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Placebo use in clinical practice by nurses in an Iranian teaching hospital

Nursing Ethics 18(3) 364–373 ª The Author(s) 2011 Reprints and permission: sagepub.co.uk/journalsPermissions.nav 10.1177/0969733011398093 nej.sagepub.com

Nayereh Baghcheghi Arak University of Medical Sciences, Islamic Republic of Iran

Hamid Reza Koohestani Arak University of Medical Sciences, Islamic Republic of Iran

Abstract The present study was carried out to explore Iranian nurses’ use of placebos in clinical practice and their knowledge and attitude towards its use. A cross-sectional, descriptive study was conducted using self-report questionnaires. All nurses working in a university hospital in Arak (n ¼ 342) were invited to participate in the study. Among 295 respondents, 221 (75%) reported that they had used at least one placebo within the past year and 179 (81%) told patients they were receiving actual medication. The most common reason and symptom for placebo use were after unjustified demand for medication and pain, respectively. Only 60 (20.33%) of the nurses believed that placebos should never be used. Results showed that most nurses in our study had used placebos and probably will continue to use them. Placebo use is viewed as ethically permissible among nurses. Some patients benefit from the placebos, but their use raises ethical questions. The role of placebo treatment, its mechanisms, and its ethics issues should be taught to nurses. Keywords clinical practice, nurses, placebo effect, placebo use

Introduction Ethical issues present important challenges in today’s practice environment. Nurses commonly encounter clinical situations that have ethical conflicts. Placebo administration to patients is one of the ethical issues that may be encountered by nurses. The term placebo comes from the Latin word meaning ‘shall please.’ A placebo has been defined as any medication or procedure that may produce an effect because of its implicit or explicit intent and not because of its specific physical or chemical properties.1 Placebo effect is the positive psychosomatic response of an individual to a treatment.2 Positive expectations gender positive outcomes; negative expectations lead to negative outcomes. For example, client expectations influence the perception of pain and the effectiveness of interventions for pain reduction or relief (expectation effect). The message nurses deliver regarding pain and pain management

Corresponding author: Hamid Reza Koohestani, Arak University of medical sciences, Basij SQ, Sardasht, Arak, Islamic Republic of Iran Email: [email protected]

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strategies can affect the client’s expectations. When clients are given placebos, they are told that the pills contain pain medication. It is not uncommon for these clients to obtain pain reduction or relief.3 Placebo responses are known to rely on multiple factors, there is no evidence of certain patients being ‘placebo responders.’ The same individuals might exhibit a placebo response under some conditions but not under others.4 A placebo efficacy response of as low as 0% to as high as 100% has been reported in the literature.5 A number of psychosocial and physiological mechanisms have been advanced to attempt to explain why placebos work. Psychosocial mechanisms include personality, cognition and social learning, which are presumed to activate psycho-physiological events that involve various body systems, although the biological mechanism through which placebo effects occur is not known.6 The person, unaware of the placebo’s properties, may find it to be effective because of the perception that it will provide comfort and because of belief in the person administrating.7 Placebos have been used since the beginning of recorded medicine, but their role in conventional medicine is ambiguous and often controversial. In clinical research the placebo effect is an experimental nuisance to be removed by placebo-controlled trials. In clinical practice, the use of placebos is controversial, mainly because of differences in how the placebo is defined and conceptualized.8 Some have supported prohibiting the use of placebos in clinical practice because of the deceit involved in administration and the possible harm to the doctor/nurse–patient relationship,9,10 whereas advocates of placebo treatments argue that promoting the placebo effect might be one of the most effective treatments available for many chronic conditions and can be accomplished without deception. This group believes that guidelines are necessary for their proper use without violating the patient’s trust and autonomy.11–13 The deception involved in administering a placebo certainly raises ethical questions. Is lying to the patient justifiable? A nurse who administers a placebo must be willing to risk the possible consequence of the patient becoming aware of the duplicity and then refusing to trust the nurse. Patients who feel themselves to be in pain are vulnerable. If such a patient discovers a seeming plot to trick him or her into feeling better, it is unlikely that the patient will respect or appreciate the intentions of the nurses involved.7 The required ignorance on the part of patients when receiving placebo treatment potentially removes their opportunity to make informed decisions about treatment. This can be considered paternalistic and not respecting patient autonomy.14 Respect for a person’s autonomy and the right to consent to or refuse treatment are now widely accepted. The word autonomy is commonly defined very broadly as ‘self-determination,’ ‘self-rule,’ ‘being your own person.’15 Autonomy is a principle that ensures individuals the freedom of choice or free will to determine what happens to them, as long as these decisions do not seriously harm them or others. This principle is grounded in respect, which means that each individual is treated as a person of moral worth and moral agency.16 As an ethical concept, autonomy is undoubtedly one of the most important concepts in modern moral and political philosophy.15 The ANA Code of Ethics for Nurses requires that the nurse, in all professional relationships, practices with compassion and respect for the inherent dignity, worth, and uniqueness of every individual.17 In practice, respect for the dignity of individuals involves allowing them to make their own choices and develop their own life plans, which is also autonomy.18 The goal of an informed consent process is to ensure that the patient or surrogate has an opportunity to accept or reject the recommended treatment without coercion. If this does not occur, his or her autonomy and dignity are compromised.19 Respecting autonomy means the nurse must: effectively communicate with patients, be truthful, enable the patient to make decisions freely, provide appropriate information, and accept patient’s preferences.15 It is wrong to tell falsehoods in those situations in which there is a reasonable expectation of the truth.18 Truthfulness, at its very simplest the obligation to tell the truth (or the ‘duty of veracity’ as it is sometimes called), means that the nurse should be

