Title: Quality of life, social support, and adherence in female patients with thyroid disorders
Version: 1 Date: 14 Jul 2023
Reviewer's report:
Kollerits et al. have examined quality of life (QoL), and two of its potential predictors - adherence
and social support - in a sample of Hungarian patients with thyroid conditions.
The paper lacks certain innovation as several studies have investigated very similar issues. There
are very recent publications both on the topic of QoL in Hungarian patients with thyroid disease
(DOI:10.1186/s41687-023-00606-7), as well as the effect of adherence on QoL in patients with
thyroid dysfunction (DOI: 10.1089/thy.2023.0066).
There also seem to be some methodological issues that question the validity of the conclusions
drawn in the manuscript. A number of these involve study design, and are thus unlikely to be
improved upon at this stage.
Introduction
-Drugs should be referred to by their chemical name instead of brand names (eg. l-thyroxine
instead of Letrox or methimazole instead of Metothyrin).
Participants and procedure
-Participants were recruited in large part from social media sites. This form of recruitment has
been suggested to disproportionately favor more dissatisfied patients leading to a bias in QoL
assessment.
-Patients are grouped by self reported diagnosis. The categories given by the authors are:
Hashimoto’s, hypothyroidism, Graves’ disease and hyperthyroidism. Given that Hashimoto’s is
the leading cause of hypothyroidism and Graves’ disease the leading cause of hyperthyroidism,
the concomitant use of these categories is ambiguous.
It is not realistic to expect patients to reliably distinguish between disease etiologies (eg. Graves’
disease and other causes of hyperthyroidism) during a self report. There is a marked risk of
cross-contamination of study groups using this methodology questioning the validity of any
assessment of between-group differences.
-There is no information regarding ongoing treatment of either conditions, which raises the
following issues:
1. QoL has previously been shown to be markedly decreased in untreated hypo- and
hyperthyroidism, and only mildly diminished in adequately treated disease. In the absence
of relevant data it is unclear where on this spectrum the results reported by the authors fall.
Assessment of symptoms and QoL, and comparison of patient groups is meaningless without
taking recent treatment and current thyroid function into consideration.
2. Some cases of thyroid dysfunction are not treated with ongoing pharmacologic therapy
(eg. surgery/ I131 in hyperthyroidism of all etiologies, Graves’ disease in remission, watchful
waiting in subclinical Hashimoto’s). Failure to exclude such patients from the assessment of the
relationship between adherence and thyroid-dependent QoL is a further source of bias.
-While the authors clearly state in the introduction that QoL in patients with thyroid disease can
be affected by comorbidities, no data is reported on comorbid conditions which adds a further
layer of potential confounders to all analysis.
Measures:
-No data is reported on the validity or reliability of the patient reported measures used.
-While two of the questionnaires had a previous Hungarian version, the authors give no
information on the translation, and validation of ThyPRO-39. It seems that this instrument
was recently validated in Hungarian (DOI:10.1186/s41687-023-00606-7) it is unclear, however,
whether the same version of the questionnaire was used, or if the authors had created a separate
translation.
-ThyPRO is repeatedly referred to as a ‘measure of QoL in thyroid patients’, however, it is an
instrument measuring thyroid-specific quality of life which is not the same concept.
Data analysis
-z-test and Cohen’s d are generally not used with ordinal data or following non-parametric tests.
-It appears that no correction was done to compensate for familywise error rate inflation
following multiple testing.
-Mediation analysis in a cross sectional study is somewhat problematic, as directionality and
causality can not be readily interpreted. The authors give no clear reasoning behind their
hypothesis that part of the effect of adherence on QoL is mediated by social support. It is equally,
if not more, likely that the effect of social support is partly mediated by adherence, or that QoL
is the mediator between adherence and social support. Thus it is dubious if this type of analysis
adds anything of substance to the information already presented beforehand.
Results
-It might be informative to present the demographic data in Table 1 by patient group, as further
analyses have also been done that way.
-The arrangement of Table 2 is misleading as it suggests that the statistical analysis concerns
differences in group means across the presented measures. The Mann-Whitney U test, however,
does not test differences of group means and results should not be interpreted as such. The issue
is somewhat similar to my point on Cohen’s d above.
-The footnote of Table 3 does not clarify what numbers are presented in the table. The text
suggests it is Spearman's rho, however, this should be made clear in the legend.
-It is not made clear either on Figure 1 or in the figure legend which coefficients belong to which
patient group.