quinta-feira, dezembro 09, 2004
Carta dos activistas tailandeses sobre ensaio com tenofovir
8 December 2004
Dear Dr. Alan Greenberg, Dr. Lynn Paxton, Dr. John Nkengasong, Dr. Kachit Choopanya, and Dr. Sombat Thanprasertsuk,
We, the undersigned, would like to express our concerns and recommendations for the planned “Study of the Safety and Efficacy of Daily Tenofovir to Prevent HIV Infection Among Injection Drug Users (IDU) in Bangkok, Thailand (Bangkok Tenofovir Study),” sponsored by the US Centers for Disease Control and Prevention (CDC) in partnership with the Thailand Ministry of Public Health, with pharmaceutical support from Gilead Sciences, California, USA.
While we strongly support efforts to develop promising new HIV prevention tools, we remain concerned about the possible use of unethical or substandard measures employed in the testing of such tools. Based on our understanding of this proposed trial, which is currently pending approval by three ethical review boards, we would like to express our concern regarding several aspects of the study.
Firstly, while Tenofovir as an HIV prevention tool is being tested in multiple sites around the world, including the United States, every single cohort excepting the IDU group in Thailand has been chosen for its high sexual transmission rates, and the prevention package offered study participants includes condoms, the single most effective HIV prevention tool available. However, it is our understanding that, in the Bangkok Study, which aims to enroll 1,600 IDU in studying the efficacy of Tenofovir in preventing spread associated with intravenous drug use, you will not be providing what research has shown to be the most effective prevention tool among injectors: clean needles and syringes. This is a particularly egregious departure from ethical standards since half of the trial participants will receive a placebo. Thailand-based investigators on this study have repeatedly told us that it is because the study is funded by the US government that sterile injection equipment cannot be purchased and provided as part of the trial’s risk reduction counseling and support package. Local investigators also informed us that another barrier to needle and syringe provision in the context of the trial is that such provision is illegal in Thailand. As clearly stated by paragraph 29 of the Declaration of Helsinki, and recently reaffirmed by the same World Medical Association, extreme care must be taken in making use of a placebo-controlled trial and that in general this methodology should only be used in the absence of existing proven prophylactic, diagnostic, and therapeutic methods[1].
The HIV prevalence rate among IDU in Thailand is approximately 50%, a situation that has remained consistent for nearly 15 years, due to government failure to implement effective, evidence-based prevention measures. Last year, Thai Prime Minister Thaksin Shinawatra launched an anti-drug campaign that resulted in widespread human rights violations of people allegedly involved with drugs, including the extra-judicial killing of more than 2,275 people (“Not Enough Graves: Thailand’s War on Drugs, HIV/AIDS, and Violations of Human Rights,” Human Rights Watch, July 2004). Though Prime Minister Thaksin’s discourse has included statements in support of harm reduction and the active involvement of drug users in its implementation (International AIDS Conference Opening Plenary, July, 2004), rhetoric has yet to become a reality in Thailand, and the current standard of care for IDU in Bangkok, the study site, does not embrace a comprehensive harm reduction approach as a matter of policy. We are concerned you have chosen a highly underserved, criminalized, and exploited group whose safety and best interests you are not in a position to protect, as required by the Declaration of Helsinki and other international ethical standards.
In Bangkok, HIV-positive IDU may be pressured to quit drugs in order to be eligible for health care services, including anti-retroviral therapy; in practice this is a form of discrimination in the health-care setting. Moreover, Thailand still lacks a clear and evidence-based methadone maintenance policy (methadone is primarily provided for detoxification). Peer outreach has been severely compromised by the dangerous legal and political environment. Drug treatment programs primarily promote a single model, abstinence, eschewing scientific- and therapeutic-based approaches and favoring punitive treatment. Routinely abused by law enforcement officials, IDU in Thailand find themselves at increased risk of HIV infection in pre-trial detention and prison, where injecting drug use (as well as sexual intercourse) is widespread but faces official denial.
In such a hostile environment, vis-à-vis the health and human rights of people who use illicit drugs, we understand that it is particularly difficult to design an ethical study. However, it is incumbent on investigators to provide the highest available standard of care for IDU prevention as recommended by the World Health Organization (“Evidence for Action on HIV/AIDS and Injection Drug Use” series, WHO, 2004) and human rights bodies such as the Committee on Economic, Social, and Cultural Rights in an effort to positively improve that environment. First-hand accounts of participants’ negative experiences in previous vaccine and other clinical trials among IDU in Bangkok (“Not Enough Graves: Thailand’s War on Drugs, HIV/AIDS, and Violations of Human Rights,” Human Rights Watch, July 2004; pages 3–5), bode poorly for the ability of your trial investigators and staff to ensure quality of referrals, support, treatment and care that the trial participants will receive through the public health care system, given that effective, evidence-based prevention interventions are unavailable in the standard package of care for IDU.