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honest with patient, i.e. not lie to or deceive them. But truthfulness describes much more than simply passing on accurate information. Rather, it reflects an attitude towards another person that aims to create open and mutually respectful communication.15 The patients have the right to be told – trust is now wildly accepted as a universal virtue and prompted in all professional codes.20 The use of informed consent is essential in all therapeutic situations, including those involving placebos.4 Whether or not a placebo is deceptive depends on the exact way in which it is presented. If the nurse or physician says, ‘I am going to administer something that often helps in these cases and has no bad side effect,’ it is hard to see how he is deceiving the patient. Certainly, he is not lying. Indeed, the nurse is far more likely to deceive with regard to a pharmacologically active drug if he says, ‘This will make you better.’ That is promising too much, whether said of a placebo or a test drug. In such a presentation, the patient knows what she needs to know in order to give informed consent.18 Indeed, there are studies that demonstrate that expectation is important in placebo positive responses, and that such responses are reduced when subjects are told they are receiving a placebo.21–23 While deception is not an ethical issue in the use of the placebo, there are other problems with placebos. Such as overpricing or using them in place of accepted treatment. Overpricing can be condemned as a form of theft and the failure to use effective treatment when it is called for is simply malpractice.18 Placebos (e.g. placebo pain medication) have also been used to ‘please’ a patient who demands an analgesic that has potentially harmful side effects when the physician does not believe that such medication is clinically indicated. Some physicians have sought to justify the deceptive use of placebos based upon beneficence – that the end (patient welfare) justifies the means (patient deception). However, placebo use to protect the patient from ‘harmful’ treatments is scientifically and ethically unacceptable.4 There is evidence that placebos can also mimic active analgesic agents in their ability to produce side effects and even toxic reactions.24 A number of organizations have advised against the use of placebo substitution, including the American Nursing Association, the American Society of Pain Management Nurses, the American Pain Society, Agency for Healthcare Policy and Research, World Health Organization, Healthcare Facilities Accreditation Program, Joint Commission on Accreditation of Healthcare Organizations, and Education for Physicians on End-of-Life Care Project.2 The American Society for Pain Management Nurses (ASPMN) agrees that placebo use is fraudulent and deceptive when used to assess and treat pain, but they support placebo use in clinical trials in which the patient has signed an informed consent and the institutional review board has approved the research.1 Despite placebo use heightened in clinical research trials, there have been few studies published on placebo use in the course of routine health care. In 2008, Sherman and colleagues reported that 45% of 231 physicians in Chicago utilized placebos.25 Another survey of 62 doctors and 31 head nurses providing hospital-based and ambulatory care in Israel found that 53% of doctors and 71% of head nurses used placebos in their practice.26 Another study by Tilburt et al. (2008) was conducted to describe the attitudes and behaviours regarding placebo treatments among a national sample of clinically active internists and rheumatologists in the USA. The results of this study showed that about half of the surveyed internists and rheumatologists reported prescribing placebo treatments on a regular basis (46–58%, depending on how the question was phrased). Most physicians (399, 62%) believed the practice to be ethically permissible.27 Results of Shah et al.’s (2009) study in India showed that medical practitioners reported 88.88% prevalence of use of placebo at least once and, of these, 80% reported using it more than 10 times a year.28 However, most of these surveys have important shortcomings and no attention has been paid to the relevant ethical challenges and theoretical references. Placebos may be effective in some areas, but, as mentioned above, their use raises ethical issues, and some institutions, for example the American Nursing Association and the American Society of Pain Management

