Dear Friends – Observations versus population predicted is considered a 
standard diagnostic plot in our field. I used to place observations on the 
x-axis and predictions on the yaxis. Then I was pointed to a publication from 
ISOP 
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321813/figure/psp412161-fig-0001/)
 which recommended plotting predictions on the xaxis and observations on the 
yaxis. To the best of my knowledge, there was no justification provided. It did 
question my decades old practice, so I did some thinking and digging. Thought 
to share it here so others might benefit from it. If this is obvious to you 
all, then I can say I am caught up!


  1.  We write our models as observed = predicted + random error; which can be 
interpreted to be in the form: y = f(x) + random error. It is technically not 
though. Hence predicted goes on the xaxis, as it is free of random error. It is 
considered a correlation plot, which makes plotting either way acceptable. This 
is not so critical as the next one.
  2.  However, there is a statistical reason why it is important to keep 
predictions on the xaxis. Invariably we always add a loess trend line for these 
diagnostic plots. To demonstrate the impact, I took a simple iv bolus single 
dose dataset and compared both approaches. The results are available at this 
link: https://github.com/jgobburu/public_didactic/blob/main/iv_sd.html.pdf. I 
used Pumas software, but the scientific underpinning is agnostic to software. 
See the two plots on Pages 5 and 6. The interpretation of the bias between the 
two approaches is different. This is the statistical reason why it matters to 
plot predictions on the xaxis.

Joga Gobburu
University of Maryland

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