Post-marketing pharmacovigilance methods: Spontaneous reports and scientifi c literature monitoring (review)

INTRODUCTION. Many aspects of the drug safety profile, including rare and delayed adverse drug reactions (ADRs), are identified only in the post-marketing period when the drug is used in real-world clinical practice. However, the drawbacks inherent in spontaneous reporting and scientific literature monitoring (the main methods of post-marketing pharmacovigilance), such as incompleteness, fragmentation, variability in data quality, and the lack of standardized approaches to their analysis necessitate the systematization of information and the unification of approaches to data processing.

AIM. To systematize information on the spontaneous reporting method and scientific literature monitoring, as well as on data processing approaches in post-marketing pharmacovigilance for risk management and ensuring drug safety.

DISCUSSION. Spontaneous reporting is the basic passive method for post-marketing drug safety monitoring, with advantages including broad population coverage and the ability to detect a wide range of ADRs, including rare, delayed, and previously unknown ones. The effectiveness of the spontaneous reporting method can be enhanced through the development of educational programs for healthcare professionals and patients, the implementation of natural language processing (NLP) technologies to automate the extraction of structured information about ADRs from unstructured text sources, and integration with real-world data (RWD) to confirm signals and quantify risks. Scientific literature monitoring serves as a bridge between the passive collection of real-world data and evidence-based findings from controlled studies. An analysis of the EAEU Good Pharmacovigilance Practice Guidelines shows that when searching for information in the scientific literature, special aspects of the drug safety profile must be taken into account: effects on pregnancy outcomes, use in pediatrics, lack of efficacy, overdose, off-label use, and preclinical data. To standardize statistical methods for signal detection and the correct interpretation of signals (disproportionality analysis in spontaneous reporting databases), the READUS-PV guideline (2024) is recommended.

CONCLUSIONS. The modern methodology of post-marketing pharmacovigilance is a dynamically evolving system. The presented systematization of approaches to spontaneous reporting and scientific literature monitoring, as well as the list of mandatory drug safety aspects, can serve as a practical tool for specialists in planning and conducting drug safety assessments.

1. Zhuravleva MV, Serebrova SYu, Kuznetsova EV, et al. Improving the pharmacovigilance system in medical organisations as an opportunity to enhance the quality of pharmacotherapy. Safety and Risk of Pharmacotherapy. 2025;13(1):94–107 (In Russ.). https://doi.org/10.30895/2312-7821-2025-13-1-94-107

2. Pitkala KH, Strandberg TE. Clinical trials in older people. Age ¬Ageing. 2022;51(5):afab282. https://doi.org/10.1093/ageing/afab282

3. Alomar M, Tawfiq AM, Hassan N, et al. Post marketing surveillance of suspected adverse drug reactions through spontaneous reporting: current status, challenges and the future. Ther Adv Drug Saf. 2020;11:2042098620938595. https://doi.org/10.1177/2042098620938595

4. Raj N, Fernandes S, Charyulu NR, et al. Postmarket surveillance: A review on key aspects and measures on the effective functioning in the context of the United Kingdom and Canada. Ther Adv Drug Saf. 2019;10:2042098619865413. https://doi.org/10.1177/2042098619865413

5. Wasiullah M, Yadav P, Yadav SK, Yadav AK. Protecting health — A pharmacovigilance analysis of drug safety. Int J Pharm Res Appl. 2025;10(2):2377–83. https://doi.org/10.35629/4494-100223772383

6. Yu X, Zhong J, Lin Z, et al. Post-marketing safety concerns with trofinetide: A disproportionality analysis of the first therapeutic agent for Rett syndrome based on the FDA adverse event reporting system (FAERS). Front Pharmacol. 2026;17:1643906. https://doi.org/10.3389/fphar.2026.1643906

7. Abedian Kalkhoran H, Zwaveling J, van Hunsel F, et al. An innovative method to strengthen evidence for potential drug safety signals using electronic health records. J Med Syst. 2024;48(1):51. https://doi.org/10.1007/s10916-024-02070-2

