scholarly journals Opportunities for selective reporting of harms in randomized clinical trials: Selection criteria for nonsystematic adverse events

2019 ◽  
Author(s):  
Evan Mayo-Wilson ◽  
Nicole Fusco ◽  
Hwanhee Hong ◽  
Tianjing Li ◽  
Joseph K. Canner ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Selection Criteria ◽  
Randomized Clinical Trials ◽  
Bipolar Depression ◽  
Selective Reporting ◽  
Journal Articles ◽  
Multiple Sources ◽  
Study Results ◽  
Meta Analyses

Abstract Background: Adverse events (AEs) in randomized clinical trials may be reported in multiple sources. Different methods for reporting adverse events across trials, or across sources for a single trial, may produce inconsistent and confusing information about the adverse events associated with interventions Methods: We sought to compare the methods authors use to decide which AEs to include in a particular source (i.e., “selection criteria”) and to determine how selection criteria could impact the AEs reported. We compared sources (e.g., journal articles, clinical study reports [CSRs]) of trials for two drug-indications: gabapentin for neuropathic pain and quetiapine for bipolar depression. We identified selection criteria and assessed how criteria affected AE reporting. Results: We identified 21 gabapentin trials and 7 quetiapine trials. All CSRs (6 gabapentin, 2 quetiapine) reported all AEs without applying selection criteria; by comparison, no other source reported all AEs, and 15/68 (22%) gabapentin sources and 19/48 (40%) quetiapine sources reported using selection criteria. Selection criteria greatly affected the number of AEs that would be reported. For example, 67/316 (21%) AEs in one quetiapine trial met the criterion “occurring in ≥2% of participants in any treatment group,” while only 5/316 (2%) AEs met the criterion, “occurring in ≥10% of quetiapine-treated patients and twice as frequent in the quetiapine group as the placebo group.” Conclusions: Selection criteria for reporting AEs vary across trials and across sources for individual trials. If investigators do not pre-specify selection criteria, they might “cherry-pick” AEs based on study results. Even if investigators pre-specify selection criteria, selective reporting of AEs will produce biased meta-analyses and clinical practice guidelines. Data about all AEs identified in clinical trials should be publicly available; however, sharing data will not solve all the problems we identified in this study. Keywords: Harms, adverse events, clinical trials, reporting bias, selective outcome reporting, data sharing, trial registration

scholarly journals Opportunities for selective reporting of harms in randomized clinical trials: Selection criteria for nonsystematic adverse events

2019 ◽  
Author(s):  
Evan Mayo-Wilson ◽  
Nicole Fusco ◽  
Hwanhee Hong ◽  
Tianjing Li ◽  
Joseph K. Canner ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Selection Criteria ◽  
Randomized Clinical Trials ◽  
Bipolar Depression ◽  
Selective Reporting ◽  
Journal Articles ◽  
Multiple Sources ◽  
Meta Analyses ◽  
Clinical Study Reports

Abstract Background: Adverse events (AEs) in clinical trials may be reported in multiple sources. Different methods for reporting adverse events across trials, or across sources for a single trial, may produce inconsistent information about the adverse events associated with interventions. Methods: We compared the methods authors use to decide which AEs to include in a particular source (i.e., “selection criteria”), including the number of different types of AEs reported (i.e., rather than the number of events). We compared sources (e.g., journal articles, clinical study reports [CSRs]) of trials for two drug-indications: gabapentin for neuropathic pain and quetiapine for bipolar depression. Electronic searches were completed in 2015. We identified selection criteria and assessed how criteria affected AE reporting. Results: We identified 21 gabapentin and 7 quetiapine trials. We found 6 gabapentin CSRs and 2 quetiapine CSRs, all written by drug manufacturers. All CSRs reported all AEs without applying selection criteria; by comparison, no other source reported all AEs, and 15/68 (22%) gabapentin sources and 19/48 (40%) quetiapine sources reported using selection criteria. Selection criteria greatly affected the number of AEs reported. For example, 67/316 (21%) AEs in one quetiapine trial met the criterion “occurring in ≥2% of participants in any treatment group,” while only 5/316 (2%) AEs met the criterion, “occurring in ≥10% of quetiapine-treated patients and twice as frequent in the quetiapine group as the placebo group.” Conclusions: Selection criteria for reporting AEs vary across trials and across sources for individual trials. If investigators do not pre-specify selection criteria, they might “cherry-pick” AEs based on results. Even if investigators pre-specify selection criteria, selective reporting will produce biased meta-analyses and clinical practice guidelines. Data about all AEs identified in clinical trials should be publicly available; however, sharing data will not solve all the problems identified in this study.

