TY - JOUR A1 - Mueller-Schoell, Anna A1 - Groenland, Stefanie L. A1 - Scherf-Clavel, Oliver A1 - van Dyk, Madele A1 - Huisinga, Wilhelm A1 - Michelet, Robin A1 - Jaehde, Ulrich A1 - Steeghs, Neeltje A1 - Huitema, Alwin D. R. A1 - Kloft, Charlotte T1 - Therapeutic drug monitoring of oral targeted antineoplastic drugs JF - European journal of clinical pharmacology N2 - Purpose This review provides an overview of the current challenges in oral targeted antineoplastic drug (OAD) dosing and outlines the unexploited value of therapeutic drug monitoring (TDM). Factors influencing the pharmacokinetic exposure in OAD therapy are depicted together with an overview of different TDM approaches. Finally, current evidence for TDM for all approved OADs is reviewed. Methods A comprehensive literature search (covering literature published until April 2020), including primary and secondary scientific literature on pharmacokinetics and dose individualisation strategies for OADs, together with US FDA Clinical Pharmacology and Biopharmaceutics Reviews and the Committee for Medicinal Products for Human Use European Public Assessment Reports was conducted. Results OADs are highly potent drugs, which have substantially changed treatment options for cancer patients. Nevertheless, high pharmacokinetic variability and low treatment adherence are risk factors for treatment failure. TDM is a powerful tool to individualise drug dosing, ensure drug concentrations within the therapeutic window and increase treatment success rates. After reviewing the literature for 71 approved OADs, we show that exposure-response and/or exposure-toxicity relationships have been established for the majority. Moreover, TDM has been proven to be feasible for individualised dosing of abiraterone, everolimus, imatinib, pazopanib, sunitinib and tamoxifen in prospective studies. There is a lack of experience in how to best implement TDM as part of clinical routine in OAD cancer therapy. Conclusion Sub-therapeutic concentrations and severe adverse events are current challenges in OAD treatment, which can both be addressed by the application of TDM-guided dosing, ensuring concentrations within the therapeutic window. KW - targeted antineoplastic drugs KW - tyrosine kinase inhibitors KW - therapeutic KW - drug monitoring KW - oral anticancer drugs KW - personalised medicine Y1 - 2020 U6 - https://doi.org/10.1007/s00228-020-03014-8 SN - 0031-6970 SN - 1432-1041 VL - 77 IS - 4 SP - 441 EP - 464 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Weck, Florian A1 - Junga, Yvonne Marie A1 - Kliegl, Reinhold A1 - Hahn, Daniela A1 - Brucker, Katharina A1 - Witthöft, Michael T1 - Effects of competence feedback on therapist competence and patient outcome BT - a randomized controlled trial JF - Journal of consulting and clinical psychology N2 - Objective: Therapist competence is considered essential for the success of psychotherapy. Feedback is an intervention which has the potential to improve therapist competence. The present study investigated whether competence feedback leads to an improvement of therapist competence and patient outcome. Method: Sixty-seven master-level clinical trainees were randomly assigned to either a competence feedback group (CFG) or a control group (CG). Patients with a diagnosis of major depression (N = 114) were randomly assigned to CFG or CG. Treatment included 20 individual sessions of cognitive behavioral therapy (CBT). In CFG, therapists received, parallel to the treatment, five competence feedbacks, based on videotaped therapy sessions. Independent raters assessed therapist competence with the Cognitive Therapy Scale (CTS) and provided the competence feedback. Patient outcome was evaluated with the Beck Depression Inventory-II (BDI-II) and therapeutic alliance (Helping Alliance Questionnaire [HAQ]) from both therapist's (HAQ-T) and patient's (HAQ-P) perspective were evaluated after each of the 20 sessions. Results: (a) Therapist competence (CTS) increased significantly more for CFG than CG. (b) Depression (BDI-II) decreased significantly across sessions for both groups, but without evidence for a group-differential benefit for the CFG. (c) Therapeutic alliance (HAQ-T/P) increased significantly across sessions for both groups from both perspectives, but without group differences. (d) There is a positive effect of BDI-II on CTS at the beginning and a negative effect of CTS on BDI-II at the end of therapy. Conclusion: Competence feedback improves therapists' independently rated competence, but there is no evidence that competence feedback in CBT leads to better outcome. What is the public health significance of this article? This study suggests the substantial value of systematic competence feedback for improving therapist competence in the psychotherapy of depression. No significant effect of competence feedback on the reduction of reported depressive symptoms was found. KW - feedback KW - outcome KW - major depression KW - therapeutic alliance KW - therapeutic KW - competencies Y1 - 2021 U6 - https://doi.org/10.1037/ccp0000686 SN - 0022-006X SN - 1939-2117 VL - 89 IS - 11 SP - 885 EP - 897 PB - American Psychological Association CY - Washington ER -