By Terence Zimwara
An HIV positive Zimbabwean woman has alleged that she has become partially blind after taking part in a clinical trial for a new second line HIV treatment drug and she has not been compensated for the injury.
Europe-Africa Research Network for Evaluation of Second Line Therapy (EARNEST ) is the name of the study for a clinical trial of HIV positive people who have failed to respond well to regular anti-retroviral treatment, also known as first line treatment.
The Medical Research Council (MRC) based in the United Kingdom is sponsoring this study through its Clinical Trials Unit (CTU).
The clinical trial began in late 2010 and it is expected to end in 2014 with about 1,277 patients having enrolled for the study.
It is the endeavor of the study’s sponsors to develop a second line drug that will help HIV positive people who have experienced treatment failure to regular anti-retroviral therapy (ART)drugs. EARNEST is conducting these trials at 14 sites in Kenya, Uganda, Malawi, Zambia and Zimbabwe.
Memory (not her real name), born 24 years ago, became an orphan at the age sixteen after her mother succumbed to the AIDS pandemic in 2005. Before she passed on, Memory provided care for her sick mother, whom she says was losing a lot of blood. Memory suspects that is how she contracted the virus herself.
A partially-blind Memory in the hospital.
“After my mother passed on I then moved in with my grandmother who later encouraged me to go and get tested for the HIV virus,” explained Memory. After she got tested, she discovered that she had contracted the HIV virus and was immediately placed on anti-retroviral therapy (ART).
Her first stint with HIV treatment was with what she identified as being the normal drugs for most HIV positive patients. “I started taking the drugs called Stalanev and Cotrimoxazole as part of my ART treatment regimen,” said Memory.
During the time that she was on these drugs, Memory says she was relatively healthy and had neither been bedridden nor been very sick. She explains that she was on this treatment course since 2005. For six years this first line treatment regimen managed to keep her alive before everything changed dramatically.
She goes on to explain that an organization, which she did not previously know, approached her and told her that they could help her through a different treatment regimen that they wanted to try.
“In 2010, people from EARNEST suddenly came home and informed me that they were conducting clinical trials for people that had not responded well to regular anti-retroviral therapy,” she said.
When she asked them how they got information about her, they told her they saw her file at Rutsanana Clinic in the high density township of Highfields in Harare. It was at this clinic that she first tested positive for HIV, the same clinic where she had been collecting her HIV treatment drugs.
Memory alleges that at the time when people from EARNEST approached her, her CD4 count was 75 according to her records at Rutsanana. “However, these people from EARNEST took me to Baines [an area common with private physicians just outside the CBD of Harare] to a specialist doctor, who then tested my CD4 and told me my count had dropped to four,” said a bemused Memory.
Memory said it was strange for her CD4 count to be that low when she had never been very sick or bed ridden once she was on ART and, according to her understanding, such a low count would normally be seen in very sick people who could no longer help themselves.
“When these people came I was actually working at OK Mart [a mega store] along Chiremba road in Braeside where I was doing catering,” said Memory.
Consistent with Memory’s claims, the EARNEST clinical report, which we are in possession of, states that her CD4 count on 26 October 2010, prior to the clinical trial, was just four. It rose to 202 by 22 April 2013.
According to EARNEST, potential patients for the study were excluded if their condition was deemed too bad and if their life expectancy was determined to be less than one month by an evaluating physician.
After she was tested and when her CD4 count was determined to be four, EARNEST representatives then explained to her that they had three drugs they wanted to test to see if they could help people with a low CD4. Having developed what EARNEST calls ‘treatment failure’ – where the first line drugs are no longer working – Memory was convinced to join the study.
After verbally agreeing to become a participant of this clinical trial, Memory was given an informed consent form to sign; she did and she was given a copy. Memory insists the informed consent form never mentioned anything about insurance cover for participating in the trial or compensation in case of permanent injury.
