Ito et al.
Journal of Pharmaceutical Policy and Practicehttps://doi.org/10.1186/s40545-022-00470-8(2022) 15:79

Open Access

RESEARCH

Patients’ acceptance of placebo antibiotics
in Japan: a prescription for antimicrobial
resistanceAtsushi Ito1, Yuichi Watanabe2 and Takashi Okumura3*   

Abstract
Background: The generalized use of antibiotics has led to the emergence of bacteria which are resistant to antimicrobial agents. This stems in part from the patient’s tendencies to seek antibiotics for diseases when not necessary.
Hence, this article investigated patient acceptance of prescribing placebos as a substitute for unnecessary antibiotics in Japan, where physicians are under severe time constraints and are unable to offer explanations and persuadepatients who demand unnecessary antibiotics prescription.
Methods: A web-based questionnaire was administered to assess patients’ acceptance of the placebo treatment
under informed consent. One thousand participants representing all genders and age-class were randomly selectedfrom the online panel of a web-survey company.
Results: The results showed that 67.9% of the participants were “satisfied” to receive such treatments, whereas 20.6%
indicated acceptance of the prescription but without satisfaction. In total, 88.5% of the participants accepted theprescription of placebo, a result consistent with that of a preceding study on placebo treatments conducted in the
United States. In the survey, tone of persuasion did not affect the patients’ attitudes; however, patients who were loyal
to their physicians exhibited lower refusal rates.
Conclusion: The survey results showed that the prescription of “ethical placebos” could be an acceptable option forthe patients in Japan. For ethical concerns, an additional literature survey was conducted and the result suggested
that such a radical treatment option could be justified, provided that the prescription benefits patients and informed
consent is properly obtained. Albeit it is impractical to use, because of ethical and operational concerns, it would be
worth further investigation to ensure diversity in the countermeasures for antimicrobial resistance, a major publichealth threat nowadays.
Keywords: Antimicrobial resistance, Ethical placebos, Antibiotic
BackgroundThe discovery and development of antibiotics
has rendered obsolete many infections that haveplagued humankind. However, the generalized use*Correspondence: taka@wide.ad.jp
3
School of Regional Innovation and Social Design Engineering, Kitami
Institute of Technology, Kitami City, Hokkaido 090‑8507, Japan
Full list of author information is available at the end of the articleof antibiotics has resulted in an increasing numberof resistant bacteria. The growing number of multidrug-resistant bacteria can lead to intractable bacterial
infections, resulting in a global public health issue [1].
One of the causes of this problem is the inappropriateprescription of antibiotics for diseases such as common cold and influenza that cannot be cured by antibiotics [2]. Antibiotics are unnecessary for patients withviral infections. In acute rhinosinusitis, antibiotics
and placebo prescriptions showed almost equivalent© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to theoriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images orother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line
to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of thislicence, visit http://​creat​iveco​mmons.​org/​licen​ses/​by/4.​0/. The Creative Commons Public Domain Dedication waiver (http://​creat​iveco​
mmons.​org/​publi​cdoma​in/​zero/1.​0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Ito et al. Journal of Pharmaceutical Policy and Practice(2022) 15:79

outcomes [3]. Moreover, excessive use of antibiotics
can have harmful effects on a patient’s intestinal flora.
However, some patients demand antibiotic prescriptions, and some doctors continue to prescribe them.
For example, an investigation of general practitioners (GPs) in Australia showed that over half of theGPs had prescribed antibiotics in response to patient
expectations [4]. In the context of the increasing senseof patients’ rights and the risk of lawsuits, medical
providers might be responding excessively to patientdemands.
Patients in Japan are reportedly less knowledgeable
about antibiotics than the patients in the European
Union, and many patients demand antibiotic prescriptions even for conditions that do not require such[5]. The lack of patient awareness of anti-microbial
resistance (AMR) has been considered an underlying
factor of the situation, and the government has developed a national action plan for AMR [6, 7]. However,such attempts have not yielded a decisive solution
for patients seeking antibiotic prescriptions. An evenmore serious problem is the medical practice workload
in Japan. The estimated number of patient consultations per doctor reaches up to 5,633 for a year, which is
2.5 times higher than the average of the Organisation
for Economic Co-operation and Development (OECD)
countries, which is 2,277 [8]. Therefore, outpatient
clinical care places a significant burden on physicians in the country, and the amount of time that canbe spent on each patient is severely limited. In such asituation, physicians find it difficult to secure enoughtime to offer explanations and persuade patients who
demand unnecessary antibiotics because there is ahigh pressure on physicians to prescribe antibiotics[5].
Therefore, we conceptualized an impractical, buttheoretically effective, method that allows physicians to
reduce unnecessary prescription of antibiotics by prescribing a placebo instead of antibiotics, presupposing
the extreme situation in Japan. To avoid ethical issues
associated with prescribing placebos to patients who
demand antibiotics, the prescription should be issued
under informed consent. Additionally, such a placebo prescription should be made only when patientsdemand antibiotics although evidence indicates that theplacebo outweighs antibiotics. This present study conducted an online survey to determine patient acceptance of such a radical treatment option. In this article,
we first define the ethical placebo concept, referring torelated works. Second, the methodology of the survey
is shown, followed by the results. Then, analysis anddiscussion are provided. The last section concludes thearticle and suggests future directions.

