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Daily Maverick
13-05-2025
- Health
- Daily Maverick
The dual nature of clinical trials: Unpacking the risks and rewards for South African participants
Clinical trial participants appear to be well protected in South Africa, particularly as the country's guidelines recognise the risks of research with international collaborators. The sudden end of US-funded clinical trials, however, is exposing some limitations of ethics codes and guidelines, argues Dr Andy Gray. Participation in a clinical trial that involves the use of an investigational product, such as an unapproved medicine, can be viewed from two different perspectives. On the one hand, it may represent an opportunity for someone with an unmet medical need to access a promising new treatment or a means to prevent a condition for which the individual is at high risk. On the other hand, it can be seen as an altruistic act, accepting possible risks from the use of the investigational product in order to contribute to the development of new knowledge. Modern research ethics procedures recognise the vulnerability of trial participants and seek to protect them from exploitation and potential harms. The 2003 National Health Act created a new structure in South Africa, the National Health Research Ethics Council (NHREC). Appointed by the Minister of Health, the council is required to develop guidelines for health research ethics committees, register and audit such committees, and set the norms and standards for conducting clinical trials. Section 73 of the act requires every institution or health establishment where health research is conducted to 'establish or have access to a health research ethics committee' registered by the council. The necessary regulations that enabled Section 73 to come into effect were finally published in 2014. In addition, all clinical trials of medicines require prior approval by the South African Health Products Regulatory Authority (Sahpra). A Sahpra staff member also forms part of the council. At first glance, therefore, clinical trial participants in South Africa appear to be well protected. Ethics committees Two locally developed official documents guide the appraisal of applications by health research ethics committees and Sahpra. The national Department of Health issued an updated, third edition of the South African Ethics in Health Research Guidelines: Principles, Processes and Structures in 2024. The guidelines were developed by the council, in accordance with its legislative mandate. The third edition of the South African Good Clinical Practice: Clinical Trial Guidelines were issued by the department, with Sahpra, in 2020. Both of these documents acknowledge the existence of global guidance documents and codes, most notably the World Medical Association's Declaration of Helsinki, which was last updated in late 2024. Although developed by a federation of medical associations, the Declaration of Helsinki is considered to be authoritative and is commonly referenced by national guidelines and regulatory documents. The revision of the Declaration of Helsinki, which commenced in 2022, involved reconsideration of a number of clauses, including the protection of participants in economically vulnerable settings, and post-trial provisions and benefits. Post-trial access ensures that those who have been shown to benefit from a new medicine are not denied the use of that medicine until it is routinely available in their country and health system. These provisions are even more important when new and expensive medicines may not be accessible in low- or even middle-income countries because of high prices or delays in marketing. Clause 20 now reads: 'Medical research with individuals, groups, or communities in situations of particular vulnerability is only justified if it is responsive to their health needs and priorities and the individual, group, or community stands to benefit from the resulting knowledge, practices, or interventions. Researchers should only include those in situations of particular vulnerability when the research cannot be carried out in a less vulnerable group or community, or when excluding them would perpetuate or exacerbate their disparities.' Clause 34 now reads: 'In advance of a clinical trial, post-trial provisions must be arranged by sponsors and researchers to be provided by themselves, healthcare systems, or governments for all participants who still need an intervention identified as beneficial and reasonably safe in the trial. Exceptions to this requirement must be approved by a research ethics committee. Specific information about post-trial provisions must be disclosed to participants as part of informed consent.' When studies are stopped abruptly Since January 2025, a number of executive orders issued by the new United States administration and other actions have led to the abrupt cessation of USAid-funded clinical trials being conducted in South Africa. There is ongoing uncertainty regarding trials that are funded by other US federal agencies, notably the National Institutes of Health. These include multi-centred studies conducted by the Division of Aids clinical trials networks. Hence the question: are participants in South Africa protected, sufficiently, when a sponsor withdraws support for an ongoing clinical trial? That South African trial participants are particularly vulnerable is indisputable. In a