An op-ed from our friends Mark Barnes and Barbara Bierer at Harvard’s Multi-Regional Clinical Trials Center on recent legal changes to India’s clinical trial requirements, arguing that using theclinical trial context to promote a social or political policy agenda in India may sacrifice scientific integrity in the service of social justice. A quick snippet:
The overbreadth of these requirements, and how poorly tailored they are to achieve the specific goal of protecting clinical trial participants from risks directly caused by trials themselves, leaves one wondering whether the regulatory authorities fully comprehend the clinical trial process and the nuances of complex medical and biological processes. One further wonders whether what animates these measures may be less a concern for specific justice in individual cases than the goal of righting social wrongs and achieving social justice, unrelated to but prompted by clinical trial experiences. Achieving social justice and a more just allocation of social resources may be completely laudable – even desirable – as social or political policy, but unconsciously using the clinical trial context to promote this agenda threatens to corrupt science and to undermine health, with results that may create more social distress than social justice.
The following information has been extracted from the webpage of the BioBanking and Molecular Resource Infrastructure of Sweden on the course Biobanking as a Resource for Biomedical Research, February 9-13, 2015 at Karolinska Institutet (Stockholm).
Purpose and Goal
Biobanks constitute a powerful resource in medical research with access to millions of samples and associated data collected within health care and in specific research studies. New “omic-technologies” with high-throughput analytical platforms now permit large scale analyses without the need to wait for years while new samples are being collected.
However, successful research based on human biological samples and associated data requires applied knowledge about how the samples have been collected and processed. Standardized procedures, controlled pre-analytical variables and study documentation are key factors for the reliability and validity of the analytical findings.
This one week course addresses fundamental concepts in biobank infrastructures and biobank research, ethical and legal frameworks, technologies, sample analysis and practical considerations when new samples are to be collected. Continue reading →
Undoubtedly, the death toll in West Africa would be much lower if Guinea, Liberia, and Sierra Leone had better health care systems or if an Ebola vaccine had been developed already. But as Fran Quigley has observed, Ebola is much more a problem of poverty than of health. Ebola has caused so much devastation because it emerged in countries ravaged by civil wars that disrupted economies and ecosystems.
Ultimately, this Ebola epidemic will be contained, and a vaccination will be developed to limit future outbreaks. But there are other lethal viruses in Africa, and more will emerge in the coming years. If we want to protect ourselves against the threat of deadly disease, we need to ensure that the international community builds functioning economies in the countries that lack them.
Our humanitarian impulses in the past have not been strong enough to provide for the needs of the impoverished across the globe. Perhaps now that our self-interest is at stake, we will do more to meet the challenge.
In the wake of Craig Spencer’s decision to go bowling in Brooklyn, governors of three major states—Illinois, New Jersey, and New York—have imposed new Ebola quarantine rules that are inconsistent with national public health policy, are not likely to protect Americans from Ebola, and may compromise the response to Ebola in Africa, as health care providers may find it too burdensome to volunteer where they are needed overseas. Don’t we have an Ebola czar who is supposed to ensure that our country has a coherent and coordinated response to the threat from Ebola?
Of course, the term “czar” was poorly chosen precisely because Ron Klain does not have the powers of a czar. He will oversee the federal response to Ebola, but he cannot control the Ebola policies of each state. Unfortunately, on an issue that demands a clear national policy that reflects medical understanding, public anxieties will give us something much less desirable.
