scholarly journals Benefits and harms of the human papillomavirus (HPV) vaccines: comparison of trial data from clinical study reports with corresponding trial register entries and journal publications

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Lars Jørgensen ◽  
Peter C. Gøtzsche ◽  
Tom Jefferson
Keyword(s):  
Systematic Review ◽  
Clinical Study ◽  
Hpv Vaccine ◽  
Meta Analysis ◽  
Trial Data ◽  
Link Type ◽  
Trial Register ◽  
Journal Publications ◽  
Meta Analyses ◽  
Clinical Study Reports

Abstract Background No study has looked at differences of pooled estimates—such as meta-analyses—of corresponding study documents of the same intervention. In this study, we compared meta-analyses of human papillomavirus (HPV) vaccine trial data from clinical study reports with trial data from corresponding trial register entries and journal publications. Methods We obtained clinical study reports from the European Medicines Agency and GlaxoSmithKline, corresponding trial register entries from ClinicalTrials.gov and corresponding journal publications via the Cochrane Collaboration’s Central Register of Controlled Trials, Google Scholar and PubMed. Two researchers extracted data. We compared reporting of trial design aspects and 20 prespecified benefit and harm outcomes extracted from each study document type. Risk ratios were calculated with the random effects inverse variance method. Results We included study documents from 22 randomized clinical trials and 2 follow-up studies with 95,670 healthy participants and non-HPV vaccine comparators (placebo, HPV vaccine adjuvants and hepatitis vaccines). We obtained 24 clinical study reports, 24 corresponding trial register entries and 23 corresponding journal publications; the median number of pages was 1351 (range 357 to 11,456), 32 (range 11 to 167) and 11 (range 7 to 83), respectively. All 24 (100%) clinical study reports, no (0%) trial register entries and 9 (39%) journal publications reported on all six major design-related biases defined by the Cochrane Handbook version 2011. The clinical study reports reported more inclusion criteria (mean 7.0 vs. 5.8 [trial register entries] and 4.0 [journal publications]) and exclusion criteria (mean 17.8 vs. 11.7 and 5.0) but fewer primary outcomes (mean 1.6 vs. 3.5 and 1.2) and secondary outcomes (mean 8.8 vs. 13.0 and 3.2) than the trial register entries. Results were posted for 19 trial register entries (79%). Compared to the clinical study reports, the trial register entries and journal publications contained 3% and 44% of the seven assessed benefit data points (6879 vs. 230 and 3015) and 38% and 31% of the 13 assessed harm data points (167,550 vs. 64,143 and 51,899). No meta-analysis estimate differed significantly when we compared pooled risk ratio estimates of corresponding study document data as ratios of relative risk. Conclusion There were no significant differences in the meta-analysis estimates of the assessed outcomes from corresponding study documents. The clinical study reports were the superior study documents in terms of the quantity and the quality of the data they contained and should be used as primary data sources in systematic reviews. Systematic review registration The protocol for our comparison is registered on PROSPERO as an addendum to our systematic review of the benefits and harms of the HPV vaccines: https://www.crd.york.ac.uk/PROSPEROFILES/56093_PROTOCOL_20180320.pdf: CRD42017056093. Our systematic review protocol was registered on PROSPERO on January 2017: https://www.crd.york.ac.uk/PROSPEROFILES/56093_PROTOCOL_20170030.pdf. Two protocol amendments were registered on PROSPERO on November 2017: https://www.crd.york.ac.uk/PROSPEROFILES/56093_PROTOCOL_20171116.pdf. Our index of the HPV vaccine studies was published in Systematic Reviews on January 2018: 10.1186/s13643-018-0675-z. A description of the challenges obtaining the data was published on September 2018: 10.1136/bmj.k3694.

scholarly journals Considering the methodological limitations in the evidence base of antidepressants for depression: a reanalysis of a network meta-analysis

BMJ Open ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. e024886 ◽  
Author(s):  
Klaus Munkholm ◽  
Asger Sand Paludan-Müller ◽  
Kim Boesen
Keyword(s):  
Systematic Review ◽  
Clinical Study ◽  
Effect Size ◽  
Meta Analysis ◽  
Evidence Base ◽  
Risk Of Bias ◽  
Depression Symptom ◽  
Meta Analyses ◽  
The Impact ◽  
Clinical Study Reports

