Pharmacovigilance quality system for vaccine monitoring (COVID-19) using quality indicators: a scoping review


  • Mayra M. Moura de Oliveira Clinical Safety and Risk Management Center, Pharmacoepidemiology – Pharmacovigilance, Instituto Butantan, São Paulo, Brazil; and Escola Paulista de Enfermagem, Universidade Federal de São Paulo, São Paulo, Brazil
  • Gabriela Arantes Wagner Departamento de Medicina Preventiva, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo-SP, Brasil
  • Vera L. Gattás Clinical Safety and Risk Management Center, Pharmacoepidemiology – Pharmacovigilance, Instituto Butantan, São Paulo, Brazil
  • Larissa de Souza Arruda Escola Paulista de Enfermagem, Universidade Federal de São Paulo, São Paulo, Brazil
  • Monica Taminato Escola Paulista de Enfermagem, Universidade Federal de São Paulo, São Paulo, Brazil



pharmacovigilance, adverse drug reaction reporting systems, drug monitoring, COVID-19 vaccines, active surveillance, World Health Organization


This scoping review responds to the appeal of the scientific community for collaboration between different entities for pharmacovigilance and active surveillance of coronavirus disease 2019 (COVID-19) vaccines. The objective is to identify, systematically evaluate, and synthesize the best scientific evidence available on the indicators used in pharmacovigilance systems. Our results demonstrate that approximately 50% of the 25 studies used in this review have been carried out in the past 5 years. Of these, only four used the pharmacovigilance indicators proposed by the World Health Organization (WHO). Eighty-seven pharmacovigilance indicators were identified, of which seven (8.0%) related to signal detection. While the WHO advocates signal detection as routine pharmacovigilance, in special situations – such as accelerated clinical studies where adverse events are not yet well known – other indicators related to signal detection appear to be good options for maintaining quality pharmacovigilance and active surveillance in the development of the COVID-19 vaccine. However, the less robust pharmacovigilance systems in low-income countries will necessitate greater involvement of health professionals from public and private sectors, pharmaceutical companies, academic institutions, and the general public, to ensure information security and detection of signals for the COVID-19 vaccine.


Download data is not yet available.


Luo C, Yao L, Zhang L, Yao M, Chen X, Wang Q, et al. Possible transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a Public Bath Center in Huai’an, Jiangsu Province, China. JAMA Netw Open 2020; 3(3): e204583. doi: 10.1001/jamanetworkopen.2020.4583

Lee GM, Romero JR, Bell BP. Postapproval vaccine safety surveillance for COVID-19 vaccines in the US. JAMA 2020; 324(19): 1937–38. doi: 10.1001/jama.2020.19692

Shimabukuro TT, Nguyen M, Martin D, DeStefano F. Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS). Vaccine 2015; 33(36): 4398–405. doi: 10.1016/j.vaccine.2015.07.035

World Health Organization. The safety of medicines in public health programmes: pharmacovigilance an essential tool. Geneva, Switzerland: WHO Press; 2006.

Martins AS, Pedro M, Guimarães M. SCOPE Work Package 7 Quality Management Systems – compliance and performance: management and indicators. European Medicines Agency; 2016.

Petousis-Harris H. Assessing the safety of COVID-19 vaccines: a primer. Drug Saf 2020; 43(12): 1205–10. doi: 10.1007/s40264-020-01002-6

Koike ME, Gattás VL, Lucchesi MBB, Moura de Oliveira MM, Vanni T, Thomé BDC, et al. Pharmacovigilance capacity strengthening for WHO prequalification: the case of the trivalent influenza vaccine manufactured by Instituto Butantan. Vaccine 2019; 37(52): 7560–5. doi: 10.1016/j.vaccine.2019.09.082

Shah A, Marks PW, Hahn SM. Unwavering regulatory safeguards for COVID-19 vaccines. JAMA 2020; 324(10): 931–2. doi: 10.1001/jama.2020.15725

Tricco AC, Lillie E, Zarin W, O’Brien KK, Colquhoun H, Levac D, et al. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med 2018; 169(7): 467–73. doi: 10.7326/M18-0850

Arksey H, O’Malley L. Scoping studies: towards a methodological framework. Int J Soc Res Methodol 2005; 8(1): 19–32. doi: 10.1080/1364557032000119616

Peters MDJ, Godfrey CM, McInerney P, Soares CB, Monash HK, Parker D. The Joanna Briggs Institute reviewers’ manual 2015: methodology for JBI scoping reviews. Adelaide, Australia: The Joanna Briggs Institute; 2015.

