When a patient starts a new drug or therapy, what matters most to any given person is often a very simple question: “Is this treatment safe for me?”
When someone becomes or is trying to become pregnant while on a medication, that same question extends to consider not one, but two or more people. It’s crucial for patients, providers, life sciences organizations and regulators to understand the impact any medication may have on both patient and infant.
Historically, it’s been challenging to gain information about drug and vaccine safety during pregnancy. There are two reasons for this.
First, pregnant women are often excluded from clinical trials due to concerns about increased vulnerability. So, trials may not generate any data about a drug’s safety for this patient population.
Second, the data themselves are complicated. They need to link together maternal exposures and infant health outcomes.
After government agencies like the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approve a drug, they often ask the drug manufacturer to conduct additional studies to track safety during and after pregnancy.
To better understand the special requirements for this type of research, I spoke with Dr. Florence Wang and Dr. Monica Bertoia from the Optum Life Sciences Epidemiology team. This group designs and conducts research on the safety and effectiveness of drugs, devices, biologics and health care delivery.
Florence, how does your team approach these pregnancy-related projects?
The importance of this kind of information is something that resonates with all of us. The need for these investigations isn’t going away anytime soon.
To help sponsors and regulatory agencies answer these types of questions, we created a capability called the Dynamic Assessment of Pregnancies and Infants, or DAPI.
DAPI has the powerful capability to link the health data of women and their infants within the Optum claims-based research database. It includes about 200,000 pregnancies per calendar year.
The resulting database allows researchers to track women’s exposures, medications they took before and during pregnancy, and link the exposures to infants in utero.
We examine these exposures in relation to pregnancy outcomes and infant health outcomes. The DAPI dataset offers unparalleled depth and breadth for answering questions about maternal and infant health.
The de-identified dataset we utilize includes live and non-live pregnancy outcomes. We can pull in additional information from medical records, like vital signs, comorbidities and lifestyle variables. In-hospital labor, delivery care and medication administrations can also be captured in detail.
Could you take a moment and talk about the rigor that goes into generating this regulatory-grade evidence?
Sure. The FDA released guidance for the industry about post-approval pregnancy safety studies in 2019. We know our work needs to stand up to a level of scrutiny that meets regulatory standards, and our results can be submitted to these governing agencies to support post-marketing requirements and commitments.
DAPI has all of the key elements required for the rigorous examination of many research questions related to maternal and infant health.
Additionally, by abstracting medical records and linking with claims data, we can confirm the pregnancy and infant outcomes that are initially identified from the claims. That’s an essential element of post-approval pregnancy studies.
Monica, can you walk us through what this looks like in practice?
These projects are multi-year studies. Drug manufacturers might approach us after a regulatory agency requests a post-approval study, or they can pursue this research proactively. Often, we’re asked to look at treatments for common conditions that may be used by women of reproductive age.
We’re doing a project now for a drug that treats atopic dermatitis, also known as eczema. The study examines the use of the drug during pregnancy, evaluating risk of miscarriage, stillbirth and infant congenital malformation.
This study is still in progress, and the results have the potential to help lay out recommendations for women who require treatment for atopic dermatitis while pregnant.
We have conducted pregnancy studies for many years, but recently the FDA has been requesting more and more of these long-term studies.
Some of them find no increased risks for mothers or their infants. Others have resulted in drug labeling changes that include a warning against use of a particular medication during pregnancy, or a recommendation for additional monitoring.
It’s really fulfilling to directly contribute to the information that’s going into those drug labels, as well as to public health knowledge in general, helping patients and providers make important decisions about their care.
The reports Florence and Monica prepare are meant for the scientific community and public health officials. But we all have a vested interest in better understanding the effects of medications on mothers-to-be and their children.
By translating real-world data into real-world evidence, Florence and Monica’s team helps fill in the gaps in data on the safety of medicines when used during pregnancy. This also helps allay some of the fear and uncertainty that accompanies one of the most exciting periods in many peoples’ lives.
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