What is pharmacovigilance?

Pharmacovigilance is a branch in clinical research that involves all activities related to drug surveillance to track, detect, and assess adverse events and possible idiosyncrasies related to the drug. In response to the thalidomide tragedy in 1961, the WHO promoted global pharmacovigilance programs to ensure patient care and safety.1 The WHO program for International Drug Monitoring in Uppsala, Sweden has 136 countries as members. The Uppsala Monitoring Centre (UMC) is an independent and non-profit foundation that handles the WHO global pharmacovigilance network based on robust scientific and technical research data.2 In addition to WHO and UMC, pharmacovigilance centers at the national level, hospitals, academic institutions, health care professionals, and patients play pivotal roles in maintaining the efficiency of a good pharmacovigilance system.

Global pharmacovigilance trend

It is estimated that the global pharmacovigilance market size will reach approximately 13.11 billion by the year 2027 at a compound annual growth rate of 13.2%. The key drivers to this would be advanced age, chronic diseases, and existing comorbidities leading to increased incidences of adverse drug reactions. There has been a significant rise in the availability of medication, stressing the need for intense monitoring of serious and non-serious adverse drug reactions. To cater to increased surveillance needs and escalating costs, many pharmaceutical giants have outsourced their pharmacovigilance services to contract research organizations in various developing countries with skilled manpower.3

Pharmacovigilance Methods

As per the ICH Harmonized Tripartite Guideline (E2E) for pharmacovigilance planning, there are different methods that can be chosen to identify and address drug safety and adverse drug reactions. They are:4

  • Passive surveillance
  • Active surveillance
  • Targeted Clinical investigations
  • Stimulated reporting
  • Descriptive studies
  • Comparative Observational Studies

Passive surveillance can be of two types, i.e., case series and spontaneous reporting. Spontaneous reporting helps in identifying safety signals after a product is marketed. This kind of reporting is unsolicited and can be made by regulatory authorities, health care workers, or consumers. However, spontaneous reporting should be accompanied by robust scientific data as many of them turn out to be incomplete or inaccurate. Case series are used to generate hypotheses to establish if the adverse events are related to the drug.4

Active surveillance involves a process where the patients who are prescribed a drug are followed-up through a pre-determined risk management program. However, these patients are contact at a later timepoint only if they provide their consent. This kind of surveillance can be carried out by selecting sentinel sites, or by monitoring drug events from automated insurance databases, or from drug or disease registries. Registries are particularly useful for evaluating safety of orphan drugs because such registries usually contain a population that has the same medical condition or that uses the same therapy.4

Targeted clinical investigations are large, randomized trials that do not follow a typical clinical trial formula. They are conducted to understand the risk-benefit profile a product in simple settings. Examples of such targeted clinical studies are pharmacodynamic studies, pharmacokinetic studies, and genetic testing studies.

Stimulated reporting is especially usefully during the early phase of post-marketing surveillance. It involves online reporting of adverse events and their systematic stimulation using tested methods or programs. However, data from stimulated reporting is generally not used to calculate incidence rates.

Descriptive studies help scientists understand the prevalence of use of a particular drug in a population and to capture background data on the rate of adverse drug reactions. Such epidemiological trials study the natural history of disease and use data from drug utilization studies to understand the frequency of the adverse events of interest.

Comparative observational studies can also evaluate the frequency of adverse events using cohort, case-control, or cross-sectional designs. These studies can collect prospective or retrospective data.

Pharmacovigilance Guidance by USFDA

Apart from adverse events related to a drug, USFDA considers data generated from pharmacoepidemiologic activities to also fall under the purview of pharmacovigilance activities. Any safety signal that arises is further investigated to confirm whether the adverse event was related/was not related to the drug. Descriptive analysis is carried out from the case series that are developed from data available in case reports. This analysis usually includes, but is not limited to, occurrence of the adverse event and its clinical and laboratory manifestation, demographic data of the patient, duration of drug exposure and drug dosage/misuse, use of con-concomitant medications for existing co-morbidities, route of administration, and product lot number. Data mining is carried out using statistical methods to examine the adverse events reported. The tools used for data mining help in identifying any trends, patterns or events related to drug-drug interactions.5

Guidance for pharmacoepidemiological studies: FDA recommends pharmacoepidemiological studies to develop protocols that have specific study objectives and detailed review of literature along with elaborate description of research method to minimize bias and possible confounding factors. FDA also encourages such studies to be conducted in more than one environment to ensure that observations are robust.5

Guidance for observational studies using registries: Many epidemiological studies also make use of registries to identify safety signals by collecting data from automated databases that have access to multiple sources such as patient medical history, doctor’s prescriptions, pathology reports and more. In addition to review of literature in protocols using registries, FDA also suggests description of patient recruitment and data collection methods including size of registry and validation of registry. Validation of registry for data quality should be carrier out through questionnaires or interviews with medical care providers linked to the registry.5

Guidance for observational studies using surveys: FDA suggests validation of the survey system by carrying out a pilot study before the Sponsor initiates the actual survey. As with registry studies, FDA recommends detailed description of the research methods, methods for patient recruitment and follow-up, intended sample size, as well as data management methods for data collection and analysis.5

Pharmacovigilance Plan for Unusual Safety Risks

For unusual safety risks that are identified after a product is marketed or before approval of a product, FDA recommends the Sponsor to develop a pharmacovigilance plan that expedites safety information beyond routine spontaneous safety reporting. The plan should be feasible logistically and should be backed with scientific data such as frequency of occurrence and severity of adverse event, population for which product is indicated, sources through which product is available such as pharmacies or performance linked systems, and at-risk population. Active surveillance systems are also recommended to report adverse drug reactions that may not be captured through passive surveillance.5

Periodic re-evaluation of pharmacovigilance plans by the Sponsor is necessary to improve design of observational studies that can hasten detection of adverse events at an earlier stage. Thus, FDA may convene the Drug Safety and Risk Management Advisory Committee or FDA Advisory Committee to brainstorm on improvising risk mitigation plans to enhance the effectiveness of an existing pharmacovigilance plan.5

Future of Pharmacovigilance

Artificial intelligence is being applied to many pharmacovigilance analytical methods especially for data extraction from multiple sources. This helps in considerable reduction of time and costs while maintaining data quality and accuracy. While artificial intelligence solutions would be much sought after, equally important would be the need for service providers that have the technical know-how to handle such high end technology to ensure smooth functioning of pharmacovigilance-related activities.6


  1. WHO. Essential Medicine and Health Products. Pharmacovigilance. Accessed on May 05, 2020.
  2. Uppsala Monitoring Centre. Who were are. Accessed on May 05, 2020.
  3. Research and Markets. Pharmacovigilance Market Size, Share & Trends Analysis Report by Clinical Trial Phase (Pre-Clinical, Phase I, II, III, IV), by Service Provider (In-House, Contract Outsourcing), by Type, by End Use, and Segment Forecasts, 2020 – 2027. Accessed on May 05, 2020.
  4. International Conference On Harmonisation Of Technical Requirements For Registration Of Pharmaceuticals For Human Use. (2004). Pharmacovigilance Planning, E2E. Accessed May 05, 2020.
  5. U.S. Department of Health and Human Services, FDA, CDER CBER. (2005). Guidance for Industry. Good Pharmacovigilance Practices and Pharmacoepidemiologic assessment. Accessed on May 05, 2020.
  6. Genpact. The future of Pharmacovigilance. Accessed on May 05, 2020.

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