country still marked by poverty and high unemployment, combined with a high burden of HIV and tuberculosis, and with most of the population dependent on an over-stretched and under-resourced public health sector, participation in a clinical trial offers the opportunity to access services that might not otherwise be available or of an acceptable standard. However, whether 'the individual, group, or community stands to benefit from the resulting knowledge, practices, or interventions' is less clear. Long-acting injectable antiretrovirals for the prevention of HIV remain out of reach, despite the contribution of South African participants in the pivotal trials of these technologies. That such trials could be conducted most efficiently in areas of high HIV incidence adds to the moral imperative to ensure access to the benefits that accrued. Apart from standard provisions for the fair selection of participants, the South African guidelines recognise the risks of research with international collaborators. The guidelines call for explicit memoranda of understanding covering expectations, roles and contributions, including financial arrangements. The Good Clinical Practice guidelines state that a 'signed declaration must be provided by the Sponsor which states that there are sufficient funds available to complete the trial'. Sahpra has a specific guideline on post-trial access or continued access which states: 'Where appropriate and available, the possibility of post-trial access/continued access should be disclosed to and discussed with potential participants during the initial informed consent process or via a separate consent process.' Immediate action The abrupt withdrawal of funding for clinical trials has meant that researchers have had to take immediate action to protect participants from potential harm. For example, when USAid funding for a vaginal ring study was withdrawn, participants were brought back to the trial clinic to remove the rings and provide counselling on alternative HIV prevention options. Researchers are trying to cover the costs of ethically closing studies, providing final clinic visits and referral for all participants. However, the sponsors of these prematurely cancelled studies appear to be evading their responsibilities, even to the extent that they are covered in codes and guidelines. The limitations of those codes and guidelines have been cruelly exposed. South African researchers involved in US-funded studies are required to complete Human Subjects Protection training, covering such US documents as the 1979 Belmont Report and the 'Common Rule'. Every training course includes coverage of the object lessons from the ' Tuskegee Study of Untreated Syphilis in the Negro Male' — a study conducted between 1932 and 1972 that grossly violated several basic principles of medical ethics. Will the events of 2025 and the consequences for clinical trials participants who consented in good faith, only to be abandoned for ideological and political reasons, be among the examples of unethical conduct provided to future health researchers undergoing ethics training? DM *Gray is a Senior Lecturer at the University of KwaZulu-Natal and Co-Director of the WHO Collaborating Centre on Pharmaceutical Policy and Evidence Based Practice. This is the third of a new series of #InsideTheBox columns he is writing for Spotlight.
Irish Daily Mirror
02-05-2025
- Health
- Irish Daily Mirror
Gynaecologist guilty of misconduct for procedure on five women without consent
A consultant gynaecologist has been found guilty of professional misconduct for carrying out unauthorised research on five female patients without their consent during a routine surgical procedure at St Luke's Hospital in Kilkenny seven years ago. A fitness-to-practise inquiry of the Medical Council found that three allegations of professional misconduct against Professor Ray O'Sullivan were proven beyond reasonable doubt. They related to the consultant's insertion of an abdominal rectal pressure catheter to measure intravaginal pressure while carrying out a hysteroscopy on five different women on September 4-5, 2018 at St Luke's Hospital. A separate allegation related to Professor O'Sullivan's failure to obtain advance approval, to produce a research protocol or to comply with professional guidelines about the use of the catheter. The inquiry held this week heard that Professor O'Sullivan had made admissions in relation to all the allegations and had accepted since February 2020 that his actions represented 'an error of judgement' on his behalf. A letter from his solicitors accepted at the time that with the benefit of hindsight, the consultant should have sought ethical approval for what he was doing in accordance with the Declaration of Helsinki – a set of ethical principles adopted internationally for medical research involving humans. The chairperson of the inquiry, Jill Long, said the fitness-to-practise committee also noted that medical records contained no reference to any consent having been obtained from any of the five female patients in advance of the procedure. Ms Long said the committee's conclusions were also based on a systems analysis review of what happened by the Ireland East Hospital Group, of which St Luke's Hospital in Kilkenny is a part. She also observed that the issue arose while Professor O'Sullivan alone had taken the decision to conduct a feasibility study of using the catheter to