scholarly journals Opportunities for selective reporting of harms in randomized clinical trials: Selection criteria for non-systematic adverse events

Trials ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Evan Mayo-Wilson ◽  
Nicole Fusco ◽  
Hwanhee Hong ◽  
Tianjing Li ◽  
Joseph K. Canner ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Selection Criteria ◽  
Randomized Clinical Trials ◽  
Selective Reporting

Percutaneous Closure of Patent Foramen Ovale – Data from Randomized Clinical Trials and Meta-Analyses

2015 ◽  
Vol 10 (1) ◽  
pp. 45 ◽  
Author(s):  
Stefan Stortecky ◽  
Stephan Windecker ◽  
◽  
Keyword(s):  
Clinical Trials ◽  
Patent Foramen Ovale ◽  
Randomized Clinical Trials ◽  
Paradoxical Embolism ◽  
Percutaneous Closure ◽  
Primary Study ◽  
Foramen Ovale ◽  
Study Results ◽  
Meta Analyses ◽  
Pfo Closure

Data from epidemiologic studies have indicated a close association between the presence of a patent foramen ovale (PFO) and cryptogenic stroke that is suggestive of paradoxical embolism as the underlying cause. Percutaneous closure of PFO has been proposed for the secondary prevention among patients suffering from paradoxical embolism. While observational data support this strategy, three randomized trials investigating percutaneous PFO closure with medical therapy have failed to detect a statistically significant reduction of the primary endpoint of recurrent ischemic cerebrovascular events, peripheral embolism, and death in the intention-to-treat analysis. Several reasons have been discussed as basis for the negative primary study results, including long recruitment rates, low number of recurrent events, and the use of different devices. In order to provide an answer to these unresolved factors, several meta-analyses have been published that have provided conflicting results. This article will review the available evidence of percutaneous PFO closure, will provide an overview on randomized clinical trials, and summarize the evidence from meta-analyses.

scholarly journals Vaccines to prevent COVID-19: a protocol for a living systematic review with network meta-analysis including individual patient data (The LIVING VACCINE Project)

2020 ◽  
Author(s):  
STEVEN KWASI KORANG ◽  
Sophie Juul ◽  
Emil Eik Nielsen ◽  
Joshua Feinberg ◽  
Faiza Siddiqui ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Individual Patient Data ◽  
Viral Vector ◽  
Risk Of Bias ◽  
Serious Adverse Events ◽  
Meta Analyses ◽  
Harmful Effects

Abstract Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes corona virus disease 2019 (COVID-19) which has rapidly spread worldwide. Several human randomized clinical trials assessing potential vaccines are currently underway. There is an urgent need for a living systematic review that continuously assesses the beneficial and harmful effects of all available vaccines for COVID-19.Methods/design: We will conduct a living systematic review based on searches of major medical databases (e.g. MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify relevant randomized clinical trials. We will update the literature search once a week to continuously assess if new evidence is available. Two review authors will independently extract data and conduct risk of bias assessments. We will include randomized clinical trials comparing any vaccine aiming to prevent COVID-19 (including but not limited to messenger RNA; DNA; non-replicating viral vector; replicating viral vector; inactivated virus; protein subunit; dendritic cell; other vaccines) with any comparator (placebo; ‘active placebo’; no intervention; standard care; an ‘active’ intervention; another vaccine for COVID-19) for participants in all age groups. Primary outcomes will be all-cause mortality; a diagnosis of COVID-19; and serious adverse events. Secondary outcomes will be quality of life, and non-serious adverse events. The living systematic review will include aggregate data meta-analyses, Trial Sequential Analyses, network meta-analyses, and individual patient data meta-analyses. Risk of bias will be assessed with domains, our eight-step procedure to assess if the thresholds for clinical significance are crossed, and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) will assess certainty of evidence. Observational studies describing harms identified during the search for trials will also be included and analyzed separately. Discussion: COVID-19 has become a pandemic with substantial mortality. A living systematic review assessing the beneficial and harmful effects of different vaccines is urgently needed. This living systematic review will regularly inform best practice in vaccine prevention and clinical research of this highly prevalent disease.Systematic review registration: PROSPERO CRD42020196492

