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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
J Pain Symptom Manage. Author manuscript; available in PMC 2011 August 16.
Published in final edited form as:
PMCID: PMC3156553

An Exploratory Study on the Effects of an Expectancy Manipulation on Chemotherapy-Related Nausea



Previous research has shown that the effectiveness of acupressure bands in reducing chemotherapy-related nausea is related to patients’ expectations of efficacy.


To test whether an informational manipulation designed to increase expectation of efficacy regarding acupressure bands would enhance their effectiveness.


We conducted an exploratory four-arm randomized clinical trial in breast cancer patients about to begin chemotherapy. All patients received acupressure bands and a relaxation CD. This report focuses on Arm 1(expectancy-neutral informational handout and CD) compared to Arm 4 (expectancy-enhancing handout and CD). Randomization was stratified according to the patient’s level of certainty that she would have treatment-induced nausea (two levels: high, low). Experience of nausea and use of antiemetics were assessed with a 5-day diary.


Our expectancy-enhancing manipulation resulted in improved control of nausea in the 26 patients with high nausea expectancies, but lessened control of nausea in 27 patients having low nausea expectancies. This interaction effect (between expected nausea and intervention effectiveness) approached statistical significance for our analysis of Average Nausea (P = 0.084) and reached statistical significance for our analysis of Peak Nausea (P = 0.030). Patients receiving the expectancy-enhancing manipulation took fewer antiemetic pills outside the clinic (meanenhanced = 12.6; meanneutral = 18.5, P = 0.003).


This exploratory intervention reduced antiemetic use overall and also reduced nausea in patients who had high levels of expected nausea. Interestingly, it increased nausea in patients who had low expectancies for nausea. Confirmatory research is warranted.

Keywords: Acupressure bands, expectation, chemotherapy, nausea, suggestion, targeted information


The shift in the healthcare system towards patient-centered care has increasingly made communication between caregiver and patient a two-way street. Healthcare professionals need to impart information about treatment to the patient while listening to the patient’s fears, hopes, and wishes. Working together, a treatment plan is developed. Patient and caregiver communication is crucial in the development of patients’ expectancies for treatment outcomes, termed response expectancies. This anticipation can influence physical, emotional and mental outcomes throughout the treatment process.18

The effect of response expectancies can be considerable, particularly on subjective outcomes such as nausea. Nausea expectancies are, in fact, often robust predictors of actual nausea and frequently account for variance in subsequent nausea above and beyond the emetogenicity of the chemotherapeutic agent.18 For example, Roscoe et al. studied 194 breast cancer patients about to begin their first cancer treatment regimen containing doxorubicin and found that patients who believed that they were “very likely” to experience severe nausea from their chemotherapy were five times more likely to experience severe nausea than those who believed that they were “very unlikely” to do so.5

Although expectancies may represent an acknowledgement of one’s propensity to develop nausea based on past experience (e.g., nausea during pregnancy or susceptibility to motion sickness), these expectancies are also influenced by socio-cultural factors and what patients are told to expect from the range of information they receive from clinicians, hospital staff, other patients, family, friends, and the world at large. Thus, nausea expectancies can be considered to have both internal and external sources, and it is these external sources that might provide a way of reducing chemotherapy-induced nausea. Unlike other risk factors for nausea, nausea expectancies are malleable and provide an opportunity for intervention.

An intriguing example of a successful non-pharmacological intervention to reduce chemotherapy-related nausea that likely was effective due to its positive influence on nausea expectancies can be seen in our prior work with acupressure bands. In a multicenter study of 739 chemotherapy patients randomized to either acupressure bands, an acustimulation band, or a no-band control for relief of chemotherapy-induced nausea, we found significantly less nausea in patients who received the acupressure wrist bands and who also expected them to be effective compared to all other groups.9 Patients who received the acupressure bands and did not expect them to be effective had no difference in reported nausea compared to the acustimulation and control groups. Results from two other research groups showing that sham acupressure bands were effective in reducing nausea suggests that an expectancy/placebo effect was also present.10,11 From this combined research a logical question arises – can the effectiveness of acupressure bands in reducing nausea be enhanced by boosting patients’ expectancy?

