end of 1999. Subsequent releases of the system will include clinical trials data from other Federal agencies and from private industry. The database will be available through several locations on the Internet, including the NIH home page at http://www.nih.gov/ and the NLM home page at http://www.nlm.nih.gov/.
Acknowledgment: The author wishes to thank Deborah Katz for helpful comments on earlier drafts of this paper.