Article

DARU Journal of Pharmaceutical Sciences
https://doi.org/10.1007/s40199-024-00508-z
REVIEW ARTICLE
Educational interventions in pharmacovigilance to improve

the knowledge, attitude and the report of adverse drug reactions
in healthcare professionals: Systematic Review and Meta-analysis
Mónica J. Cervantes‑Arellano1 · Osvaldo D. Castelán‑Martínez2 · Yolanda Marín‑Campos3 ·
Juan L. Chávez‑Pacheco4 · Olga Morales‑Ríos5 · Laura M. Ubaldo‑Reyes1
Received: 22 December 2022 / Accepted: 15 February 2024

© The Author(s) 2024
Abstract
Objectives Underreporting of adverse drug reactions (ADRs) limits and delays the detection of signs. The aim of this
systematic review with meta-analyses was to synthesize the evidence of educational interventions (EIs) efficacy in health
professionals to increase ADR reporting, attitudes, and knowledge of pharmacovigilance.
Evidence acquisition A systematic literature review was carried out to identify randomized clinical trials evaluating the
efficacy of EI in pharmacovigilance in health professionals to improve ADR reports, knowledge, and attitude toward phar-
macovigilance. ADR reports were pooled by calculating Odds Ratio (OR) with a 95% confidence interval (95%CI), while
pharmacovigilance knowledge and attitude were pooled by calculating a mean difference (MD) with 95%CI. In addition,
the subanalysis was performed by EI type. Meta-analysis was performed with RevMan 5.4 software. PROSPERO registry
CRD42021254270.
Results Eight hundred seventy-five articles were identified as potentially relevant, and 11 were included in the systematic
review. Metanalysis showed that EI increased ADR reporting in comparison with control group (OR = 4.74, [95%CI, 2.46
to 9.12], I2 = 93%, 5 studies). In subgroup analysis, the workshops (OR = 6.26, [95%CI, 4.03 to 9.73], I2 = 57%, 3 studies)
increased ADR reporting more than telephone-based interventions (OR = 2.59, [95%CI, 0.77 to 8.73], I 2 = 29%, 2 stud-
ies) or combined interventions (OR = 5.14, [95%CI, 0.97 to 27.26], I2 = 93%, 3 studies). No difference was observed in
pharmacovigilance knowledge. However, the subanalysis revealed that workshops increase pharmacovigilance knowledge
(SMD = 1.85 [95%CI, 1.44 to 2.27], 1 study). Only one study evaluated ADR reporting attitude among participants and
showed a positive effect after the intervention.
Conclusion EI improves ADR reports and increases pharmacovigilance knowledge. Workshops are the most effective EI to
increase ADR reporting.
Keywords Pharmacovigilance · Educational interventions · Adverse drug reaction reporting · Systematic review · Meta-
analysis
3
* Osvaldo D. Castelán‑Martínez Pharmacology Department, Facultad de Medicina,
castelan@unam.mx Universidad Nacional Autónoma de México (UNAM),
Mexico City, Mexico
1
Anatomy Department, Facultad de Medicina, Universidad 4
Clinical Pharmacology Laboratory, Instituto Nacional de
Nacional Autónoma de México (UNAM), Mexico City,
Pediatría, Mexico City, Mexico
Mexico
5
2 Unidad Habilitada de Apoyo al Predictamen, Hospital
Clinical Pharmacology Laboratory, UMIEZ, Facultad
Infantil de México Federico Gómez, Mexico City, Mexico
de Estudios Superiores Zaragoza, Universidad Nacional
Autónoma de México (UNAM), Batalla 5 de Mayo
s/n Esquina Fuerte de Loreto, Col. Ejército de Oriente,
Iztapalapa, Mexico City C.P. 09230, Mexico
Vol.:(0123456789)
Introduction not limited by years or language. The strategy search was

constructed using the following MeSH terms and keywords:
Drugs are essential for the treatment of various diseases, but “health personnel”, “physicians”, “pharmacists”, “nurses”;
there are drug-related problems, such as adverse drug reac- “models educational”, “education medical”; “adverse drug
tions (ADR) [1]. Post-marketing information on medicines reaction reporting systems”, “pharmacovigilance”, “adverse
reports a benefit-risk balance obtained from clinical stud- drug reaction reporting”. The search strategy was adapted to
ies. Nevertheless, drug surveillance is necessary to evalu- each database (Suppl. 2). In addition, all references identi-
ate safety in real-life and long-term conditions [2]. For this fied by systematic reviews were analyzed to identify poten-
reason, ADR voluntary reports are needed, thus spontaneous tially relevant studies.
