ABSTRACT

The study aimed to evaluate a group of health professionals' knowledge, attitudes, and practices on pharmacovigilance in the context of COVID-19 in the Peruvian Social Health Insurance (EsSalud). A descriptive secondary analysis was carried out on a database that included responses from an online survey conducted by the Institutional Referral Center for Pharmacovigilance and Technovigilance of EsSalud. Of 144 participants, 66% showed a high level of knowledge and 81.2% had a positive attitude; however, 71.5% had an inadequate level of pharmacovigilance practice. Although EsSalud professionals demonstrated a high level of knowledge and positive attitude to implement pharmacovigilance, this is not reflected in the practice of this activity during the SARS-CoV-2 pandemic. Strategies should be implemented to integrate pharmacovigilance into healthcare activities to benefit patient safety.

Keywords:
Drug Safety; Pharmacovigilance; Health Knowledge, Attitudes, Practice; Healthcare Workers; COVID-19

INTRODUCTION

Pharmacovigilance is the science and activity related to the detection, evaluation, understanding and prevention of adverse effects of drugs or any related problem that causes unintended harm to the patient; one of its essential components is the reporting of adverse drug reactions (ADRs) ¹1. Farmacovigilancia - OPS/OMS | Organización Panamericana de la Salud [Internet]. [citado 29 de marzo de 2022]. Disponible en: https://www.paho.org/es/temas/farmacovigilancia.
https://www.paho.org/es/temas/farmacovig... . The Peruvian Pharmacovigilance System has been in place since 2000 and is managed by the General Directorate of Medicines, Supplies and Drugs (DIGEMID). One of the institutions that is part of this system is the Peruvian Social Health Insurance (EsSalud) through the Institutional Referral Center for Pharmacovigilance and Technovigilance (CRI-EsSalud) ²2. Dirección General de Medicamentos, Insumos y Drogas. Directiva que regula el Sistema de Farmacovigilancia y Tecnovigilancia de EsSalud, MINSA; 2016 [citado el 26 de octubre de 2021]. Disponible en: https://www.digemid.minsa.gob.pe/farmacovigilancia-y-tecnovigilancia.
https://www.digemid.minsa.gob.pe/farmaco... .

Despite the fact that pharmacovigilance is part of health care activities, there is little evidence regarding the knowledge and practice of pharmacovigilance by health care professionals in some parts of the world. A recent study estimated that slightly more than half (52.2%) of healthcare personnel had inadequate knowledge of pharmacovigilance ³3. Syed A, Azhar S, Raza MM, Saeed H, Jamshed SQ. Assessment of knowledge, attitude, and barriers towards pharmacovigilance among physicians and pharmacists of Abbottabad, Pakistan. Pharmacy. 2018;6(2):29. doi: 10.3390/pharmacy6020029.
https://doi.org/10.3390/pharmacy6020029... and up to 86.6% were unaware of the impact of ADR reporting ⁴4. Ali MD, Hassan YA, Ahmad A, Alaqel O, Al-Harbi H, Al-Suhaimi NM. Knowledge, Practice and Attitudes Toward Pharmacovigilance and Adverse Drug Reactions Reporting Process Among Health Care Providers in Dammam, Saudi Arabia. Curr Drug Saf. 2018;13(1):21-25. doi: 10.2174/1574886313666171218123802.
https://doi.org/10.2174/1574886313666171... ^,55. Al Rabayah AA, Hanoun EM, Rumman RH. Assessing knowledge, attitude, and practices of health-care providers toward pharmacovigilance and adverse drug reaction reporting at a comprehensive cancer center in Jordan. Perspect Clin Res. 2019;10(3):115. doi: 10.4103/picr.PICR_4_18.
https://doi.org/10.4103/picr.PICR_4_18... . There are healthcare professionals who consider that reporting ADRs is an obligation rather than a healthcare task ⁶6. Alshammari TM, Alamri KK, Ghawa YA, Alohali NF, Abualkol SA, Aljadhey HS. Knowledge and attitude of health-care professionals in hospitals towards pharmacovigilance in Saudi Arabia. Int J Clin Pharm. 2015;37(6):1104-10. doi: 10.1007/s11096-015-0165-5.
https://doi.org/10.1007/s11096-015-0165-... ; however, it has also been reported that non-prescribing professionals report ADRs more frequently and with less knowledge of pharmacovigilance ⁷7. Ergün Y, Ergün TB, Toker E, Ünal E, Akben M. Knowledge attitude and practice of Turkish health professionals towards pharmacovigilance in a university hospital. Int Health. 2019;11(3):177-84. doi: 10.1093/inthealth/ihy073.
https://doi.org/10.1093/inthealth/ihy073... .

