Aluminium adjuvants versus placebo or no intervention in vaccine randomised clinical trials: a systematic review with meta-analysis and Trial Sequential Analysis
Objectives To assess the benefits and harms of aluminium adjuvants versus placebo or no intervention in randomised clinical trials in relation to human vaccine development.Design Systematic review with meta-analysis and trial sequential analysis assessing the certainty of evidence with Grading of Re...
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| Format: | Article |
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BMJ Publishing Group
2022-06-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/12/6/e058795.full |
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| author | Christian Gluud Marija Barbateskovic Sara Russo Krauss Janus C Jakobsen Sesilje Bondo Petersen Sarah Louise Klingenberg Snezana Djurisic Mette Kenfelt De Zhao Kong |
| author_facet | Christian Gluud Marija Barbateskovic Sara Russo Krauss Janus C Jakobsen Sesilje Bondo Petersen Sarah Louise Klingenberg Snezana Djurisic Mette Kenfelt De Zhao Kong |
| author_sort | Christian Gluud |
| collection | DOAJ |
| description | Objectives To assess the benefits and harms of aluminium adjuvants versus placebo or no intervention in randomised clinical trials in relation to human vaccine development.Design Systematic review with meta-analysis and trial sequential analysis assessing the certainty of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE).Data sources We searched CENTRAL, MEDLINE, Embase, LILACS, BIOSIS, Science Citation Index Expanded and Conference Proceedings Citation Index-Science until 29 June 2021, and Chinese databases until September 2021.Eligibility criteria Randomised clinical trials irrespective of type, status and language of publication, with trial participants of any sex, age, ethnicity, diagnosis, comorbidity and country of residence.Data extraction and synthesis Two independent reviewers extracted data and assessed risk of bias with Cochrane’s RoB tool 1. Dichotomous data were analysed as risk ratios (RRs) and continuous data as mean differences. We explored both fixed-effect and random-effects models, with 95% CI. Heterogeneity was quantified with I2 statistic. We GRADE assessed the certainty of the evidence.Results We included 102 randomised clinical trials (26 457 participants). Aluminium adjuvants versus placebo or no intervention may have no effect on serious adverse events (RR 1.18, 95% CI 0.97 to 1.43; very low certainty) and on all-cause mortality (RR 1.02, 95% CI 0.74 to 1.41; very low certainty). No trial reported on quality of life. Aluminium adjuvants versus placebo or no intervention may increase adverse events (RR 1.13, 95% CI 1.07 to 1.20; very low certainty). We found no or little evidence of a difference between aluminium adjuvants versus placebo or no intervention when assessing serology with geometric mean titres or concentrations or participants’ seroprotection.Conclusions Based on evidence at very low certainty, we were unable to identify benefits of aluminium adjuvants, which may be associated with adverse events considered non-serious. |
| format | Article |
| id | doaj-art-9ddb181ae491422bbf9ed8acceed10a9 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2022-06-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-9ddb181ae491422bbf9ed8acceed10a92025-01-24T04:05:13ZengBMJ Publishing GroupBMJ Open2044-60552022-06-0112610.1136/bmjopen-2021-058795Aluminium adjuvants versus placebo or no intervention in vaccine randomised clinical trials: a systematic review with meta-analysis and Trial Sequential AnalysisChristian Gluud0Marija Barbateskovic1Sara Russo Krauss2Janus C Jakobsen3Sesilje Bondo Petersen4Sarah Louise Klingenberg5Snezana Djurisic6Mette Kenfelt7De Zhao Kong8The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, DenmarkThe Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital – Rigshospitalet, Copenhagen, DenmarkThe Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital – Rigshospitalet, Copenhagen, DenmarkCentre for Clinical Intervention Research, Copenhagen Trial Unit, Rigshospitalet, Copenhagen, DenmarkDepartment of Occupational and Environmental Medicine, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Copenhagen, DenmarkThe Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital – Rigshospitalet, Copenhagen, DenmarkThe Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital – Rigshospitalet, Copenhagen, DenmarkStationsvej 2, Farum, DenmarkThe Evidence-Based Medicine Research Center of Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, ChinaObjectives To assess the benefits and harms of aluminium adjuvants versus placebo or no intervention in randomised clinical trials in relation to human vaccine development.Design Systematic review with meta-analysis and trial sequential analysis assessing the certainty of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE).Data sources We searched CENTRAL, MEDLINE, Embase, LILACS, BIOSIS, Science Citation Index Expanded and Conference Proceedings Citation Index-Science until 29 June 2021, and Chinese databases until September 2021.Eligibility criteria Randomised clinical trials irrespective of type, status and language of publication, with trial participants of any sex, age, ethnicity, diagnosis, comorbidity and country of residence.Data extraction and synthesis Two independent reviewers extracted data and assessed risk of bias with Cochrane’s RoB tool 1. Dichotomous data were analysed as risk ratios (RRs) and continuous data as mean differences. We explored both fixed-effect and random-effects models, with 95% CI. Heterogeneity was quantified with I2 statistic. We GRADE assessed the certainty of the evidence.Results We included 102 randomised clinical trials (26 457 participants). Aluminium adjuvants versus placebo or no intervention may have no effect on serious adverse events (RR 1.18, 95% CI 0.97 to 1.43; very low certainty) and on all-cause mortality (RR 1.02, 95% CI 0.74 to 1.41; very low certainty). No trial reported on quality of life. Aluminium adjuvants versus placebo or no intervention may increase adverse events (RR 1.13, 95% CI 1.07 to 1.20; very low certainty). We found no or little evidence of a difference between aluminium adjuvants versus placebo or no intervention when assessing serology with geometric mean titres or concentrations or participants’ seroprotection.Conclusions Based on evidence at very low certainty, we were unable to identify benefits of aluminium adjuvants, which may be associated with adverse events considered non-serious.https://bmjopen.bmj.com/content/12/6/e058795.full |
| spellingShingle | Christian Gluud Marija Barbateskovic Sara Russo Krauss Janus C Jakobsen Sesilje Bondo Petersen Sarah Louise Klingenberg Snezana Djurisic Mette Kenfelt De Zhao Kong Aluminium adjuvants versus placebo or no intervention in vaccine randomised clinical trials: a systematic review with meta-analysis and Trial Sequential Analysis BMJ Open |
| title | Aluminium adjuvants versus placebo or no intervention in vaccine randomised clinical trials: a systematic review with meta-analysis and Trial Sequential Analysis |
| title_full | Aluminium adjuvants versus placebo or no intervention in vaccine randomised clinical trials: a systematic review with meta-analysis and Trial Sequential Analysis |
| title_fullStr | Aluminium adjuvants versus placebo or no intervention in vaccine randomised clinical trials: a systematic review with meta-analysis and Trial Sequential Analysis |
| title_full_unstemmed | Aluminium adjuvants versus placebo or no intervention in vaccine randomised clinical trials: a systematic review with meta-analysis and Trial Sequential Analysis |
| title_short | Aluminium adjuvants versus placebo or no intervention in vaccine randomised clinical trials: a systematic review with meta-analysis and Trial Sequential Analysis |
| title_sort | aluminium adjuvants versus placebo or no intervention in vaccine randomised clinical trials a systematic review with meta analysis and trial sequential analysis |
| url | https://bmjopen.bmj.com/content/12/6/e058795.full |
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