This is a response to replies 1 and replies 2.

Katz's comments are useful in clarifying issues. For instance he states re factor analysis  " it was because we first sought measures of the facets of psychopathology". 

I don't think that factor analysis can  effectively  resolve  mixtures. That has been a major problem for statistical diagnosis from Lazarsfeld to Meehl. I refer to this problem in my first text. Bech appears to agree,"We are forced more and more  (to)...  an early recognition of specific sub-syndromes"..

Bech also states ," Responsiveness to change is not a separate dimension, but an aspect of validity which factor analysis is not able to test for. However, because item difficulty is a parameter in the Rasch model, the same difference between two levels of depressive states will be given in the Rasch confirmed rating scales whether the individual item covers mild, moderate or severe depression".

I would appreciate  it if Bech could refer me to studies where differences in Rasch scores provided effective  comparative measures. A comparison to standard techniques, such as ANCOVA , would be valuable.

Katz agrees that,"Separating the placebo from the drug effect in a patient is an important problem" and that  currently we cannot distinguish patients who require medication from those who got better while on placebo.   However his suggestion, "utilizing “early response” to treatment as a predictor, ... an approach that can help reopen the issue" , seems to have the same problem with mixtures  as factor analysis.

I would appreciate knowing  the views of Katz and Bech about "intensive analysis" as such an approach. If it succeeds in isolating patients who require a medication to maintain gains , it seems  a step towards homogeneity . Using a number of medications , that seem to differ in their proposed mechanisms of action, might further elicit subsyndromes--although it may require very large samples.

Katz states ,correctly, that  scales loaded with items that respond differentially to drug A and placebo,might fail in a study of drug B. However,if therapeutic drug action requires a normalizing interaction with the dysfunction underlying the manifest disorder--then if on this loaded scale,  drug A works but drug B does no t--but drug B has been shown effective ,using a different scale-- I believe this amounts to a mixture reduction . 

Donald F Klein

March 27, 2014