The role of pharmacovigilance during the COVID-19 pandemic is even more important because therapeutic alternatives have been used without sufficient scientific evidence for the treatment of COVID-19 ⁸8. Chandler RE, McCarthy D, Delumeau J-C, Harrison-Woolrych M. The role of pharmacovigilance and ISoP during the global COVID-19 pandemic. Drug Saf. 2020;1-2. doi: 10.1007/s40264-020-00941-4.
https://doi.org/10.1007/s40264-020-00941...

9. Tuccori M, Convertino I, Ferraro S, Cappello E, Valdiserra G, Focosi D, et al. The Impact of the COVID-19 "Infodemic" on drug-utilization behaviors: implications for pharmacovigilance. Drug Saf. 2020;43(8):699-709. doi: 10.1007/s40264-020-00965-w.
https://doi.org/10.1007/s40264-020-00965... ^-1010. Desai MK. Pharmacovigilance and assessment of drug safety reports during COVID 19. Perspect Clin Res. 2020;11(3):128-31. doi: 10.4103/picr.PICR_171_20.
https://doi.org/10.4103/picr.PICR_171_20... , which could result in more risks than benefits because their safety profiles in this type of patients are unknown. Therefore, this study aims to describe the knowledge, attitudes and practices regarding pharmacovigilance in the context of the COVID-19 pandemic in a group of Peruvian social security health professionals.

THE STUDY

Design of the study

A descriptive secondary analysis conducted on a database that contains responses from an online survey conducted by the ESSALUD Institutional Referral Center for Pharmacovigilance and Technovigilance (CRI-ESSALUD) regarding pharmacovigilance knowledge, attitudes and practices in the context of COVID-19, aimed at health professionals during the months of June to August 2020.

Records of EsSalud health personnel were included. Duplicate records and those with at least one missing response in the database were excluded.

Procedures

In January 2021, we requested authorization from CRI-ESSALUD to access the database with the responses from the pharmacovigilance survey. This database included 156 records and 40 variables distributed in information regarding: a) sociodemographic characteristics b) knowledge c) attitudes and d) pharmacovigilance practices. The database was sorted and the records that met the selection criteria were identified and then analyzed.

Variables

The sociodemographic information included sex, profession, city and work center, which included the variables “healthcare center” and “service” that was dichotomized into centers with or without inpatient care service, in accordance with what is described in numeral 6.8 about the activities of public and private health facilities of the NTS 123-MINSA/DIGEMID-V.01 “Technical health standard that regulates pharmacovigilance and technovigilance activities of pharmaceutical products, medical devices and sanitary products” ¹¹11. Ministerio de Salud. Resolución Ministerial 593-2016-MINSA [Internet]. Lima: Dirección General de Intervenciones Estratégicas en Salud Pública. MINSA; 2020 [citado 29 de marzo de 2022]. Disponible en: https://cdn.www.gob.pe/uploads/document/file/193341/192066_RM_539-2016-MINSA.pdf20180904-20266-13w2m1c.pdf.
https://cdn.www.gob.pe/uploads/document/... .

The items that measure knowledge, attitudes and practices were standardized in categories and dichotomized as correct and incorrect answers. Scores were assigned to each section by adding them together. Binary responses were assigned a value of 1 if they were correct and 0 if they were incorrect. Likert scale questions were assigned a score of 0 when answered as “never”, 1 “rarely”, 2 “sometimes” and 3 “always”. The overall score for knowledge, attitudes and practices was dichotomized into “low” and “high” considering the median as the cut-off point.

Statistical analysis

For the univariate descriptive analysis of the categorical variables, we used relative and absolute frequencies. During the bivariate analysis for the comparison of proportions in contingency tables, we used the chi-square test and Fisher’s exact test when more than 20% of the cells had expected values less than 5 or when any expected value was less than 1. To evaluate statistical significance, we considered a p-value of less than 0.05. All analyses were performed with STATA version 15.0.

Ethical criteria

This study was approved by the Specific Research Ethics Committee for COVID-19 of EsSalud. Likewise, the study was registered in the PRISA platform of the National Institute of Health with the registration code 1F00730F- EA69-4FD2-87B8-391F081B76D6 in strict compliance with current regulations.

FINDINGS

Out of the 156 records in the database with complete pharmacovigilance survey results, eight were excluded because they were responses from health professionals from institutions other than EsSalud; and four were duplicates. Finally, the records of 144 health professionals were included, of which 63.9% were female, 42.4% were from Lima and the majority were pharmacists (36.1%) and physicians (35.4%) (Table 1).

Most had a high level of knowledge about pharmacovigilance (Figure 1); 97.2% adequately defined pharmacovigilance and 78.5% recognized its importance in the identification of new ADRs. Likewise, 81.3% recognized the existence of the Peruvian Pharmacovigilance System, 91% answered that all ADRs (known and unknown) should be reported for drugs used in COVID-19. It is noteworthy that 89.6% considered ivermectin to be an unsafe drug in the treatment of COVID-19 (Table 2). The level of knowledge was dependent on the profession p<0.001, 90% of the pharmacists and 54.9% of the physicians had a high level of knowledge in contrast to other health professionals. The city where the professionals work also showed significant differences (p=0.018), those from Lima and Trujillo had a higher level of knowledge (Table 3).

