Infectious Diseases

You are planning to conduct and HIV vaccine trial among intravenous drug users. The trial is estimated to last 3 years. Because of the nature of their activities it is highly likely that a substantial portion of your study population will spend some time in jail during the study period. If they are incarcerated while they are in the study, you would have to contact them in jail, and conduct the follow up activities there, otherwise they would be lost to follow up and it would jeopardize the results of the study. You have to decide how to handle this issue.

While thinking of this, you are afraid that if you mention to potential participants that you will follow them up if they become incarcerated you will create the impression among them that they are placed at risk of incarceration if they decide to participate in the study, and that a high proportion of them will decline participation as a result. You therefore decide that you will not mention the possibility of incarceration in the informed consent form. Instead, you will ask for their permission to be contacted if they do not show up for a scheduled visit, and you will ask them to name a contact person that will know how they in turn can be contacted. You feel that since they are drug users, they know that they might be incarcerated, and that they therefore know that this would mean that they would be contacted in jail if necessary.

1. Do you agree with this strategy? Why? Why not?

When somebody is incarcerated, and you have identified the institution where they are located, you plan to send a letter to the jail, on institution letterhead saying that they are part of a clinical trial and that you ask the prison director for permission to conduct follow up activities while they are in the jail. You will not mention that they are part of an HIV vaccine trial.

2. Any comments on this procedure?

Based on the discussion of these two points, please formulate the relevant section of the informed consent form addressing the issue of how to contact participants if they do not show up for scheduled appointments.

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Standards of Care

Early versus delayed initiation of antiretroviral therapy

The government, biomedical researchers, and health-care providers of a country in sub- Saharan Africa are committed to the implementation of a programme of antiretroviral therapy. They have identified a relatively inexpensive HAART regimen based on generic drugs, as well as the resources to provide it to some, but not all, of the country’s HIV-infected population. To maximize the number of people who could ultimately be treated, they seek to determine whether delaying initiation of therapy until symptoms appear would result in a clinical benefit that is comparable to that achieved by beginning therapy earlier in asymptomatic individuals. This latter approach, which is standard practice in many developed nations, entails initiating HAART in asymptomatic HIV-infected individuals who have specified levels of CD4+ T-cell count and/or plasma viraemia. It also requires serial measurements of these laboratory parameters be taken to monitor progress, a strategy that is neither affordable nor feasible within the context of the health-care system of the developing country in question. Therefore, the researchers, care providers and government hope to validate a promising patient-management algorithm that is based on total lymphocyte count (roughly correlated with CD4+ T-cell count), and various clinical parameters for decisions regarding initiation of therapy and continuing patient management. A study to address these two objectives is proposed by a collaboration of African investigators and US investigators. They plan to identify and recruit a cohort of previously untreated, HIV-infected individuals from publicly funded health clinics. They will immediately initiate HAART treatment of individuals who are clinically symptomatic. They will randomize patients who are asymptomatic to either begin treatment when their total lymphocyte count declines to a specified threshold, or begin treatment when they become symptomatic, regardless of total lymphocyte count. Throughout the study, management decisions for all patients will be based on the investigational algorithm of total lymphocyte count and clinical parameters. More intensive CD4+ T-cell and viral-load assessment will be carried out in a subset of
patients to validate the new approach. Longterm clinical outcomes of the two randomized groups will be determined and compared. The study, the proposed procedures for obtaining informed consent and the plan for interim monitoring of data have all been reviewed and approved by competent and duly constituted scientific and ethical review groups, both in the host country and in the United States.

Should this study be approved?

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Behavioral and Records Research

A team of social scientists involved in the preparation for an HIV vaccine trial is interested in learning why some do not return to the hospital for the results of their HIV tests. They are carrying out a research project to follow-up clients a who are at high risk of HIV infection, who have been tested, but who have not received the results of their test. The aim of the research is to find out how to improve retention of potential participants to an HIV vaccine trial.

The chiefs of service in the hospital grant permission to the social scientists to conduct their investigations. Physicians provide the researchers with access to hospital records from which the researchers obtain the names and addresses of the patients without their knowledge or consent. The researchers then visit the patients in their homes. The social scientists identify themselves as researchers and ask permission to enter the patients' homes for an interview. If the person grant permission to enter their homes, the researchers then interview the patients and give them information about the results of their HIV test.

The researchers inform the women that they should return to the hospital for follow-up care. The researchers actually facilitate this process by giving the clients the names of physicians that they may go to directly, thereby enabling them to avoid the usual bureaucratic obstacles. The researchers defend their methodology by stating; (1) that the clients receive health benefits as a result of the study; (2) that the clients are helped to gain more rapid and easier access to the appropriate services; and (3) that patients' records in public hospitals belong to the hospital and not to the patient. Furthermore, the study is likely to reveal information that will enable the hospital to improve its services to patients by effecting better follow-up.

Questions for discussion

1. Is it justified for the chiefs of service to grant permission to use the records to the social scientists without the consent of the patients? Is confidentiality breached?

2. Is it justified that the social scientists provide the results of the HIV test to the patients?

3. Do you see any problems with the home visits by the social scientists?

4. Is it relevant that the clients receive some benefit by taking part in this study?