Research paperAttitudes toward placebo-controlled clinical trials among depressed patients in Japan
Introduction
Depression is a serious affective illness with heterogeneous symptomatology expressed as a combination of emotional, physical, cognitive, and social aspects. The age at onset of depression is typically young adulthood, and the prevalence of depression remains elevated throughout the entire lifespan (Kessler et al., 2007). The World Health Organization has projected that major depressive disorder will rank second in worldwide disability-adjusted life-years (DALYs) by the year 2020 (World Health Organization, 2001). However, the results of depression treatment with currently available antidepressants are still unsatisfactory. To achieve more effective and safe pharmacotherapy, new anti-depressive agents should be developed that are based not only on serotonin but also on other biochemical mechanisms (Su, 2009). As the social and economic costs of depression continue to increase, research is needed to compare the efficacy of new drugs in clinical trials (Murray and Lopez, 1997).
To identify new drug applications, the placebo arm is still the gold standard in the design of clinical studies (Tashiro et al., 2012). However, article 33 of the Declaration of Helsinki describes that "where no proven intervention exists, the use of placebo or no intervention is acceptable" (World Medical Association, 2013). The Pharmaceutical and Medical Devices Agency (Subcommittee on Placebo-controlled Studies, 2016), a Japanese regulatory agency, also stated that "the conduct of a placebo-controlled study should be carefully discussed on a case-by-case basis for individual clinical trials based on the severity and irreversibility of the target disease, and, if appropriate, relief measures may be prepared". In the case that there are good reasons for placebo use or the condition being studied is minor and the additional risk is negligible, placebo-controlled clinical trials in depressed patients would be acceptable. However, controversy remains due to ethical and medical concerns. Furthermore, the attitudes of depressed patients toward placebo-controlled clinical trials are an unexplored yet critical factor.
The objectives of this investigation were (1) to obtain information on patients’ attitudes toward placebo-controlled clinical trials and (2) to assess factors related to the willingness to participate in placebo-controlled clinical trials among depressed patients in Japan. To the best of our knowledge, this article presents the first study on attitudes toward placebo usage in clinical trials in depressed populations.
Section snippets
Participants
This study was conducted between June 2015 and March 2016. The data collection protocol for this study (2013-324) was approved by the Ethics Committee of the Hirosaki University School of Medicine, and all subjects provided written informed consent before participating in this study. This protocol was conducted in accordance with the Declaration of Helsinki. The subjects included 206 outpatients (153 males and 53 females) at three psychiatric hospitals in Japan who were diagnosed with major
Results
The mean age of the full sample was 49.5 ± 15.7 years, the mean number of years of education was 9.5 ± 1.8 years, and the mean duration of illness was 6.4 ± 5.0 years. The average QIDS-J, CGI-S, and GAF scores were 9.2 ± 6.2, 3.1 ± 1.1, and 71.2 ± 15.3, respectively. Among all the participants, 46.6% indicated that they would hypothetically participate in a placebo-controlled clinical trial (Q1) (Table 1).
When analyzing the influence of sociodemographic data (Table 2) on the willingness to
Discussion
The risks and benefits of placebo use in clinical trials are still controversial, and there have been few studies evaluating the attitudes of depressed patients toward placebo-controlled clinical trials. A better understanding of depressed patients’ attitudes toward placebo-controlled clinical trials would likely improve the designs of clinical trials and enrollment. The present study is the first to investigate the attitudes of patients with depression toward placebo-controlled clinical
Author disclosure
Norio Sugawara has received grant/research support from Grant-in-Aid for Young Scientists (B) (25860983), the Ministry of Education, Culture, Sports, Science and Technology, Japan Grant B, the Karoji Memorial Fund for Medical Research Grant and SENSHIN Medical Research Foundation. Norio Yasui-Furukori has received research support or honoraria from Astellas Pharma Inc., Dainippon Sumitomo Pharma Co., Ltd., Eli Lilly Japan, K.K., GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., Meiji Seika
Role of the funding source
The funders had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Acknowledgments
The authors are grateful to all volunteers who participated in this study. The authors declare that they have no competing interests.
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