Friday 8 August 2014

That every i be dotted, and every t crossed

Vox did some digging into the promising new Ebola treatment. They find:
  • The TKM-Ebola treatment developed by Canada's Tekmira was funded by the US Defense Department after primate trials proved completely effective. They got $140 million from the DoD. 
  • The FDA halted the Phase One trials in July. From Tekmira's news release, linked-to by Vox:
    "We have completed the single ascending dose portion of this study in healthy volunteers without the use of steroid pre-medication. The FDA has requested additional data related to the mechanism of cytokine release, observed at higher doses, which we believe is well understood, and a protocol modification designed to ensure the safety of healthy volunteer subjects, before we proceed with the multiple ascending dose portion of our TKM-Ebola Phase I trial," said Dr. Mark Murray, President and CEO of Tekmira Pharmaceuticals. "We will continue our dialogue with the FDA, provided for under our Fast Track status, in order to advance the development of this important therapeutic agent."
  • A vaccine also is hitting the FDA Fast-Track, with human testing to start in September.
I expect that a Canadian company becomes subject to FDA approval processes for a drug to be used in Africa because of the link to DoD money; FDA approval presumably was part of the DoD requirements. 

It is pretty unlikely that any sponsored prize could match the level of funding that the DoD is throwing at Ebola. And I can't see how additional money helps somebody like Tekmira spring over those rigid FDA walls. 

I wonder why the Phase One trials are being conducted on healthy volunteer subjects rather than field tested on individuals known to have been exposed to Ebola. I suppose it could then be harder to distinguish side-effects, but why couldn't they run the field trials in parallel with the FDA trials?

Prof Paul Hunter, Professor of Health Protection, University of East Anglia, comments:“I welcome the latest initiative from the World Health Organization to convene the group of ethicists to discuss using experimental therapies in the management of Ebola. Given the likely outcome in most patients with infection without specific therapy, I think that most doctors would want to try such therapies for their patients and for themselves if infected. The current system of ethical review of trials of medical interventions have made substantial contributions to protection patients from potentially ineffective or harmful treatments. However, it would be intolerable if this system was so inflexible that it contributed to the deaths of patients who could be saved.
“In my view the ethical case is unequivocal. If a patient is likely to die and an experimental therapy has a reasonable chance to prevent death then it should be given. However, this does not mean that any old drug could be given. For an experimental compound to be given there should be good prior evidence that the therapy will work, the patient or his relatives should give informed consent wherever possible and whenever the therapy is given proper records must be kept and the outcome reported to WHO. Ideally the WHO should produce a list as soon as possible of experimental drugs/therapies where there is sufficient evidence for them to be considered.”
From the same Science Media Centre release, and by contrast, Professor Jonathan Ball:
“Giving unlicensed and untested (at least in humans) treatments and vaccines is a very thorny ethical issue.
The infected US healthcare workers are receiving a type of treatment (antibodies that specifically target the virus) that has a reasonably long safety track record, so it isn’t surprising – given the high fatality rate in the current outbreak – that they are happy to receive the therapy.
“But not all drugs are safe – that’s why we have very stringent clinical trials. One could argue that the current outbreak provides a perfect arena in which to test new drugs, but that isn’t without risk. We don’t know their safety, we don’t know if they are likely to work – sure they have been tested in animals but these studies don’t always tell us what will happen in humans.
“Also, who do you give the drugs to – infected people from the general populace, or healthcare workers battling in the frontline? Restricting treatment only to healthcare workers and volunteers could be seen as unethical, but treating the larger number of local infected people isn’t easy; the supply isn’t large enough and trying untested treatments that may or may not work and may or may not be safe might reverse all the efforts made building trust and goodwill.
“At the end of the day, good infection control is what is going to beat this virus.” 
There's one good way of finding out what happens in humans. We know that the fatality rate is about 60% among those with this strain of Ebola. Get the drug to one of the hospitals, use it on patients there, and see if the survival rate is substantially above 40%. If the drugs don't work, the patients are no worse off. If they have side effects, those side effects are likely preferable to the disease's effects in at least 60% of cases. I'd be pretty mad if some medical ethicists stood between an Ebola-infected me and a treatment that, while unproven in humans, had been very effective in primate trials. Perhaps mad enough to give them a great big sloppy kiss.

Ball's right that in the long term, it'll be infection control that stops things like Ebola. Does that mean we should abandon those infected until cultural practices around treatment of the dead in West Africa change?


  1. As a useful reference: a paper by Medicins San Frontieres folks: "Treatment of Marburg and Ebola hemorrhagic fevers: A strategy for testing new drugs and vaccines under outbreak conditions":,%2520Bausch,%25202008.pdf

  2. Regarding the lack of field tests, I wasn't hearing a lot about Ebola back in July. Isn't it possible the healthy volunteer trial was set up well before the latest outbreak?

  3. Of course. That isn't a particular reason for not running some field trials now that the opportunity's come up though.