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To the editor:
The paper by Barkan (1) casts doubt on the ability of the "Assessment of Growth Hormone Deficiency in Adults" (AGHDA) questionnaire (2, 3) to detect a quality of life (QoL) improvement during GH replacement therapy. In our opinion, Barkan’s (1) arguments are based on assumptions that do not represent the current state-of-the-art in QoL research (4).
Barkan’s (1) main argument line can be summed up in the alleged inability of the AGHDA questionnaire to distinguish between the state of severe GH deficiency (GHD) and the state of GH excess or acromegaly. This single reasoning ignores or overlooks the complex process of establishing the validity of a QoL instrument.
Validity is an overall evaluative judgement of the degree to which empirical evidence and theoretical rationales support the adequacy and appropriateness of interpretations and actions on the basis of test scores or other modes of assessment (5). Given the extensive elaboration and width of questions asked when validating a QoL questionnaire, there are many ways of establishing it (4). A frequent way of assessing the validity of QoL instruments is in terms of an extreme groups strategy (4). The simplest approach of such a maneuver implies the administration of the questionnaire to two groups, one of which is supposed to have a bad QoL, and the other which does not. If the instrument is valid and really measures what it intends to, the two groups should score significantly differently in the questionnaire. Further complicating this design, Barkan (1) administered the AGHDA to 30 normal control subjects, 20 patients with severe GHD, and 22 patients with active acromegaly. AGHDA scores in controls were significantly better than in patients with GHD and acromegaly, but scores were indistinguishable between the latter. Barkan (1) has used this fact to discredit the AGHDA.
Although this type of design seems quite straightforward, it has methodological problems (4) that raise questions about the appropriateness of Barkan’s (1) conclusions. The main concern with the method is how the groups are selected: if we are trying to develop a new tool to measure QoL, how can we select the extreme groups in terms of their extreme QoL? There is no objection to the inclusion of a control group of healthy subjects, but we would like to formulate a cautionary warning regarding the enrollment of patients with GH excess. The subjects with acromegaly were selected based on the fact that the AGHDA was specifically developed for patients with GHD and with the intention "to assess the performance of the questionnaire in populations with widely different GH status" (1). In our view, acromegalic patients do not constitute a sufficiently extreme group to be compared with GHD-deficient patients in terms of QoL affectation. Areas such as body image, social relationships, energy and strength level, temper, physical and mental drive, are likely to be affected in both situations of excess and deficiency of GH. The bad correlation between AGHDA scores and the plasma IGF-I levels that Barkan (1) has observed support our hypothesis. Unlike Barkan’s (1) opinion, this low correlation does not reflect the lack of validity of the instrument, nor implies that abnormal levels of GH do not play any role in determining patients’ QoL, but that both types of parameters (i.e. QoL and biochemical) address different constructs and are, thus, complementary but different. Moreover, standard clinical measurements only represent a part of the pathological and physiological processes involved in a disease.
When questioning the validity of the AGHDA, at the most, Barkan’s (1) results would suggest that the questionnaire is less specific than it had initially been thought. Thus, additional empirical research should be undertaken to assess the extent to which AGHDA score meaning and action implications hold across patients with both GHD and excess, as well as across different settings or contexts. Doubtless, Barkan’s (1) results indicate that further effort should be devoted to the achievement and improvement of new specific instruments capable of assessing GH abnormalities on QoL even more validly and reliably.
Footnotes
b Address correspondence to: S. M. Webb, M.D., Department of Endocrinology, Hospital de Sant Pau, Pare Claret 167, 08025-Barcelona, Spain.
Received August 2, 2001.
References
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  K. Rafferty, K. M. Davies, and R. P. Heaney Potassium Intake and the Calcium Economy J. Am. Coll. Nutr., April 1, 2005; 24(2): 99 - 106. [Abstract] [Full Text] [PDF]
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