Page 2 of 12

Related works

The prescription of a placebo could reduce the number ofactual prescriptions while avoiding dissensions between
physicians and patients. However, placebo prescription
against a patient’s will is considered unethical. Hence,
informed consent must be obtained from patients for theprescription of placebos. This may appear contradictory,
as this will compromise the purpose of a placebo if thepatients know the content of the prescription. Therefore,
we propose obtaining prior consent by means of a notice(on-wall signage) in the institution, rather than obtaining consent at the time of prescription. Additional file 1:
Appendix 1 further discusses the ethical issues in the
proposal, which indicates that the placebos can be justified under certain conditions with appropriate informed
consent.
Although placebos have primarily been used in clinical trials, physicians use various placebo-like techniques
out of clinical necessity [9, 10]. A review of 22 studies
from 12 countries revealed that 17–80% of the physicians
engaged in placebo-like treatments, such as injection ofsaline [10]. Such acts have been investigated from various
viewpoints in medical ethics and have been justified only
when certain conditions are met, namely benefit of thepatients, considering the advantages and disadvantagesof prescribing placebos [11].
In this context, although several studies have investigated physicians’ opinions of placebos [9, 10], patient
acceptance has received less attention. Hull performed
one such study investigating how patients think aboutplacebo treatments and whether they are willing to accept
such a treatment option [12]. The study was performedin Northern California and targeted adult patients
who had visited an outpatient clinic at least once in the
6 months prior to the study. The structured interviews
were administered by phone, and eligible participants
were requested to voice their opinions on four scenarios of placebo treatments, each of which featured different patients who sought doctors for specific reasons.
Each interview took 20 min on average, and the participants were sent $20 gift cards afterward. In this setting,
53.4% of patients accepted the interview, and 78.1% of
the responders accepted the use of placebos in general.
Regarding placebo use for common cold, which resembles our situation, 65.6% accepted the placebo prescription. Nevertheless, results of opinion surveys can differ
significantly depending on the contexts and the questionnaires. Besides, the elaborated interview asked hypothetical questions regarding others and not about thepatients themselves. Further, the interview setting might
have compromised the anonymity of the answers about
the ethical issues. Accordingly, we investigated patient
opinions on the placebos for unnecessary antibiotics, inIto et al. Journal of Pharmaceutical Policy and Practice(2022) 15:79

different cultural backgrounds with differently phrased
questions, ensuring anonymity.

Methods
To address the aforementioned problems, the survey wasadministered through a web-survey company, Rakuten
Insight, Inc., which has one of the largest online panels in Japan (2.2 million members as of April 2019). We
recruited online monitors who agreed to participate in
the survey and randomly sampled 1000 people as participants. The survey was administered from January 15
to 17, 2019, on their online survey platform, as described
below. In this study, the inclusion criterion of prior visits
to clinics was omitted because Japanese residents usually
visit doctors 12.9 times a year, on average, which is threetimes higher than the number of the United States [8].
We used a questionnaire that included 22 questions.
Its English translation, together with the detailed protocol, is provided in Additional file 2: Appendix 2. Basedon our conjecture that the author and tone of the explanation could affect patient acceptance, we prepared fourtypes of in-hospital notices and randomly assigned theparticipants into four groups to determine their levels of
acceptance of each notice. Table 1 shows the authors of
the four types of in-hospital notices and explanations of
their prescription content. For Notice type 1, the author
was the clinic director and the notice emphasized thatthe prescription was based on practice guidelines from
the Ministry of Health. For Notice type 2, the author wasan academic and the prescription was based on practiceguidelines from the academic society. For Notice type 3,
the author was the clinic director and the notice emphasized that the prescription was based on the prescription
policy of the clinic, in a rational tone. Finally, for Noticetype 4, the author was the clinic director and the noticeincluded an appeal to the patients’ emotions while stating that the prescription was based on clinic policy.
Hence, we investigated the type of authority and explanation tones that might help improve the acceptance rateof the paternalistic intervention of physicians in patientdecision-making. To analyze the various factors thatmight affect patient attitudes, we included questions that
could be categorized into four types: compliance (Q.12,
Q.13, and Q.14), health literacy (Q.9, Q.10, and Q.19),

Page 3 of 12

health awareness (Q.5, Q.6, and Q.8), access to healthcare
facilities (Q.3, Q.4, and Q.7), and basic attributes (Q.1 and
Q.2). This study was approved by the Institutional Review
Board for Research with Human Subjects at the Kitami
Institute of Technology (Approval Number 1016).

Results
Additional file 3: Appendix 3 gives the counts of all the
responses to the questionnaire. First, we analyzed thedegree of patient approval of the proposed placebo prescriptions as described by in-hospital notices at a clinic(Table 2a). In response to the question, “What will you
do when you see the notice above?”, 668 (67.9%) participants answered, “I am satisfied with the policy and accept
the prescription that my physician provides” (Active
approval). In addition, 203 (20.6%) subjects answered, “I
am not satisfied with the policy; or I do not understandit, but accept the prescription that my physician provides” (Passive approval), whereas 113 (11.5%) subjects
answered, “I would tell my physician that I am dissatisfied
with the policy or that I do not consent” (Refusal). We
excluded 16 questionnaires from the results of this question due to missing answers (others). Overall, the results
showed that 88.5% of the subjects would accept placebos
instead of antibiotics, whereas 11.5% would not consent
to such prescriptions. These results are similar to thoseobtained by an investigation conducted in the USA [12],which had a significantly different cultural background.
As these responses concern attitudes toward the inhospital notices, the content of such notices could havegreatly affected the responses. Therefore, we compared
the results of four different types of in-hospital notices.
Notice type 2 received the highest (177 subjects; 71.4%)
active approval, followed by Notice types 3 and 4 (168subjects; 68.6%), which indicated the clinic director as theauthor. Notice type 1, which indicated that the prescription was based on guidelines from the Ministry of Health,
had the lowest score (155 subjects; 63.3%). Meanwhile,
21 (8.5%), 29 (11.8%), 31 (12.6%), and 32 (13.1%) subjects
indicated clear refusal, “I would tell my physician that I
am dissatisfied with the policy or that I do not consent”
for Notice types 2, 1, 4, and 3, respectively. However, theChi-squared test indicated no statistically significant differences among these proportions of responses. Hence,

