Why the WHO ethics advisory group is a start but hardly sufficient

Screen Shot 2014-08-12 at 5.37.18 PMThe much awaited WHO ethics advisory group on the use of experimental drugs to combat Ebola has issued its statement.  While a start it is no more than a baby step.

The advisory panel did decide that they found the case for using experimental drugs in African populations ethical.  While they did not say much about why they reached this conclusion it seems valid in that when facing a deadly plague the overwhelming majority of people infected would want a drug, even one that has barely been tested, to try to save themselves or a family member.  In reaching this conclusion the committee puts to rest the argument that experimental drugs could not go to Africans at all or ought to go to Americans or Europeans first in order to avoid the charge of exploitation.  In a plague that kills 90% of its African victims complaints about unwarranted exploitative research seem a bit ridiculous even against a long history of misuse and abuse of poor desperate persons in poor African nations.

The committee did not say a good deal more other than that informed consent and choice ought to be respected.  This is far less helpful.

Informed consent and choice are wonderful values but they need spelling out in the context of a deadly plague impacting desperately poor and often uneducated populations with little access to health care.  Who is to get the consent.  What help will be given to potential subjects to insure their comprehension?  If those who get a new drug or vaccine are injured by it do they have any redress?  Who will pay the costs of getting the treatment and of travel, food and housing that associate with experimentation?  And who will consent for children, prisoners, the mentally ill or those rendered incompetent by Ebola?  Can a government or tribal leader consent for a community.  Must an IRB or research ethics committee review all scripts be they written or oral that will be used to get consent?

The committee also had nothing to say about the obligation of companies to make experimental drugs available.  Consent does not matter if a company will not release an experimental drug for reasons of money, fear of adverse events or worries that they cannot manage a large scale release.

 And even if a company is willing to release its drug shouldn’t some independent scientific body vouch for its reasonableness.  There are quacks, charlatans, fast buck artists and crooks more than willing to say their remedy, potion, nostrum and gris gris stick is the answer to Ebola.  Who is to stop them or at least restrain them when the infected are looking for any life-preserver?

Lastly, the committee gave no advice about who ought to go first when supplies of experimental (or for that matter proven) therapies are scarce.  Should children get priority?  Only those who can be monitored over time to assess the outcome of an intervention.  What about health care workers, funeral directors, cleaning personnel and food providers who go in harms way—ought they get priority over others?

Ethical choices are hard.  Ebola has left us with many more than the WHO committee addressed.

Arthur L Caplan is Director of the Division of Medical Ethics at NYU Langone Medical Ctr and the head of the Division’s Project on Compassionate Care


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20 replies »

  1. Wonjderful blog you have hhere but I wass wondering if you
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  2. Cyndy,
    You might want to take a look at the Health Impact Fund idea developed by Thomas Pogge and Aidan Hollis; they argue that if pharamceutical companies received rewards not because of patenting exclusivity but based on the impact (in terms of added QALYs or DALYs or the like), they would be incentivized to produce new molecules/treatments for the diseases that contribute the most to the global burden of disease rather than to create another me-too drug or to rejigger their existing drugs in order to extend the patent. There are large challenges in implementing the idea, but it is a creative response to the problem you mention.

  3. This is rather a delicate issue and i guess one of the reasons the WHO committee gave the verdict they gave was because they are as desperate as the victims themselves!,

    But while this is the truth of the matter, there surely aught to be some form of regulation on this. The WHO ethics committee’s verdict sounds rather blanket to me and may pose a great danger to our poor African community. Clearly, using a drug substance that is still in its early preclinical stage poses a greater danger than one that has gone through at least the whole preclinical phase using guinea pig, monkeys etc, if not a phase 1 trial. With the committees decision, its possible that any pharma can rush and take advantage of the directive to test a drug that is at any given stage of the drug development chain. It must be noted that informed consent is practically impossible in this situation as both victims and their caretakers are going through serious psychological distress. What structures have been considered to take care of this. I think the committee should have set at least some threshold of some sort to allow for protection of these already vulnerable population eg allow for vaccines that meet a certain basic minimum requirement..As we get excited about just giving any vaccines that comes around, its really important to think about the long term effect of this. What if such a vaccine were to cause entirely a new communicable health condition that could be more lethal than Ebola?…just a weird thought!