A previous study conducted by our group in radiation-related nausea attempted to answer this question. Patients were randomized to one of three arms which consisted of standard care (arm 1), acupressure bands plus a neutral handout concerning the bands’ efficacy (arm 2), and acupressure bands plus a positive handout concerning the bands’ efficacy (arm 3). While both arms 2 and 3 had reduced nausea compared to arm 1, there was no difference between arms 2 and 3. This lack of difference between neutral and positive handouts may have been due to the failure of the informational manipulation to change patients’ expectancies regarding the effectiveness of acupressure bands.12

The efficacy of an expectancy-enhancing manipulation was also examined by Wise et al in a randomized controlled trial of 601 asthmatic patients.13 Participants were randomly assigned to one of 4 treatment groups in a 2 × 2 factorial design (i.e., placebo with enhanced messages, placebo with neutral messages, active drug with enhanced messages, or active drug with neutral messages) or to usual care. The enhanced message, which was designed to increase expectation of benefit from the study medication, did not affect lung function. It did, however result in improved patient-reported asthma control for those patients receiving placebo. Interestingly, the enhanced message conferred no benefit to patients receiving the active medication.

The present report describes a pilot study designed to enhance the effectiveness of acupressure bands in reducing nausea through an expectancy manipulation. We conducted a double-blind, four-arm, randomized, controlled intervention testing the efficacy of 1) information and 2) suggestion to modify expectations for nausea as a way of reducing nausea in breast cancer patients about to receive their first course of chemotherapy. Patients were randomized to receive one, both, or neither of these interventions. All patients received a relaxation CD and acupressure bands (Sea-Band International, England, Figure 1) as vehicles for delivering the intervention. (Note: While both relaxation1416 and acupressure bands9,12 have shown efficacy in reducing nausea associated with cancer treatments, they were not being studied per se in this trial as they were held constant for all patients.) The informational intervention is described in detail later, and the suggestion intervention was derived from hypnosis theory, described immediately below.

Figure 1

Hypnosis, also known as suggestive therapy, has been described as a non-deceptive psychological procedure to alter expectancy.17 The client is given therapeutic suggestions that he or she will experience changes in sensation, perception, thought and/or behavior.18 Evidence suggests that both hypnotic and placebo effects share the common mechanism of response expectancy and that they are therapeutic because they change patients’ expectations of outcome.19 Both can be viewed as instances of the broader phenomenon of suggestion.20 Interventions that make use of suggestions (with or without the induction of a hypnotic trance) have been used successfully to control nausea related to chemotherapy,18,2123 and after anesthesia.24 In this study, a hypnotic trance was not induced. Instead, we made use of the therapeutic technique of providing a suggestion as a method of increasing positive expectancies concerning the acupressure bands.



Chemotherapy-naïve, female, breast cancer patients about to begin a cancer treatment regimen containing doxorubicin, cyclophosphamide, and/or carboplatin, without concurrent radiotherapy or interferon were potentially eligible for the study. Patients with clinical evidence of lymphedema, current bowel obstruction, or symptomatic brain metastases were excluded. In addition to the intervention materials, all patients received standard care during the 5-day study, and all ancillary treatments as appropriate for control of symptoms caused by the cancer or its treatment were allowed. Type and amount of antiemetic medication taken during the intervention were not regulated. The protocol was approved by the Institutional Review Board of our Medical Center, and all patients provided written informed consent. The planned accrual was 67 patients.