We are also concerned that you are recruiting participants (only) from Bangkok Metropolitan Authority (BMA) methadone clinics, where clients may feel coerced into enrolling in your trial if they feel the services they receive may otherwise be compromised. We believe strongly that any organization involved in this study has an absolute obligation to identify ways in which coercion to participate will be precluded. As well, there are clear limitations to this approach as you may be recruiting a biased treatment-based sample that may not be representative of the larger IDU population. We would like it to be clear that our comments are not a criticism of health care workers who try to do their best in difficult circumstances, but refer to the ethical commitment of researchers to study participants.
We raise the issue of benefits to the study participants and the general population of Thailand because investigators have stated that Gilead Sciences, Inc. has only agreed to provide free daily Tenofovir as HIV-prevention (if found effective) to the RECIPIENTS OF THE PLACEBO during the trial, for one year following the completion of the trial. This is against all international ethical standard, as clearly stated by article 30 of the Declaration of Helsinki[2]. During its 167th Council session in Divonne-les-Bains, France (May 13-15) the World Medical Association issued a note of clarification on paragraph 30 of the WMA Declaration of Helsinki stating that “it is necessary during the study planning process to identify post-trial access by study participants to prophylactic, diagnostic and therapeutic procedures identified as beneficial in the study or access to other appropriate care. Post-trial access arrangements or other care must be described in the study protocol so the ethical review committee may consider such arrangements during its review”.
In spite of what is clearly stated in the Helsinki Declaration, the US CDC has agreed, according to investigators, to purchase Tenofovir at cost for one year following the completion of the trial for recipients of Tenofovir during the trial. We believe that all sero-converters in the trial should also receive lifetime antiretroviral therapy as a benefit of participating in the trial, especially if it is not possible to deliver all harm-reduction measures known to be helpful in lessening contagion. Also, Tenofovir should be made available both as a prevention and antiviral therapy to the host country at Thailand’s asking price, or license should be given to produce Tenofovir by the Government Pharmaceutical Organization (GPO).
Our deepest concern over the planning of this trial is that no IDU or AIDS NGO community representatives have been involved from the outset on any official committee to discuss all aspects of the trial, only a few of which we discuss here. We have been told that the protocol must be reviewed by three ethical committees before a community advisory board (CAB) would be set up, but at that point there would be little opportunity to make the changes we as the community are suggesting here. We request that investigators immediately postpone the trial and withdraw its draft protocol from the three committees currently reviewing it. The community that will comprise the participants must be included at the very outset of deliberations by those whose endorsement is required. The community, particularly the Thai Drug Users’ Network (TDN), should be treated as equal partners in the planning of a more ethical trial with genuine community involvement. Any relationship short of this is unacceptable.
In this respect, our request is that an advisory committee involving all stakeholders, including IDU, people living with HIV/AIDS, human rights advocates, and AIDS NGO community representatives, urgently be established, PRIOR to the final review and approval of the study protocol, with a genuine intention to consider and make changes in the basic prevention, care and support aspects of the trial. We insist on true involvement in the process of planning, implementing, monitoring and analyzing/disseminating results of the trial, and will not accept a token role on a Community Advisory Board (CAB) that is established after the protocol, which we find deeply flawed, is essentially fixed.
We have appreciated the Thailand-based researchers’ willingness to meet and openness in discussing the trial, and for sharing documents related to the trial, including informed consent forms and the protocol (in both Thai and English).
We send this letter in a spirit of support for and camaraderie in the fight for safe and effective prevention tools, in particular for highly vulnerable groups, and appreciate that everyone in Thailand, in particular the study target group, might benefit from this trial. Therefore, we look forward to receiving your detailed response (in both Thai and English, if possible) to our concerns and suggestions and hope to receive them at your earliest convenience, since local investigators tell us they expect to begin recruitment for this trial in January 2005.
Yours sincerely,
Thai AIDS Treatment Action Group (TTAG)
Thai Drug Users’ Network (TDN)
Thai NGO Coalition on AIDS (TNCA)
MSF-Belgium/Thailand
Center for AIDS Rights (CAR)
AKA “Tenofovir Community Working Group”
Cc:
Dr. Jordan Tappero
Dr. Taweesap Siraprapasiri
Dr. Frits van Griensven
Dr. Michael Martin
Dr. Rutt Chuachoowong
[1] As clearly stated by paragraph 29 of the Declaration of Helsinki, and recently reaffirmed by the same World Medical Association, extreme care must be taken in making use of a placebo-controlled trial and that in general this methodology should only be used in the absence of existing proven prophylactic, diagnostic, and therapeutic methods.
[2] article 30, Declaration of Helsinki , “At the conclusion of the study, every patient entered into the study should be assured of access to the best proven prophylactic, diagnostic and therapeutic methods identified by the study”.