I have a new paper in a theme issue of Law and Contemporary Problems (one of two, I’ll post the second as well when it is available) titled Organs Without Borders? Allocating Transplant Organs, Foreigners, and the Importance of the Nation State (?) This paper is related to but separate from my work on medical tourism, which has dealt among other things with “transplant tourism,” such as traveling abroad to buy a kidney. In this work I deal with the legally sanctioned distribution of organs. It will surprise many that in the U.S. a non-resident and non-citizen may be listed on the wait list for an organ for transplantation and if he or she is so listed he or she must, as a matter of law, be given the exact same priority as a similarly situated U.S. citizen-resident. Is that policy just or unjust. These are among the topics I tackle in this article. Here is the full abstract:
Most of the discussion of market or non-market forms of allocating and procuring organs takes as its unit of analysis the nation state, or, less commonly a particular state or province, and asks what should the system look like as to this unit. In this article, the second of two articles I contribute to this issue of Law and Contemporary Problems, I want to expand the viewfinder and examine an issue that has received peculiarly little attention in the scholarly and policy discourse: the desirability of treating the nation state (or its subdivisions) as the right level of distribution for organs, whether through market systems or non-market allocation systems. I will show that when we flirt with using a more global viewfinder, a series of difficult (and thus far largely unexplored) ethical and regulatory questions arise relating the inclusion of “outsiders.” At the very end of this article I explore what relevance this analysis may have to allocation within the nation-state as well.A large number of questions could be discussed under this title, but for this article I largely limit myself to two related questions. For both I will use the U.S. as the “home country” for rhetorical clarity, but the basic issues are the same for any home country. The first issue is: Should the U.S. allow “foreigners” to be on the list of those eligible to receive organs in the U.S. when they become available, and, if so, at what level of priority? Surprisingly the current law allows them to be listed to receive organs and if they are so listed it prohibits any discrimination against them for priority based on their being foreign. Second: should the U.S. maintain its own organ distribution network that is limited to the nation state instead of participating in a more globalized system? I should emphasize that my interest here is organs that come to recipients through typical government-run (or at least government-approved) organ allocation systems rather than foreigners who come to U.S. centers and bring their own living donor.
I first describe the two issues and then offer a normative analysis of each. This cluster of issues applies equally to the current U.S. distribution system with its hostility to markets and any of the potential alterations discussed in other articles in this issue of Law and Contemporary Problems. Continue reading →
There’s been an interesting mini-debate over at the FCPA Blog about whether, or to what extent, corruption is partly responsible for the severity of the Ebola crisis in West Africa. Richard Cassin, the publisher and editor of the FCPA Blog, argued that it is. He made this argument initially in a post from this past August entitled “Ebola tragedy is also a story of graft.” He offered as evidence the following observations: (1) the WHO and other observers estimate that a very high percentage–perhaps up to 25%–of global spending on public health is lost to corruption; (2) the very high Ebola fatality rates in West Africa have been attributed in part to the lack of adequate intensive care facilities to administer the treatments; and (3) the countries hardest hit by the Ebola outbreak–Guinea, Liberia, Sierra Leone, and Nigeria–are reputed to be highly corrupt, as indicated by their very poor scores on Transparency International’s Corruption Perceptions Index.
Many critics who commented on Cassin’s initial post complained that the evidence offered did not in fact support the strong claim in the title that corruption has contributed significantly to the Ebola outbreak. In particular, the critics pointed out that: (1) the fact that a great deal of public health spendinggenerally is lost to corruption does not actually tell us whether corruption was a major factor in the particular case of the Ebola outbreak, and (2) the low ranking of the affected countries on the CPI likewise–even if we concede that the CPI is a decent measure of actual corruption–does not indicate that corruption caused (in any significant way) the Ebola outbreak to be as lethal as it has been; at most it shows a correlation that might be explained by any number of other factors.
Cassin responded with a second post last month in which he rebutted the critics. He acknowledged that while one can never establish with “scientific certainty” that corruption has a causal effect on the severity of the Ebola outbreak, there is powerful circumstantial evidence that corruption is a “gateway” to this and other public health crises (as well as other problems like terrorism and crime), because it siphons off public resources. Cassin cites to a couple of research papers that purport to show that corruption in general has adverse impacts on public health, in particular because it adversely affects access to clean water and sanitation.
It seems like the debate over banning flights from West African Ebola stricken countries has become instantly political, with many Conservatives calling for a flight ban. See here. One author, in response to these calls, points to the history of Liberia’s relationship with the United States as a reason that the US should not consider a flight ban. Arguments against a flight ban that are not based on public health principles provide fodder for the talking heads and individuals who want to see this as a political issue.
The real question should be how much good a flight ban would do to halt the spread of Ebola to the United States. Many public health experts, from the CDC to the WHO, do not think a ban would make us safer.
