Pharmacovigilance: Drug Safety in Clinical Trials

One of the most essential ethical principles established by the International Conference on Harmonization – Good Clinical Practice (ICH-GCP) states, “The rights, safety, and well-being of [human research] trial subjects are the most important considerations and should prevail over interests of science and society.” Hence, pharmacovigilance is extremely crucial while conducting clinical trials involving human research subjects.

What is pharmacovigilance (PV)?

Pharmacovigilance is defined as “the science and activities relating to the detection, assessment and understanding and prevention of adverse effects or any other drug-related problem” by the World Health Organization (WHO). Pharmacovigilance (PV), also known as drug safety, is central to any investigational drug trial. Investigational drug trials or clinical trials are utilized worldwide to determine the safety, tolerability, and efficacy of a chemical compound or a biological compound targeting a specific mechanism of a disease pathway. Pharmacovigilance propels clinical drug trials to provide vital data on the risks and benefits of the Investigational Medicinal Product (IMP) that is under current investigation. Pharmacovigilance in clinical drug trials attempts to develop a risk-benefit analysis for the protection of human research subjects. Benefits resulting from the drug must exceed risks for drug developers and manufacturers to proceed with market approval of the new drug.

How does pharmacovigilance ensure human research subjects’ safety in clinical drug trials?

Clinical drug trials are rigorously monitored by a Principal Investigator (PI), a team of sub-investigators, and the sponsor, pharmaceutical company, or manufacturer providing the IMP and funding the trial. In addition, Institutional Review Boards (IRB) and other regulatory agencies are also involved in the process to ensure that the rights, safety, and well-being of human research subjects are protected and that the clinical drug trials are being conducted strictly based on the approved clinical study protocols. Pharmacovigilance equals this procedure by providing an additional level of security to guarantee the safety and efficacy of IMPs in clinical trials. All professionals involved in clinical drug trials such as investigators, sub-investigators, drug sponsors/developers, and drug manufacturers are liable for employing the paramount care that is achievable for future patients globally.

Before a new medicinal product’s market application approval, Phase I, II, and III clinical drug trials are necessary to be conducted by a pharmaceutical company or a Contracted Research Organization (CRO). These entities are accountable for the clinical conduct of the trials strictly based on the IRB-approved study protocols while keeping the integrity of the clinical studies and data collection.

Data collected during clinical trials are analyzed particularly for Serious Adverse Events (SAEs) and determined whether they are caused by the drug that is under investigation. SAEs would be categorized as Adverse Drug Reactions (ADRs) if causality has been established. These data will be provided to the CRO or the sponsor’s Pharmacovigilance (PV) department for further assessments of side effects and will be reported to the U.S. Food and Drug Administration (FDA) and other relevant regulatory authorities. Moreover, the PV department also determines the investigational drug’s advancement to the next phase of clinical trials or application for market approval based on its drug safety and efficacy evaluation. Phase IV clinical trials may also be conducted by the sponsor or CRO post-market approval of the drug to collect additional data on the safety and efficacy of the drug while being utilized by the public.

Pharmacovigilance is an emerging field that is vital to the success of conducting clinical trials. In 2020, it is reported that the global pharmacovigilance market size was estimated at approximately $5.8 million. In 2021, the market size was approximately $6.7 million. It is projected to grow at a Compound Annual Growth Rate (CAGR) of ~14.79% to reach ~$13.4 million by the year 2026. Both pharmaceutical companies and Contracted Research Organizations (CROs) are considered the major players in the pharmacovigilance field. As pharmaceutical companies focus on research and development of new chemical and biological compounds, more and more clinical trial duties are being outsourced to CROs. However, both entities certainly have pharmacovigilance sectors that focus on diligently monitoring and reporting observed Adverse Events (AEs) or Adverse Drug Reactions (ADRs) to all involved regulatory agencies.

Ultimately, pharmacovigilance in clinical trials truly is key and exceedingly crucial not only to clinical trial investigators but also to healthcare professionals and the public. It allows for updates on prospective risks of post-market approved medications. In such cases, post-marketing drug safety surveillance may be facilitated by pharmaceutical companies to continuously observe the safety and efficacy profile of the medication in a real-life setting since it is impossible to foresee all potential drug side effects during pre-market approval investigational studies. Pharmacovigilance aims to not only protect the rights, safety, and well-being of human research subjects participating in clinical drug trials but also the rights, safety, and well-being of the general public.