McGowan J, Sampson M, Salzwedel DM, Cogo E, Foerster V, Lefebvre C. PRESS peer review of electronic search strategies: 2015 guideline statement. J Clin Epidemiol 2016; 75: 40–6. doi: 10.1016/j.jclinepi.2016.01.021

Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan-a web and mobile app for systematic reviews. Syst Rev 2016; 5(1): 210. doi: 10.1186/s13643-016-0384-4

Ejekam CS, Isah A, Fourrier-Réglat A. Evaluation of the pharmacovigilance activities in the national malaria, tuberculosis and HIV/AIDS control programmes in Nigeria using the WHO PV indicators. Abstracts of the 33rd international conference on pharmacoepidemiology & therapeutic risk management, Palais des congrès de Montréal, Montréal, Canada. Pharmacoepidemiol Drug Saf 2017; 26(Suppl. 2): 3–636. doi: 10.1002/pds.4275

Qato DM. Current state of pharmacovigilance in the Arab and Eastern Mediterranean region: results of a 2015 survey. Int J Pharm Pract 2018; 26(3): 210–21. doi: 10.1111/ijpp.12372

Opadeyi AO, Fourrier-Réglat A, Isah AO. Assessment of the state of pharmacovigilance in the South-South zone of Nigeria using WHO pharmacovigilance indicators. BMC Pharmacol Toxicol 2018; 19(1): 27. doi: 10.1186/s40360-018-0217-2

Elsidig M, Elkheir H, Osman A. Evaluation of pharmacovigilance system in Sudan using WHO indicators. Abstracts of the 18th ISoP annual meeting ‘Pharmacovigilance without borders’ Geneva, Switzerland. Drug Saf 2018; 41: 1103–1273. doi: 10.1007/s40264-018-0719-2

Klepper MJ. The periodic safety update report as a pharmacovigilance tool. Drug Saf 2004; 27(8): 569–78. doi: 10.2165/00002018-200427080-00008

Gunawardena S, Sri Ranganathan S, Fernandopulle R. Pharmacovigilance through consumer feedback (reporting) in the mass treatment of lymphatic filariasis using diethylcarbamazine and albendazole in two districts of Sri Lanka. Trop Med Int Health 2008; 13(9): 1153–8. doi: 10.1111/j.1365-3156.2008.02120.x

Kshirsagar NA, Olsson S, Ferner RE. Consideration of the desirable features and possible forms of practical indicators of the performance of pharmacovigilance centres. Int J Risk Saf Med 2010; 22(2): 59–66. doi: 10.3233/JRS-2010-0495

Prabhakar U, Edwards B. Postmarketing safety surveillance: issues with data collection for postmarketing pharmacovigilance. Pharmaceut Med 2010; 24(6): 343–8. doi: 10.1007/BF03256835

Ogami T, Imaizumi T, Ishiguro C, Matsuda T. Assessment of postmarketing safety-related regulatory actions in Japan. Pharmaceut Med 2012; 26(6): 395–403. doi: 10.1007/BF03262383

Gagne JJ, Walker AM, Glynn RJ, Rassen JA, Schneeweiss S. An event-based approach for comparing the performance of methods for prospective medical product monitoring. Pharmacoepidemiol Drug Saf 2012; 21(6): 631–9. doi: 10.1002/pds.2347

Bres V, Robin P, Pinzani V, Philibert C, Bos-Thompson MA, Hillaire-Buys D, et al. The ATHE Score: a new indicator for data quality management of spontaneous reporting in pharmacovigilance. Abstracts of the 13th ISoP annual meeting: ‘The Renaissance of Pharmacovigilance’ Pisa, Italy. Drug Saf 2013; (36): 793–951. doi: 10.1007/s40264-013-0087-x

Motola D, Melis M, Lo Bianco S, Buccellato E, Biagi C, Vaccheri A. Ten years of pharmacovigilance in Italy: the experience of Emilia-Romagna region in the monitoring of drug’s safety profile. Expert Opin Drug Saf 2014; 13(7): 867–73. doi: 10.1517/14740338.2014.916687

Castro-Pastrana LI, Pedraza-Montero P, Ortiz-Islas R, Isis B-C, Ivette R-H, Silvia S-R, et al. Gestión de la calidad en Unidades de Farmacovigilancia Hospitalaria. Propuesta de indicadores de la red ASEGUREMHOS: a quality management model for hospital-based pharmacovigilance units. Quality indicators for benchmarking from the ASEGUREMHOS network. Rev Mex Cienc Farm 2014; 45(1): 57–77.

