POST-MARKETING SAFETY SURVEILLANCE: DETECTING ADVERSE EVENTS
INTRODUCTION:
Post-marketingpost-marketing surveillance (PMS) of medications is the process by which marketed medicines are monitored for adverse drug reactions (ADRs) post clinical trials. Since most drugs do not reach the market without passing phase III clinical trials, PMS studies are considered to be phase IV studies. The safety and efficacy evaluations of any new drug via clinical trials will provide only limited information on ADRs. Discovering very rare ADRs usually occurs only in the post marketing phase. This is mainly due to the limited variety of conditions, narrow patient selection criteria, and sample size along with the short duration of clinical studies. PMS gives more realistic results and afford evidence to safeguard or enhance the safety of approved drugs.
TYPES OF POST-MARKETING SURVEILLANCE:
Spontaneous/Voluntary reporting:
Voluntary reporting by physicians and other healthcare providers, hospitals, and customers may act to alert FDA and pharmaceutical firms to possible adverse effects of the drugs.
Voluntary reporting of the cases are done by,
WHO international system
National Pharmacovigilance System INDIA
Local or Regional (Joint Commission requirement)
Scientific literature publications
US-FDA Medwatch
UK yellow card system
Australia blue card system
Observational studies:
Case reports: They are descriptions of individual patients who are exposed to a drug and develop suspected ADRs.
Case series: These are reports of a series of patient with a particular drug exposure and their subsequent clinical course. They can be effective in quantitating the frequency of medical events after drug exposure.
Case control studies: This study identifies group of patients with the disease of interest and compares them with a control group of patients without the disease. Both groups are examined for antecedent drug exposure and rates of exposure are compared.
Cohort studies: This study compares patients exposed to a drug with a control group of unexposed patients or patients exposed to another drug and look forward in a time at subsequent clinical trials.
Randomised control trials: Also called as experimental studies. They differ from cohort studies in that the investigator controls the drug exposure, one or more of these studies are nearly always performed prior to the marketing, primarily to test the efficacy of drugs. They are performed on highly selected group of patients who are not under any studies or drugs. In post marketing surveillance, they are mainly used to evaluate the efficacy of the drugs for new indications.
NEED FOR POST MARKETING SURVEILLANCE (PMS):
Primary objective of PMS is to develop information about drugs under customary conditions of drug use. Rare adverse events may not be detected in Pre-license studies because even large CTs have limitations.
ADVANTAGES OF PMS:
No fixed duration/patient population.
Report all adverse drug reactions (ADRs).
Helps to detect ADRs and drug interactions.
PMS starts immediately after marketing.
TYPES OF SAFETY SURVEILLANCE:
Active surveillance:
Active surveillance is defined as the ongoing, proactive monitoring of product use and potential adverse events (AEs) “to ascertain more completely the number of adverse events in a given population via a continuous organised process."
Passive surveillance:
Passive surveillance primarily includes the analysis of spontaneous adverse event reports. Involves assembling a series of cases to examine specific types of events, such as overdose and product re-challenge.
Stimulated reporting:
Stimulated reporting is achieved through direct encouragement of event reporting through communication with potential reporters.
Comparative observational studies:
Comparative observational studies can be analytic, such as case-control studies, or descriptive, including cross sectional surveys and cohort studies. Cross-sectional surveys examine a "snapshot" in time to quantify prevalence of an outcome of interest, such as a disease, within a defined population. Cohort studies compare data from an exposed-population to an unexposed-population in order to analyse predictive risk factors for an outcome of interest.
Targeted clinical investigations:
Targeted clinical investigations include large-streamlined trials (LSTs) and randomized controlled trials (RCTs). Double-blind RCTs are considered the "gold standard" of research.
Natural history studies:
Natural history studies are resources for background morbidity and mortality rates, as well as background incidence of serious adverse events (SAEs).
Drug utilization studies:
Drug utilization studies can be used to assess disease prevalence, but also provide information on how drug use (prescribing patterns, administration, dosing) relate to outcomes of interest.
DATA COLLECTION AND ANALYTICAL METHODS:
There are many tools and resources available for post-marketing safety surveillance;
Spontaneous adverse event report databases.
Large administrative databases (e.g., Medicaid, managed care organizations, insurers).
Registries.
Electronic medical records.
Larger automated databases, can be used in retrospective cohort studies to identify users of a new product and an appropriate matched control cohort treated with conventional drugs. Patients can be matched based on demographics such as age, gender, and other factors including medical history. These databases may provide large sample sizes and are amenable to computerized processing.
For a registry/prospective cohort study, the treating physician can collect data from patients treated with the new product or treated for the same disease. These data can include baseline data, such as medical history, disease severity/duration, and treatment history. Enrolled patients are typically followed up for a defined period of time, and data on product exposure and AEs is evaluated to compare the active cohort with the historic controls.
Analytic observational studies, such as case-control studies and cohort studies can also make use of mail, phone, or face-to-face interview surveys to collect data. A case-control network organizes multiple hospitals and/or treatment facilities to prospectively identify cases of newly-diagnosed outcomes of interest. The facilities also identify appropriate controls (based on age, gender, medical history, etc.) to allow drug exposure histories prior to the onset of the event to be compared between the cases of interest and controls. The odds ratio can be calculated to assess an association between the outcome of interest and product use.
CONCLUSION:
PMS is based on the core principle that patient health and patient safety are critical factors to be considered when manufacturing and marketing pharmaceutical products. PMS fulfills the post-approval requirements of assessing and monitoring the potential risks associated with the use of pharmaceutical products in a larger patient population. In addition to potential risks, unknown adverse reactions can also be recognized during the PMS of drugs. For this reason post marketing safety surveillance is essentials. Such surveillance involves passive case reporting and assessment, active surveillance and a variety of study options.
REFERENCES:
Vlahović-Palčevski V, Mentzer D. Postmarketing surveillance. In: Seyberth H, Rane A, Schwab M. (eds) Pediatric clinical pharmacology. Berlin: Springer-Verlag, 2011, pp.339–351.
Spelsberg A, Prugger C, Doshi P, et al. Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies. BMJ 2017; 356: j337.
https://www.pharmasug.org/proceedings/2011/HS/PharmaSUG-2011-HS11.pdf
Analytical Methods for Post-Marketing Safety Surveillance Annette Stemhagen, DrPH, FISPE, United BioSource Corporation, Blue Bell, PA Juliane K. Mills, United BioSource Corporation, Blue Bell, PA
Student Name: Roshini. S
Student ID: 124/072023
Qualification: BPT
e-Mail ID: roshinisuresh97@gmail.com
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