Many of the articles this week criticize the use of strictly regulated clinical trials for being unable to treat research subjects as members of unique communities, or fully evaluate the holistic impact of a drug or intervention on a community. Simultaneously, authors like Adriana Petryna in Ethical Variability argue that the ethical standards used for research subjects in developing nations differ from those in developed nations, and she alludes to the need to implement further regulatory practices to equitize the way human subjects are treated.

I would argue that to ensure all populations are treated ethically, regulations for trials intended to create reproducible results need to be even more strict than they are now. For example, in almost no circumstances should for-profit companies be given regulatory passes, or be allowed to follow different ethical standards during situations of humanitarian crisis, becuase too often these situations are used to exploit suffering populations further. For example, when Pfizer wanted to expedite FDA approval of Trovan in 1996, they were able to successfully take advantage of a meningitis outbreak in Nigeria to conduct faster clinical trials by ignoring getting patient consent and giving their experimental pill to Nigerians who did not know they had safe and proven alternatives available to them (Petryna, 2013). Ultimately, the use of an expedited clinical process resulted in an easy way for Pfizer to hide evidence that Trovan causes severe liver damage (Petryna, 2013). Additionally, Dr. Chan of the WHO denounced how pharmaceutical companies handled developing an Ebola vaccine, claiming that there is no vaccine because “a profit-driven industry does not invest in products for markets that cannot pay” (Gladstone, 2014). Furthermore, she noted that it is subjects in the United States who were initially targeted to be the subjects for upcoming vaccines, rather than those in developing nations. This is problematic since subjects for risky clinical trials are almost always recruited from developing countries, but are unable to benefit from this vaccine that could immediately directly benefit those citizens.

Rather, if a situation is severe enough that it requires expedited processes, third party organizations that are not-for-profit should be used for conducting trials when removing certain regulations. It is not in any sense altruistic for a for-profit company to perform legally required trials in cheap areas of the world, regardless of the humanitarian need or perceived benefit in the local community, and FDA regulations should reflect this reality by ensuring that pharmaceutical companies are treating subjects the same way they would in any developed nation. It is far too naive to assume a for-profit company is acting out of humanitarian obligation, and thus the use of scrutinized trials and regulations are necessary, no matter how impersonal. Randomized clinical trials (RCTs) are considered “the gold standard” of research methods because they prove an outcome is not due to chance, and are designed to avoid observer bias (Adams, 2013). RCTs are absolutely necessary for any drug, treatment, or intervention intended to be replicated on a large scale, especially those done by  for-profit entities. Of course, RCTs will not report on many unintended consequences, but there is no guarantee unstructured observation will either.

The larger question is, how often is it preferable not to create interventions that are replicable on a mass scale? It is crucially important to recognize that the most beneficial health interventions are often purposefully tailored to a specific community and culture, and are not intended to be reproducible in other contexts around the globe. In When People Come First, Vincanne Adams talks about how problematic it has become that showing that a study is reproducible is more important than showing an intervention positively impacts health. In settings in which non-profits are performing health interventions or responding to humanitarian crises, it is essential that time, money, and health outcomes not be jeopardized by turning interventions into research studies.
In an increasingly for-profit sphere, money intended to go towards impacting communities is instead going into designing and proving the effectiveness of interventions as research studies. There is often a mandate to turn interventions into research, and hire research and consulting firms and for-profit NGOs, as well as purchase expensive ‘reliable’ assessment instruments in order for an intervention to be seen as credible. While cost-effectiveness analysis should never be the only justification for performing an intervention, it is clear in this situation that performing an RCT would be a much more inefficient use of money in the short-term. In the long-term, if we understand that different communities have individual needs, interventions must constantly evolve, so a specific RCT would not be cost-effective in the long-term either. Ultimately, nonprofit interventions should only be designed to have the most beneficial local impact, while for-profit interventions should be intensely regulated no matter the humanitarian need.