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Nurses, have banned their use. However, the authors’ personal observations and experiences in various medical departments, as well as informal discussions with colleagues, suggest the practice still occurs. There has been a little significant research on the use of placebos in clinical practice by nurses. The present study was undertaken to explore practice and pattern of use of placebos among nurses and their knowledge and attitude regarding placebo use in clinical practice.

Method Design and sample This descriptive cross-section study was conducted during the summer of 2009. Statistical population for this study consisted of employed nurses at a university hospital at the Arak University of Medical Sciences in Iran. The sampling criterion was nurses that have worked in hospital settings for a minimum period of one year. All nurses working at a university hospital in Arak (n ¼ 342) were invited to participate in the study. For comparison of frequency of placebo use according to age and professional experience, researchers decided to study placebo use within the past year instead of across the total professional experience period, similar to previous research.

Questionnaire The data gathering tool was a questionnaire consisting of two parts. In the first section of the questionnaire, background data, gender, age and professional experience were included, and in the second part, there were questions about knowledge, attitudes and experiences towards use of placebo. Questionnaire items measured: frequency of placebo use in clinical practice; information given to patients who receive a placebo treatment; perceived therapeutic value of placebos; circumstances accompanying placebo use; perceived mechanism of action of placebos; and ethical stances concerning the use of placebos in routine health care practice. This questionnaire was developed through a review of related existing empirical surveys on the use of placebo in clinical practice by nurses.26,29 For this purpose, we performed a subject search using key words of our research topic; for example: ‘placebo use,’ ‘clinical practice,’ ‘patient care,’ ‘nurse,’ ‘placebo therapy’, ‘use of placebo’ and ‘ethics’. In order to be included, surveys on the use of placebos in clinical practice had to meet the following criteria: they should be a full-length article in English, they should be original reports, and participants had to be nurses or other health care professionals. The content validity of the questionnaire was examined by literature review and experts’ judgment. For this purpose, we asked 10 experts – members of nursing faculty, who had clinical experience in a hospital and knowledge of the theoretical frameworks regarding placebos – to rate each question in terms of clarity and relevance. The responses from each expert was then compared and subsequently a few changes were made to the questionnaire. Test-retest method was used for ascertaining for reliability of tool. Researchers performed a pretest to identify any potential misinterpretations of the questions and difficulties the respondents might have in answering the questions. In order to avoid misinterpretation, brief notes and definitions about the words and questions were given. The questionnaires were delivered to and collected in nurses meetings in hospital units by researchers over a 2-week period. Participants were authorized to answer the questionnaire during their working time or at home.

Analysis Data were analysed using SPSS version 13 at an alpha level of 0.05 by computing descriptive statistics, independent samples t-test, and Fisher’s exact test.

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Table 1. Demographic data for respondents to questionnaire on use of placebos

Sex Age (years)

Professional Experience (years)

Male female 23–30 30–40 40–50 15

Total

Number

%

62 233 103 137 55 100 139 56 295

21.01 78.98 34.91 46.44 18.64 33.89 47.11 18.99 100

Table 2. Placebo use in clinical practice by nurses according to background data Placebo use in clinical practice yes Mean (SD) age (years) Mean (SD) professional experience (years) Sex: Male: No (%) Female: No (%)

37.72 (7.91) 10.61 (8.54) 47 (75.8%) 174 (74.67%)

no 37.89 (8.33) 10.94 (8.9) 59 (25.33) 15 (24.2)

P > 0.05 P > 0.05 P > 0.05

Ethical considerations This study was neither mandatory, nor disadvantageous in any way for the participants. Identities were kept strictly confidential and anonymous throughout the study. Additionally, the questionnaires were not coded (to identify non-respondents) and names were not requested because it was felt that coding might discourage respondents to answer and return the questionnaire. Consent was implied by returning the questionnaire. The participants could withdraw at any time from the study. The study was approved by the ethics committee of Arak University of Medical Sciences.

