Understanding post-market surveillance
Real-world examples of drug recalls
Regulatory and industry response
Future of post-approval monitoring
Imagine taking a prescription drug for months — only to learn it increases your risk of stroke or heart failure. When a new drug receives regulatory approval, doctors and patients assume it is safe. But what if hidden risks emerge years later? How are these dangers identified, and what safeguards exist to protect patients? Furthermore, how do regulators and pharmaceutical companies react when an approved medication starts harming people?
The approval of a pharmaceutical product by regulatory bodies, such as the United States (U.S.) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) mark the culmination of extensive research, clinical trials, and regulatory scrutiny. Drugs that are approved by these regulatory bodies are then considered safe for clinical use.
However, historical evidence shows that approval does not guarantee long-term safety and efficacy. Post-market surveillance has revealed safety concerns and unforeseen risks associated with many drugs, sometimes leading to their withdrawal or restriction.
The case of Vioxx (rofecoxib), which was withdrawn by the biopharmaceutical company Merck due to cardiovascular risks, highlights the necessity of ongoing pharmacovigilance.8
This article explores what happens when an approved drug fails in the real world and discusses post-market surveillance mechanisms, regulatory responses, case studies, and future improvements in drug safety monitoring.
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Understanding post-market surveillance
Unlike pre-approval clinical trials, which involve limited and controlled populations, real-world use exposes drugs to diverse patient demographics, comorbidities, and polypharmacy interactions and often reveals unexpected adverse effects.
Post-market surveillance, also known as Phase IV monitoring, ensures continuous assessment of a drug’s safety profile after it reaches a broader patient population.
Pharmacovigilance systems collect safety data through spontaneous adverse event reporting databases, including the Adverse Event Reporting System (FAERS) and Vaccine Adverse Event Reporting System (VAERS) established by the FDA and the European Medicines Agency’s EudraVigilance.8
The Risk Evaluation and Mitigation Strategies (REMS) framework is another critical component in managing known or potential risks associated with high-risk drugs.11
Additionally, active surveillance using large-scale electronic health records and insurance claims databases improves the early detection of safety signals.10
Regulatory agencies also encourage post-marketing studies further to evaluate a drug’s long-term safety and efficacy.
These studies may be mandated as a condition of approval for drugs with potential risks. Furthermore, newer methodologies such as patient-centered monitoring and digital health technologies are being increasingly used to enhance post-market surveillance.
Wearable health devices, mobile applications, and patient-reported outcomes provide real-time safety data that supplement traditional pharmacovigilance methods.
These innovations are helping regulators and researchers identify adverse effects earlier and with greater accuracy.10
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Real-world examples of drug recalls
Several drugs have been withdrawn post-approval due to safety concerns. One of the most notable cases is Vioxx, the brand name for rofecoxib, a cyclooxygenase-2 (COX-2) inhibitor and nonsteroidal anti-inflammatory drug.
Initially approved for pain management in arthritis patients, Vioxx was later found to double the risk of cardiovascular events, leading to its voluntary withdrawal by Merck in 2004.8
Another case involves Rezulin (troglitazone), an anti-diabetic drug withdrawn in 2000 due to severe hepatotoxicity. Initial clinical trials did not fully capture the risk, but post-market data showed a significant increase in liver failure cases associated with Rezulin use.7
Similarly, Zelnorm (tegaserod) was recalled from the market in 2007 due to cardiovascular risks but was later reintroduced under restricted use.5 These cases underscore the limitations of pre-market trials in detecting rare but serious adverse effects.
Beyond full withdrawals, some drugs remain on the market but with significant restrictions. For instance, fluoroquinolone antibiotics have undergone multiple safety label changes due to associations with tendon rupture, aortic aneurysms, and neuropsychiatric effects.1
While not entirely banned, the use of such drugs has been limited, and additional warnings have been added to inform healthcare providers and patients about potential risks.
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Regulatory and industry response
Regulatory agencies employ several measures to deal with post-market safety concerns before resorting to drug withdrawal. The FDA and EMA issue black box warnings, which are issued when there is reasonable evidence of a serious hazard associated with the drug. Black box warnings alert healthcare professionals and patients to significant safety concerns.5
These regulatory bodies then update prescribing guidelines and mandate post-authorization safety studies. In some cases, risk minimization measures such as restricted distribution programs or mandatory patient monitoring are implemented to allow continued use of those drugs under controlled conditions.5
Pharmaceutical companies also have a responsibility to conduct post-market studies and disclose emerging safety data. Failure to do so can result in legal and financial consequences. Moreover, transparency in safety reporting is emphasized and is crucial for maintaining public trust.5
Regulators are also increasingly holding manufacturers accountable for post-market safety. Legislative changes have expanded regulatory authority, which has allowed agencies to enforce stricter monitoring requirements.