ObjectivesTo investigate whether the conclusion of a recent systematic review and network meta-analysis (Ciprianiet al) that antidepressants are more efficacious than placebo for adult depression was supported by the evidence.DesignReanalysis of a systematic review, with meta-analyses.Data sources522 trials (116 477 participants) as reported in the systematic review by Ciprianiet aland clinical study reports for 19 of these trials.AnalysisWe used the Cochrane Handbook’s risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate the risk of bias and the certainty of evidence, respectively. The impact of several study characteristics and publication status was estimated using pairwise subgroup meta-analyses.ResultsSeveral methodological limitations in the evidence base of antidepressants were either unrecognised or underestimated in the systematic review by Ciprianiet al. The effect size for antidepressants versus placebo on investigator-rated depression symptom scales was higher in trials with a ‘placebo run-in’ study design compared with trials without a placebo run-in design (p=0.05). The effect size of antidepressants was higher in published trials compared with unpublished trials (p<0.0001). The outcome data reported by Ciprianiet aldiffered from the clinical study reports in 12 (63%) of 19 trials. The certainty of the evidence for the placebo-controlled comparisons should be very low according to GRADE due to a high risk of bias, indirectness of the evidence and publication bias. The mean difference between antidepressants and placebo on the 17-item Hamilton depression rating scale (range 0–52 points) was 1.97 points (95% CI 1.74 to 2.21).ConclusionsThe evidence does not support definitive conclusions regarding the benefits of antidepressants for depression in adults. It is unclear whether antidepressants are more efficacious than placebo.

scholarly journals Naltrexone–bupropion (Mysimba) in management of obesity: A systematic review and meta‐analysis of unpublished clinical study reports

2020 ◽  
Vol 86 (4) ◽  
pp. 646-667 ◽  
Author(s):  
Igho J. Onakpoya ◽  
Joseph J. Lee ◽  
Kamal R. Mahtani ◽  
Jeffrey K. Aronson ◽  
Carl J. Heneghan
Keyword(s):  
Systematic Review ◽  
Clinical Study ◽  
Meta Analysis ◽  
Clinical Study Reports

scholarly journals Benefits and harms of Risperidone and Paliperidone for treatment of patients with schizophrenia or bipolar disorder: a meta-analysis involving individual participant data and clinical study reports

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Alexander Hodkinson ◽  
Carl Heneghan ◽  
Kamal R. Mahtani ◽  
Evangelos Kontopantelis ◽  
Maria Panagioti
Keyword(s):  
Bipolar Disorder ◽  
Clinical Study ◽  
Relative Risk ◽  
Adverse Events ◽  
Meta Analysis ◽  
Data Sources ◽  
Individual Participant Data ◽  
Journal Publications ◽  
Individual Participant ◽  
Clinical Study Reports