reporting is the pillar of pharmacovigilance. In countries
with pharmacovigilance programs well-established, the Study selection
report number is about 200 or more per million inhabit-
ants [3]. However, in many countries, pharmacovigilance Studies were included if they met the following criteria: (1)
programs are still under development, and this fact may RCT, including multi-arm trials; (2) participants were health
result in a low drug safety culture that translates into under- professionals (physicians, consultants, nurses, pharmacists,
reporting of ADR. Low notification rates make it difficult and dentists); (3) participants received an educational inter-
to detect signs in the general population that, limits evalu- vention in pharmacovigilance including telephone-based
ation of ADR causality and the issuance of health alerts. interventions, workshop, educational material, electronic
Underreporting can be explained by the low participation of supplementary material, letters, lectures, sessions group,
health professionals due to a lack of knowledge and negative email and combined intervention; in the control group, par-
attitudes toward pharmacovigilance, such as ignorance (only ticipants did not receive educational activity or received
important serious ADR reports) or lethargy (disinterest in training from their pharmacovigilance unit; (4) study results
reporting) [3–5]. were a number of ADR reports and knowledge and attitude
Different strategies have been evaluated to increase mean scores obtained through a questionnaire, in both
ADR notification, such as the implementation of educa- groups. Studies were excluded if the educational interven-
tional interventions (EI) for health professionals [6–8]. EI tion was aimed at patients or if the comparison was made
purpose is to raise awareness about drug safety issues to between health professionals and patients, as well as stud-
improve ADR reporting to obtain statistical assessments by ies that were sponsored by the pharmaceutical industry or
detecting signs and issuing health alerts [9, 10]. Therefore, involved economic incentives.
the aim of this systematic review with meta-analyses was to Two independent reviewers (MJC and LMU) assessed all
synthesize the evidence of EI efficacy in health profession- titles and abstracts to identify studies via the inclusion cri-
als to increase ADR reporting, attitudes, and knowledge of teria and excluded non-relevant studies. All potentially rel-
pharmacovigilance. evant articles were retrieved and read in full text. Reviewers
were blinded to each other’s decisions. Discrepancies were
discussed and resolved with a third reviewer (ODC). The
inter-rater reliability was evaluated using kappa coefficient.
Methods
A systematic review and meta-analyses were conducted Data extraction and risk of bias assessment
according to the PRISMA statement (Suppl. 1) [11], and the
protocol was prospectively registered in PROSPERO with Selected studies were reviewed independently by two
registration number CRD42021254270. reviewers (MJC and LMU) to extract in an Excel database
the following data: publication year, author, health profes-
sionals, EI, time of intervention, control group, the sample
Search strategy size of the intervention group as the control group, partici-
pants in both groups, follow-up time, the number of ADR
A systematic literature search was carried out in the fol- reports, knowledge, and attitude in pharmacovigilance mean
lowing electronic databases: PubMed, LILACS, Cochrane score, country, attitude, and knowledge questionnaire (vali-
Central Register of Controlled Trials (CENTRAL), Scopus dated or not), change of result over time, ADR type (severe,
and Epistemonikos. Unpublished literature was looked up in unexpected, high-causality and new-drugs). Discrepancies in
the abstracts of randomized controlled trials (RCTs) indexed data extraction were resolved by consensus. In case any data
in Scopus Conference Papers and ScienceDirect. Searches was not reported in the article, the authors were contacted
were conducted from inception until January 2022 and were to obtain it.
When ADR results were reported in a thousand pharma- was performed to identify the most effective intervention,
cist-months, a conversion was made to the number of ADR as well as to explore heterogeneity between studies. The
reports, multiplying the rate per person-month, and dividing results’ consistency was evaluated using a leave-one-out
by one thousand [12]. sensitivity analysis, the study with the highest bias was
Potential biases related to individual RCT were assessed excluded in each comparison. Only studies that reported
with the Cochrane risk-of-bias tool (RoB 2) [13]. Rev- the ADR reports numbers (totals, serious, high probabil-
Man 5.4 was used to generate the risk of bias figures. [14]. ity, unexpected, and new drugs by control and intervention
The risk of bias was assessed in duplicates by two authors groups before and after the educative intervention), knowl-
independently (MJC and LMU). Any disagreement was edge scores, or changes in attitude were included in the
addressed by reappraisal in conjunction with a third reviewer meta-analysis.
(ODC).
Data analysis Results
Statistical analyses were performed using RevMan 5.4 [14]. Characteristics of the studies
ADR reports were pooled using an odds’ ratio (OR) with
95% confidence intervals (95%CI). Knowledge and attitude In the systematic search, a total of 875 citations were iden-
in pharmacovigilance scores were analyzed with a stand- tified in databases, and the study selection process is illus-
ardized mean difference (SMD) with 95%CI. All analyses trated in Fig. 1. After duplicate removal, 705 articles were
were performed with a random-effects approach. I² test was screened by title and abstract for potential eligibility. In addi-
used to assess the heterogeneity of each evaluate results, tion, 29 unpublished records were identified. No additional
and I² > 50% was considered with signification heteroge- studies were identified in references of previously published
neity [15]. Subanalysis by type of educational intervention systematic reviews. After screening, twenty-four studies
Fig. 1 Flowchart for systematic review and meta-analysis (PRISMA) of educational intervention in pharmacovigilance, screening of articles, and
selection process
were assessed for eligibility, and 13 studies were excluded analysis, after removed Herdeiro et al. [31], educational
[16–28]. Non-comparative studies were the main cause of interventions showed consistency in increasing ADR report-
exclusion, and all reasons are shown in the Suppl. 3. Inter- ing (OR = 6.06 [95%CI, 2.50 to 14.71], I 2 = 94%, 4 studies).
rater agreement was suitable (kappa = 0.83). Eleven studies In subgroup analysis, workshops (OR = 6.26, [95%CI, 4.03
fulfilled the inclusion criteria of the systematic review, and to 9.73], I 2 = 57%, 3 studies) increased ADR reporting, more
the characteristics of the included studies are summarized in than combined interventions (OR = 5.14, [95%CI, 0.97 to
Table 1. Two authors were contacted for data to be included 27.26], I2 = 98%, 3 studies), while telephone-based interven-
in the meta-analyses [29, 30], only one responded, however tions no showed a difference (OR = 2.59, [95%CI, 0.77 to
the information could not be pooled. Eight studies were 8.73], I2 = 29%, 2 studies) (Figs. 2).
included in the meta-analysis [29, 31–37]. ADR reporting change over time is shown in Table 2.
