Clinical trials: active control vs placebo — What is ethical?

The quest for effective medicines is very old. In modern times two important tools have been developed to evaluate efficacy of drugs: superiority and non-inferiority types of clinical trials. The former tests the null hypothesis of μ (the difference between a tested drug and comparator) ≤ 0 against μ > 0; the latter tests the null hypothesis of μ ≤ - Δ against, μ > - Δ, where Δ is the clinical difference from the comparator. In a superiority trial, a new drug is tested against a placebo; in a non-inferiority trial, a new drug is tested against active treatment. In this paper, arguments are presented to show that a superiority trial against a placebo is scientifically sound but ethically unacceptable, whereas a non-inferiority trial against active treatment is ethically sound but scientifically not reliable. Switching from a superiority type of trial with placebo to a non-inferiority trial with an active-control — following the latest revision of Declaration of Helsinki — is in practice switching from the violation of the uncertainty principle to uncertainty of results. Given human and financial resources, it appears an academic question as to which is more unethical: to violate patients’ rights or to produce results without scientific value. All presented considerations lead to the conclusion that the use of a superiority trial of design with an active control instead of placebo will satisfy scientific needs, expectation of patients, and the ancient quest for effective medicines. In the era of Good (Clinical, Laboratory, Manufacture) Practice, the attention of those performing clinical trials is focused on the procedure, not always on its essence. However even the excellent performance of a trial which is not worth doing is fruitless. An earlier version of this paper was presented at an international conference, “Placebo: Its Action and Place in Health Research Today,” held in Warsaw, Poland on 12–13 April, 2003.     

Löb's Theorem in a Set Theoretical Setting

We present a semantic proof of Löb's theorem for theories T containing ZF. Without using the diagonalization lemma, we construct a sentence AUT _T, which says intuitively that the predicate autological with respect to T (i.e. applying to itself in every model of T) is itself autological with respect to T. In effect, the sentence AUT _T states I follow semantically from T. Then we show that this sentence indeed follows from T and therefore is true.     

The role of social support in women’s health and recovery processes

The aim of this study was to assess the psychological state of women who have undergone surgery for breast cancer or cardiac surgery, including examination of the role of social support in both groups. The study included 48 women (mean age: 66.04?±?8.3 years). They were divided into two groups according to diagnosis: 23 women (mean age: 69.2?±?8.6 years) who underwent heart surgery (cardiac group, CG) and 25 women (mean age: 63.2?±?7.0 years) treated for breast cancer and associated with the Women After Mastectomy Club (oncology group, OG). In addition to the assessment of socio-demographic variables, the following self-report questionnaires were administered: Satisfaction with Life Scale, Acceptance of Illness Scale, Beck Depression Inventory, Spielberger State-Trait Anxiety Inventory as well as Berlin Social Support Scale. In the CG, the severity of depressive symptoms was two times higher than in OG (p?=?.003). In both groups, there was a high percentage (80%) of women with severe symptoms of anxiety (p?=?.37). In both groups, the level of life satisfaction was similar (p?=?.58), but OG was characterized by a higher level of acceptance of the disease (p?=?.003). The correlation analysis showed that in both groups, social support was related differently to the parameters of emotional state. Women treated for breast cancer were in a better mental condition than women treated for heart disease. The support coming from other women in similar circumstances (Women After Mastectomy Club) seems to be more effective than the support coming from the patient’s immediate environment. The results for social support ought to be interpreted not only through the prism of mean values of received support, but also with regard to the information on the sources of support.     

Quality of Life and Optimism in Patients with Morphea

Despite extensive knowledge about quality of life of people suffering from dermatological diseases, data on patients with morphea are scarce. The aim of our study was to compare the quality of life of healthy controls and morphea patients, as well as to determine the correlation of this variable with the level of dispositional optimism. The study included 47 patients with morphea and 47 healthy controls, matched for gender and age. Cantril’s Ladder and Life Orientation Test-Revised were used to assess the levels of life satisfaction and dispositional optimism, respectively. LoSSI was used for the objective assessment. The anticipated level of life quality and the level of dispositional optimism were statistically significantly lower in morphea patients (p?=?0.032 and p?=?0.014, respectively) when compared to controls. There were no differences in the assessment of current (p?=?0.168) and past (p?=?0.318) levels of life quality. Also, we proved that type of morphea did not differentiate the current (p?=?0.175), past (p?=?0.620) and future (p?=?0.356) assessment of the quality of life. In the group of morphea patients there was a statistically significant correlation between the level of dispositional optimism and current (p?=?0.002, r?=?0.43), as well as anticipated (p?r?=?0.57) levels of life quality. Current level of life quality of healthy controls and morphea patients is comparable, whereas the latter anticipate their future life situation to be significantly worse than the former. Higher level of life satisfaction correlates with higher level of optimism.     

Emotion Dysregulation,Mentalization and Romantic Attachment in the Nonclinical Adolescent Female Sample

The main goal of the current study is to verify the relationships between emotion dysregulation, mentalization, and romantic attachment in late adolescent girls (N = 120). Adolescence is a very dynamic and sensitive period, in which many changes occur in attachment and emotion regulation. The role of the primary attachment figures is gradually taken over by peers, and the beginnings of the development of romantic attachment are seen. In summary, this study was able to determine that the level of dysregulation of emotions in girls during late adolescence can be partially explained by mentalization and levels of anxiety (though not of avoidance) regarding a romantic partner, though attachment anxiety is more important for explaining emotion dysregulation than the level of mentalization. Only two aspects of emotion dysregulation show relationships with mentalization: nonacceptance of emotional responses and lack of emotional clarity. Adolescence is considered to be a critical period for interventions to protect against the onset of psychopathology. Confirmation of these relationships appears to be important for the design of therapeutic interventions. Our findings may suggest that attachment patterns, mentalization and emotion dysregulation may be good targets for therapeutic intervention in adolescence.