Table 1 Authors of the in-hospital notices and explanations of the prescriptions within the texts
Notice type

AuthorExplanation of the prescription

Type 1

Clinic director

Based on practice guidelines from the Ministry of HealthType 2

Academic society

Based on practice guidelines from an academic societyType 3Clinic director

Explained in a rational tone as a prescription policy of the clinic

Type 4

Clinic director

Explained in an emotional tone as a prescription policy of the clinic

Ito et al. Journal of Pharmaceutical Policy and Practice(2022) 15:79

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Table 2 Answer summary to questions(a) “What will you do when you see the notice above?”
Notice type

Active approval

Passive approval

Refusalp valueType 1

155

63.3%

61

24.9%

29

11.8%

Type 2

177

71.4%

50

20.2%

21

8.5%

Type 3

168

68.6%

45

18.4%

32

13.1%

Type 4

168

68.3%

47

19.1%

31

12.6%

Total

668

67.9%

203

20.6%

113

11.5%

n.s

(b) “How would you consider visiting the medical institution that displayed such a notice?”
Notice typeContinue visiting

Change, if possible

Never revisit

p valueType 1

177

71.7%

62

25.1%

8

3.2%

Type 2

187

75.7%

51

20.6%

9

3.6%

Type 3

171

69.8%

67

27.3%

7

2.9%

Type 4

179

72.8%

53

21.5%

14

5.7%

Total

714

72.5%

233

23.7%

38

3.9%

n.s

Chi-squared test
n.s. not significant

our results did not prove whether author authority or thetone of expression altered patient attitudes toward ethicalplacebos.
Next, we analyzed whether displaying a policy regarding the prescription of placebos instead of antibiotics
would affect the revisit behaviors of patients (Table 2b).
In response to the question, “How would you consider
visiting the medical institution that displayed such a
notice?”, 714 subjects (72.5%) responded “I would continue to visit, as necessary” (Continue visiting), whereas
233 subjects (23.7%) responded “I would visit anotherhospital if possible” (Change, if possible) and 38 subjects(3.9%) responded “I would never again visit the hospital”(Never revisit). We excluded 15 questionnaires from theresults of this question due to missing answers (others).

Because attitudes are formed as a response to inhospital notices, the notice contents could also haveaffected the revisit behaviors. Therefore, we compared
the responses according to the four types of in-hospital
notices. Notice type 2 received the highest (187 subjects;
75.7%) active approval, followed by Notice types 4, 1, and3 with responses from 179 (72.8%), 177 (71.7%), and 171(69.8%) participants, respectively. Seven (2.9%), eight(3.2%), and nine (3.6%) subjects refused for Notice types
3, 1, and 2, respectively. The Chi-squared test indicatedno statistically significant differences for this question
between attitudes caused by the types of notice.
Next, we analyzed the impact of ethical placebos inpatients who demanded antibiotics for the common cold,
which was our original theme (Table 3). Among the 984

Table 3 Approval and revisit behavior of patients who demand antibiotics for common cold(a) Approval of ethical placebos
Demands antibiotics for common cold

Active approval

Passive approval

Refusalp valueYes/relatively, yes

233

67.7%

82

23.8%

29

8.4%

No/relatively, no

313

67.7%

84

18.2%

65

14.1%

Do not know

122

68.5%

37

20.8%

19

10.7%

n.s

(b) Revisit behavior of patients
Demands antibiotics for common cold

Continue visiting

Yes/relatively, yes

248

71.7%

90

No/relatively, no

336

72.4%

108

Do not know

130

74.3%

35

Chi-squared test
n.s. not significant

Change, if possible

Never revisit

p value

26.0%

8

2.3%

n.s

23.3%

20

4.3%

20.0%

10

5.7%

Ito et al. Journal of Pharmaceutical Policy and Practice(2022) 15:79

participants, 344 (35.0%) requested antibiotics (Table 3a).
A total of 462 (47.0%) participants do not request antibiotics, and 178 (18.1%) chose “do not know” as theiranswer to the question. Among those requesting antibiotics, 233 approved the ethical placebos, indicatingthat 67.7% of patients who demanded antibiotics would
accept this treatment option. “Passive approval” was indicated by 82 (23.8%) participants; thus, 91.5% approved
the treatment option, at some level. Only 8.4% indicated rejection. This trend was consistent across groups
regardless of their having requested antibiotics; thisresult indicates that ethical placebos may be an alternative for prescribing unnecessary antibiotics upon patient
request. The revisit behaviors of patients (Table 3b) also
demonstrated similar results: 71.7% of participants whorequested antibiotics would continue visiting the clinic,
26.0% might change if possible, and 2.3% would neverrevisit. There were no significant differences between
those who did and who did not request antibiotics.
Evaluation of the correlations between placebo acceptance and patient attributes revealed no statistically significant differences in acceptance in relation to sex, age,or educational background (Table 4a).
Moreover, the cross-analysis of the correlations
between attributes and revisit behaviors after viewing inhospital notices indicated no differences for sex or academic background (Table 4b). However, we observed astatistically significant difference for age, indicating thatthe motivation to continue attending the institution may
increase with age.
Analysis

