The two studies described here have made a useful contribution towards the psychometric validation of two well-being questionnaires for use in adult growth hormone deficiency: the General Well-being Index and the 12-item version of the Well-being Questionnaire.
Despite only minor changes made to a few words and to item order when adapting the Psychological General Well-being Index for use in Britain , a forced 6-factor analysis of the British GWBI did not find the 22 items factoring out separately into PGWB subscales such as anxiety or self-control. Unforced factor analysis, however, produced three factors (albeit with substantial double loading), largely confirming the factors labelled as 'general mood/affect', 'life satisfaction/vitality', 'poor physical health/somatic complaints' in the earlier study by Gaston and Vogl, conducted with a non-clinical sample . GWBI Factor 1 items (present study) covered several aspects of affect, and positive and negative well-being did not factor out separately as in the W-BQ12. Vitality (GWBI) items loaded together with positive well-being on Factor 2, but with the W-BQ12, the value of having a separate energy subscale was demonstrated in that W-BQ12 Energy was the only scale sensitive to change in the GH-Withdrawal study. Although the GWBI has a weak physical health factor, accounting for just 11% or the variance, this reflects the fact that one of the six subscales of the original PGWB concerned general health. However, the GWBI could not be described as a measure of health status as only a small proportion of items (3/22) concern physical health perceptions.
The internal consistency reliability of the whole GWBI scale was very high (>0.95) indicating that there may well be redundancy of items, particularly as two pairs of items are similarly worded, adding unnecessarily to respondent burden. The two general health items loading on Factor 3 in the unforced factor analysis had similar wording, and one or the other would appear to be redundant (if either were deleted from the scale then only two factors emerged in the unforced analysis). Although the reliability of the three potential GWBI subscales was high, overlap is considerable and we agree with the recommendation by McKenna et al  that there are no clear subscales to the questionnaire, and only a total score should be calculated.
Factor analysis of the W-BQ12 indicated three relatively clean factors providing evidence for W-BQ12 subscales of Negative Well-being and Positive Well-being and, although two W-BQ12 Energy items double loaded, it was possible to interpret the third W-BQ12 factor as an Energy subscale. There was support for the calculation of a total score for the questionnaire. The internal consistency reliability of subscales and W-BQ12 General Well-being combined scale was excellent. This high value would not indicate item redundancy, however, (as in the case of the GWBI), because the W-BQ12 is considerably shorter than the GWBI and none of the items are similar to each other (as in the GWBI).
Both well-being questionnaires had very high completion rates indicating good acceptability to patients, an indication of face validity. The strong correlations of both questionnaires with appropriate scales of the SF-36 (Mental Health and Vitality) but lower correlations with SF-36 Physical Functioning gave support for the concurrent validity of both questionnaires. The moderate correlations with Physical Functioning, however, indicate that well-being is associated with some aspects of health status.
There was preliminary evidence for construct validity in both GWBI and W-BQ12, although no prior hypotheses were formulated. Both questionnaires found significant differences between men and women, with women having generally lower well-being than men. It is a common finding that, in the general population, women have reduced well-being compared with men [43, 44], although not all studies have found this . Women with GHD have also tended to exhibit lower levels of well-being than men . Both questionnaires showed correlations indicative of improving well-being for GH-treated patients with longer periods of GH treatment, as seen in previous research . However, neither questionnaire found significant GH treatment-group differences either because the questionnaires were insufficiently sensitive to treatment-group differences, or there were no real differences in well-being between the two groups, possibly as a result of the fact that symptomatic patients were more likely to have been selected for treatment by the doctors in the clinics. Indeed none of the other questionnaires used in the study found GH-treated patients to have significantly better patient-reported outcomes (including health status and condition-specific quality of life) than non-treated patients . It is possible, but perhaps more unlikely, that those receiving GH were not all adhering to the injection regimen (the patients' Insulin-like Growth Factor-I data at the time of the study were not collected).
The small sample size in the GH-Withdrawal study resulted in low power of analysis but, as anticipated, W-BQ12 Energy found a significant between-treatment-group difference in change scores over the withdrawal period, with reduced energy in placebo-treated patients at end-point. This provided a very preliminary indication of the W-BQ12's sensitivity to change, (there was no significant finding for the GWBI). This is in line with results of a study in which GH was discontinued in young adults with GHD  where a significant increase in psychological complaints (on the Hopkins Symptom Checklist ) was found after 6 months' discontinuation, although not across 12 months' discontinuation. It is possible that the 3-month withdrawal period of the present study was not long enough for significant change to be registered by the GWBI. All the previous studies of GH-replacement therapy that found significant improvement in psychological well-being using the PGWB, had a minimum 6 months' duration [13, 14, 17]. Further work on sensitivity to change with this patient group would be valuable in a larger and longer-term longitudinal intervention study, where GH treatment is being offered, not withdrawn.
The American PGWB has been the most widely used measure of psychological well-being in adult GHD, its six subscales sensitive to change in several studies of GH replacement. The British GWBI, on the hand, has no subscales, and the present study has confirmed that none can be recommended. This could be a disadvantage in this hormonal condition where low energy, increased anxiety and depression are key psychological aspects. Therefore, on the evidence provided by the present studies, the W-BQ12 can be recommended in preference to the GWBI to measure psychological well-being in adult GHD because the W-BQ12 has:
excellent reliability, both of the whole scale and of the three subscales, with no indication of item redundancy;
a clear factor structure supporting the use of subscales of Negative Well-being, Energy and Positive Well-being;
fewer items (12 compared with 22 in the GWBI) and shorter response options (these are relatively long and vary from item to item in the GWBI, causing greater respondent burden);
preliminary evidence of sensitivity to change.
To cover a wider range of patient-reported outcomes in adult GHD, it is recommended that the generic W-BQ12 be used in a battery of questionnaires that includes a generic measure of health status (e.g. the SF-36 ) and the HDQoL hormone deficiency-specific quality of life questionnaire .