prescription event monitoring- rumana hameed
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Prescription Event Monitoring (PEM)
Rumana Hameed Pharm D 5th Year
170310820021
What is PEM?
PEM is a non-interventional, observational cohort form of pharmacovigilance.
It is the method of studying the safety of new medications used by the general practitioner.
PEM was developed by Professor Bill Inman at the Drug Safety and Research Unit (DSRU) at Southampton in 1981.
Evolution of PEM
Pre-marketing clinical trials are effective in studying the efficacy of medicine but are not able to define many aspects of drug safety because:
1. Small no of patients2. Large no of patients receiving the drug for
small durations3. Doses and formulations of the drug may
change during drug development4. Exclusion of special population from the
clinical trials
The contribution of spontaneous reporting system in detecting hazards such as oculomucocutaneous syndrome with practolol led Inman to establish the system of Prescription Event Monitoring (PEM) at DSRU.
In New Zealand, the medicines adverse reaction committee (MARC) is responsible for conducting such studies for academic purposes and the programme is known as Intensive medicine monitoring programme(IMMP).
In UK, all the patients are registered with NHS-GP provides the primary care and act as a gateway to specialist and hospital care
File notes in general practice contains information about primary care, secondary and tertiary care (life long record)
GP issues prescription for medications he considers medically warranted
Patient takes the prescription to the pharmacist, who dispenses the medication and sends the prescription to the PPD (which is a part of NHS-BSA), for reimbursement
PPD provides DSRU with electronic copies of all the prescriptions issued throughout UK, for the drugs being monitored
Products that are selected for study by PEM
1. New drugs, expected to be used widely2. Established products, used for new
indication/ new population
Collection of exposure data begins soon after the new product is launched
These arrangements operate for a length of time necessary for the DSRU to collect first 50,000 prescriptions, that identify 20,000-30,000 patients given the new drug being monitored
For each patient in the study, DSRU prepares a computerized longitudinal record in the date order of drug use
After 3-12 months from the date of first prescription for each patient, the DSRU sends the prescriber a green form questionnaire
This is done on an individual patient basis
Doctor receives maximum of 4 green forms in a month
Green form for PEM study on Celecoxib
Request information on:
Age Sex Indication for Rx Dose Start date Stop date Concurrent
diseases Concomitant
therapy All events that
have occurred since Rx
Cause of death
Each green form is reviewed by a medical/ scientific officer monitoring the study, to identify possible serious ADRs or events requiring action
Events are coded and entered in database using a hierarchical dictionary arranged by system-organ class with specific lower terms grouped under broader higher terms
PEM process
Advantages
1. PEM is non-interventional2. The method is national in scale and thus
provides real world data3. Exposure data is derived from dispensed
prescriptions4. Method can detect adverse reactions or
syndromes that none of the reporting doctors suspected to be due to the drug
5. Method allows close contact between the research staff and reporting doctors
6. ADR reporting is more complete by this method
7. Method is found to be successful in regularly producing data in 10,000 or more patients given newly marketed drugs
8. Method identifies patient with ADRs who can be studied further
9. Allows comparison of safety profile of drugs belonging to the same therapeutic group
10.Evaluate signals generated by other systems or databases
Disadvantages
1. Not all green forms are returned2. PEM depends upon reporting by
doctors. Underreporting is possible3. PEM is currently restricted to
general practice4. Its not known whether the patient
took the dispensed medication5. Detection of rare ADRs is not always
possible
Applications of PEM
1. Searching for signal2. Assessment of important AE3. Medically important events4. Reason for stopping the drug5. Analysis of events during the study
while on drugs6. Ranking of ID and reason for
withdrawal7. Automated signal generation8. Long latency adverse reactions
9. Comparison with external data10.Outcomes of pregnancy11.Studies to examine hypothesis
generated by other methods12.Studies of background effects and
diseases
Example for PEM
A study was carried out to assess the sedation properties of 4 anti-histaminic in the market loratadine, cetrizine, fexofenadine and acrivastine
Objectives: To investigate the frequency with which sedation was reported in post marketing surveillance studies of four second generation antihistamines: loratadine, cetrizine, fexofenadine, and acrivastine
Design: Prescription event monitoring studies.