Prior to first chemotherapy, patients completed baseline questionnaires which included an assessment of expected nausea on a 5-point scale (see Measures Section). Patients then received two acupressure bands and were instructed in their proper placement, i.e., approximately 2 inches proximal to the distal skin crease of the wrist joint. Patients were allowed to wear or remove the bands throughout the five days at their own discretion. Patients were told that we were studying the use of acupressure bands and a relaxation CD and how information was delivered. At no point did we inform patients we were examining the role of expectancy and that we were testing an expectancy manipulation.

Patients were then randomized to one of four trial arms according to a computer-generated random table with block size eight. Randomization was stratified by whether the patient received doxorubicin (two levels: yes, no) and by the patient’s level of certainty that she would have treatment-induced nausea (two levels: ≤ 3, > 3 when assessed on a 5-point scale). The four trial arms were 1) expectancy-neutral handout and expectancy-neutral CD, 2) expectancy-enhancing handout and expectancy-neutral CD, 3) expectancy-neutral handout and expectancy-enhancing CD, and 4) expectancy-enhancing handout and expectancy-enhancing CD.

Immediately following randomization, patients were given a portable CD player that they were allowed to keep and a sealed packet that contained the intervention materials. Patients listened to the CD at that time using provided earphones to ensure they heard it at least once. They were encouraged to listen to the CD later if they found it helpful and to record how many times they did so. Patients were also provided with a take-home five-day daily diary to record antiemetic use and the severity of their nausea and vomiting, as well as a quality of life (QOL) assessment to complete on Day 5.

In accordance with optimal experimental design, the study was double-blinded. Researchers with patient contact and the treating physicians were blinded as to randomization condition by the judicious use of sealed envelopes, earphones, and carefully worded descriptions of the study. The handouts and audio CD were prepared for each patient and group assignment recorded by study personnel who did not have patient contact.

Intervention Materials

The one-page expectancy-enhancing handout (Figure 2) that was given to patients in trial Arms 2 and 4 to enhance expected acupressure band efficacy had a bar graph and about 140 words of text. It was printed on Cancer Center letterhead and signed by a medical oncologist and two of the study investigators. The handout presented a very positive (and truthful) interpretation of the data from two prior acupressure band studies. For example, the caption under the graph reads, “Only 3 patients wearing Seabands had nausea compared to 15 patients not wearing Seabands.” The bar in Figure 2 representing the three patients with no nausea was red and the other bar was black. Patients in trial Arms 2 and 4 also received a medical prescription instructing them to use the acupressure bands for relief of nausea. The prescription was signed by a medical oncologist and had the instruction, “Wear Seabands for up to five days as needed to prevent or alleviate nausea.” It was designed to enhance the credibility of the acupressure bands for nausea control and was not intended to imply that they are prescription-only devices.

Figure 2
Expectancy-enhancing handout

All patients were informed that they are sold over-the-counter. In order to make it clear that the acupressure bands were to be used in addition to their antiemetic regimen and not in place of it, we placed a sticker on the prescription with the wording, “Use the acupressure bands in addition to your regular medication.” Patients’ names were not on the prescription.

The expectancy-neutral handout given to patients in Arms 1 and 3 simply thanked patients for participating in the study. It was also printed on Cancer Center letterhead and signed by a medical oncologist and two study investigators. The wording of the letter was, “Thank you for agreeing to participate in this study regarding the use of acupressure bands to control chemotherapy-related nausea. The information you will provide is extremely valuable. It is only with the assistance of individuals, like you, who are willing to give their time that we can learn new ways to better control the side effects of cancer treatment. Wear the acupressure bands for up to five days, if helpful, to prevent or alleviate nausea. We are very appreciative of your contribution to this study.” Handouts provided to these patients did not have a prescription attached but did include a piece of paper the size of a prescription that said, “Use the acupressure bands in addition to your regular medication.”