measure intravaginal pressure while performing a diagnostic hysteroscopy. Ms Long said the purpose of the research on the five patients was to see if a future proposed study was even possible. She explained that the research was to determine if there was a better alternative that could be developed to the traditional method of carrying out such an examination as the use of a speculum caused 'so much more discomfort'. The three-member committee concluded that the proven allegations represent professional misconduct in so far as they represented a serious falling short of the standards of conduct expected of medical practitioners. Ms Long said it did not consider that the actions represented professional misconduct on the basis that doctors of experience, competence and good repute would consider them 'disgraceful or dishonourable' or amounted to poor professional performance. She said the committee were satisfied with the finding of professional misconduct notwithstanding the fact that Professor O'Sullivan's motivation was 'benign' as he had failed to carry out the 'fundamental step' of obtaining consent from the patients for an additional and separate procedure. The use of the abdominal rectal pressure catheter by Professor O'Sullivan had already been the subject of extensive legal proceedings over the past few years. In May 2023, the Supreme Court ruled by a 4-1 majority that the HSE had acted fairly and reasonably when it suspended the consultant and recommended that he should be dismissed from his former job at St Luke's Hospital. The previous year, Professor O'Sullivan settled a long-running legal battle with the HSE over his suspension on foot of a complaint made in 2019 about his use of unauthorised and unapproved actions and procedures on the five female patients. However, the HSE sought to have one discrete issue relating to the fairness of its decision to suspend Professor O'Sullivan and to recommend his dismissal determined by the Supreme Court after the Court of Appeal had ruled in March 2022 that the consultant was entitled to an order quashing the HSE's decision. Professor O'Sullivan currently works at the First IVF fertility clinic in Clane, Co Kildare.
Yahoo
06-03-2025
- Health
- Yahoo
Why I'm sounding the alarm on the next puberty blockers scandal
Few issues in contemporary medicine have generated as much controversy as the use of puberty blockers in gender distressed children. The Government, responding to the findings of the Cass Review, has rightly banned the prescription of these drugs. Many other countries have, too. However the Government last week announced an £11 million clinical trial of these medicines to gather evidence of their effects. This raises a fundamental question: can a clinical trial of puberty blockers on children experiencing gender distress be done ethically? The answer, upon scrutiny, is a resounding 'no'. I have witnessed firsthand the grave dangers posed by the rush to medicalise childhood gender distress. As a former psychiatrist at the Tavistock and Portman NHS Trust, I was one of the whistleblowers who raised concerns about the practices at the now shuttered Gender Identity Development Service (Gids). What we uncovered was a service driven more by ideology than by robust clinical reasoning. Many distressed children, often same-sex attracted and with autistic comorbidities, were put on a medical pathway to transition by some clinicians who had been captured by 'trans' ideology and, as a result, cast aside ordinary sound clinical judgment. A clinical trial risks repeating these ethical failures. These trials are governed by rigorous ethical and legal standards, designed to protect participants from harm. The foundation of these standards is the Declaration of Helsinki, alongside the Good Clinical Practice guidelines and the UK's Medicines for Human Use (Clinical Trials) Regulations. These frameworks exist to ensure that the benefits of any new medical intervention outweigh the risks. The Cass Review has made it clear that the evidence base for the safety and effectiveness of puberty blockers is extraordinarily weak, and that their risks are significant. Existing studies suggest serious concerns, including negative impacts on bone density, cognitive development, and future sexual function. Further, over 95 per cent of children started on a medical pathway will proceed to cross sex hormones and many to surgical intervention. Thus starting any child on PBs is freighted with that knowledge, and of course the ethical implications of that knowledge. To be clear, the prescription of puberty blockers in the context of a trial would, in effect, introduce a known risk of systemic physical harm to a physically healthy child. To put it mildly, this is a divergence from normal clinical trial practice. One of the core principles of medical research is that a clinical trial must seek to answer a question that cannot be resolved by other means. Yet in the case of puberty blockers, safer research avenues remain unexplored. We should be conducting robust long-term follow-up studies of those who have already undergone such treatment, qualitative research into the experiences of the growing numbers of detransitioners, and further animal studies to understand the biological impact of these drugs on adolescent brain development. Another major ethical concern is the question of informed consent. Children under 16 cannot legally provide informed