Ebola is only contagious when the patient is symptomatic, and the first symptom is almost always a fever. If a patient does not have a fever, and is asymptomatic, they are not contagious. Thus they do not provide a serious risk of infecting other people, even in the confined quarters of an airplane. This makes temperature screening especially important. This easy screening tool is already in use at airports in Ebola affected Countries. Continue reading →
SG Global Chat Harvard Effective Altruism — Using Evidence and Reason to Maximize the Impact of Efforts to Make the World Better
October 8, 2014 12:30-1:20pm, Kresge G-2
Harvard Effective Altruism (HEA) is a student group at Harvard College and Harvard Business School. The group is dedicated to spreading the ideas of effective altruism to better the global community. Previous HEA speakers include Peter Singer, Nick Bostrom, Max Tegmark and Thomas Pogge. This year, HEA plans to became a Harvard University-wide student organization. Come to the first SG Global Chat of the year to hear more about HEA, the events the group has planned, and ways to get involved. Presented by Anders Huitfeldt (ScD Candidate in Epidemiology) and Eric Gastfriend (Student at Harvard Business School).
It’s been over half a year since the beginning of the current Ebola outbreak in West Africa, yet the number of cases and deaths from the disease continue to rise. The total case count as of September 29, 2014 is 6,574 and total deaths are at 3,091. Even so, the international response, as a whole, seems to be lacking. As I lived near the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia this past summer, I was acutely aware of the Ebola epidemic’s magnitude while it had the media’s attention. The attention given was similar to that given to a car accident on the side of a road as onlookers drive on by without stopping to offer help. Unfortunately, it was quite clear that aid efforts were woefully inadequate and that the disease would continue to spread rapidly without a stronger response. It seemed that though our curiosity about this virus was at an all-time high, our national concern for the epidemic and its casualties were extremely minimal other than in the brief moments when we were faced with prospect of flying in two of our own infected citizens. Continue reading →
Richard is talking about post-trial responsibilities. He points out that there is a justice issue here with ensuring access to health care and up to date interventions. He points out that while the FDA can encourage Post-Trial Access (PTA), it has no authority to require or ensure it. He points to moral authority, rather than legal. Foreign trials, however, are a different story, as the FDA has sway over protocol applications that are submitted in the US. Richard begins highlighting some specific considerations for protocol drafters and IRBs: particularly focusing on determining monitoring plans, as well as figuring out financial responsibilities for the provision of PTA.
He moves on to highlight that there is more of a moral obligation than a legal obligation. FDA is supportive of the provision of PTA. He believes that enthusiasm must be tempered, as there are situations when PTA is not appropriate. These include studies that have significant safety concerns, studies of bio-markers as well as validation studies that do not specifically examine safety and effectiveness. There are also situations where PTA is simply not feasible, particularly if additional drugs do not exist (one thinks of the recent Ebola treatment), if there is insufficient safety data, or if there is no practical capacity or resources to provide safety monitoring. We must also be aware of financial limitations, especially for start-up biotech firms that might not have deep pockets. Continue reading →
For all those who are interested in issues of global health, access to medicines, and drug pricing, yesterday Gilead formally announced its access program for enabling many developing countries to purchase its new Hepatitis C drug, Sovaldi, at low prices. This announcement is particularly noteworthy because Sovaldi represents a significant improvement over the current standard of care for Hepatitis C, as it can cure a much greater percentage of sufferers than could standard therapies, and it does so with many fewer negative side effects. Gilead’s partnership-based program will permit seven Indian generic drug companies to produce and sell the drug in 91 developing countries. The discounts are significant: although Gilead formally charges $1,000 a pill (or $84,000 for a course of treatment) for Sovaldi in the United States, it will charge just 1% of that, or $10 a pill, in India (the total cost there is estimated at $1,800, given the difference in strain prevalence).
The global health community has reacted to the announcement with mixed reviews. The 91 countries in the program include more than half of the world’s Hepatitis C patients. But tens of millions of other patients in large nations like China, Brazil, Mexico, and Thailand are left out of the program. Going forward, some of the excluded nations may seek to issue compulsory licenses in an effort to expand access to Sovaldi.
Gilead has also drawn fire in the United States for Sovaldi’s $84,000 sticker price (which, for various reasons, very few if any will actually pay), to the degree that members of both houses of Congress haveasked Gilead to justify the price of the drug. Those opposing Sovaldi’s price have generally not come out publicly against the high price of many orphan drugs, which can cost $250,000-$350,000 per year. But because Hepatitis C afflicts about 2.7 million people in the US, as compared to the few thousand people with one of the relevant orphan diseases, its impact on insurers (both public and private) is likely to be much larger (as this very blog has previously noted). Continue reading →
Post-Trial Access (PTA) is emerging as an important topic in the design of ethical clinical trial protocols. PTA refers to the provision of study drug to the participants in a successful clinical trial (and maybe others) during the crucial period after a clinical trial phase is over, but before the drug is widely available or approved for the market (or maybe longer/in other circumstances). At issue is the question of the commitment a clinical trial sponsor owes the participants of their trial (and maybe others) in the period after a clinical trial phase, but before market approval of the tested pharmaceutical (or maybe longer).
