Debate Intensifies on Trial Design for Ebola Treatments

Experts have supported the deployment of alternative trial designs to fast-track the evaluation of new Ebola treatments. In a letter published on Friday by The Lancet, 17 senior health professionals and medical ethicists from Africa, Europe, and the US argue that although randomized controlled trials (RCTs) provide robust evidence in most circumstances, the lack of effective treatment options for Ebola, high mortality with the current standard of care, and the paucity of effective health care systems in the affected regions mean that alternative trial designs need to be considered.

“No-one insisted that western medical workers offered zMapp and other investigational products were randomized to receive the drug or conventional care plus a placebo. None of us would consent to be randomized in such circumstances,” they wrote. “In cancers with a poor prognosis for which there are no good treatments, evidence from studies without a control group can be accepted as sufficient for deployment, and even for licensing by regulators, with fuller analysis following later. There is no need for rules to be bent or corners to be cut: the necessary procedures already exist, and are used.”

Everybody accepts that RCTs can generate strong evidence in ordinary circumstances, but not in the midst of the worst Ebola epidemic in history, they point out.

“The urgent need is to establish whether new investigational drugs offer survival benefits, and thus which, if any, should be recommended by WHO to save lives. We have innovative but proven trial designs for doing exactly that. We should be using them, rather than doggedly insisting on gold standards that were developed for different settings and purposes,” explained the article.

The signatories to the letter are Clement Adebamowo, Oumou Bah-Sow, Fred Binka, Roberto Bruzzone, Arthur Caplan, Jean-François Delfraissy, David Heymann, Peter Horby, Pontiano Kaleebu, Jean-Jacques Muyembe Tamfum, Piero Olliaro, Peter Piot, Abdul Tejan-Cole, Oyewale Tomori, Aissatou Toure, Els Torreele, and John Whitehead.

Read the full release here.