Bapatla KB, Close P, Sharma G, Naidu M, Valliappan R. Timeliness of a signal detection process as a component of effectiveness assessment in a drug safety department of a large pharmaceutical company: review over a 5-year period. Ther Innov Regul Sci 2014; 48(6): 734–40. doi: 10.1177/2168479014527285

Chen L, Jiang L, Shen A, Wei W. Development of a quality instrument for assessing the spontaneous reports of ADR/ADE using Delphi method in China. Eur J Clin Pharmacol 2016; 72(9): 1135–42. doi: 10.1007/s00228-016-2081-6

Suwankesawong W, Dhippayom T, Tan-Koi WC, Kongkaew C. Pharmacovigilance activities in ASEAN countries. Pharmacoepidemiol Drug Saf 2016; 25(9): 1061–9. doi: 10.1002/pds.4023

Adesina AA, Hussain Q, Pandit S, Rejzek M, Hochberg AM. Assessing the value of system theoretic process analysis in a pharmacovigilance process: an example using signal management. Pharmaceut Med 2017; 31: 267–78. doi: 10.1007/s40290-017-0195-5

Lei J, Balakrishnan MR, Gidudu JF, Zuber PLF. Use of a new global indicator for vaccine safety surveillance and trends in adverse events following immunization reporting 2000–2015. Vaccine 2018; 36(12): 1577–82. doi: 10.1016/j.vaccine.2018.02.012

Glamočlija U, Tubić B, Kondža M, Zolak A, Grubiša N. Adverse drug reaction reporting and development of pharmacovigilance systems in Bosnia and Herzegovina, Croatia, Serbia, and Montenegro: a retrospective pharmacoepidemiological study. Croat Med J 2018; 59(3): 124–31. doi: 10.3325/cmj.2018.59.124

Wang J, Zhao L, Ye Y, Zhang Y. Adverse event detection by integrating twitter data and VAERS. J Biomed Semantics 2018; 9(1): 19. doi: 10.1186/s13326-018-0184-y

Smith K, Golder S, Sarker A, Loke Y, O’Connor K, Gonzalez-Hernandez G. Methods to compare adverse events in Twitter to FAERS, drug information databases, and systematic reviews: proof of concept with Adalimumab. Drug Saf 2018; 41(12): 1397–410. doi: 10.1007/s40264-018-0707-6

Farcas A, Huruba M, Mogosan C. Study design, process and outcome indicators of post-authorization studies aimed at evaluating the effectiveness of risk minimization measures in the EU PAS Register. Br J Clin Pharmacol 2019; 85(3): 476–91. doi: 10.1111/bcp.13824

Lam L, Desitter C, Maison P. L’activité de recueil des centres régionaux de pharmacovigilance est-elle influée par des déterminants régionaux démographiques ou sanitaires. Therapies 2019; 74(3): 333–41. doi: 10.1016/j.therap.2018.05.002

Karapetiantz P, Audeh B, Faille J, Lillo-Le Louët A, Bousquet C. Qualitative and quantitative analysis of web forums for adverse events detection: ‘Strontium Ranelate’ case study. Stud Health Technol Inform 2019; 264: 964–8. doi: 10.3233/SHTI190367

Stergiopoulos S, Fehrle M, Caubel P, Tan L, Jebson L. Adverse drug reaction case safety practices in large biopharmaceutical organizations from 2007 to 2017: an industry survey [published correction appears in Pharmaceut Med 2020 Feb; 34(1): 81]. Pharmaceut Med 2019; 33(6): 499–510. doi: 10.1007/s40290-019-00307-x

World Health Organization. Global vaccine safety Blueprint 2.0 background research. Geneva, Switzerland: WHO Press; 2019.

Kochhar S, Salmon DA. Planning for COVID-19 vaccines safety surveillance. Vaccine 2020; 38(40): 6194–8. doi: 10.1016/j.vaccine.2020.07.013

World Health Organization. WHO pharmacovigilance indicators: a practical manual for the assessment of pharmacovigilance systems. Geneva, Switzerland: WHO Press; 2015.

Olsson S, Pal SN, Dodoo A. Pharmacovigilance in resource-limited countries. Expert Rev Clin Pharmacol 2015; 8(4): 449–60. doi: 10.1586/17512433.2015.1053391

Castro AV, Rezende M. The Delphi Technique and its use in brazilian nursing research: bibliographical review [A técnica Delphi e seu uso na pesquisa de Enfermagem: revisão bibliográfica]. Rev Min Enferm 2009; 13(3): 429–34.

World Health Organization. Global vaccine action plan: monitoring, evaluation & accountability. Secretariat Annual Report 2018. Geneva, Switzerland: WHO Press; 2018.



How to Cite

de Oliveira, M. M. M., Wagner, G. A., Gattás, V. L., Arruda, L. de S., & Taminato, M. (2021). Pharmacovigilance quality system for vaccine monitoring (COVID-19) using quality indicators: a scoping review. International Journal of Infection Control, 17(1).



Review Articles