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PloS One 2011It has been argued that placebos may not have important clinical impacts in general. However, there is increasing evidence of a publication bias among trials published... (Review)
Review
BACKGROUND
It has been argued that placebos may not have important clinical impacts in general. However, there is increasing evidence of a publication bias among trials published in journals. Therefore, we explored the potential for publication bias in randomized trials with active treatment, placebo, and no-treatment groups.
METHODS
Three-armed randomized trials of acupuncture, acupoint stimulation, and transcutaneous electrical stimulation were obtained from electronic databases. Effect sizes between treatment and placebo groups were calculated for treatment effect, and effect sizes between placebo and no-treatment groups were calculated for placebo effect. All data were then analyzed for publication bias.
RESULTS
For the treatment effect, small trials with fewer than 100 patients per arm showed more benefits than large trials with at least 100 patients per arm in acupuncture and acupoint stimulation. For the placebo effect, no differences were found between large and small trials. Further analyses showed that the treatment effect in acupuncture and acupoint stimulation may be subject to publication bias because study design and any known factors of heterogeneity were not associated with the small study effects. In the simulation, the magnitude of the placebo effect was smaller than that calculated after considering publication bias.
CONCLUSIONS
Randomized three-armed trials, which are necessary for estimating the placebo effect, may be subject to publication bias. If the magnitude of the placebo effect is assessed in an intervention, the potential for publication bias should be investigated using data related to the treatment effect.
Topics: Humans; Placebos; Publication Bias; Randomized Controlled Trials as Topic
PubMed: 21655196
DOI: 10.1371/journal.pone.0020679 -
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 -
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 -
Clinics (Sao Paulo, Brazil) Apr 2007To carry out a systematic review and meta-analysis of the efficacy of chemonucleolysis in the treatment of lumbar disc herniation. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To carry out a systematic review and meta-analysis of the efficacy of chemonucleolysis in the treatment of lumbar disc herniation.
METHODS
Clinical trials were selected from 3 electronic databases (The Cochrane Controlled Trials Register, MEDLINE, and EMBASE). Data were analyzed with the software STATA, using the meta command.
RESULTS
Twenty-two clinical trials were eligible. For chemonucleolysis versus placebo, the summary risk ratio estimate for pain relief as outcome was 1.51 (95% CI: 1.27-1.80). The summary estimate was 1.07 (95% CI: 0.95-1.20) for the comparison between chymopapain and collagenase. Regarding chemonucleolysis with chymopapain versus surgery, the fixed-effect summary estimate of effect for pain relief was 0.93 (95% CI: 0.88-0.98) with surgery as the reference group. In this case, heterogeneity was statistically significant.
CONCLUSIONS
Chemonucleolysis with chymopapain was superior to placebo and was as effective as collagenase in the treatment of lumbar disc prolapse. Results for studies comparing chemonucleolysis with surgery were heterogeneous, making it difficult to interpret the summary measure of effect.
Topics: Chymopapain; Collagenases; Controlled Clinical Trials as Topic; Databases, Bibliographic; Humans; Intervertebral Disc Chemolysis; Intervertebral Disc Displacement; Placebos; Randomized Controlled Trials as Topic
PubMed: 17505703
DOI: 10.1590/s1807-59322007000200013 -
PloS One 2016There are few drugs with proven efficacy in cutaneous leishmaniasis (CL), and pentavalent antimonial derivatives are still the main first-line therapeutic agents... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
There are few drugs with proven efficacy in cutaneous leishmaniasis (CL), and pentavalent antimonial derivatives are still the main first-line therapeutic agents worldwide, despite their recognized high toxicities. Randomized controlled clinical trials assessing the efficacy and safety of new therapeutic modalities are of high priority, and the definition of the design of such trials raises debate about the use of placebo as a comparator. To support the use of placebo as a comparator, two main points need to be addressed: 1--the cure rate without any therapeutic intervention and 2--the damage caused by CL and its impact on patients.
OBJECTIVE
The aim of this study was to systematically assess the spontaneous cure rate for American CL and to broaden the discussion about placebo use in CL trials.
METHODS
The PRISMA guidelines for systematic reviews and the Cochrane manual were followed. The sources used were the PubMed and LILACS databases. Studies were included if they reported cure rates using placebo or no treatment in American CL.