Immediately after consenting, Memory was placed on treatment with one of the research drugs.
Memory explained that she would go to the University of Zimbabwe Clinical Research Centre (UZCRC) to get replenishment of the drugs once every month, as well as to get instructions on the number of drugs she had to take each time. In order to ensure that participants did not miss any dosage of these drugs, Earnest Study would give each participant a transport ‘allowance’ of $30 each time they came to collect drugs.
Lamivudine and Tremodovir Disoproxil Fumarate
Some of the drugs which we are in possession are packaged in capsules clearly marked ‘clinical trial use only.’ Memory was randomized for the drugs listed as follows:
- One capsule is marked Lopinavir/Ritonavir and it initially contained 120 tablets with the name of the drug manufacturer listed as Abbott GmbH &Co, KG, 67061 Ludwigshafen, Germany.
- The other capsule has tablets called Lamivudine and Tenofovir Disoproxil Furmarate and the manufacturer is Hetero Labs Limited, Hyderabad in India.
Lopinavir/Ritonavir
Memory explains that the promoters of this clinical trial “told me the drugs which they identified as A, B and C were just like ordinary HIV drugs(ART) and all drugs had an after effect.”
According to information on EARNEST website, patients were divided into three intervention and control groups, namely Arm A: bPi+2NRTIs; Arm B: bPi+ raltegravir; and Arm C: bPi alone.
They informed her that the known side effects of these drugs were diarrhea and a skin rash and that these would only occur at the beginning of the treatment course but would eventually cease as the participant progressed with the drugs.
“They told me that if these side effects started and persisted, I had to inform them as soon as possible or to visit the nearest health Centre,” explained Memory.
A few months after she started taking this new drug her nightmare began.
“I started to have problems with my eyes. I could not even walk to the Centre (UZCRC) because my eyesight was getting poor.”
Memory tells us when she started the second line clinical trial she would travel by herself to collect the drugs but now she could not due to the impairment.
“Before I signed the informed consent form, I read the form with my own eyes and I signed with representatives of Earnest witnessing this,” she said.
Now Memory says her sight is poor during the day although she can only move around familiar places with little or no assistance. However, after 5pm she does not move as she cannot see completely.
Her last clinical report does not mention anything about the problem she now has with her eyes. The clinical report, which curiously understates her age by three years, was signed as well as endorsed by Dr. Chimusoro and only mentions the scar she got on her left upper eyelid when she was hit by a car.
Upon realizing that she was becoming blind, Memory went back to EARNEST to seek assistance and was then advised to go and see an optometrist.
When she told them that she did not have money to see such a specialist, they drafted a letter which she then used to get an appointment with an optometrist at Kaguvi eye Centre at Parirenyatwa Hospitals. It was then when she was told chilling news about the condition of her eyes.
“The optometrist who examined me told me there was nothing he could do anymore because the second line treatment drugs (ART) that I was on had caused the wilting of a vein in my head.”
“This resulted in my becoming partially blind. He told me that getting medication to treat the eyes at this stage was not going to help because the damage had already been done,” she said.
On realizing this, the optometrist then referred Memory to Dorothy Duncan Centre, a centre that helps the blind through training and provision of materials like braille. Memory says she does not know who paid for her to be enlisted with this Centre but she remembers she had to go to this place for three months as part of the course.
However, Memory tells us she only went there for two weeks and she left the training when she was given a walking stick.
Meanwhile, Memory says she was still taking the same drugs that had caused her partial blindness because she had been advised to continue doing so by the optometrist.
“The optometrist told me to continue with the drugs until I saw an HIV virus specialist who would then recommend new drugs that would not injure my eyes as had happened,” she said.
Memory says she then went back to EARNEST to seek help in getting an appointment with a specialist doctor who could help her. She would spend hours waiting for help only to be told to return some other day.
She explains that her only encounter with one of the study’s coordinators, Dr. Andrew Reid, ended with him asking her to get a quotation for spectacles which she could use to help her failing eyesight.