The results of this study revealed that > 80% of patients
accepted the use of placebos as a substitute for antibiotics. In contrast, 11.5% of all patients clearly rejected
this method and 23.7% indicated that they would seek
future treatment at another hospital or clinic next time.
To clarify the problems associated with the proposed
method, it is necessary to identify the reasons for thepatients’ refusal to accept this method and to analyze thereasons why patients expressed a desire to seek treatment
at another medical facility. Thus, we analyzed the factorsthat may explain why some patients did and other did notconsent to the display of notices regarding the use of placebos in hospitals as well as the subsequent behavior ofpatients regarding their hospital visits.
Attitudes regarding in‑hospital noticeFirst, we conducted a cross-analysis of the relationshipbetween attitudes toward notices in the hospital and thefour factors regarding the respondents: “Compliance”,“Health literacy”, “Health awareness”, and the “Access tohealthcare facilities” (Table 5).

Page 5 of 12

In regard to questions on “Compliance”, we found asignificant difference in the degree of acceptance of the
in-hospital notices between the group that felt compliance was important and the group that did not. The specific items for which a significant difference was foundin this category were “Compliance with instructions
for medication”, “Compliance with physicians’ instructions”, and “Understanding of physician explanation.” Forexample, the rate of acceptance of in-hospital notices
was low in the group that did not always follow instructions, although those who tended to follow a physician’s
instructions were more likely to consent to the use ofplacebos.
Next, we examined the responses to questions regarding “health literacy.” The non-consent rate among thosewith the correct perception of antibiotics was 8.0%,
whereas the non-consent rate among those with mistaken perceptions was 14.6%, indicating that patientswith mistaken perceptions of antibiotics had a higher
non-consent rate. Nevertheless, no significant difference was found among respondents who did or did not
demand “influenza vaccination” (Q.10) and who usedtheir medicine notebook or not (Q.9).
Examination of the responses to the questions on“health awareness” revealed no significant differences inconsent rates between the groups in terms of “awarenessof health management” (Q.5), “walking habit” (Q.6), and“experience with denial of recommended examinations
and treatments” (Q.8).
Upon examination of the responses to the questions
regarding “access to healthcare facilities”, the consent
rates were significantly higher among those who regularly visited a medical facility and those with a regularphysician than the rate among those who avoid being
examined at a medical institution. However, no difference was found in the consent rates regarding the “Number of hospitals and clinics nearby” (Q.3) and “Easiness totake a sick leave” (Q.7).
Motivation for subsequent hospital visit

Next, we performed cross-analysis to determine the relationship between the motivation for seeking medicalcare at medical facilities and the following four factors,“Compliance”, “Health literacy”, “Health awareness”, and“Access to healthcare facilities”, after having seen a notice
regarding placebos (Table 6).
Our examination of questions related to “Compliance”
revealed a significant difference between the group thatwas likely to abide by a physician’s instructions and thegroup that was not likely to abide by a physician’s instructions regarding behaviors related to the hospital visit.
This trend is clearly indicated in the result observed forthe percentage of those who said that they would “not

Ito et al. Journal of Pharmaceutical Policy and Practice(2022) 15:79

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Table 4 Approval and revisit behavior of patients explained by basic attributes(a) Approval of ethical placebos
Category/variable

Active approval

Passive approval

Refusalp value

Sex
Male

345

69.8%

94

19.0%

55

11.1%

Female

323

65.9%

109

22.2%

58

11.8%

n.s

Age groups
20s
30s

123

62.8%

46

23.5%

27

13.8%

128

65.3%

46

23.5%

22

11.2%

40s

142

72.1%

37

18.8%

18

9.1%

50s

136

68.0%

42

21.0%

22

11.0%

Over > 60

139

71.3%

32

16.4%

24

12.3%

n.s

Educational background
Junior high school

12

60.0%

5

25.0%

3

15.0%

High school

208

68.6%

59

19.5%

36

11.9%

Junior college

64

74.4%

16

18.6%

6

7.0%

University

268

66.0%

89

21.9%

49

12.1%
14.0%

Graduate school

34

68.0%

9

18.0%

7

Vocational school

70

68.0%

25

24.3%

8

7.8%

Technical college

12

80.0%

0

0.0%

3

20.0%

Others

0

0.0%

0

0.0%

1

100.0%n.s(b) Revisit behavior of patients
Category/variable

Active approval

Passive approval

Refusalp value

Male

369

74.4%

106

21.4%

21

4.2%

Female

345

70.6%

127

26.0%

17

3.5%

20s

133

66.5%

56

28.0%

11

5.5%

30s

128

66.0%

56

28.9%

10

5.2%

40s

151

75.9%

38

19.1%

10

5.0%

50s

147

73.9%

48

24.1%

4

2.0%

Over > 60

155

80.3%

35

18.1%

3

1.6%

Junior high school

12

63.2%

6

31.6%

1

5.3%

High school

224

73.9%

65

21.5%

14

4.6%

Junior college

68

78.2%

17

19.5%

2

2.3%

University

284

70.3%

108

26.7%

12

3.0%

Graduate school

37

71.2%

11

21.2%

4

7.7%

Sex
n.s

Age groups*

Educational background

Vocational school

78

75.0%

23

22.1%

3

2.9%

Technical college

11

73.3%

2

13.3%

2

13.3%

Others00.0%

1100.0%

0

0.0%

n.s

Chi-squared test
*p < 0.05; n.s., not significant

visit this hospital again”, which rose sharply from 2.2% to14.6%. Q.13 showed that the respondents who “comply”
to physicians’ instructions tended to continue their visit,
although others did not. Q.14 showed that the respondents who were satisfied with physician explanations(Q.14) continued their visit more than those who were

not always satisfied. Based on these findings, we conclude
that those patients who followed instructions regarding medication and physician instruction and those who
were always satisfied with the explanations they received
showed a willingness to continue receiving medical care

