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Annals of African Medicine 2017The use of control group in clinical trials has been universally acclaimed by researchers to effectively help discriminate between the actual effects of an intervention... (Review)
Review
The use of control group in clinical trials has been universally acclaimed by researchers to effectively help discriminate between the actual effects of an intervention and those arising from other factors. However, the choice of the control that provided both scientific and ethical acceptability among researchers has been a source of intense debate. We conducted a literature search on the use of placebo and active controls in clinical trials and X-ray the arguments for and against both choices in randomized control trials and concluded by highlighting the scenarios where the use of placebo is justified.
Topics: Antipsychotic Agents; Biomedical Research; Ethics, Medical; Humans; Mental Disorders; Placebos; Randomized Controlled Trials as Topic
PubMed: 28671148
DOI: 10.4103/aam.aam_211_16 -
Parkinsonism & Related Disorders Aug 2016Previous studies have assessed the placebo response in clinical trials on PD using the individual data of participants from the placebo-assigned group. The aim of this... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Previous studies have assessed the placebo response in clinical trials on PD using the individual data of participants from the placebo-assigned group. The aim of this study was to examine the group predictors of the placebo response in randomized placebo-controlled trials on PD using a meta-analysis with meta-regression models.
METHODS
The placebo response was defined as the mean change in the UPDRS part III score from baseline to the primary efficacy end point in the placebo group. The impacts of the predictors were assessed with meta-regression analyses, and significant predictors were used in a multivariable analysis. Subgroup analyses were conducted in studies that enrolled PD patients with or without motor fluctuations.
RESULTS
Forty-eight studies (consisting of 5618 participants on placebo) were included. Motor fluctuation and baseline UPDRS part III score were significant predictors in the univariable analyses. The high baseline UPDRS part III score (β = -0.21, 95% CI -0.34, -0.08; p = 0.005) significantly increased the magnitude of the positive placebo response in the multivariable analysis. In the subgroup analyses, the positive placebo response was significant only in studies that enrolled patients with motor fluctuations; high baseline UPDRS part III score and low baseline daily levodopa dose increased the positive placebo response independently in the subgroup with motor fluctuations.
CONCLUSION
Researchers should consider the positive placebo response when they design clinical trials in advanced PD patients with motor fluctuations and severe motor symptoms. Baseline daily levodopa dose may be the independent predictor in studies that enrolled fluctuating patients.
Topics: Antiparkinson Agents; Clinical Trials as Topic; Humans; Levodopa; Parkinson Disease; Placebos; Predictive Value of Tests; Severity of Illness Index
PubMed: 27237106
DOI: 10.1016/j.parkreldis.2016.05.019 -
The Cochrane Database of Systematic... Apr 2021Dietary supplements with ginseng, or ginseng alone, are widely used for a broad range of conditions, including erectile dysfunction. Ginseng is particularly popular in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dietary supplements with ginseng, or ginseng alone, are widely used for a broad range of conditions, including erectile dysfunction. Ginseng is particularly popular in Asian countries. Individual studies assessing its effects are mostly small, of uneven methodological quality and have unclear results.
OBJECTIVES
To assess the effects of ginseng on erectile dysfunction.
SEARCH METHODS
We conducted systematic searches on multiple electronic databases, including CENTRAL, MEDLINE, Embase, CINAHL, AMED, and loco-regional databases of east Asia, from their inceptions to 30 January 2021 without restrictions on language and publication status. Handsearches included conference proceedings.
SELECTION CRITERIA
We included randomized or quasi-randomized controlled trials that evaluated the use of any type of ginseng as a treatment for erectile dysfunction compared to placebo or conventional treatment.
DATA COLLECTION AND ANALYSIS
Two authors independently classified studies and three authors independently extracted data and assessed risk of bias in the included studies. We rated the certainty of evidence according to the GRADE approach.