RESULTS
Thirteen studies of a total of 352 patients were ultimately included in this review. The summarized global cure rates for all Leishmania species according to the intention-to-treat analyses performed at approximately three ("initial cure") and nine ("definitive cure") months after "no treatment" or placebo use were 26% (CI95%: 16 to 40%) and 26% (CI95%:16 to 38%), respectively. Notably, a significantly lower cure rate was observed for L. braziliensis infection (6.4%, CI95%:0.2 to 20%) than for L. mexicana infection (44%, CI95%:19 to 72%), p = 0.002. Of note, relapse occurred in 20% of patients with initial healing (CI95%:9.2 to 38.9%).
CONCLUSION
These results clearly demonstrate a low spontaneous cure rate following no-treatment or placebo use, confirming that this strategy for the control group in CL studies expose patients to greater morbidity, especially for CL caused by L. braziliensis. Therefore, from this point, the crucial question to consider regarding placebo use is the seriousness of the suffering caused by this disease.
Topics: Antiprotozoal Agents; Humans; Leishmaniasis, Cutaneous; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 26894430
DOI: 10.1371/journal.pone.0149697 -
Canadian Journal of Psychiatry. Revue... Apr 2011The history of placebos in psychiatry can be understood only in the context of randomized controlled trials (RCTs). Placebo treatments are as old as medicine itself, and... (Review)
Review
The history of placebos in psychiatry can be understood only in the context of randomized controlled trials (RCTs). Placebo treatments are as old as medicine itself, and are particularly effective in dealing with psychosomatic symptoms. In psychiatry, placebos have mainly been featured in clinical drug trials. The earliest controlled trial in psychiatry (not involving drugs) occurred in 1922, followed by the first crossover studies during the 1930s. Meanwhile the concept of randomization was developed during the interwar years by British statistician Ronald A Fisher, and introduced in 3 trials of tuberculosis drugs between 1947 and 1951. These classic studies established the RCT as the gold standard in pharmaceutical trials, and its status was cemented during the mid-1950s. Nevertheless, while the placebo became established as a standard measure of drug action, placebo treatments became stigmatized as unethical. This is unfortunate, as they constitute one of the most powerful therapies in psychiatry. In recent years, moreover, the dogma of the placebo-controlled trial as the only acceptable data for drug licensing is also being increasingly discredited. This backlash has had 2 sources: one is the recognition that the US Food and Drug Administration has been too lax in permitting trials controlled with placebos alone, rather than also using an active agent as a test of comparative efficacy. In addition, there is evidence that in the hands of the pharmaceutical industry, the scientific integrity of RCTs themselves has been degraded into a marketing device. The once-powerful placebo is thus threatened with extinction.
Topics: Cross-Over Studies; Ethics, Medical; Ethics, Research; History, 20th Century; Humans; Placebo Effect; Placebos; Psychiatry; Psychophysiologic Disorders; Psychosomatic Medicine; Randomized Controlled Trials as Topic
PubMed: 21507275
DOI: 10.1177/070674371105600402 -
The Yale Journal of Biology and Medicine Sep 2013Studies designed to elicit the full strength of the placebo effect differ from those in which the placebo effect represents a nuisance factor to be accounted for in...
Studies designed to elicit the full strength of the placebo effect differ from those in which the placebo effect represents a nuisance factor to be accounted for in order to establish the efficacy of a treatment. In the latter, informed consent is the rule; in the first, while consent may be informed in some narrow sense of the word, deception is common. However, the trickery of placebo experimentation goes beyond straightforward lies to include the use of crafty ambiguities, half-truths, and deliberate omissions in scripts read to the subjects of these studies. As words come to resemble therapeutic agents in their own right, it is only to be expected that researchers would methodically exploit verbal effects to evoke the responses they are looking for. Even experiments in which placebo is disclosed as placebo have used language in leading and misleading ways. Such studies are conducted in the hope of yielding results that might translate into clinical practice, but it should be noted that good clinical practice has a placebo value of its own--that is, confers a benefit over and beyond the specific effects of treatments--even if nothing like a sugar pill is administered.
