The Ebola Vaccine and the Ethics of Drug Trials

By Greg Mercer

The World Health Organization recently announced that a trial of the VSV-EBOV Ebola virus vaccine in Guinea has been “highly effective,” and that randomization in the trial would be stopped to allow for expansion of the range of subjects and protection of more people against the virus.  The trial began in March, and until recently, randomized subjects so that some received the vaccine immediately, while others received it later, after the virus’ gestation period.

A paper published in The Lancet details the study, and finds that the vaccine is highly effective and likely safe to use in the affected population.  The “recombinant, replication-competent vesicular stomatitis virus-based” vaccine is administered in a single dose via the deltoid muscle.  4,123 people received the vaccination immediately, while 3,528 people received the delayed vaccination (more on the study methodology in a moment). The researchers found that no subjects developed a case of Ebola after receiving the immediate or delayed vaccination, meaning that the vaccine proved 100% effective (with p=0.0036 at 95% CI).  These findings are excellent news for researchers, government officials, and those in the affected counties, and are fascinating from a scientific standpoint.

At The New Republic, Timothy Lahey, of Dartmouth, argues that these results, while promising, aren’t necessarily confirmed.  He notes that the lack of a placebo (because of the study’s particular methodology) makes it difficult to determine effectiveness, the vaccine could have failed to protect subjects from infection in a way that the study didn’t detect, and that a statistical aberration could mean that while the vaccine is not actually 100 % effective.  Regardless of whether these potential pitfalls affected the study or not, Lahey raises an important issue in drug testing for a disease like Ebola.  He is concerned that a lower standard for vaccines could mean that lower-income countries might not receive drugs of the same quality as rich countries, and points to past failed vaccines to illustrate the fallacy of believing that all vaccines work as intended.

The ethical dilemmas of drug testing have been front and center in the Ebola crisis.  Back in November, 2014, Nature reported on public health officials weighing the question of whether to use control groups when testing treatments for a disease with 70% mortality.  At the time, some advocated for applying experimental treatments (like the ZMapp antiviral cocktail, which had been used in patients but whose effectiveness was not entirely determined) to all patients, while others argued that these treatments might not be more effective than standard care, and that randomized trials guard against harmful side effects and provide a clearer picture of a drug’s effectiveness.

The VSV-EBOV vaccine was tested in the “ring” method that was previously used in the eradication of Smallpox.  This method eschews the double-blind placebo treatments commonly associated with drug trials.  Instead, this method creates a “ring” around new cases.  Contacts and contacts of contacts were identified by Guinea’s tracking system, and eligible adults were entered into randomization blocks, and received either the immediate or delayed vaccination.  This way, all of the subjects received the treatment, but in varying circumstances to establish effectiveness.  The full study is available via The Lancet.

Ethical drug testing is a crucial consideration, and has an imperfect past.  The National Institutes of Health’s own ethics guide cites a study that led to the United States’ ethics rules: a study that withheld syphilis treatment from 400 African-American men.  And for many, there’s good reason to be concerned about the actions of international organizations and multinational corporations.  In 1996, Pfizer conducted a study of an experimental drug on children with meningitis in Nigeria. While Pfizer maintained that the study was philanthropic, allegations arose from Nigerians and international organizations that children and parents were not informed that they were part of a study, and that Pfizer withheld treatment without consent or administered dangerous drugs.  The incident spawned a series of lawsuits and a panel of Nigerian medial experts condemned Pfizer’s actions in 2006, as reported by The Washington Post.

Epidemics and drug testing present a multitude of practical and ethical concerns, but careful consideration of the issues and sound methodology can, as they did in Guinea, produce exciting scientific and humanitarian results.

Image Credit: Psychonaught

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