Timeliness of a Signal Detection Process as a Component of Effectiveness Assessment in a Drug Safety Department of a Large Pharmaceutical Company: Review Over a 5-Year Period.

The effectiveness of a signal detection process integrating traditional and data-mining techniques was evaluated retrospectively in the real-world setting of a drug safety department at a large pharmaceutical company. To this effect, annual metrics on all signals detected internally or externally for all approved Novartis drugs were reviewed from January 1, 2007, to December 31, 2011. Timeliness (ie, the ability of the signal detection process to detect signals prior to any regulator) was taken as a main component of effectiveness. Over this 5-year period, 568 (about 17%) of the 3481 signals submitted by the safety management team at the signal escalation boards were identified as new or changing signals. Of these 568 signals, 53 (10%) were detected first by health authorities (a quarter of which were class signals). In conclusion, the signal detection process at Novartis Pharmaceuticals could detect at least 9 of 10 signals prior to them being detected by health authorities.

Patients with a major depressive episode responding to treatment with repetitive transcranial magnetic stimulation (rTMS) are resistant to the effects of rapid tryptophan depletion.

Repetitive transcranial magnetic stimulation (rTMS) appears to be efficacious in the treatment of major depression based on the results of controlled studies, but little is known about its antidepressant mechanism of action. Mood sensitivity following rapid tryptophan depletion (RTD) has been demonstrated in depressed patients responding to SSRI antidepressants and phototherapy, but not in responders to electroconvulsive therapy (ECT). We sought to study the effects of RTD in patients with major depression responding to a course of treatment with rTMS. Twelve subjects treated successfully with rTMS monotherapy underwent both RTD and sham depletion in a double-blind crossover design. Depressive symptoms were assessed using both a modified Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). The differential change in depression scores across the procedures was compared. No significant difference in mood symptoms was noted between RTD and the sham-depletion procedure on either continuous measures of depression, or in the proportions of subjects that met predefined criteria for a significant degree of mood worsening. Responders to rTMS are resistant to the mood perturbing effects of RTD. This suggests that rTMS does not depend on the central availability of serotonin to exert antidepressant effects in major depression.