Thesis (Ph. D.)--University of Chicago, Dept. of Economics, August 2003. / Includes bibliographical references. Also available on the Internet.

This investigation examined the impact of a potent source of social influence—the placebo—on verbal and nonverbal pain expression. Placebos exert a powerful influence on pain in both clinical and laboratory settings; nevertheless, the placebo remains a poorly understood phenomenon. In the present study the placebo was employed as a social influence designed to alter subjects' expectations or beliefs concerning their response to a noxious event. Furthermore, an attempt was made to classically condition a placebo response in accordance with the conditioning theory of placebo. The pain stimulus consisted of 500-millisecond electrical shocks. The placebo was an inert white cream described as an effective and quick-acting local anaesthetic. To gain a broad assessment of verbal and nonverbal pain expression, two self-report measures and an objective behavioural measure—facial expression—were used. Self-report comprised the "Sensory" and "Unpleasantness" ratio scales (derived from Gracely, McGrath, & Dubner, 1978). Facial expressiveness was coded using the Facial Action Coding System (FACS) developed by Ekman and Friesen (1978). Psychological interventions have been said to primarily alter patients' affective response to pain, thus it was expected that the greatest impact of the placebo would be reflected by the Unpleasantness Scale. The Sensory ratings and facial activity were expected to reflect less of a change. Sex differences were analyzed but were not expected because the pain stimulus intensity was individualized. Anxiety ratings taken before the trials with placebo were expected to be lower than anxiety ratings before the no-placebo trials; this was expected to be positively related to a placebo response (defined as lower pain expression during placebo trials than during no-placebo trials). In the baseline phase, subjects were tested with and without the placebo. They received the expectation manipulation that the analgesic cream would act as a local anaesthetic. Next, to condition a placebo response, in the positive conditioning group shocks administered with placebo cream were surreptitiously decreased; in the negative conditioning group shocks were increased; and in the baseline (control) group shocks remained at baseline levels. A final return-to-baseline phase tested the conditioned placebo response. A significant placebo response was found to be most clearly represented by the self-report measures and less by the facial activity. Control group subjects, who were exposed only to the verbal directive that they were receiving an analgesic cream, demonstrated a clear placebo response on both the Unpleasantness and Sensory self-report scales. Thus both self-report measures reflected a substantial placebo effect. Nonverbal expression reflected an effect only with half of the control group—the males—who exhibited significantly less facial activity during the placebo trials compared to the no-placebo trials. However, neither of the two groups exposed to manipulated shock levels demonstrated a significant conditioned placebo effect on any dependent measure. There was a modest relationship between facial activity and self-report. Self-reported anxiety was somewhat predictive of the degree to which subjects rated placebo trials as less painful than no-placebo trials, but the direction of this relationship was opposite to that hypothesized. In brief, subjects led to expect an analgesic cream, but not exposed to the conditioning manipulation, reliably exhibited a placebo response on both self-report scales; the males in this group also exhibited a placebo response as measured by facial activity. No support was found for the conditioning theory of placebo effects. / Arts, Faculty of / Psychology, Department of / Graduate

Thesis (Ph.D.)--Memorial University of Newfoundland, 2002. / Bibliography: leaves 148-157.

Thesis (M.S.)--Ohio University, November, 2006. / Title from PDF t.p. Includes bibliographical references.

Pilot Study: a) 21 Generalised Anxiety Disorder (GAD) patients were treated double-blind with either diazepam or placebo for 6 weeks. This active treatment period was preceded by one-week single-blind placebo 'wash-in', and followed by two-week single-blind 'washout'. Results showed that diazepam used in moderate doses for 6 weeks produced anxiety recurrence and withdrawal symptoms. b) 10 GAD patients were randomly allocated to Cognitive-Behaviour Therapy (CBT) and compared with the above diazepam and placebo groups. All treatments were balanced for degree of Psychologist/patient contact. At cessation of active treatment CBT superiority was indicated. Post-Study psychotropic prescription and psychological treatment were assessed at 12 months follow-up. The CBT group had the lowest incidence of subsequent treatment interventions. Main Study : 101 GAD patients were randomly allocated to diazepam, placebo, CBT, CBT + diazepam, and CBT + placebo, and treated over 10 weeks. Outcome measures at end of treatment and at 6 months follow-up revealed the superiority of all CBT treatments; especially CBT alone, and CBT + diazepam. Diazepam was more effective than placebo. CBT + diazepam, and diazepam groups showed no anxiety recurrence during graded withdrawal. Secondary Study : 205 long-term benzodiazepine users were matched for age and sex with controls. Inspection of medical case notes showed that benzodiazepine users had higher rates of previous physical illness, GP attendance, and non-psychotropic drug prescription. Differences emerged between anxiolytic, hypnotic, and anxiolytic + hypnotic benzodiazepine users in age, history of physical illness, and previously prescribed medication. Tertiary Study : 44 long-term benzodiazepine users were interviewed. The incidence of psychological ill-health and social problems was lower than expected. Patients were dependent on medication, and reported concern if their medication were to be stopped. Nevertheless 40% considered stopping benzodiazepines. Results from the above studies are discussed in relation to clinical management of GAD, and current concerns about benzodiazepine dependence and withdrawal.

Thesis (M.A.)--Carleton University, 2000. / Includes bibliographical references. Also available in electronic format on the Internet.

Thesis--Catholic University of America. / Bibliography: p. 31-33.

