HIV transmission in Africa: A plea for fairness

 In developed countries around the world HIV transmission from mother to infant has effectively been curtailed through the AIDS Clinical Trial Group Protocol 076 (ACTG 076).  However, this protocol is extremely extensive, and it requires the pregnant mother to take a lengthy oral regimen and get intravenous injections of the relatively expensive drug zidovudine, among other things.  Because of this, undeveloped regions of the world, such as parts of Africa, can neither afford this protocol nor do they have the proper facilities and personnel to implement it.  As a result, in most parts of Africa, HIV positive mothers don’t have access to any treatment or medications to stop the transmission of HIV to their children, and this is becoming an increasingly large problem.

 In response to this need, researchers from the World Health Organization are attempting to find cheaper and less intensive treatments (and most probably less effective) which can be implemented in Africa.  Of course, to test the effectiveness of these treatments, researchers have run clinical trials in Africa, and in them they have had one group that undergoes the treatment, and one group that gets a placebo.  This use of placebo control groups have led to great contention around the world, and critics claim that since an alternate, effective treatment (ACTG 076) is available the new treatments should be tested against that, so no one is denied treatment altogether.  This notion can find its roots in the Declaration of Helsinki, which states, “The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods”.

Although this argument is valid in a country where ACTG 076 is available (because then a placebo control group would really be denying people treatment), it is not valid in a region where ACTG 076 is unavailable in the first place, because no one is being denied treatment they would otherwise receive.  In effect, in such a region there is no “best current treatment”, and in such cases, no one denies that a placebo group is ethical. And yet, critics still claim that the trials shouldn’t have a placebo group, and should have an ACTG 076 group instead, so everyone in the trial at least gets some sort of treatment.  But, objectively, this is no different than simply running the trials with a placebo group and then giving certain random people in Africa the ACTG 076 treatment – because either way the rest of the African population gets no treatment, and is, in a sense, a placebo group.  However, these same critics generally do not argue that we should give everyone in Africa ACTG 076. Thus, from this it becomes clear that it is not the placebo group in itself that is troublesome to critics but rather, the trials bring the blatant inequality in the world to the forefront.  The placebo group emphasizes the inequality between the African population and people in developed countries (who would get ACTG 076 rather than a placebo), and consequently people are more emotionally motivated to have an ACTG 076 group rather than a placebo group.

Admittedly, this social and economic inequity is indeed a problem that should be resolved, but it does not intrinsically make the use of a placebo group unethical, all it does is blur the issue.  Because the placebo group makes the inequity ever more visible, people jump to the conclusion that the placebo group is actually exacerbating the problem.  On the contrary, the very purpose of the placebo group is to alleviate the inequity by finding cheaper, more readily accessible treatments for African mothers.  As David Satcher, a researcher, notes, the use of the placebo group will make the trials more efficient and will give more definitive results.  Since the expectation is that the new treatment will be less effective than ACTG 076, if the control group is ACTG 076 then it will be difficult to tell whether the new treatment is better than nothing – further prolonging the development of new treatments, which actually exacerbates the inequity even more.

 Therefore, the use of the placebo group in the case of these clinical trials in Africa will actually help reduce the inequalities between Africa and more developed regions faster and more efficiently than if an ACTG 076 control group is used.  Of course, it would be fantastic if all pregnant women in Africa had access to ACTG 076, but the sad reality is that they don’t.  The sooner critics realize this, the sooner these women will be able to get access to at least some form of treatment. 