For country, RCTs were principally conducted in Portugal In the workshop intervention, the increase in the number
(four articles) and Sweden (two articles). Geographically, all of reports was significant up to 16 months after IE for total
the studies were conducted in Europe and Asia. The EI var- and severe ADRs, but only increased over 12 months for
ied from one day to nine months, and follow-up ranged from unexpected, high-causality, and new drug ADRs. In contrast,
0 to 20 months. The average participation rate (a healthcare telephone-based interventions only increased the number of
professional who agreed to participate into the study) varies total reports and serious ADRs by 4 months. Interestingly,
in each study between 7.9 and 84.0%, and participants had the combined interventions increased the number of unex-
more adherence to combined interventions and electronic pected and new drug ADRs for at least 12 months, although
ADR information. for total, serious, and high-causality ADRs, the effect was
Four studies involved physicians [29, 31, 33, 35], two seen from 12 months onwards.
involved nurses [29, 36], four involved pharmacists [32, 34,
37, 38], and two studies evaluated primary healthcare units Knowledge, and attitude in pharmacovigilance
that included physicians and nurses [30, 39]. The profession-
als mainly studied were physicians (six studies with 5097 Regarding the change in knowledge in pharmacovigilance,
participants and 136 primary healthcare units), followed by three studies [29, 36, 37] evaluated 4 educative interven-
the pharmacist (four studies with 887 participants) (Table 1). tions. The meta-analysis results showed a tendency to
Workshops were the most common educative interven- increase pharmacovigilance knowledge mean scores in
tions used into studies [31, 33, 34, 36], followed by inter- participants who received EI in comparison with the con-
vention combined (session group and educative material) trol group (SMD = 1.12, [95%CI, -0.12 to 2.36], I 2 = 98%,
[29, 32, 35], telephone-based interventions [31, 34], lecture 4 studies). After removing the highest risk of bias study
[36], educational material (transparencies, brochures, and [29], participants in EI group shown an augmented their
posters) [38], electronic information sheet of ADR [37], pharmacovigilance knowledge (SMD = 1.53 [95%CI, 0.58
E-mail interventions [39] and one-page ADR information to 2.47, I 2 = 92%, 3 studies]). In subgroup analysis, the par-
letter [30]. Three studies included continuing education by ticipants who received lecture (SMD = 2.23 [95%CI, 1.81 to
the pharmacovigilance unit as a control group [32, 35, 37], 2.65], 1 study) and workshop (SMD = 1.85 [95%CI, 1.44 to
while eight studies did nothing [29–34, 36, 38, 39] (Table 1). 2.27], 1 study) increased their knowledge; this effect was not
observed in those who received the combined intervention
ADR reports or letter with ADR information (Fig. 3).
Two studies evaluated ADR reporting attitudes among
Ten studies informed the number of ADR reports [29–35, health professionals (Table 1), however, the measurement
37–39]. Five studies were excluded from the meta-analy- scales obtained by the questionnaire are different, so it was
sis because these have incomplete data such as number of not possible to perform a meta-analysis. One study con-
participants, or the total number of ADR reports [29, 30, ducted in pharmacist showed a positive attitude toward ADR
37–39]. Five studies present complete data for meta-anal- reporting after the intervention [38]. Likewise, a positive
ysis, and classified ADR as total, serious, high probabil- effect in behavior related to reporting was observed in physi-
ity, unexpected, and new drugs by control and intervention cians and nurses after educative intervention [29].
groups [31–35]. Two studies presented three arms (work-
shop, telephone-based interventions, and control group) [31, Risk of bias assessment
34], and three studies with two arms (combined intervention
or workshop vs. control group) [32, 33, 35]. In risk of bias assessment (Fig. 4), 73% of studies had
Educational interventions increased the reporting of adequate random sequence generation [29, 32–38]. Only
all ADRs in comparison with control group (OR = 4.74, 54% describe the randomization process completely [29,
[95%CI, 2.46 to 9.12], I2 = 93%, 5 studies). In the sensitivity 30, 35–37, 39], presenting low-risk allocation concealment,
Table 1 Characteristics and descriptions of the randomized controlled trials are included in the systematic review
Author (Year)/ country Health professionals Educative intervention Control group Follow-up Outcomes* Questionnaire
(month) attitude/ valida-
Intervention N Control group N tion
Potlog SM (2020)/ Israel [29] physicians and nurses Combined intervention: 205 Received no intervention 225 09 The score of “behavior Yes/No validated
Program promotion (visit- related to reporting”
ing medical staff), distant Intervention:
learning, lecture, and edu- Mean ± SD = 2.87 ± 2.37;
cational material (posters), control:
for five months. Mean ± SD = 2.48 ± 2.12,
p = 0.79.