MAIN RESULTS
We included nine studies with 587 men with mild to moderate erectile dysfunction, aged from 20 to 70 years old. The studies all compared ginseng to placebo. We found only short-term follow-up data (up to 12 weeks). Primary outcomes Ginseng appears to have a trivial effect on erectile dysfunction when compared to placebo based on the Erectile Function Domain of the International Index of Erectile Function (IIEF)-15 instrument (scale: 1 to 30, higher scores imply better function; mean difference [MD] 3.52, 95% confidence interval [CI] 1.79 to 5.25; I² = 0%; 3 studies; low certainty evidence) assuming a minimal clinically important difference (MCID) of 4. Ginseng probably also has a trivial effect on erectile function when compared to placebo based on the IIEF-5 instrument (scale: 1 to 25, higher scores imply better function; MD 2.39, 95% CI 0.89 to 3.88; I² = 0%; 3 studies; moderate certainty evidence) assuming a MCID of 5. Ginseng may have little to no effect on adverse events compared to placebo (risk ratio [RR] 1.45, 95% CI 0.69 to 3.03; I² = 0%; 7 studies; low certainty evidence). Based on 86 adverse events per 1000 men in the placebo group, this would correspond to 39 more adverse events per 1000 (95% CI 27 fewer to 174 more). Secondary outcomes Ginseng may improve men's self-reported ability to have intercourse (RR 2.55, 95% CI 1.76 to 3.69; I² = 23%; 6 studies; low certainty evidence). Based on 207 per 1000 men self-reporting the ability to have intercourse in the placebo group, this would correspond to 321 more men (95% CI 158 more to 558 more) per 1000 self-reporting the ability to have intercourse. Ginseng may have a trivial effect on men's satisfaction with intercourse based on the Intercourse Satisfaction Domain of the IIEF-15 (scale: 0 to 15, higher scores imply greater satisfaction; MD 1.19, 95% CI 0.41 to 1.97; I²=0%; 3 studies; low certainty evidence) based on a MCID of 25% improvement from baseline. It may also have a trivial effect on men's satisfaction with intercourse based on item 5 of the IIEF-5 (scale: 0 to 5, higher scores imply more satisfaction; MD 0.60, 95% CI 0.02 to 1.18; 1 study; low certainty evidence) based on a MCID of 25% improvement from baseline. No study reported quality of life as an outcome. We found no trial evidence to inform comparisons to other treatments for erectile dysfunction, such as phosphodiesterase-5 inhibitors. We were unable to conduct any predefined subgroup analyses.
AUTHORS' CONCLUSIONS
Based on mostly low certainty evidence, ginseng may only have trivial effects on erectile function or satisfaction with intercourse compared to placebo when assessed using validated instruments. Ginseng may improve men's self-reported ability to have intercourse. It may have little to no effect on adverse events. We found no trial evidence comparing ginseng to other agents with a more established role in treating erectile dysfunction, such as phosphodiesterase-5 inhibitors.
Topics: Adult; Aged; Coitus; Confidence Intervals; Erectile Dysfunction; Humans; Male; Middle Aged; Panax; Patient Satisfaction; Phytotherapy; Placebos; Randomized Controlled Trials as Topic; Young Adult
PubMed: 33871063
DOI: 10.1002/14651858.CD012654.pub2 -
Beneficial Microbes Oct 2017Our objective was to conduct a systematic review and meta-analysis for the use of modified (heat-killed or sonicated) probiotics for the efficacy and safety to prevent... (Meta-Analysis)
Meta-Analysis Review
Our objective was to conduct a systematic review and meta-analysis for the use of modified (heat-killed or sonicated) probiotics for the efficacy and safety to prevent and treat various diseases. Recent clinical research has focused on living strains of probiotics, but use in high-risk patients and potential adverse reactions including bacteremia has focused interest on alternatives to the use of live probiotics. We searched MEDLINE/PubMed, Embase, Cochrane Central Register of Controlled Trials, CINAHL, Alt Health Watch, Web of Science, Scopus, PubMed, from inception to February 14, 2017 for randomised controlled trials involving modified probiotic strains. The primary outcome was efficacy to prevent or treat disease and the secondary outcome was incidence of adverse events. A total of 40 trials were included (n=3,913): 14 trials (15 arms with modified probiotics and 20 control arms) for the prevention of diseases and 26 trials (29 arms with modified probiotics and 32 control arms) for treatment of various diseases. Modified microbes were compared to either placebo (44%), or the same living probiotic strain (39%) or to only standard therapies (17%). Modified microbes were not significantly more or less effective than the living probiotic in 86% of the preventive trials and 69% of the treatment trials. Modified probiotic strains were significantly more effective in 15% of the treatment trials. Incidence rates of adverse events were similar for modified and living probiotics and other control groups, but many trials did not collect adequate safety data. Although several types of modified probiotics showed significant efficacy over living strains of probiotics, firm conclusions could not be reached due to the limited number of trials using the same type of modified microbe (strain, daily dose and duration) for a specific disease indication. Further research may illuminate other strains of modified probiotics that may have potential as clinical biotherapeutics.