Expectancy-enhancing and expectancy-neutral relaxation CDs

The script used in both the expectancy-neutral and expectancy-enhancing CDs is about 12 minutes in length and utilizes guided imagery in which the individual visualizes pleasant, soothing images or scenes while relaxed. It is based upon a published script.25,26 The CDs differ from one another only in that the expectancy-enhancing CDs (for subjects randomized to Arms 3 and 4) had additional language inserted concerning efficacy of the acupressure bands and control of nausea. This additional language is under one minute in length and intended to strengthen patients’ beliefs that the acupressure bands would be effective by focusing patients’ attention on how effective the acupressure bands have been in reducing or eliminating nausea for other patients. In addition, it was suggested that since the acupressure bands were helpful to others, they might be helpful to them as well. The actual language that has been inserted in the expectancy- enhancing CD, but not in the neutral CD, is as follows and is located near the end of the CD when the patient is deeply relaxed:

“I’d like you to imagine feeling this way as you begin your treatment, and receive it …and then afterwards…you can call up these calm, pleasant feelings at any time…return whenever you wish to this special, safe place…and I wonder, too, if you might be able to use the wristband you now have as a reminder of these relaxed, pleasant sensations you are now experiencing…free of stress, nausea or other unpleasant sensations…I wonder if directing your attention to the wristband in the future can call up these feelings for you…of being quiet, relaxed, with no queasiness…others who have had chemotherapy have found the wristbands useful in providing relief of that unpleasant feeling, and I wonder if you will too…knowing you can use the bands to call up the peace you feel now, the feeling of being free of nausea that you are hopefully feeling …and regain the sense of calm…peace and relaxation you have now”


Nausea and emesis were measured using a five-day patient report diary developed by Burish27 and Carey28 and used by us in previous large clinical trials.4,9,29 Each day was divided into 4 sections: morning, afternoon, evening, and night. Patients reported severity of nausea for each period daily. Severity of nausea was assessed on a 7-point rating scale, anchored at one end by 1 = “Not at all nauseated” and at the other end by 7 = “Extremely nauseated.” The description “Moderately nauseated” was centered on the scale below the 4. Average Nausea was the mean severity for the 20 reporting periods and Peak Nausea was defined as the highest nausea rating at any time. We also assessed the amount of antiemetic medication taken and the number of vomiting episodes. A variable indicating the sum total of antiemetic pills taken outside of the treatment clinic during the five-day study period was created for each patient. (Note: dexamethasone and lorazepam are included in these totals.)

The measure of patients’ expectation for nausea is based on a questionnaire used previously by our group.1,8,30 Nausea expectancy was assessed on separate 5-point Likert-scales that are anchored at one end by 1 = “I am certain I WILL NOT have this,” and at the other end by 5 = “I am certain I WILL have this.” Expected efficacy of the wrist bands was assessed on a 5-point scale anchored at one end by 1 = “Not at all effective” and at the other end by 5 = “Very effective”.

An On-Study Data questionnaire was used to record demographic and clinical information and patients’ history of nausea from various causes.

A feedback questionnaire was completed by patients at the conclusion of the study period concerning use of and recommendations for the acupressure bands and the relaxation CD. The recommendation questions were on 5-point scales anchored by 1 = “Do not recommend” and 5 = “Strongly Recommend”.

Statistical Analyses

The stated primary purpose for conducting this pilot study was to gather preliminary efficacy and feasibility data for the development of a planned RO1 submission with the primary analyses consisting of calculating means and standard deviations on nausea for the four study arms. Although we knew our statistical power would be limited by the small sample size in each treatment arm, we also planned to use a 2 × 2 (i.e., two levels of expectancy CDs and two levels of expectancy handouts) full factorial analysis of variance (ANOVA) to examine the efficacy of these two methods of expectancy enhancement in reducing Average Nausea as well as any interaction effects.