A double-blind comparison was conducted using typical doses of soporific agents from three drug classes and a placebo. Drugs which were used in the study included secobarbital, flurazepam hydrochloride, and thioridazine. Subjects were 40 outpatient volunteers whose primary complaint was difficulty in falling to sleep. Subjects were randomly assigned to one of the three drug groups or the placebo group. One of the drugs or the placebo was administered to each subject for 3 nights. Half of the subjects in each of the four groups were told the drug had caused any observed changes in their sleep behavior and were in this way led to attribute any changed sleep behavior externally to the drug. The other half were told the drugs were not typically used to treat insomnia and changes in their sleep were due to changes made in their own behavior, thus attributing any changes in sleep behavior internally. The implication for clinicians was that a short course of drug therapy using a placebo or one of several soporific drugs might be used equally effectively to treat primary latency insomnia. Additionally, the results demonstrated that clinicians might expect the effectiveness of treatment to be maintained following treatment. Recommendations included a suggestion for future research with soporific drugs in other classes.

Conclusions. The retractable non-invasive needle seems to have reasonably good capability of blinding patients and is more successful in acupuncture-naive subjects than in experienced ones. The failure to produce similar sensation of stimulation in the sham acupuncture group may be the major reason for incomplete blinding. (Abstract shortened by UMI.) / Design, participants and outcomes. We conducted a randomized controlled trial of 398 acupuncture-naive subjects and 197 acupuncture-experienced subjects who were recruited from the outpatients clinic of a university hospital in China. Acupuncture-naive and experienced subjects were randomized separately to receive the real acupuncture treatment or the placebo acupuncture at acupoint Hegu on the left hand. After the intervention, the percentage of patients who thought they had received real acupuncture was compared between the real and sham acupuncture groups. We defined the degree of blinding as 100% minus the difference in the percentage between the two groups. The score of pain, soreness, numbness, heaviness and distension during the treatment was also compared between the two groups. / Introduction. The newly designed retractable needle which can be used to produce non-invasive placebo or (sham) acupuncture seems promising and has been used in clinical trials. Several studies investigated the credibility of the retractable needle in blinding patients. These studies are generally small and mostly in acupuncture-naive patients and mainly focused on the difference in acupuncture-related sensations rather than the successfulness of blinding. / Objectives. To quantify the degree of blinding of the retractable non-invasive placebo needle in blinding both acupuncture-naive and experienced subjects in clinical trials and to explore possible reasons for incomplete blinding of the sham needle. / Results. In acupuncture-naive subjects, the percentage of those who thought they had received real acupuncture was 70.4% and 42.7% respectively in the real and sham acupuncture groups. The degree of blinding was 72.3% (95% CI: 62.9%, 81.7%). In acupuncture-experienced subjects, the degree of blinding was 58.9 (95% CI: 46.2%, 71.6%). The difference in degree of blinding between acupuncture-naive and experienced subjects was statistically significant (P<0.05). The score of pain, soreness, numbness, heaviness and distension in the real acupuncture group was all statistically significantly higher than that in the sham acupuncture group in both acupuncture-naive and experienced subjects (P<0.001). / Zhang Hongwei. / "February 2005." / Adviser: Jin Ling Tang. / Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0161. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 93-102). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

The ultimate goal of personalized or precision medicine is to identify the best treatment for each patient. An N-of-1 trial is a multiple-period crossover trial performed within a single individual, which focuses on individual outcome instead of population or group mean responses. As in a conventional crossover trial, it is critical to understand carryover effects of the treatment in an N-of-1 trial, especially in situations where there are no washout periods between treatment periods and high volume of measurements are made during the study. Existing statistical methods for analyzing N-of-1 trials include nonparametric tests, mixed effect models and autoregressive models. These methods may fail to simultaneously handle measurements autocorrelation and adjust for potential carryover effects. Distributed lag model is a regression model that uses lagged predictors to model the lag structure of exposure effects. In the dissertation, we first introduce a novel Bayesian distributed lag model that facilitates the estimation of carryover effects for single N-of-1 trial, while accounting for temporal correlations using an autoregressive model. In the second part, we extend the single N-of-1 trial model to multiple N-of-1 trials scenarios. In the third part, we again focus on single N-of-1 trials. But instead of modeling comparison with one treatment and one placebo (or active control), multiple treatments and one placebo (or active control) is considered. In the first part, we propose a Bayesian distributed lag model with autocorrelated errors (BDLM-AR) that integrate prior knowledge on the shape of distributed lag coefficients and explicitly model the magnitude and duration of carryover effect. Theoretically, we show the connection between the proposed prior structure in BDLM-AR and frequentist regularization approaches. Simulation studies were conducted to compare the performance of our proposed BDLM-AR model with other methods and the proposed model is shown to have better performance in estimating total treatment effect, carryover effect and the whole treatment effect coefficient curve under most of the simulation scenarios. Data from two patients in the light therapy study was utilized to illustrate our method. In the second part, we extend the single N-of-1 trial model to multiple N-of-1 trials model and focus on estimating population level treatment effect and carryover effect. A Bayesian hierarchical distributed lag model (BHDLM-AR) is proposed to model the nested structure of multiple N-of-1 trials within the same study. The Bayesian hierarchical structure also improve estimates for individual level parameters by borrowing strength from the N-of-1 trials of others. We show through simulation studies that BHDLM-AR model has best average performance in terms of estimating both population level and individual level parameters. The light therapy study is revisited and we applied the proposed model to all patients’ data. In the third part, we extend BDLM-AR model to multiple treatments and one placebo (or active control) scenario. We designed prior precision matrix on each treatment. We demonstrated the application of the proposed method using a hypertension study, where multiple guideline recommended medications were involved in each single N-of-1 trial.