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Incidence; Placebos; Probiotics; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 28884589
DOI: 10.3920/BM2017.0032 -
Scientific Reports Oct 2016Considered an antidepressant and anti-anxiety agent, Hypericum perforatum affects multiple neurotransmitters in a non-competitive synergistic manner, and may have... (Meta-Analysis)
Meta-Analysis Review
Considered an antidepressant and anti-anxiety agent, Hypericum perforatum affects multiple neurotransmitters in a non-competitive synergistic manner, and may have nootropic potential. We quantitatively reviewed the pre-clinical literature to examine if there is a cognitive-enhancing effect of H. perforatum in healthy rodents. Additionally, within these studies, we compared the effects observed in intact rodents versus those whose performance has been impaired, mostly through stress manipulations. The meta-analysis incorporated studies that examined the effect of H. perforatum versus placebo on memory indices of task performance. All analyses were based on weighting different studies according to their inverse variance. Thirteen independent studies (published 2000-2014) involving 20 experimental comparisons met our inclusion criteria. The results showed a large positive effect of H. perforatum on cognitive performance for intact, healthy rodents (d = 1.11), though a larger effect emerged for stress-impaired rodents (d = 3.10 for restraint stress). The positive effect on intact rodents was observed in tasks assessing reference memory as well as working memory, and was not moderated by the type of memory or motivation (appetitive versus aversive). Thus, while primarily considered as a medication for depression, H. perforatum shows considerable nootropic potential in rodents.
Topics: Animals; Hypericum; Memory; Nootropic Agents; Placebos; Rodentia
PubMed: 27762349
DOI: 10.1038/srep35700 -
The Cochrane Database of Systematic... Apr 2018Panic disorder is characterised by repeated, unexpected panic attacks, which represent a discrete period of fear or anxiety that has a rapid onset, reaches a peak within... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Panic disorder is characterised by repeated, unexpected panic attacks, which represent a discrete period of fear or anxiety that has a rapid onset, reaches a peak within 10 minutes, and in which at least four of 13 characteristic symptoms are experienced, including racing heart, chest pain, sweating, shaking, dizziness, flushing, stomach churning, faintness and breathlessness. It is common in the general population with a lifetime prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions. Amongst pharmacological agents, the National Institute for Health and Care Excellence (NICE) and the British Association for Psychopharmacology consider antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), as the first-line treatment for panic disorder, due to their more favourable adverse effect profile over monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). Several classes of antidepressants have been studied and compared, but it is still unclear which antidepressants have a more or less favourable profile in terms of effectiveness and acceptability in the treatment of this condition.
OBJECTIVES
To assess the effects of antidepressants for panic disorder in adults, specifically:1. to determine the efficacy of antidepressants in alleviating symptoms of panic disorder, with or without agoraphobia, in comparison to placebo;2. to review the acceptability of antidepressants in panic disorder, with or without agoraphobia, in comparison with placebo; and3. to investigate the adverse effects of antidepressants in panic disorder, with or without agoraphobia, including the general prevalence of adverse effects, compared to placebo.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders' (CCMD) Specialised Register, and CENTRAL, MEDLINE, EMBASE and PsycINFO up to May 2017. We handsearched reference lists of relevant papers and previous systematic reviews.
SELECTION CRITERIA
All double-blind, randomised, controlled trials (RCTs) allocating adults with panic disorder to antidepressants or placebo.