Ito et al. Journal of Pharmaceutical Policy and Practice(2022) 15:79

Page 7 of 12

Table 5 Acceptance of the notice according to different variables
Category/variable

Active approval

Passive approval

Refusalp value

Compliance
Compliance with instructions for medication (Q.12)
  Complies

389

72.4%

98

18.2%

50

9.3%

  Not always

279

62.4%

105

23.5%

63

14.1%

  Complies

616

69.8%

183

20.7%

83

9.4%

  Not always/Do not know

52

22.2%

122

52.1%

60

25.6%

  Satisfied

484

74.2%

114

17.5%

54

8.3%

  Not always satisfied

146

54.9%

72

27.1%

48

18.0%

  Good

320

69.0%

107

23.0%

37

8.0%

  Poor

348

66.9%

96

18.5%

76

14.6%

  Positive

240

66.7%

85

23.6%

35

9.7%

  Negative

399

68.3%

112

19.2%

73

12.5%

  Neither/do not know

29

72.5%

6

15.0%

5

12.5%

  Full use

371

70.0%

105

19.8%

54

10.2%

  Not really

297

65.4%

98

21.6%

59

13.0%

  Yes/relatively, yes

379

69.0%

102

18.6%

68

12.4%

  No/relatively, no

232

66.7%

82

23.6%

34

9.8%

  Neither/do not know

57

65.5%

19

21.8%

11

12.6%

  Yes/relatively, yes

367

67.6%

111

20.4%

65

12.0%

  No/relatively, no

236

69.4%

69

20.3%

35

10.3%

  Neither/do not know

65

64.4%

23

22.8%

13

12.9%

  Yes/relatively, yes

367

67.6%

111

20.4%

65

12.0%

  No/relatively, no

236

69.4%

69

20.3%

35

10.3%

  Neither/do not know

65

64.4%

23

22.8%

13

12.9%

  > 10

207

69.0%

56

18.7%

37

12.3%

  4–9

224

70.2%

58

18.2%

37

11.6%

  1–3

188

66.2%

71

25.0%

25

8.8%

  0

10

50.0%

8

40.0%

2

10.0%

  Neither none of the above/do not know

39

63.9%

10

16.4%

12

19.7%

  Visiting a specific facility periodically

268

70.0%

66

17.2%

49

12.8%

  Visiting not periodically, but regularly

92

64.8%

34

23.9%

16

11.3%

  Visit convenient facilities as needed

259

69.8%

82

22.1%

30

8.1%

  Trying to avoid seeing a doctor

47

54.7%

21

24.4%

18

20.9%

**

Compliance with physician instructions (Q.13)**

Understanding of explanation by physicians (Q.14)**

Health literacy
Understanding of Antibiotics (Q.19)**

Attitude toward influenza vaccination (Q.10)
n.s

Utilization of medicine notebook (Q.9)
n.s

Health awareness
Walking habit (Q.6)
n.sAwareness of health management (Q.5)
n.sExperience with the denial of recommended examinations
and treatment (Q.8)
n.sAccess to healthcare facilities
Number of hospitals and clinics nearby (Q.3)
n.sFrequency of hospital/clinic visits (Q.4)**

Ito et al. Journal of Pharmaceutical Policy and Practice(2022) 15:79

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Table 5 (continued)
Category/variable