    On the other had, am asking myself how different is this situation from the Pfizer scenario in Nigeria. If anything bad happened to those being exposed to the untested vaccines, what would stop them from suing the pharmas involved…this is indeed a catch 22

  4. “Gouging is not incompatible with value, it is reflective of the value one places in extreme scarcity.” followed by the Sahara desert argument.

    Saurabh, in economic terms I believe the word “scarcity”, when involving a product, shouldn’t be used because there is no scarcity if the price is permitted to adjust up and down in a marketplace.

    The middle of the Sahara desert isn’t a marketplace for Coca Cola or mineral water, sparkling or otherwise. It is a place where one should be prepared. Thus I believe except where there are ‘price gouging’ laws the word shouldn’t be used unless there is some type of swindle associated with the high price.

  5. “Gouging is a relative term. The value of a product is what one is willing to pay for it”

    Gouging is not incompatible with value, it is reflective of the value one places in extreme scarcity.

    If you were dying from thirst in the Sahara desert and someone decided to charge $100, 000 for a large bottle of mineral water, and you agree, as it’s a matter of life and death, that is the value of the water in those circumstances.

    Gouging is merely the understanding of the scarcity and desperation and use of that understanding towards higher profits.

  6. Cyndy, I don’t think comparing a new entry drug with the gold standard is all that difficult. It does cost money. The difficulty lies in the fact that as we learn more additional metrics might come into play. [ie the gold standard talks about lowering cholesterol but later the metrics also include HDL]

    I also don’t believe this type of policy stops the consumer from choosing from the drugs available. It might however limit the number of me too drugs for the consumer to choose from and thus leave a family member without as many variations of the drug. However it will leave the researchers and capital available to investigate drugs that might provide more benefit to a wider number of people.

  7. Gouging is a relative term. The value of a product is what one is willing to pay for it. Every company would “gouge”, but they recognize that without sales they make no money so it is in the interests of the buyer and the seller to compromise on price. Generally there is more than one way to skin a cat so the consumer will look for the alternative if the price is too high or will incentivize the production of a less expensive product. That might mean that just like with TV’s we have to place our desires on hold (as horrid as that might sound) and wait for that 100 inch TV until the price falls.

    Insurance is a mechanism for spreading the risk of unaffordable but necessary products. The consumer should be making the choice as to what they are willing to pay. Sometimes costs are too high and therefore consumers forgo the possibility of a treatment that later becomes available. But that always occurs and all we need to do is take note of the treatments and costs Steve Jobs paid for. Most of us can’t afford it, nor can we pay the premiums that would provide such care. Thus we do without. The market place has set limits as to how much is available to be spent. If that is not done then one sector of the economy brings the other sectors down causing more harm than good ultimately leading to a lower standard of living which is the great determiner of lifespan and other metrics we frequently measure.

    In the case of Ebola most Americans rightfully don’t perceive a threat so they are unlikely to put up their own dollars to find a cure for such a disease. That means the treatment of Ebola is not in the market place and nor is it an American responsibility though I support such research. Since it is outside of the marketplace there are alternative ways of funding such a project if there are willing funders.

  8. Allan,
    How will we compare “gold standard?” It’s a slippery slope. I’ve written before, so I apologize if you hear this more than once: I have a fam member who cannot take the cheapest statin, nor any other statin, than the one used right now. It’s not the gold standard, nor the most popular, nor the cheapest. But without it, his heart disease worsens. This is why it’s imperative to get the end users into the mix, so we can discover the attributes of populations that are best served and where adherence (if there’s long term adherence needed) can be promoted.
    That said, you are completely correct on 3rd parties. But it’s terribly hard to take a person’s livelihood away from him/her.

  9. As long as big pharma knows it can price gouge in the free market it will innovate & we need not fear Ebola.

    All regulatory stuff & surveillance you’ve suggested is fine, so long as pharma can make a killing for stopping a killing.

    This is capitalism, warts & all.

  10. What is the likelihood that a new drug at this stage will have deadly side effects? If it’s less than the 90% death rate of Ebola, and I have Ebola, I’ll take it my chances, but all patients should be aware of risks on both sides, but hwo well can we determine those risks?

