The Awareness of and Adherence to the Pregnancy Prevention Program for Oral Retinoids and Valproate: A Questionnaire Survey among Pharmacy Technicians Denmark

A 2025 questionnaire survey of Danish pharmacy technicians revealed that while most are aware of the teratogenic risks of oral retinoids, knowledge regarding valproate is significantly poorer, with many lacking familiarity with the required Pregnancy Prevention Program measures, highlighting an urgent need for targeted educational interventions.

The Gist

Imagine a pharmacy as a busy train station. The pharmacy technicians are the conductors who hand out the tickets (medications) to passengers. Some of these tickets are for very special, high-speed trains that can be dangerous if the passenger is carrying a fragile, precious cargo (a developing baby). Two of these "dangerous trains" are oral retinoids (used for severe skin issues like acne) and valproate (used for seizures and mood disorders).

To keep everyone safe, the European Union (the "Head Office") created a Safety Checklist called the Pregnancy Prevention Program (PPP) in 2018. This checklist includes things like warning signs on the ticket, special cards for passengers, and rules for the conductors to follow.

This study asked the Danish train conductors (pharmacy technicians): "Do you know these trains are dangerous? Are you using the Safety Checklist?"

Here is what they found, explained simply:

1. The Knowledge Gap: One Train is Well-Known, the Other is a Mystery

• The "Acne Train" (Oral Retinoids): Most conductors knew this train was dangerous. They had heard about the risks from their training or their coworkers.
• The "Seizure Train" (Valproate): This is where things got shaky. About one-third of the conductors didn't even know this train could hurt a baby. They were flying blind on this one.
• The Comparison: The study noted that these technicians generally knew less about these risks than the "Station Managers" (pharmacists), especially regarding the Seizure Train.

2. How They Used the Safety Checklist

The Safety Checklist had several tools, like a big red warning sticker on the box, a checklist for the staff, and reminder cards for passengers.

• What they actually used: The most popular tool was the big red warning sticker on the outside of the box. It was the easiest to see, so 54% of technicians used it for the Acne Train and 19% for the Seizure Train.
• What they ignored: The more complex tools, like the staff checklist or the patient reminder cards, were rarely used.
• Future Plans:
  • For the Seizure Train, many technicians said, "I didn't know about these tools, but now that I do, I want to use them."
  • For the Acne Train, even though they knew the risks, many said, "I know the rules, but I probably won't use the extra tools in the future."

3. How They Talked to Passengers

• Acne Train: When handing out these tickets, most technicians (72%) would stop and say, "Hey, this medicine can hurt a baby, make sure you're using birth control."
• Seizure Train: When handing out these tickets, they were less likely to bring up the baby topic directly. Instead, if they thought a passenger might be pregnant, they would say, "I need to call the doctor who prescribed this to check."

4. Why Didn't They Use the Full Checklist?

The researchers asked the technicians why they didn't use all the safety tools, and the answers were like excuses you might hear from a busy worker:

• "I didn't know it existed": They hadn't been shown the materials.
• "It's too complicated": The forms were hard to fill out or understand.
• "I'm too busy": The station was chaotic, and they didn't have time to stop and read a long checklist.
• "It's not my job": Some felt the doctor who wrote the prescription was the one responsible for the safety talk, not them.
• "It's awkward": Talking about pregnancy and birth control with young women felt too personal or sensitive.
• "I forgot": For the Seizure Train, they said, "We rarely give out these tickets, so the safety rules just slipped my mind."

The Bottom Line

The study concludes that while Danish pharmacy technicians are generally good at their jobs, they need more help and training, specifically regarding the Seizure Train (valproate). They need to know the risks better and need the Safety Checklist tools to be simpler and easier to fit into their busy day.

Important Note: This study is a "preprint," meaning it is a draft report that hasn't been officially peer-reviewed yet. It highlights a problem in the system but doesn't offer a final, proven solution for doctors to use in clinics right now. It simply says, "Hey, we found some gaps in the safety net; let's fix the training."