Topics: Biomedical Research; Deception; Ethics, Research; Female; Humans; Male; Placebos
PubMed: 24058307
DOI: No ID Found -
Journal of the Royal Society of Medicine Jan 2000
Topics: Germany; History, 19th Century; Homeopathy; Humans; Placebo Effect; Placebos
PubMed: 10700854
DOI: 10.1177/014107680009300119 -
Antimicrobial Agents and Chemotherapy Oct 2017Finafloxacin is a novel fluoroquinolone exhibiting enhanced activity under acidic conditions and a broad-spectrum antibacterial profile. The present study assessed the... (Randomized Controlled Trial)
Randomized Controlled Trial
Finafloxacin is a novel fluoroquinolone exhibiting enhanced activity under acidic conditions and a broad-spectrum antibacterial profile. The present study assessed the pharmacokinetic properties and the safety and tolerability of finafloxacin following intravenous infusions. In this mixed-parallel-group, crossover study, healthy male and female volunteers received single ascending doses (18 volunteers, 200 to 1,000 mg) or multiple ascending doses (40 volunteers, 600 to 1,000 mg) of finafloxacin or placebo. Plasma and urine samples were collected by a dense sampling scheme to determine the pharmacokinetics of finafloxacin using a noncompartmental approach. Standard safety and tolerability data were documented. Finafloxacin had a volume of distribution of 90 to 127 liters (range) at steady state and 446 to 550 liters at pseudoequilibrium, indicating the elimination of a large fraction before pseudoequilibrium was reached. Areas under the concentration-time curves and maximum plasma concentrations (geometric means) increased slightly more than proportionally (6.73 to 45.9 μg · h/ml and 2.56 to 20.2 μg/ml, respectively), the terminal elimination half-life increased (10.6 to 17.1 h), and the urinary recovery decreased (44.2% to 31.7%) with increasing finafloxacin doses (single doses of 200 to 1,000 mg). The pharmacokinetic profiles suggested multiphasic elimination by both glomerular filtration and saturable tubular secretion. The values of the parameters were similar for single and multiple administrations. The coefficient of variation for the between-subject variability of exposure ranged from 10% (≤600 mg) to 38% (>600 mg). Adverse events were mild and nonspecific, with no dependence of adverse events on dose or treatment (including placebo) being detected. Despite a relatively high interindividual variability at higher doses, the level of exposure following intravenous administration of finafloxacin appears to be predictable. Individual elimination processes should be evaluated in more detail. Finafloxacin exhibited a favorable safety and tolerability profile. (This study has been registered at ClinicalTrials.gov under registration no. NCT01910883.).
Topics: Administration, Intravenous; Anti-Bacterial Agents; Double-Blind Method; Female; Fluoroquinolones; Healthy Volunteers; Humans; Male; Placebos
PubMed: 28784673
DOI: 10.1128/AAC.01122-17 -
Indian Journal of Medical Ethics 2021The world is currently facing another severe pandemic, Covid-19, just four decades after the start of AIDS, and the still increasing incidence of HIV infection continues...
The world is currently facing another severe pandemic, Covid-19, just four decades after the start of AIDS, and the still increasing incidence of HIV infection continues to be one of the greatest global health challenges. The way the latter was confronted is of fundamental importance for a serious discussion on global health, ethics and human rights, and this experience could and can still be applied to Covid-19. The Covid-19 pandemic has specific characteristics and these will be discussed, in relation to vaccine research and especially to the global right to equal access to products proven to be safe and effective. The article focusses primarily on issues related to Covid-19 vaccines, especially the appropriate use and limits on placebo, the right to post-trial access to placebo arm participants, and the use of an active control for subsequent Phase-3 trials after the approval of other safe and efficacious vaccines. Most importantly, it will emphasise that access to Covid-19 vaccines is a human right, which presupposes the establishment of appropriate ethical standards to ensure universal, equal, and affordable access to healthcare and to vaccines for all, and the imperative need for suspension of patents for products developed for Covid-19. It will consider the role of social determinants that contribute to the severity of Covid-19 and that must be addressed to effectively curb the current syndemic.
Topics: Biomedical Research; COVID-19; COVID-19 Vaccines; Ethics, Medical; Guidelines as Topic; Health Services Accessibility; Human Rights; Humans; Pandemics; Placebos; SARS-CoV-2
PubMed: 33908350
DOI: 10.20529/IJME.2021.027