Post Marketing Surveillance

  • Postmarketing surveillance (PMS) is the practice of monitoring the safety of a pharmaceutical drug or medical device after it has been released on the market and is an important part of the science of pharmacovigilance
  • Post-marketing surveillance (PMS) to assure the efficacy and safety of drugs after they go on the market and to establish proper methods of use of drugs consists of three systems:
    • the ADR collecting and reporting system,
    • the reexamination system, and
    • the reevaluation system.

Difference between PMS and Phase 4

Phase 4 includes all post marketing studies.

  • PMS is one type of Phase IV study to obtain additional information about the risks and benefits resulting from long term usage of drug. PMS primarily is a surveillance of safety of new drug.
  • Another type of Phase IV study is that is designed to evaluate the marketed drug in specifically designed studies, which have inclusion/exclusion criteria, objectives and end points. The drug is used for the labeled indication in these studies
  • Another type of Phase IV study involves evaluation of the drug for a new indication of a marketed drug,
  • For Phase 4, EC permission is essential. In addition, DCGI approval also essential

Not all Phase IV studies are postmarketing surveillance (PMS) studies but every PMS study is a phase IV study.

In particular, the real world effectiveness of a drug as evaluated in an observational, non-interventional trial in a naturalistic setting which complements the efficacy data that emanates from a pre-marketing randomized controlled trial (RCT).

Surveillance of spontaneously reported adverse events continues as long as a product is marketed. And so Phase IV in that sense never ends.

  • In the real world no patient can be excluded; even pregnant and lactating women, those with hepato-renal dysfunction, on multiple concomitant medications for concomitant clinical conditions must be treated.
  • How the drug performs in such real world conditions is a test of its effectiveness.

All studies conducted in a phase IV setting, i.e., after marketing authorization approval per label are called phase IV studies.

Of these, those mandated by the regulatory authority to be conducted as observational studies in a naturalistic setting per label are called PMS studies.

Post marketing surveillance

  • PMS studies exemplify the difference between efficacy and effectiveness.
  • Efficacy is judged within the controlled environment of a clinical trial with strict inclusion and exclusion criteria and close monitoring and ensured compliance.
  • Effectiveness is the real test of a drug when it is used in a much larger population, with varied organ system function, concomitant drugs and where monitoring and compliance are not always ensured.
  • In other words, a PMS study is a noninterventional study requested by regulatory authorities to verify the safety, tolerability and effectiveness of a marketed drug in a particular population per the locally approved label.
  • In India, PMS data used to be submitted to the Drugs Controller General of India (DCGI) within 2 years of launch.
  • Now Periodic Safety Update Reports (PSURs) are filed at regular intervals as specified in the revised Schedule Y of the Drugs and Cosmetics Act.
  • The outcomes of such studies could be signals, pharmaco-epidemiological information, need for controlled studies, labeling changes with modified undesirable effects section, indications and dosing schedules, and regulatory action (boxed warning, risk minimization action plan, withdrawal).

The common types of post-marketing surveillance are

  • passive and active surveillance,
  • stimulated reporting,
  • comparative observational studies,
  • targeted clinical investigations, and other descriptive studies.

a) Active surveillance

  • 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.”
  • objective à detect safety issues early in the post-marketing environment that were not identified during development, such as rare events or latent onset.
  • can also quantify the effects of misuse or overdose.
  • characterize drug use patterns, including profiles of prescribers and patients, indications, and dosing and discontinuation.
  • can include the regular, periodic and stimulated collection of case reports from healthcare providers or facilities, such as sentinel sites.
  • The use of sentinel sites may involve the review of medical records or patient and/or physician interviews for complete and accurate date on reported adverse events.
  • This method may allow for a focus on patient subgroups that would not be available in a passive reporting system, and is most efficient when employed in the surveillance of products frequently used in an institutional setting.
  • However, the use of sentinel sites is limited by small sample size, selection bias, and expense.
  • Additional methods à prescription monitoring, patient registries, and database and/or electronic medical record research

b) Passive surveillance

  • primarily includes the analysis of spontaneous adverse event reports.
  • often involves assembling a series of cases to examine specific types of events, such as overdose and product re-challenge.
  • This method of safety surveillance is limited by incomplete reporting information (which can impede determination of causality), potential underreporting of events, and unknown parameters for calculation of incidence (denominator and numerator).
  • A component of passive surveillance is data mining looking for disproportionality patterns

Comparative observational studies

  • can be analytic, such as case-control studies, or descriptive, including cross-sectional surveys and cohort studies.
  • Observational studies do not recruit participants into a controlled environment, as in a random-controlled trial, but instead observe the outcome of interest in a population that already takes the drug compared to a population that does not.
  • These studies are commonly used to identify side effects rather than evaluate treatment effectiveness,
  • 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 analyze predictive risk factors for an outcome of interest.

Drug Utilisation Studies (DUS)

  • Such studies describe how a drug is marketed, prescribed, and used in a population, and how these factors influence outcomes, including clinical, social, and economic outcomes.
  • These studies provide data on specific populations, such as the elderly, children, or patients with hepatic or renal dysfunction, often stratified by age, gender, concomitant medication, and other characteristics.
  • DUS have been used to describe the effect of regulatory actions and media attention on the use of drugs, as well as to develop estimates of the economic burden of the cost of drugs.
  • DUS can be used to examine the relationship between recommended and actual clinical practice.
  • These studies can help to determine whether a drug has the potential for drug abuse by examining whether patients are taking escalating dose regimens or whether there is evidence of inappropriate repeat prescribing.
  • Important limitations of these studies can include a lack of clinical outcome data or information of the indication for use of a product.


  • A prospective observational study of patients with certain shared characteristics (e.g., particular disease, exposure, or risk factor) that collects ongoing and supporting data over time on well defined outcomes of interest for analysis and reporting.
  • Properly designed and executed, registries can provide a real world view of clinical practice, patient outcomes, safety, and comparative effectiveness.

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