Introduction
Research is a key pillar of scientific progress. Through research, scholars and scientists are able to gain insights into a wide range of important issues. While research is important, it also presents some risks. For example, when conducting research, scholars may expose the participants to some health risks. To ensure that research is conducted in a proper fashion, ethical guidelines have been developed. These guidelines outline the procedures and measures that researchers should adhere to. Thanks to the guidelines, the welfare of the participants in research is guaranteed. It is unfortunate that some of these guidelines were developed in response to unethical research practices. The clinical trials that were carried out in the 1990s on pregnant women in Thailand and Sub-Saharan Africa are among the events that prompted the development of stricter ethical guidelines. These trials challenged the research community to prioritize the welfare of participants and to protect vulnerable communities against exploitation. More importantly, the controversy that arose from the trials underscores the need for stricter ethical guidelines that govern human clinical research. Summary of research project
The primary purpose of this research project is to explore the ethical issues that arose from the clinical trials introduced above. The project focuses on how the researchers in these trials violated the rights and compromised the wellbeing of the participants. Particular attention is given to the importance of shielding participants against health risks. The project also examines the need for researchers to be indiscriminate and fair in their selection of participants. As the literature review and the subsequent discussion will reveal, the researchers in these trials preyed on vulnerable women who could not speak out to demand that their rights be respected. Overall, this research project aims to challenge the research community to always adhere to ethical guidelines when conducting trials that involve human subjects.
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Literature review
The clinical trials that were conducted in the 1990s involved pregnant women who were HIV positive in Thailand and such Sub-Saharan countries as Uganda, South Africa, Cote d’Ivoire and Burkina Faso (Cunningham, 1994). The purpose of these trials was to examine the impact that the regimen of a drug called zidovudine had on the risk of transmission of HIV from a mother to her unborn child. The ethical concerns that these trials elicited have been the subject of much scholarly debate and discussion. Jennifer Hawkins and Ezekiel Emanuel are among the scholars who have offered their thoughts on the ethical status of the trials. In their discussion, they argue that these trials amounted to an exploitation of vulnerable women who endure such challenges as poverty and desperation (Hawkins & Emanuel, 2008). The researchers behind the trials appear to have deliberately selected powerless women who would not object to the trial. These women desperately wished to shield their unborn children against HIV. Their desire to safeguard the health of their children compelled them to issue consent to participate in the trials. It is evident that the desperate situation that the women faced impaired their judgment. Therefore, the consent that they gave cannot be considered valid.
The controversy surrounding the AZT trials extended beyond the questions about the validity of the consent that the women issued. The use of placebo is another issue that stirred controversy. At the time that the trials were being conducted, the Helsinki Declaration which contained ethical guidelines for research involving human participants stipulated that when carrying out research, researchers should provide their participants with the best available treatment (Nwabueze, 2016). Even before the trials were conducted, it had long been established that the AZT intervention was effective in the reducing mother-to-child infections. Therefore, adhering to the ethical guidelines, the researchers carrying out the trials should have provided all the women participating in the trials with AZT. This did not happen as a number of women were placed in the placebo group (Lie, 1998). It was reported that some of the women in the placebo group died during the trial. It is important to note that the parties that funded and conducted the trials vehemently defended the design. For example, in a letter to the editor of the New England Journal of Medicine, Michael Merson defended the inclusion of women in the placebo group. He provides a number of justifications for the creation of this group. He argues that the placebo group was created because the researchers lacked any information regarding the impact of the regimen on breast-feeding women and women who are anemic (Merson, 1998). Merson added that the placebo group was intended to justify the expenditure resulting from the trials and that thanks to the design of the trials, it would be possible to obtain insights that could be applied to a larger population (Merson, 1998). The justifications that Merson offered appear valid and sound. His arguments underscore the complexity of the debate on the ethical issues in the trials. It is nearly impossible to determine if the trials were entirely unethical especially when one considers the helpful insights that the trials delivered.
The arguments that Merson raised are indeed sound and reasonable. However, for a more balanced perspective, it is important to consider the views of those who found the trials to be unethical. James McIntyre is among those who condemned the researchers for designing the trials poorly. He notes that the researchers denied the participants who were in the placebo group access to treatment that had been found to be effective in reducing mother-to-child infection (McIntyre, 1998). McIntyre goes as far as likening these trials to the Tuskegee Syphilis trials. In the Tuskegee trials, the researchers withheld treatment from the participants. Dozens of the participants succumbed to the disease. McIntyre is not a lone voice in his condemnation of the trials. Claire Wendland joined him in criticizing the researchers for placing some participants in the placebo group. She contends that the researchers violated the ethical guideline that stipulates that participants should be provided with the best available treatment (Wendland, 2008). Wendland adds that the trials went beyond a violation of ethical guidelines. She argues that these trials perpetuated inequalities of resources and power ( Wendland, 2008 ). There appears to be some consensus within the scholarly community that the placebo group amounted to a violation of ethical guidelines. The researchers carrying out the trials either overlooked or disregarded the ethical provision that they needed to ensure that all participants are provided with the best available treatment.
