Ebola and the ethics of international drug testing

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.

Grief Story: Daughter recalls her father’s death in the UK

The following is the recollection of a woman in middle age reflecting on her father’s illness and death some years earlier. I’ve heard many people from the UK who express similar gratitude for the NHS.

Memory is not my strong point. I say that because, when someone is dying, memory can get fuzzy anyway and I will remember some things about my Dad’s dying and death clearly and some things less so.

I guess Dad’s illness became most obvious about a year before he died. I can’t remember whether I knew it was Myelodysplasia – MDS (a form of leukemia in which the bone marrow does not function normally and produces insufficient number of normal blood cells ). What I do remember is that he started to feel tired and listless and started to have regular blood transfusions, at first once a month, then once every two weeks and finally weekly (and it could have even been more often). This trek to the hospital for the transfusions was quite a burden for him and for Mum. I was living 200 miles away at the time so heard about it in our weekly phone calls. Mum would tell me how he was doing. It seemed at first that everything was under control and there was nothing really to worry about. Life went on.

I think the first time I began to realize that something was really wrong was when I went home for a visit and saw the weight Dad was losing and how his mood was really affected by the illness. He was irritable, not his usual cheerful self. Someone had come to visit, a neighbor who, if I remember right, was also going through some illness himself. I Despairremember Dad only being able to tolerate a very few minutes of the social interaction before he had to give his apologies and go back to bed because he was so tired. I think this was a shock to me. This had to be about 6 months in.

I tried to visit more often of course, but a life in another city and a busy job kept me from doing so. I would hear in more regular phone calls with Mum about Dad’s slow deterioration. I marvel at the fact that the intense regime of transfusions and the treatments associated with them were free to Dad – a function of the British National Health Service (NHS). Over their years of working Mum and Dad had contributed their National Insurance contributions and now the NHS was doing what is was supposed to do – support them in their hour of need. Unlike here in the US, my parents never had a moment of worry about having to pay for the treatment – a true blessing at a time when any extra worry would have been overwhelming.

I learned later that Mum really knew what was happening, despite downplaying the seriousness to us (adult) children. I also learned later from her that she had tried to talk to Dad about the inevitable end point that she knew was coming – his imminent death, but, either because of his fear or discomfort for both of them in talking about such a taboo subject, she couldn’t get him to talk to her until a few days before his death and then only briefly.   My heart aches for the lack of this conversation, and I tear up now imagining what more discussions could have meant to them both.

Over the months, I think I had been hearing the stress in Mum’s voice and came to see them more often. However, she never asked for help – a Northern British trait if ever there was one. The first time she did tell me she needed me to come was on the day of the General Election in May of 1997. I will never forget that day. I was volunteering for the Labour Party that day, taking numbers at the polling station. Mum and I talked and she finally told me that she feared the worst – would I come? I, of course, said yes. I stayed up to watch Michael Portillo lose his seat  and got on the earliest train home the next morning.

When I arrived at home, I remember the stress, grief and fear that I encountered in Mum. I also remember seeing Dad, in bed, so tired, exhausted and drained. And thin, stick thin. A shock to me after not seeing him for a few weeks. That afternoon, the doctor came (yes, a home visit – a rarity these days). Dad had also been tended to by the District Nurse (as a side note, my recollection was that he had been looked after by Macmillan Nurses – an amazing free service via the Macmillan Cancer Support charity in the UK. In later conversations with Mum for this article, she reminded me that although they had applied for this help, everything happened so fast in those last days that Dad died before she got their help).   All of us, the doctor, the nurse, myself and Mum sat outside in the garden on the afternoon of 2nd May. I remember that scene so very clearly. I remember the doctor telling us about Dad’s condition and how he had deteriorated. I remember asking the doctor directly “How long does he have? Days? Weeks? Months?” I remember the doctor telling us that we should prepare for Dad’s death in the next hours and days.   It’s hard to convey to those who haven’t experienced this kind of interaction what a profoundly awful, sad and gut-wrenching feeling is engendered by this information. I think that’s why I remember it so vividly still today, 17 years later. There is something good about knowing this though, of course. It gave us just a little time to prepare.

So, with that time, Mum and I contacted my brother and sister who made plans to come straight away. That night I told Mum I would spend the night with Dad to give her some rest. In hindsight I don’t really know whether I regret that decision or not. It was probably one of the most traumatic and harrowing times of my life. I won’t go into details here but suffice to say that Dad was hallucinating on morphine and coming in and out of rational thought. It was a powerful and devastating experience, for both of us.

On Saturday my sister made it in the morning. She spent some time with Dad and then Mum and us girls made it through the day. Dad was in bed, still gravely ill but hanging on. What I now believe is that he hung on determinedly and staved off death until my brother made it home in the late afternoon. What an amazing gift he gave us for us all to be together at this profound moment. All of us were downstairs a couple of hours after he arrived and I heard a noise upstairs. Mum and I went to check on Dad and sat with him a while. Then he died.   Once more, it’s hard to convey the gravity of this experience. I was so glad we were with him to hold his hand and let him know that he was loved as he journeyed out of this world.   Once his spirit was gone and his body remained, we all as a family spent time with him, in his own bed, sitting with him, drinking whiskey and sharing tears and memories. The doctor and funeral directors came later that night and he was truly gone, spiritually and physically. To be honest much of these activities are a blur to me now.