While the provision of Post-Trial Access may seem to be an ethical “no-brainer,” there are numerous variables that make the decision of whether to provide PTA difficult. One major question is whether all arms of the trial deserve access to the therapy, even those who were on placebo or in the control arm. If the therapy tested shows less efficacy than a more or less expensive treatment modality, is there a responsibility to provide the more effective treatment, regardless of the cost? What if said therapy is far beyond the standard of care for the condition in the particular country where the trial took place? Furthermore, how long do PTA obligations extend? While the simple answer is that they end after market approval, the truth is that many drugs have long approval processes, with complicating factors that can result in significant delays. This is an even more difficult question if the trial is a multi-regional study, and takes place in a country where the sponsor does not intend to market the product.
The question of how to provide PTA also poses logistical issues, as many sponsor sites close after a clinical trial is finished. This can make provision of post-trial access extremely expensive, and perhaps unduly burdensome, especially if the trial is sponsored by a biotech start-up without the deep pockets of a large pharmaceutical company. These costs can skyrocket depending on whether we believe the sponsor should be responsible for costs that might result from improper use of the therapy, or failure of the participants to comply with proper treatment. Continue reading →
On Saturday, Sept. 6 at 3pm in Sever 111, we are holding a giving game / donation discussion and an information session for Harvard students interested in our organization. We’ll explain what effective altruism is and what HCEA does here on campus. If you’re new to HCEA, you should definitely check it out!
Wednesday, Sept. 10 at 4:30pm in Science Center Hall A: Prof. Michael Kremer – a development economist at Harvard – will give a talk entitled “How can individuals reduce global poverty?” He’ll discuss the ways that individuals can use both their money and their careers to contribute to poverty reduction and international development.
All semester long! HCEA is hosting its third Philanthropy Fellowship program for Harvard undergrads and graduate students. Fellows will attend talks from speakers like Harvard professor Steven Pinker, Rob Mather of the Against Malaria Foundation, and Center for Applied Rationality president Julia Galef; learn about effective altruism at weekly dinners with other fellows and speakers; get to know likeminded students at discussions and social events; and fundraise for effective charities! You can find more information and apply on our website before 11:59pm on Sunday, Sept. 14th.
We hope to see soon! Altruistically yours,
Ales and John
Art Caplan has a new video on Medscape laying out the principles behind rationing limited supplies of experimental ebola treatments. As he explains:
I believe the answer to the question of who should receive the drug is: people we can both learn from and potentially help the most. I believe those are the 2 values we use when trying to ration access to an experimental drug. If we do not learn whether something is safe and effective, then we have missed an opportunity, even in the middle of an epidemic, to find out whether it is worth giving out drugs that are new, untested, and unapproved. People who should be included are those who can be observed and kept under surveillance — not for a day or a week but probably for months and years. That favors people who are not in rural villages. That favors people who will have access to hospital facilities. Those criteria will drive the selection of who receives a new, unapproved drug.
In “Ethical considerations of experimental interventions in the Ebola outbreak“, published yesterday by The Lancet, Zeke Emanuel and I discuss what we take to be the key ethical questions about the use of Zmapp and other investigational agents in the current Ebola epidemic. In essence, we argue that the national and international response to the epidemic should focus on containment and strengthening health systems, rather than experimental treatments and vaccines; that experimental interventions, if they are used, should be distributed fairly and only in the context of clinical trials; and that advance planning is needed for research in future Ebola and other epidemics, as well as for making any proven interventions against Ebola accessible in affected regions.
In “Is it ethical to hire sherpas when climbing Mount Everest?,” a short piece out today in the British Medical Journal, I suggest that the question of whether it is ethical to pay sherpas to assume risks for the benefit of relatively affluent Western climbers is a variant of cases–common in medical ethics–where compensation and assumption of risk coincide. Consider offers of payment to research subjects, organ sales, and paid surrogacy. As a result, medical ethics can offer helpful frameworks for evaluating the acceptability of payment and, perhaps, suggest protections for sherpas as we look forward to the next climbing season on Everest.