The score of “knowledge

related to behavior”
Intervention:
Mean ± SD = 3.67 ± 2.16;
control:
Mean ± SD = 3.73 ± 2.14,
p = 0.79.
Cheema E (2019)/ Saudi pharmacists Information sheet of ADR 23 Information sheet of coro- 23 03 Knowledge score Yes/ No validated
Arabia [37] and reporting (electroni- navirus Intervention:
cally) Mean ± SD = 7.67 ± 2.1;
control:
Mean ± SD = 6.71 ± 2.3,
p = 0.66.
Sarayani A (2015)/ Iran [36] nurses 1. Lecture: didactic sessions, 143 Received no intervention 212 03 Workshop: Knowledge Yes/ No validated
two sessions of two hours score = 73.7 ± 11.3
in one day. Lecture: Knowledge
2. Workshop: brainstorming, 141 score = 79.1 ± 11.9
two sessions of two hours
in one day.
López-González E (2015)/ physicians Combined intervention: 1) A 2120 Continuing education course 3614 08 ADR total RR = 1.65 No available
Spain [35] group session (25 min) (pharmacovigilance center) [95%CI, 1.08 to 2.53],
2) Educational material. p = 0.021; report of ADR
high-causality RR = 1.13
[95%CI, 0.72 to 1.77],
p = 0.603; report severe
ADR = 1.62 [95%CI, 0.99
to 2.65], p = 0.056; report
unexpected ADR = 2.06
[95%CI, 1.19 to 3.55],
p = 0.010.
Table 1 (continued)
Herdeiro MT (2012)/ Portu- physicians 1. Telephone intervention: 438 Received no intervention 5107 20 1. Telephone interview: ADR No available
gal [31] conversation between total RR = 1.02 [95%CI,
3–8 min. 1.00 to 1.04], p = 0.052;
report of ADR high-causal-
2. Workshop: one hour. 1034 ity RR = 0.75 [95%CI, 0.73
to 0.76], p < 0.001; report
severe ADR = 0.93 [95%CI,
0.91 to 0.94], p < 0.001.
2. Workshop: ADR total
RR = 3.97 [95%CI, 3.86
to 4.08], p < 0.001; report
of ADR high-causality
RR = 3.58 [95%CI, 3.51
to 3.66], p < 0.001; report
6.69 to 6.98], p < 0.001.
Johansson M (2011)/ Sweden physicians and nurses Letter: (Information sheet of 77a Received no intervention 74a 00 Mean number of reports per No available
[30] ADR and reporting, 3 times unit ± SD = 1.03 ± 2.46,
in 9 months) p = 0.34; N Total of ADR
reports = 79; N ADR
reports serious = 12, N
unexpected ADR = 20, N
new drug-related = 7.
Ribeiro-Vaz I (2011)/ Portu- pharmacists 1. Telephone intervention: 261 Received no intervention 1103 20 Report od ADR RR = 3.22 No available
gal [34] between four and 12 min [95%CI, 1.33 to 7.80],
for 18 days. p = 0.010; report of ADR
2. Workshop: by one month. 103 high level of probability
RR = 2.02 [95%CI, 0.74
to 5.49], p = 0.168; report
1.29 to 11.61], p = 0.016;
report unexpected ADR
RR = 5.02 [95%CI, 1.33 to
18.93], p = 0.017.
Granas AG (2007)/ Norway pharmacists Educational material: trans- 158 Received no intervention. 184 00 Attitude: More positive in the Yes/ No validated
[38] parencies, brochures, and intervention (p < 0.001) and
posters. more positive in reporting
ADR (p = 0.01).
Report ADR: half (54/105)
reported one or more
ADRs.
Table 1 (continued)
Figueiras A (2006)/ Portugal physicians Workshop (visit), reminder 1388 Received no intervention 5063 13 ADR total RR = 10.23 No available
[33] card, and report form: two [95%CI, 3.81 to 27.51],
sessions of 30 min. p < 0.001; report of ADR
high-causality RR = 8.75
[95%CI, 3.05 to 25.07],
p < 0.001; report severe
ADR = 6.32 [95%CI, 2.09
to 19.16], p = 0.001; report

[95%CI, 4.54 to 200.84],
p < 0.001; new drug related
ADR = 8.04 [95%CI, 2.10
to 30.83], p = 0.002.
Johansson M (2009)/ Sweden physicians and nurses E-mails: attached file about 59a Received no intervention 58a 00 N Total of ADR reports = 56, No available
[39] new drugs, ADR is impor- p = 0.037; N ADR reports
tant, instructions of the serious = 10, N previously
report of ADR (3 times in not known ADR = 16, N
9 months) new drug-related = 4.
Herdeiro MT (2008)/ Portu- pharmacists Combined intervention: 1) 342 Continuing education course 1091 12 ADR total RR = 5.87 No available
gal [32] A group session (30 min (pharmacovigilance center) [95%CI, 1.98 to 17.39],
of presentation + 30 min of p = 0.001; report of ADR
discussion). high-causality RR = 8.67
2) Educational material on [95%CI, 2.12 to 35.42],
pharmacovigilance for 4 p = 0.002; report severe
months. ADR = 9.79 [95%CI, 2.24
to 42.66], p = 0.002; report
[95%CI, 1.11 to 17.53],
p = 0.04; new drug related
ADR = 9.33 [95%CI, 2.53
to 34.40], p < 0.001.
