The relation between the placebo response, observed treatment effect, and failure to meet primary endpoint: A systematic review of clinical trials of preventative pharmacological migraine treatments

Cephalalgia ◽  
2020 ◽  
pp. 033310242096002
Author(s):  
Kathryn Evans ◽  
Heather Romero ◽  
Egilius LH Spierings ◽  
Nathaniel Katz
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Primary Endpoint ◽  
Response Rate ◽  
Placebo Response ◽  
Cochrane Central Register ◽  
Double Blind ◽  
Assay Sensitivity ◽  
Central Register ◽  
Significant Difference

Objective To evaluate the association between the degree of response to placebo in migraine studies and the observed difference between drug and placebo across studies of preventative treatments for migraine. Methods A systematic review was performed using MEDLINE and the Cochrane Central Register of Controlled Clinical Trials from January 1988 to June 2019. Randomized, double-blind, parallel-group, placebo-controlled trials on oral or injection preventative treatments for migraine were included. Single- and multi-variable linear regression analyses were performed on the placebo-subtracted response rate (i.e. placebo responders subtracted from active responders), and the proportion of placebo responders. Fisher’s exact tests were performed on the level of placebo response and the success in meeting the study’s primary endpoint. Results After adjusting for route of administration and number of randomized subjects, there was a statistically significant association between the proportion of patients who were placebo responders and the placebo-subtracted response rate (b = −0.27, p = 0.02). There was a statistically significant difference in trial success rate (60%) between studies with ≤20% placebo responders and studies with > 30% placebo responders ( p = 0.03). Conclusion Considering the detrimental impact that high placebo response can have on clinical trials, it is imperative to find effective solutions to decrease the placebo response and increase assay sensitivity.

scholarly journals EFFECTIVENESS OF ACAMPROSATE FOR TINNITUS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF CLINICAL TRIALS

2021 ◽  
Author(s):  
Osmar Clayton Person ◽  
Fernando Veiga Angelico Junior ◽  
Rodrigo Lima de Godoy Santos ◽  
William Marasini de Rezende ◽  
Maria Fernanda Giusti ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Medical Science ◽  
Placebo Response ◽  
Cochrane Central Register ◽  
Significant Difference ◽  
Tinnitus Treatment

Introduction: The effectiveness of tinnitus treatment represents a huge gap in the medical science. Acamprosate is a glutamatergic antagonist drug and GABA-agonist that could be used to control tinnitus due to its action on peripheral and central neurotransmission. Purpose: To assess the effectiveness of acamprosate in the treatment of tinnitus. Material and Methods: This is a systematic review and we searched for randomized clinical trials linking acamprosate to tinnitus in six databases: Cochrane - Central Register of Controlled Trials - CENTRAL (2021), PUBMED (1966-2021), EMBASE (1974-2021), IBECS (1982-2021), QINSIGHT (2021) and SCOPUS (2021). Two researchers independently extracted the data and assessed the quality of the studies. Results: Two trials involving 121 patients were included. The methodological quality of these studies was low. Both studies evaluated as primary outcome the efficacy of acamprosate in improving tinnitus. The meta-analysis by random model resulted in no significant difference between the groups treated with acamprosate and placebo (RR = 3,69, 95% CI 0,87-15,62; p=0,08), considering tinnitus improvement. Conclusions: There is no evidence that acamprosate is effective for tinnitus treatment. We recommend new trials using rigorous methodology. Randomization and blinding should be of the highest quality, given the subjective nature of tinnitus and the strong likelihood of a placebo response. The CONSORT statement should be used in the design and reporting of future studies.

scholarly journals Azithromycin in patients with Covid-19; a systematic review and metanalysis

2021 ◽  
Author(s):  
Luis Ayerbe ◽  
Ivo Forgnone ◽  
Carlos Risco-Risco ◽  
Maria Perez-Pinar ◽  
Salma Ayis
Keyword(s):  
Systematic Review ◽  
Clinical Severity ◽  
Future Research ◽  
Controlled Trials ◽  
Clinical Settings ◽  
Cochrane Central Register ◽  
Random Effects Models ◽  
Central Register ◽  
Significant Difference ◽  
Observational Design