Active approval

Passive approval

Refusalp value  Easy/relatively easy

377

69.6%

107

19.7%

58

10.7%

  Not easy/relatively not easy

179

64.4%

65

23.4%

34

12.2%

  Neither/do not know

112

68.3%

31

18.9%

21

12.8%

Easiness to take a sick leave (Q.7)
n.s

Chi-squared test
*p < 0.05, **p < 0.01; n.s., not significant

at the same medical institution even after seeing the placebo notices posted in the facility.
Our examination of questions related to health literacy did not indicate significant impact of the correct
perception of antibiotics on their hospital visit behavior.
The history of influenza vaccinations (Q.10) did not also
affected their behavior, however, those who responded“I do not know/I am not sure” to the vaccination history indicated four times higher refusal rate. However, interms of the general trend, health literacy did not appear
to have a major effect on the desire to continue seeking
medical care at the same medical facility.
Examination of the questions related to “health awareness” revealed that there was no difference among the
respondents in terms of “walking habit”. However, “I donot know” group of the “awareness of health management” question (Q.5) indicated approximately 3 times
higher refusal rate to their continued visit. Likewise, “I
do not know” group of the “Experience with the denialof recommended examinations and treatment” question (Q.8) indicated two to four times higher refusal rate.
Overall, participants who showed a high degree of healthawareness were likely to continue undergoing treatment
at the same facility, whereas those with a low degree of
health awareness were more likely to seek treatment at
another facility.
Questions related to the “access to healthcare facilities” included three questions. First, the “number ofnearby medical facilities” (Q.3) indicated a general trendthat the higher percentage of residents of communities with several medical facilities from which to choose
would continue receiving medical care at the same facility, compared with the percentage of those living in areas
without medical facilities. This result may look contradictory. However, residents of communities with choices
in medical facilities selected their doctors on their own,
whereas residents of communities without nearby medical facilities might be forced to visit a facility. This might
be explained by the loyalty to the clinics, suggested by apreviously mentioned finding. Examination of the questions related to how often respondents visited a medical facility (Q.4) revealed that those respondents who
normally visited a medical facility regularly and have aregular physician had higher desires to continue visiting
the same medical facility than that among those who did
not visit medical facilities, consistent with the finding
above. Finally, examination of the questions related to theability to take a sick leave (Q.7) indicated that 77.1% of
the respondents who said that it was easy and 64.7% of
the respondents who said that it was not easy expressed
the desire to continue visiting the same medical facility.
This finding suggests that those respondents who experienced no hardships when they wanted to visit a medical facility were more likely to continue visiting the same
medical facility.
Factors determining patient attitudes toward placebos

Finally, we performed a cross-analysis of the questions related to the degree of acceptance of the proposed method and questions related to subsequenthospital visits (Table 7). The results indicated that 92.5%of those who said they would continue visiting and who
responded that they were satisfied with the hospital’s
policy would accept the prescription (active approval),
whereas 38.5% responded that they were not satisfied
with the policy or did not understand it but would accept
the physician’s prescription (passive approval) and 15.2%
refused the prescription. However, examination of thepercentage of those who said they would “change hospitals, if possible” indicated that 7.1% responded withactive approval, 59.5% responded with passive approval,
and 57.1% refused. These findings indicate that although
at least 90% of those who were satisfied with the prescription for a placebo would continue receiving medical careat the same facility, ~ 30% of those who did not accept thepolicy, those who could not understand it, and those who
were dissatisfied with the policy of prescribing placebos
and would tell their physician that they do not consent tothis type of prescription might seek treatment at anothermedical facility.
The fact that as many as 30% of patients might seek
treatment at other medical facilities is an unacceptably
high number. However, the fact that 90% of those who
consented to the prescription of placebos said that theywould continue to seek medical care at the same facility
suggests that medical facilities may be able to efficiently

Ito et al. Journal of Pharmaceutical Policy and Practice(2022) 15:79

Page 9 of 12

Table 6 Revisit behavior according to different variables
Category/variable

Continue visiting

Change, if possible

Never revisit

p value  Complies

522

56.4%

383

41.4%

20

2.2%

  Not always

24

50.0%

17

35.4%

7

14.6%

  Complies

662

75.1%

201

22.8%

19

2.2%

  Not always/do not know

52

50.5%

32

31.1%

19

18.4%

  Satisfied

509

77.8%

130

19.9%

15

2.3%

  Not always satisfied

169

63.8%

80

30.2%

16

6.0%

  Good

349

75.5%

99

21.4%

14

3.0%

  Poor

365

69.8%

134

25.6%

24

4.6%

  Positive

257

72.0%

89

24.9%

11

3.1%

  Negative

429

72.7%

139

23.6%

22

3.7%

  Neither

28

73.7%

5

13.2%

5

13.2%

  Full use

394

74.6%

122

23.1%

12

2.3%

  Not really

320

70.0%

111

24.3%

26

5.7%

  Yes/relatively, yes

413

75.1%

117

21.3%

20

3.6%

  No/relatively, no

245

70.4%

91

26.1%

12

3.4%

  Neither/do not know

56

64.4%

25

28.7%

6

6.9%

  Yes/relatively, yes

397

73.0%

132

24.3%

15

2.8%

  No/relatively, no

253

74.6%

73

21.5%

13

3.8%

  Neither/do not know

64

62.7%

28

27.5%

10

9.8%

  Yes/relatively, yes

102

73.4%

30

21.6%

7

5.0%

  No/relatively, no

563

74.4%

174

23.0%

20

2.6%

  Neither/do not know

49

55.1%

29

32.6%

11

12.4%

  More than > 10

221

73.2%

69

22.8%

12

4.0%

  4–9

234

73.1%

78

24.4%

8

2.5%

  1–3

207

73.4%

68

24.1%

7

2.5%

  0

13

68.4%

5

26.3%

1

5.3%

  Neither none of the above/do not know

39

62.9%

13

21.0%

10

16.1%

  Visiting a specific facility periodically

291

76.4%

80

21.0%

10

2.6%

  Visiting not periodically, but regularly

107

74.8%

31

21.7%

5

3.5%

  Visit convenient facilities as needed

263

70.5%

98

26.3%

12

3.2%

  Trying to avoid seeing a doctor

52

60.5%

23

26.7%

11

12.8%

Compliance
Compliance with medication instructions (Q.12)**

Compliance to physicians’ instructions (Q.13)**

Understanding of physician explanations (Q.14)**

Health literacy
Understanding of antibiotics (Q.19)
n.s

Attitude toward influenza vaccination (Q.10)*

Utilization of medicine notebooks (Q.9)*

Health awareness
Walking habit (Q.6)
n.sAwareness of health management (Q.5)**

Experience with the denial of recommended examinations and treatment (Q.8)**

Access to healthcare facilities
Number of hospitals and clinics nearby (Q.3)**

Frequency of hospital/clinic visits (Q.4)**

Ito et al. Journal of Pharmaceutical Policy and Practice(2022) 15:79

Page 10 of 12

Table 6 (continued)
Category/variable

Continue visiting

Change, if possible

Never revisit

p value  Easy/relatively easy

417

77.1%

110

20.3%

14

2.6%

  Not easy/relatively not easy

180

64.7%

85

30.6%

13

4.7%

  Neither/do not know

117

70.5%

38

22.9%

11

6.6%

Easiness to take a sick leave (Q.7)**

Chi-squared test
n.s. not significant*p < 0.05, **p < 0.01

Table 7 Approval of the policy and revisit behaviors, a cross-analysis
Continue visiting

