-
Scientific Reports Jan 2018Among the serious consequences of alcohol abuse is the reduced ability to process visual information. Diminished vision from excessive consumption of alcohol has been... (Randomized Controlled Trial)
Randomized Controlled Trial
Among the serious consequences of alcohol abuse is the reduced ability to process visual information. Diminished vision from excessive consumption of alcohol has been implicated in industrial, home, and automobile accidents. Alcohol is also generally recognized as an inhibitor in the brain by potentiating GABA-ergic transmission. In this study, we focused on visual motion processing and explored whether moderate alcohol intoxication induced changes in inhibitory mediated motion repulsion in a center-surround configuration. We conducted a double-blind, placebo-controlled, within-subjects study on the effect of alcohol on visual motion repulsion. Each subject underwent three experimental conditions (no alcohol, placebo and moderate alcohol) on separate days. The order of the placebo and moderate alcohol conditions was counterbalanced. The results showed that the effects of the surround context on the perception of the center motion direction were similar in both the sober (no alcohol) and placebo conditions. However, contextual modulations were significantly stronger during intoxication compared to both the sober and placebo conditions. These results demonstrate that moderate alcohol consumption is associated with altered neural function in visual cortical areas and that motion repulsion deficits might reflect the inhibitory effects of alcohol on the central nervous system.
Topics: Adult; Alcoholic Intoxication; Alcohols; Double-Blind Method; Female; Healthy Volunteers; Humans; Male; Motion Perception; Placebos; Visual Cortex; Young Adult
PubMed: 29371672
DOI: 10.1038/s41598-018-19932-8 -
Pain Research & Management 2011To determine whether the nonspecific effects that occur following the use of sham interventions to treat nonspecific low back pain (LBP) are large enough to be... (Review)
Review
OBJECTIVE
To determine whether the nonspecific effects that occur following the use of sham interventions to treat nonspecific low back pain (LBP) are large enough to be considered clinically meaningful.
DESIGN
Electronic databases were searched systematically for randomized placebo-controlled trials of interventions for LBP that used sham ultrasound, sham laser or sham drug therapy as the placebo control. Study selection was accomplished via independent evaluation of scientific admissibility by three reviewers and final decisions of inclusion were based on consensus.
RESULTS
None of the studies using sham ultrasound as the placebo control in the treatment of LBP were acceptable for inclusion. Twelve studies were included in the present evaluation of the placebo effect - eight trials that met the strict inclusion criteria for best evidence (three using sham laser placebo and five using sham medication placebo) and four sham medication studies that 'just missed' the inclusion criteria for best evidence. Although the evidence from studies using sham laser was inconclusive, the present review did find a clinically meaningful change in LBP scores following the use of sham oral medications.
CONCLUSIONS
The present best-evidence review found a clinically meaningful change in pain scores following the use of sham oral medications for the treatment of nonspecific LBP. This finding suggests that further clinical research is warranted to identify which patient subgroups could benefit most from such treatment and to distinguish the true contribution of the placebo effect from other nonspecific effects.
Topics: Databases, Factual; Humans; Low Back Pain; Observation; Placebo Effect; Placebos; Treatment Outcome
PubMed: 21369541
DOI: 10.1155/2011/625315 -
Annals of Oncology : Official Journal... Nov 2019In the SPARTAN study, compared with placebo, apalutamide added to ongoing androgen deprivation therapy significantly prolonged metastasis-free survival (MFS) and time to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In the SPARTAN study, compared with placebo, apalutamide added to ongoing androgen deprivation therapy significantly prolonged metastasis-free survival (MFS) and time to symptomatic progression in patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC). Overall survival (OS) results at the first interim analysis (IA1) were immature, with 104 of 427 (24%) events required for planned final OS analysis. Here, we report the results of a second pre-specified interim analysis (IA2).
METHODS
One thousand two hundred and seven patients with nmCRPC were randomized 2 : 1 to apalutamide (240 mg daily) or placebo. The primary end point of the study was MFS. Subsequent therapy for metastatic CRPC was permitted. When the primary end point was met, the study was unblinded. Patients receiving placebo who had not yet developed metastases were offered open-label apalutamide. At IA2, pre-specified analysis of OS was undertaken, using a group-sequential testing procedure with O'Brien-Fleming-type alpha spending function. Safety and second progression-free survival (PFS2) were assessed.
RESULTS
Median follow-up was 41 months. With 285 (67% of required) OS events, apalutamide was associated with an improved OS compared with placebo (HR 0.75; 95% CI 0.59-0.96; P = 0.0197), although the P-value did not cross the pre-specified O'Brien-Fleming boundary of 0.0121. Apalutamide improved PFS2 (HR 0.55; 95% CI 0.45-0.68). At IA2, 69% of placebo-treated and 40% of apalutamide-treated patients had received subsequent life-prolonging therapy for metastatic CRPC. No new safety signals were observed.