DATA COLLECTION AND ANALYSIS
Two review authors independently checked eligibility and extracted data using a standard form. We entered data into Review Manager 5 using a double-check procedure. Information extracted included study characteristics, participant characteristics, intervention details and settings. Primary outcomes included failure to respond, measured by a range of response scales, and treatment acceptability, measured by total number of dropouts for any reason. Secondary outcomes included failure to remit, panic symptom scales, frequency of panic attacks, agoraphobia, general anxiety, depression, social functioning, quality of life and patient satisfaction, measured by various scales as defined in individual studies. We used GRADE to assess the quality of the evidence for each outcome MAIN RESULTS: Forty-one unique RCTs including 9377 participants overall, of whom we included 8252 in the 49 placebo-controlled arms of interest (antidepressant as monotherapy and placebo alone) in this review. The majority of studies were of moderate to low quality due to inconsistency, imprecision and unclear risk of selection and performance bias.We found low-quality evidence that revealed a benefit for antidepressants as a group in comparison with placebo in terms of efficacy measured as failure to respond (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.66 to 0.79; participants = 6500; studies = 30). The magnitude of effect corresponds to a number needed to treat for an additional beneficial outcome (NNTB) of 7 (95% CI 6 to 9): that means seven people would need to be treated with antidepressants in order for one to benefit. We observed the same finding when classes of antidepressants were compared with placebo.Moderate-quality evidence suggested a benefit for antidepressants compared to placebo when looking at number of dropouts due to any cause (RR 0.88, 95% CI 0.81 to 0.97; participants = 7850; studies = 30). The magnitude of effect corresponds to a NNTB of 27 (95% CI 17 to 105); treating 27 people will result in one person fewer dropping out. Considering antidepressant classes, TCAs showed a benefit over placebo, while for SSRIs and serotonin-norepinephrine reuptake inhibitor (SNRIs) we observed no difference.When looking at dropouts due to adverse effects, which can be considered as a measure of tolerability, we found moderate-quality evidence showing that antidepressants as a whole are less well tolerated than placebo. In particular, TCAs and SSRIs produced more dropouts due to adverse effects in comparison with placebo, while the confidence interval for SNRI, noradrenergic reuptake inhibitors (NRI) and other antidepressants were wide and included the possibility of no difference.
AUTHORS' CONCLUSIONS
The identified studies comprehensively address the objectives of the present review.Based on these results, antidepressants may be more effective than placebo in treating panic disorder. Efficacy can be quantified as a NNTB of 7, implying that seven people need to be treated with antidepressants in order for one to benefit. Antidepressants may also have benefit in comparison with placebo in terms of number of dropouts, but a less favourable profile in terms of dropout due to adverse effects. However, the tolerability profile varied between different classes of antidepressants.The choice of whether antidepressants should be prescribed in clinical practice cannot be made on the basis of this review.Limitations in results include funding of some studies by pharmaceutical companies, and only assessing short-term outcomes.Data from the present review will be included in a network meta-analysis of psychopharmacological treatment in panic disorder, which will hopefully provide further useful information on this issue.
Topics: Adult; Agoraphobia; Antidepressive Agents; Humans; Numbers Needed To Treat; Panic Disorder; Patient Dropouts; Placebos; Randomized Controlled Trials as Topic; Treatment Failure
PubMed: 29620793
DOI: 10.1002/14651858.CD010676.pub2 -
JAMA Psychiatry Jan 2022Single-blind placebo run-in (PRI) periods are common in randomized clinical trials (RCTs) of treatment for depression. They aim to increase sensitivity to detect drug... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Single-blind placebo run-in (PRI) periods are common in randomized clinical trials (RCTs) of treatment for depression. They aim to increase sensitivity to detect drug effects; however, the association of PRI periods with study outcomes remains unclear. This is concerning given the costs of PRI periods to patients and investigators.
OBJECTIVE
To examine the association of the use of PRI periods with the placebo response, drug response, and drug-placebo difference among RCTs of antidepressants.
DATA SOURCES
MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and PsycINFO, as well as repositories of unpublished studies, were systematically searched up to July 2021.
STUDY SELECTION
Included studies were double-blind, placebo-controlled RCTs of antidepressant medication among adults with depressive disorders.
DATA EXTRACTION AND SYNTHESIS
Data were extracted into a coding sheet, including the characteristics of studies, the characteristics of PRI periods, and the outcomes of studies.
MAIN OUTCOMES AND MEASURES
Study outcomes were the primary depression symptom measure reported by the RCT. These outcomes were used to calculate effect sizes (Hedges g) of the within-group drug response and placebo response as well as the drug-placebo difference. Random-effects meta-analysis was used to calculate effect sizes, and subgroup analyses were used to compare outcomes depending on use of PRI periods.