Technical Summary

Technical Summary: Awareness of and Adherence to the Pregnancy Prevention Program for Oral Retinoids and Valproate among Danish Pharmacy Technicians

Problem Statement
Oral retinoids (e.g., isotretinoin, acitretin) and valproate are essential medications for severe dermatological and neurological conditions, respectively. However, both classes carry significant teratogenic risks, capable of causing congenital malformations and neurodevelopmental impairments. In response to persistent prenatal exposure, the European Medicines Agency (EMA) revised Pregnancy Prevention Programs (PPPs) in 2018, introducing comprehensive risk minimization measures including educational materials, patient reminder cards, and pharmacy checklists.

While previous multi-country surveys (2019–2020) assessed the knowledge and adherence of physicians, pharmacists, and patients, a critical gap remained regarding pharmacy technicians. In Denmark, pharmacy technicians constitute a key professional group responsible for dispensing prescription medications and counseling customers. Despite their frontline role in interacting with women of childbearing potential, no prior research had examined their knowledge of teratogenicity, their adherence to PPPs, or their dispensing practices for these high-risk medications.

Methodology
The study employed a cross-sectional survey design conducted in spring 2025 (March–May). Two separate questionnaires were utilized, adapted from instruments previously developed and tested in an international project involving Danish pharmacists.

• Data Collection: Surveys were distributed online via the SurveyXact system. Recruitment channels included relevant Facebook groups, invitations to members of the Danish Pharmacy Practice Research Network, and emails sent to every second pharmacy listed on the Danish medicine information site.
• Participants: The study analyzed responses from two cohorts: 80 respondents for the oral retinoid survey and 41 respondents for the valproate survey. The majority were female (95% and 90.2%, respectively) and working as pharmacy technicians or students.
• Analysis: Descriptive statistics (frequencies and percentages) were used for categorical variables. Open-ended questions regarding barriers to PPP implementation were analyzed using qualitative content analysis.

Key Results

• Awareness of Teratogenicity:
  • Oral Retinoids: Awareness was high; only 2.5% of respondents were unaware that oral retinoids are teratogenic. Knowledge was primarily derived from academic/professional studies (54%) and colleagues (39%).
  • Valproate: Awareness was significantly lower. Approximately one-third (29.3% "just now" + others unaware) of respondents were unaware of valproate's teratogenicity.
• Adherence to PPP Measures:
  • The most frequently used PPP measure for both medications was the warning label on the outer packaging (54% for retinoids, 19% for valproate).
  • Future Intentions: Patterns diverged between the two drugs. For oral retinoids, respondents who did not currently use PPP materials were generally unlikely to use them in the future. Conversely, for valproate, respondents who did not currently use the materials expressed a higher intention to use them in the future.
• Dispensing Practices:
  • For oral retinoids, the most common practice was informing women about teratogenic effects (72%).
  • For valproate, the most common practice was referring suspected pregnancies to the prescribing physician (62%), followed by informing women of risks (45%).
  • Only a small minority of respondents reported that their dispensing practices changed following the 2018 EMA PPP update.
• Barriers to Implementation:
  Qualitative analysis identified five recurring themes: lack of knowledge about PPP materials, impractical design of materials (e.g., cards getting lost, complexity), time pressure in routine work, the perception that risk communication is solely the physician's responsibility, and the sensitivity of the topic (pregnancy). For valproate specifically, the rarity of dispensing the drug led to forgetfulness regarding the PPP.

Significance and Claims
The paper claims that Danish pharmacy technicians possess knowledge regarding the teratogenicity of oral retinoids that is comparable to that of pharmacists, but their knowledge regarding valproate is substantially poorer. This discrepancy is attributed to the longer history of risk minimization for retinoids and differences in educational pathways (technicians rely more on practice-based learning and colleagues, whereas pharmacists engage more with postgraduate education).

The study concludes that the feasibility of PPP measures for both drug classes requires optimization. Specifically:

1. For Valproate: The primary barrier appears to be a lack of awareness and knowledge. Educational interventions to disseminate information about PPP requirements are necessary, as there is a demonstrated willingness among technicians to adopt these measures once informed.
2. For Oral Retinoids: The barrier is not knowledge but rather attitudinal or workflow-related (e.g., perceived lack of added value, role ambiguity). Nuanced exploration is needed to clarify professional responsibilities and improve the usability of PPP tools in daily workflows.

The authors emphasize that while the sample size was small (particularly for valproate), the findings suggest that current knowledge gaps among pharmacy technicians regarding high-risk medications may be even more pronounced than reported, necessitating targeted educational programs to ensure patient safety.