Experimental Drugs in the Face of Epidemic

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The death toll from the Ebola virus has now broken 1,000 including native and foreign health workers. On 11 August the World Health Organization (WHO) determined that “…provided certain conditions are met …it is ethical to offer unproven interventions with as yet unknown efficacy and adverse effects” (source)

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This release was swiftly followed by a report that the last doses of the experimental drug, ZMAPP, which may have played a role in two Ebola-stricken Americans’ recoveries, had been exhausted. One wonders how the WHO’s decision will impact the distribution of other experimental drugs if the Ebola problem gets further out of hand. (source)

In 2012 Sanofi-Pasteur (the world’s largest vaccine manufacturer) conducted a study in Thailand involving 4,000 children and an experimental Dengue vaccine. The study was largely a flop; it provided protection against three of four dengue fever strains- but no protection against the one most common in Thailand. (source)

According to the CDC and follow-up studies, this trial involved a vaccine candidate that has left child-volunteers with “…a significant… risk factor forsevere illness among children in a dengue hemorrhagic fever endemic region.” (source)

A bioethics expert from Johns Hopkins points out, there are many reasons to pursue using experimental drugs as a tactic to slow Ebola (source) and if there’s a chance it will help, why shouldn’t be offered to those infected?

Right now, the supplies of Zmapp have been exhausted. Imagine if we had the capacity to produce large quantities quickly. Since it is widely accepted that we don’t know if Zmapp contributed to the two American recipients’ improving conditions- or even if they improved despite Zmapp, what would that mean for the people elsewhere if they were also administered it? What if Zmapp or another experimental Ebola drug caused an unforeseen increase in transmission? 

The media has amply covered the potential benefits to using experimental drugs. There has been little discussion of the potential risks. These drugs need to be understood more comprehensively as they stand to hurt an unknown number of people as they stand to help. 

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8 Responses to “Experimental Drugs in the Face of Epidemic”

  1. guidojaramillo Says:

    This is a really difficult topic and unfortunately there is no easy answer. I fully agree that we need to be very careful in how we use these experimental drugs as there is currently only limited information. Furthermore, we cannot expect that the impact of providing these experimental drugs to impacted people in northwest Africa will have a similar results as the two people treated in some of the best hospitals in the US. The level of care cannot be compared in the situations. Nevertheless, if patients in northwest Africa do not have an alternative and some experimental drugs do show promising results it would also not be fair to completely exclude these patients from receiving these drugs. One thing is for certain, if these experimental drugs are given to infected people in northwest Africa, these patients needs to be monitored closely and information needs to be collected in order to be able to quickly identify any significant side effects in case they would appear and also to assess the efficacy and efficiency of these drugs (because if the experimental drugs are a flop, a system needs to be in place to identify that as quickly as possible).

  2. sawsanjabri Says:

    I think, this is a very challenging issue. Giving a drug that is untested on human to patients suffering Ebola in an epidemic is a double edge sword.
    While the administration of the untested medicine could help, of which there is no previous data to compare with and prove that its solely the medicine that helped… however, it could also hurt and produce side effects, of which, also no data to prove the link of side effects to it. In such situation, confusion and errors would be highly expected. Any complication of Ebola infection can be interpreted as side effect of the medicine and demands further studies to prove it,
    On the other hand, from ethical point of view, I think, such approach of giving untested or not approved drug to human, will open the door wide for future applications in similar cases. The world will continue encounter medical crisis and epidemic, and I think, the WHO should adhere to the standard protocol for dealing with epidemics, and if there is a need to break the rules, it should be carefully studied and researched.
    I totally agree with a Dr Rosoff saying: “Desperation doesn’t necessarily breed good science or good medicine.”
    http://www.vox.com/2014/8/17/6003477/the-case-against-experimental-unproven-treatments-ebola-outbreak/in/5712456

  3. teitg Says:

    What a challenging decision regarding ZMapp and at what cost? Without a randomized control trial, it seems that we are jumping to conclusions regarding efficacy, but like the JH bioethics reference above, if there’s a chance, shouldn’t it be offered? Unfortunately the unintended consequences including the social repercussions, cost, not to mention the medical or unintended patient consequences will exceed any good if the drug proves to be futile. Xigris, a medication we once used in the ICU for critically ill septic patients (a very expensive intervention often used as one of our final efforts for our sickest patients) ultimately proved to be useless and was withdrawn from the market in 2011. Dr. Rosoffs quotation mentioned above certainly resonates. NYT just wrote an interesting article regarding the difficult decision and controversy of providing ZMAPP to Dr. Khan in Sierra Leone. Tough decisions and makes me question what I would do/want done if I were faced with the same situation…

    http://www.nytimes.com/2014/08/13/world/africa/ebola.html

  4. kwells32014 Says:

    This is a well written and insightful article. I have been very perplexed with this issue myself. As a clinician, one does wonder could we do more harm than good? The huge problem here goes back to the current state of the pharmaceutical industry, I hate to be negative here, but the current state of Pharma research goes toward drugs that stand to make the manufactures significant dividends. The market for new antibiotics is not as lucrative, therefore very few “new” antibiotics are being created and thus researched to help combat some of our most dangerous drug resistant illnesses. The concept is similar with diseases like Ebola. Unfortunately, this disease primarily occurs in many of the “forgotten” parts of the world. This is incredibly unfortunate, because a human life is worth the same no matter what part of the world they were born into, whether it is a resource rich or a resource poor country. The world, and by that I am also including the global health community, was not prepared for an epidemic like this. Through international travel, and the globalization of our society, what happens in what part of the world has the potential to effect us all no matter where we live. I agree with the JH ethicist, if there is hope in a medical intervention that is ravaging communities why wouldn’t we do it? This is a scary and difficult problem that has no easy answer, there is so much more at play than just giving a serum, this problem comes down to infrastructure, the manpower for containment, the education to halt the spread, and the compassion from the World’s global health community to get involved.