Abstract Background Schizophrenia and bipolar disorder are severe mental illnesses which are highly prevalent worldwide. Risperidone and Paliperidone are treatments for either illnesses, but their efficacy compared to other antipsychotics and growing reports of hormonal imbalances continue to raise concerns. As existing evidence on both antipsychotics are solely based on aggregate data, we aimed to assess the benefits and harms of Risperidone and Paliperidone in the treatment of patients with schizophrenia or bipolar disorder, using individual participant data (IPD), clinical study reports (CSRs) and publicly available sources (journal publications and trial registries). Methods We searched MEDLINE, Central, EMBASE and PsycINFO until December 2020 for randomised placebo-controlled trials of Risperidone, Paliperidone or Paliperidone palmitate in patients with schizophrenia or bipolar disorder. We obtained IPD and CSRs from the Yale University Open Data Access project. The primary outcome Positive and Negative Syndrome Scale (PANSS) score was analysed using one-stage IPD meta-analysis. Random-effect meta-analysis of harm outcomes involved methods for coping with rare events. Effect-sizes were compared across all available data sources using the ratio of means or relative risk. We registered our review on PROSPERO, CRD42019140556. Results Of the 35 studies, IPD meta-analysis involving 22 (63%) studies showed a significant clinical reduction in the PANSS in patients receiving Risperidone (mean difference − 5.83, 95% CI − 10.79 to − 0.87, I2 = 8.5%, n = 4 studies, 1131 participants), Paliperidone (− 6.01, 95% CI − 8.7 to − 3.32, I2 = 4.3%, n = 13, 3821) and Paliperidone palmitate (− 7.89, 95% CI − 12.1 to − 3.69, I2 = 2.9%, n = 5, 2209). CSRs reported nearly two times more adverse events (4434 vs. 2296 publication, relative difference (RD) = 1.93, 95% CI 1.86 to 2.00) and almost 8 times more serious adverse events (650 vs. 82; RD = 7.93, 95% CI 6.32 to 9.95) than the journal publications. Meta-analyses of individual harms from CSRs revealed a significant increased risk among several outcomes including extrapyramidal disorder, tardive dyskinesia and increased weight. But the ratio of relative risk between the different data sources was not significant. Three treatment-related gynecomastia events occurred, and these were considered mild to moderate in severity. Conclusion IPD meta-analysis conclude that Risperidone and Paliperidone antipsychotics had a small beneficial effect on reducing PANSS score over 9 weeks, which is more conservative than estimates from reviews based on journal publications. CSRs also contained significantly more data on harms that were unavailable in journal publications or trial registries. Sharing of IPD and CSRs are necessary when performing meta-analysis on the efficacy and safety of antipsychotics.

scholarly journals Which patients benefit specifically from short-term psychodynamic psychotherapy (STPP) for depression? Study protocol of a systematic review and meta-analysis of individual participant data

BMJ Open ◽  
2018 ◽  
Vol 8 (2) ◽  
pp. e018900 ◽  
Author(s):  
Ellen Driessen ◽  
Allan A Abbass ◽  
Jacques P Barber ◽  
Mary Beth Connolly Gibbons ◽  
Jack J M Dekker ◽  
...  
Keyword(s):  
Systematic Review ◽  
Psychodynamic Psychotherapy ◽  
Meta Analysis ◽  
Grey Literature ◽  
Prospective Trial ◽  
Individual Participant Data ◽  
Short Term ◽  
Link Type ◽  
Individual Participant ◽  
Meta Analyses

IntroductionShort-term psychodynamic psychotherapy (STPP) is an empirically supported treatment that is often used to treat depression. However, it is largely unclear if certain subgroups of depressed patients can benefit specifically from this treatment method. We describe the protocol for a systematic review and meta-analysis of individual participant data (IPD) aimed at identifying predictors and moderators of STPP for depression efficacy.Method and analysisWe will conduct a systematic literature search in multiple bibliographic databases (PubMed, PsycINFO, Embase.com, Web of Science and Cochrane’s Central Register of Controlled Trials), ‘grey literature’ databases (GLIN and UMI ProQuest) and a prospective trial register (http://www.controlled-trials.com). We will include studies reporting (a) outcomes on standardised measures of (b) depressed (c) adult patients (d) receiving STPP. We will next invite the authors of these studies to share the participant-level data of their trials and combine these data to conduct IPD meta-analyses. The primary outcome for this study is post-treatment efficacy as assessed by a continuous depression measure. Potential predictors and moderators include all sociodemographic variables, clinical variables and psychological patient characteristics that are measured before the start of treatment and are assessed consistently across studies. One-stage IPD meta-analyses will be conducted using mixed-effects models.Ethics and disseminationInstitutional review board approval is not required for this study. We intend to submit reports of the outcomes of this study for publication to international peer-reviewed journals in the fields of psychiatry or clinical psychology. We also intend to present the outcomes at international scientific conferences aimed at psychotherapy researchers and clinicians. The findings of this study can have important clinical implications, as they can inform expectations of STPP efficacy for individual patients, and help to make an informed choice concerning the best treatment option for a given patient.PROSPERO registration numberCRD42017056029.

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