N, number ADR report; SD, standard deviation, ADR, Adverse Drug Reaction, 95% CI, Confidence Interval 95%. aPrimary Healthcare Units
Fig. 2 Forest plot of total adverse drug reactions reported for each educational intervention at the end of the study. Sub-analysis was performed
by type of intervention
because the randomization was carried out by a person pharmacovigilance knowledge and attitude in health care
outside the study, or they avoided contamination between professionals.
groups by randomizing health centers. To synthesize the best available evidence on the role of
The performance bias had a high risk in at least 81% of EI in increasing ADR reporting, only RCTs were included in
articles, due to differences in interventions ranging from this systematic review. Study results show that EI increases
a phone call to a combined intervention [29–35, 38, 39]. by about four times the ADR report. Similar results were
With respect to blinding outcome assessment, in 4 studies reported in a systematic review that synthesized the evidence
the ADR reports evaluator was blinding [32–35]. In 63% of on interventions to increase the spontaneous reporting of
the studies [30–34, 37, 39], no missing data were seen, while ADRs in healthcare professionals and patients [8]. Likewise,
reporting bias was considered a low risk in 72% of studies two previous systematic reviews, which included pre-post
[30–35, 37, 39]. Additionally, in other potential sources of experimental design, quasi-experimental and RCT studies,
bias, 80% (9 of 11 studies) of the selected studies were rated concluded that the interventions evaluated were considered
with a low risk of bias [29–34, 37, 39]. effective [6, 8]. However, no previous systematic review has
evaluated efficacy by intervention type. In this study, the
workshops have greater ADR reporting efficacy compared
Discussion to others, that could be explained by the person-person inter-
action of the workshop allows a better understanding of the
ADR report is paramount for causality analysis and drug concept compared to reading information in a letter. In this
safety assessment. Nonetheless, ADR occurrence gener- sense, the score of knowledge observed in workshop partici-
ates distrust in health professionals due to the fear of being pants is two-fold increase in comparison with participants
judged and punished [40]. To avoid this, EIs in pharma- who received a letter with an ADR information. Previous
covigilance are intended to increase knowledge about drug results indicated that interactive sessions enhance participant
safety, improve attitudes towards ADRs, and consequently activity and provide the opportunity to practice skills can
increase the reporting. The results of this systematic review effect change in professional practice [41].
with meta-analysis showed that EI in pharmacovigilance In addition, the effectiveness over time reveals that EI
increases the ADR reports, and present positive changes in with interaction between people such as workshops and
Fig. 3 Forest plot of the difference in means of the effect of EI in the score of knowledge about pharmacovigilance at the end of the study. Sub-
analysis was performed by type of intervention
combined interventions maintain their effect on the ADR The educative interventions dependent on complex fac-
report for up to 16 months. This effect was not observed in tors such as intrapersonal, interpersonal, professional edu-
telephone-based intervention, it suggests the necessity for a cation, context, and material quality [41]. The educational
re-intervention. intervention could work depending on the population, the
Furthermore, educational combined intervention can rein- objective sought, and due to the training of the participant.
force and increase the understanding of pharmacovigilance In RCTs included in this systematic review have no harmoni-
issues and modify the attitude about ADR and increase the zation in the type of educational intervention and length. In
report in comparison with a simple intervention [7, 42]. this way, EI investigated in pharmacovigilance are different,
Similarly, Forsetlund L., recommends using combined inter- regardless of the study design, and have durations ranging
ventions with interactive formats that increase attention, to from a few minutes to six years [7]. These differences can
increase the effectiveness of the interventions [43]. It is not be explained by cultural gaps, and social situations in each
certain that printed educational materials, as a single inter- region that could modify the intervention type according to
vention, can maintain the change in results over time [44]. the context of each country, such as the geographical loca-
In contrast, regular delivery of drug safety information can tion and status of the pharmacovigilance system [23]. EI
be an effective and inexpensive technique, but it loses its explored into the studies included in this systematic review
effect if delivery is stopped [45]. In this systematic review, were evaluated in Europe and Asia countries, appraisal of
all the studies that evaluated the combined intervention used these interventions in other countries using RCTs approach
the continuing education of the pharmacovigilance unit as may provide information on the efficacy of EI in regions
a comparator. This could explain why, although there is a whose drug safety culture may be different.
