Abstract
In 2012, the drug levofloxacin was approved by the Food and Drug Administration (FDA) for plague caused by Yersinia pestis. Efficacy was established in an African green monkey model of pneumonic plague. Levofloxacin had previously been approved for other respiratory infections (i.e. nosocomial and community-acquired pneumonias), yet the licence for use in pneumonic plague was based solely on efficacy data from the animal model (FDA, 2012). If caught early, bubonic plague could be treated, thus making the threat of an outbreak of pneumonic plague a remote possibility.
With such a regulatory precedent in mind, it seems strange why one of the many drug candidates for treating Ebola were not similarly licensed for general use on the basis of animal data alone given the real urgency and population need (albeit subject to inevitable delays in manufacture and distribution). In a 2007 letter published in Nature Biotechnology, the Alliance for Biosecurity appealed for clarification over use of the Animal Efficacy Rule (Animal Rule), with an eerie foresight of Ebola (Gronvall et al., 2007).
The Animal Rule went into effect under 21 CFR Part 314 in July 2002, and in 2014 was revised but reiterated its main condition: animal data could be sufficient if and only if human efficacy studies could not be conducted on grounds that they would be unethical or infeasible (FDA, 2002). Here, ‘unethical’ refers only to the deliberate exposure of healthy human volunteers to a lethal or permanently disabling toxic biological, chemical, radiological or nuclear substance.
The 2014 Ebola crisis has not yet been fully eradicated, and we are already faced with another public health concern, Middle East Respiratory Syndrome (MERS-Cov), against which we are similarly unprepared with effective treatments. Meanwhile, the pursuit of an ethical design for human trials in the midst of a fast spreading and highly fatal pandemic continues. Yet contemporary discussion has almost completely ignored the existing regulatory mechanism which permits the marketing (at least in the US) of a new product on the basis of animal data alone. The reasons for such neglect are not at all obvious, especially when, in theory, a new drug for Ebola could have gained such a licence before it became a real public health threat, as it would have been deemed unethical to infect a human with the viral for research purposes. When we were faced with multiple deaths from Ebola, however, research restrictions took hold and human trials were deemed both feasible and, at least in principle, ethical. The timing of a licensing application seems curiously decisive.
The FDA has another regulatory mechanism designed for public health crises, bioterrorist attacks or natural disasters, through which an untested product may be approved, namely the Emergency Use Authorisation (EUA). Peramivir was approved in 2009 under an EUA for adults and children with H1N1 influenza after phase 1 trials but with little heed paid subsequently to keeping records for monitoring in practice. The Animal Rule, by contrast, explicitly requires formal post-marketing studies, such as field studies, to verify and describe the drug’s clinical benefit and to assess its safety when used as indicated when such human studies are feasible and ethical (FDA, 2009).
It remains contentious how human trials of new treatments can proceed ethically during a pandemic, and until this question is resolved, the possible application of the Animal Rule ahead of the Emergency Use Authorisation during a pandemic may seem a rather academic exercise.
In this issue
In this Issue, there are two articles concerning ethics committees in New Zealand. The first, by Martin Tolich, examines how each committee justifiably develops its own practices and precedents in ‘How idiocultures and warrants operate independently in New Zealand health ethics review boards.’ The second, by Helen Gremillion, Martin Tolich, and Ralph Bathurst concerns the role and function of lay members in ‘Lay members of New Zealand ethics committees: Who and what do they represent?’
Neil Armstrong, Jonathan Price and John Geddes then address the problem of relaying information about risk to potential recruits of research in ‘Serious but not solemn: Rebalancing the assessment of risks and benefits of patient recruitment materials.’
Finally, Holly Crossen-White examines the growing issue of digital archiving in the face of recent legal cases, revealing that individuals have certain legal rights to be forgotten, in ‘Using digital archives in historical research: What are the ethical concerns for a ‘forgotten’ individual?’