For instance, the FDA Amendments Act of 2007 granted the agency additional power to mandate post-marketing trials and impose fines on companies that fail to comply.9
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Future of post-approval monitoring
Advancements in real-world evidence (RWE) and artificial intelligence (AI) are transforming post-market drug safety monitoring. RWE, derived from electronic health records, claims data, and patient registries, provides more comprehensive safety insights compared to traditional reporting systems.2
Additionally, AI-driven signal detection tools are improving the efficiency of identifying adverse drug reactions in large datasets.4
Furthermore, global collaboration among regulatory agencies is also strengthening post-market surveillance. Initiatives such as the International Council for Harmonisation (ICH) and the Pan American Health Organization (PAHO) aim to standardize safety data collection and reporting across countries.6
Additionally, increased patient engagement in adverse event reporting through digital platforms is enhancing data collection accuracy.
The integration of machine learning algorithms with pharmacovigilance efforts is expected to improve drug safety monitoring further. Machine learning algorithms can analyze vast datasets in real-time and detect safety signals that may not be apparent through conventional reporting methods.
Furthermore, predictive modeling can assess potential drug interactions and long-term effects before they become widespread public health concerns.4
As the field of pharmacovigilance evolves, greater emphasis is being placed on proactive rather than reactive measures.
Preemptive risk assessment tools, enhanced genetic profiling, and biomarker-driven safety evaluations are being developed to predict which patient populations are most susceptible to adverse effects.
This personalized approach to drug safety monitoring may help prevent large-scale drug failures and ensure better patient outcomes in the future.
References
- Anwar, A.I., Lu, L., Plaisance, C.J., Daniel, C.P., Flanagan, C.J., Wenger, D.M., McGregor, D., Giustino Varrassi, Kaye, A.M., Shahab Ahmadzadeh, Cornett, E.M., Sahar Shekoohi and Kaye, A.D. (2024). Fluoroquinolones: Neurological Complications and Side Effects in Clinical Practice. Cureus, 16(2). doi: 10.7759/cureus.54565.
- Dang, A. (2023). Real-World Evidence: A Primer. Pharmaceutical Medicine, 37(1), pp.25–36. doi: 10.1007/s40290-022-00456-6.
- Delong, C. and Preuss, C.V. (2020). Black Box Warning. [online] PubMed. Available at: https://www.ncbi.nlm.nih.gov/books/NBK538521/ [Accessed 2 Apr. 2025].
- Dsouza, V.S., Leyens, L., Kurian, J.R., Brand, A. and Brand, H. (2025). Artificial intelligence (AI) in pharmacovigilance: A systematic review on predicting adverse drug reactions (ADR) in hospitalized patients. Research in Social and Administrative Pharmacy, [online] 21(6). doi: 10.1016/j.sapharm.2025.02.008.
- Gibbons, R.D., Amatya, A.K., Brown, C.H., Hur, K., Marcus, S.M., Bhaumik, D.K. and Mann, J.J. (2010). Post-Approval Drug Safety Surveillance. Annual Review of Public Health, 31(1), pp.419–437. doi: 10.1146/annurev.publhealth.012809.103649.
- Lomeli-Silva, A., Contreras-Salinas, H., Barajas-Virgen, M.Y., Romero-Lopez, M.S. and Rodríguez-Herrera, L.Y. (2024). Harmonization of individual case safety reports transmission requirements among PAHO reference authorities: a review of their current regulation. Therapeutic Advances in Drug Safety, [online] 15. doi: 10.1177/20420986241228119.
- Sharrar, R.G. and Dieck, G.S. (2013). Monitoring product safety in the postmarketing environment. Therapeutic Advances in Drug Safety, [online] 4(5), pp.211–219. doi: 10.1177/2042098613490780.
- Sibbald, B. (2004). Rofecoxib (Vioxx) voluntarily withdrawn from market. Canadian Medical Association Journal, [online] 171(9), pp.1027–1028. doi: 10.1503/cmaj.1041606.
- U.S. FDA (2019). Notice to Industry: Postmarketing Requirements - Postmarket studies and clinical trials. FDA. [online] Available at: https://www.fda.gov/drugs/guidance-compliance-regulatory-information/notice-industry-postmarketing-requirements-postmarket-studies-and-clinical-trials [Accessed 2 Apr. 2025].
- U.S. FDA (2023a). Postmarket surveillance with a novel mHealth platform. [online] U.S. Food and Drug Administration. Available at: https://www.fda.gov/science-research/advancing-regulatory-science/postmarket-surveillance-novel-mhealth-platform?utm_source=chatgpt.com [Accessed 2 Apr. 2025].
- U.S. FDA (2023b). Risk Evaluation and Mitigation Strategies (REMS). [online] U.S. Food and Drug Administration. Available at: https://www.fda.gov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-rems
Further Reading