Prescription Event Monitoring (PEM)
Prescription Event Monitoring (PEM) is an important post-marketing surveillance method used to evaluate the safety of new medicines under real-world conditions. Unlike clinical trials, which involve limited and highly selected populations, PEM observes drug safety in large, diverse patient groups during routine clinical practice. As a non-interventional, observational cohort method, PEM bridges the gap between clinical trials and large-scale pharmacoepidemiologic evidence.
Introduction to Prescription Event Monitoring
PEM is a form of pharmacovigilance designed to identify and evaluate adverse events associated with newly marketed drugs. It follows a cohort of patients identified through prescriptions and monitors them for a defined period—usually six to twelve months—to capture all medical events occurring after exposure to the drug.
This approach is particularly valuable because pre-marketing clinical trials have limitations, including:
- Small sample sizes
- Short treatment durations
- Limited patient diversity
- Exclusion of special populations (elderly, pregnant women, children, comorbid patients)
- Controlled settings that do not reflect real-world usage
PEM helps address these gaps by collecting data from everyday clinical use without altering clinicians’ prescribing behavior.
Evolution of PEM
The spontaneous reporting system has historically played a major role in identifying early drug safety concerns. However, several limitations—especially under-reporting—led to the development of more structured pharmacoepidemiologic methods.
One such trigger was the failure of spontaneous reporting to detect the oculomucocutaneous syndrome associated with Practolol. This event prompted Professor William Inman to establish the Prescription Event Monitoring system at the Drug Safety Research Unit (DSRU) in Southampton, UK, in 1981.
Other countries adopted similar approaches. For example:
- New Zealand implemented the Intensive Medicines Monitoring Programme (IMMP), overseen by the Medicines Adverse Reaction Committee (MARC).
Today, PEM forms an essential part of many national pharmacovigilance programs.
Process of Prescription Event Monitoring
The PEM process in the UK—still considered the gold standard—involves several organized steps. These ensure systematic identification, follow-up, and evaluation of patients exposed to the drug of interest.
1. Identification of New Drug for Monitoring
The DSRU selects a newly marketed drug for PEM based on expected clinical relevance, safety concerns, or regulatory requirements.
2. Notification to Prescription Pricing Authority (PPA)
Once a drug is selected, the DSRU informs the PPA that prescriptions for this medicine need to be tracked.
3. Patient Prescription Capture
When patients present prescriptions at pharmacies, the pharmacist processes them for dispensing and reimbursement. The prescription data is forwarded to the PPA in confidence.
4. Transfer of Data to DSRU
The PPA securely sends anonymized copies of relevant prescriptions to the DSRU. These records form the basis of the PEM cohort.
5. Creation of Patient Records
The DSRU constructs longitudinal patient records, documenting the sequence of prescriptions and follow-up timelines.
6. Green Form Questionnaire Distribution
After sufficient time has passed from the first prescription, the DSRU sends Green Forms (structured questionnaires) to the prescribing general practitioners (GPs). These forms request information on:
- Any medical events experienced since starting the drug
- Hospitalizations
- Dose changes
- Therapy discontinuation reasons
- Pregnancy outcomes
- Deaths and their causes
Physicians return completed forms to the DSRU, where they are scanned, reviewed, and entered into the database.
7. Follow-up and Special Event Monitoring
If certain adverse events of special interest occur—such as pregnancy exposure or serious outcomes—additional questionnaires are sent to gather detailed information.
Advantages of Prescription Event Monitoring
- Real-world data: PEM evaluates drug safety under natural prescribing and usage conditions.
- Large population coverage: Conducted at a national scale, ensuring broader representation.
- Incidence density calculation: Enables estimation of event rates based on person-time exposure.
- Useful for newly marketed drugs: Identifies early risks that may not emerge in pre-marketing studies.
- Non-interventional: Does not alter prescribing behavior, reducing bias.
- Hypothesis generation and testing: Can detect new safety concerns and support causal analysis.
- Structured follow-up: Green Form system ensures consistent data capture from physicians.
Limitations of PEM
- Lack of control group: As an observational cohort study, causal associations may require further analytical studies.
- Dependence on physician response: Non-response to questionnaires may reduce data completeness.
- Event identification challenges: PEM captures medical events, not necessarily confirmed ADRs, requiring further evaluation.
- Delayed reporting timelines: Time gaps between prescribing, questionnaire dispatch, and return can slow analysis.
Role of PEM in Pharmacoepidemiology
PEM plays a vital role in pharmacovigilance by:
- Detecting rare or delayed adverse events
- Identifying drug-use patterns in clinical practice
- Helping characterize the benefit–risk profile after marketing
- Supporting regulatory decisions and label changes
- Providing evidence for hypothesis generation and confirmatory studies
Detailed Notes:
For PDF style full-color notes, open the complete study material below:
PATH: PHARMD/ PHARMD NOTES/ PHARMD FIFTH YEAR NOTES/ PHARMACOEPIDEMIOLOGY AND PHARMACOECONOMICS/ PRESCRIPTION EVENT MONITORING.