CONCLUSION
In patients with nmCRPC, apalutamide was associated with a 25% reduction in risk of death compared with placebo. This OS benefit was observed despite crossover of placebo-treated patients and higher rates of subsequent life-prolonging therapy for the placebo group.
Topics: Androgen Receptor Antagonists; Cross-Over Studies; Disease Progression; Humans; Male; Middle Aged; Placebos; Progression-Free Survival; Prostatic Neoplasms, Castration-Resistant; Thiohydantoins; Time Factors
PubMed: 31560066
DOI: 10.1093/annonc/mdz397 -
PloS One 2014Lack of knowledge concerning the nature of placebo and why it is necessary may influence the participation of patients in clinical trials. The objective of the present...
AIM
Lack of knowledge concerning the nature of placebo and why it is necessary may influence the participation of patients in clinical trials. The objective of the present study is to review how placebo is described in written information for participants in clinical trials to be evaluated by a Human Research Ethics Committee.
METHODS
All research protocols submitted for evaluation in a Spanish hospital during 2007-2013 were reviewed. The main characteristics of the studies using a placebo were collected. Three authors read each of them to determine how the term "placebo" was explained and if there was any comment on its efficacy and safety.
RESULTS
Two thousand seven-hundred and forty research protocols were evaluated, of which three hundred and fifty-nine used a placebo. Pharmaceutical companies sponsored most placebo-controlled clinical trials (91.9%), and phase III studies were the commonest (59.9%). Oncology (15.0%), cardiology (14.2%), and neurology (13.1%) made the greatest contributions. A review of the informed consent forms showed that placebo was described in a similar manner in most studies: the explanation was limited to between four and eight words. Very few gave information about the risks of its use or adverse reactions from its administration. None of the studies provided details about the placebo effect. And 23 lacked any information about placebo at all.
CONCLUSIONS
Explanations about placebo in informed consent forms is often scarce, and information about the placebo effect and associated risks are absent. This situation may influence a full understanding of placebo by participants in clinical trials and might reduce their informed decision to participate.
Topics: Clinical Trials as Topic; Informed Consent; Placebos
PubMed: 25423149
DOI: 10.1371/journal.pone.0113654 -
The Journal of Neuroscience : the... Mar 2017Placebo treatments can strongly affect clinical outcomes, but research on how they shape other life experiences and emotional well-being is in its infancy. We used fMRI... (Randomized Controlled Trial)
Randomized Controlled Trial
Placebo treatments can strongly affect clinical outcomes, but research on how they shape other life experiences and emotional well-being is in its infancy. We used fMRI in humans to examine placebo effects on a particularly impactful life experience, social pain elicited by a recent romantic rejection. We compared these effects with placebo effects on physical (heat) pain, which are thought to depend on pathways connecting prefrontal cortex and periaqueductal gray (PAG). Placebo treatment, compared with control, reduced both social and physical pain, and increased activity in the dorsolateral prefrontal cortex (dlPFC) in both modalities. Placebo further altered the relationship between affect and both dlPFC and PAG activity during social pain, and effects on behavior were mediated by a pathway connecting dlPFC to the PAG, building on recent work implicating opioidergic PAG activity in the regulation of social pain. These findings suggest that placebo treatments reduce emotional distress by altering affective representations in frontal-brainstem systems. Placebo effects are improvements due to expectations and the socio-medical context in which treatment takes place. Whereas they have been extensively studied in the context of somatic conditions such as pain, much less is known of how treatment expectations shape the emotional experience of other important stressors and life events. Here, we use brain imaging to show that placebo treatment reduces the painful feelings associated with a recent romantic rejection by recruiting a prefrontal-brainstem network and by shifting the relationship between brain activity and affect. Our findings suggest that this brain network may be important for nonspecific treatment effects across a wide range of therapeutic approaches and mental health conditions.
Topics: Adolescent; Adult; Affect; Analgesia; Brain Stem; Female; Frontal Lobe; Humans; Male; Nerve Net; Neural Pathways; Pain Perception; Placebo Effect; Placebos; Psychological Distance; Suggestion; Young Adult
PubMed: 28264983
DOI: 10.1523/JNEUROSCI.2658-16.2017 -
JAMA Network Open Jan 2022Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Adverse events (AEs) after placebo treatment are common in randomized clinical drug trials. Systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide especially because concern about AEs is reported to be a reason for vaccination hesitancy.
