Quantitative Sensory Testing (QST) - Does assessing ... - TI Pharma

6. General discussion and Summary
To harmonize the QST approach, standardized assessment areas such as dorsal hand
and dorsal foot were introduced. For the purpose of our studies, we have followed these
recommendations and used age- and gender-matched controls to compare QST data
obtained from patients to identify somatosensory abnormalities.
Z-score transformation of QST data revealed that one or more somatosensory
abnormalities are also present in healthy controls, but its frequency was considerable
lower than in patients. The likelihood in a healthy subject that all QST parameters (with
exception of DMA, which is not present in healthy controls) are within the normal range
can be calculated to be 54% (0.95 12 ). In accordance, our data showed normal sensory
function for 53% of the healthy controls (n=209). In contrast, only 9% of patients showed
normal sensory function (see chapter 3). Although overall, our healthy volunteer data
is in line with data reported by others, there are differences encountered (Rolke et al
2006a; Rolke et al 2006b). For instance, we found Paradoxical Heat Sensations (PHS)
>1 occurred in 1.4% at the test site “dorsal hand” and in 9.3% at the test site “dorsal
foot”. PHS >1 in healthy subjects were not observed in previous studies (Rolke et al
2006a; Rolke et al 2006b). Such differences could be explained by the fact that z-score
transformations depend on reference values. In this context minimum numbers needed
as controls incorporating the complexity of the QST battery have not been established.
There is a considerable variation in the literature concerning the choice of percentiles
used to define reference values (Shy et al 2003). Ultimately, the choice of percentiles is
dependent on a combination of clinical, disease-specific, personal and financial factors
(O’Brien & Dyck 1995). Exchange of QST reference data between institutes would be
favourable allowing QST access to the research and clinical community. A certified
QST training is advantageous in this context to expand the QST database in co-operation
with different institutes. We have participated in the QST training provided by the
DFNS and differences in QST values in healthy subjects between institutions observed
could be based on numbers of controls and/or regional differences in somatosensory
function. The exchange of reference values could address potential regional differences
and ultimately increases overall numbers of references by reduced costs. Such a scenario
might be also valuable to be implemented beyond European boundaries.
Furthermore, detailed insight into normative QST values could be helpful in a more
objective testing of drug efficacy in various neuropathic pain states. For regulatory
purposes the FDA suggests pain as primary outcome measure for the evaluation of
novel pain compounds. In clinical practice a pain decrease > 50% is desirable, however,
this is only achieved in less than one-third of the cases (Argoff et al 2006; Farrar et
al 2001; McQuay et al 1996; Sindrup & Jensen 1999; Ziegler 2008). For approval of a
novel pain treatment a pain reduction of >30% on the visual analogue pain scale (VAS)
compared to placebo is required. Secondary outcome, which may play a major role in
providing supportive evidence for approval of pain medication, can be, amongst others,