Microbicide Clinical Trials: Medical Research Council briefing

HEALTH PORTFOLIO COMMITTEE
20 February 2007
MICROBICIDE CLINICAL TRIALS: MEDICAL RESEARCH COUNCIL BRIEFING

Chairperson: Mr LV Ngculu (ANC)

Documents handed out:
MRC presentation

SUMMARY
The Medical Research Council briefed the Committee on the Conrad microbicide clinical trials in South Africa that had to be terminated when certain participants became infected with the HI virus. The Committee raised concerns about inspection of clinical trials, ethical approaches, the fact that most such trials were occurring in the developing world, compensation for the infected persons and perverse incentives to lure people into participating in clinical trials.

MINUTES
Presentation by Medical Research Council (MRC)

Prof Anthony Mbewu, MRC President, introduced Prof G Ramgee, Director: HIV Prevention Research Unit, and Dr Govinden, Laboratory Manager: HIV Prevention Research Unit. He thanked the Committee for the opportunity to brief it on the subject of microbiscides especially with the controversy surrounding the termination of the Conrad clinical trial. The MRC was the statutory Health Research Council for South Africa. It was supported by a parliamentary grant and its main job was to conduct research to improve the health and the quality of life of South Africans. He provided a global view of HIV infection in sub-Saharan Africa, current HIV prevention strategies and what precisely a Microbicide was. Microbicide clinical and randomized trials were explained, as well as those in the development pipeline. The presentation also outlined the tests study sites and enrollment targets and the risks involved. He finished by informing the Committee that other trials were continuing.

Discussion
Dr R Rabinowitz (IFP) remarked that her first impressions of the Conrad trials were that they were unethical. She asked whether the MRC Ethics Committee and the equivalent committee at the University of KwaZulu-Natal were functioning properly.

Prof Mbewu replied that the National Research Ethics Committee (NREC) established under the National Health Act had the primary function of performing oversight of clinical trials held in South Africa to make sure that norms and standards were met. The NREC had an inspectorate that inspected clinical trials. The inspectorate visited the Conrad clinical trial site in Durban where the MRC was conducting trials for the microbicide. The ethics committees insisted on reports of the clinical trials.

Dr Rabinowitz asked about the consequences when there was a breach of ethics.

Prof Mbewu replied that currently there was nothing that dealt satisfactorily with a breach of ethics. There was no effective means of inspecting trials and to make sure that consequences followed a breach of ethics. Currently, the people responsibly for policing the trials were the same institutions that conducted the trials.

Dr Rabinowitz asked whether it was mandatory to register every clinical trial with the Department of Health.

Prof Mbewu replied that the Department had established a clinical trials register in the last year. It could be accessed on the Department’s website and all human clinical trials in South Africa had to be listed in the register. In addition, it was one of the ways they checked up on clinical trials. The general public also had a database that informs them about the trials if they wanted to participate.

Ms MM Madumise (ANC) asked why the clinical trials were being held in developing countries and in particular why there were a high number of people who were infected during the Conrad trial.

Prof Mbewu replied that the Conrad clinical trials were held in South Africa, Benin, Ghana and India. Phase two of the trial was conducted in various countries, including the United States. Out of the 11 trials, 6 were conducted in the United States. They were not aware that South Africa had the highest number of people who became positive during the trial because they did not have all the information. Nevertheless, of the 1333 persons that participated, 35 were infected during the course of the trial. South Africa had 604 participants and 20 of these participants were infected. However, to date they were not aware of any adverse effects of the microbicide. The normal procedure was that when a trial is terminated the results are analyzed and released when all the answers were available. But due to the fact that they were dealing with HIV/AIDS they decided to inform the public of the termination as soon as it occurred.

Ms Madumise asked if the clinical trials were ever monitored by external monitors and in which manner and with what frequency.

Dr Govinden replied that the Conrad study in Durban had various layers of monitoring. They had an internal monitoring system conducted by their unit who went on site and produced monthly reports. In addition Conrad hired an external examiner who was not connected to the trials that came for a week every month checking to see if protocol was followed. The report she produced was then handed over to the sponsors and to the MRC. Moreover, Conrad had oversees monitors that visited the site every three months to ensure that the studies were conducted ethically.