Positive attitudes to implement pharmacovigilance in the context of COVID-19 were found in 81.2% of health professionals; and 95.1% recognized that reporting ADRs would benefit the patient. However, 16% considered that reporting ADRs could have legal implications and 22.2% thought that this activity was time-consuming. Furthermore, a high percentage of women had positive attitudes to implement pharmacovigilance in the context of COVID-19 (Table 2).

The level of pharmacovigilance practices in the context of COVID-19 was low in 71.5% of the health professionals; 43% never reported an ADR and 10.4% identified an ADR and reported it to the CRI-EsSalud. Only 11.8% received training and less than 15% implemented intensive monitoring of patients exposed to “off-label” drugs (drugs outside the indications for which it was approved or used in a different way) against COVID-19. Of all the health professionals, 63.2% read the drug safety communications on “off-label” treatments for COVID-19 issued by the CRI- EsSalud and most (55.6%) “sometimes” reviewed the technical data sheet of the drugs approved by the regulatory agencies. Finally, a higher proportion of professionals working in centers without inpatient service had a “low” level of pharmacovigilance practices in the context of COVID-19 as opposed to those working in centers with inpatient service (p=0.018) (Table 3).

DISCUSSION

We found that most participants had a high level of pharmacovigilance knowledge in the context of COVID-19. One possible explanation is that, since the beginning of the pandemic, the CRI-EsSalud trained the institution’s professionals in the reporting of ADRs, mainly due to the use of drugs that have not been approved for the treatment of COVID-19. Therefore, it is possible that those who responded to the survey are those who received the training or were directly involved with pharmacovigilance activities at the institution, i.e., personnel of the pharmacovigilance committees or frequent ADR reporters.

Pharmacists had the highest level of knowledge about pharmacovigilance, followed by physicians and other professionals. It is possible that this professional group identifies with issues regarding drug safety and receives training from DIGEMID, which is responsible for conducting the Peruvian Pharmacovigilance System. Outside the context of the pandemic, in Peru, the training of pharmacists is focused on pharmacotherapeutic follow-up, an activity that includes detection and reporting of ADRs. In addition, national regulations and the labor law require pharmacist participation in the access and rational use of medicines ¹²12. Ley del Trabajo del Químico Farmacéutico del Perú, Ley 28173 [Internet]. Colegio Químico Farmacéutico del Perú 2006. Disponible en: http://www.cqfp.org.pe/wp-content/uploads/2017/02/Ley_28173-Ley_del_Trabajo_Farmac%C3%A9utico_17-Feb-2004.pdf.
http://www.cqfp.org.pe/wp-content/upload... and in the Peruvian Pharmacovigilance and Technovigilance System. The results of studies carried out in other parts of the world are controversial when it comes to the professionals with the greatest knowledge of pharmacovigilance; some studies identify the pharmacist ¹³13. Shanko H, Abdela J. Knowledge, attitudes, and practices of health care professionals toward adverse drug reaction reporting in Hiwot Fana Specialized University Hospital, Harar, Eastern Ethiopia: A Cross-sectional Study: Hosp Pharm. Hosp Pharm. 2018;53(3):177-187. doi: 10.1177/0018578717737430.
https://doi.org/10.1177/0018578717737430... ^,1414. Fadare JO, Enwere OO, Afolabi AO, Chedi B, Musa A. Knowledge, Attitude and Practice of Adverse Drug Reaction Reporting among Healthcare Workers in a Tertiary Centre in Northern Nigeria. Trop J Pharm Res.2011;10(3):235-242. doi: 10.4314/tjpr.v10i3.4.
https://doi.org/10.4314/tjpr.v10i3.4... and others, the physician ¹⁵15. Gidey K, Seifu M, Hailu BY, Asgedom SW, Niriayo YL. Healthcare professionals'knowledge, attitude and practice of adverse drug reactions reporting in Ethiopia: a cross-sectional study. BMJ Open. 2020;10(2):e034553. doi: 10.1136/bmjopen-2019-034553.
https://doi.org/10.1136/bmjopen-2019-034... ^,1616. Nisa ZU, Zafar A, Sher F. Assessment of knowledge, attitude, and practice of adverse drug reaction reporting among healthcare professionals in secondary and tertiary hospitals in the capital of Pakistan. Saudi Pharm J. 2018;26(4):453-61. doi: 10.1016/j.jsps.2018.02.014.
https://doi.org/10.1016/j.jsps.2018.02.0... ^,1717. Gurmesa LT, Dedefo MG. Factors Affecting Adverse Drug Reaction Reporting of Healthcare Professionals and Their Knowledge, Attitude, and Practice towards ADR Reporting in Nekemte Town, West Ethiopia. Biomed Res Int. 2016;2016:5728462. doi: 10.1155/2016/5728462.
https://doi.org/10.1155/2016/5728462... .