Dear Dr. Alan Greenberg, Dr. Lynn Paxton, Dr. John Nkengasong, Dr. Kachit Choopanya, and Dr. Sombat Thanprasertsuk,
We, the undersigned, would like to express our concerns and recommendations for the planned “Study of the Safety and Efficacy of Daily Tenofovir to Prevent HIV Infection Among Injection Drug Users (IDU) in Bangkok, Thailand (Bangkok Tenofovir Study),” sponsored by the US Centers for Disease Control and Prevention (CDC) in partnership with the Thailand Ministry of Public Health, with pharmaceutical support from Gilead Sciences, California, USA.
While we strongly support efforts to develop promising new HIV prevention tools, we remain concerned about the possible use of unethical or substandard measures employed in the testing of such tools. Based on our understanding of this proposed trial, which is currently pending approval by three ethical review boards, we would like to express our concern regarding several aspects of the study.
Firstly, while Tenofovir as an HIV prevention tool is being tested in multiple sites around the world, including the United States, every single cohort excepting the IDU group in Thailand has been chosen for its high sexual transmission rates, and the prevention package offered study participants includes condoms, the single most effective HIV prevention tool available. However, it is our understanding that, in the Bangkok Study, which aims to enroll 1,600 IDU in studying the efficacy of Tenofovir in preventing spread associated with intravenous drug use, you will not be providing what research has shown to be the most effective prevention tool among injectors: clean needles and syringes. This is a particularly egregious departure from ethical standards since half of the trial participants will receive a placebo. Thailand-based investigators on this study have repeatedly told us that it is because the study is funded by the US government that sterile injection equipment cannot be purchased and provided as part of the trial’s risk reduction counseling and support package. Local investigators also informed us that another barrier to needle and syringe provision in the context of the trial is that such provision is illegal in Thailand. As clearly stated by paragraph 29 of the Declaration of Helsinki, and recently reaffirmed by the same World Medical Association, extreme care must be taken in making use of a placebo-controlled trial and that in general this methodology should only be used in the absence of existing proven prophylactic, diagnostic, and therapeutic methods[1].
The HIV prevalence rate among IDU in Thailand is approximately 50%, a situation that has remained consistent for nearly 15 years, due to government failure to implement effective, evidence-based prevention measures. Last year, Thai Prime Minister Thaksin Shinawatra launched an anti-drug campaign that resulted in widespread human rights violations of people allegedly involved with drugs, including the extra-judicial killing of more than 2,275 people (“Not Enough Graves: Thailand’s War on Drugs, HIV/AIDS, and Violations of Human Rights,” Human Rights Watch, July 2004). Though Prime Minister Thaksin’s discourse has included statements in support of harm reduction and the active involvement of drug users in its implementation (International AIDS Conference Opening Plenary, July, 2004), rhetoric has yet to become a reality in Thailand, and the current standard of care for IDU in Bangkok, the study site, does not embrace a comprehensive harm reduction approach as a matter of policy. We are concerned you have chosen a highly underserved, criminalized, and exploited group whose safety and best interests you are not in a position to protect, as required by the Declaration of Helsinki and other international ethical standards.
In Bangkok, HIV-positive IDU may be pressured to quit drugs in order to be eligible for health care services, including anti-retroviral therapy; in practice this is a form of discrimination in the health-care setting. Moreover, Thailand still lacks a clear and evidence-based methadone maintenance policy (methadone is primarily provided for detoxification). Peer outreach has been severely compromised by the dangerous legal and political environment. Drug treatment programs primarily promote a single model, abstinence, eschewing scientific- and therapeutic-based approaches and favoring punitive treatment. Routinely abused by law enforcement officials, IDU in Thailand find themselves at increased risk of HIV infection in pre-trial detention and prison, where injecting drug use (as well as sexual intercourse) is widespread but faces official denial.
In such a hostile environment, vis-à-vis the health and human rights of people who use illicit drugs, we understand that it is particularly difficult to design an ethical study. However, it is incumbent on investigators to provide the highest available standard of care for IDU prevention as recommended by the World Health Organization (“Evidence for Action on HIV/AIDS and Injection Drug Use” series, WHO, 2004) and human rights bodies such as the Committee on Economic, Social, and Cultural Rights in an effort to positively improve that environment. First-hand accounts of participants’ negative experiences in previous vaccine and other clinical trials among IDU in Bangkok (“Not Enough Graves: Thailand’s War on Drugs, HIV/AIDS, and Violations of Human Rights,” Human Rights Watch, July 2004; pages 3–5), bode poorly for the ability of your trial investigators and staff to ensure quality of referrals, support, treatment and care that the trial participants will receive through the public health care system, given that effective, evidence-based prevention interventions are unavailable in the standard package of care for IDU.