RESULTS
A total of 347 trials (representing 89 183 participants) were included; 174 studies (50%) reported using a single-blind PRI period. Response outcome data were available for 189 studies. Studies using PRI periods reported a smaller placebo response (g = 1.05 [95% CI, 0.98-1.11]; I2 = 82%) than studies that did not use a PRI period (g = 1.15 [95% CI, 1.09-1.21]; I2 = 81%; P = .02). Subgroup analysis showed a larger drug response size among studies that did not use a PRI period (g = 1.55 [95% CI, 1.49-1.61]; I2 = 85%) than those that did use a PRI period (g = 1.42 [95% CI, 1.36-1.48]; I2 = 81%; P = .001). The drug-placebo difference did not differ by use of PRI periods (g = 0.33 [95% CI, 0.29-0.38]; I2 = 47% for use of a PRI period vs g = 0.34 [95% CI, 0.30-0.38]; I2 = 54% for no use of PRI periods; P = .92). The likelihood of response to drug vs placebo also did not differ between studies that used a PRI period (odds ratio, 1.89 [95% CI, 1.76-2.03]) and those that did not use a PRI period (odds ratio, 1.77 [95% CI, 1.65-1.89]; P = .18).
CONCLUSIONS AND RELEVANCE
This study suggests that RCTs using PRI periods yield smaller within-group changes across both placebo and drug groups compared with RCTs without PRI periods. The reduction in effect size across groups was equivalent in magnitude. Consequently, PRI studies do not observe larger drug-placebo differences, suggesting that they do not increase trial sensitivity. As such, given the resources and probable deception required and risk to external validity, the practice of using PRI periods in RCTs of antidepressants should be ended.
Topics: Antidepressive Agents; Humans; Placebos; Randomized Controlled Trials as Topic; Single-Blind Method
PubMed: 34757405
DOI: 10.1001/jamapsychiatry.2021.3204 -
Alcohol and Alcoholism (Oxford,... Oct 2021Previous research indicates that acute alcohol intoxication and placebo can inhibit people's control over consumption behaviour and heighten attentional bias (AB)...
AIMS
Previous research indicates that acute alcohol intoxication and placebo can inhibit people's control over consumption behaviour and heighten attentional bias (AB) towards alcohol-related stimuli and craving. We designed a study to disentangle anticipated from pharmacological effects of alcohol in order to gain a clearer view of their relative contributions to alcohol consumption.
METHODS
In a within-participants design (moderate alcohol dose, placebo and control), and over a minimum 2-week period, participants completed a battery of questionnaires and cognitive tasks, followed by a bogus taste task to measure ad libitum consumption.
RESULTS
Both alcohol preload and placebo resulted in cognitive and psychological changes, including impaired inhibitory control, heightened AB and craving. However, ad libitum consumption only increased following alcohol and not placebo. Furthermore, inhibitory control impairments did not mediate the relationship between initial intoxication and ad libitum consumption, and findings indicate that increases in craving may mediate this association.
CONCLUSION
Psychological processes such as craving may be more important in driving consummatory behaviour relative to transient changes in cognitive processes, such as inhibitory control.
Topics: Adult; Alcohol Drinking; Attentional Bias; Craving; Executive Function; Female; Humans; Male; Mediation Analysis; Placebos; Research Design; Young Adult
PubMed: 33693481
DOI: 10.1093/alcalc/agab011 -
The Cochrane Database of Systematic... Jun 2015This review has been withdrawn due to non‐compliance with Cochrane's Commercial Sponsorship Policy. The editorial group responsible for this previously published... (Review)
Review
This review has been withdrawn due to non‐compliance with Cochrane's Commercial Sponsorship Policy. The editorial group responsible for this previously published document have withdrawn it from publication.
Topics: Antidepressive Agents; Dysthymic Disorder; Humans; Placebos; Randomized Controlled Trials as Topic
PubMed: 26087170
DOI: 10.1002/14651858.CD001130.pub2 -
British Journal of Community Nursing Apr 2019
Topics: Community Health Nursing; England; Humans; Nurse Practitioners; Placebos; Practice Patterns, Nurses'; State Medicine
PubMed: 30969857
DOI: 10.12968/bjcn.2019.24.4.196