trend in favor of the combined intervention for the increase In clinical practice, the effectiveness of EI in pharma-
in the total ADR reports, this is not statistically significant. covigilance can be increased by existence of continuous
Table 2 Report of the total, serious, high-causality, unexpected, and new drugs ADRs over time, once the application of the intervention has ended
Follow-up, 4 8 12 16 4 8 12 16 4 8 12 16
months
Intervention Workshop [31, 33, 34] Telephone interview [31, 34] Combined intervention: Session group and educative
material [29, 32, 35]
Comparator No intervention No intervention/continuing course
OR (95% IC), p
Total 17.0 (11.6– 4.0 3.5 3.1 4.3 (2.0-9.3), 1.7 2.5 0.7 8.48 3.1 4.0 7.3 (2.3–
25.1), 0.00 (2.5–6.6), (2.2–5.7), (1.3–7.5), 0.00 (0.7–3.9), (0.9–6.6), (0.3–1.8), (0.8–88.1), (0.9–11.2), (2.3–6.9), 24.0), 0.00
0.00 0.00 0.01 0.25 0.07 0.46 0.007 0.08 0.00
Serious 8.7 1.4 4.1 2.6 5.0 (2.0- 2.5 1.8 0.8 9.8 (0.7- 3.2 3.3 55.5 (3.2-
(5.1–14.8), (0.6–3.6), (2.2–7.9), (1.2–6.1), 12.6), 0.00 (0.7–8.2), (0.6–5.7), (0.2–2.6), 137.1), (0.6–18.1), (1.5–7.4), 963.6), 0.01
0.00 0.46 0.00 0.02 0.14 0.32 0.69 0.09 0.19 0.00
High causal- 13.6 3.9 (2.2-7.0), 3.3 (2.0-5.7), 2.7 2.5 2.2 2.8 0.5 7.6 3.6 3.9 (2.0- 7.6 (2.0-29.5),
ity (8.9–20.7), 0.00 0.00 (0.9–8.3), (0.9–6.6), (0.9–5.3), (0.9–8.2), (0.2–1.6), (0.8–73.4), (0.4–31.9), 7.6), 0.00 0.00
0.00 0.08 0.07 0.09 0.07 0.22 0.08 0.25
Unexpected 108.0 (13.8- 3.6 7.0 5.6 14.4 (0.6- 3.0 1.7 0.6 7.4 (2.0- 3.2 4.3 0.6 (0.0-13.3),
846.6), (1.2–10.7), (2.5–20.0), (0.4–82.2), 364.2), (0.7–12.4), (0.2–15.9), (0.1–4.9), 26.9), 0.00 (1.4–7.3), (1.5–12.6), 0.77
0.00 0.02 0.00 0.21 0.10 0.14 0.67 0.65 0.01 0.01
New drugs 10.9 3.5 4.8 3.2 (0.29– 2.5 0.4 1.0 0.2 (0.0-2.9), 20.51 (7.06– 8.1 3.6 (1.5- 9.7 (2.0-48.4),
(4.2–28.3), (1.2–10.4), (2.3–10.0), 36.2), 0.34 (0.7–8.2), (0.1–2.7), (0.1–8.5), 0.22 59.55), (3.3–19.7), 9.0), 0.01 0.01
0.00 0.02 0.00 0.14 0.31 0.99 0.00 0.00
N total studies, OR odds ratio, 95% IC 95% confidence intervals, p p-value, 4: four months after ending educational intervention, 8: eight months after ending educational intervention, 12:
twelve months after ending educational intervention, 16: sixteen months after ending educational intervention. Statistically significant results are shown in bold
Fig. 4 Risk of bias graph, review authors’ judgments about each risk of bias item presented as percentages across all included studies. A Risk of
bias overall assessment, the proportion of assessment studies. B Risk of bias assessment summary for included studies
training in the study, reporting promotion by regional cent- Only one RCT in this systematic review evaluated attitude
ers, the unit’s requirement to report cases of a new drug, after educative intervention, with a positive effect [38].
an industry study, incentive programs for reporting, elec- ADR reporting in post-marketing surveillance is a corner-
tronic methods of ADR report, and monetary incentives stone for signal detection and contribute to establish guide-
[6, 42, 46, 47]. Against, the effectiveness can be decreased lines or policies for medication use. Consequently, it allows
due to factors such as high workload that does not allow identifying serious or unexpected adverse drug reactions
reporting, limited time to take courses and lack of interest that represent a major problem in patient safety and increase
in pharmacovigilance [45, 48]. In this sense, the attitude hospital costs; thus, educative interventions sensitize health
to ADR underreporting can be explained by Inman and professionals about its importance [54]. In this review, the
its seven deadly sins: complacency, ignorance, diffidence, workshops and combined interventions increase the serious,
financial incentives, legal aspects, lethargy, and indiffer- unexpected, high causality, and new drug ADR reporting for
ence [4]. Furthermore, the fact that health professionals at least 12 months.
have a high knowledge of pharmacovigilance does not
imply that they have a good attitude towards the report [49, Limitation of study
50]. Previous studies based on questionnaires of Knowl-
edge, Attitude, and Practice (KAP) in pharmacovigilance This systematic review has the following limitations, which
support that an educational intervention could generate a should be considered when interpreting the results: (1) the
change in a positive behavior on ADR report [6, 50–53]. educational interventions are different, such as workshops,
combined interventions, telephone-based interventions, let- References

ters, or lectures; (2) the studies were evaluated with two dif-
ferent types of controls (continuing education and nothing); 1. Sánchez I, Amador C, Plaza JC, Correa GAR. Assessment of an
(3) No study that evaluated knowledge or attitude performed active pharmacovigilance system carried out by a pharmacist. Rev
Med Chil. 2014;142:998–1005. https://doi.org/10.4067/S0034-
a prior validation of the questionnaire; (4) the workshop var- 98872014000800007.
iate between brainstorming with two sessions of two hours in 2. Vlahović-Palčevski V, Mentzer D. Postmarketing surveillance.
one day, one session of one hour, a session every month, or Handb Exp Pharmacol. 2011;205:339–51. https://d oi.o rg/1 0.1 007/
reminder card and report form with two sessions of 30 min. 978-3-642-20195-0_17.
