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Wednesday, 22.03.2017

Reply (Per Bech)

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When reviewing my ”Clinical Psychometrics”, Donald F. Klein recalls the massive criticism put forth by psychoanalysts against measurement-based therapies. With reference to the randomized double-blind trials introduced in the 1950’s in clinical medicine, the psychoanalysts found it a meaningless procedure to use rating scales in psychiatry, adding up very different symptoms to give a total score was considered impossible.

When the Danish statistician Georg Rasch introduced his Item Response Theory (IRT) model in the 1960’s, he used the term “specific objectivity” as a general scientific principle in trials of antidepressants when comparing patients from baseline to endpoint by rating scales that fulfilled his criteria of unidimensionality. As outlined by Klein, the Rasch model for specific objectivity is based on Guttmann’s model of scalability, which implies that scorings on lower prevalence items presupposes scorings on higher prevalence items.

Klein refers to  his “widely unnoticed” paper from 1963 in which he demonstrates the great discrepancy between global judgment of change and factor-analytically derived rating scales in placebo-controlled clinical trials of antidepressants or antipsychotics. This is actually a problem of transferability which is the degree to which a scale continues to measure the same thing psychologically across the different rating occasions during a clinical trial. 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. This is crucial for measuring changes in placebo-controlled trials of antidepressants or antipsychotics.

It is on the other hand important to point out that Rasch himself was always very careful to examine the nature of the items that did not fulfill his model of measurement. Klein’s chapter from 2001 on causal thinking for objective psychiatric diagnostic criteria actually includes the Rasch reasoning in clinical psychometrics. We need to have a clinically based observation about the dimension we are examining before the psychometric analysis is performed. This holds both for dimensions of depression severity like Klein’s 1963 paper and for predictors of clinical response. The sub-syndrome of panic attacks within anxiety disorder as a predictor of the response to imipramine is such an example (Klein DF,Psychopharmacology 1964; 5: 397-408). Another is the sub-syndrome of atypical depression within major depression. In this case increased appetite and hypersomnia are symptoms that are both excluded from the Rasch model of depression severity, but both have predictive validity when showing the superiority of phenelzineover imipramine.

This subsyndromal distinction of atypical depression has not been captured in the antidepressant trials performed over the past decades by the industry because the goal of these placebo-controlled trials is primarily to obtain an FDA marketing approval. As concluded by Klein, the group average outcomes on more or less validated ratings scales in these FDA oriented trials do not determine which patients actually require medication for a positive response. We are forced by the fact of more and more patients with treatment-resistant depression to prevent this development by an early recognition of specific sub-syndromes. It is to be hoped that this specific issue will be discussed in more detail in this INHN framework.

Per Bech

January 16, 2014