Sources

https://blackboard.princeton.edu/@@/664683C27709CA2175BB52BC68E90A1B/courses/1/WRI167_S2012/content/_1289369_1/background.pdf
https://blackboard.princeton.edu/@@/664683C27709CA2175BB52BC68E90A1B/courses/1/WRI167_S2012/content/_1289370_1/Complexities_of_Cond_1F6C72.pdf

Clinical Trials and Tribulations: A Look at Overseas Clinical Trials

Making sure that clinical trials are ethical is a classical problem in the study of bioethics. How do we properly regulate, however, for trials done in foreign countries? This is an increasing problem, as many pharmaceutical companies have shipped their clinical trials almost exclusively overseas, particularly to countries that have less stringent ethical boundaries. One possible benefit of this idea is to check the effectiveness of drugs on variety of racial backgrounds. That being said, this is clearly not what companies are after. With fewer ethical restrictions in place in poorer countries, the companies can pay their test subjects less, and it is easier to gather information if the wellbeing and ethical treatment of a patient is less of a concern. Ideally medical ethics should be applied uniformly regardless of geographic boundaries, but there is an issue; how can we enforce our brand of ethics in countries where the same standards don’t apply? One possible way to check that standard medical procedures are followed in these foreign trials is for the FDA to conduct audits of the companies before allowing their drug to appear on the market. These audits, however, are extremely expensive, and the FDA has been long strapped for cash. One possible solution to this problem (besides somehow finding more governmental funding, which I don’t see happening) is to be less accommodating to the drug companies. For example, rather than just approving drugs with clinical trials that don’t adhere to standard formats, we can force them to standardize, making the databases of clinical data more complete. In addition, attempts to force companies to register their foreign trials would make monitoring for unethical behavior much simpler and more organized. In these extenuating circumstances, this seems to be the best option.

http://www.nytimes.com/2010/06/22/health/research/22trial.html

Secrets, Secrets are no fun: Is it unethical to leave dead end research unpublished?

          Have you ever thought of a great concept or joke and later found out that someone else thought of the exact same thing earlier than you? You may feel dejected if your idea was a joke, but what if it was a plan for taking certain courses, or to try making a certain type of food in an unorthodox manner? Chances are you could benefit greatly from the experiences of the person who tried it out before you – if the method of cooking ended in disaster, you can save yourself and whoever you are cooking for a lot of time and stomachache by avoiding it and trying something else. Now imagine, if your predecessor decided not to tell anyone about his failure – whether out of shame or because he intended to try again – the result would be that you would never get the chance to learn from him, and would be doomed to the same fate.

            This is the current state of affairs in the world of Clinical Trials. A law passed by Congress in 2007 requires that clinical researchers release most of the detailed results of their trials to the public. However, they are only required to do so once their product becomes approved by the FDA – meaning if they terminate the study early, or it fails for some other reason, they are never legally required to release the information. Even if it isn’t illegal, is invoking this loophole unethical? The hypothetical situation above shows how sharing can lead to benefit for a group of people, even if the result was not as expected. Additionally, it could help clear up current medical assumptions that we don’t even know are problematic. Science Daily uses the example that Michael Rogawski, Chair of the UC Davis School of Medicine Neurology Department, presents. He says new antiepileptic drugs are tested on mouse models, which are assumed to be effective simply because there is no contradictory evidence. However, if it is being withheld by the companies that failed, then this evidence could exist somewhere.

            The article in Science Daily concludes that when researchers fail to publish failed results, they are violating “an implicit moral contract between sponsors and study participants.” While I agree that it should become standard practice, if not law, for research companies to release all of their results – failed or successful – I would not go far as condemning those that have not chosen to as of yet. Research dead ends for a number of reasons – dangerous side effects, running out of funding, or simply a change in the market. It is understandable that in some of these cases, a company may want to keep their methods secret in case they want to return to the research at some point, and there is no strongly suggestive evidence to say they are harming anyone by doing so. For this reason we should avoid condemning anyone for what has been done up until now. Nevertheless, I think it is time for a change. The law should be changed in order to require that all results be published, just in case we are missing something that could benefit everyone.

http://www.sciencedaily.com/releases/2011/09/110928142444.htm

Trust Me, I'm a Neurochemist

Paul Zak claims to have found the reason that we trust others: a complex molecule called oxytocin. Zak, a professor at Claremont Graduate University in Southern California and a self-described “neuroeconomist,” investigates the factors that make people more generous and trusting towards others.

