Research challenges for drug‐induced birth defects

Mitchell, Allen A.

doi:10.1002/cpt.374

Cited by 8 publications

(8 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Secondly, an important limitation of these risk classification systems in general is that specific CAs are not identified for high‐risk medications. However, the teratogenic risk of a medication is almost always specific to one (or more) particular CA(s), rather than an increased risk of malformations in general . The identification rate used in this study does not differentiate between a medication associated with only one CA and one associated with a number of CAs.…”

Section: Discussionmentioning

confidence: 95%

Identifying signals of potentially harmful medications in pregnancy: use of the double false discovery rate method to adjust for multiple testing

Cavadino

Prieto‐Merino

Morris

2018

Brit J Clinical Pharma

View full text Add to dashboard Cite

Aims Surveillance of medication use in pregnancy is essential to identify associations between first trimester medications and congenital anomalies (CAs). Medications in the same Anatomical Therapeutic Chemical classes may have similar effects. We aimed to use this information to improve the detection of potential teratogens in CA surveillance data. Methods Data on 15 058 malformed fetuses with first trimester medication exposures from 1995–2011 were available from EUROmediCAT, a network of European CA registries. For each medication‐CA combination, the proportion of the CA in fetuses with the medication was compared to the proportion of the CA in all other fetuses in the dataset. The Australian classification system was used to identify high‐risk medications in order to compare two methods of controlling the false discovery rate (FDR): a single FDR applied across all combinations, and a double FDR incorporating groupings of medications. Results There were 28 765 potential combinations (523 medications × 55 CAs) for analysis. An FDR cut‐off of 50% resulted in a reasonable effective workload, for which single FDR gave rise to eight medication signals (three high‐risk medications) and double FDR 50% identified 16 signals (six high‐risk). Over a range of FDR cut‐offs, double FDR identified more high‐risk medications as signals, for comparable effective workloads. Conclusions The double FDR method appears to improve the detection of potential teratogens in comparison to the single FDR, while maintaining a low risk of false positives. Use of double FDR is recommended in routine signal detection analyses of CA data.

show abstract

Section: Discussionmentioning

confidence: 95%

Identifying signals of potentially harmful medications in pregnancy: use of the double false discovery rate method to adjust for multiple testing

Cavadino

Prieto‐Merino

Morris

2018

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…Furthermore, almost a third of the medications in the EUROmediCAT data were not present in the Australian risk classification database. In practice, teratogenic risk is nearly always specific to certain CAs . This may have affected our “identification rate,” which does not reflect the number of different CAs that a medication is associated with.…”

Section: Discussionmentioning

confidence: 99%

“…In practice, teratogenic risk is nearly always specific to certain CAs. 29 This may have affected our "identification rate," which does not reflect the number of different CAs that a medication is associated with. In this analysis, any associations arising due to confounding by indication cannot be identified.…”

Section: Evaluation and Comparison Of Methodsmentioning

confidence: 99%

Bayesian hierarchical methods in the detection of potentially teratogenic first‐trimester medications

Cavadino

Prieto‐Merino

Morris

2020

Pharmacoepidemiology and Drug

View full text Add to dashboard Cite

Purpose Bayesian hierarchical models (BHMs) have been used to identify adverse drug reactions, allowing information sharing amongst adverse reactions and drugs expected to have similar properties. This study evaluated the use of BHMs in the routine signal detection analyses of potential first‐trimester teratogens, where these models have not previously been applied. Methods Data on 15 058 malformed foetuses exposed to first trimester medications (1995‐2011) from 13 European congenital anomaly (CA) registries were analysed. The proportion of each CA in women taking a specific medication was compared with the proportion of that CA in all other women in the dataset (55 CAs × 523 medications). BHMs were grouped by either medications or CAs or by both simultaneously, and the results compared with analysing each medication‐CA combination separately and adjusting for multiplicity using a double false discovery rate (FDR) procedure. The proportions of “high‐risk” medications (medications which have been shown to carry a moderate to high risk of foetal malformations) identified as potential signals were compared, as well as the total number of potential signals requiring follow up (the effective workload). Results BHMs identified more high‐risk medications than the double FDR method, but the effective workload was larger. A BHM grouping both medications and CAs, for example, identified 23% of high‐risk medications compared with 14% by the double FDR; however, there was an increase from 16 to 71 potential signals requiring follow up. Conclusion For comparable effective workloads, BHMs did not outperform the double FDR, which is comparatively straightforward to implement and is therefore recommended for continued use in teratogenic signal detection analyses.

show abstract

“…Investigation is challenging because retrospective reporting after an affected child is born can be notoriously biased: the mother of the affected child may be much more scrupulous about remembering presumed exposures compared to mothers of healthy newborns. In addition to drugs, teratogenic effects noted in a newborn or child can be secondary to intrauterine exposure to infection, chemicals in the environment, or some maternal disorders . A partial explanation for why the safety of drugs used by women of reproductive age has not been sufficiently assessed during the preapproval process for drugs that is required by the FDA lies in the history of the FDA itself.…”

Section: Teratogensmentioning

confidence: 99%

The 2015 US Food and Drug Administration Pregnancy and Lactation Labeling Rule

Brucker¹,

King²

2017

J Midwife Womens Health

View full text Add to dashboard Cite

As of 2015, the US Food and Drug Administration (FDA) discontinued the pregnancy risk categories (ABCDX) that had been used to denote the putative safety of drugs for use among pregnant women. The ABCDX system has been replaced by the FDA Pregnancy and Lactation Labeling Rule (PLLR) that requires narrative text to describe risk information, clinical considerations, and background data for the drug. The new rule includes 3 overarching categories: 1) pregnancy, which includes labor and birth; 2) lactation; and 3) females and males of reproductive potential. This article reviews the key components of the PLLR and clinical implications, and provides resources for clinicians who prescribe drugs for women of reproductive age.

show abstract

Research challenges for drug‐induced birth defects

Cited by 8 publications

References 7 publications

Identifying signals of potentially harmful medications in pregnancy: use of the double false discovery rate method to adjust for multiple testing

Identifying signals of potentially harmful medications in pregnancy: use of the double false discovery rate method to adjust for multiple testing

Bayesian hierarchical methods in the detection of potentially teratogenic first‐trimester medications

The 2015 US Food and Drug Administration Pregnancy and Lactation Labeling Rule

Contact Info

Product

Resources

About