Background: Azithromycin (AZM) has been widely used in the management of Covid-19. However, the evidence on its actual effects remains disperse and difficult to apply in clinical settings. This systematic review and metanalysis summarizes the studies on the beneficial and adverse effect of AZM in patients with Covid-19. Methods: The PRISMA 2020 statement criteria were followed. Randomized controlled trials (RCTs) and observational studies comparing clinical outcomes of patients treated, and not treated, with AZM, indexed until the 5th of July 2021, were searched in PubMed, Embase, The Web of Science, Scopus, The Cochrane Central Register of Controlled Trials, and MedRXivs. We used Random-effects models to estimate pooled effect size from aggregate data. Results: The initial search produced 4950 results. Finally, 16 studies, five RCTs and 11 with an observational design, with a total of 22984 patients, were included. The metanalysis showed no difference in mortality for those treated, or not, with AZM, OR: 0.95 (0.79-1.13). There was also no significant difference for those treated, and not, with AZM in need for hospital admission or time to admission from ambulatory settings, clinical severity, need for intensive care, or adverse effects. Conclusions: These results presented in this review do not support the use of AZM in the management of Covid-19. They also show that any harm caused to the patient who received it is unlikely. Future research on treatment for patients with Covid-19 may need to focus on other drugs

scholarly journals Systematic Review of Randomized Clinical Trials of Acupressure Therapy for Primary Dysmenorrhea

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Hui-ru Jiang ◽  
Shuang Ni ◽  
Jin-long Li ◽  
Miao-miao Liu ◽  
Ji Li ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Statistical Analysis ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Primary Dysmenorrhea ◽  
Randomized Controlled ◽  
Central Register

The evidence of acupressure is limited in the management of dysmenorrhea. To evaluate the efficacy of acupressure in the treatment of primary dysmenorrhea based on randomized controlled trials (RCTs), we searched MEDLINE, the Chinese Biomedical Database (CBM), and the Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception until March 2012. Two reviewers independently selected articles and extracted data. Statistical analysis was performed with RevMan 5.1 software. Eight RCTs were identified from the retrieved 224 relevant records. Acupressure improved pain measured with VAS (−1.41 cm 95% CI [−1.61, −1.21]), SF-MPQ at the 3-month followup (WMD −2.33, 95% CI [−4.11, −0.54]) and 6-month followup (WMD −4.67, 95% CI [−7.30, −2.04]), and MDQ at the 3-month followup (WMD −2.31, 95% CI [−3.74, −0.87]) and 6-month followup (WMD −4.67, 95% CI [−7.30, −2.04]). All trials did not report adverse events. These results were limited by the methodological flaws of trials.

scholarly journals Acupuncture in oncological pain relief: A systematic review of randomized clinical trials

2021 ◽  
Vol 34 ◽  
Author(s):  
Michel Marcos Dalmedico ◽  
Caroline Machado de Toledo ◽  
Paula Karina Hembecker ◽  
Juliana Londero Silva Ávila ◽  
Chayane Karla Lucena de Carvalho ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Cancer Pain ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Cochrane Central Register ◽  
Opioid Use ◽  
Central Register ◽  
Considerable Impact ◽  
Analgesic Use

Abstract Introduction: Cancer pain has a considerable impact on patients’ health and quality of life, and its treatment is essentially based on opioid use. Objective: To report the effectiveness of acupuncture in relieving cancer pain (secondary to the disease or to the corresponding therapy) or in decreasing opioid use compared to other interventions. Methods: A systematic review of randomized clinical trials was conducted following the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. The trials were selected from the PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Results: The search strategy resulted in the inclusion of eight trials, of which five compared acupuncture and drug therapy and three compared acupuncture and placebo. Seven trials reported decreased pain and analgesic use. The trials showed clinical heterogeneity, making a meta-analysis unfeasible. Conclusion: The findings herein provided no robust evidence to support the routine use of acupuncture as an adjuvant therapy in the treatment of cancer pain. However, its use is promising since the results showed a trend toward decreased pain and analgesic use, thus justifying further studies in the future.

scholarly journals Effect of Rapid Maxillary Expansion on Mandibular Rotation—A Systematic Review

2020 ◽  
Vol 54 (1) ◽  
pp. 5-13
Author(s):  
Priyanka Chhutani ◽  
Sonali Deshmukh ◽  
Sandeep Jethe ◽  
Sanket Agarkar ◽  
Sujata Yerawadekar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Rapid Maxillary Expansion ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Maxillary Expansion ◽  
Eligibility Criteria ◽  
Maxillary Molars ◽  
Central Register ◽  
Clinical Trials Registry

