Written by Bassem Toeama
From my position as a pharmacovigilance consultant at Axiom Real-Time Metrics, I acquired an in-depth perception of the different career pathways in the biotechnology/pharmaceutical industry. I will walk you through these career pathways. Today I will explain in depth the tasks and responsibilities of the diverse career levels in pharmacovigilance, relate each career level with the required knowledge, experience, and set of soft skills, and advise on how to progress up the career ladder.
The etymological roots for the word “pharmacovigilance” provide an overview for the job role. The prefix “pharmaco-“ comes from the Greek noun “pharmakon” which means a biologically active substance, and is used broadly to describe medicinal products including drugs, vaccines, or medical devices. The noun “vigilance” comes from the Latin verb “vigilāre” which means keep an eye out for danger. Hence the keywords that define the tasks and responsibilities of a pharmacovigilance professional include: monitor, code, and assess any adverse event (any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and doesn’t necessarily have a causal relationship with this medicinal product), submit a report to the regulatory authorities, and communicate the findings to all involved stakeholders.
A pharmacovigilance professional will monitor for an adverse event either in a pre-market clinical trial setting or in a post-market real world setting. In the pre-market, the clinical trial subject who experiences the adverse event is monitored. The adverse event is reported within the context of phase I-III studies. The source who reports the adverse event is a clinical research coordinator, nurse, fellow, sub investigator, or principal investigator. In the post-market, the patient who experiences the adverse event is unmonitored. The adverse event is reported either spontaneously or within the context of phase IV and non-interventional studies. The source who reports the adverse event is a healthcare provider, an end consumer (patient), scientific literature, electronic health records, patient registries, the internet, etc.
A pharmacovigilance professional will code the reported adverse event by its preferred term (PT) (a code that classifies the reported adverse event by symptom or sign) and system organ class (SOC) (a code that classifies the reported adverse event by etiology or manifestation site) as per the Medical Dictionary for Regulatory Activities (MedDRA), in accordance with the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Multidisciplinary guidelines (ICH M1).
- Assess and Understand
A pharmacovigilance professional will assess and understand the causality, expectedness or listedness, seriousness, and severity of the adverse event. From these assessments, the pharmacovigilance professional will build up a case narrative.
Using different assessment scales such as the Naranjo Adverse Drug Reaction probability scale or the World Health Organization – Uppsala Monitoring Centre causality scale, the pharmacovigilance professional will check for temporal relationship (timing between the administration of the medicinal product and the occurrence of the adverse event), time plausibility (time reasoning that can establish a cause-and-effect relationship between administration of the medicinal product and the occurrence of the adverse event), dechallenge (stopping the administered medicinal product and observing for disappearance of the adverse event), rechallenge (restarting the same administered medicinal product and observing for recurrence of the same adverse event), alternative causes, and culprit evidence.
b) Expectedness or Listedness:
The pharmacovigilance professional will cross check the reference safety information (RSI) for expectedness (the adverse event is assessed as expected in the clinical trial subject if it has been previously documented in the RSI) or listedness (the adverse event is assessed as listed in the patient if it has been previously documented in the RSI). Unexpectedness is one of the pre-market requirements for expedited regulatory reporting. Listedness and unlistedness are post-market requirements for aggregate regulatory reporting. In the pre-market, the RSI for expectedness is the investigator’s brochure, while in the post-market one of the RSIs for listedness is the product monograph.
The pharmacovigilance professional will check if the adverse event has one of the seriousness criteria (fatal, life threatening, requires in-patient hospitalization, prolongs existing hospitalization, results in persistent or significant disability or incapacity, results in congenital anomaly or birth defect, an important medical event) or not. Seriousness is one of the pre-market requirements for expedited regulatory reporting and one of the post-market requirements for either expedited or aggregate regulatory reporting.
The pharmacovigilance professional will assess for the severity of the adverse event whether it is mild (tolerated adverse event not interfering with the usual activity), moderate (uncomfortable adverse event interfering with the usual activity), or severe (incapacitating adverse event that warrants intervention which doesn’t necessarily have to be hospitalization).
e) Case Narrative:
The pharmacovigilance professional will build up a case narrative, which is a detailed summary of an adverse event eligible for expedited regulatory reporting. This is a pre-market requirement and a Good Pharmacovigilance Practice (GVP) mandate. In the case narrative, the pharmacovigilance professional will comment on the patient background including medical and drug history, the suspicious drug / medical device, the adverse event eligible for expedited regulatory reporting and the action taken to alleviate and/or treat the adverse event.
- Regulatory Report
A pharmacovigilance professional will confirm the guidance and regulations published on the websites of the different regulatory agencies including Health Canada, FDA, European National Competent Authorities, and others to observe regulatory submission compliance. The pharmacovigilance professional will determine the awareness date (which is vital for expedited regulatory reporting clock), the regulatory report due date, regulatory report type, and regulatory report format.
A pharmacovigilance professional will liaise with all possible stakeholders to ensure commitment to patient safety. The identified stakeholders depend on whether the reported adverse event occurs in a pre-market clinical trial setting or in a post-market real world setting.
How can a pharmacovigilance professional progress up the career ladder? As an associate, a pharmacovigilance professional must have the adequate level of knowledge and experience in clinical research and regulatory affairs with a bit of data management skills to monitor, code, report to regulatory authorities, and communicate with all possible stakeholders. To become an expert, a pharmacovigilance professional must have, in addition to the previously mentioned skills, knowledge, and experience:
- Clinical medicine knowledge for causality assessment and writing up the case narrative.
- Clinical statistics skills with the ability to analyze the safety data both quantitatively and qualitatively, mine the statistical data, and detect safety signals.
- Medical writing skills to write up the medical management safety plans, data safety and monitoring board reports, risk management plans, and benefit-risk assessment studies.
- A bit of the translational research knowledge.
In the next blog, I will explain in depth the tasks and responsibilities of the diverse career levels in data management and relate each career level with the required knowledge, experience, and set of soft skills.
Aronson JK, Ferner RE. Joining the DoTS. New approach to classifying adverse drug reactions. BMJ. 2003;327:1222–1225. doi: 10.1136/bmj.327.7425.1222.
ICH Harmonised Tripartite Guideline (E2E) “Pharmacovigilance Planning” 2004, International Conference On Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, accessed 4 January 2018, https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E2E/Step4/E2E_Guideline.pdf
As a former Pharmacovigilance Consultant at Axiom Real-Time Metrics, Bassem has learned the ins and outs of working at a biotechnology/pharmaceutical company. He shares his knowledge and expertise in a Blog Series on the LSCDS website.