8. Paul AE, Sasidharanpillai S. Role of pharmacovigilance in drug safety monitoring. Indian Dermatol Online J. 2025;16(4):545–50. https://doi.org/10.4103/idoj.idoj_771_24

9. Desai M. Pharmacovigilance and spontaneous adverse drug reaction reporting: Challenges and opportunities. Perspect Clin Res. 2022;13(4):177–9. https://doi.org/10.4103/picr.picr_169_22

10. Dedefo MG, Kassie GM, Gebreyohannes EA, et al. Completeness of spontaneously reported adverse drug reactions in 4 databases. Br J Clin Pharmacol. 2025;91(12):3389–400. https://doi.org/10.1002/bcp.70182

11. Hammad TA, Naylor M, Ely DM, et al. Exploring the complexities of disproportionality analysis in pharmacovigilance: Reflections on the READUS-PV guideline and a call to action. Front Pharmacol. 2025;16:1573353. https://doi.org/10.3389/fphar.2025.1573353

12. Bondareva IB, Zyryanov SK, Asetskaya IL, et al. Some features of statistical analysis of spontaneous adverse drug reporting data. Good Clinical Practice. 2024;(3):40–54 (In Russ.). https://doi.org/10.37489/2588-0519-2024-3-40-54

13. Li Y, Wu Y, Jiang T, et al. Opportunities and challenges of pharmacovigilance in special populations: A narrative review of the literature. Ther Adv Drug Saf. 2023;14:20420986231200746. https://doi.org/10.1177/20420986231200746

14. Milchakov KS. Recommendations on informational monitoring of the safety and efficacy of medicinal products in the Russian Federation as part of pharmacovigilance. Safety and Risk of Pharmacotherapy. 2022;10(3):218–29 (In Russ.). https://doi.org/10.30895/2312-7821-2022-10-3-218-229

15. Shubnikova EV. Postmarketing surveillance: Review of open sources of drug safety data. Safety and Risk of Pharmacotherapy. 2024;12(3):309–30 (In Russ.). https://doi.org/10.30895/2312-7821-2024-12-3-309-330

16. Litvinenko TS, Safronenko AV, Maklyakov YS, et al. Analysis of spontaneous reports as a methodological pharmacovigilance tool. Journal Biomed. 2022;18(2):40–5 (In Russ.). https://doi.org/10.33647/2074-5982-18-2-40-45

17. Kazakov AS, Darmostukova MA, Bukatina TM, et al. Comparative analysis of international databases of adverse drug reactions. Safety and Risk of Pharmacotherapy. 2020;8(3):134–40 (In Russ.). https://doi.org/10.30895/2312-7821-2020-8-3-134-140

18. Dubrall D, Christ P, Domgörgen S, et al. Factors associated with the completeness of information provided in adverse drug reaction reports of physicians, pharmacists and consumers from Germany. Sci Rep. 2025;15(1):23751. https://doi.org/10.1038/s41598-025-07973-9

19. Brand JS, Gauffin O, Sartori D, et al. VigiBase: Resource profile update with a summary of global patterns and trends in adverse event reports for medicines and vaccines. Drug Saf. 2026;49:613–29. https://doi.org/10.1007/s40264-025-01642-6

20. Postigo R, Brosch S, Slattery J, et al. EudraVigilance medicines safety database: Publicly accessible data for research and public health protection. Drug Saf. 2018;41(7):665–75. https://doi.org/10.1007/s40264-018-0647-1

21. Potter E, Reyes M, Naples J, et al. FDA Adverse Event Reporting System (FAERS) essentials: A guide to understanding, applying, and interpreting adverse event data reported to FAERS. Clin Pharmacol Ther. 2025;118(3):567–82. https://doi.org/10.1002/cpt.3701

