A Spanish priest and two Americans - a doctor and a hygienist – who contracted the Ebola virus disease were evacuated from Liberia recently. Lengthy testing of several drugs that may save the lives of hundreds of Ebola patients or vaccinate communities against a future epidemic has never been done because no one has stepped forward to fund the final necessary research.
Guinea, Liberia, Sierra Leone and Nigeria are prepared to offer risks that could mean life of death for more than a thousand people.
Doctors for all three sought access to Z-Mapp, a drug treatment that has not been tested on humans. Whether the Madrid hospital where 75-year-old Father Miguel Pajares died this morning had time to give him the drug is not certain. The two Americans, Dr. Kent Brantly and hygienist Nancy Writebole, are being treated with the same drug in an Atlanta hospital, but their recovery is not yet assured.
The World Health Organization (WHO) yesterday approved the use of untested drugs on the grounds that the deadly virus has turned into an international medical emergency. But first, they spent several days wrestling with the ethics of approving Z-Mapp and several other drugs not yet tested in humans.
Do the drugs harm the patient?
“Drugs obviously usually have to go through a three-step process for both safety and effectiveness before they can ever be given to human beings,” says Nancy Kass, a professor of bioethics at John Hopkins University and the Bloomberg School of Public Health. “None of these Ebola drugs have gone through any kind of human testing.”
The four West African governments now seek access to the experimental drugs. Kass says these governments and WHO need to figure out whether it is appropriate to give an experimental “to a few people with Ebola to see what the effects are or - at the very least – do they need to wait until some safety trials are done to make sure that the drug is at very least not harmful?”
The Liberian ministry of health seeking access to experimental drugs for patients now in quarantine has received permission to receive the Z-Mapp experimental treatment. All four African governments face two critical questions, according to Kass. Will patients experience minor or major side effects of the drugs? Even if the drugs don’t harm the patient, do they do any good?
What if Z-Mapp doesn’t work?
“There is a whole other kind of question about whether the drug is effective,” says the bioethicist. “Giving people an ineffective drug sometimes can also be harmful because it can create distrust or it makes public health people think that they have a solution when they don’t.
“But the biggest risk is the safety risk.”
Will those administering the drugs decide to test the toxicity and dosage of the drugs on uninfected volunteers first? “It depends how long they want to wait to see what kind of bad effects there are,” Kass says.
“Safety studies done properly also go gradually. You probably wouldn’t give five people the drug all at the same time in case there is a very serious toxic effect in humans. The best way to do it ethically is to give the drug to humans one at a time and at least wait a couple of days … in case person number one has this horrible an unexpected reaction …To do that safety study would take about a month.”
Experience with drug trials in low-resource countries in Africa, for example, has a politically toxic history in which patient advocates have charged that drug makers in developed countries are exploiting poor populations. Kass says the countries that produce the drugs now seek paid volunteers within their own country in order to monitor risks of serious side effects.
Kass speculates that given the odds that more than one-thousand Ebola victims currently face a 40-percent chance of survival without any drug, medical authorities and public health administrators may skip the safety trials and hope the drugs they give are not only not dangerous but effective.
Nothing to lose
Kass says Ebola patients do have something to lose if they do not take try a new drug that may not be effective. But she says the decisions are not that easy to make for patients or medical personnel.
“A critical question there would be giving it to people who really understand. There is a way you can figure out whether they really understand that it’s still at a fairly experimental stage.” She says researchers usually find that those who are very sick have a hard time understanding, “not because they are sick but because they’re so hopeful that the treatment will be effective.
"And particularly with it having been given to these two Americans, I think there may be a perception problem now that someone has concluded that these drugs are effective, and it couldn’t be further from the truth.”