Arthur Caplan

Can Ethical Review Be Automated?

R. Horton

I often told my students of the connection between comedy and philosophy, noting that many popular comedians have an academic background in philosophy. [Editor’s note: insert generic list of philosophical comedians here.] Hoping to validate my statement and gain interest points for himself, one student approached me to say he went to the comedy club and the comedian joked that he started doing comedy after graduating with a philosophy degree and learning that “all the big philosophy firms” were not hiring.

It is a good joke, but I’m assuming this comedian was not a bioethicist. According to the prominent and well-paid bioethicist Arthur Caplan (whose comments appeared in this article by Sheila Kaplan for STAT), for-profit review boards complete almost all institutional review of research ethics. He is quoted as saying, “If you want to work in research ethics,” he said, “you work with them.’’

In other words, institutions developing research protocols, farm out the review of the protocols to for-profit ethical review. If you’ve ever reviewed research proposals, you know that it is a little bit mechanical, anyway. You ask basic questions: 1. Is there a consent form? 2. Is the consent form complete? 3. Are appropriate disclosures included? And so on. Most people involved in review, tick through a checklist to make sure everything is in order.

The work is tedious and mostly clerical, if we are honest. It makes sense to just pay someone to go through and make sure everything is in order. Leave it to the professionals. It saves time and may ensure nothing is overlooked. It is worth the investment to make sure nothing slows down your project or results in embarrassment down the line. The professionals know exactly what they are doing, and you want it done right.

While it makes perfect sense to hire a professional review of your protocol to ensure it meets all legal and regulatory requirements, I fear a professional reviewer will work to find ways to make the protocol successful rather than questioning whether the whole venture passes ethical muster.

The problem is that I’m not sure how you move from “How can we do this according to established ethical standards?” to “How can we act ethically in the pursuit of the good?” Is it possible to seek the good life for hire? Or, is it possible for competent ethicists to exist if they are not paid for their work? How do we create space for genuine soul searching among ethicists?

Of course, ethicists need to be paid for their expertise and work, but it raises problems when how much they earn is tied to what answer they give. A commercial IRB won’t get much businesses if it tells all its customers their research is unethical, so at least some ethicists need to be free to comment on research and all other areas of life and work without their specific answers affecting their income.

Further, the work of such independent ethicists must not be disregarded specifically because they are outsiders. Ethicists working within a system are necessary and their expertise is valuable, but only outsider ethicists are able to comment freely and honestly.

At some point, you have to ask how your work looks to outsiders. People within a system are often amazed that anyone outside the system could possibly doubt their motives, but it may be the outsider who sees your motives most clearly.

Privatization eliminates spaces for free inquiry. While private enterprise certainly has a role in medicine and research, it is imperative that we preserve or create public spaces for ethical discourse. It isn’t a question of experts versus non-experts. It is a question of ethicists with something to gain compared to those with nothing to lose. Sometimes, you have to listen to the voices of those with nothing to lose.

Ebola and the ethics of international drug testing

R. Horton

Ebola has been around for nearly 40 years now, and until recently the public was unaware of any available treatments or treatments in development for the disease. In fact, there is no market incentive for pharmaceutical companies to develop treatments as most of its victims are too poor to buy medicines. If and when Ebola spreads to more affluent parts of the world, of course, pharmaceutical companies will adjust their research and development strategies.

As market incentives for development of treatments do not exist, it falls to governments to fund research into possible treatments and vaccines. As Marie-Paule Kieny, assistant director-general of the World Health Organization (WHO), pointed out, “If it hadn’t been for the investment of a few governments in the development of these drugs, we would be nowhere.” Much of the funding for research has come from the United States, not from humanitarian concerns for Africans, but for domestic concerns. According to a Globe and Mail article by Geoffrey York, “most of the research on Ebola treatments has been financed by the U.S. government, often because of fears that the Ebola virus could be used aesculab-stabas a form of bioterrorism.” Be that as it may, it is a relief to know that someone is working on treatment and prevention.

As the disease has occurred in Africa, you might expect that research on it should also occur in Africa with robust drug trials being conducted in an ongoing basis, Bioethicist Arthur Caplan  says it is unreasonable to expect the research to happen in Africa. He wrote, “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.” ZMapp is the drug given to the Americans who contracted Ebola in Africa before being flown back to the US for treatment.

It might be possible for pharmaceutical companies to build such infrastructure, but Caplan encapsulates the real reason research does not happen in Africa nicely: “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.” Enthusiastically give away? No, they won’t even develop the drug in the first place.

Now that an experimental treatment (ZMapp) does exist, should it be tested on Africans? Bioethicist George Annas says, “If the drugs we are currently working on have been shown to be reasonably safe, and if there is realistic and robust African review and individual informed, voluntary consent, use of American-developed drugs in Africa could be justified.” Annas is here emphasizing the protection of possible African research participants rather than explaining why only the privileged should receive the drug, and he has good reason.

It isn’t as though the lack of infrastructure in Africa has prevented drug trials from taking place there in the past as you might imagine from the debate over Ebola drugs. In fact, testing has raised serious issues of exploitation in the past as drugs were tested on vulnerable populations with no intention of ever providing those same populations with any treatments that might be developed. In 1994, the HIV drug, AZT (zidovudine) was found (in a study known as AIDS Clinical Trials Group 076)  to prevent transmission from HIV-positive mothers to their infants. The study was considered important in the development of drugs to treat AIDS, but there were no plans to provide AZT to the communities where it was tested once the clinical trials concluded. Research subjects in Africa bore the risks associated with taking experimental medications but would not see the benefits of the medications developed.

As there is no market incentive for pharmaceutical companies to develop treatments while protecting research subjects in vulnerable populations, it is up to governments to help promote treatments for unprofitable diseases. This has obviously happened to an extent., but we could, and should, do more. Philosopher Thomas Pogge has initiated a plan to help improve the situation. He has proposed a Health Impact Fund  that would provide a sort of artificial market incentive for companies to develop otherwise unprofitable treatments. Under the plan, governments would contribute to a fund that would then be distributed to pharmaceutical companies based on their ability to develop drugs that would have the greatest health impact. In order to receive payments from the HIF, companies would agree to provide treatments at cost anywhere in the world. I don’t know whether the Health Impact Fund will provide a solution to treating diseases that primarily affect the poor, but it certainly represents the kind of thinking required to address these serious issues.

If we are not motivated by the suffering of others in the world, and it appears many in affluent countries are not, we may do well to recognize that diseases do spread beyond all borders. Diseases that do not affect us today may well affect us tomorrow. The so-called “free” market is obviously not the solution, so we will do well to consider other options.