In a recent study, he found that people who had been exposed to the chemical oxytocin, a neuropeptide that has been shown to be related to social attachment in other mammals, chose to give about one and a half times as much money to charity as a control group who had been exposed to a placebo.

In another study, Zak found that subjects who had been exposed to oxytocin were twice as likely to donate all of their money to an anonymous trustee, trusting that that other participant would give them some back.

While it may not be a trust serum quite yet, Zak’s research serves as a reminder that the black box surrounding the functioning of our brains is ever-shrinking. As we become more capable of manipulating feelings and even thoughts by using chemicals, we must ask ourselves what the appropriate uses of these chemicals might be.

For example, one could easily imagine the dangers that a trust-inducing substance might produce in the hands of a con man or corrupt politician. But one could also see applications that are less morally clear-cut. Would a doctor be justified in prescribing oxytocin to an autistic person to allow him or her to more easily empathize with others? Would caretakers of a mentally deranged person be justified in giving that person oxytocin in order to reduce the risk of violent outbursts?

It seems a fundamental tenet of morality that we should never change another person’s thoughts without that person’s consent. After all, what privacy do we have if not that of our own mind? But what if the patient is incapable of giving consent? Our idea of personhood is so intimately tied up with our thoughts that I believe that traditional methods of proxy consent (parents for children or caretakers for the mentally disabled) may not be strong enough to justify the application of a drug capable of creating significant and lasting mental change.

The idea of consent itself also becomes clouded when mind-altering drugs come into play. If a patient were initially skeptical of taking an oxytocin pill, but became so trusting of his or her doctor when on the pill that he or she would not choose to go off the pill while its effects were active, can we consider that patient to still be consenting to continued treatment?

Such questions seem to border on science fiction, but it is more and more likely that they will become concrete issues within our lifetimes. I believe that we should continue to research the chemical composition of the brain for the sake of greater scientific discovery and for the potential medical applications, but that we should not allow any such chemicals to be released as publicly available drugs. They have too great a potential to compromise our humanity and we are better off without them.

Trust me.

Sources:

Barraza, JA, et al. “Oxytocin infusion increases charitable donations regardless of monetary resources.” Hormones and Behavior, 8 May 2011

Kosfeld, Michael, et al. “Oxytocin increases trust in humans.” Nature, 435: 673-676 (2 June 2005)

Zak, Paul. "Trust, Morality, -- and Oxytocin." TED Talk. www.ted.com/talks/paul_zak_trust_morality_and_oxytocin.html

Understanding the brain – courtesy of your military

        The Defense Advanced Research Projects Agency, or DARPA, is a Department of Defense agency that is known for funding research into new technologies ranging from the outlandish – flying cars – to the slightly more tractable – autonomous vehicles.   With these developments, the agency and many other military research groups have developed close relationships with the scientific world.   Recently, US national security groups have come to see neuroscience as a key frontier in the 21^st century.  The nature of neuroscience research, however, means that research of interest to the military is often begun without any interest in military applications.  This interplay between civilian and military technologies is nothing new.  The internet and GPS were originally developed for military use.

        In a paper published in PLoS Biology, an open-access journal, Michael Tennison and Jonathan Moreno explored the balance between military interests and scientific ethics.  They argue that while the goal of science is to expand knowledge via rigorous validation, the military aims to utilize new technologies as quickly as possible for national defense.  They hold that, as a result of this conflict, neuroscientists should remain conscious of the possibility of dual-uses, both civilian and military, for they research.

        Should this possibility of dual-use for new research be a real cause for worry?  The authors discuss a few technologies such as brain-computer interfaces, mental enhancement, and technologies developed toward the possibility of brain-reading.  Each military technology goes hand in hand with scientific research, yet the goals of the research that yielded each were not the creation of new military weapons.  I believe that while continued military use of neuroscience research is a cause for concern, there is not much that can be done if we hope to continue advancing our knowledge of the brain.  The nature of neuroscience research means that as we increase our understanding of the brain and develop new technologies, these new ideas will continue to play a role in military operations. 

http://www.sciencedaily.com/releases/2012/03/120320195800.htm

Unnecessary Tests and What They Mean for the Healthcare System

NPR reported today that “…as much as one-third of all procedures performed in the United States are of ‘questionable benefit’” (1). The news agency explained: “These procedures drive up cost and don’t help patients.”