OBJECTIVE
To compare the frequencies of AEs reported in the placebo groups of COVID-19 vaccine trials with those reported in the vaccine groups.
DATA SOURCES
For this systematic review and meta-analysis, the Medline (PubMed) and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched systematically using medical subheading terms and free-text keywords for trials of COVID-19 vaccines published up to July 14, 2021.
STUDY SELECTION
Randomized clinical trials of COVID-19 vaccines that investigated adults aged 16 years or older were selected if they assessed solicited AEs within 7 days of injection, included an inert placebo arm, and provided AE reports for both the vaccine and placebo groups separately. Full texts were reviewed for eligibility by 2 independent reviewers.
DATA EXTRACTION AND SYNTHESIS
Data extraction and quality assessment were performed independently by 2 reviewers, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and using the Cochrane risk-of-bias tool. Meta-analyses were based on random-effects models.
MAIN OUTCOMES AND MEASURES
The primary outcomes were the proportions of placebo recipients reporting overall, systemic, and local (injection-site) AEs as well as logarithmic odds ratios (ORs) to evaluate group differences. Outcomes were tested for significance using z tests with 95% CIs.
RESULTS
Twelve articles with AE reports for 45 380 participants (22 578 placebo recipients and 22 802 vaccine recipients) were analyzed. After the first dose, 35.2% (95% CI, 26.7%-43.7%) of placebo recipients experienced systemic AEs, with headache (19.3%; 95% CI, 13.6%-25.1%) and fatigue (16.7%; 95% CI, 9.8%-23.6%) being most common. After the second dose, 31.8% (95% CI, 28.7%-35.0%) of placebo recipients reported systemic AEs. The ratio between placebo and vaccine arms showed that nocebo responses accounted for 76.0% of systemic AEs after the first COVID-19 vaccine dose and for 51.8% after the second dose. Significantly more vaccine recipients reported AEs, but the group difference for systemic AEs was small after the first dose (OR, -0.47; 95% CI, -0.54 to -0.40; P < .001; standardized mean difference, -0.26; 95% CI, -0.30 to -0.22) and large after the second dose (OR, -1.36; 95% CI, -1.86 to -0.86; P < .001; standardized mean difference, -0.75; 95% CI, -1.03 to -0.47).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, significantly more AEs were reported in vaccine groups compared with placebo groups, but the rates of reported AEs in the placebo arms were still substantial. Public vaccination programs should consider these high rates of AEs in placebo arms.
Topics: Arm Injuries; COVID-19; COVID-19 Vaccines; Fatigue; Headache; Humans; Injections, Intramuscular; Placebos; SARS-CoV-2
PubMed: 35040967
DOI: 10.1001/jamanetworkopen.2021.43955 -
Frontiers in Bioscience (Scholar... Jan 2010The placebo effect has been extensively studied in many disease states, some of the most notable being pain and depression. Utilizing a Medline search, studies were... (Review)
Review
The placebo effect has been extensively studied in many disease states, some of the most notable being pain and depression. Utilizing a Medline search, studies were identified that reported on areas of the brain shown to be involved in either placebo analgesia or mood response. This paper presents a distillation of this research, in an effort to identify a common "placebo pathway" between mood and pain. Placebo-related responses to both analgesia and relief from depression were reported to be associated with an increase in activity in the frontal cortex and a decrease in activity in the thalamus.
Topics: Depression; Frontal Lobe; Humans; Pain; Placebos; Thalamus
PubMed: 20036932
DOI: 10.2741/s49 -
Contemporary Clinical Trials May 2012Randomized controlled trials have reported lower mortality among patients who adhere to placebo compared with those who do not. We explored this phenomenon by... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Randomized controlled trials have reported lower mortality among patients who adhere to placebo compared with those who do not. We explored this phenomenon by reanalyzing data from the placebo arm of the Beta Blocker Evaluation of Survival Trial (BEST), a randomized, double-blind, placebo-controlled trial of bucindolol and mortality.
AIMS
Our primary aim was to measure and explain the association between adherence to placebo and total mortality among the placebo-allocated participants in the BEST trial. Secondary aims included assessment of the association between placebo adherence and cause-specific mortality.
METHODS
Participants with "higher placebo adherence" were defined as having taken at least 75% of their placebo study medication over the entire course of each individual's participation in the study, while those with "lower placebo adherence" took <75%. Primary outcome was in-study all-cause mortality. To account for confounding, we adjusted for all available modifiable, non-modifiable and psychosocial variables.
