Overview
Primary care (MPEM)
The technique of Prescription-Event Monitoring (PEM) is a well established post-marketing surveillance technique designed to monitor the use, general safety and the identification of possible new unexpected risks of newly marketed medicines as used in real-life clinical practice. Dispensed prescription data are used to identify general practitioner (GPs) who prescribe a new medicine to a new user cohort of patients.
These GPs are then asked to abstract event information from the patients existing medical charts in relation to a specific time-period since the patient first started treatment with the medicine. The questionnaires are then returned to the DSRU for review and inclusion onto the study database.
PASS Design
Designing Post-authorisation Safety Studies (PASS) for Risk Management
- Why?
- Study Process
- Methodology
Why?
The Move to Modified Prescription-Event Monitoring (M-PEM)
In parallel with scientific developments in pharmacoepidemiology and regulatory requirements in pharmacovigilance and risk management, the technique has evolved to become a more targeted safety surveillance known as Modified PEM (M-PEM). These studies use enhanced customized data collection questionnaires to examine specific recognised or suspected safety risks of a medicine. Such studies are usually specifically designed to examine potential risks, identified risks and missing information identified in Risk Management Plans (RMPs). The DSRU is grateful to GPs for continuing to complete these more complex forms.
Study Process
Modified Prescription-Event monitoring (M-PEM) study processes
The figure below describes the step wise approach by which data is obtained and processed for M-PEM studies:
- DSRU notifies NHS Business
Services Authority of study drug - DSRU receives data from dispensed primary care NHS prescriptions issued in England by GPs from the date of market launch
- M-PEM questionnaires sent to GPs (e.g. ≥3/6/12 months after first primary-care prescription issued for patient)
- Information requested on questionnaire includes baseline demographic and general health data,
e.g. body mass index; causes of death if died; study drug treatment start date and starting dose details; indication and duration of indication; first initiation-responsible clinician and setting; co-morbidities at treatment initiation and new onset events during/after treatment; other selected medication use within pre-defined period prior to starting and during treatment; study drug treatment stop date and reasons for stopping - M-PEM questionnaires returned,
scanned, reviewed and data entered into DSRU database - Selected events of medical
interest ,deaths (where cause not known) and pregnancies followed up
Methodology
- Monitor the rate of introduction of new drugs onto the market and study the reasons for physician prescribing preferences
- Provide drug utilisation information and the characteristics of patients using specific medications, such as the patients’ previous medical history, concomitant medication use and concordance to the prescribed medication under study. Such information frequently fulfils the requirements to study missing information identified in the RMP.
- Conduct targeted surveillance on a particular event or outcome of interest, such as potential or identified risks highlighted in the RMP
- Quantify and compare the incidence of events reported prior, during or after treatment (with appropriate comparators) and explore patterns of onset over time
- Characterise factors that are associated with onset of particular events
PASS Studies
Secondary care (SCEM)
One of our key capabilities is undertaking Post-authorisation Safety Studies (PASS) in the hospital setting. These studies follow our Specialist Cohort Event Monitoring (SCEM) methodology, which we created to address the need to provide safety studies in secondary care, specifically for patients who receive initial or all drug treatment in hospitals or hospital outpatient clinics.
Our ability to conduct hospital-based PASS studies and access a network of prescribers in secondary or specialist care is almost unique in the fields of pharmacovigilance and pharmacoepidemiology.
SCEM Methodology
Our SCEM methodology for studies in secondary care is explained in this short video:
Event Data
For these hospital PASS studies, event data is gathered from medical records of consented patients by hospital prescribers or care teams.
A team of DSRU regional study facilitators works with the NIHR CRN (National Institute for Health Research Clinical Research Network) and other networks across the UK to identify secondary or specialist care prescribers in the relevant speciality.
- Methodology
- SCEM Study Process
- Differences
- Oasis SCEM Study
Methodology
Our SCEM methodology complements the already well-established technique of Modified Prescription Event Monitoring (M-PEM), which we have used to conduct PASS on many medicines prescribed in primary care. By conducting studies in specialist care using SCEM methodology, safety data is collected on patients who may be more complex in terms of underlying disease, co-morbidities and concomitant medications than in the general disease population. We can also monitor prescribing that is transferred from hospital to primary care by obtaining outcome data from both the specialist and the general practitioner.
Hospital patients are identified through a network of specialists and are enrolled into the study only after the clinical decision to prescribe the study drug has been made by the clinician.
Using secondary care medical records, data is collected at treatment initiation and post initiation (the length of the observation period depends on the research question).
In SCEM studies, data on individual patients’ general health, medical history, exposure and outcomes on exposure are captured. SCEM methodology is naturalistic in nature, reflecting clinical practice, is non-interventional, and allows for broad inclusion criteria. SCEM studies can also allow collection of comparative cohorts.
SCEM Study Process
The SCEM study process is shown below, describing the step-wise approach through which data is collected during a SCEM study:
The DSRU is already conducting SCEM studies across a range of therapeutic areas. Further information on the current active SCEM studies can be found here.
Differences
Differences between M-PEM and SCEM
Oasis SCEM Study
Observational Assessment of Safety in Seroquel (OASIS) SCEM study
The DSRU has recently completed the Observational Assessment of Safety in Seroquel (OASIS) SCEM study. The OASIS study was conducted as part of the risk management plan for the product Seroquel XL. It was designed to examine the short-term (up to 12 weeks) safety and use of quetiapine fumarate in the prolonged-release formulation (Seroquel XL™), along with a comparator group started on the immediate-release formulation, quetiapine IR. Any adult patients in England were eligible for inclusion once the clinical decision had been made to prescribe either the XL or IR preparation as part of normal clinical practice for the clinical diagnosis of schizophrenia and mania associated with bipolar disorder. The DSRU worked in collaboration with the Mental Health Research Network (MHRN) to recruit over 900 patients. The study enabled the systematic collection and reporting of safety data on patients newly initiated on treatment with quetiapine XL within the mental health care trust setting. Data from the OASIS study will be published shortly.