consent for a Clinical Trial of an Investigational Medicinal Product, meaning that parental consent would be required. Yet, given the politicised environment surrounding gender identity, it is difficult to see how true informed consent can be obtained. For example, parents, subjected to trans activist narratives claiming that refusal to provide puberty blockers increases their child's risk of suicide, will not be in a position to make a free and uncoerced decision. The argument that puberty blockers prevent suicide is completely unsubstantiated. For example, a recent Finnish study found no significant difference in suicide rates among youth diagnosed with gender dysphoria when adjusted for mental health comorbidities. In the UK, Professor Louis Appleby, the leading authority on suicide prevention, has called for caution on the use of false assertions as regard risk of suicide in this group . Informed consent is meaningless when it is obtained under conditions of misinformation and fear. There are moments in medical history when the imperative to 'pause and reflect' must override the drive to push forward. Now is one such moment. Given the absence of an established safety profile, the lack of high-quality evidence supporting their efficacy, and the well-documented risks, any such trial would violate our ethical and regulatory frameworks. The medical community, politicians, and regulators need to draw a line under this scandalous piece of medical history. Instead of experimenting on confused children with medical interventions that do more harm than good, we should be dedicating our resources to understanding and addressing the root causes of gender distress, researching psychosocial treatments and following up on the 9,000 children who went through Gids. Let us not repeat mistakes of the past. Dr David Bell is a retired consultant psychiatrist and was a Governor of the Tavistock and Portman NHS Foundation Trust Broaden your horizons with award-winning British journalism. Try The Telegraph free for 1 month with unlimited access to our award-winning website, exclusive app, money-saving offers and more.
Telegraph
06-03-2025
- Health
- Telegraph
Why I'm sounding the alarm on the next puberty blockers scandal
Few issues in contemporary medicine have generated as much controversy as the use of puberty blockers in gender distressed children. The Government, responding to the findings of the Cass Review, has rightly banned the prescription of these drugs. Many other countries have, too. However the Government last week announced an £11 million clinical trial of these medicines to gather evidence of their effects. This raises a fundamental question: can a clinical trial of puberty blockers on children experiencing gender distress be done ethically? The answer, upon scrutiny, is a resounding 'no'. I have witnessed firsthand the grave dangers posed by the rush to medicalise childhood gender distress. As a former psychiatrist at the Tavistock and Portman NHS Trust, I was one of the whistleblowers who raised concerns about the practices at the now shuttered Gender Identity Development Service (Gids). What we uncovered was a service driven more by ideology than by robust clinical reasoning. Many distressed children, often same-sex attracted and with autistic comorbidities, were put on a medical pathway to transition by some clinicians who had been captured by 'trans' ideology and, as a result, cast aside ordinary sound clinical judgment. A clinical trial risks repeating these ethical failures. These trials are governed by rigorous ethical and legal standards, designed to protect participants from harm. The foundation of these standards is the Declaration of Helsinki, alongside the Good Clinical Practice guidelines and the UK's Medicines for Human Use (Clinical Trials) Regulations. These frameworks exist to ensure that the benefits of any new medical intervention outweigh the risks. The Cass Review has made it clear that the evidence base for the safety and effectiveness of puberty blockers is extraordinarily weak, and that their risks are significant. Existing studies suggest serious concerns, including negative impacts on bone density, cognitive development, and future sexual function. Further, over 95 per cent of children started on a medical pathway will proceed to cross sex hormones and many to surgical intervention. Thus starting any child on PBs is freighted with that knowledge, and of course the ethical implications of that knowledge. To be clear, the prescription of puberty blockers in the context of a trial would, in effect, introduce a known risk of systemic physical harm to a physically healthy child. To put it mildly, this is a divergence from normal clinical trial practice. One of the core principles of medical research is that a clinical trial must seek to answer a question that cannot be resolved by other means. Yet in the case of puberty blockers, safer research avenues remain unexplored. We should be conducting robust long-term follow-up studies of those who have already undergone such treatment, qualitative research into the experiences of the growing numbers of detransitioners, and further animal studies to understand the biological impact of these drugs on adolescent brain development. Another major ethical concern is the question of informed consent. Children under 16 cannot legally provide informed consent for a Clinical Trial of an Investigational