RESULTS
Adherent participants had a significantly lower total mortality compared to less-adherent participants (HR=0.61, 95% Confidence Interval: 0.46-0.82). Adjusting for available confounders did not change the magnitude or significance of the estimates. When considering cause-specific mortality, CVD and pump failure showed similar associations.
CONCLUSIONS
Analyses of the BEST trial data support a strong association between adherence to placebo study medication and total mortality. While probably not due to publication bias or simple confounding by healthy lifestyle factors, the underlying explanation for the association remains a mystery. Prospective examination of this association is necessary to better understand the underlying mechanism of this observation.
Topics: Adrenergic beta-Antagonists; Confidence Intervals; Double-Blind Method; Female; Humans; Hypertension; Kaplan-Meier Estimate; Male; Medication Adherence; Middle Aged; Placebo Effect; Placebos; Propanolamines; Treatment Outcome; United States
PubMed: 22265975
DOI: 10.1016/j.cct.2011.12.003 -
Pain Nov 2018Network meta-analysis uses direct comparisons of interventions within randomized controlled trials and indirect comparisons across them. Network meta-analysis uses more... (Review)
Review
Network meta-analysis uses direct comparisons of interventions within randomized controlled trials and indirect comparisons across them. Network meta-analysis uses more data than a series of direct comparisons with placebo, and theoretically should produce more reliable results. We used a Cochrane overview review of acute postoperative pain trials and other systematic reviews to provide data to test this hypothesis. Some 261 trials published between 1966 and 2016 included 39,753 patients examining 52 active drug and dose combinations (27,726 given active drug and 12,027 placebo), in any type of surgery (72% dental). Most trials were small; 42% of patients were in trials with arms <50 patients, and 27% in trials with arms ≥100 patients. Response to placebo in third molar extraction fell by half in studies over 30 to 40 years (171 trials, 7882 patients given placebo). Network meta-analysis and Cochrane analyses provided very similar results (average difference 0.04 number needed to treat units), with no significant difference for almost all comparisons apart from some with small patient numbers or small effect size, or both. Network meta-analysis did not detect significant differences between effective analgesics. The similarity between network meta-analysis and Cochrane indirect analyses probably arose from stringent quality criteria in trials accepted in Cochrane reviews (with consequent low risk of bias) and consistency in methods and outcomes. Network meta-analysis is a useful analytical tool that increases our confidence in estimates of efficacy of analgesics in acute postoperative pain, in this case by providing similar results.
Topics: Adult; Analgesics; Female; Humans; Male; Network Meta-Analysis; Pain, Postoperative; Placebos; Retrospective Studies; Treatment Outcome
PubMed: 29965830
DOI: 10.1097/j.pain.0000000000001322 -
PloS One 2015Physicians around the world report to using placebos in a variety of situations and with varying degrees of frequency. Inconsistent methodologies, however, complicate... (Comparative Study)
Comparative Study
BACKGROUND
Physicians around the world report to using placebos in a variety of situations and with varying degrees of frequency. Inconsistent methodologies, however, complicate interpretation and prevent direct comparisons across studies. While US- and Canada-based physicians share similar professional standards, Canada harbours a less-litigious universal healthcare model with no formal placebo-related policy-factors that may impact how physicians view and use placebos.
METHODS
To compare American and Canadian data, we circulated an online survey to academic physicians practicing in Canada, collected anonymous responses, and extracted those of internists and rheumatologists for comparison to US data obtained through parallel methodologies.
RESULTS
Whereas our data show overall concordance across the border-from definitions to ethical limitations and therapeutic potential-differences between American- and Canadian-based placebo practices merit acknowledgement. For example, compared to 45%-80% among US-based respondents, only 23±7% of Canada-based respondents reported using placebos in clinical practice. However, 79±7% of Canada-respondents-a figure comparable to US data-professed to prescribing at least one form of treatment without proven or expected efficacy. Placebo interventions including unwarranted vitamins and herbal supplements (impure placebos) as well as sugar pills and saline injections (pure placebos) appear more common in Canada, where more doctors described placebos as "placebos" (rather than "medications") and used them as a "diagnostic" tool (rather than a means of placating patient demands for treatment).
INTERPRETATION
Cross-border variation in the use of clinical placebos appears minor despite substantial differences in health care delivery system, malpractice climate, and placebo-related policy. The prevalence of impure placebos in both Canadian and US clinics raises ethical and practical questions currently unaddressed by policy and warranting investigation.
Topics: Attitude of Health Personnel; Canada; Drug Prescriptions; Female; Humans; Male; Middle Aged; Physicians; Placebos; Plant Preparations; Practice Patterns, Physicians'; Surveys and Questionnaires; United States; Vitamins
PubMed: 26606749
DOI: 10.1371/journal.pone.0142804