In an earlier discussion, it was argued that the researchers conducting the HIV trials were essentially exploiting poor and powerless women in developing countries. This argument remains valid. However, it is helpful to consider the defenses that the researchers gave to tackle the narrative that their actions amounted to an exploitation of the women. The researchers held that these women would never be able to access the treatment that they offered (Skolnik, 2015). They added that before conducting the trials, they obtained the informed consent of the women. The researchers added that the developing countries were selected because they were the most appropriate. In the developed world, it had been established that the AZT regimen was indeed effective in preventing mother-to-child infection of HIV. However, the adoption of this regimen proved too complex and costly for developing countries (Skolnik, 2015). This prompted the researchers to develop a simpler version of the regimen which was then offered to the participants in Thailand and the sub-Saharan countries. Essentially, the researchers contended that without their intervention, the women would be left to their own devices. They basically argued that the trials did more good than harm.
Joining forces with Wolfe, Lurie penned a thought-provoking article in which he condemns the clinical trials carried out in Thailand and Sub-Saharan Africa. While they recognize that the trials delivered gains for developing countries, they reiterate that the researchers violated ethical guidelines that govern biomedical research. They state that they “ oppose the use of placebo-controlled trials as unethical in the search for alternative antiretroviral drug regimens to prevent the perinatal transmission of HIV” (Lurie & Wolfe, 1997, p. 853). In addition to shedding light on the inappropriateness of including a placebo group in the study, Wolfe and Lurie also discuss the double standards in the application of ethical principles and guidelines. They suggest that the researchers disregarded ethical guidelines because the participants were from poor countries. They state that “ an urgent need exists to develop and adhere to a universally recognized code of ethics for medical research upon human subjects” (Lurie & Wolfe, 1997, p. 853). Marcia Angell (1997) joins Lurie and Wolfe in criticizing the researchers behind the HIV trials. She takes particular issue with the defenses that the researchers offered and went as far as comparing the trials with the Tuskegee trial. She stated that “ some of the same arguments that were made in favor of the Tuskegee study many years ago are emerging in a new form in the AZT studies in the third world” (Stolberg, 1997). Angell’s outrage is indeed justified since the researchers denied dozens of women treatment that could have shielded their unborn children against HIV infection. According to Angell (1997) investigators are required to ensure that human subjects are not made subordinate to the welfare of a study’s objectives, but the trial in question violated this ethical code. Meghan Landes (2005) shared the sentiments that Lurie, Wolfe and Angell expressed. In her article, she criticizes the scholars for double standards and violating the rights of the subjects. She notes that these researchers disregarded the gold standard that is used in human biomedical research. Landes (2005) proceeded to argue that the mere fact that the researchers faced challenges with resources does not justify the violations that they committed. When combined with the views that the other scholars express, Landes’ arguments make it clear that the clinical trials were a flagrant violation of ethical guidelines.
The discussion above has given much focus to the arguments that scholars have raised against the HIV clinical trials. For a more comprehensive and fair discussion, it is important to include the thoughts of those who endorse the trials. The researchers who conducted the trials are among their strongest supporters. In an article in which they outline how the trial was carried out and the results, they note that the AZT regimen was effective in reducing mother-to-child infections. They conclude that “ In pregnant women with mildly symptomatic HIV disease and no prior treatment with antiretroviral drugs during the pregnancy, a regimen consisting of zidovudine given ante partum and intra partum to the mother and to the newborn for six weeks reduced the risk of maternal-infant HIV transmission by approximately two thirds” (Connor et al., 1994, 1173). While they do not explicitly address the ethical concerns that their trial raised, the conclusion that the researchers arrive at is essentially an endorsement of the trial and dismissal of the ethical concerns.
Ethical concerns are not the only issue that the clinical trials provoked. These trials also elicited legal responses. A number of local and international organizations responded to the trials through revisions to their legal guidelines. For example, the Declaration of Helsinki underwent some changes in the wake of the controversy resulting from the trials. Previously, these guidelines required researchers to use local standards when carrying out trials (Pavone, 2016). These standards varied by region and offered participants from different places varying levels of protection. To ensure uniformity and to safeguard the wellbeing of all human subjects, the Declaration of Helsinki adopted a gold standard (Pavone, 2016). This standard applies to all clinical trials that involve human subjects. The European Union also made changes to its guidelines in response to the clinical trials. This organization adopted rules and regulations that governed how medical products developed in third world countries are developed (Pavone, 2016). The Council of Europe and UNESCO are some of the other organizations that have adopted stricter guidelines to ensure that human subjects recruited in clinical trials are not exposed to any harm. The response from these organizations suggests that the global community finds that the researchers violated ethical guidelines. With the stricter guidelines now in place, it is hoped that clinical trials will always safeguard the health and overall wellbeing of human subjects.
