Laboratory markers as potential surrogates for clinical outcomes in AIDS trials

Article Abstract:

Surrogate end points are markers that can be used in clinical trials instead of an end point that occurs infrequently, or one that occurs far along in the progression of disease. Markers that can be examined in the laboratory were evaluated as potential surrogate end points for clinical trials in patients with AIDS. The criteria for a marker to be acceptable as an end point include: the end point should show a dose-response effect for drugs that are active against AIDS; the end point should correlate with the progression of the disease in untreated patients; and changes in the end point in response to the drug should correlate with improvement of the clinical state of the patient. A workshop entitled "Surrogate end points in evaluating the effectiveness of drugs against HIV infection and AIDS" was held in September 1989 by the Institute of Medicine. The workshop considered three viral markers: the level of the human immunodeficiency virus (HIV) protein p24; a quantitative assay for HIV by the polymerase chain reaction; and the levels of virus in the blood. Three immunological markers were also considered: levels of CD4 T lymphocytes; levels of beta2-microglobulin in the blood; and levels of the chemical neopterin. However, none of these criteria could be agreed upon as surrogate end points. It was felt that the p24 viral antigen was the best viral marker, and although there were arguments for the use of p24 antigen as a surrogate marker, there were also arguments against its use; these opinions are discussed. The number of CD4 cells was the best immunological marker, but there are also problems with its use as an end point. Although CD4 cell levels may eventually be used as a surrogate end point, most scientists felt more confident in the use of CD4 levels and some clinical symptoms as end points. It is hoped that in the future, as more is learned about AIDS, a combination of laboratory markers can be used as surrogate end points instead of relying upon clinical end points. (Consumer Summary produced by Reliance Medical Information, Inc.)

Evaluation, Diagnosis, Laboratory, Laboratory diagnosis

---

Design of clinical trials - end points

Article Abstract:

The goal of clinical trials in AIDS research is to determine the effectiveness of a drug as quickly as possible, with results that are applicable to a wide range of patients. There are variables that affect the findings of clinical trials, including variability among patients and the stage of the disease. Many trials are stratified by immunological criteria, such as the number of CD4 T cells. There are many parameters that might affect the levels of CD4 cells, including pre-existing infection. The levels of virus existing in individuals and the specific immune function against HIV should also be used to stratify clinical trials. Clinical symptoms are now used as end points to determine the effectiveness of drugs. Survival was previously used as an end point, however, survival is not an acceptable end point when seeking treatments for a fatal disease, because the results come too slowly. Markers that can be measured in the laboratory are now being developed as end points. Data on these laboratory markers are being collected from clinical trials. The use of laboratory markers should increase the speed of obtaining results from clinical trials. However, an acceptable laboratory marker has not yet been found. More data are needed to see if changes in the laboratory markers accurately reflect changes in clinical conditions. The choice of end points is critical to the evaluation of the drugs. It must be remembered that patients with AIDS understand their disease and the medications that are being used in clinical trials. Patients must be willing to participate in the clinical studies, therefore, these trials must be designed so that their needs are addressed. This includes use of acceptable end points. Thus, the development of laboratory end points in clinical trials for the evaluation of AIDS treatments is necessary. (Consumer Summary produced by Reliance Medical Information, Inc.)

Research, Anti-infective agents

---

Evaluation of active control trials in AIDS

Article Abstract:

Active control trials are clinical trials in which a new drug is compared with a drug whose effectiveness is known. The test is devised to see if the experimental treatment is at least as effective as the standard therapy. These types of trials are desirable in AIDS, since there is treatment available that enhances survival or prevents sickness. Therefore, in clinical trials of AIDS, patients can either be treated with a new therapy or with the standard therapy. The statistical analysis of the effectiveness of new treatments in these types of studies reveals whether the experimental treatment is an improvement over the standard treatment. An assessment is also made of the side effects, toxicity, and costs of the experimental drug compared with the standard drug. Guidelines are given for termination of the active control trial before the proposed end of the study, if the results are dramatic enough to justify early termination. This type of analysis also allows the substitution of other end points, such as a decrease in the number of CD4 T cells in patients, for hard clinical outcomes such as progression to AIDS; end points are used in determining the effectiveness of a treatment. In studies where the standard treatment is quite effective, large numbers of patients are not required for this type of trial. (Consumer Summary produced by Reliance Medical Information, Inc.)

Similar abstracts:

• Abstracts: Fluconazole compared with amphotericin B plus flucytosine for cryptococcal meningitis in AIDS: a randomized trial
• Abstracts: The relationship of abruptio placentae with maternal smoking and small for gestational age infants. Combined estrogen and progestin hormone replacement therapy in relation to risk of breast cancer in middle-aged women
• Abstracts: Birthweight ratio and outcome in preterm infants. Plasma prolactin and clinical outcome in preterm infants. Comforters and night waking
• Abstracts: Relapse from safer sex: the next challenge for AIDS prevention efforts. Decisions to get HIV tested and to accept antiretroviral therapies among gay/bisexual men: implications for secondary prevention efforts

This website is not affiliated with document authors or copyright owners. This page is provided for informational purposes only. Unintentional errors are possible.