Medicinal Product, meaning that parental consent would be required. Yet, given the politicised environment surrounding gender identity, it is difficult to see how true informed consent can be obtained. For example, parents, subjected to trans activist narratives claiming that refusal to provide puberty blockers increases their child's risk of suicide, will not be in a position to make a free and uncoerced decision. The argument that puberty blockers prevent suicide is completely unsubstantiated. For example, a recent Finnish study found no significant difference in suicide rates among youth diagnosed with gender dysphoria when adjusted for mental health comorbidities. In the UK, Professor Louis Appleby, the leading authority on suicide prevention, has called for caution on the use of false assertions as regard risk of suicide in this group . Informed consent is meaningless when it is obtained under conditions of misinformation and fear. There are moments in medical history when the imperative to 'pause and reflect' must override the drive to push forward. Now is one such moment. Given the absence of an established safety profile, the lack of high-quality evidence supporting their efficacy, and the well-documented risks, any such trial would violate our ethical and regulatory frameworks. The medical community, politicians, and regulators need to draw a line under this scandalous piece of medical history. Instead of experimenting on confused children with medical interventions that do more harm than good, we should be dedicating our resources to understanding and addressing the root causes of gender distress, researching psychosocial treatments and following up on the 9,000 children who went through Gids. Let us not repeat mistakes of the past. Dr David Bell is a retired consultant psychiatrist and was a Governor of the Tavistock and Portman NHS Foundation Trust
New York Times
06-02-2025
- Health
- New York Times
Abandoned in the Middle of Clinical Trials, Because of a Trump Order
Asanda Zondi received a startling phone call last Thursday, with orders to make her way to a health clinic in Vulindlela, South Africa, where she was participating in a research study that was testing a new device to prevent pregnancy and infection. The trial was shutting down, a nurse told her. The device, a silicone ring inserted into her vagina, needed to be removed right away. When Ms. Zondi, 22, arrived at the clinic, she learned why: The U.S. Agency for International Development, which funded the study, had withdrawn financial support and had issued a stop-work order to all organizations around the globe that receive its money. The abrupt move followed an executive order by President Trump freezing all foreign aid for at least 90 days. Since then, the Trump administration has taken steps to dismantle the agency entirely. Ms. Zondi's trial is one of dozens that have been abruptly frozen, leaving people around the world with experimental drugs and medical products in their bodies, cut off from the researchers who were monitoring them, and generating waves of suspicion and fear. The State Department, which now oversees U.S.A.I.D., replied to a request for comment by directing a reporter to which no longer contains any information except that all permanent employees have been placed on administrative leave. Secretary of State Marco Rubio has said that the agency is wasteful and advances a liberal agenda that is counter to President Trump's foreign policy. In interviews, scientists — who are forbidden by the terms of the stop-work order to speak with the news media — described agonizing choices: violate the stop-work orders and continue to care for trial volunteers, or leave them alone to face potential side effects and harm. The United States is signatory to the Declaration of Helsinki that lays out ethical principles under which medical research must be conducted, requiring that researchers care for participants throughout a trial, and report the results of their findings to the communities where trials were conducted. Ms. Zondi said she was baffled and frightened. She talked with other women who had volunteered for the study. 'Some people are afraid because we don't know exactly what was the reason,' she said. 'We don't really know the real reason of pausing the study.' The stop-work order was so immediate and sweeping that the research staff would be violating it if they helped the women remove the rings. But Dr. Leila Mansoor, a scientist with the Centre for the AIDS Programme of Research in South Africa (known as CAPRISA) and an investigator on the trial, decided she and her team would do so anyway. 'My first thought when I saw this order was, There are rings in people's bodies and you cannot leave them,' Dr. Mansoor said. 