In 2009 the European Medicines Agency (EMA) launched PROTECT (Pharmacoepidemiological Research on Outcomes of Therapeutics by a European Consortium), a new research program designed to strengthen the monitoring of the benefit risk of medicines in Europe. PROTECT was part of the original €2 billion public-private partnership – The Innovative Medicines Initiative (IMI) – between the European Union and EFPIA (European Federation of Pharmaceutical Industries and Associations.)
PROTECT consists of 35 partners (regulators, patient associations, industry, academia and small/medium enterprises) working together to develop new methods to enhance early detection of adverse drug reactions from different data sources. One of the first projects launched through PROTECT was the Pregnancy Study, an observational study designed to capture data from pregnant women about their lifestyle choices and medication and drug use.
Stella Blackburn, vice president and global head of risk management for QuintilesIMS, was heavily involved with this groundbreaking study both in her previous role at the EMA and subsequently at QuintilesIMS. She recently sat down with Clinical Leader to discuss how the program worked, and the valuable insights gathered.
Ed Miseta: What makes the Pregnancy Study so unique?
Stella Blackburn: The Pregnancy Study is the first time any research group has tried to collect data directly from pregnant women without the involvement of healthcare professionals. Most observational studies gather data through healthcare providers or electronic health records (EHR), but we went directly to the patients. We wanted to know whether the data we collected directly from patients would be suitable for research purposes.
Miseta: Why is this a big deal?
Blackburn: Not much is known about the effect of a medicine on a developing fetus at the time a medicine is authorized. Virtually all knowledge is gained during real world use of the medicine. Many factors, not just medicines, can affect the outcome of a pregnancy. Pregnant women may not always be totally honest with their physicians about recreational drug and alcohol use, and they often aren’t asked about over-the-counter prescriptions or whether they actually took the medications they were prescribed. We decided the only way to collect such information was to ask the women directly.
The Pregnancy Study was designed to test whether the data collection tools developed by PROTECT are suitable to collect research quality information about medication use and lifestyle factors and whether these methods could also be used in other patient populations.
Miseta: Why is it so important to capture this information from pregnant women?
Blackburn: Since the thalidomide tragedy was revealed in 1962, everyone is concerned about use of medicines during pregnancy. For ethical reasons, pregnant women are usually excluded from clinical trials unless the drug specifically treats a pregnancy related condition. As a result there is very little information available about which drugs are safe for these women. This is especially concerning for women with chronic conditions, like hypertension or epilepsy, who can’t just stop their medications because they are pregnant.
Currently much information on the use of medicines during pregnancy is through reports of “accidental exposure” when a women is taking a medicine before she realizes she is pregnant. This has created a huge knowledge gap about the impact of drugs on pregnant women that we are trying to close.
Miseta: How did you convince women that sharing this information with you would be safe?
Blackburn: We guaranteed that the medical data they shared with us would be stored in a secure and confidential form under a study number and that it would not be shared with their healthcare providers. All medical data was stored completely separately from contact information and any personal identifiers to ensure their privacy and only aggregated data would be used in any publication.
Miseta: What method of data collection did you use?
Blackburn: We recruited the women through adverts, social media, leaflets at health centers and other marketing efforts. Then we asked participants to complete a series of questionnaires at the PROTECT website. The first questionnaire gave us a baseline of their health and chronic medicine use, then they completed subsequent questionnaires every two-to-four weeks throughout their pregnancy outlining any new medicines they had consumed since the last survey and any changes to their chronic medicine usage. We sent text alerts and other reminders to encourage participation.
Miseta: How did you ensure data quality?
Blackburn: Each set of questions were standardized, but we personalized them based on prior responses. For example, if a participant previously reported taking omeprazole, we asked if they were still taking it. We provided the names of the medicines used most commonly in each of the countries to treat particular conditions and also included brand names to clarify questions – so if we asked if they used acetaminophen, we also provided the top brands in their country to ensure they understood the question.
Miseta: What were some of the most valuable insights gleaned from this study?
Blackburn: The study provided a number of interesting insights into the choices pregnant women make about drug use. For example, of the more than 2000 women who participated, 83 percent said they used one or more medicines during pregnancy, and 19 percent used 5 or more medications. Of these, 41 percent had used a medicine available without prescription. We also found roughly one percent of participants had taken medications that were prescribed to someone else, and seven percent decided not to take medications that had been prescribed to them. Twenty-three percent of women drank alcohol during their pregnancy.
Miseta: What does that information tell you?
Blackburn: Our results showed that significant discrepancies between what pregnant women tell their physicians and what they admitted to us. It also showed that many pregnant women take non-prescription medication. This suggests that traditional avenues for collecting healthcare data doesn’t provide a complete picture of total drug-use or lifestyle habits during pregnancy.
We also found that the self-reported data from study participants contained a lot of valuable information about medicines used for short-term conditions, and medications used intermittently. This is valuable information that can inform how physicians talk to pregnant women about drug use.
Miseta: What do you think the industry learn from this study?
Blackburn: These results reinforced our belief that direct-to-patient studies are vital to gaining insight into how pregnant women use medication. It also proved that it’s possible to successfully conduct this research, and that women are willing to share private information given an anonymous environment.
We also learned a lot about what not to do. For example, we lost a lot of participants in the first questionnaire because it was too long. If we were to do it again, we would break the questionnaires into shorter chunks and maybe add games or useful information to the website to make participation more engaging. It would also be valuable to link the data directly to the participants’ EHRs so we could track the outcomes of their pregnancies. Many women were too busy with their new baby to let us know the outcome of the pregnancy. We attempted some data linkage in this study, but due to it being a pilot study we only had moderate success.
Despite these bumps, we think the study was a great success. It generated incredible data about the lifestyle choices pregnant women make, and what medicines they actually take during pregnancy. We also enrolled some women in a very early stage of their pregnancy – before they would normally be studied using traditional methods. This method can collect data that are never normally collected during traditional pregnancy studies but which is essential to understanding the effects of medicines. Expanding this across Europe and combining it with EHR data would give a fantastic insight into which medicines are safe to use during pregnancy which would be a huge help to all pregnant women and a major contribution to public health.