Abstract
Objective
The findings in retrospective pregnancy registries related to prenatal drug exposure
(collected after pregnancy outcome is known) are commonly reported in regulatory documents
and in the medical literature. However, there is little information about the accuracy
of the estimates of risk from such registries. We therefore sought to compare the
rates of major congenital malformations reported in retrospective and prospective
registries for the same drug to quantify the potential bias of retrospective reports.
Methods
We searched for all fetal safety reports related to medications for which information
from both prospective and retrospective registries was available. These were published
either in the peer-reviewed literature or as pharmaceutical company documents between
1984 and 2011.
Results
For all drugs registries studied, estimates of major congenital malformations from
retrospective registries tended to be higher than the rates in prospective registries;
median estimates of risk were higher by a factor of 4.18 ± 1.23 (range 2.13–5.97).
Conclusions
The present study confirms a major and consistent bias against the null hypothesis
in studies of teratogenic risk using retrospective registries, and this must be considered
when interpreting such data. Spontaneous reporting of outcomes after exposure to a
drug is highly selective towards adverse events, which families with normal pregnancy
outcomes are less likely to report.
Résumé
Objectif
Les constatations tirées de registres rétrospectifs d’exposition prénatale aux médicaments
(dont les données sont recueillies une fois l’issue de la grossesse connue) sont régulièrement
citées dans des documents réglementaires et dans la littérature médicale. Toutefois,
les renseignements quant à l’exactitude de l’estimation des risques effectuée à partir
de ces registres sont limités. Nous avons donc cherché à comparer le taux de malformations
congénitales majeures déclarées dans des registres rétrospectifs et prospectifs pour
un même médicament afin de quantifier le biais potentiel associé aux rapports rétrospectifs.
Méthodologie
Nous avons cherché tous les rapports sur l’innocuité pour le fœtus portant sur des
médicaments pour lesquels nous disposions de données tirées de registres rétrospectifs
et prospectifs. Il s’agissait de documents produits par des pharmaceutiques ou d’articles
publiés dans des revues évaluées par les pairs entre 1984 et 2011.
Résultats
Dans l’ensemble, les estimations du taux de malformations congénitales majeures basées
sur les données de registres rétrospectifs avaient tendance à être supérieures à celles
associées aux registres prospectifs. L’estimation médiane du risque était supérieure
d’un facteur de 4,18 ± 1,23 (étendue: 2,13–5,97).
Conclusions
La présente étude a confirmé l’existence d’un biais important et constant contre l’hypothèse
nulle dans les études sur le risque tératogène fondées sur des registres rétrospectifs.
Il faut être conscient de ce biais au moment d’interpréter les données de ces registres.
La déclaration spontanée de l’issue de grossesse après l’exposition à un médicament
dépend grandement de la survenue d’événements indésirables; en effet, les familles
sont moins susceptibles de déclarer une issue de grossesse normale.
Key Words
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Article info
Publication history
Accepted:
September 1,
2016
Received:
June 23,
2016
Footnotes
Competing Interests: None declared.
Identification
Copyright
Copyright © 2016 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.