Sources:

Biehl, João Guilherme., and Adriana Petryna. “Evidence-Based Global Public Health.” When People Come First: Critical Studies in Global Health. Princeton: Princeton UP, 2013. Print.

Petryna, Adriana. “Ethical Variability: Drug Development and Globalizing Clinical Trials.” American Ethnologist 32.2 (2005): 183-97. Print.

Gladstone, Rick. “W.H.O. Assails Delay in Ebola Vaccine.” The New York Times. 03 Nov. 2014. Web.

Discussion Questions:

1. Should global health interventions and responses to humanitarian crises be regulated differently in situations in which for-profit companies and non-profit companies are performing global health work?
2. Is it always justified for nonprofit humanitarian global health work to avoid using the research methods of randomized controlled trials (RCTs)? Do RCTs offer substantial benefits when evaluating global health work?
3. Ultimately does turning a health intervention into a controlled research trial create an inherent tension of academic good and rigour vs. social benefit, as Petryna suggests?

As we have seen continuously through our study of global health, healthcare provided by a foreign organization in a developing country affects and is affected by the local culture to a great extent. We have studied the necessity of expecting the unexpected when it comes to the possible consequences of our actions. We have learned about the ways in which cultural sensitivity and understanding have not been adopted in past interventions, thereby permanently changing perceptions of the West and sometimes negatively affecting communities an that intervention had intended to help. The readings about clinical trials in the global sphere, and the ways in which pharmaceutical companies have both benefited as well as manipulated populations in “drug-naïve” regions, are prime examples of these concepts.

Another theme we have considered in our readings and discussions has been losing sight of the people we are trying to help. Modern day methods of creating interventions rely mostly on numerical or statistical credibility, and it has caused many to ignore the humanity of the lives in question. Chapter two of When People Come First, entitled ‘Evidence-Based Global Public Health,’ illustrates the shortcomings of evidence-based medicine (EBM) and evidence based public health (EBPH) interventions. In the modern landscape of health interventions, lack of statistical evidence is equal to a lack of reliability in terms of the potential success or failure of a given intervention (Biehl and Petryna, 2013). Even so, without EBM, the safety of many treatments could not be determined with certainty. Though it could change the outlook and the questions asked, it is ultimately necessary for EBM work to be done to insure efficacy and safety. It is, however, also necessary to do qualitative studies that examine the greater social contexts and effects of interventions, and without those studies, we are missing vital pieces of information that could be used to better actuate change.

The readings all present a few reasons why global clinical trials and EBM are positive; however, they mostly discuss failures and problems with these recent developments in global health. Looking only at the three assigned readings, it is easy to become cynical about the involvement of pharmaceutical companies in global health, taking ethical advantage of needy populations for their own economic gain. In her article ‘Ethical Variability: Drug Development and the Globalization of Clinical Trials,’ Adriana Petryna talks about Chernobyl and the manner in which the crisis was taken advantage of politically, and subsequently scientifically. Those who wanted to experiment with therapies for the horrific damage that was caused by the nuclear accident were welcomed in by the Soviet Union’s leaders, casting all questions of the ethics of these studies aside in the name of aid. Petryna questions the ethics of these decisions made in times of crisis, and laments the variability in the reasoning behind them. While there are different reactions necessary to different crises, she argues that the underlying moral code of the regulation surrounding clinical trials should not allow for such variability (Petryna, 2005).

Today, though the FDA and other U.S. agencies cannot regulate trials in other countries, pressure from humanitarian organizations as well as the general public causes pharmaceutical companies to act in a less variable manner when performing research abroad. Clinical trials performed abroad also will not get the approval of the U.S. or other Western countries if done in a manner that is explicitly harmful. Of course, as the Leach and Fairhead article demonstrates, interventions or clinical trials can change the “therapeutic landscape” of a place forever. The ways in which people had previously experienced health and health care in Sukuta in the Gambia was permanently altered, shifting cultural paradigms and values. Though this particular intervention was mainly beneficial to the community, the consequences of it, and other similar projects, appear to be almost in the vein of colonialism—both invasive and patriarchal, insensitive to whatever structures or beliefs are already in place in a community.