Change, if possible

Never revisit

p value

Active approval

615

92.5%

47

7.1%

3

0.5%

Passive approval

77

38.5%

119

59.5%

4

2.0%

Refusal

17

15.2%

64

57.1%

31

27.7%

**

Chi-squared test
*p < 0.01

screen patients who are well-matched to their policies.
As shown in Table 2b, the decline from 27.3% to 20.6%
according to the type of notice regarding the use of placebos suggests that there may be further declines in
the non-consent ratio with further improvement of
the notices. In the future, we would conduct a detailed
analysis of the psychology and behaviors of patients who
do not consent to such polices and of patients who seek
medical care at other medical facilities.

Discussion
In this study, we investigated the acceptance level of placebo prescriptions, instead of antibiotic prescription, asa method of reducing the unnecessary use of antibiotics.
A previous study conducted in a Christian nation foundthat 78.1% of patients might approve of placebos in general clinical use and 65.6% as a substitute for antibiotics,
using a hypothetical question [12]. We investigated patient
opinions on placebos for unnecessary antibiotics in different cultural backgrounds with an improved study setting
and confirmed that placebo prescriptions as a substitutefor antibiotic prescription satisfied 67.9% of patients andcould be accepted by 88.5% of them. Further, our study
identified sub-classes of patients with higher acceptance
rates: patients who exhibited compliance, who accepted
the recommended examinations and treatments, who
had high health literacy, who did not tend to refuse recommended tests and treatment, who periodically visited acertain medical institution, and who had family physicians.
The results also indicated that subjects who did not meet
the above criteria were likely to refuse consent to placeboprescriptions. Although Japanese patients may respond insimilar way to any type of prescriptions, the impact of thisstudy will not be compromised by such results.
Advantages

It is more preferable for physicians to provide an explanation for not prescribing antibiotics compared with prescribing placebos. In Japan, however, time constraints are
too severe for physicians to give detailed and educationalcomments for each prescription [13]. Even worse, Japanese are less knowledgeable about the appropriate useof antibiotics [5], and there is a high demand for antibiotic prescriptions. Hence, it is unrealistic for physiciansin Japan to provide explanations for refusing to prescribe
antibiotics to each patient.
In such situations, another option for patients who
demand antibiotics is “delayed prescription”, which lies
between the prescription and non-prescription options.
In this approach, a prescription is provided for antibiotics but the physician asks the patient to wait for a certain
amount of time before they deliver the prescription to
the pharmacy, hoping that the symptoms subside by thattime. During the waiting period, patients may observechanges in their symptoms. Such prescriptions havebeen shown to be effective in reducing antibiotic use[14], but unfortunately, this prescription strategy is nothighly evaluated by physicians or patients [15]. Although
they result in greater satisfaction than the no antibiotics
option, patient satisfaction is somewhat lower than thatfor an immediate prescription [14].

Ito et al. Journal of Pharmaceutical Policy and Practice(2022) 15:79

Ethical placebos can benefit patients by reducing
unnecessary prescriptions that can harm the entire society; they also help save the physicians’ time spent on
explanations and help retain patient satisfaction. The
obligation to provide an explanation can be fulfilled bymaking it mandatory to provide an explanation of theprescription content at the next visit. When a patient’s
condition does not require antibiotics, experiencing recovery without antibiotics by means of a placebo
can have significant educational value to the patient, as
delayed prescription can help avoid unnecessary antibiotic use [16]. It is also an ideal timing to provide educational intervention, when patients demand antibiotics.
Disadvantages

The results of our analysis indicated that there were differences in acceptance levels between patients who had
at least one medical institution near their residence andthose who had none. If there are no other medical institutions near the one with the notice, patients might beforced to continue visiting it against their will. Thus, if
there is a limited number of medical facilities in an area,
placebo prescriptions could result in a significant breachof the patients’ right to self-determination in treatment.
To avoid this problem, it might be best to limit the useof ethical placebos to medical institutions in competitive
urban environments. Patients with a reasonable numberof choices in medical institutions can exercise their rights
to self-determine their treatment by selecting anotherinstitution or by refusing a placebo prescription. Patients
who do not periodically or regularly attend an institution
might also be excluded from the approach because thephysicians may fail to provide explanations afterward.
In this paper, we proposed a method of obtaining
patient consent for the use of ethical placebos by meansof an in-hospital notice. However, in reality, patients may
not recognize such a notice. In addition to this, the factthat 18.1% of the subjects responded “do not know” when
asked whether they would demand antibiotics for a common cold suggests that some patients found it difficult
to understand the meaning of such in-hospital notices.
Hence, to ensure the efficacy of the in-hospital notice, itis essential to further study how to promote awarenessand understanding of the notice and its contents.
Limitation

Ethical placebos are designed to maximize the welfare ofboth the patients and the society, which are under severe
resource limitations. However, 11.5% of the participants
refused to accept this method (Table 2a) and 23.7% statedthat they would subsequently change hospitals if possible (Table 2b). Clearly, such a treatment should not

Page 11 of 12

compromise the patients’ rights, as we further discussed
in Additional file 1: Appendix 1. Decisions of the patients
who passively approve ethical placebos or deny consent
warrant further study.
This survey on the acceptance of the intervention was
based on responses obtained from a structured questionnaire. Therefore, the reasons for the acceptance orrefusal of the patients are unknown. It remains as subject
for future work to examine the differences in attitudes
toward prescriptions other than placebo and the extent
to which posterior explanations of ethical placebo canchange patients’ attitudes. It is desirable to investigate theissues further, possibly with qualitative interviews.