scholarly journals The effects of adding glucocorticosteroids to standard care for children with sepsis. A systematic review of randomized clinical trials with meta-analysis and Trial Sequential Analysis

2021 ◽  
Author(s):  
Steven Kwasi Korang ◽  
Sanam Safi ◽  
Christian Gluud ◽  
Janus C Jakobsen
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Standard Care ◽  
Sequential Analysis ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Trial Sequential Analysis ◽  
Serious Adverse Events ◽  
Meta Analyses

Abstract Background: Glucocorticosteroids are widely used to treat severe sepsis in pediatric intensive care units. However, the evidence on the clinical effects is unclear.Objective: To assess the benefits and harms of glucocorticosteroids for children with sepsis. Data Sources: We conducted a systematic review of randomized clinical trials with meta-analysis and Trial Sequential Analysis (TSA) (PROSPERO CRD42017054341). We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, and more. Study Selection: Randomized clinical trials assessing the effects of adding glucocorticosteroids to standard care for children with sepsis. Data Extraction: Two independent reviewers screened studies and extracted data. Evidence was assessed by GRADE according to our published protocol.Data Synthesis: We included 24 trials randomizing 3073 participants. Meta-analyses showed no evidence of an effect of adding glucocorticosteroids for children with sepsis with a mixed focus for any of our outcomes. Meta-analyses suggested evidence of a beneficial effect of dexamethasone for children with meningitis when assessing serious adverse events (risk ratio (RR) 0.68, 95% confidence interval (CI) 0.53 to 0.86; P = 0.001, very low certainty of evidence) and ototoxicity (RR 0.63, 95% CI 0.45 to 0.88; P = 0.007, low certainty of evidence). TSAs showed that we did not have sufficient data to confirm or reject these results. We found insufficient evidence to confirm or reject an effect on mortality or our other outcomes. No trials reported quality of life or organ failure. Most trials were at high risks of bias. We found high clinical heterogeneity between participants. None of our TSAs showed benefits, harms or futility. Conclusions: Generally, we found no evidence of an effect of glucocorticosteroids for children with sepsis without meningitis. Dexamethasone for sepsis in children due to meningitis may decrease serious adverse events and ototoxicity.

The Detection of Adverse Events in Randomized Clinical Trials: Can we Really Say New Medicines are Safe?

2013 ◽  
Vol 8 (2) ◽  
pp. 104-113 ◽  
Author(s):  
Izyan Wahab ◽  
Nicole Pratt ◽  
Lisa Kalisch ◽  
Elizabeth Roughead
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Randomized Clinical Trials

scholarly journals Acupuncture for post-stroke depression: a systematic review and meta-analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ran Liu ◽  
Kun Zhang ◽  
Qiu-yu Tong ◽  
Guang-wei Cui ◽  
Wen Ma ◽  
...  
Keyword(s):  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Quality Of Evidence ◽  
Post Stroke ◽  
Assessment Development ◽  
Significant Difference ◽  
Post Stroke Depression ◽  
Meta Analyses