Though there have been some sickening and disastrous outcomes from corporate involvement in global health—often from what is nominally humanitarian or philanthropic work—there have been many positive outcomes in recent years. During the Ebola epidemic this past year, many Western pharmaceutical companies jumped into action, quickly creating possible vaccines and launching animal and then human trials as fast as possible. What selfish motive could these companies have had in working to create vaccines for people at extremely high risk for a devastating disease? Yes, it would help their image, create positive PR, give people cause to stop hating “big pharma” as an impenetrable anathema, etc. However, these companies were at the forefronts of the effort because they had the money to back the research and the resources  ready to be mobilized for serious innovation. In their press release about the Ebola vaccine being tested, Johnson and Johnson lists organizations like Direct Relief International, Partners in Health, and other NGOs as organizations they are working with. Collaboration between the public and private sector is increasingly prevalent and is more successful than either one working without the other. While NGOs may have more expertise in countries of interest, pharmaceutical companies have the innovation and technology that is the basis of many interventions. The three vaccines shown in this image have all gone through Phase I clinical trials in Sierra Leone, Liberia, and Guinea, with mostly positive results. Can we really say that they took advantage of people in the developing world for completely selfish reasons when the outcome was not merely for their gain?

A 2015 article in the Journal of Medical Ethics ‘Can Informed Consent to Research be Adapted to Risk?’ discusses the question of consent in different contexts, and how it can be improved to fit different research situations better.First and foremost, the article sets down the importance of consent: “Autonomy rights protect competent adults from unwanted interference and they also give them the opportunity to live their lives in accordance with their own interests, preferences and values” (Bromwich and Rid, 2014). The article states that as risk to participants in a study increases, the l consent of a patient becomes less meaningful. When performing studies, at home or abroad, language and literacy are a huge barrier between scientists and patients. As much as interventions and medications can be simplified, what details are being lost in this simplification? How can communication of risks and benefits be enhanced, and how can we ensure that these conversations are always clear on the part of the investigator as well as understood by the patient? Articles like this one are not uncommon in today’s medical and public health journals, and the way in which hulking industries and corporations, especially those coming from the West, are now treating issues like consent has become extremely visible. It seems to me that one of the more difficult issues in global clinical trials is no longer a question of blatant human rights violations, but rather more subtle consequences to the communities that participate in these trials. Though these consequences may often be unintended, at what point, in a world where cultural and anthropological knowledge is very available to those who trouble themselves to look, do these things become the result of calculated carelessness?

A qualitative study performed in Kenya in 2005, surrounding clinical trials for HIV/AIDS treatments, used focus groups to gain an in-depth understanding of the needs of participants. The study joins a large body of work on how to make clinical trials more beneficial to those who participate as well as reducing any potential long-term damage to communities. This, along with anthropological work like that of Biehl and Petryna, gives me hope for the future of clinical trials, so that, under the public eye, innovation will no longer come at the expense of vulnerable populations. However, many questions are still unanswered about the current state of medical research and the ethics and methods surrounding it. Scientists and companies that do not move forward in a humanistic way, considering the impacts of their actions down the road, may still do harm until more clearly agreed upon standards arrive.

Sources:

1. Agnandji, S. T., et al. “Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe — Preliminary Report.” The New England Journal of Medicine (2015): n. pag. The New England Journal of Medicine. Web. 9 Nov. 2015.<http://www.nejm.org/doi/full/10.1056/NEJMoa1502924#t=abstract>.
2. Berkowitz, Bonnie, and Patterson Clark. “How Trials Will Work for Ebola Vaccines.” The Washington Post. N.p., 8 Feb. 2015. Web. 9 Nov. 2015.<https://www.washingtonpost.com/apps/g/page/world/how-trials-will-work-for-ebola-vaccines/1594/>.
3. Bromwich, Danielle, and Annette Rid. “Can Informed Consent to Research Be Adapted to Risk?” Journal of Medical Ethics 41 (2015): 521-28. Print.
4. “Ebola vaccines, therapies, and diagnostics.” WHO. World Health Organization, 6 Oct. 2015. Web. 9 Nov. 2015.<http://www.who.int/medicines/emp_ebola_q_as/en/>.
5. “Johnson & Johnson Announces Start of Clinical Trial of Ebola Vaccine Regimen in Sierra Leone.” Johnson and Johnson. Johnson & Johnson Services, 9 Oct. 2015. Web. 9 Nov. 2015. <http://www.jnj.com/news/all/johnson-johnson-announces-start-of-clinical-trial-of-ebola-vaccine-regimen-in-sierra-leone>.
6. Leach, Melissa and James Fairhead. 2011. “Being ‘with the Medical Research Council’: Infant Care and the Social Meanings of Cohort Membership in Gambia’s Plural Therapeutic Landscapes.” In Evidence, Ethos and Experiment: The Anthropology and History of Medical Research in Africa. P. Wenzel Geissler and Catherine Molyneux, eds. New York: Berghahn Books.
7. Petryna, Adriana. 2005. “Ethical Variability: Drug Development and the Globalization of Clinical Trials.” American Ethnologist 32(2): 183-197.
8. Petryna, Adriana, and João Biehl, eds. When People Come First. Princeton: Princeton UP, 2013. Print.
9. Shaffer, D. N., et al. “Equitable Treatment for HIV/AIDS Clinical Trial Participants: A Focus Group Study of Patients, Clinician Researchers, and Administrators in Western Kenya.” Journal of Medical Ethics 32 (2006): 55-60.

Discussion Questions:

• What is the best way to create ethical standards that apply worldwide for clinical trials? Or at least reduce the variability in ethical decisions? Is this even practical?
• How can clinical trials be designed in a way that is beneficial to the health of populations in need, but not a cultural burden that follows in the footsteps of colonialism?

In the expansive organism of research regimes, a.k.a contract research organizations (CROs), there seems to be a baseline standard for which all research is considered “ethical”. As Petryna notes in Ethical Variability: Drug Development and the Globalization of Clinical Trials, “the ethical universe in which researchers operate [is] an essentially procedural one” with the basic but critical concerns of obtaining informed consent from subjects and assuring investigator responsibility in case of adverse reaction or death.  Especially in the context of globalized drug development, I believe it’s incredibly important to explore the ways in which these procedural ethical standards are warped according to and “across distinct political and economic contexts”.

Still, I get a nagging feeling that at the core of the research regime’s baseline ethical standard lies a more subtle danger: it seems to me  that the definition of “informed consent” is built in to whatever subjective understanding the Independent Review Boards (IRBs) and CROs may have of it. Seeing as “informed consent” acts as foundational language for an entire ethical standard, a subjective or shaky definition of the phrase is problematic in a way Petryna does not explore at length. When taken across differential political and economic contexts, the ambiguous language of “informed consent” is further destabilized.

In the U.S., informing subjects can be relatively simple if the population is english-speaking and if they have already been exposed to the culture of research, whether through ads  for subjects or through lived experience. When in a place in which research is not the norm or is in the process of becoming a norm, language barriers, stigmatization, and local knowledges seem to lead subjects to create their own understanding of the research purpose.  In Fairhead’s article, which focuses on the MRC project in The Gambia, many parents seemed to believe that the taking of blood samples was for insidious purposes.  Although MRC fieldworkers attempted to inform subjects by “explaining the immune system as the body’s soldiers” and framing their research in an attempt to understand such a system, local knowledges still prevented people from fully accepting the idea. In the end, participants were primarily concerned about the health care that they and their infants were receiving that was unavailable through the government.

