Study design

Introduction

The SHCS is a collaboration of seven outpatient clinics and ten laboratories, involving practically all researchers implicated in patient-oriented HIV research in Switzerland. These institutions are located at the five university hospitals of Switzerland, in Basel, Bern, Geneva, Lausanne and Zurich, and at the two hospitals of Lugano and St. Gallen. The clinics can delegate recruitment of participants and follow-up visits to other outpatient clinics or to specialized private physicians, provided that the requirements of the protocol can be entirely fulfilled and controlled. The laboratories can contract other laboratories for some of the analyses.

Protocol

The ethical committees of all participating institutions have approved the general study protocol. Additional approval may be requested for certain nested projects (e.g.intervention studies)

Any HIV-infected patient being at least 18 years old can be enrolled in the SHCS. A signed informed consent is required from all patients. A specific consent is required for genetic studies (Core genetic project).

Demographic data and specific data are registered at enrollment : date of birth, sex, nationality, ethnicity, educational degree and last held professional position, sexual preference. Other specific data are collected : results of earlier HIV tests, the most probable mode of HIV transmission, history of antiretroviral treatment, smoking history, and hypertension awareness and treatment.

Many data are collected every six months at the follow-up visits, such as : source of income, ability to work, family situation, sexual partnership and condom use. A gynecological form enquires whether the patient has undergone a gynecological examination and if a cervical smear has been performed.

At each follow-up visit, the physician has to report on following events : opportunistic diseases of HIV infection, any diagnosis of cancer, myocardial infarction, stroke, diabetes and lipodystrophy.

The follow-up visit includes the measurement of weight, blood pressure as well as waist and hip circumference.

At registration and at each follow-up visit, a spectrum of laboratory analysis is collected (all belonging to the standard of care of an HIV-positive patient). Any result concerning CD3, CD4 and CD8 cell counts and plasma viral load has to be notified, including the method used for viral load measurement and in case of undetectable viremia, the detection limit of the given analysis. The following laboratory analysis are required every six months : leukocyte and lymphocyte counts, hemoglobin and platelets; cholesterol, HDL cholesterol, triglyceride, glucose, lactate; for patients under antiretroviral treatment ALAT, ASAT, alkaline phosphatase and creatinine also have to be reported.

Some laboratory analysis have to be done only once, normally at registration : tuberculin skin reactivity, the hepatitis B markers, serology for Toxoplasma gondii and cytomegalovirus and syphilis. Antibodies against Hepatitis C are looked for at registration and, if the result is negative every two years thereafter. Any HCV viremia and available HCV genotype are documented.

At registration and at every follow-up visit, plasma samples are frozen for further analysis. Once a year a sample of viable cells is obtained, prepared and stored. The laboratory informs the coordination and data center about the number of aliquots and the attributed storage number of each frozen sample.

Drugs are registered in the database if they relate to one of the following:

For antiretroviral treatment the physician has to indicate the dosage and in case of treatment interruption the reason of withdrawal. Since July 2003, adherence to drug treatment is also assessed.

A special form is used to transmit information about participants who are lost from follow-up or have died. For participants lost from follow-up, the latest date he was known to be alive is documented. For patients who have died, the center has to indicate the cause of death using the ICD-10 codes, with the exception of violent deaths, for which a simple coding system is used.

All these data are registered in a central anonymous database. A unique patient number identifies all information registered.

Quality control

After having passed a quality control procedure at the local site by a study nurse, all data are transmitted to the data center by paper (clinical data) or by electronic transfer. The quality and consistency of the data are checked again by qualified collaborators and by computer programs, and are entered into the central database. Each time a follow-up visit has been registered, a graphical summary of the most relevant clinical data is sent to the physician. This feedback is a supplementary quality control and motivates the physician in reporting data of good quality.

At least once a year, a collaborator of the data center visits each of the 7 collaborating centers. The quality of the information collected at the follow-up visits is checked on a random sample of documents. The collaborator of the data center extracts the data from the patient chart and compares the result with the data previously reported.

Use of the data

Research projects use the SHCS data (and specimens) to a variable degree. Some projects are based on analysis of available data, whereas some others use the database to identify potential candidates for basic research issues or psychosocial studies. For many recent projects, additional data has to generated, e.g through the use of the repositorium.  Any use of data for scientific projects requires the Scientific Board's agreement.

Each center receives monthly a copy of the database. This information can be used for administrative purposes (convene the patient to a visit) as well as for the evaluation of the feasibility of planned research projects. Each center has designated a responsible person for the database, and any other person authorized to use the database is registered in a log-book.

Nested research projects

All research projects are submitted to the Scientific Board.

The process is following : Projects that comply with the guidelines are sent to the chairman of the SB. The chairman allocates each project to 2 members of the SB for written critical review, which is sent to all members before the meeting. Each project is discussed during the meeting for both, scientific and financial content. Most projects are revised by their authors before final acceptance by the Executive Board. Funding is scaled over time, and full payment is conditioned to publications (or a final scientific report). All submitted protocols are sent to the SNSF with the minutes of the meeting.