22. Combi C, Zorzi M, Pozzani G, et al. From narrative descriptions to MedDRA: Automagically encoding adverse drug reactions. J Biomed Inform. 2018;84:184–99. https://doi.org/10.1016/j.jbi.2018.07.001

23. Jiao XF, Pu L, Lan S, et al. Adverse drug reaction signal detection methods in spontaneous reporting system: A systematic review. Pharmacoepidemiol Drug Saf. 2024;33(3):e5768. https://doi.org/10.1002/pds.5768

24. Fusaroli M, Salvo F, Begaud B, et al. The reporting of a disproportionality analysis for drug safety signal detection using individual case safety reports in pharmacovigilance (READUS-PV): Development and statement. Drug Saf. 2024;47(6):575–84. https://doi.org/10.1007/s40264-024-01421-9

25. Fusaroli M, Salvo F, Begaud B, et al. The reporting of a disproportionality analysis for drug safety signal detection using individual case safety reports in pharmacovigilance (READUS-PV): Explanation and elaboration. Drug Saf. 2024;47(6):585–99. https://doi.org/10.1007/s40264-024-01423-7

26. Graeff V, Wehler M, Dormann H, et al. Comparative analysis of drugs frequently suspected of causing adverse drug reactions reported via the spontaneous reporting system versus in a prospective multicentre cohort study in hospital emergency departments. J Clin Med. 2025;14(17):5921. https://doi.org/10.3390/jcm14175921

27. Noguchi Y, Tachi T, Yoshimura T. Is it appropriate to conduct a disproportionality analysis using a spontaneous reporting database to investigate whether drug-related adverse events are dose-dependent? Front Pharmacol. 2025;16:1563524. https://doi.org/10.3389/fphar.2025.1563524

28. Kiguba R, Isabirye G, Mayengo J, et al. Navigating duplication in pharmacovigilance databases: A scoping review. BMJ Open. 2024;14(4):e081990. https://doi.org/10.1136/bmjopen-2023-081990

29. Lavertu A, Vora B, Giacomini KM, et al. A new era in pharmacovigilance: Toward real-world data and digital monitoring. Clin Pharmacol Ther. 2021;109(5):1197–202. https://doi.org/10.1002/cpt.2172

30. Mugoša S, Meštrović A, Vukićević V, et al. SMART Pharmacist — The impact of education on improving pharmacists’ participation in monitoring the safety of medicine use in Montenegro. Pharmacy (Basel). 2025;13(2):57. https://doi.org/10.3390/pharmacy13020057

31. Saad AH, Bondok R, Sayeg F, et al. Enhancing medication error reporting through interprofessional education: Analysis of Medwatch reporting accuracy and completion rates between teams and individuals. BMC Med Educ. 2025;25(1):756. https://doi.org/10.1186/s12909-025-07349-7

32. Crisafulli S, Bate A, Brown JS, et al. Interplay of spontaneous reporting and longitudinal healthcare databases for signal management: Position statement from the real-world evidence and big data Special Interest Group of the International Society of Pharmacovigilance. Drug Saf. 2025;48(9):959–76. https://doi.org/10.1007/s40264-025-01548-3

33. Warner J, Prada Jardim A, Albera C, et al. Artificial intelligence: Applications in pharmacovigilance signal management. Pharmaceut Med. 2025;39(3):183–98. https://doi.org/10.1007/s40290-025-00561-2

34. van der Weg W, von Kreijfelt G, Davidson L, et al. Strengthening spontaneous reporting-based signal detection during a pandemic with cases from electronic health records using a natural language processing tool. Vaccine. 2025;62:127549. https://doi.org/10.1016/j.vaccine.2025.127549

35. Khemani DB, Malave DS, Shinde S, et al. AI-driven pharmacovigilance: Enhancing adverse drug reaction detection with deep learning and NLP. MethodsX. 2025;15:103460. https://doi.org/10.1016/j.mex.2025.103460