If informing subjects according to time and place can be tricky, then obtaining  valid consent might prove to be exceptionally difficult.  Although most CROs would agree that the patients in the MRC study have consented despite being limitedly informed, they fail to take into consideration the structural elements involved in these people’s lives that lead them to agree to a study despite limited understanding or informed hesitancy. It begs the question: can true consent exist in structurally violent circumstances? Even if the subject is informed, outside forces such as political instability, governmental inadequacy, and economic constraints may push people in impoverished conditions towards “consenting” to a study. In this way, consent becomes antithetical to a person’s true desires.  In that case, can it even be called consent?  CROs have no  interest or responsibility in addressing  “how true” consent may be, therein perpetuating inequality while creating ethical variability across specific populations that exploits in a way that is distinct from the crises that Petryna explores. In the article by Fairhead, some people that were not able to get the care they needed from the government consented to the  MRC study because of the benefits to them and their family.

A recent October article presents a case which is not entirely analogous but still relevant to the exploitation of vulnerable populations through research.  In their WashingtonPost article, Gowen and Lakshmi discuss the “Rent-a-Womb” industry  in India that allows foreign couples to find surrogate mothers.  If the nick-name of service and commodification of the womb is not concerning, these surrogate mothers are “often poor and illiterate women from rural areas who are paid little.” It is a largely unregulated business supported by fertility clinics and produces a whopping $400 million dollar a year. Although the “Rent-a-Womb” industry is not necessarily a research study, it is again a moment in which biological bodies are used in a manner that is exploitative, in which monetary gains drive poor women to “consent” to the use of their wombs.

In this way, the shaky foundational language of ethical standards is a powerful means to exploit vulnerable populations in quite subtle ways. Informed or not, consent hinges on the socioeconomic status of subjects in a way that perpetuates inequalities between privileged and impoverished bodies. Consent is not given by subjects, but rather created by CROs to benefit their own goal of cost-effective and rapid research.

Sources:

Leach, Melissa and James Fairhead. 2011. “Being ‘with the Medical Research Council’: Infant Care and the Social Meanings of Cohort Membership in Gambia’s Plural Therapeutic Landscapes.” In Evidence, Ethos and Experiment: The Anthropology and History of Medical Research in Africa. P. Wenzel Geissler and Catherine Molyneux, eds. New York: Berghahn Books.

Gowen, Annie, and Rama Lakshmi. “India’s ‘rent-a-womb’ Industry Could Close Doors to Foreigners.” Washington Post. The Washington Post, 28 Oct. 2015. Web. 8 Nov. 2015. <https://www.washingtonpost.com/news/worldviews/wp/2015/10/28/indias-rent-a-womb-industry-could-close-doors-to-foreigners/>

Petryna, Adriana. 2005. “Ethical Variability: Drug Development and the Globalization of Clinical Trials.” American Ethnologist 32(2): 183-197.

Questions:

Can the consent of people in such impoverished communities ever be taken as true, regardless of whether they have been informed?  How does allowing these people to have bodily autonomy complicate the issue?

How can IRBs or other bodies claiming to uphold ethical standards prevent exploitation of vulnerable communities given that structural violence often drives such individuals to use their biology in order to benefit themselves and their families?

Since the 1990s there has been rapid growth in the number of people participating in clinical research. Even though most clinical research is funded and controlled by more developed countries like the United States, the rise in human participants is primarily coming from developing low-income countries. There are a multitude of reasons why researchers are now going to low-income countries to find human subjects. Research guidelines may not be as strict, allowing researchers more freedom in conducting their studies. People may be more willing to partake in clinical trails because they are getting drugs they may not get under other circumstances. Lastly, the testing population in the United States has been gradually shrinking despite the increasing demand. Thus, compelling more researchers to adamantly search abroad from human participants (Petryna 185).