These planned analyses were modified after interim analyses revealed an interaction between our intervention and our stratification variable of expected nausea, with patients having low nausea expectancies doing best in Arm 1, and patients with high nausea expectancies doing best with Arm 4. While the effect was not statistically significant, it was in line with our previous findings with acupressure bands31 and potentially important both theoretically and clinically. With approval of our NCI Program Officer, we increased our total target accrual, stopped recruiting patients to Arms 2 and 3 of the study, and focused our accrual and intended analyses on the examination of the interaction between the two remaining intervention conditions (Arm 1 = fully neutral, Arm 4 = fully enhanced) with expected nausea. Expected nausea for these analyses was dichotomized to low and high based upon the stratification level we used for randomization, i.e., by the patient’s level of certainty that she would have treatment-induced nausea (two levels: ≤ 3, > 3 when assessed on a 5-point scale).

In line with our redirected focus on the interaction effect, a 2 × 2 [i.e., two levels of expectancy (high, low) and two levels of intervention (neutral, enhanced)] ANCOVA to examine the efficacy of the intervention in reducing Average Nausea was conducted on patients in study Arms 1 and 4. Patients in Arms 2 and 3 were excluded from these analyses. Six variables frequently related to nausea report, i.e., age, doxorubicin-based chemotherapy or not, having a 5-HT3 receptor antagonist antiemetic or not, having aprepitant or not, susceptibility to motion sickness or not, and morning sickness or not, were tested as potentially meaningful covariates in the model. Only covariates testing at P > 0.1 were left in the final model. A parallel analysis was conducted with Peak Nausea as the dependent variable. A similarly structured exploratory analysis examining the effect of the intervention on the amount of antiemetic medication used was also conducted. All analyses were conducted with SPSS Version 16, and results were considered significant if P < 0.05, two-tailed. As fewer than 15% of the patient sample reported any vomiting episodes during the 5-day assessment period, no analyses were conducted on this variable.


Patient Sample

Approximately 89% (N = 74) of the 83 randomized women provided evaluable data. Three of the original 83 women were excluded from the analyses because of randomization errors; one was excluded because of an error regarding eligibility, and five failed to return the nausea diary. One of the remaining 74 patients did not complete all of the post-intervention measures but did complete the first day of the nausea diary. As her highest nausea recorded on that day was a 6, which was near the top end of the range of the 1–7 nausea scale, we included her in the analyses of Peak Nausea. We did not include her in the analysis of Average Nausea. Six of the 74 patients did not complete the antiemetic questionnaire and are not included in the analyses of antiemetic use.

Of these 74 patients, 69 were White, two were African-American, two were Asian and one was American Indian. These patients ranged in age from 28–74 years (mean = 51.5) and most (76%) were married. Sixty-six percent had graduated from or attended college, and an additional 33% were high school graduates. Sixty-one of the 74 patients received doxorubicin-based chemotherapy. The remaining 13 patients (8 in Arm 1 and 5 in Arm 4) received taxotere combined with either cyclophosphamide or carboplatin. Of the eight patients not receiving doxorubicin in Arm 1, three were stratified as expecting nausea and five were not. For the five patients not receiving doxorubicin in Arm 4, three were stratified as expecting nausea and two were not. All patients receiving doxorubicin-based chemotherapy received a 5-HT3 receptor antagonist antiemetic and/or aprepitant with their chemotherapy. Twenty-eight patients were randomized to Arm 1, 10 to Arm 2, 11 to Arm 3, and 25 to Arm 4. All study subjects received their treatments as outpatients.

Patients in the four study arms did not differ on susceptibility to motion sickness, coded yes or no, nor on experience of morning sickness during pregnancy, coded yes or no (note: a response of not applicable was recoded as no. Patients in the four study arms did, however, differ significantly by age, (P = 0.024; means: Arm 1 = 47.6, Arm 2 = 55.2, Arm 3 = 48.4, Arm 4 = 55.6).

Primary Analyses

Forty patients were included in the interim analysis, and the means and standard deviations for Average and Peak Nausea, categorized by expected nausea (high, low), are shown in Tables 1 and and2.2. The means and standard deviations for these two variables in the 34 patients accrued following the interim analysis are also shown as are means and standard deviations for the combined patient sample.

