Søren Dinesen Østergaard1, Per Bech2, Kamilla Woznica Miskowiak3. 1. Research Department P, Aarhus University Hospital, Risskov, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus and Copenhagen, Denmark. 2. Psychiatric Research Unit, Psychiatric Center North Zealand, Copenhagen University Hospital, Hillerød, Denmark. Electronic address: Per.bech@regionh.dk. 3. Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Abstract
BACKGROUND: In the development of new antidepressant treatments, the failed study has unfortunately become a prevalent problem. The number of failed studies could probably be reduced significantly by applying more informative outcome measures. Previous studies have indicated that the 6-item melancholia subscale (HAM-D6) of the 17-item Hamilton Depression Rating Scale (HAM-D17) may be more informative than other scales, due to its superior psychometric properties. In the present study we investigated whether the HAM-D6 had higher informativeness than the HAM-D17 based on data from a randomized placebo-controlled trial (RCT) testing the effect of erythropoietin (EPO) as augmentation therapy in patients with treatment-resistant depression. METHODS: We assessed the scalability (Mokken analysis of unidimensionality), responsiveness (item responsiveness analysis) and ability to show drug-placebo separation (estimation of sample size needed to detect statistically significant difference between EPO and placebo) of the HAM-D6 and the HAM-D17. RESULTS: The HAM-D6 demonstrated higher scalability, higher responsiveness, and better drug-placebo separation compared to the HAM-D17. As a consequence, only 39 participants per group would be required to detect a statistically significant difference between EPO and placebo when using the HAM-D6 as outcome measure, whereas the required group size for HAM-D17 would be 146 participants. LIMITATIONS: The EPO RCT was not originally designed to investigate the research questions addressed in this study. CONCLUSIONS: Both for ethical and financial reasons it is of interest to minimize the number of participants in clinical trials. Therefore, we suggest employing the HAM-D6 as outcome measure in clinical trials of depression.
RCT Entities:
BACKGROUND: In the development of new antidepressant treatments, the failed study has unfortunately become a prevalent problem. The number of failed studies could probably be reduced significantly by applying more informative outcome measures. Previous studies have indicated that the 6-item melancholia subscale (HAM-D6) of the 17-item Hamilton Depression Rating Scale (HAM-D17) may be more informative than other scales, due to its superior psychometric properties. In the present study we investigated whether the HAM-D6 had higher informativeness than the HAM-D17 based on data from a randomized placebo-controlled trial (RCT) testing the effect of erythropoietin (EPO) as augmentation therapy in patients with treatment-resistant depression. METHODS: We assessed the scalability (Mokken analysis of unidimensionality), responsiveness (item responsiveness analysis) and ability to show drug-placebo separation (estimation of sample size needed to detect statistically significant difference between EPO and placebo) of the HAM-D6 and the HAM-D17. RESULTS: The HAM-D6 demonstrated higher scalability, higher responsiveness, and better drug-placebo separation compared to the HAM-D17. As a consequence, only 39 participants per group would be required to detect a statistically significant difference between EPO and placebo when using the HAM-D6 as outcome measure, whereas the required group size for HAM-D17 would be 146 participants. LIMITATIONS: The EPO RCT was not originally designed to investigate the research questions addressed in this study. CONCLUSIONS: Both for ethical and financial reasons it is of interest to minimize the number of participants in clinical trials. Therefore, we suggest employing the HAM-D6 as outcome measure in clinical trials of depression.
Authors: Søren D Østergaard; Maria S Speed; Charles H Kellner; Martina Mueller; Shawn M McClintock; Mustafa M Husain; Georgios Petrides; William V McCall; Sarah H Lisanby Journal: J Affect Disord Date: 2020-05-23 Impact factor: 4.839
Authors: Benjamin S C Wade; Gerhard Hellemann; Randall T Espinoza; Roger P Woods; Shantanu H Joshi; Ronny Redlich; Anders Jørgensen; Christopher C Abbott; Ketil J Oedegaard; Shawn M McClintock; Leif Oltedal; Katherine L Narr Journal: J ECT Date: 2020-06 Impact factor: 3.692
Authors: Lucas Primo de Carvalho Alves; Marcelo Pio de Almeida Fleck; Aline Boni; Neusa Sica da Rocha Journal: PLoS One Date: 2017-01-23 Impact factor: 3.240
Authors: Beatrice Bortolato; Kamilla W Miskowiak; Cristiano A Köhler; Michael Maes; Brisa S Fernandes; Michael Berk; André F Carvalho Journal: BMC Med Date: 2016-01-22 Impact factor: 8.775