Setting: Prescriptions were obtained for each cohort in the immediate post marketing period.
Subjects: Event data were obtained for a total of 43,363 patients.
Main outcome measure: Reporting of sedation or drowsiness.
Results: The odds ratios for the incidence of sedation were 0.63 (95% confidence interval 0.36 to 1.11; P = 0.1) for fexofenadine; 2.79 (1.69 to 4.58; P < 0.0001) for acrivastine, and 3.53 (2.07 to 5.42; P < 0.0001) for cetrizine compared with loratadine. No increased risk of accident or injury was evident with any of the four drugs.
Conclusions: Although the risk of sedation was low with all four drugs, fexofenadine and loratadine may be more appropriate for people working in safety critical jobs. This study not only showed the sedative effects of the anti-histaminic, and compared them, it also gave an idea about the incidence of other ADRs associated with the 4 drugs.
Incidence density of ADRs in first moth of treatment with 4 anti-histaminics
Incidence density of events related to sedation in first month of treatment with 4 anti-histaminics
Record Linkage Systems
What is Record Linkage?
Record linkage is the process of bringing together two or more records relating to the same individual (person), family or entity (e.g. event, object, geography, business etc).
It is the process of assembling the outcomes of drug exposure into a single database
Record linkage can be considered as part of the data cleaning process
Provides rapid access to records of thousands of patients and thus reduces the time required for exploring the relationship between drug exposure and outcomes
Diagrammatic representation of a linkage between two or more independent entries
An ideal database would include records from inpatient, outpatient, emergency care, mental health care, laboratory and radiological tests, prescribed and over-the-counter medications as well as alternative therapies
All the parts should be easily linked by a unique patient identifier
It should be updated regularly
Need for record linkage?Researchers and the community‘s demand for detailed statistical information
Reducing respondent burden and costs
Improving data quality and timeliness
In response to increasing business and health needs.
In reducing the complexity of data
International collaborative works
Objective of record linking The objective of the linking process
is to determine whether two or more records refer to the same person, object or event
Types of record linkage methods
Types of Record Linkage
Strategies
Probabilistic
Deterministic
Deterministic record linkage
A pair of records is said to be a link if the two records agree exactly on each element within a collection of identifiers called the match key.
For example, when comparing two records on last name, street name, year of birth, and street number, the pair of records is deemed to be a link only if the names agree on all characters, the years of birth are the same, and the street numbers are identical.
Probabilistic Record Linkage
Pairs of records are classified as links, possible links, or non-links.
Here, we consider the probability of a match in the given observed data.
In probability matching, a threshold of likelihood is set (which can be varied in different circumstances) above which a pair of records is accepted as a match, relating to the same person, and below which the match is rejected
General record linkage system
Claims databases Patient goes to pharmacy drug
gets dispensed pharmacy bills the insurance carrier for cost of that medication
Should specify which drug was dispensed, amount dispensed, etc.
Patient goes to hospital/physician for medical care bills the insurance carrier for cost of the medical care
Should justify the bill with diagnosis Common patient identification no:
link pharmacy and medical care claims
Medical record databases
Recent development with increased use of computerization in medical care
Computers are used to record medical information
Advantages
Provide large sample size, esp. for pharmacoepidemiological studies
Inexpensive Data will be complete Population based Include information on outpatient
drugs and diseases Avoid recall and interviewer bias
Disadvantages
Uncertainty of diagnosis data May not contain information regarding
smoking, alcohol, date of menopause, etc.
May not contain data of medications obtained without prescription or outside insurance carriers prescription plan
Instability of population due to job changes, changes in insurance plans, etc.
Include illnesses severe enough to come to medical attention
Applications
1. Data Quality2. Bias3. Coverage4. Tracing Tool5. Benchmarking/Calibration6. Building New Data Sources (e.g.,
Registries)7. Creation of patient-oriented, rather than
event-oriented statistics8. Reducing costs and respondent burden
Thank you!