36. Sharma R. Recent advances in pharmacovigilance: Artificial intelligence, real world evidence, and global harmonization. Int J Sci Res. 2025;14(2):1123–8. https://doi.org/10.21275/SR251226122226

37. Hu Q, Li J, Li X, et al. Machine learning to predict adverse drug events based on electronic health records: A systematic review and meta-analysis. J Int Med Res. 2024;52(12):3000605241302304. https://doi.org/10.1177/03000605241302304

38. Malikova MA. Practical applications of regulatory requirements for signal detection and communications in pharmacovigilance. Ther Adv Drug Saf. 2020;11:2042098620909614. https://doi.org/10.1177/2042098620909614

39. Sartori D, Aronson JK, Norén GN, et al. Signals of adverse drug reactions communicated by pharmacovigilance stakeholders: A scoping review of the global literature. Drug Saf. 2023;46(2):109–20. https://doi.org/10.1007/s40264-022-01258-0

40. Matveev AV, Krasheninnikov AE, Matveeva EA, et al. Differences between the European and Eurasian Good Pharmacovigilance Practices. Safety and Risk of Pharmacotherapy. 2021;9(2):75–84 (In Russ.). https://doi.org/10.30895/2312-7821-2021-9-2-75-84

41. Shafi J, Virk MK, Kalk E, et al. Pharmacovigilance in pregnancy studies, exposures and outcomes ascertainment, and findings from low-and middle-income countries: A scoping review. Drug Saf. 2024;47(10):957–90. https://doi.org/10.1007/s40264-024-01445-1

42. Abadie D, Hurault-Delarue C, Damase-Michel C, et al. Medication exposure and spontaneous abortion: A case-control study using a French medical database. Clin Exp Obstet Gynecol. 2015;42(4):431–6. PMID: 26411206

43. Kelesidou V, Tsakiridis I, Virgiliou A, et al. Combination of mifepristone and misoprostol for first-trimester medical abortion: A comprehensive review of the literature. Obstet Gynecol Surv. 2024;79(1):54–63. https://doi.org/10.1097/ogx.0000000000001222

44. Leichombam R, Bawiskar D. Exploring the safety and efficacy of medical termination of pregnancy: A comprehensive review. Cureus. 2023;15(10):e46444. https://doi.org/10.7759/cureus.46444

45. Dubucs C, Plaisancié J, Courtade-Saidi M, et al. The first review on prenatal drug exposure and ocular malformation occurrence. Front Pediatr. 2024;12:1379875. https://doi.org/10.3389/fped.2024.1379875

46. Wang T, Jiang R, Yao Y, et al. Anti-hypertensive therapy for preeclampsia: A network meta-analysis and systematic review. ¬Hypertens Pregnancy. 2024;43(1):2329068. https://doi.org/10.1080/10641955.2024.2329068

47. Akre S, Sharma K, Chakole S, et al. Eclampsia and its treatment modalities: A review article. Cureus. 2022;14(9):e29080. https://doi.org/10.7759/cureus.29080

48. Lu H, Rosenbaum S. Developmental pharmacokinetics in pediatric populations. J Pediatr Pharmacol Ther. 2014;19(4):262–76. https://doi.org/10.5863/1551-6776-19.4.262

49. Gavrilenko L. Current problem in pediatrics: Features of the use of “children’s” and “adult” forms of preparations in children. Prescription. 2024;27(3):481–7 (In Russ.). https://doi.org/10.34883/PI.2024.27.3.014

50. Wong IC, Ghaleb MA, Franklin BD, Barber N. Incidence and nature of dosing errors in paediatric medications: A systematic review. Drug Saf. 2004;27(9):661–70. https://doi.org/10.2165/00002018-200427090-00004

51. Meesters K, Balbas-Martinez V, Allegaert K, et al. Personalized dosing of medicines for children: A primer on pediatric pharmacometrics for clinicians. Paediatr Drugs. 2024;26(4):365–79. https://doi.org/10.1007/s40272-024-00633-x

