Guideline for collection, analysis and presentation of safety data in clinical trials of vaccines in pregnant women

Jones, Christine E; Muñoz, Flor M.; Spiegel, Hans; Heininger, Ulrich; Zuber, Patrick L. F.; Edwards, Kathryn M.; Lambach, Philipp; Neels, Pieter; Kohl, Katrin; Gidudu, Jane; Hirschfeld, Steven; Oleske, James M.; Khuri‐Bulos, Najwa; Bauwens, Jorgen; Eckert, Linda O.; Kochhar, Sonali; Bonhoeffer, Jan; Heath, Paul T

doi:10.1016/j.vaccine.2016.07.032

Cited by 44 publications

(47 citation statements)

References 37 publications

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“…Multiple factors complicate the introduction of new vaccines, including epidemiological data on specific disease burden and background on pregnancy outcomes in the target population [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Adverse pregnancy outcomes among women presenting at antenatal clinics in Ouélessébougou, Mali

Andemel

Gaoussou²,

Issiaka³

et al. 2020

Reprod Health

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Background: In sub-Saharan Africa, malaria continues to scourge the population and is the primary cause of morbidity and mortality in young children and pregnant women. As current preventative measures such as intermittent preventive treatment and use of insecticide-treated nets provide incomplete protection, several malaria vaccines are currently under development, including one to specifically prevent pregnancy malaria. Prior to conducting vaccine trials, it is important to obtain background information on poor pregnancy outcomes in the target population to establish a baseline. Methods: Pregnant women presenting at community health care centers for antenatal care were recruited to the study. Gestational age was determined by ultrasound examination following recruitment. Antenatal care and pregnancy outcome information were collected during a visit 4-8 weeks post-delivery. Results: One thousand eight hundred fifty women completed the study, and analysis included 1814 women after excluding multiple gestations (n = 26) and missing/incomplete data (n = 10). The percentage (95% CI) of adverse pregnancy outcomes is as follows: miscarriage, 0.28% (0.04-0.52); stillbirth, 1.93% (1.30-2.56); early neonatal death, 1.65% (1.03-2.24); late neonatal death, 0.39%, (0.10-0.68); and preterm delivery (PTD), 4.74% (3.76-5.73). The percentages of early and late neonatal deaths and PTD were significantly higher (p < 0.01) in primigravid compared to multigravid women. In primigravidae, 3.1, 1.1 and 7.1% of pregnancies resulted in early neonatal death, late neonatal death and PTD, respectively, while these outcomes in multigravidae were 1.0, 0.1 and 2.7%, respectively. Major malformations were identified in 4 newborns. Conclusions: Low gravidity and young age predict perinatal death and PTD. The information collected here can be used as a baseline for adverse pregnancy outcomes in future vaccine trials in pregnant women.

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Section: Introductionmentioning

confidence: 99%

Adverse pregnancy outcomes among women presenting at antenatal clinics in Ouélessébougou, Mali

Andemel

Gaoussou²,

Issiaka³

et al. 2020

Reprod Health

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“…23 The Brighton Collaboration Guidelines have been developed to aid the ongoing assessment of safety surveillance of vaccines already recommended for use in pregnant women. 20 Results of pre-and post-licensing safety studies also tend be limited by low statistical power related to the rarity of adverse pregnancy outcomes. 18 Long-term follow up of infants and their postnatal care needs is also required to assess the risk of congenital anomalies developing.…”

Section: Discussionmentioning

confidence: 99%

“…However, these are acknowledged to be challenging to implement in resource-limited settings, where cholera is endemic. 20…”

Section: Strengths and Limitationsmentioning

confidence: 99%

Pregnancy outcomes after a mass vaccination campaign with an oral cholera vaccine: a systematic review and meta‐analysis