Findings A total of 342 nurses were recruited by census; 295 nurses returned the questionnaires (response rate 86.25%). Most of the participants were female (78.98%, N ¼ 233) (Table 1). The mean age of the participants was 37.77 years (SD 8.2, range: 23–50), their mean professional experience was 10.69 years (SD 8.7, range: 1–26 years). Among 295 respondents, 221 (74.99%) reported that they had used at least one placebo for clinical care within the past year. The age, sex, and professional experience of respondents did not affect results (P > 0.05) (Table 2). Table 3 shows the frequency of placebo use in clinical practice by nurses. Approximately 12% of nurses (n ¼ 26) had used a placebo only based on oral order of physicians. When asked about the practices of other nurses, 84.74% of respondents (n ¼ 250) believed their colleagues used placebos during routine care (27.11% ‘rarely,’ 47.45% ‘sometimes,’ and 10.17% ‘often’).

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Table 3. Frequency of placebo use in clinical practice by nurses Frequency of placebo use

Number

%

On a daily basis Once a week on average Once a month on average Once a year in average never

5 51 141 24 74

2.26 23.07 63.08 10.85 25.01

Table 4. Circumstances in which placebo was administered by nurses Circumstances After ‘unjustified’ demand for medication(i.e. demand for soporific) To calm patient To buy time before next regular dosage of medication As diagnostic tool (i.e. in order to distinguish between a genuine and imaginary symptom) To satisfy/mollify a patient As a supplement to medication As a treatment for a nonspecific symptom other conditions

Number

%

100 81 52 41

45.24 36.65 23.52 18.55

13 11 10 2

5.88 4.97 4.52 0.9

Table 5. Signs and symptoms for which the placebos were used Signs and symptoms pain withdrawal syndrome in addicted patients sleep problems agitation anxiety vertigo other conditions

Number

%

93 71 49 49 42 12 2

42.08 32.12 22.17 22.17 19 5.42 0.9

Regarding effectiveness of placebos, of those who used a placebo, most (141 of 221, or 63.79%) found that it was either usually (46, or 20.81%) or sometimes (95, or 42.98%) effective, and 80 (36.21%) found that it was never effective. Of those who used placebos, 179 (80.99%) told the patient that he or she was receiving a real medicine, and 31 (13.53%) said nothing at all. Nurses used placebos in a variety of situations. The situations for placebo use are presented in Table 4. Respondents were permitted to propose more than one option. The most common reasons for placebo use were after ‘unjustified’ demand for medication (18%) and to calm the patient (18%). In addition, 30% of respondents agreed with the statement, ‘I think a positive response to a placebo (e.g. reduction in pain) indicates that the symptom certainly is not real.’ The signs and symptoms for which the placebos were used are listed in Table 5. Placebos usually were given in the form of saline infusions or intravenous injections of distilled water. Regarding the appropriateness of prescribing placebos, of 295 responses only 60 (20.33%) believed that placebos should never be used. Most of the others considered placebo use conditional on certain

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circumstances, such as permitted if the experience in the department supports its efficiency (141, or 47.76%), or permitted if research supports its efficiency (91, or 30.84%). About 74% (218/295) of the respondents opined in favor of psychological mechanism for placebo response. An additional 20% (59/295) of respondents suggested a combination of psychological and biochemical effects. Respondents were permitted to propose more than one mechanism of action for placebos.

