Elsevier

Journal of Affective Disorders

Volume 225, 1 January 2018, Pages 313-316
Journal of Affective Disorders

Research paper
Attitudes toward placebo-controlled clinical trials among depressed patients in Japan

https://doi.org/10.1016/j.jad.2017.08.061Get rights and content

Highlights

  • A total of 206 depressed subjects were studied.

  • Only 47% of the patients would be willing to participate in placebo-controlled trial.

  • Clinical features could relate to possible participation for such trials.

  • Placebo-controlled design could cause selection bias of participants.

Abstract

Background

Placebo-controlled clinical trials are the standard in the design of clinical studies for the licensing of new drugs. Medical and ethical concerns regarding placebo use still exist in clinical trials of depressed patients. The aim of this study was to investigate the attitudes toward placebo-controlled clinical trials and to assess factors related to the willingness to participate in such trials among depressed patients in Japan.

Methods

A total of 206 depressed patients aged 49.5 ± 15.7 years (mean ± SD) who were admitted to three psychiatric hospitals were recruited for a cross-sectional study from June 2015 to March 2016. After a thorough explanation of the placebo, the study participants completed a brief 14-item questionnaire developed to evaluate patients' attitudes regarding possible participation in placebo-controlled clinical trials. The Quick Inventory of Depressive Symptomatology was also administered to assess depressive symptoms.

Results

The results indicated that 47% of the patients would be willing to participate in a placebo-controlled clinical trial. Expectations for the improvement of disease, desire to receive more medical care, encouragement by family or friends, and desire to support the development of new drugs were associated with the willingness to participate in such trials, whereas a belief that additional time would be required for medical examinations and fear of exacerbation of symptoms due to placebo use were associated with non-participation.

Limitations

Patients were asked about possible participation in placebo-controlled clinical trials.

Conclusions

Less than half of the respondents were willing to participate in placebo-controlled clinical trials. Attitudes toward participation in a placebo-controlled clinical trial need to be considered when deciding whether to conduct such a trial.

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.

References (27)

  • R.C. Kessler et al.

    Lifetime prevalence and age-of-onset distributions of mental disorders in the World health organization's World Mental health survey Initiative

    World Psychiatry

    (2007)
  • I. Kirsch et al.

    Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration

    PLoS Med.

    (2008)
  • S. Kudo et al.

    The low level of understanding of depression among patients treated with antidepressants: a survey of 424 outpatients in Japan

    Neuropsychiatr. Dis. Treat.

    (2015)
  • Cited by (3)

    • Stressful events and coping strategies associated with symptoms of depression: A Japanese general population survey

      2018, Journal of Affective Disorders
      Citation Excerpt :

      This discrepancy could be because of the age difference in the populations of the two studies, which suggests that the psychological burden of stressful life events could change according to age; that is, “Unemployment” and “Health/illness/care of family” could be more serious events for younger than for older people, while the opposite could be true for “Death of a close person”. In the present study, the two avoidant strategies, “Bearing without action” and “Lying down on the bed”, were positively associated with symptoms of depression, which is in line with previous results in clinical (Billings and Moos, 1984; Dekker and Oomen, 1999; Schouws et al., 2001) and epidemiological settings (Nagase et al., 2009; Sugawara et al., 2018). Because of the cross-sectional design of our study, it is unclear whether avoidant coping strategies might have caused symptoms of depression or whether symptoms of depression might have altered the coping strategies of the participants.

    • Surveys of clinician and patient attitudes to an add-on for in vitro fertilisation

      2022, Australian and New Zealand Journal of Obstetrics and Gynaecology
    View full text