{"id":3153,"date":"2017-04-11T16:00:47","date_gmt":"2017-04-11T15:00:47","guid":{"rendered":"https:\/\/blogs.bmj.com\/medical-ethics\/?p=3153"},"modified":"2017-04-12T03:51:35","modified_gmt":"2017-04-12T02:51:35","slug":"individually-randomized-controlled-trials-of-vaccines-against-the-next-outbreak","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/medical-ethics\/2017\/04\/11\/individually-randomized-controlled-trials-of-vaccines-against-the-next-outbreak\/","title":{"rendered":"Individually-Randomized Controlled Trials of Vaccines Against the Next Outbreak"},"content":{"rendered":"

Guest Post: Nir Eyal, Marc Lipsitch<\/strong><\/em><\/p>\n

Paper: Vaccine testing for emerging infections: the case for individual randomisation\u00a0<\/a><\/strong><\/em><\/p>\n

The humbling experience of international response to Ebola taught the world a thing or two on preparing for Zika and for other emerging infections.<\/p>\n

Some of those lessons pertain to vaccine development against emerging infections. One lesson was that vigorous vaccine development should start long in advance of outbreaks. CEPI, the Coalition for Epidemic Preparedness Innovations<\/a>, was recently launched with an initial investment of half a billion US dollars from the Gates Foundation, Britain\u2019s Wellcome Trust and the governments of Japan, Norway and Germany. There is also growing recognition that best practices on vaccine testing should be developed prior to outbreaks<\/a>, from a study methodology viewpoint.<\/p>\n

By contrast, in Zika, ethical guidelines on response in general<\/a> and on an aspect of vaccine testing<\/a> were created only once the pandemic erupted. Shouldn\u2019t ethical disputes, e.g. on trial design for vaccine candidates, be ironed out in advance of emerging infections?<\/p>\n

One persistent ethical question in vaccine testing pertains to individually-randomized control in efficacy trials. At the height of the 2014-5 Ebola outbreak, individually-randomized controlled trials were much maligned. Our paper at the Journal of Medical Ethics<\/em> <\/a>sets out to defend that approach for vaccine efficacy testing in emerging infections, including highly fatal and untreatable ones in developing countries.<\/p>\n

<\/p>\n

Nearly everyone agrees that scientifically, individually-randomized controlled trials are the gold standard of clinical research. But during the Ebola outbreak, ethicists, leaders, and humanitarian workers opposed them. For testing vaccine against a highly fatal infection without approved drugs or vaccines, they deemed these designs unethical<\/a>. In October 2014, Science Magazine<\/em> reported that \u2018Doctors Without Borders (MSF), which has treated more Ebola patients in West Africa than any other group, emphatically opposes [randomized controlled trials] in affected countries for either treatments or vaccines. MSF\u2019s Annick Antierens, who oversees \u201cinvestigational platforms\u201d for experimental Ebola products, says \u201cthis cannot be defended ethically.\u201d\u2019<\/p>\n

In advance of similar controversies for future outbreaks, we show that these ethical concerns about individually-randomized control are misplaced. Whenever individual randomization is feasible\u2014and it often will be\u2014it tends to save more lives than alternative designs. And for emerging infections, individual randomization also tends as such to improve care, access to the experimental vaccine, and prospects for all participants relative to their opportunities absent the trial. It does so no less than alternative designs that opponents proffered would. That obtains even under placebo control and without equipoise\u2014requiring which would undermine not only individual randomization but also the alternative designs. Our arguments expound four often-neglected factors: benefits to nonparticipants, benefits to participants once a trial is over including post-trial access to the study intervention, participants\u2019 prospects before randomization to arms, and the near-inevitable disparity between arms in in any randomized controlled trial.<\/p>\n

Recommended reading: <\/em><\/strong><\/p>\n