Memory tells us that the doctor was always busy and out of the country most of the time and could not help her. Eventually she gave up trying to get help from EARNEST.
In the meantime, Memory gave birth to an HIV negative baby girl in July 2013. To compound her woes, the father of the child has since refused to support her. The father told Memory he could not live with a visually impaired mother who was also on ART treatment.
Memory is now forced to look after her baby on her own and yet she cannot work because of her disability.
“People now exclude me from participating in many activities because they think my blindness means I am helpless,” said an emotional Memory.
She makes an appeal to anyone who could help her, particularly with anything that could help her eyesight to improve. She remains confident that she can still work despite this condition.
Memory expressed her disappointment with EARNEST officials for failing to help her in spite of her value to their study.
“They acquired knowledge about the side effects of these drugs through me and maybe now this drug has been withdrawn yet I am now struggling as result of the side effects,” said a visibly angry Memory.
Memory also tells us she knows a number of others who were enrolled for the same program and who have since suffered serious and varying side effects and just like in her case, nothing has been done to compensate them.
Currently Memory stays as a caretaker for a relative’s house outside Harare in conditions which can described as difficult. She did eventually stop taking in the trial drugs and has returned to the ART regimen she initially began with. She believes her CD4 count has improved significantly as result.
Who is involved in the EARNEST clinical trial?
EARNEST study, the clinical trial that Memory got recruited into, is a multinational and multi-faceted study that includes a European Commission funded body, universities and drug companies.
European and Developing Countries Clinical Trials Partnership (EDCTP) is a partnership of 14 European Union (EU) countries, Switzerland, Norway and 47 African countries. It has its head offices in the Hague, The Netherlands while the European Commission provides part of the budget for this partnership.
EDCTP is funding the EARNEST study.
We asked EDCTP about guidelines and standards of clinical research that they endorse and finance. The EDCTP responded by revealing that it requires all sponsors of EDCTP-funded clinical trials to abide by the principles of the International Conference on Harmonization Guidelines for Good Clinical Practice (ICH GCP).
Gert Onne van de Klashorst, communications officer with EDCTP told us that his organization only provides funding and does not conduct clinical trials.
“The sponsor of clinical trial has to undertake all legal obligations to make sure that all legal liabilities are covered. This usually includes the obligation to take insurance to meet legal obligations,” said Gert Onne van de Klashorst in a written response to our enquiries.
Thus the EDCTP requires all sponsors of clinical trials it funds to obtain adequate clinical trial insurance to cover claims that might arise from the trial.
In the terminology of clinical trials and the guidelines for Good Clinical Practice, a sponsor has a specific task to guarantee the quality of the trial while the funding organization in this case EDCTP, provides the financial means.
The sponsor of this study is the Medical Research Council (MRC) which is based in the United Kingdom and it is conducting the trials through its Clinical Trials Unit (CTU). MRC confirmed that they were sponsoring the EARNEST study and insisted that they conduct clinical trials in accordance with the principles of ICH GCP.
Responding to our inquiry of a participant who suffered adverse effects from the study, Cathy Beveridge, Senior Press Officer of MRC, defended the drugs used in the trial, although she directed the victim to approach local authorities for a review of her case.
“We are sorry to hear about the EARNEST trial participant [Memory] and her experiences. [However] the drugs used in the trial are in widespread use and there has been no previous evidence to demonstrate that they cause blindness,” said Cathy Beveridge.
“If the participant would like to pursue the matter further, then we recommend that she bring this to the attention of the MRCZ the body responsible for oversight of clinical research in the country.”
When questioned further about Memory’s particular case, the MRC, citing patient confidentiality, said it could not discuss this individual case.
“If a patient has concerns, they should discuss this issue, in the first instance, with the hospital where they receive ongoing care.”