Discussion In the clinical setting, the use of a placebo without the patient’s knowledge may undermine trust, compromise the patient–nurse relationship, and result in medical harm to the patient. Our study shows that administration of placebos for clinical purposes still continues. Our survey indicates that placebos are used frequently and maybe will continue to be used in clinical practice by nurses. About three-fourths of the 295 nurses admitted using at least one placebo in clinical care. Our results are consistent with the findings of other studies. Recently, Sherman and Hickner (2008) surveyed a convenience sample of 231 academic physicians in the Chicago area and found that 45% (n ¼ 104) had used placebo treatments in clinical practice with 15% doing so 1 to 10 times, and 8% more than 10 times, in the last year.25 Results of Nitzan and Lichtenberg’s (2004) study showed that 53% of doctors and 71% of head nurses reported using at least one placebo, and among users, 33 (62%; 37% of the total sample) used a placebo as often as once a month or more.26 A Danish survey reported that 86% of 545 general practitioners used a placebo treatment at least once within the past year, and 48% reported using placebo treatments more than 10 times in the past year.29 A national survey of US internists and rheumatologists showed 55% prevalence of use of placebos.27 In our study, only less than one-quarter of participants thought that the use of placebos should be categorically prohibited. This finding indicted use of placebos in clinical practice is viewed as ethically permissible among the nurses. In the two previous studies, the majority of respondents agreed that use is ethical under certain circumstances.26,29 Considering this finding, it seems probable that many such nurses will continue to administer placebos. As mentioned before, placebos can themselves cause harmful side effects and might delay specific treatments, thereby leading to disease or symptom escalation.4 Placebo can act as a failure to treatment and result in harm to the patient. This can conflict with beneficence and non-maleficence principles. In its most general form, the principle of beneficence says no more than ‘Do good,’ and includes actions, attitudes and values of caring such as compassion, competence, conscience, commitment, empathy and sympathy. Similarly, the principle of non-maleficence tells us to ‘Avoid evil’; acting in such a manner to avoid causing harm (e.g. pain and suffering) to patients.18 In health-care situations the principle of beneficence initially seems very straightforward. This is because in a very general sense beneficence means that a nurse must act in ways that benefit others. The principle of beneficence requires the nurse to act in ways that promote the well-being of patients.15 Truth-telling is one of the most significant aspects of the relationship between health-care professionals and patients. Our results indicated, of those using placebos, 179 (80.99%) told the patient that he or she was receiving a real medicine. This result is consistent with Nitzan and Lichtenberg’s study. In this study, of those who reported using the placebo, the majority (68%) told the patient that he or she was receiving a real medicine.26 However, in Sherman and Hickner’s study, of the respondents who reported using placebos in the course of routine health care, the majority (34%) introduced the placebo to the patient as ‘a substance that may help and will not hurt.’25 Lying to the patient conflicts with autonomy and veracity principles. The health care formulation of the principle of autonomy can be expressed as flow: you shall not treat a patient without the informed consent of the patient or his or her lawful surrogate, except in emergencies. The principle clarifies the meaning of respect for the person and his or her freedom in the context of health care.18

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Patients are entitled to refuse any and all medical treatment if they possess adequate decision-making capacity to do so. Deception of patients about clinical treatments violates the right of patients to consent to or refuse treatment. The use of informed consent is essential in all therapeutic situations, including those involving placebos.4 Veracity, or truthfulness, is a fundamental part of informed consent and hence of respect for autonomy. However, the use of placebo can conflict with the veracity principle and it can severely undermine the relationship between patient and nurse. A positive response to a placebo (e.g. reduction in pain) should never be interpreted as an indication that the person’s pain is not real.7 Nonetheless, in our study, 30% of nurses agreed with the statement, ‘I think a positive response to a placebo (e.g. reduction in pain) indicates that the symptom certainly is not real.’ This finding indicated that this group’s knowledge regarding the placebo effect is low. It is an injustice to judge a person experiencing relief from pain after use of a placebo as a malingerer.7 A placebo effect is not an indication that the person does not have pain, rather, it is a true physiological response.30 It is important to note, however, that even when there is objective evidence of tissue damage, including postoperatively, many patients with pain complaints report relief from placebos.31,32 In our study, the most common symptom for placebo use was pain. In previous studies the circumstances and the reasons for placebo use were not clearly separated. Pain is one of the predominant symptoms that prompts patients to seek medical advice and treatment from nurses. Pain is a universal experience and is subjective by nature. Despite the common colloquialism, ‘I feel your pain,’ no individual can truly experience another’s pain. There are no laboratory tests or consistently reliable physical findings for assessing pain. Patient self-report remains the ‘gold standard’ for pain assessment.33 Placebos should never be used to test the person’s trustfulness about pain. The American Society for Pain Management Nurses (ASPMN) comments that placebos (tablets or injection of no active ingredients) should not be used to assess or manage pain in any patient, regardless of age and diagnosis. A patient should never be given a placebo as a substitute for an analgesic medication. Although a placebo can produce analgesics, patients receiving placebo may report that their pain is relieved or that they feel better simply to avoid disappointing the nurse.30 The American Pain Society (APS) opposes the inadequate treatment of pain using any therapeutic modality including the use of placebos. The deceptive use of placebos and the misinterpretation of the placebo response to discredit the patient’s pain report are unethical and should be avoided.4 In our study, 32.12% of nurses administered at least one placebo to addicted patients for withdrawal symptoms. Frequent use of placebo for withdrawal symptoms can be potentially harmful to addicted patients. The American Society for Pain Management Nursing’s position is that patients with addictive disease and pain have the right to be treated with dignity, respect, and the same quality of pain assessment and management as all other patients. Providing this care addresses the potential for increased drug use or relapse associated with unrelieved pain. Nurses are in an ideal position to advocate and intervene for these patients across all treatment settings.34 In our study, 23.52% of nurses administered at least one placebo to buy time before the next regular dosage of medication. In this situation nurses can, in place of using a placebo, produce a placebo-like effect through the skillful use of reassurance and encouragement. In this way, the nurse builds respect and trust, promotes the patient nurse relationship, and improves health outcomes. Our result showed that about 12% of nurses had used placebos only based on orders from physicians. However, it is remarkable to know, the nurse has firm legal and ethical ground for refusing to administer a placebo.7 The only appropriate use of a placebo is in approved clinical research with informed consent.2 In placebo controlled clinical trials, patients consent to the possibility of receiving a placebo rather than the active, experimental treatment. It is generally agreed that the use of placebos in clinical trials is ethical when harm to patients from delayed treatment is limited, when the alternative active treatment is unsubstantiated, and when there is a substantial potential benefit to future patients in establishing efficacy and/or avoiding harmful side effects of a treatment.4