'For me ethics and participants come first. There is a line.' In the communities where her organization works, people have volunteered for more than 25 years to test H.I.V. treatments, prevention products and vaccines, contributing to many of the key breakthroughs in the field and benefiting people worldwide. That work relied on a carefully constructed web of trust that has now been destroyed, Dr. Mansoor said. Building that trust took years in South Africa where the apartheid regime conducted medical experiments on Black people during the years of white rule. Those fears are echoed in a long history of experimentation by researchers and drug companies in developing countries and in marginalized populations in the United States. The Times identified more than 30 frozen studies that had volunteers already in the care of researchers, including trials of: It is difficult to know the total number of trials shut down, or how many people are affected, because the swift demolition of U.S.A.I.D. in recent days has erased the public record. In addition to the disabled website, the agency no longer has a communications department. And the stop-work order prohibits any implementing agency from speaking publicly about what has happened. In England, about 100 people have been inoculated with an experimental malaria vaccine in two clinical trials. Now, they no longer have access to the clinical trial staff if that vaccine were to cause an adverse reaction in their bodies. The trial is an effort to find a next-generation vaccine better than the one now used in Africa; that shot protects children against about a third of malaria cases, but researchers hoped to find a vaccine that offered much more protection. Malaria remains a top global killer of children; 600,000 people died of the disease in 2023, the latest figure available. Had the trial not been frozen, the participants would be coming to a clinic routinely to be monitored for adverse physical effects, and to have blood and cell samples taken to see whether the vaccine was working. The participants are meant to be followed for two years to assess the vaccine's safety. A scientist who worked on the trial said she hoped that partners at the University of Oxford, where it was being conducted, were shuffling staff to respond if any participant fell ill. But she was fired last week and no longer has access to any information about the trial. She spoke on condition of anonymity because she feared jeopardizing her ability to work on malaria research the U.S. might conduct in the future. 'It's unethical to test anything in humans without taking it to the full completion of studies,' she said. 'You put them at risk for no good reason.' Had the stop-work order come later this year, the newly-vaccinated volunteers might have been in an even more precarious position. They were scheduled to be deliberately infected with malaria to see if the experimental vaccine protected them from the disease. Dr. Sharon Hillier, a professor of reproductive infectious diseases at the University of Pittsburgh, was until this week director of a five-year, $125 million trial funded by U.S.A.I.D. to test the safety and efficacy of six new H.I.V. prevention products. They included bimonthly injections, fast-dissolving vaginal inserts and vaginal rings. With the study suspended, she and her colleague cannot process biological samples, analyze the data they have already collected, or communicate findings to either participants or the partnering government agencies in countries where the trials were conducted. These are requirements under the Helsinki agreement. 'We have betrayed the trust of ministries of health and the regulatory agencies in the countries where we were working and of the women who agreed to be in our studies, who were told that they would be taken care of,' Dr. Hillier said. 'I've never seen anything like it in my 40 years of doing international research. It's unethical, it's dangerous and it's reckless.' Even trials that were not funded in whole or part by U.S.A.I.D. have been thrown into turmoil because they were using medical or development infrastructure that was supported by the agency and is no longer operational. Millions of dollars of U.S. taxpayer funds already spent to start those trials will not be recuperated. The shutdowns have business consequences as well. Many of those trials were partnerships with U.S. drug companies, testing products they hoped to sell overseas. 'This has made it impossible for pharmaceutical companies to do research in these countries,' Dr. Hillier said. Another H.I.V. trial, called CATALYST, has thousands of volunteers in five countries testing an injectable drug called long-acting cabotegravir. Participants were receiving bimonthly injections to maintain a sufficient level of the drug in their bodies to prevent H.I.V. infection. Without regular injections, or a carefully-managed end to use of the drug, the participants will not have enough cabotegravir to stop a new infection, but there will be enough in their systems that, if they were to contract the virus, could easily mutate to become drug-resistant, said Dr. Kenneth Ngure, president-elect of the International AIDS Society. This is a significant threat to the trial volunteers and also to the millions of people living with H.I.V. because cabotegravir is closely related to a drug that is already used worldwide in standard treatment of the virus. Development of resistance could be catastrophic, Dr. Ngure said: 'It's wrong on so many levels — you can't just stop.' A clinical trial run by the development organization FHI 360, which implemented many U.S.A.I.D.-funded health programs and studies, was testing a biodegradable hormonal implant to prevent pregnancy. Now there are women in the Dominican Republic with the devices in their bodies without continuing care. Another trial, in Uganda, was testing a new regimen of tuberculosis treatment for children. The stop-work order cuts those children off from potentially lifesaving medication. 'You can't walk away from them, you just can't,' a researcher in that trial said.