“The medical history of all trial participants prior to their consent to participation in the trial, as well as during the study itself, including all adverse effects are carefully documented. The trial protocol ensures that all participants are regularly followed up,” added Cathy Beveridge.
On the issue of the competence of staff and the capacity of its sites, the MRC only responded to the latter part of the question.
“The sites for the EARNEST trial were carefully chosen and monitored both before the start of the trial and during the course of the trial. This is to be sure that they have the appropriate levels of care and can deliver to the trial protocol effectively and safely,” continued Cathy Beveridge.
We also asked about the safety of the drugs used in the trial, given the complaints from Memory, and Cathy Beveridge responded as follows:
“The trial only uses drugs that have been licensed for the treatment of HIV infection. These drugs have been tested extensively are used worldwide and are ‘not considered to be new or experimental drugs.’
“Indeed the EARNEST trial is an ‘open labelled’ study which means that both researchers and participants know which drug is being tested,” she said.
According to information available on EARNEST website, the trial has been undertaken with the objective of identifying the best ART for HIV positive individuals who need to switch ART in ‘resource limited’ settings.
The Chief investigator for this study is Professor Nick Paton; in Zimbabwe the principal investigator is Professor James Hakim.
In Zimbabwe, EARNEST study is represented at the University of Zimbabwe Clinical Research Centre (UZCRC) which is located at Parirenyatwa Hospitals Annexe Clinic.
Memory is only able to identify two figures from this organization, a one lady ‘Mai Mutsai’ who she says was responsible for recruiting patients and Dr. Andrew Reid, an HIV researcher as well as a founder of Champions for Life, a non-governmental organization which claims to assist HIV positive youths.
According to Memory, Dr. Reid’s Champions for Life used to conduct gospel seminars for the HIV positive youths from Harare’s poor suburbs of Epworth, Hopely and Seke.
The seminars were mostly held at the Celebration Centre church which is located in the upmarket Harare suburb of Borrowdale and the youths would sometimes be collected from Parirenyatwa Hospitals.
Memory and some of her fellow participants in the EARNEST clinical trial have attended these seminars, although Memory says she has since stopped attending.
According to information gleaned from EARNEST’s website, Dr. Andrew Reid is one of the senior officials for the clinical research team in Zimbabwe. In 2010 Dr. Reid was part of a group of doctors that were arrested in Harare for allegedly practicing medicine without a license.
They were also accused of operating an HIV/AIDS clinic and distributing ART drugs without a permit from authorities. They were eventually granted bail and released.
The EARNEST study clinical trial commenced in October 2009 and 1,277 patients from five African countries have since been recruited into this study. Uganda, which previously had the highest HIV/AIDS rate in the world, has nine study sites; Malawi has two; Zambia, Kenya and Zimbabwe all have one each.
The EARNEST website also lists the partners to the study which are grouped into countries, researching institutions and the drug companies providing the clinical drugs.
The Pharma partners or drug companies include renowned global pharmaceutical companies like Pfizer, Abbvie, Merck, GlaxoSmithKline, Gilead and Abbott. In Memory’s case, Abbott provided some of the drugs she took as her second line treatment.
The European-based research bodies and institutions that are involved in this study include Instituto Superiore di Sanita, Institute of Tropical Medicine, La Paz Hospital, Cineca, University College Dublin and the MRC CTU.
The website of EARNEST does not have typical details, such as the physical contact address, phone numbers, fax or names of persons heading the secretariat. The only contact detail is one email address.
What does the Zimbabwean law say?
The Medical Research Council of Zimbabwe (MRCZ) is mandated with regulating and monitoring all medical and health research taking place in the country.
Dr. Paul Ndebele is the executive director of MRCZ and he told us in a letter that his organization requires researchers to report on drug reactions.
“We also receive and conduct investigations on research participants’ complaints to ensure that corrective action is taken,” added Dr. Ndebele. He said that they took participants’ complaints seriously and expressed his desire to get further information on Memory’s case so that action could be taken.