  11. Isn’t third party payer a stumbling block in our ability to get the best value for the dollar?

    Let’s assume third party was eliminated (not eliminating insurance) and patients were more directly affected by price. Without interfering with what the pharmaceutical companies produce couldn’t the FDA require studies to have head to head comparisons with the gold standard of the day so we have a metric for the consumer to compare me too drugs? Wouldn’t that lower prices and reduce the search for more me too drugs?

    Wouldn’t that leave more investigators open to research in other areas?

  12. I agree. That’s why I think we need deeper, broader, faster input from patients about the drugs they are prescribed. Pharma should not collect this–it’s gotta be completely socially driven, 1-3 questions, potential follow up with permission.
    It’s not my intent to reduce players or manage Rx bottom line. It is my intent to align goals so that people get healthier–that benefits everyone.
    Let’s do be sure that Gilead’s diabetes drugs were not the success that Sovaldi, as an example, appears to be. Let’s be sure, too, that ZMapp is coming from a new player. I believe there will always be smart folks who want to solve a large problem, and that coaxing and info from the patients/families/communities can help to encourage their efforts.

  13. Remembering the health battles that occurred in this first world Nation’s history: The treatment of childhood leukemia, HIV, etc. They were not neat and organized battles that many bureaucrats like to see. They were messy. The innovators were frequently faced with disagreeable circumstances blocking their inevitable advancements.

    Ethics are not completely static. They vary with the nature of the battle. The ethical details cannot be created by those that do not have their feet in the ground. Those specific ethics will have to be formed on the spot where the catastrophe exists based upon those most responsible for treatment and the political leaders of the nation. Meaningful support will come from what Saurabh Jha calls the “much maligned big pharma” because the “greater good nonsense” has little to offer to remediate the problems faced in Africa.

  14. I understand your sentiment but I’m not sure there’s an easy answer.

    One way of discouraging “me too” drugs, i.e. incremental improvements, or slightly newer wine in slightly newer bottles, is not to set a threshold of cost per QALY for approval.

    That is make the approval process arbitrary, where unless pharma comes up with something ground breaking in terms of incremental effectiveness or a Sovaldi essentially, the compound won’t be approved.

    The trouble is that would reduce the number of players in the system. Drug discovery is essentially a game of dice throwing, there will be fewer players willing to throw the dice.

    Currently, the profits from “me too” help create other “me toos” but increase the chances that Sovaldis, malaria and HIV vaccine, treatments for VHFs, are created.

    No easy answer here.

    As always, trade-offs.

  15. If that’s the case, then we need a bigger say in what drug gaps need to be filled, what we are willing to pay, etc. That destroys the open marketplace of capitalism. We should, IMO, find a partnership avenue that distinguishes between me-too drugs and new molecules/treatments, prioritizes through payment recognition, and encourages new, small companies to develop and promote.

  16. Big pharma needs money, loads a money (greed, profits, etc). The more we demonize them for making hay on suffering, the less likely we will be bailed out when we need to.

    Faustian bargain. But if wish to live longer, it will cost.

  17. Another story that hit my inbox says that 2-3 medical groups will decide who in America gets the new HepC drugs. Dr. Caplan, perhaps your efforts could pull together a broader band of folks that are not all clinical in order to create a framework for these beginning ethics and the pioneers who are stepping into the art and science of health value. I’d be happy to work with you to broaden the reach beyond clinical.

  18. Two stories in the news this morning that shouldn’t surprise anyone:

    West Africans are taking to Twitter to demand access to the vaccine, using the hashtag #giveustheserum

    And drug’s maker reports that (obviously) limited supplies are exhausted.

    Comparisons to the Tamiflu scenario will now be made by all.

  19. As Dr. Caplan has alluded. ethics do not operate in vacuum.

    There are ethics and then there is common sense, which is the mother of all ethics, meta-ethics. Suspension of common sense is gravely unethical.

    Common sense tells us that to worry about, even suggest informed consent (and other first world indulgences) when there is an epidemic of Ebola is akin to Marie Antoinette playing the fiddle (mixed metaphor there).

    The WHO is, how do I put it politely, of constrained usefulness.

    No, it is US’s much maligned big pharma that can most likely come to the rescue here.

    Might this be a lesson for all that demonizing profits and lauding “for the greater good” nonsense can actually be quite injurious to health? Thought not.