Pharmacovigilance stands as an integral and irreplaceable aspect within the realm of clinical research. Both post-marketing Pharmacovigilance and the safety aspects of clinical trials play pivotal roles throughout a product’s existence. Pharmacovigilance, defined as the scientific discipline dedicated to identifying, evaluating, comprehending, and averting adverse effects—especially the enduring and immediate impact of medications—is paramount in ensuring public health. In India, the understanding of Pharmacovigilance remains somewhat limited, as the field is still in its early stages of development.
While Western nations have made significant advancements in Pharmacovigilance, progress in India has been comparatively slower. Understanding the importance of Pharmacovigilance and its impact on the life cycle of a product is crucial. Integrating effective Pharmacovigilance practices into systems is vital to enhance clinical trial safety, post-marketing surveillance, and regulatory compliance. In fact, India has been practicing Pharmacovigilance since 1998 when the country joined the Uppsala Centre for Adverse Event Monitoring. Regulatory authorities, the media, and consumers have all acknowledged the importance of Pharmacovigilance as the benefits and risks of medications have become evident. According to the FDA, an adverse event is any unfavorable medical occurrence during treatment with a medicine, regardless of its relationship with its use. An adverse drug reaction is any harmful, unplanned effect of a medicine occurring at a dose used in humans.
Spontaneous reporting of adverse drug reactions and early detection of safety information are essential approaches for data acquisition. Many Indian companies have increased their research and development spending, enhancing their capacity to develop and commercialize new pharmaceutical products. The growth of a center for clinical research activity in India is attributed to its large population, high enrollment rates, and cost-effectiveness.
The duration between the initial launch of a drug in the United States, Europe, Japan, or other global markets and its subsequent introduction in India has significantly diminished. Consequently, comprehensive information regarding the commercialization timeline and long-term safety data for such pharmaceuticals is often lacking in India. Notably, several high-profile drugs that were recently withdrawn from sale in other regions continue to be available in the Indian market. Due to these disparities, Indian regulatory agencies face challenges in assessing the benefit-risk balance of medications, as they cannot solely rely on insights from other markets. Effectively managing and mitigating the adverse effects of medications emerge as primary concerns in ensuring the safety of pharmacological therapy.
Medication analysts lack the ability to alter side effects, as these are inherent characteristics of the drug compound itself. Their primary focus lies in ensuring the quality of both bulk medication components and drug formulations, a critical aspect directly linked to safety concerns. Medication quality encompasses identity, strength, and purity as its key components. Purity, especially concerning bulk drug materials, plays a vital role in detecting and quantifying impurities and degradation products through structural elucidation. This process aims to minimize the potential contribution of these elements to the side effect profile of therapeutic materials. Historically, a meticulous examination of spontaneously reported cases has been a common practice to identify and quantify adverse medication responses. Causality determination (imputation) has been a crucial aspect of scrutinizing individual case reports, and this has been complemented by the analysis of aggregated cases and disproportionality studies within databases of spontaneous reports. These findings have led to the discovery of numerous new adverse reactions, altering medication information, given the absence of more specialized information sources. While this has resulted in the removal of many drugs from the market, its applicability to risk quantification remains uncertain. The recent availability of databases containing population-wide claims or electronic health records has underscored the prevalence of spontaneous reporting in generating hypotheses for significant adverse medication reactions, particularly those leading to hospitalization or death. In these instances, incidents are identifiable at the population level and can be systematically quantified using modern Pharmacoepidemiology technologies, facilitating customized benefit-risk assessments. Despite its inherent limitations, spontaneous reporting remains pivotal in generating signals and alerts for medication safety. Exploring additional systematic and quantitative tools, such as claims databases for responses resulting in hospital admissions, is imperative for enhancing signals and conducting thorough analyses.
Pharmacovigilance revolves around the collection of Adverse Drug Reaction (ADR) reports, facilitating the timely identification of new signs of adverse reactions. Rather than insisting on the reporting of every ADR, it is more practical to have an appropriate number of reports containing the correct information for an accurate causation assessment. Requiring the disclosure of all potential ADRs would be impractical, considering the sheer volume of data, and no national reporting system is equipped to handle such a load. Given that each report must be independently examined to enable a thorough causality assessment and provide the reporting party with appropriate feedback, identifying significant occurrences within this vast amount of information would be akin to finding needles in a haystack. As Finney has previously emphasized, it is crucial to precisely specify which adverse events necessitate reporting.
Some of the serious adverse events include
- THALIDOMIDE TRAGEDY Fig.1
Fig.1 Both pictures include survivor babies of Thalidomide tragedy
- CLIOQUINOL TRAGEDY
Fig.2 The peculiar example of clioquinol: a medication for dyspepsia linked to a crippling disease
In the WHO’s Asian Region, Pharmacovigilance is gaining traction nearly 50 years after the thalidomide incident. India has recently become a full participant in the WHO’s global drug monitoring program. The tragic event in Gambia, where 66 children lost their lives due to cough syrup manufactured by an Indian company, highlights the urgent need for comprehensive considerations and actions to prevent such catastrophes and save lives. At the heart of Pharmacovigilance is the identification of signs of adverse drug reactions based on patient experiences reported by physicians and pharmacists.
Meyboom defined a signal as a compilation of information supporting a theory related to the reasonable and safe use of a medicine in people. Pharmacovigilance’s primary objective is to validate and support such theories. As mentioned earlier, the data forming the basis of signals emerge from the routine interactions between doctors and pharmacists, manifesting in certain patients. Therefore, it is vital to have appropriate means to facilitate the collection of these experiences and observations. Numerous techniques for this purpose have been developed in recent decades. The predominant method employed in pharmacovigilance is the Spontaneous Reporting System (SRS), which proves particularly effective in detecting rare and severe adverse events associated with medications. This system is applied to all drugs throughout their lifecycle, urging healthcare professionals and increasingly patients to report any observations or information to a Pharmacovigilance center. These reports need to provide sufficient details for a precise evaluation and a robust assessment of the causality— the relationship— between the suspected adverse drug reaction (ADR) and the specific medication in question.
In addition to the SRS, Pharmacovigilance leverages various other sources. It taps into data collected through different (pharmacy) epidemiological research techniques, offering valuable information that can support existing concerns. This thesis will delve into intensive monitoring techniques like prescription event monitoring, which has a successful track record in the UK and New Zealand. Case reports published in scientific literature serve as another significant data source, aiding in signal identification and strengthening existing ones.
Moreover, analytical techniques for identifying signals in extensive ADR datasets, a subject explored in several global studies, provide an additional information source. It’s crucial to note that while this method does not serve as a comprehensive solution for clinical case examinations, it serves as a supplementary data source. Enhancing these aspects of Pharmacovigilance forms a central focus of this thesis.