52. Butranova OI, Kustov YuO, Zyryanov SK, et al. Safety profile of ciprofloxacin in the pediatric population: analysis of the database of spontaneous reports. Good Clinical Practice. 2025;(4):55–64 (In Russ.). https://doi.org/10.37489/2588-0519-GCP-0005

53. Sultana S, Mitu FH. Pharmacovigilance in paediatric population: An evolving landscape in drug safety monitoring. Mugda Medical College Journal. 2025;8(2):150–6. https://doi.org/10.3329/mumcj.v8i2.85830

54. Rosenberg N, Post HC, Schutte T, et al. Access to anticancer and orphan medicines through compassionate use programs and named patient basis in seven European countries. ESMO Open. 2025;10(11):105855. https://doi.org/10.1016/j.esmoop.2025.105855

55. Polak TB, Cucchi DGJ, van Rosmalen J, et al. Generating evidence from expanded access use of rare disease medicines: Challenges and recommendations. Front Pharmacol. 2022;13:913567. https://doi.org/10.3389/fphar.2022.913567

56. Polak TB, van Rosmalen J, Uyl-de Groot CA. Expanded access as a source of real-world data: An overview of FDA and EMA approvals. Br J Clin Pharmacol. 2020;86(9):1819–26. https://doi.org/10.1111/bcp.14284

57. Vermeulen SF, Polak TB, Bunnik EM. Expanded access to investigational drugs in psychiatry: A systematic review. Psychiatry Res. 2023;329:115554. https://doi.org/10.1016/j.psychres.2023.115554

58. Polak TB, Cucchi DGJ, Schelhaas J, et al. Results from expanded access programs: A review of academic literature. Drugs. 2023;83(9):795–805. https://doi.org/10.1007/s40265-023-01879-4

59. Marsal J, Barreiro-de Acosta M, Blumenstein I, et al. Management of non-response and loss of response to anti-tumor necrosis factor therapy in inflammatory bowel disease. Front Med (Lausanne). 2022;9:897936. https://doi.org/10.3389/fmed.2022.897936

60. Hirschfeld RM, Montgomery SA, Aguglia E, et al. Partial response and nonresponse to antidepressant therapy: Current approaches and treatment options. J Clin Psychiatry. 2002;63(9):826–37. https://doi.org/10.4088/jcp.v63n0913

61. Gajdács M, Albericio F. Antibiotic resistance: From the bench to patients. Antibiotics (Basel). 2019;8(3):129. https://doi.org/10.3390/antibiotics8030129

62. Akhmadhodjaeva MM. Modern strategies for overcoming antibiotic resistance. Medical Journal of Young Scientists. 2025;16(12):190–7 (In Russ.).

63. Balew M, Abeje G, Mekonnen A, et al. Prevalence of HIV drug resistance among patients experiencing first-line treatment failure in Ethiopia: A systematic review and meta-analysis. BMC Public Health. 2025;25(1):2059. https://doi.org/10.1186/s12889-025-23193-2

64. Zhukova OV, Chesnokova NN, Vorobeva OA, et al. Ineffectiveness of carbapenems in real-world clinical practice according to therapeutic drug monitoring data and Roszdravnadzor AIS reports. Good Clinical Practice. 2024;(2):66–71 (In Russ.). https://doi.org/10.37489/2588-0519-2024-2-65-71

65. Gaikwad V, Kumbhar S, Chougule N. Pharmacovigilance and over counter drugs ensuring safety. Int J Pharm. Sci. 2024;2(12):1193–212. https://doi.org/10.5281/zenodo.14361696

66. Murshed M, Salim M, Boyd BJ. Existing and emerging mitigation strategies for the prevention of accidental overdose from oral pharmaceutical products. Eur J Pharm Biopharm. 2022;180:201–11. https://doi.org/10.1016/j.ejpb.2022.10.002

