Given the unprecedented scale of the epidemic, a panel of bioethicists and infectious disease specialists convened by the World Health Organization (WHO) in August unanimously decided that it was ethical to use treatments and unproven prejudices against this deadly disease. The group also said there was a "moral obligation" to gather and share scientific data relevant to whether these products were safe and effective. But he did not indicate how it should happen, and that the testimony of the FDA's representative said, new views are still emerging while others are under development.
In recent months, WHO further consultations and articles of important public opinion by experts and health ethicists statement detailed visions on how to conduct experimental Ebola drug tests. The questions, both practical and ethical, are radically different for drugs and vaccines. unproven medicines go to the sick, who are fighting for their lives and often have few options, while the experimental vaccines were tested in healthy people the most are the frontline workers to protect against the deadly virus. "The ethical arguments are not the same for all levels of risk," noted 17 leading researchers and ethicists from 11 countries in an editorial on screening for Ebola published online drugs on 10 October in The Lancet .
the gold standard for the design of clinical trials for drugs and vaccines is the randomized controlled trial (RCT) in which half the participants are distributed random to receive experimental medicine, while the control group received conventional care, including sometimes a placebo. Médecins Sans Frontières (MSF) has treated more patients Ebola in West Africa than any other group, opposes ECR in the affected countries either for treatments or vaccines. Annick Antierens MSF, who oversees "experimental platforms" for experimental products Ebola, said "this can not be defended ethics."
The Lancet Editorial, led by Piero Olliaro wHO and the United Kingdom of Oxford University, sided with MSF for treatment. in their case, the authors question the sense of "balance" a fundamental ethical principle behind RCTs told investigators should not know whether an intervention is better than what is offered to the control group. "Equipoise is a useful principle, but it can decompose when conventional treatments offer little benefit and mortality is extremely high," write the . authors "This is precisely the problem with the Ebola virus: current standard care does not change much clinical outcomes and mortality is as high as 70%. When conventional care means such a high probability of death, it is problematic to insist on randomization of patients to it when the intervention arm has at least the opportunity to benefit. "
The editorial refutes an article published online September 11 in the Journal of the American Medical Association by Steven Joffe bioethicist at the University of Pennsylvania (Penn) and a previous by bioethicists Annette Rid of king's College London and Ezekiel Emanuel Penn who ran online August 21 in the Lancet. These authors state that "compassionate use" experiments Ebola drugs outside the ECR, as has happened in some patients with the antibody cocktail called zmapp and a drug manufactured by Tekmira, jeopardize the ability to gather scientific evidence and, Joffe wrote, "will not necessarily prevent more deaths than would the drug in a well designed clinical trial. "
Rid said Olliaro and co-authors wrongly assume that receiving an experimental treatment is necessarily better than receiving care that is effective support not available to many people infected in West Africa. She further contends that the editorial "minimizes the possibility that experimental interventions can make people worse" and "neglected concerns the population level, even if interventions are not the worst individuals, they may be ineffective and we would end badly allocate scarce resources. "
the design of real-world studies to test whether the Ebola virus vaccines work has even triggered heated discussions. Many researchers at a WHO consultation held on 29 and September 30 came to the meeting thinking that traditional RCTs were on the table: The feeling seemed to be leaning towards a strategy known as tiered corner that name give all participants the Ebola vaccine at different points in time and then look to see if people who received later were more vulnerable to infection. But at the meeting, Ripley Ballou of GlaxoSmithKline (GSK), which has most of Ebola vaccines in development, has won wide support for its argument that the fastest, most ethical to determine if the product works with RCT is using an "active control" -as a vaccine against a disease proved to be rather irrelevant to a dummy placebo shot.
following that meeting, some wonder if a check active is more ethical than placebo. Peter Smith, an epidemiologist at the London School of Hygiene & Tropical Medicine, who attended the meeting and a consultation 2013 wHO on the use of placebos in trials vaccines, argues the question is practical, not ethics: an active control can convince more participants to join the study "While it is easier to criticize if you use an active control rather than a placebo. then fine, try it this way, "says Smith. "But believe it is more ethical than the other is not the issue." He stressed that the main advantage of joining a vaccine trial, especially in tense resource countries such as these, is that people who develop the disease "are usually looked after better than people not in testing. "
Arthur Caplan, a bioethicist at the University of New York in New York who co-wrote the last editorial Lancet ECR for opposing Ebola drugs, supports their use of Ebola vaccines. But he fears that an active control can cause problems. The immune responses triggered by the vaccine in the active control arm, he notes, "might complicate the interpretation of results" in people who received the Ebola vaccine. It also raises ethical dilemmas if an active control arm uses a vaccine that the country can not afford to use consistently.
Bioethicist Nir Eyal of the Harvard School of Public Health in Boston, who also supports ECR for the Ebola vaccine, said it is "a huge privilege" to offer a chance to participate in a trial that gives people a chance to receive a vaccination with some promise of success of 50%. "Of course, nobody wants to placebo," said Eyal. "But the point of medical tests is not to provide the procedure is medically best for the research topic. It is to establish something that is important and this is crucial-for a much larger population and to prevent a human catastrophe. "
Even MSF does not exclude other types of tests that offer the Ebola vaccine to all participants. Apart from the regime intensified corner, researchers could hold less rigorous testing" observation "which are usually used after the vaccines arrive on the market to see how they work in entire populations." after licensure, there are many observational studies that give us results very, very that we believe useful and meaningful, "said Arthur Reingold epidemiologist at the University of California, Berkeley.
In this scheme, the vaccine is distributed without an organized study and investigators should examine the Ebola rate in a cohort of vaccinated people say, health care workers in a hospital or evaluate vaccination rate in people who develop Ebola. "The key question when you start to calculate vaccine efficacy is whether people who receive the vaccine and those who did not receive the vaccine are relatively comparable," Reingold said.
Yet another hot issue is one that should be entitled to receive experimental drugs or treatments. unusual treatments such zmapp preferably have gone to health care workers because, as the consultation in August WHO stressed, they put their lives at risk for others and they are required to control the epidemic. Emanuel Rid matter and if it makes sense, noting that health workers have close ties with the medical community and relatively high levels of income. "Their priority may be considered more focus on the well-off already, especially in contrast to those who provide care without being trained as health professionals."
On the front of vaccines, GSK can have up to 20,000 doses ready for effectiveness testing in January, but it still means there will likely participants much more interested in the product. The latest WHO consultation said frontline workers should go first, not only doctors and nurses to a group that includes anyone who helps care for patients or even bury those who die.
For convenience, participants meet Michael Selgelid Monash University, Clayton, Australia said it is more logical to offer the vaccine to the "traditional design" concept of a worker Health care. "They are better able to give proper informed consent, and it is crucial in this scenario that we really good informed consent," he said. At the end of the day, Selgelid said, regulators such as the FDA probably will strongly influence the trial design as it is they who will ultimately decide whether these products can come to market. "Just how flexible the regulators will be is a matter for them rather than me," he said
* Ebola files :. Given the current Ebola outbreak unprecedented terms of number of people killed and the rapid geographic spread, science and science Translational Medicine made a collection of research articles and news on the viral disease available for researchers and the general public.
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