The United States drug testing pool has been shrinking since the 1970s. This was when the “use of prisoners as subjects was exposed and severely limited” (Petryna 185). Researchers had to turn directly to the American public to find human subjects since incarcerated individuals made up a large portion of their previous subject pool. The current issue at hand is slightly different. The US population has become a “treatment saturated” population (Petryna 185). Most individuals are on some sort of medication. Using medicalized individuals in clinical research could result in drug interactions and bias data. Some researchers have found a solution in using international individuals instead. Many individuals in less affluent countries have not had the same access and exposure to medications. This makes them naïve test subjects. This desire for the naïve subject is pushing American research initiatives abroad.

There are significant downsides to conducting medical researcher abroad. This current situation puts developed countries at risk for exploitation (Emanuel et al). In developed countries this risk is minimized because there is infrastructure that protects individuals. However, developing countries are less likely to have this framework in place, leaving individuals in these communities more susceptible. Ethical Variability by Adriana Petryna presents a good example. Researchers in developed countries usually target individuals in neighborhoods with easy access to hospitals and centralized healthcare. However, while searching for research participants abroad, many researchers seek out communities with broken health care systems. These areas are more likely to have more willing participants because the people there have no other access to healthcare. It is clear that the primary goal is getting as many subjects as quickly and cheaply as possible (Petryna 187). On a similar note, Petryna also discusses questionable clinical trials shortly after Chernobyl. She claims that chaos enabled researchers to perform trials they usually would not get permission to perform (Petryna 191). Even though some kind of attention was being directed toward the issue at hand, corners were likely cut and subjects were valued less as humans and more as unique testing opportunity. An element of humanity is definitely lost in this kind of approach.

Research projects themselves have become more about the numbers produced and less about the individuals themselves. This is a concern thoroughly discussed in When People Come First by Petryna and Biehl. Evidence Based Medicine, especially Randomized Controlled Trials, are now considered research standard (Petryna and Biehl 58). The issue is that these rigid research methods are not always applicable to the broad, complicated and unpredictable field of global health. Furthermore, studies resulting in defined measurements and statistical significance do not necessarily provide helpful conclusions or a useful platform for future initiatives (Petryna and Biehl 83). Recently, studies that actually aim to help individuals are often shut down because they will not produce the desired numerical results. Forcing determined NGOs to seek private funding if they want to implement effective projects.

When faced with such a problem, it is important to consider possible solutions. If companies desire to perform research beyond their own borders it is important that some regulatory system is established. As stated in the article What Makes Clinical Research in Developing Countries Ethical? such systems should prioritize participant protection. It should set guidelines to prevent researchers from taking advantage of research subjects. Another possible solution could be achieved through partnership. Although it was not completely perfect, the Leach and Fairhead article demonstrated a relatively effective solution: combining research and direct aid. Health workers provided new mothers with good health care and then performed research on the side (Leach and Fairhead 96). This approach allows beneficial research to done while still maintaining a humanistic element. If implemented correctly the motivation to perform research may even eventually foster more sustainable experimental and medical support systems.

Discussion questions:

1. What do you think about the research performed after Chernobyl? Even if controversial research produces favorable results is still ethically acceptable? Should medical research guidelines be loosened in a state of emergency or crisis? Who would such an act benefit more: the researchers or the participating individuals?
2. Not all countries have sustainable systems that can regulate medical research. Who should implement medical research regulations? What research guidelines would be essential in these scenarios?

Sources:

Petryna, Adriana. 2005. “Ethical Variability: Drug Development and the Globalization of Clinical Trials.” American Ethnologist 32(2): 183-197.

Biehl and Petryna. 2013. “Evidence Based Global Public Health.” When People Come First (Ch. 2).

Emanuel et al. 2004. “What Makes Clinical Research in Developing Countries Ethical? The Benchmarks of Ethical Research.” Perspective.

Leach, Melissa and James Fairhead. 2011. “Being ‘with the Medical Research Council’: Infant Care and the Social Meanings of Cohort Membership in Gambia’s Plural Therapeutic Landscapes.” In Evidence, Ethos and Experiment: The Anthropology and History of Medical Research in Africa. P. Wenzel Geissler and Catherine Molyneux, eds. New York: Berghahn Books.