Positive attitudes towards pharmacovigilance were found in 81.2% of the participants. It is important to note that more than 90% considered that reporting ADRs of drugs used in COVID-19 benefits the patient. Therefore, positive attitudes are important to assess the predisposition of health professionals regarding the report ADRs of drugs without sufficient scientific evidence of their safety and efficacy against SARS-CoV-2. However, we identified that 15% considered that ADR reporting may have legal consequences, which could affect the motivation for reporting. Although no studies that evaluate the attitudes of professionals to report ADRs outside the context of COVID-19 were found, the proportions we obtained coincide with those found in other studies on the positive attitudes of professionals towards the implementation of pharmacovigilance, being 92% in Pakistan ¹⁶16. Nisa ZU, Zafar A, Sher F. Assessment of knowledge, attitude, and practice of adverse drug reaction reporting among healthcare professionals in secondary and tertiary hospitals in the capital of Pakistan. Saudi Pharm J. 2018;26(4):453-61. doi: 10.1016/j.jsps.2018.02.014.
https://doi.org/10.1016/j.jsps.2018.02.0... and 82.2% in India ¹⁸18. Gupta SK, Nayak RP, Shivaranjani R, Vidyarthi SK. A questionnaire study on the knowledge, attitude, and the practice of pharmacovigilance among the healthcare professionals in a teaching hospital in South India. Perspect Clin Res. 2015;6(1):45-52. doi: 10.4103/2229-3485.148816.
https://doi.org/10.4103/2229-3485.148816... .

In April and May 2020, MINSA established the need for monitoring and reporting adverse reactions to drugs such as hydroxychloroquine, chloroquine and ivermectin, which are used against COVID-19 ¹⁹19. Ministerio de Salud. Resolución Ministerial 193-2020-MINSA [Internet]. Lima: Dirección General de Intervenciones Estratégicas en Salud Pública. MINSA; 2020 [citado 20 de mayo de 2021]. Disponible en: https://www.gob.pe/institucion/minsa/normas-legales/473575-193-2020-minsa.
https://www.gob.pe/institucion/minsa/nor... ^,2020. Ministerio de Salud. Resolución Ministerial 270-2020-MINSA [Internet]. Lima: Dirección General de Intervenciones Estratégicas en Salud Pública. MINSA; 2020 [citado 7 de mayo de 2021]. Disponible en: https://www.gob.pe.
https://www.gob.pe... . Our analysis evidenced that the majority of respondents had an inadequate level of pharmacovigilance practices in the context of COVID-19; only 10% reported at least one ADR to “off-label” drug treatment; 14% participated in the implementation of intensive pharmacovigilance in EsSalud; and less than half reviewed updates on the safety of “potential” drug treatments for COVID-19. Lack of time to report ADRs, because of the high demand for medical care due to the pandemic, could explain the limited pharmacovigilance practice in the institution. We also found that a higher proportion of hospital professionals had a high level of pharmacovigilance practices, possibly because they receive more training from pharmacovigilance committees, which by national regulations only exist in centers with inpatient care.

The main limitation of this study is that it was a secondary analysis of a database that included data collected by a survey previously carried out by the CRI-EsSalud; therefore, we analyzed the information assuming that it had been adequately registered. Besides, the database did not have epidemiologically important variables such as age, length of professional experience, among others. Furthermore, it is not clear how the survey was validated, and we can’t confirm that the responses were not biased by a relationship of authority between the surveyors and the respondents. In addition, the measurement of results may be biased, since the lack of defined intervals can have little discriminatory capacity. Likewise, according to the responses, it is possible that some questions do not have enough alternatives, which could lead to a bias due to forced selection. It should be noted that our results cannot be extrapolated to all EsSalud personnel, much less to Peruvian health professionals. Despite this, our study provided important information on the knowledge, attitudes and practices of a group of EsSalud health professionals -of voluntary participation- on pharmacovigilance in the context of COVID-19.

In conclusion, although most of the participating health professionals showed a high level of knowledge and positive attitudes, they had an inadequate level of pharmacovigilance practices in the context of COVID-19. Pharmacovigilance is of vital importance during the current pandemic due to the high demand for pharmaceuticals without sufficient scientific evidence of their efficacy and safety. Strategies should be implemented to strengthen knowledge and practices regarding pharmacovigilance among health professionals, in order to ensure patient safety.

Acknowledgments:

We thank Dr. Héctor Miguel Garavito Farro (specialist in Public Health) for reviewing this manuscript.

References

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History