Monsanto Roundup Lawsuit

Monday, April 27, 2009

Hamilton Depression Scale and GSK

According to Wikipedia The Hamilton Rating Scale for Depression (HRSD), also known as the Hamilton Depression Rating Scale (HDRS) or HAM-D, is a 21-question multiple choice questionnaire that clinicians may use to rate the severity of a patient's major depression. Max Hamilton originally published the scale in 1960 and reviewed and evaluated it in 1966,1967,1969 and 1980.

A paper released in 2008, that a reader kindly sent me, entitled, 'Sensitivity of the individual items of the Hamilton depression rating scale to response and its consequences for the assessment of efficacy', begs to differ.

The conclusion of the paper:

In conclusion, this study adds further data to the body of evidence that HAM-D17 is not the most sensitive measure of treatment effect in depression trials. This is especially important in early clinical development studies, in which relatively small patient populations are included, increasing the risk of false negative results. The social and financial costs of false negative results are not acceptable in an indication which urges for medicines with a better efficacy profile.

Furthermore, we show that a considerable reduction in population size can be achieved when the subscales are used due to an increase in statistical power to detect differences from placebo. Such a smaller group size does not only reduce the run time of a study, it is also limits the unnecessary exposure of patients to placebo treatment. From the two subscales we have devised, subscale 1, derived from graphical analysis of the longitudinal patterns of individual items, performs better in the detection of treatment effect than subscale 2. Therefore,we recommend the use of this response-based HAM-D7 subscale as primary endpoint for the statistical analysis of efficacy data rather than the HAM-D17.

As with all papers, a conflict of interest declaration was made:

There are no arrangements of financial nature, or of any other kind, that could lead to conflict of interests with regard to this manuscript.

One look at two of the three co-authors of this paper would suggest otherwise.

Meindert Danhof works at the Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, Verona, Italy


Oscar Della Pasqua is part of Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, Greenford, United Kingdom.

Role of funding source:

This manuscript is part of a PhD research fellowship programme sponsored by GlaxoSmithKline, UK. GlaxoSmithKline had no further role in the research rationale, collection, analysis and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication.

In this particular study they assessed the sensitivity of the individual HAM-D17 items in differentiating responders from non-responders over the typical treatment period used in clinical efficacy trials. Based on data from randomised, placebo controlled trials with paroxetine, a graphical analysis and a statistical analysis were performed to identify the items that are most sensitive to the rate and extent of response irrespective of treatment.

It's very scientific in nature but when paroxetine is used in any study it raises an eyebrow, particularly from me. Even more so when part of the team doing the study work for the manufacturer of paroxetine.

Basically, paroextine is about as useful as a chocolate teapot but to hide that fact, this paper claims that the Hamilton Depression Scale is not sensitive enough to detect responders to their drug!

Paroxetine is useless so they don’t think the HAM-D scale should be used in its entirety – just those parts of it that make their drug look better than placebo.

Genius marketing once again from the boys of Glaxo.

Didn't Glaxo manipulate data in the 329 study too?

The paper can be downloaded here.