Table 1
Average nausea categorized by expected nausea level and inclusion in the interim analysis or accrued following it
Table 2
Peak nausea categorized by expected nausea level and inclusion in the interim analysis or accrued following it

Fifty-two patients were included in the 2 × 2 (i.e., two levels of expectancy and two levels of intervention) ANCOVA to examine the efficacy of the intervention in reducing Average Nausea, and 53 patients were included in the parallel analyses examining Peak Nausea. The only one of the six possible covariates remaining in the two analyses was having morning sickness or not with a p-value of 0.076 in the analysis on Average Nausea and 0.099 in the analysis on Peak Nausea. The interaction term in the analysis on Average Nausea approached but did not reach conventional levels of statistical significance, P = 0.084. The interaction term with Peak Nausea was statistically significant, P = 0.030. The main effects in these two analyses were not statistically significant, all Ps ≥ 0.40. (See Figure 3)

Figure 3
Interaction of low versus high nausea expectancy with neutral versus enhanced information on nausea in 53 patients following first chemotherapy

Exploratory Analysis

The ANCOVA (N = 48) examining the efficacy of the intervention on total number of antiemetic pills taken outside the clinic had two covariates remaining in the model, having morning sickness or not at P = 0.075 and receiving aprepitant or not at P < 0.000. The analysis showed a main effect for treatment arm: patients in Arm 4 (enhanced information) took significantly fewer pills than patients in Arm 1 (neutral information) [adjusted meanenhanced = 10.8, s.e. = 1.6; adjusted meanneutral = 18.7, s.e. = 1.4; P = 0.001]. Neither the main effect for expected nausea nor the interaction was significant (both, Ps > 0.4). To further explore between-group differences in antiemetic use, we conducted two additional post-hoc analyses. The first was a descriptive analyses of antiemetic use, by study arm, in the entire data set (N = 68). The mean number of antiemetic pills taken at home in the four study arms were: Arm 1 = 18.3, s.d. = 9.6; Arm 2 = 19.1, s.d. = 7.8; Arm 3 = 14.9, s.d. = 7.2; and Arm 4 = 11.3, s.d. = 6.0. Because the means of Arms 1 and 2 were higher than the means of Arms 3 and 4, we examined the hypothesis that between-group differences in antiemetic use were related to differences in the type of handout received. For this analysis, we used a t-test to compare antiemetic use in patients receiving the expectancy-neutral handout (Arms 1 and 2 combined, N = 36) with patients receiving the expectancy-enhancing handout (Arms 3 and 4 combined, N = 32). This analysis was statistically significant (meanenhanced = 12.6, s.d. = 6.6; meanneutral = 18.5., s.d. = 9.1; P = 0.003).

Satisfaction with Bands and CD and Duration of Use

Seventy-three of the 74 evaluable patients provided feedback. Twenty-five (34%) of these patients reported that they wore the wrist bands for more than 48 hours (the longest of the five “duration of time worn” categories on the feedback questionnaire). An additional 10 (14%) patients indicated they wore the bands for more than 24 hours. Nine patients (12%) wore the bands for less than five hours. The overall mean on the 1–5 scale for recommending acupressure bands to other patients was relatively high at 4.04. Recommendations concerning the relaxation CD were slightly lower at 3.80 but still positive. The average number of times patients listened to the CD outside of the clinic was 6.2, and 56% of the patients listened to it four or more times at home. Patients in Arm 1 tended to wear the bands more than patients in Arm 4 with 39% (n = 11) of Arm 1 patients wearing the wrist bands for more than 48 hours and an additional 18% (n = 5) wearing the bands for at least 24 hours. By contrast, only 33% (n = 8) of patients in Arm 4 wore the wrist bands for more than 48 hours with an additional 4% (n = 1) wearing the bands for at least 24 hours. For patients in study Arms 1 and 4, no difference was reported in wrist band use when examined according to the stratification variable of expected nausea with 48% of patients in each expectancy grouping wearing the wrist bands 24 hours or more.