According to regulations for conducting clinical trials, a standard consent form must clearly state the compensation for participants who may suffer adverse effects during a trial or immediately after the trial.
The Medicines and Allied Substance Control Act (MASCA) Chapter 15:03 and IS 150 state it is a requirement to have insurance cover for trial related injuries. It reads: “The actual amount of the clinical trial cover is calculated in terms of the risk of the study. Insurance cover is required to be set aside and the informed consent form should not include a disclaimer for clinical trial related injuries.”
Ethical approval of the HIV vaccines clinical trials is granted by the MRCZ and the Research Council of Zimbabwe (RCZ) including regulation of foreign researchers.
Additionally, according to the Medicines Control Authority of Zimbabwe (MCAZ), guidelines on reporting adverse effects, what happened to Memory qualifies as a serious adverse effect (SAE) and this has to be reported to authorities within 48 hours who must then determine the next course of action.
Information obtained from SAE report then provides MCAZ and investigators with an early toxicity profile of an investigational product. This information might also be used during the application for registration of a new medicine to determine if a product is safe for marketing.
However, Memory alleges that the consent form that she signed never mentioned anything about compensation or insurance cover.
Now, she says her life has taken a turn for the worst as she finds it very difficult to make ends meet due to the partial blindness that she is adamant was brought about by the clinical trial drugs.
The allegation is supported by her clinical report, which seems to suggest that there were efforts to cover up her injury. According to the report, Memory’s medical history during the trial only lists one event: ‘left upper eyelid cut’ and its severity is listed as grade 3. The cut was reported to have occurred on the 27th of April 2012 and this event was resolved by the 17th of May 2012. The next section of the report, which asks for any additional information on the patient, is blank and marked nil. The report is dated 23 July 2013.
Meanwhile, Memory’s relatives are adamant that something happened to her eyes during this trial because she never had problems with her eyes before.
Roy, a sibling of Memory, tells us that he heard of his sister’s visual impairment while he was working in Botswana. “She called and told me that she could not see any more but I did not understand this because she had never had problems with her eyes before,” said Roy. Roy told us their appeal now was for help in getting his sister treated and possibly having her eyesight restored.
Memory’s grandmother, with whom she has stayed with for most of her life since the passing on of her mother, was even more emotional when she narrated what has happened to her granddaughter.
“She went through from grade one (her primary education) up to form four (secondary school) and she never had problems with her eyes,” said Memory’s grandmother. She explained that there was no way her granddaughter would have gone through these two stages of school as well as writing her Ordinary Level examination in normal institution if she was blind.
Memory’s grandmother remains adamant that the drugs Memory took from this clinic were responsible for her loss of eyesight. Before Memory enrolled for this study her grandmother had questioned why they (EARNEST study officials) had chosen Memory for this study and she says she was not satisfied with answers given to her. She tells us she was not surprised when her granddaughter started having problems with her eyes immediately after she started taking the drugs.
“I warned her against enrolling for this study because the people conducting the study (UZCRC) were experimenting and she could get hurt,” she said.
“She even finds it difficult to feed her baby because she has to use her hands to locate the baby’s mouth before she can feed her,” explained Memory’s grandmother.
Memory’s grandmother told us what was done to her granddaughter was unfair and that people responsible for this had to be held accountable. She says she is prepared to face authorities and tell everything that might help in bringing those responsible to book.
Memory passed away on the 6th of April, 2014. The cause of her death is currently unknown.
Terence Zimwara is an award winning journalist and socio-economic commentator from Zimbabwe. He writes on economic, health and finance matters and 2013 he was named Zimbabwe’s national health journalist of the year. He has written for a number of local publications including the Financial Gazzette, Business Herald, The Parade Magazine among others. Terence has idealist views and he advocates for a world that treats the less privileged fairly. You can visit him on www.temra-temra.blogspot.com.