67. Soumerai SB, Koppel R, Naci H, et al. Intended and unintended outcomes after FDA pediatric antidepressant warnings: A systematic review. Health Aff (Millwood). 2024;43(10):1360–9. https://doi.org/10.1377/hlthaff.2023.00263

68. Hannibal GD, Vithanage N, Madhushika MT, et al. A systematic review of prescription errors in paediatric care. BMC Health Serv Res. 2025;25(1):967. https://doi.org/10.1186/s12913-025-13109-6

69. Naseralallah L, Stewart D, Price M, et al. Prevalence, contributing factors, and interventions to reduce medication errors in outpatient and ambulatory settings: a systematic review. Int J Clin Pharm. 2023;45(6):1359–77. https://doi.org/10.1007/s11096-023-01626-5

70. Day RO. Ongoing challenges of off-label prescribing. Aust Prescr. 2023;46(4):86–9. https://doi.org/10.18773/austprescr.2023.022

71. Taylor J, Blockman M. Wrong-route drug administration errors: A review of the literature. S Afr Med J. 2023;113(12):29. https://doi.org/10.7196/samj.2023.v113i12.1043

72. Somova MN, Batishcheva GA, Abramyan AA, Klyukin AA. Pharmaceutical drug interactions: Current aspects in real clinical practice. Medical Scientific Bulletin of Central Chernozemye. 2024;25(2):30–7 (In Russ.). https://doi.org/10.18499/1990-472X-2024-25-2-30-37

73. Sorokina AV, Alekseeva SV, Miroshkina IA, et al. Study of acute toxicity of GIZh-298. Pharmacokinetics and Pharmacodynamics. 2023;(1):51–7 (In Russ.). https://doi.org/10.37489/2587-7836-2023-1-51-57

74. Ye Q, Xing W, Hu X, et al. Preclinical pharmacokinetics, ADME, and drug-drug interaction evaluation of S024, a novel p38/MK2 inhibitor for rheumatoid arthritis. Drug Des Devel Ther. 2026;20:591017 https://doi.org/10.2147/DDDT.S591017

75. Dande A, Chandra Mouli HM, Nandy J, et al. Risk assessment, detection and control of mutagenic impurities in pharmaceuticals: Emphasis on nitrosamines. Crit Rev Anal Chem. 2025;1–42. https://doi.org/10.1080/10408347.2025.2517357

76. Yu J, Zhu M, Zhu Y, et al. From class effects to specificity FAERS evi-dence and network mapping of adverse events in NSCLC targeted therapy. Int J Surg. 2026;112(4):9520–34. https://doi.org/10.1097/JS9.0000000000004704

77. Zeng X, Dai L, Li Z, et al. Comparative efficacy and safety of imrecoxib versus celecoxib: A systematic review and meta-analysis. Front Pharmacol. 2026;16:1707079. https://doi.org/10.3389/fphar.2025.1707079

78. Radulian IL, Nitulescu G, Zanfirescu A, et al. Comparative analysis of adverse effects: Protein kinase inhibitors versus traditional anticancer therapies. Sci Pharm. 2025;93(2):20. https://doi.org/10.3390/scipharm93020020

79. Skov K, Sædder AE, Madsen GK, et al, Hypersensitivity to opioids: Prevalence, mechanisms, diagnosis and management. Basic Clin Pharmacol Toxicol. 2026;138(2):e70182. https://doi.org/10.1111/bcpt.70182

80. Tchijevitch O, Hansen SM, Hallas J, et al. Methodological approaches for analyzing medication error reports in patient safety reporting systems: A scoping review. Jt Comm J Qual Patient Saf. 2025;51(1):46–73. https://doi.org/10.1016/j.jcjq.2024.10.005

81. Martenot V, Masdeu V, Cupe J, et al. LiSA: An assisted literature search pipeline for detecting serious adverse drug events with deep learning. BMC Med Inform Decis Mak. 2022;22(1):338. https://doi.org/10.1186/s12911-022-02085-0