Analyses Examining Expected Nausea

For the combined 74 patients, the measure of expected nausea, taken at the time of consent, correlated significantly with both Average Nausea (r = .28; P = 0.014) and Peak Nausea (r = .355; P = 0.002) during the subsequent 5-day intervention period. Expected nausea was not significantly correlated with total number of antiemetic pills taken outside the clinic (r = .05; P = 0.69).


This study provides support for the hypothesis that the effectiveness of acupressure bands in reducing nausea can be enhanced through an expectancy manipulation, but it comes with the qualification that such manipulations should be targeted. Our expectancy manipulation resulted in improved control of nausea in patients with high nausea expectancies but lessened control of nausea in patients having low nausea expectancies. This interaction effect approached statistical significance for our analysis of Average Nausea and reached statistical significance for our analysis of Peak Nausea, even though this was a small pilot study.

Understanding that a medical intervention is appropriate for some people but not all is basic to the practice of medicine, and researchers endeavor to find out not only if an intervention is effective, but also for whom it is effective. The present study provides important data regarding both objectives. Our findings support the use of expectancy-enhancing information as an aid to nausea control, at least when acupressure bands are used, and also provides initial evidence that such information may be beneficial only to patients expecting to have nausea. In very simplistic terms, it is as if a negative expectancy for nausea held by a patient can be neutralized by providing an expectancy-enhancing intervention regarding nausea control. We note that negative expectancies such as those for nausea targeted in this study are significant predictors of actual nausea, as detailed in the introduction. Nausea, in turn, is a particularly significant problem in breast cancer patients receiving chemotherapy, the patient group for this study.8

Our intervention also affected the amount of antiemetic medication used; patients who received the expectancy-enhancing information took significantly less than patients who received the expectancy-neutral information. Thus, it appears that in the group of patients expecting nausea, the intervention had a double effect for those receiving the expectancy-enhancing information. This group not only experienced less nausea but also used less antiemetic medication compared to patients who received expectancy-neutral information. It is also possible that the difference in medication use between intervention arms affected nausea levels in the group of patients not expecting nausea and accounts for the increase in nausea in patients receiving the expectancy-enhancing information compared to patients who did not.

The reduction in antiemetic use may have been an unintended consequence of our expectancy-enhancing handout, specifically, the prescription to use the acupressure bands for relief of nausea. Even though a sticker was placed on the prescription with the instruction to use the bands in addition to their antiemetic medication, patients may have reduced their antiemetic use thinking the imprimatur of a doctor’s signed prescription to use the acupressure bands meant the bands alone would control their nausea. Further studies should be done using the expectancy-enhancing materials without the prescription to see if these materials also reduce antiemetic use when used alone. Future studies should use a study design that more rigorously specifies the antiemetic regimen.

While acupressure bands and a relaxation CD were used in this study, our data cannot speak to their actual efficacy because all patients received them. We do know they were well-received and used extensively by most patients. Most of the patients in the study also indicated they would recommend their use to other patients.

A plausible explanation for how expectancies affect nausea is that a patient expecting nausea following chemotherapy might be more likely to interpret vague or ambiguous sensations as nausea than an individual not expecting the symptom.32 Theoretical support for this explanation comes from schema theory which holds that cognitive schemas act as information processing systems that filter and interpret new data, with greater attention being paid to schema congruent information.3335 In this sense, a nausea expectancy can be considered a schema that can override sensory information.36 As stated by Posner, “The idea that perceptions can be manipulated by expectations is fundamental to the study of cognition.”36