Discussion
The literature review offered above has revealed that there are deep divisions within the scholarly community regarding the ethical issues in the HIV clinical trials. To settle the debate and provide a way forward, it is helpful to consult ethical guidelines that govern clinical trials that recruit human subjects. Informed consent is among the issues that these guidelines shed light on. Before conducting a clinical trial, researchers are required to obtain consent from the participants (Nardini, 2014). They should inform the participants that they are taking part in the trial. The researchers should not deceive the participants. For example, it is unethical to secure consent from participants through the promise of a cure. Various standards have been adopted to assess the validity of consent. For consent to be considered valid, the subject must be competent, informed and acting voluntarily (Nardini, 2014). When these standards are applied to the participants in the HIV clinical trials, it becomes evident that the consent was not valid. One can argue that the participants were neither competent nor expressing themselves voluntarily. Poverty and a desperate desire to protect their children robbed them of independence and objectivity. Therefore, the researchers violated the ethical guideline that requires informed consent.
Another ethical guideline that is relevant to the HIV clinical trials concerns use of placebo. Placebos are standard in many clinical trials. They allow the researchers to establish that the intervention under investigation is indeed responsible for the observed outcomes (Nardini, 2014). However, ethical guidelines limit the use of placebos. The problem with placebos is that they amount to a deception. Ethical guidelines require that researchers maintain transparency at all times. When they introduce a placebo group, the researchers essentially withhold information from the subjects (Nardini, 2014). The researchers in the HIV clinical trials can be accused of having deceived the participants. The women participating in the study understood that they would be provided with treatment. Another issue that makes the use of placebos contentious is the risk that the participants could suffer harm (Nardini, 2014). Those placed in the treatment group are guaranteed of positive outcomes while those in the placebo group stare at the threat of harm. This was indeed the case in the HIV clinical trials. Since the AZT intervention helped to prevent HIV infection from mother to child, it is fair to expect that those in the placebo group transferred the infection to their children.
Protection of subjects without compromising the integrity of a clinical trial is yet another ethical issue that surrounds research with human subjects (Nardini, 2014). The Helsinki Declaration is among the authorities on the ethics of clinical research. One of the key provisions of this policy document is that “ the wellbeing of the individual research subject must take precedence over all other interests” (Nardini, 2014). This provision is primarily aimed at protecting participants in developing countries. In these countries, strict and tight regulations and ethical guidelines that secure participants are lacking (Nardini, 2014). It is clear that the researchers behind the HIV clinical trials exploited the lack of stringent ethical guidelines in the developing countries. In defending their decisions, the researchers argued that the findings from the trials presented benefits that far outweighed the risks and harm that the subjects faced. While this argument sounds valid, it falls short of the requirements stipulated in the Helsinki Declaration. According to this declaration, the welfare of the participants should never be sacrificed. The mere fact that the clinical trials helped to establish that the AZT intervention was effective does not justify the poor design of the trial. Therefore, the clinical trials violated various ethical guidelines. While these trials offered vital insights, the world cannot and must not forget that the researchers flouted ethical guidelines.
When conducting clinical trials, researchers have an obligation to secure the wellbeing of the participants (Nijhawan et al., 2013). This obligation includes providing the participants with treatment as needed. The researchers conducting the HIV clinical trials clearly disregarded this obligation. It has been established from the discussion this far that the AZT intervention held promise. All the participants stood to gain when provided with the treatment. The researchers’ unwise and unacceptable decision to place some of the participants in the placebo group meant that these participants could not benefit from the AZT treatment. Therefore, the researchers abandoned their duty to protect the health of the subjects.
Personally, I appreciate the complexity of the ethical debate arising from the clinical trials. I understand that the researchers simply aimed to confirm that the short course AZT intervention was effective. I also recognize that the researchers set out to make this treatment affordable and accessible to the thousands of poor HIV positive women in the developing countries. While their intentions may have been pure and noble, it is difficult to forget that these researchers flouted and disregarded ethical provisions. These researchers clearly preyed on vulnerable women. The women were poor, uneducated and vulnerable. They were the perfect target for a group of researchers that did not wish to be bound by ethical principles and guidelines. The researchers also failed to protect the women. They placed some of the women in the placebo group despite understanding full well that the AZT intervention worked and would deliver benefits to all the subjects. All in all, the actions of the researchers are unacceptable and must never be repeated. The fact that the outcomes of the clinical trials were positive is not enough to redeem the researchers. As they conduct clinical trials with human subjects, researchers need to remember that the welfare of the subjects should always take precedence. Nothing, not even gains for the entire society should ever be pursued at the expense of the wellbeing of human subjects.
Conclusion
Today, the research community has invested greater effort in updating its ethical guidelines. This community has learnt from mistakes made in the past. The HIV clinical trials that were conducted in the 1990s are among the mistakes that have provided the research community with lessons. Thanks to these trials, the community now recognizes that the wellbeing of participants should never be compromised. The trials have also challenged the research community to be objective, fair and unbiased. As they select the participants, researchers need to avoid conveniently targeting vulnerable populations which lack any significant power or protections. Advances in research and science are meaningless if they occur at the expense of individuals. Therefore, going forward, researchers should uphold all relevant ethical principles, standards and guidelines.
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