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The use of placebos in clinical practice raises ethical issues and it is important that nurses worldwide reflect on these issues in their daily nursing practice.

Limitations of the study Whereas the guarantee of anonymity aimed to eliminate reporting bias, some respondents may have misreported their use of placebos. Also, we rely on self reports made retrospectively. This can be a problem when respondents are asked to look back and estimate the frequency of a particular behavior (recall bias). This small sample was limited to nurses from one hospital, and the results cannot be generalized to all Iranian nurses. Placebo use in clinical practice by nurses might vary from city to city, even if nurses’ demographic characteristics are similar. This study needs to be replicated with a larger number of nurses outside of this hospital.

Conclusion Most nurses in our study had used placebos, and probably will continue to use them. Use of placebos in clinical practice is viewed as ethically permissible among nurses. Some patients benefit from the placebos, but their use raises ethical questions. In general, the nurse’s attitude and practice toward placebo use in patient care is not good. Many of the reasons commonly offered for the use of placebo cannot be justified on either a clinical or an ethical basis. It seems that educational programs are necessary to improve the knowledge and attitude of nurses toward placebo use in patient care. The role of placebo treatment, its mechanisms, and its ethical issues should be taught to nurses. Also, educational programs should be conducted to educate nurses about effective pain management and management of addicted patients. This topic should be highlighted in nursing educational programs. Acknowledgments The authors would like to thank all the nurses for their cooperation in performing the survey. The authors gratefully acknowledge Arak University of Medical Sciences for its support of this project. Conflict of interest statement The authors declare that there is no conflict of interest. References 1. McCaffery M and Arnstein P. The debate over placebos in pain management. Am J Nurs 2006; 106(2): 62–5. 2. Nichols KJ, Galluzzi KE, Bates B, et al. AOA’s position against use of placebos for pain management in end-of-life care. J Am Osteopath Assoc 2005; 105(3): S2–5. 3. Black J and Hawks JH. Medical-surgical nursing: clinical management for positive outcomes, eighth edition. Philadelphia, PA: Elsevier Saunders, 2008. 4. Sullivan M, Terman GW, Peck B, et al. APS position statement on the use of placebos in pain management. J Pain 2005; 6(4): 215–17. 5. Staats P, Hekmat H and Staats A. Suggestion/placebo effects on pain: negative as well as positive. J Pain Symptom Manage 1998; 15(4): 235–43. 6. Chan CW and Thompson DR. The use of placebo in clinical nursing research. J Clin Nurs 2006; 15(5): 521–4. 7. Taylor C, Lillis C and LeMone P. Fundamentals of nursing: the art and science of nursing care, sixth edition. Philadelphia, PA: Lippincott Williams & Wilkins, 2008. 8. Margo CE. The placebo effect. Surv Ophthalmol 1999; 44(1): 31–44. 9. De Deyn PP and d’Hooge R. Placebos in clinical practice and research. J Med Ethics 1996; 22(3): 140–6. 10. Hill J. Placebos in clinical care: for whose pleasure? Lancet 2003; 362(9379): 254.