Objective: To evaluate the effect of rapid maxillary expansion (RME) on mandibular rotation. Materials and Method: A systematic review of articles selected from 4 electronic databases—PUBMED, Cochrane Central Register of Controlled Trials, Clinical Trials Registry, and Google Scholar—was carried out. Additional studies were hand-searched and retrieved from the reference lists of relevant articles. Studies published till August, 2019, were included in this study. Results: A total of 28 articles were identified through electronic database searching. 16 articles were obtained after elimination of duplicates which were then screened. Full-text articles were assessed according to the eligibility criteria. 2 randomized controlled trials (RCTs) and 14 clinical trials (CTs) were identified for inclusion in the review. These studies effectively highlighted the effect of RME on mandibular rotation, primarily in the clockwise direction. Conclusion: There is a moderate sum of evidence to illustrate the effect of RME on mandibular rotation. It can be concluded that RME brings about clockwise rotation of the mandible, ie in downward and backward directions, thereby increasing the lower anterior facial height. This effect could be attributed to the vertical maxillary movement and the extrusion of the maxillary molars.

scholarly journals Efficacy of miltefosine compared with glucantime for the treatment of cutaneous leishmaniasis: a systematic review and meta-analysis

2019 ◽  
Vol 41 ◽  
pp. e2019011 ◽  
Author(s):  
Sohrab Iranpour ◽  
Ali Hosseinzadeh ◽  
Abbas Alipour
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Cutaneous Leishmaniasis ◽  
Publication Bias ◽  
Meta Analysis ◽  
World Health ◽  
Cochrane Central Register ◽  
Significant Difference ◽  
Meta Regression ◽  
Trim And Fill

Cutaneous leishmaniasis (CL) is most common form of leishmaniasis and is characterized by ulcerative skin lesions. The objective of this study was to conduct a systematic review and meta-analysis of clinical trials that compared the efficacy of miltefosine and glucantime for the treatment of CL. We searched the following databases: Cochrane, PubMed, Embase, Scopus, Web of Science, ProQuest, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform search portal of World Health Organization, Sid, Irandoc, Magiran, and clinicaltrials.gov. We used keywords including “miltefosine,” “glucantime,” and “Leishmania.” The quality of studies was assessed using the Cochrane risk of bias tool. A random-effects model was employed for the analysis. We assessed heterogeneity by the chi-square test and the I2 index statistic. When heterogeneity was present, meta-regression analyses were performed. The Egger method was used to assess publication bias; when it was significant, the trim-and-fill method was used to test and adjust for publication bias. A total of 1,570 reports were identified, of which 10 studies were included in the meta-analysis. In the meta-analysis, there was no significant difference between the efficacy of miltefosine and glucantime; however, subgroup analysis showed that, regarding parasite species other than Leishmania braziliensis, miltefosine was significantly superior to glucantime (intention to treat; relative risk, 1.15; 95% confidence interval, 1.01 to 1.32). In the meta-regression, only the glucantime injection type was significant at the p=0.1 level. The Egger test found statistically significant publication bias; however, including the 3 missing studies in the trim-and-fill analysis did not change the results. This meta-analysis found that miltefosine seems to be more effective than glucantime, at least in species other than L. braziliensis, for treating CL.

scholarly journals Treatments for subacute cough in primary care: systematic review and meta-analyses of randomised clinical trials

2018 ◽  
Vol 68 (675) ◽  
pp. e694-e702 ◽  
Author(s):  
Benjamin Speich ◽  
Anja Thomer ◽  
Soheila Aghlmandi ◽  
Hannah Ewald ◽  
Andreas Zeller ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Treatment Options ◽  
Combined Treatment ◽  
Randomised Clinical Trials ◽  
Cochrane Central Register ◽  
Central Register ◽  
Severity Scores ◽  
Drug Treatments ◽  
Meta Analyses

