Re: Do we need BQL?

Date: Tue, 3 Aug 1999 18:23:22 +0100 (GMT) From: "J.G. Wright" <J.G.Wright@newcastle.ac.uk> Subject: Re: Do we need BQL? BQLs returned from laboratories are unnecessary in pharmacokinetics, but may have value in toxicokinetics. I am sure the lab people would argue that we really don't know (and can't determine) the behaviour of the assay in this range. Fortunately most of us don't believe that the assay is all that important compared to other sources of variation in the data and so we couldn't care less. The problem is that once we have BQLs we have to deal with them. The best solution is the sophisticated coding suggested by Lew Sheiner, however if I was in a regulatory body I might look on this sceptically, not because of any theoretical flaws, but because it is complicated and you could argue your support is chosen to be overly consistent with the other data, difficulties in evaluating integrals and propagating the error through to your estimates etc. Lew may wish to crushingly refute these comments but I think he would agree it is difficult to implement. Is there a publication somwhere with details of how to do this? All of the single imputation methods with inflated variance have a more sinister problem, in that the variance function is dependent on the individual observed values, rather than the predicted values. This is kind of similar to weighting observations according to their observed values and is good way to get inconsistent estimators. Multiple imputation is better than single imputation as you do not have to inflate the BQl variance to approximate uncertainty in your analysis. Although, if I remember my undergarduate days correctly, ten repetitions gives excellent approximations to confidence intervals and mean values for fixed effects, I do not know if theory extend to mixed effects models, especially if you are interested in your variance components. Also if you are doing some other kind of sensitivity analysis alongside this and now have to do all of these runs x number of times this will rapidly become impractical. BQL is bad but once you are stuck with them, we have to do something. Some labs are evn reluctant to tell you what their QL is for a given assay... James