3. Uppsala Monitoring Centre. Safety monitoring of medicinal prod-
ucts. In: Guidelines for setting up and running a Pharmacovigi-
lance Centre. World Health Organization (WHO); 2000. https://
Conclusions who-umc.org/media/1703/24747.pdf. Accessed 13 Oct 2022.
4. Inman W. Attitudes to adverse drug-reaction reporting. Br J Clin
Pharmacol. 1996;41:433–5.
The educative interventions in pharmacovigilance increased 5. Khan SA, Goyal C, Chandel N, Rafi M. Knowledge, attitudes, and
the number of ADR reports and score in the knowledge. The practice of doctors to adverse drug reaction reporting in a teach-
workshop and combined intervention are the EI with greater ing hospital in India: an observational study. J Nat Sci Biol Med.
efficacy and duration. More RCTs are needed to assess the 2013;4:191–6. https://doi.org/10.4103/0976-9668.107289.
6. Li R, Zaidi STR, Chen T, Castelino R. Effectiveness of interven-
role of educational interventions in changing attitudes tions to improve adverse drug reaction reporting by healthcare
towards pharmacovigilance. professionals over the last decade: a systematic review. Pharma-
coepidemiol Drug Saf. 2020;29:1–8. https://doi.org/10.1002/pds.
Supplementary Information The online version contains supplemen- 4906.
tary material available at https://doi.org/10.1007/s40199-024-00508-z. 7. Khalili M, Mesgarpour B, Sharifi H, Daneshvar-Dehnavi S,
Haghdoost AA. Interventions to improve adverse drug reac-
Acknowledgements Cervantes-Arellano Mónica Janette is a doctoral tion reporting: a scoping review. Pharmacoepidemiol Drug Saf.
student from the Programa de Maestría y Doctorado en Ciencias Médi- 2020;29:965–92. https://doi.org/10.1002/pds.4966.
cas, Odontológicas y de la Salud, Investigación Clínica Experimental 8. Paudyal V, Al-Hamid A, Bowen M, Abdul-Hadi M, Shahzad-
en Salud (ICES). CMJ receive a fellowship from Consejo Nacional de Hasan S, Jalal Z, Stewart D. Interventions to improve spontaneous
Ciencia y Tecnología (CONACyT) with CVU number 777686. adverse drug reaction reporting by healthcare professionals and
patients: systematic review and meta-analysis. Expert Opin Drug
Author contributions Conception of the work LMU; design of the work Saf. 2020;19:1173–91. https://doi.org/10.1080/14740338.2020.
MJC, LMU, ODC; data acquisition MJC and LMU; data analysis MJC, 1807003.
LMU, ODC; data interpretation MJC, ODC, LMU, YM, JLC, OM; all 9. Abubakar AR, Simbak NB, Haque M. A systematic review of
authors contribute in manuscript drafting and approved the final version. knowledge, attitude and practice on adverse drug reactions
and pharmacovigilance among doctors. J Appl Pharm Sci.
Funding No specific funding for this study was obtained. 2014;4:117–27. https://doi.org/10.7324/JAPS.2014.40121.
10. Faillie JL, Montastruc F, Montastruc JL, Pariente A. Pharma-
Data availability Databases generated for this systematic review are coepidemiology and its input to pharmacovigilance. Therapie.
available from the corresponding author upon reasonable request. 2016;71:211–6. https://doi.org/10.1016/j.therap.2016.02.016.
11. Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC,
Declarations Mulrow CD, et al. PRISMA 2020 explanation and elaboration:
updated guidance and exemplars for reporting systematic reviews.
Ethics approval This study was register in Division de Investigation at BMJ. 2021;372. https://doi.org/10.1136/bmj.n160.
the Faculty of Medicine, UNAM FM/DI/003/21 to LMU. 12. Deeks JJ, Higgins JPT, Altman DG. Chapter 9: Analysing data
and undertaking meta-analyses. In: Higgins JPT, Green S, edi-
Consent for participate Not applicable. tors. Cochrane Handbook for Systematic Reviews of Interven-
tions. Cochrane; 2008. https://www.radioterapiaitalia.it/wp-conte
Consent for publication Not applicable. nt/uploads/2017/01/cochrane-handbook-for-systematic-reviews-
of-interventions.pdf. Accessed 15 Oct 2022.
