Learning lessons from MVA85A, a failed booster vaccine for BCG

The development and testing of new treatments is complicated. Many approaches are developed through the laboratory, and most involve animal studies—to give confidence in the biological concept underpinning the treatment, to show safety, or to show efficacy in animal models of the disease in question. These purposes are regulated differently: safety studies must be conducted according to established principles of good laboratory practice, but there is no such requirement for proof of concept or efficacy studies. The regulatory requirements around safety are, understandably, better developed for marketing authorisation of new treatments than they are around approvals for clinical trials.

The development of MVA85A for the prevention of tuberculosis (TB) gives us an opportunity to reflect on these processes. This promising intervention was designed to boost the effectiveness of the well established BCG vaccine. It was reported to show efficacy in laboratory studies in animals but did not show benefit when tested in a large clinical trial in infants.1 In the linked feature (doi:10.1136/bmj.j5845),2 Deborah Cohen raises important questions about the development of MVA85A and, in particular, the extent to which emerging findings from animal studies were communicated to clinical trial regulators, funders, ethics committees, and potential participants.

It seems that while the human clinical trial was in the late stages of …