Mr AF Madella (ANC) asked if they were providing any incentives to people as it seemed that most participants were poor and in the end they might sign up illiterate and semi-literate people.

Prof Mbewu replied that recruitment was on a voluntary basis and they advertised in all communities in South Africa; however some clinics had more volunteers than others. They offered incentives and paid participants R150 per day to reimburse them for transport costs and the day of work. Recruiting illiterate and semi-literate people was a potential problem, but they got around this by making sure that the participants were between 18 and 35 years of age in the Conrad trial. They would then ask the participant to repeat to them all the information the participant gleaned from the counseling they provided before the trial. Here they could determine whether the participant understood what was required of them. This was important not only to protect illiterate people from being taken advantage of, but also the trials included complex procedures and they needed the participant to understand what they were undertaking as these trials were of such a high standard that they could be registered with the American Federal Drug Administration or the South African Medicines Control Council (MCC)

Ms ML Matsemela (ANC) asked about the usage of the gel, in particular whether it oxygenated sperm.

Dr Govinden replied that the gel was a contraceptive and it inactivated the sperm.

Prof Mbewu added that the gel was a cotton extract that had no effect on the vaginal wall except acting as a barrier to the entry of the virus into the cells of the vaginal lining.

Ms Matsemela asked about the status of the clinical trials in Uganda.

Prof Mbewu replied that they did not have data on what had happened to the participants in the Ugandan trial and they were still waiting for the results.

Dr Rabinowitz remarked that she could not understand why they did not have the results since the data existed; it only required analysis. The termination of the trial defeated the good that could have come from it.

Dr Govinden replied that the trial was conducted in a random manner. They had no way of knowing who received which gel and as such “the data blinded” them. However, the trial had to be closed down because a certain number of people were infected and in accordance with the DSNB rules the trail had to be stopped.

Ms Madumisa asked how the participants who were infected in the trial were going to be compensated.

Prof Ramgee replied they had a serial converter plan for people who turned positive during the trial. This converter had different forms of care programs that also provided counseling. They also had a PEF program where they monitored the converted participants and Conrad set aside money for the serial converters if ever they were in need of ARV treatment.

The Chairperson asked if they were able to effectively trace all the participants.

Prof Ramgee replied that they had over 95% retention when it came to tracing the participants. They used the locator information which would have the address of the participant and contact numbers. With the permission of the participant they could also use GPS to locate the participant.

Ms Matsemela asked for clarification on the usage of the gel.

Dr Govinden replied that the gel should be applied within one hour of having sex; no more than one hour should elapse before application and sex. It could be applied minutes before sex and this had to be done every time the user has sex. Moreover they encouraged women to apply the gel with their partner so that it would not be something they hid.

The Chairperson thought this would defeat the purpose of discrete usage.

Prof Ramgee replied that there are different types of women in the world. Some could discuss sexual choices with their partners and others could not, but this would give the women an option to tell the partner or to be discreet.

The Chairperson asked how they were going to inform people of the importance of clinical trials.

Prof Mbewu replied that the tests were important in order to test new drugs and in the Conrad trial they used both the print media and the radio media to publicise this fact.

Mr MW Sibuyana (IFP) asked if they were the only organisation that was engaged in looking for an AIDS cure.

Prof Ramgee replied that institutions such as the University of the Witwatersrand and the University of Cape Town were involved in vaccine research, but most international organisations preferred to work with the MRC because their work was of a high caliber.

Dr Rabinowitz asked if they were still using old medicines for TB and if there were new ones in development.

Prof Mbewu replied that the drugs available to treat XDR-TB were toxic and they took a long time to work but they were working on new drugs. Unfortunately this might take up to years.

The Chairperson asked if the trials that were going to be concluded in April 2007, December 2007 and 2009 were taking place in South Africa.

Prof Ramgee confirmed that they would be conducted in South Africa by the MRC. These were the Caragat trial and the Pro 2000 trials.

The meeting was adjourned.