Abstract Background Acupuncture for post-stroke depression (PSD) has been evolving, but uncertainty remains. To assess the existing evidence from randomized clinical trials (RCTs) of acupuncture for PSD, we sought to draw conclusions by synthesizing RCTs. Methods An exhaustive literature search was conducted in seven electronic databases from their inception dates to April 19, 2020, to identify systematic reviews (SRs) and meta-analyses (MAs) on this topic. The primary RCTs included in the SRs/MAs were identified. We also conducted a supplementary search for RCTs published from January 1, 2015, to May 12, 2020. Two reviewers extracted data separately and pooled data using RevMan 5.3 software. The quality of evidence was critically appraised with the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system. Results A total of 17 RCTs involving 1402 patients were included. Meta-analysis showed that participants who received a combination of acupuncture and conventional treatments exhibited significantly lower scores on the HAM-D17, HAM-D24 and HAM-D (MD, − 5.08 [95% CI, − 6.48 to − 3.67], I2 = 0%), (MD, − 9.72 [95% CI, − 14.54 to − 4.91], I2 = 65%) and (MD, − 2.72 [95% CI, − 3.61 to − 1.82], respectively) than those who received conventional treatment. However, there was no significant difference in acupuncture versus antidepressants in terms of the 17-item, 24-item and HAM-D scales (MD, − 0.43 [95% CI, − 1.61 to 0.75], I2 = 51%), (MD, − 3.09 [95% CI, − 10.81 to 4.63], I2 = 90%) and (MD, − 1.55 [95% CI, − 4.36 to 1.26], I2 = 95%, respectively). For adverse events, acupuncture was associated with fewer adverse events than antidepressants (RR, 0.16 [95% CI, 0.07 to 0.39], I2 = 35%), but there was no significant difference in the occurrence of adverse events between the combination of acupuncture and conventional treatments versus conventional treatments (RR, 0.63 [95% CI, 0.21 to 1.83], I2 = 38%). The quality of evidence was low to very low due to the substantial heterogeneity among the included studies. Conclusions The current review indicates that acupuncture has greater effect on PSD and better safety profile than antidepressants, but high-quality evidence evaluating acupuncture for PSD is still needed.

scholarly journals Recombinant Human Adenovirus-p53 Therapy for the Treatment of Oral Leukoplakia and Oral Squamous Cell Carcinoma: A Systematic Review

Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 438
Author(s):  
Jagadish Hosmani ◽  
Shazia Mushtaq ◽  
Shahabe Saquib Abullais ◽  
Hussain Mohammed Almubarak ◽  
Khalil Assiri ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Oral Cancer ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Oral Leukoplakia ◽  
Research Articles ◽  
Original Research ◽  
Therapeutic Effects ◽  
The World

Background and Objectives: Oral cancer is the 6th most common cancer in the world and oral leukoplakia is an oral potentially malignant disorder that could develop into oral cancer. This systematic review focusses on randomized clinical trials for recombinant adenovirus p-53 (rAD-p53) therapy for the treatment of oral leukoplakia and cancer. Materials and Methods: We searched for research articles on various databases such as Pubmed/Medline, Embase, CNKI (China National Knowledge Infra-structure), Springerlink, cochrane and Web of sciences from 2003 to 2020. MeSH (Medical Subject Headings) terms were used for the search. Inclusion criteria included original research, randomized clinical trials and articles only in English language. Exclusion criteria were any articles that were not research articles, not randomized trials, non-human studies, etc. The articles were further graded on the Jadad scale. Results: 578 articles were assessed from various databases; only 3 articles were found to be appropriate for this review. Thus, meta-analysis was not performed because of heterogeneity and lack of data. In the three studies, whether rAD-p53 was used as a standalone therapy or with other therapies, there was a beneficial effect of the therapy. Furthermore, there were no serious adverse events and the only adverse events reported were fever, pain at the local injection site, flu-like symptoms and lowered WBC count. Conclusions: Thus, we can conclude that this therapy has a potential for beneficial therapeutic effects and further clinical trials with more patients need to be performed to get better understanding of the effect of rAD-p53 therapy, which probably will pave the way to its approval in other parts of the world.

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