Conclusion
The emergence and spread of multidrug-resistant bacteria are major threats to public health. Although various
campaigns have been initiated in Japan as countermeasures, none of the efforts have been able to regulate theunnecessary use of antibiotics, either for patients orprescribing physicians. The strategy of prescribing ethical placebos proposed in this paper might work in cases
where the disadvantages of unnecessary prescription outweigh the advantages to reduce the number of unnecessary antibiotic prescriptions while maintaining patientsatisfaction and easing physicians’ burden of providing
explanations. However, various aspects of the ethicalplacebo are controversial, including ethical issues, technical issues in designing actual operations conforming tocurrent health insurance systems, and, above all, patient
acceptance.
At this point of time, it is unrealistic to put this proposal into actual practice. First, the prescription would
be considered inappropriate, and further investigations on ethical issues are required. Second, there must
be technical issues to realize the scheme under healthinsurance systems. Third, the psychology and behaviorof patients who indicated their non-consent to placebosor intention to change their medical institutions must be
investigated to clarify the problems associated with our
proposal. Nevertheless, the acceptance by 67.9% participants deserves attention because the ethical placebos
can deliver educational opportunities for the patients toaccept the evidence-based approaches. Because multilateral interventions have been shown to be more effective
as countermeasure than single interventions [1], it would
worth further investigation to ensure the diversity in the
countermeasure for antimicrobial resistance, a major
public health threat nowadays.
Abbreviation
AMR: Anti-microbial resistance.

Ito et al. Journal of Pharmaceutical Policy and Practice(2022) 15:79

Supplementary Information
The online version contains supplementary material available at https://​doi.​
org/​10.​1186/​s40545-​022-​00470-8.

Page 12 of 127.
8.

Additional file 1: Appendix 1. Discussion and literature survey on thequalifications for the ethical placebo.

9.

Additional file 2: Appendix 2. Survey Protocol and Questionnaire used in
the online survey (English translation).

10.

Additional file 3: Appendix 3. Responses to the questionnaire used in
the study.

11.

Authors’ contribution
All authors read and approved the final manuscript.
Funding
This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Availability of data and materials
The datasets generated and/or analyzed during the current study are notpublicly available due to the data policy submitted to the review board, but
are available from the corresponding author on reasonable request.

Declarations
Ethics approval and consent to participate
This study was approved by the Institutional Review Board for Research with
Human Subjects at the Kitami Institute of Technology (Approval Number
1016). The survey was administered through a web-survey company, and randomly sampled monitors who agreed to participate joined the online survey.

12.
13.
14.
15.
16.

The Government of Japan, National Action Plan on Antimicrobial Resistance (AMR) 2016–2020, April 5, 2016,pp.1–69. https://​www.​mhlw.​go.​jp/​file/​06-​Seisa​kujou​hou-​10900​000-​Kenko​ukyoku/​00001​38942.​pdf.
OECD. Indicators: health at a glance 2015. Available from: https://​www.​oecd-​ilibr​ary.​org/​docse​r ver/​healt​hglan​ce-​2015-​en.​pdf.
Tilburt JC, Emanuel EJ, Kaptchuk TJ, et al. Prescribing ”placebo treatments”: results of national survey of us internists and rheumatologists.
BMJ. 2008;337: a1938.
Fässler M, Meissner K, Schneider A, et al. Frequency and circumstances ofplacebo use in clinical practice—a systematic review of empirical studies.
BMC Med. 2010;8(1):15.
Foddy B. A duty to deceive: placebos in clinical practice. Am J Bioeth.
2009;9(12):4–12.
Hull SC, Colloca L, Avins A, et al. Patients’ attitudes about the use ofplacebo treatments: telephone survey. BMJ. 2013;347: f3757.
Hiyama T, Yoshihara M. New occupational threats to Japanese physicians:
karoshi (death due to overwork) and karojisatsu (suicide due to overwork). Occup Environ Med. 2008;65(6):428–9.
Spurling GK, Del Mar CB, Dooley L, et al. Delayed antibiotics for respiratory infections. Cochrane Database Syst Rev. 2013;4(4):CD004417.
Arroll B, Goodyear-Smith F, Thomas DR, et al. Delayed antibiotic prescriptions: what are the experiences and attitudes of physicians and patients?
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Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Consent for publication
Not applicable.
Competing interests
The authors declare they have no competing interests.
Author details
1
Faculty of Public Policy, Kyoto Prefectural University, Kyoto City, Kyoto, Japan.
2
Faculty of Health and Welfare Services Administration, Kawasaki Universityof Medical Welfare, Kurashiki City, Okayama, Japan. 3 School of Regional Innovation and Social Design Engineering, Kitami Institute of Technology, Kitami
City, Hokkaido 090‑8507, Japan.
Received: 28 February 2022 Accepted: 13 October 2022

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