BackgroundSubacute cough following a non-specific viral infection lasting 3–8 weeks is common. However, despite many treatment options there are no systematic reviews evaluating these.AimTo provide a systematic overview of treatment options and outcomes evaluated in randomised clinical trials (RCTs).Design and settingSystematic review and meta-analyses assessing the overall effects of any treatment for subacute cough.MethodThe authors systematically searched PubMed/MEDLINE and the Cochrane Central Register of Controlled Trials (last search March 2017) for RCTs in adult patients with subacute cough. The authors considered trials evaluating any outcome of any drug or non-drug treatments, apart from traditional Chinese and Asian medicines. They combined treatment effects on cough-related outcomes in random effects meta-analyses.ResultsSix eligible RCTs including 724 patients were identified. These assessed montelukast, salbutamol plus ipratropium bromide, gelatine, fluticasone propionate, budesonide, and nociception opioid 1 receptor agonist and codeine. Five studies reported effects on various cough severity scores at various timepoints. No treatment option was associated with a clear benefit on cough recovery or other patient-relevant outcomes in any of the studies or in meta-analyses for cough outcomes at 14 days and 28 days. Reported adverse events were rather mild and reported for 14% of patients across all treatments.ConclusionEvidence on treatment options for subacute cough is weak. There is no treatment showing clear patient-relevant benefits in clinical trials.

scholarly journals Nutraceuticals and nutritional supplements for the treatment of bipolar disorder: protocol for a systematic review

BMJ Open ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. e025640 ◽  
Author(s):  
Melanie M Ashton ◽  
Michael Berk ◽  
Chee H Ng ◽  
Malcolm Hopwood ◽  
Bianca Kavanagh ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bipolar Disorder ◽  
Clinical Trials ◽  
Research Question ◽  
Risk Of Bias ◽  
Published Data ◽  
Cochrane Central Register ◽  
Controlled Clinical Trials ◽  
Double Blind ◽  
Search Terms

IntroductionFirst line pharmacological treatments for bipolar disorder (BD) can leave shortfalls in recovery leading to patients seeking alternative and adjunctive treatments such as nutraceuticals. This protocol for a systematic review and proposed meta-analysis aims to answer the research question: in patients with BD, how does use of nutraceutical treatments compare with placebo in reducing depressive and mania symptoms?Methods and analysisClinical trials will be identified through database searches using PubMed via PubMed, EMBASE via embase.com, Cochrane Central Register of Controlled Clinical Trials (CENTRAL) via cochranelibrary.com and CINAHL Complete via EBSCO. Search terms for BD and specific nutraceuticals (75 total search terms) will be used. Double-blind, randomised, controlled, clinical trials of adults with BD will be included in the review. Risk of bias will be assessed using the Cochrane Collaboration’s tool for assessing risk of bias in randomised trials.Ethics and disseminationThis review will only look at published data (already reviewed for ethical compliance); therefore, ethical approval is not required. We aim to publish the systematic review in a peer-reviewed journal and present at conferences.PROSPERO registration numberCRD42019100745.

scholarly journals Placebo Response Rate in Clinical Trials of Fistulizing Crohn's Disease: Systematic Review and Meta-analysis

2014 ◽  
Vol 12 (12) ◽  
pp. 1981-1990 ◽  
Author(s):  
Alexander C. Ford ◽  
Pavit Luthra ◽  
Stephen B. Hanauer ◽  
Simon P. Travis ◽  
M. Scott Harris ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Response Rate ◽  
Meta Analysis ◽  
Placebo Response ◽  
Placebo Response Rate

scholarly journals Balance in the Blind: A Systematic Review

2021 ◽  
Vol 11 (1) ◽  
pp. 1-12
Author(s):  
Hassan Daneshmandi ◽  
◽  
Ali Asghar Norasteh ◽  
Hamed Zarei ◽  
◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Web Of Science ◽  
Cochrane Central Register ◽  
Sufficient Data ◽  
Controlled Clinical Trials ◽  
Ankle Strategy ◽  
Normal People ◽  
Central Register ◽  
Training Protocols

Purpose: This paper reviews the studies on balance in the blind. Methods: The paper comprehensively reviewed studies on balance in the blind from the following databases: PubMed, MEDLINE, Web of Science, ScienceDirect, Cochrane Central Register of Controlled Clinical Trials, Google Scholar, and Scopus, from 2001 to 2019. Also, other available papers were examined. Results: Out of 35 evaluated studies, 32 articles were fully represented and the rest were only summarized. These articles covered two issues: 1) balance adaptation in the blind, 2) the effects of training protocols on the balance in the blind. Conclusion: The blind suffer from poor balance. However, they tend not to differ from normal people, when sufficient data from the vestibular and proprioception systems are available. Also, balance in the blind improves by age, which increases the efficiency and maturity of vestibular and proprioception systems. The blind tend to be more reliant on the hip than ankle strategy. All the training protocols reviewed in this paper have positively affected balance in the blind. Nevertheless, it was impossible to determine the most efficient protocol, and further qualitative studies are required for this purpose.

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