We are also concerned that you are recruiting participants (only) from Bangkok Metropolitan Authority (BMA) methadone clinics, where clients may feel coerced into enrolling in your trial if they feel the services they receive may otherwise be compromised. We believe strongly that any organization involved in this study has an absolute obligation to identify ways in which coercion to participate will be precluded. As well, there are clear limitations to this approach as you may be recruiting a biased treatment-based sample that may not be representative of the larger IDU population. We would like it to be clear that our comments are not a criticism of health care workers who try to do their best in difficult circumstances, but refer to the ethical commitment of researchers to study participants.
We raise the issue of benefits to the study participants and the general population of Thailand because investigators have stated that Gilead Sciences, Inc. has only agreed to provide free daily Tenofovir as HIV-prevention (if found effective) to the RECIPIENTS OF THE PLACEBO during the trial, for one year following the completion of the trial. This is against all international ethical standard, as clearly stated by article 30 of the Declaration of Helsinki[2]. During its 167th Council session in Divonne-les-Bains, France (May 13-15) the World Medical Association issued a note of clarification on paragraph 30 of the WMA Declaration of Helsinki stating that “it is necessary during the study planning process to identify post-trial access by study participants to prophylactic, diagnostic and therapeutic procedures identified as beneficial in the study or access to other appropriate care. Post-trial access arrangements or other care must be described in the study protocol so the ethical review committee may consider such arrangements during its review”.
In spite of what is clearly stated in the Helsinki Declaration, the US CDC has agreed, according to investigators, to purchase Tenofovir at cost for one year following the completion of the trial for recipients of Tenofovir during the trial. We believe that all sero-converters in the trial should also receive lifetime antiretroviral therapy as a benefit of participating in the trial, especially if it is not possible to deliver all harm-reduction measures known to be helpful in lessening contagion. Also, Tenofovir should be made available both as a prevention and antiviral therapy to the host country at Thailand’s asking price, or license should be given to produce Tenofovir by the Government Pharmaceutical Organization (GPO).
Our deepest concern over the planning of this trial is that no IDU or AIDS NGO community representatives have been involved from the outset on any official committee to discuss all aspects of the trial, only a few of which we discuss here. We have been told that the protocol must be reviewed by three ethical committees before a community advisory board (CAB) would be set up, but at that point there would be little opportunity to make the changes we as the community are suggesting here. We request that investigators immediately postpone the trial and withdraw its draft protocol from the three committees currently reviewing it. The community that will comprise the participants must be included at the very outset of deliberations by those whose endorsement is required. The community, particularly the Thai Drug Users’ Network (TDN), should be treated as equal partners in the planning of a more ethical trial with genuine community involvement. Any relationship short of this is unacceptable.
In this respect, our request is that an advisory committee involving all stakeholders, including IDU, people living with HIV/AIDS, human rights advocates, and AIDS NGO community representatives, urgently be established, PRIOR to the final review and approval of the study protocol, with a genuine intention to consider and make changes in the basic prevention, care and support aspects of the trial. We insist on true involvement in the process of planning, implementing, monitoring and analyzing/disseminating results of the trial, and will not accept a token role on a Community Advisory Board (CAB) that is established after the protocol, which we find deeply flawed, is essentially fixed.
We have appreciated the Thailand-based researchers’ willingness to meet and openness in discussing the trial, and for sharing documents related to the trial, including informed consent forms and the protocol (in both Thai and English).
We send this letter in a spirit of support for and camaraderie in the fight for safe and effective prevention tools, in particular for highly vulnerable groups, and appreciate that everyone in Thailand, in particular the study target group, might benefit from this trial. Therefore, we look forward to receiving your detailed response (in both Thai and English, if possible) to our concerns and suggestions and hope to receive them at your earliest convenience, since local investigators tell us they expect to begin recruitment for this trial in January 2005.
Yours sincerely,
Thai AIDS Treatment Action Group (TTAG)
Thai Drug Users’ Network (TDN)
Thai NGO Coalition on AIDS (TNCA)
MSF-Belgium/Thailand
Center for AIDS Rights (CAR)
AKA “Tenofovir Community Working Group”
Cc:
Dr. Jordan Tappero
Dr. Taweesap Siraprapasiri
Dr. Frits van Griensven
Dr. Michael Martin
Dr. Rutt Chuachoowong
[1] As clearly stated by paragraph 29 of the Declaration of Helsinki, and recently reaffirmed by the same World Medical Association, extreme care must be taken in making use of a placebo-controlled trial and that in general this methodology should only be used in the absence of existing proven prophylactic, diagnostic, and therapeutic methods.
[2] article 30, Declaration of Helsinki , “At the conclusion of the study, every patient entered into the study should be assured of access to the best proven prophylactic, diagnostic and therapeutic methods identified by the study”.