This is appalling! How can a group of professionals who have sworn to “do no harm” conscience charging patients for these tests? On the face of it, this seems like it verges on criminal malpractice. But actually, I think the fact that doctors are overcharging patients for these unnecessary procedures is a symptom of a dysfunctional healthcare system. When doctors have to jack up prices (knowing that patients with insurance will not end up paying most of that sticker price) to pay for uninsured patients, we know that there’s a problem.

The good news is that some doctors are trying to change this norm: “In a move likely to alter treatment standards in hospitals and doctors’ offices nationwide, a group of nine medical specialty boards plans to recommend on Wednesday that doctors perform 45 common tests and procedures less often, and to urge patients to question these services if they are offered.”

However, there is still much to be done. And discussion of the healthcare system is particularly relevant now since the Supreme Court is currently deciding the fate of Obamacare. But no matter what happens, the most important thing is to change the incentive structure for doctors: the fee-for-service model that we have now is just not working, as indicated by all these unnecessary tests. This is where we should start.

(1) http://www.npr.org/local/stories/KQED/150023820

Not gender selection, but sexual orientation selection?

Gender selection, whether through embryo screening, sperm selection, or, more radically, conscious pregnancy termination, has been a hot topic of debate over the past few years. But recent research is suggesting that designing babies may go beyond selecting gender, physical traits, or even mental capacities and talents: it may be possible to select a child’s gender orientation.

More specifically, dexamethasone, or dex, is a risky, class C steroid that is nevertheless given to some pregnant women who are carrying fetuses with potential congenital adrenal hyperplasia (CAH), a disorder that gives the fetus ambiguous genitalia development. In girls, CAH means an excess of prenatal androgens that can give her male physical characteristics, but some researchers suggest that these characteristics may go beyond physical ones. Maria New, pediatric endocrinologist at Mount Sinai School of Medicine, published in a paper in 2008 on the “dose-response relationship of androgens with sexual orientation” by studying women with different types of CAH. New found that “the rates of bisexual and homosexual orientation were increased above controls . . . and correlated with the degree of prenatal androgenization.” In addition, she found that “CAH women as a group have a lower interest than controls in getting married and performing the traditional child-care/housewife role.” Thus, dex may have the potential to decrease not only the possibility of developing physical traits of the opposite gender, but also that of being homosexual.

Aside from the argument that the drug dex is dangerous and that its effects on preventing homosexuality are not yet fully understood, should a “treatment” be made widely available if further research showed reducing prenatal androgens did indeed reduce possibilities of homosexuality?

While the continuation of research to develop dex for the purpose of attempting to eliminate homosexuality is controversial, researching the link between prenatal androgen and homosexuality should be allowed to continue because it could provide more specific detail for the fact that homosexuality is natural/ biological, as opposed to a conscious life-style choice.

On the other hand, using dex as a “treatment” for homosexuality should not be widely accepted because of the coercion that it could represent for pregnant women. Unlike certain kinds of enhancement, such as minor operations that improve one’s appearance, or drugs like Adderall, which allows someone to focus but not necessarily produce better work, the dex “treatment” could be viewed by those who are strongly opposed to homosexuality as not a luxury but a way to “cure” the society of homosexuals. Giving a pregnant woman with a potential CAH fetus the freedom of choice on whether to use dex is not really giving her a freedom of choice at all. Women who choose not to use dex would face stigma from society accusing them of not preventing their children of being homosexual when they could have. Homosexuality is an identity, one that is no less valid than other identities. But unfortunately, not all of society shares that view. So unless opposing views change, we should not strive to make dex a widely available “treatment” for homosexuality, even if the drug’s risks are reduced.

http://www.physorg.com/news197211098.html

http://www.thehastingscenter.org/Bioethicsforum/Post.aspx?id=4754&blogid=140