Expectancies, when positively oriented, are at the core of theories attempting to explain the placebo effect.7,37 Stewart-Williams describes the placebo effect in its classic form as beginning with an expectancy or belief: i.e., if I take drug X, I will experience effect Y.38 Taking the drug, or something the patient thinks is the drug, then produces the placebo effect. Price and colleagues8,39 report a shifting of understanding and conceptualization of the placebo effect from a focus on the inert content of a physical placebo agent to the overall simulation of a therapeutic intervention. In this broader context, it is understood that the placebo effect occurs not only with drugs and fake drugs, but also with any medical intervention (e.g., a mother’s kiss on a boo-boo). It is also the case that the magnitude of a placebo effect may not be constant and can be enhanced under certain circumstances as shown by Wise et al,13 discussed earlier, and others.4042

Several studies have shown that information given to patients about a treatment can modify their expectations and thus their response to that treatment.36,4346 Crow and colleagues in their review of the role of expectancies in the placebo effect state that “the existing evidence justifies the use of strategies to enhance expectancies, specifically to enhance patients’ beliefs in the benefits of effective medical treatments.”47 Our findings lend support to this statement but add a caution that such interventions might be helpful only to patients who have negative response expectancies. If our findings are affirmed in subsequent studies, it would underscore the importance of two-way communication between patients and medical service providers and the need for clinicians to be mindful of patients’ expectations regarding symptoms. As most patients regard their medical professionals as knowledgeable authority entities, those patients holding negative expectancies might benefit from a more tailored communication approach that integrates information about patients’ expectancies regarding symptoms.

Limitations of the study include a small sample size and the fact that we ceased recruitment to two of the treatment arms and changed our planned primary analysis mid-study based upon an interim analysis that was not specified at the time the study began. Even though the data collected following the interim analyses closely matched the data collected before it, our findings need to be considered tentative until replicated. Because this was a small exploratory study, we did not adjust our P values for the multiple comparisons (three total) nor for the interim analysis.

These are additional reasons why our findings need to be considered tentative until replicated. Patient differences in the type of chemotherapy provided could have affected our findings despite our use of a stratified randomization schema. Similarly, differences in the kind of antiemetic medications provided, both in the clinic and for home use, could have affected study outcomes. Given that nausea expectancies are malleable, it is possible that differences in the various providers’ discussions with patients regarding nausea management could have influenced outcomes. Our randomization procedure should have adequately controlled for these factors, but it may not have. An additional study limitation is that we do not know the relative effect of the expectancy-enhancing handout vis-a-vis the expectancy-enhancing CD. Nor do we know if both are needed for a beneficial intervention effect to occur. Future studies should control for these limitations, if possible, and also include a standard care control group.

Despite general acceptance that nonspecific treatment factors such as response expectancy play an important role in health-related outcomes, relatively little randomized, controlled research has examined their effects. This is likely due in part to the abstract nature of response expectancies and the methodological difficulties that come with measuring them. Another impediment is that non-specific treatment factors, such as expectancy, are often regarded as an unquantifiable nuisance or are bundled as part of the “placebo effect,” something that randomized trials “control” for and attempt to show effects beyond. Although controlled trials clearly have their place in medical science, the element we control for in such trials, i.e., the placebo effect, may, nevertheless, be a construct that can be harnessed for improved patient well being.


Previous research provides evidence that acupressure bands are effective in reducing nausea and that their effectiveness, at least in part, can be accounted for by patients’ expectations of efficacy (i.e., a placebo effect). The present study tentatively extends these findings by showing that an informational manipulation designed to increase patients’ expectations of efficacy for the acupressure bands affects patients’ level of nausea with a bi-directional effect. The intervention reduced antiemetic use overall and also reduced nausea in patients who had high levels of expected nausea. Paradoxically, it increased nausea in patients who had low expectancies for nausea, perhaps because of the reduced use of antiemetics. Confirmatory research is warranted.


Supported by Grants 1R21CA118883 and 1R25-CA102618-01A1 from the National Cancer Institute


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