Zhang

Wang

et al. 2020

BJOG

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Background Cholera has harmful effects on the fetus but safety data on the oral cholera vaccine in pregnant women are controversial. Objectives We conducted the first meta-analysis of studies in pregnant women comparing the effect of oral cholera vaccination on pregnancy outcomes with unvaccinated women. Outcomes of interest were adverse pregnancy outcome, miscarriage, stillbirth, preterm delivery, low birthweight, abortion and malformation. Search strategy The search was run in MEDLINE/PubMed, SCOPUS and Embase databases from inception up to December 2019. Selection criteria Inclusion criteria were: (1) studies that investigated the association between oral cholera vaccines and adverse pregnancy outcomes; (2) studies that reported outcomes with appropriate estimates; and (3) studies that contained an unvaccinated control group. Data collection and analysis A random-effects model (DerSimonian and Laird) was run to evaluate the overall treatment effect (relative risk, RR). The PRISMA statement was followed in reporting this meta-analysis. Main results Five studies included in meta-analysis with 5584 women (2920 exposed and 2664 not exposed). No significant increase in adverse pregnancy outcome (RR 1.03, 95% CI 0.79-1.34), miscarriage (RR 1.15, 95% CI 0.84-1.57) or stillbirth (RR 1.11, 95% CI 0.69-1.80) following cholera vaccine administration was found compared with control group. There was also no association with an increased risk of preterm delivery (RR 0.61, 95% CI 0.35-1.06) low birthweight (RR 0.84, 95% CI 0.56-1.26), accidental abortion (RR 1.02, 95% CI 0.77-1.35) or malformation (RR 0.70, 95% CI 0.22-2.25). Conclusions This study shows no evidence of an association between oral cholera vaccination and adverse pregnancy outcomes. The findings do not rigorously exclude the possibility that the vaccine protocol may result in some degree of harm.

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“…Despite there is no universally accepted method for causality grading of adverse drug reactions, the WHO algorithm is now recommended specifically for the pharmacovigilance of vaccine adverse events and is increasingly used by researchers and epidemiologists worldwide, in Lower Middle Income Countries like India (Singh et al, 2018;Sebastian et al, 2019) but even in developed countries. For example, the WHO causality assessment guidelines are widely utilized in Italy (Lombardi et al, 2019;Stefanizzi et al, 2019), Germany (Mentzer et al, 2018), Canada (MacDonald and Law, 2017), and were recommended by the Brighton Collaboration Group for analysis of safety data of vaccines in pregnancy (Jones et al, 2016). Given the importance and universal utilization of this approach and its inadequacies in the evaluation of multifactorial diseases, the WHO manual needs to be urgently reevaluated and revised.…”

Section: Competing Interestsmentioning

confidence: 99%

Causality assessment of adverse events following immunization: the problem of multifactorial pathology

Bellavite

2020

F1000Res

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The analysis of Adverse Events Following Immunization (AEFI) is important in a balanced epidemiological evaluation of vaccines and in the issues related to national vaccine injury compensation programs. If manufacturing defects or vaccine storage and delivering errors are excluded, the majority of adverse reactions to vaccines occur as excessive or biased inflammatory and immune responses. These unwanted phenomena, occasionally severe, are associated with many different endogenous and exogenous factors, which often interact in complex ways. The confirmation or denial of the causal link between an AEFI and vaccination is determined pursuant to WHO guidelines, which propose a four-step analysis and algorithmic diagramming. The evaluation process from the onset considers all possible "other causes" that can explain the AEFI and thus exclude the role of the vaccine. Subsequently, even if there was biological plausibility and temporal compatibility for a causal association between the vaccine and the AEFI, the guidelines ask to look for any possible evidence that the vaccine could not have caused that event. Such an algorithmic method presents some concerns that are discussed here, in the light of the multifactorial nature of the inflammatory and immune pathologies induced by vaccines, including emerging knowledge of genetic susceptibility to adverse effects. It is proposed that the causality assessment could exclude a consistent association of the adverse event with the vaccine only when the presumed "other cause" is independent of an interaction with the vaccine. Furthermore, the scientific literature should be viewed not as an exclusion criterion but as a comprehensive analysis of all the evidence for or against the role of the vaccine in causing an adverse reaction. These issues are discussed in relation to the laws that, in some countries, regulate the mandatory vaccinations and the compensation for those who have suffered serious adverse effects.

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Guideline for collection, analysis and presentation of safety data in clinical trials of vaccines in pregnant women

Cited by 44 publications

References 37 publications

Adverse pregnancy outcomes among women presenting at antenatal clinics in Ouélessébougou, Mali

Adverse pregnancy outcomes among women presenting at antenatal clinics in Ouélessébougou, Mali

Pregnancy outcomes after a mass vaccination campaign with an oral cholera vaccine: a systematic review and meta‐analysis

Causality assessment of adverse events following immunization: the problem of multifactorial pathology

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