  5. sybilklaus Says:

    I agree this is a well written and very relevant blog posting. This morning on NPR they played a story about this issue. The Ministry of Health in LIberia mentioned his concern that he was concerned the ‘promise’ of an expimental drug would detract awareness and attention from the only current proven intervention “avoidance”/isolation of the infected patients. He also highlighted the local communities concerns about cohorting suspected infected individuals from different communitites together. He mentioned that they were not aware of the communities hesitancy for this type of cohorting and since they became aware, have changed how they co-hort the patients. This is such an amazing challenge for west Africa. I hope that the governmental agencies can continue to raise awareness and encourage early intervention for those infected with this serious disease.

  6. Jenna Ferrara Says:

    Thank you for posting this blog! Whether or not to use investigational drugs is certainly a difficult decision due to the numerous unknowns. Although the Ebola outbreak sparked much discussion and debate regarding compassionate use and expanded access to investigational drugs, it should be noted that this is not an entirely novel topic. Policy regarding the compassionate use and expanded access to investigational drugs ensures that several regulations are followed, stating that:

    Physicians must determine that the probable risk from the drug is not greater than the the probable risk from the disease AND

    The FDA must determine:
    -That the potential benefit justifies the potential risks of the drug and that those risks are not unreasonable in the context of the disease or condition to be treated, AND
    -That that the patient has a serious or life-threatening disease or condition and no other comparable or satisfactory therapeutic options, AND
    -That providing access will not interfere with development of the drug, AND
    -That the patient cannot obtain the drug under another protocol (such as in a clinical study of the drug)

    Although many unknowns remain despite these regulations, my interpretation is that these investigational drugs are only to be used under extenuating circumstances, under which limited to no alternative options exist. It’s been helpful to me to consider what I would wish for myself if placed in the situation of the two American Ebola patients, and under those circumstances, I would consider myself fortunate to be offered ZMAPP. Of course, this brings up another ethical question; who should be offered the limited supply of investigational drugs? To me, this question is more difficult than whether or not they should be offered at all.

  7. stonegod79 Says:

    This is a very challenging situation and topic for all of us. I really appreciate that the author chose this topic and posted it.
    Personally speaking, I’m skeptical about the effect of ZMapp. This is not because of the mechanism of the drug but the circumstances of the patient who are going to take this medicine.

    First of all, nobody wants to take or administrate a medicine that is not proven to be safe unless the disease condition is near to death. This means ZMapp may be administrated to sever patients and has to save really bad condition patients. However, from my experience as pharmacology researcher, it is almost impossible for a single agent to save such a severely infected and damaged patient. Especially, this is a viral infection.

    Alternative way to use this medicine is dosing it to a mild case and prevent it to become sever. However, nobody knows how this drug can effect the mutation of this virus and doctors do not want to make any chance of mutation.

    I think at this moment, ZMapp will be used for a patients who are in between life and death. The result does not tell whether the drug is efficacious or not. I guess WHO permitted to use this drug from a humanist perspective and not they are believing that this drug can change the situation.

  8. jegwuagu Says:

    Thanks for this insightful and timely post. It is certainly true that when considering the use of experimental drugs or vaccines, one must seriously examine the potential risk as well as benefits. When considering the negative impact of using experimental drugs, you gave an example of the consequences of experimental a Dengue fever vaccine in Thailand. I think it is important to distinguish between the use of experimental drugs in infected patients and the use of an experimental vaccine in otherwise healthy individuals and I would consider the latter far more controversial. When confronted with a disease like Ebola that has a fatality rate of 60% to 90%, it could be argued that those infected are faced with a life and death situation that warrants the use of experimental drugs for treatment. The use in this case would not be for the purpose of research or to determine the drug’s effectiveness as others have said, but instead to try and save a patient’s life. If the drugs are available (which is apparently not so in the case of ZMAPP) I think we should allow the patients to decide whether they are willing to risk potential harm by taking the drug and agree with WHOs decision to permit the use of such drugs. We must also consider the other peculiarities of this particular outbreak such as the incredibly fragile health systems of the affected countries, largely unable to provide the supportive care required to keep an Ebola patient alive (i.e. blood transfusion, life support, etc.), making an argument for the use of experimental drugs even more convincing.
    When considering a vaccine however, the consideration of potential risks becomes increasingly important because the experimental vaccine would be administered on otherwise healthy individuals, not Ebola patients. If an experimental vaccine is administered and as a result those vaccinated develop Ebola or die, the epidemic could take a dangerous turn, possibly harming not only those given the vaccine but the entire epidemic response effort. It could also worsen already festering social and cultural issues such as the use of experimental drugs on Africans, perceptions that the epidemic was brought to the region by the west and the perception that health workers are harming patients as opposed to helping them (issues already noted in some affected countries. While it is certainly humane to consider the use of experimental drugs for Ebola patients, great care should be taken to roll out experimental vaccines in Ebola affected countries.

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