A blog from the Centre for Research Ethics & Bioethics (CRB)

Tag: medicine safety

Better evidence may solve a moral dilemma

More than 5 million women become pregnant in the EU every year and a majority take at least one medication during pregnancy. A problem today is that as few as 5% of available medications have been adequately monitored, tested and labelled with safety information for use in pregnant and breastfeeding women. The field is difficult to study and has suffered from a lack of systematically gathered insights that could lead to more effective data generation methodologies. Fragmentation and misinformation results in confusing and contradictory communication and perception of risks by both health professionals and women and their families. For the doctor who prescribes the medicine, a genuine moral dilemma arises. In order not to expose the child to risks, the lack of good scientific evidence in many cases means that, for precautionary reasons, the drug treatment is discontinued or the mother is advised not to breastfeed. At the same time, the mother benefits most from the prescribed medicine and we know that breastfeeding is good for both the newborn and the mother.

Within the project ConcePTION, several studies are underway to investigate the effect of drugs both during pregnancy and during breastfeeding. Based on the need to meet regulatory requirements, procedures have been established for breast milk collection, informed consent, shipping, storage and analysis of pharmacokinetic properties (how drugs are metabolized in the body). Five demonstration studies are conducted. The University of Oslo is doing such a study on a drug called Levocetirizine, the University Hospital of Toulouse is studying Amoxicillin and the University Hospital of Lausanne is studying the drug Venlafaxine.

In Sweden, in two demonstration studies, we will collect breast milk and blood samples from the mother and the child for two drugs: metformin, which is used in the treatment of type 2 diabetes and prednisolone, which is used in the treatment of for example rheumatoid arthritis. In both cases, there is limited data, which is partly old, from the 1970s, and partly analyzed with outdated methods. Both studies are approved by The Swedish Medical Product Authority (MPA) as low intervention clinical trials (see below). 

The studies are a collaboration between Uppsala University and several clinical centers: Sahlgrenska University Hospital/East in Gothenburg, Örebro University Hospital, Center for Clinical Children’s Studies, Astrid Lindgren Children’s Hospital in Stockholm, Södra Älvsborgs Hospital in Borås and Umeå University Hospital, with adjacent biobanks. Breast milk from the woman and blood samples from both woman and child will be transported to Uppsala Biobank for storage and analyzed with mass spectrometric methods at the Department of Pharmacy at Uppsala University. Informed consent is obtained both for the sampling and for the possibility of conducting future research on the stored samples. Collaborating biobanks are: Uppsala Biobank, Biobank West in Gothenburg, Örebro Biobank, Stockholm Medical Biobank and Biobank North in Umeå. 

Through these two studies, research biobanks with breast milk and associated blood samples are established for the first time in Sweden. In the long run, doctors and women who become pregnant can get better information for their recommendations and decisions regarding the use of medicines. 

ConcePTION is funded by the Innovative Medicines Initiative (IMI), which is a collaboration between the European Commission and the European Medicines Federation. 

Approvals by the Swedish Medical Product Authority (MPA): Dnr: 5.1.1-2023-090592 and 5.1.1-2023-104170.

Mats G. Hansson, photo by Mikael Wallerstedt

Written by…

Mats G. Hansson, senior professor of biomedical ethics at Uppsala University’s Centre for Research Ethics & Bioethics.

This post in Swedish

Part of international collaborations

How do we find out if drugs are safe for groups excluded from clinical trials?

Drug development requires that the drug is tested on patients in clinical trials. Not only the drug’s effectiveness is tested on the patients, but also its safety. Does the drug have serious side effects and what dosage is safe? Thanks to such clinical research, approved drugs can be provided with safety information, which enables doctors and patients to make informed decisions about drug treatment.

However, there are vulnerable groups that are often excluded from clinical studies, such as pregnant and breastfeeding women. But this protection of a vulnerable group can make the group extra vulnerable when deciding on drug treatment. If there is no evidence, it is not known whether the medicine the woman needs risks harming her, the fetus or the child being breastfed. It is also not known what dosage should be recommended. Perhaps the woman herself refrains from taking a medicine she needs, or receives advice from the doctor to refrain from it. Not because one knows that the medicine poses risks for the group, but because one does not know.

Are there other ways to obtain evidence on medicine safety for pregnant and breastfeeding women, besides clinical studies? Yes, there are, because pregnant and breastfeeding women must of course often use medication. Several registers already contain data from women who use medicines during pregnancy. In addition, pregnant and breastfeeding women using medicines may be engaged in additional data collection activities. Thus, there is already data as well as additional opportunities to collect data, without involving the group in clinical studies.

Josepine Fernow describes in Uppsala Reports such an attempt to compile existing data and expand the possibilities of collecting new data: the European project IMI ConcePTION. This project is developing several different paths towards better future safety information about drug treatment during pregnancy and breastfeeding. One challenge is to develop a technical infrastructure where data collected in different registers and in different formats are harmonized so that they can be collected and handled in standardized ways. Another challenge is to enable pregnant women to easily report relevant data about their medication use, for example via a mobile application. The project also tries to produce new data on breastfeeding and medicine use. For example, milk is collected and analyzed from breastfeeding women who use various medicines, in order to understand and predict how these medicines are transferred to the breast milk and in what concentration. Two of these breastfeeding studies are underway in Sweden. They are coordinated by CRB and we will write about them on this blog.

ConcePTION is also developing a knowledge bank that will be available online from the end of 2024, which will make the data and knowledge generated by the project useful. There are thus several avenues for research along which one can generate evidence for better safety information about various medicines for pregnant and breastfeeding women, without involving the group in clinical studies.

Read Josepine Fernow’s description of the project here: Making medicines safer for pregnant and breastfeeding women. There you will also find several links to the project and to the project’s publications.

Pär Segerdahl

Written by…

Pär Segerdahl, Associate Professor at the Centre for Research Ethics & Bioethics and editor of the Ethics Blog.

This post in Swedish

Part of international collaborations