I suppose the reason for putting all of this down on paper is partly to remember that time and have a record so that it’s noted in this span of life when I can still recall some details. Another reason is to remark on my experience of how terminally ill people are supported and cared for in England. Mum will have her own experiences of the National Health Service treatment leading up to this final time. From what I remember it was supportive. My sister reminded me that it wasn’t all great and that sometimes Dad would be waiting on a trolley until he could get a place in a ward and that this experience made him determined to die at home. However, what I do clearly remember is the warmth, care, attention and dedication of the healthcare providers I encountered. And, what I also remember is that all of this amazing care was free at the point it was needed. No-one in this story had to have the additional stress of worrying about which treatments were covered by health insurance. No-one had to worry about co-pays or debt because of the treatment my Dad had to have. No-one had to have the additional stress of worrying about bankruptcy if things weren’t covered. I know the NHS has it’s problems – it did back then and it does now. But, even though problems exist, the fundamental principles of the NHS: that it meet the needs of everyone; that it be free at the point of delivery; that it be based on clinical need, not ability to pay substantially helped my family to experience leukemia diagnosis, treatment and ultimately death in the best and least stressful way possible. I hope you’re listening America.


When the hospital refuses to provide treatment

Few things are as horrifying as the idea that a hospital might refuse to treat you or a loved one at a time of crisis. This is so frightening, that many used the specter of “death panels” to terrify Americans from supporting the Affordable Care Act, which had no provision for such panels. All the same, we don’t get to go into hospitals demanding whatever treatments we think are appropriate. Doctors, other medical caregivers, and insurance companies all have a say over what treatments are acceptable for various conditions.

One of the most common issues before Hospital Ethics Committees is futility. In all the cases I experienced personally, a family member demanded treatment for loved ones that threedoctorsdoctors deemed inappropriate as they felt it offered no benefit to the patient. In most of these cases, the patient was either dying or already pronounced brain dead when the conflict arose, but other types of conflict over futility arise from time to time.

For a less grave example, consider people who get a cold or cough and go into the doctor demanding antibiotics to treat what is generally a viral infection. Some doctors might prescribe antibiotics just to appease their patients, but others will refuse on the grounds that the treatment offers no benefit to the patient while carrying both costs and some risks. (If you prefer an even more absurd example just to illustrate the point, imagine someone demanding cholesterol medicine to treat a broken arm.) This type treatment is futile because it will have no effect on the condition being treated.

Another kind of futility is both more common and more serious in its consequences. These cases often, though not always, involve infants on ventilators or elderly patients receiving artificial nutrition (feeding tubes) and hydration. In these cases, doctors and the family or other surrogates agree that the feeding tubes or ventilators are keeping the patient alive, but disagree on the value of doing so. In some cases, the patient may be suffering and medical providers feel the patient’s suffering makes it unconscionable to continue treatment. In other cases, the patient may be in a permanent state of unconsciousness or even be brain dead, and the healthcare providers feel the patient no longer exists as a person in any real sense. All the qualities associated with life (consciousness, will, pleasure) are already gone, so treatment has no use.

Few forces in the world are as powerful as the duty we feel to protect our children or to care for our parents or other loved ones. The one comfort we take in the face of such a devastating loss is that we “did everything we could.” When doctors tell us that doing “everything” is costly, painful, and of no value, it can be more than painful to accept. Complicating matters is that most of us have heard of miracle cases where people recovered despite dire prognoses. When told that no more than one in a million patients survive such a condition, family members often only hear that there is some chance of survival. It is a point of honor that they will “never give up” on their child or parent.

I’ve seen doctors handle futility with great skill and also with awkwardness. In one case, a man was convinced the hospital was abandoning his wife at the time she most needed care. The man felt the doctor was expressing the needs of the hospital rather than the needs of his wife. Once he was reassured that she would be cared for even in the absence of treatment, he felt much better about discontinuing treatment. In another case, the doctor made every effort to assure the parents of an infant that she and the entire staff would stay with them throughout the ordeal and do everything possible to reduce both the suffering of the child and the pain of the parents.

It is impossible, of course, to eliminate all disagreements and conflict, but I think doctors who are able to effectively communicate empathy and concern for the patient and the people who love the patient have greater success at avoiding battles with patients. We all want to know our experiences are recognized and validated. We all want to be heard. We also want the dignity of our loved ones to be promoted and protected, especially as they face death, which strips them of autonomy and self-respect. We want healthcare providers to recognize that we hold our dying loved ones in the highest regard even if they can no longer speak for themselves and show why they are worthy of such respect. When we fight for their lives, I think we are really fighting for their dignity and worth as a person. Doctors will do well to keep that in mind.