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11. Brown WA. Placebo as a treatment for depression. Neuropsychopharmacology 1994; 10(4): 265–9. 12. Brody H. Placebos and the philosophy of medicine: clinical, conceptual, and ethical issues. Chicago, IL: University of Chicago Press, 1977. 13. Lione A. Ethics of placebo use in clinical care. Lancet 2003; 362(9388): 999. 14. Clemence ML. Developing the ethics of placebos in physiotherapy. Physiotherapy 2001; 87(11): 582–6. 15. Hendrick J. Law and ethics. Foundations in nursing and health care. Cheltenham: Nelson Thorne, 2004. 16. Fowler M and Fry S. Ethical enquiry. In: Sarter B (ed.), Paths to knowledge: innovative research methods in nursing. New York: National League for Nursing, 1988. 17. ANA Code of Ethics for Nursing with Interpretive Statement. http://www.nursingworld.org/ethics/code/ethicscode 150.htm (accessed on 7 March 2010). 18. Garret TM, Baillie HW and Garrett RM. Health care ethics principle and problem, fifth edition. Upper Saddle River, NJ: Prentice Hall, 2009. 19. Ersek M, Kagawa-Singer M, Barnes D, et al. Multicultural considerations in the use of advance directives. Oncol Nurs Forum 1998; 25: 1683–90. 20. Tadd W. Ethical issues in nursing and midwifery practice. Perspectives from Europe. Basingstoke: Macmillan, 1998. 21. Benedetti F, Pollo A, Lopiano L, et al. Conscious expectation and unconscious conditioning in analgesic, motor, and hormonal placebo/nocebo responses. J Neurosci 2003; 23: 4315–23. 22. De Pascalis V, Chiaradia C and Carotenuto E. The contribution of suggestibility and expectation to placebo analgesia phenomenon in an experimental setting. Pain 2002; 96: 393–402. 23. Pollo A, Amanzio M, Benedetti F, et al. Response expectancies in placebo analgesia and their clinical relevance. Pain 2001; 93: 77–84. 24. Benedetti F, Amanzio M, Baldi S, et al. The specific effects of prior opioid exposure on placebo analgesia and placebo respiratory depression. Pain 1998; 75: 313–19. 25. Sherman R and Hickner J. Academic physicians use placebos in clinical practice and believe in the mind-body connection. J Gen Intern Med 2008; 23: 7–10. 26. Nitzan U and Lichtenberg P. Questionnaire survey on use of placebo. BMJ 2004; 329: 944–6. 27. Tilburt JC, Emanuel EJ, Kaptchuk TJ, et al. Prescribing ‘placebo treatments’: results of national survey of US internists and rheumatologists. BMJ 2008; 337: 1097–100. 28. Shah KN, Panchal DJ, Vyas BM, et al. Use of placebo: knowledge, attitude and practice among medical practitioners. Indian J Med Sci 2009; 63(10): 472–3. 29. Hrobjartsson A and Norup M. The use of placebo interventions in medical practice – a national questionnaire survey of Danish clinicians. Eval Health Prof 2003; 26: 153–65. 30. Smeltzer S, Bare B, Hinkle J and Cheever K. Brunner and Suddarth’s textbook of medical-surgical nursing, eleventh edition. Philadelphia, PA: Lippincott Williams & Wilkins, 2008. 31. Hashish I, Feinman C and Harvey W. Reduction of postoperative pain and swelling by ultra-sound: a placebo effect. Pain 1988; 33: 677–8. 32. Turner JA, Deyo RA, Loeser JD, et al. The importance of placebo effects in pain treatment and research. JAMA 1994; 217: 1609–14. 33. Portenoy RK. Contemporary diagnosis and management of pain in oncologic and AIDS patients. Newtown, PA: Handbooks in Health Care Co, 1998. 34. American Society for Pain Management Nursing. ASPMN position statement: pain management in patients with addictive disease. J Vasc Nurs 2004; 22(3): 99–101.