I owe particular thanks to Nir Eyal, Harvard Medical School Center for Bioethics and Harvard School of Public Health Department of Global Health and Population; Richard Salisbury, University of Michigan (retired); and Paul Firth, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital.
It is important that the WHO committee affirmed the morality of compassionate use. This addresses the concern that any use of unapproved drugs is inherently exploitative. But there are huge ethical issues that still remain unaddressed and unanswered regarding experimental interventions.
In the wake of the Canadian government’s offering 1,000 doses of an experimental Ebola vaccine to the stricken nations, he also extends the argument from allocation of treatment to allocation of prophylaxis in this opinion piece in NBC News Health:
It is ethically appropriate in the midst of a deadly contagious epidemic to try both untested treatments and experimental preventative vaccines that have shown some promise in animals and no safety issues. But with only 1,000 doses of vaccine available, who should get them? And what do they need to be told?
The most ethical way to distribute limited experimental vaccine, is, as the WHO ethics group noted, with an eye toward collecting information on safety and efficacy. Rather than just handing out vaccine to a small group of people in countries that have seen Ebola outbreaks, it is important to learn as much as possible about whether the vaccine has any efficacy in humans and is safe.
Amidst news from Spain that a 75-year-old Catholic priest has received the experimental treatment ZMapp for Ebola, Art Caplancritiques what he describes as the “bad science” behind choosing its recipients:
ZMapp is not the answer to the Ebola epidemic ravaging West Africa. There is no chance of getting a significant amount of this drug made for many months. Deploying more health care workers, face guards, moon suits, gloves and antiseptic, along with restrictions on travel and burying the dead, is the only way to get the epidemic under control. [...]
The fact that a 75-year-old has been given the scarce drug is especially disturbing, not because he is 75 but because 75-year-olds do not have strong immune systems — something very important in battling a virus like Ebola. Moreover 75-year-olds often have other medical problems that complicate the ability of scientists to figure out if the drug is safe and if it is really working.
In testing unapproved, highly risky drugs like ZMapp, it is crucial that recipients not be so sick that they may well die regardless of whether they get the drug or not. Indeed, the recipients ought not be very sick so that side-effects can be seen and efficacy determined. To do that, doctors need to be able to monitor experimental subjects for months to make sure the drug does not damage their livers or cause any other fatal side-effect. So not every person infected with Ebola makes for the best recipient — younger, those more recently infected and those who can be closely monitored are among the “best” candidates.
You can read more of Art Caplan’s perspective on NBC News Health here.
Earlier this week, the World Health Organization, responding both to the international outcry over the rapidly rising number of Ebola cases and deaths across sub-Saharan Africa (and critiques of the speed of their action), and the news that western health care workers and ministry had found ways to get access to the untested-in-humans Ebola drug ZMapp, convened a panel of ethicists to offer recommendations on more widespread use of experimental Ebola treatments.
1) Whether it is ethical to use unregistered interventions with unknown adverse effects for possible treatment or prophylaxis. If it is, what criteria and conditions need to be satisfied before they can be used?
2) If it is ethical to use these unregistered interventions in the circumstances mentioned above, then what criteria should guide the choice of the intervention and who should receive priority for treatment or prevention?
The reasons for different treatment are partly about logistics, partly about economics and, partly about a lack of any standard policy for giving out untested drugs in emergencies. Before this outbreak, ZMapp had only been tested on monkeys. Mapp, the tiny, San Diego based pharmaceutical company that makes the drug stated two years ago: “When administered one hour after infection [with Ebola], all animals survived…Two-thirds of the animals were protected even when the treatment, known as Zmapp, was administered 48 hours after infection.”
But privileged humans were always going to be the first ones to try it. ZMapp requires a lot of refrigeration and careful handling, plus close monitoring by experienced doctors and scientists—better to try it at a big urban hospital than in rural West Africa, where no such infrastructure exists. [...]
But it’s about more than logistics. Drugs based on monoclonal antibodies usually cost a lot—at least tens of thousands of dollars. This is obviously far more than poor people in poor nations can afford to pay; and a tiny company won’t enthusiastically give away its small supply of drug for free. It is likely that if they were going to donate drugs, it would be to people who would command a lot of press attention and, thus, investors and government money for further research—which is to say, not to poor Liberians, Nigerians or Guineans. [...]