Monday, August 08, 2005

MeNZB and Phase III trials

One of the more common things you hear and read in the news from certain 'individuals' is the problem that MeNZB has that it hasn't been subjected to a phase III clinical trial. This is harped on repeatedly like it's some sort of damning point against the use of the vaccine - the implication being of course that it is insufficiently tested and potentially harmful as a result. Unfortunately, as always this point is rather moot and in fact doesn't actually apply to the situation in New Zealand to begin with.

Firstly, the obvious question to answer is to actually define what a phase III clinical trial is to begin with. When we are talking about a phase III trial, we're asking a basic question of how well does this thing work? In other words, the goal of a phase III trial is to establish the efficacy of the treatment in question by comparing a group of people that you vaccinate with a group that you deliberately didn't vaccinate. If much less people in the vaccinated group get the disease compared to the unvaccinated group you can say that the treatment did its job. On the other hand, if the disease rate is the same then you can establish that the vaccine probably isn't going to work.

Seems like good common sense doesn't it? So why wasn't a phase III clinical trial done for MeNZB in New Zealand?

Firstly, there are in fact several vaccines that are similar to MeNZB being used at the moment, including the 'parent' vaccine that MeNZB was based on that was developed in Norway. The Norway outer membrane vesicle (OMV) vaccine had a large phase III trial performed on it with a high efficacy of the vaccine, around 87% after 10 months. This was performed on teenagers and was only done with two shots of the vaccine (we are using three, due to the 'memory' of the response waning after 3 years from only two doses so a third was added). Ultimately however, the Norweigan vaccine was never actually used in the general populace although for different reasons that Ron Law et al would have you believe.

The epidemic that Norway had been experiencing of the time from their Meningococcal B strain had clearly begun to come to its end point. It's worth noting that this was after a considerable period of time, 19 years, which is one of the reasons we are bringing out the MeNZB vaccine quickly because epidemics of Meningococcal B do tend to last a considerable amount of time. The second reason was the lab that made the Norweigan vaccine shut down, not because the vaccine was shown to be ineffective but simply because there wasn't any market for the vaccine (as the epidemic had begun to die down).

Despite this, the fact a phase III trial has already been done on the parent vaccine establishes very clearly that the current MeNZB vaccine doesn't require this to be done on it specifically. The only considerable difference between the Norweigan vaccine and MeNZB is the antigen (the bit the immune system responds to in the vaccine) is different: the two vaccines were produced in the same way. Another vaccine we use every year, that also only undergoes a change in the antigen inserted but doesn't have a phase III trial with each release is the influenza vaccine. Conceptually, there is little difference between the concept behind the MeNZB vaccine and changing the antigens in the influenza vaccine every year except that certain groups complain about one and not the other. At the very least, they could be consistent and demand that the flu shot go through a phase III clinical trial every year as well.

The final point is one ultimately about ethics. We are at the moment in an epidemic from a disease that either has an extremely high chance of causing permanent disabilities or even death in those that get it. Preventing the vaccine from being given to one group of people and not another, considering that we have data that indicates the vaccine works, would technically make the researchers directly responsible for anyone killed/disabled in the group that didn't get the vaccine. Ultimately, if we use the vaccine now with good scientific data indicating this will be an effective treatment we should use it. At worst, we've lost a few million dollars but at best we've saved peoples lives. I know which option I prefer.

So ultimately, when you hear the anti-vaccine lobbies general rhetoric on the lack of a phase III clinical trial it's probably because they haven't a clue what one is.