13. Higgins JPT, Savović J, Page MJ, Elbers RG, Sterne JAC. Chap-
Conflict of interest Nothing to declare. ter 8: Assessing risk of bias in a randomized trial. In: Higgins JPT,
Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA,
Open Access This article is licensed under a Creative Commons Attri- editors. Cochrane Handbook for Systematic Reviews of Interven-
bution 4.0 International License, which permits use, sharing, adapta- tions, version 6.3. Cochrane; 2022. Available from: https://www.
tion, distribution and reproduction in any medium or format, as long training.cochrane.org/handbook. Accessed 15 Oct 2022.
as you give appropriate credit to the original author(s) and the source, 14. The Cochrane Collaboration Review Manager (RevMan). [Com-
provide a link to the Creative Commons licence, and indicate if changes puter Program]. The Nordic Cochrane Centre, The Cochrane Col-
were made. The images or other third party material in this article are laboration; Copenhagen, Version 5.4. Denmark: 2020. Available
included in the article’s Creative Commons licence, unless indicated from: https://t raini ng.c ochra ne.o rg/o nline-l earni ng/c ore-s oftwa re/
otherwise in a credit line to the material. If material is not included in revman/revman-5-download. Accessed 15 Apr 2022.
the article’s Creative Commons licence and your intended use is not 15. Deeks JJ, Higgins JPT, Altman DG. Chapter 10: Analysing data
permitted by statutory regulation or exceeds the permitted use, you will and undertaking meta-analyses. In: Higgins JPT, Thomas J, Chan-
need to obtain permission directly from the copyright holder. To view a dler J, Cumpston M, Li T, Page MJ, Welch VA, editors. Cochrane
copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Handbook for Systematic Reviews of Interventions, version 6.3. 30. Johansson ML, Hägg S, Wallerstedt SM. Impact of information
Cochrane. 2022. Available from: https://www.training.cochrane. letters on the reporting rate of adverse drug reactions and the
org/handbook. Accessed 15 Oct 2022. quality of the reports: a randomized controlled study. BMC Clin
16. Bäckström M, Mjörndal T. A small economic inducement to Pharmacol. 2011;11.
stimulate increased reporting of adverse drug reactions—a way of 31. Herdeiro MT, Ribeiro-Vaz I, Ferreira M, Polónia J, Falcão A, Figue-
dealing with an old problem? Eur J Clin Pharmacol. 2006;62:381– iras A. Workshop- and telephone-based interventions to improve
5. https://doi.org/10.1007/s00228-005-0072-0. adverse drug reaction reporting. Drug Saf. 2012;35:655–65.
17. Bracchi RCG, Houghton J, Woods FJ, Thomas S, Smail SA, 32. Herdeiro MT, Polónia J, Gestal-Otero JJ, Figueiras A. Improving
Routledge PA. A distance-learning programme in pharmacovig- the reporting of adverse drug reactions: a cluster-randomized trial
ilance linked to educational credits is associated with improved among pharmacists in Portugal. Drug Saf. 2008;31:335–44.
reporting of suspected adverse drug reactions via the UK yellow 33. Figueiras A, Herdeiro MT, Polónia J, Gestal-Otero JJ. An educa-
card scheme. Br J Clin Pharmacol. 2005;60:221–3. https://doi. tional intervention to improve physician reporting of adverse drug
org/10.1111/j.1365-2125.2005.02419.x. reactions. JAMA. 2006;296:1086–93.
18. Srikanth MS, Adeppu R. Assessment of educational interven- 34. Ribeiro-Vaz I, Herdeiro MT, Polónia J, Figueiras A. Strategies
tion on knowledge, attitude and practices of rural comnunity to increase the sensitivity of pharmacovigilance in Portugal. Rev
pharmacists of Mysuru district toward adverse drug reaction Saude Publica. 2011;45:129–35.
reporting. Asian J Pharm Clin Res. 2018;11:242–6. 35. Lopez-Gonzalez E, Herdeiro MT, Piñeiro-Lamas M, Figueiras
19. Williams GD, Muffly MK, Mendoza JM, Wixson N, Leong K, A. Effect of an educational intervention to improve adverse drug
Claure RE. Reporting of perioperative adverse events by pedi- reaction reporting in physicians: a cluster randomized controlled
atric anesthesiologists at a tertiary children’s hospital: targeted trial. Drug Saf. 2015;38:189–96.
interventions to increase the rate of reporting. Anesth Analg. 36. Sarayani A, Naderi-Behdani F, Hadavand N, Javadi M, Farsad F,
2017;125:1515–23. Hadjibabaie M, Gholami K. A 3-armed randomized controlled
20. Gumustekin M, Arici MA, Koca P, Gelal A, Tuncok Y. Impact trial of nurses’ continuing education meetings on adverse drug
of an educatıonal interventıon on knowledge and attıtude reactions. J Contin Educ Health Prof. 2015;35:123–30.
related to adverse drug reactıons reported by Physıcıans ın an 37. Cheema E, Almualem AA, Basudan AT, Salamatullah AAK, Rad-
Unıversıty Hospıtal. Clin Ther. 2017. https://doi.org/10.1016/j. hwi SO, Alsehli AS. Assessing the impact of structured education
clinthera.2017.05.184. on the knowledge of hospital pharmacists about adverse drug reac-
21. Kane-Gill SL, Hanlon JT, Fine MJ, Perera S, Culley CM, Studen- tions and reporting methods in Saudi Arabia: an open-label ran-
ski SA, Nace DA, Boyce RD, Castle NG, Handler SM. Physician domised controlled trial. Drugs Ther Perspect. 2019;35:296–300
perceptions of consultant pharmacist services associated with an Springer International Publishing.
intervention for adverse drug events in the nursing facility. Consult 38. Granas AG, Buajordet M, Stenberg-Nilsen H, Harg P, Horn
Pharm. 2016;31:708–20. https://doi.org/10.4140/TCP.n.2016.708. AM. Pharmacists’ attitudes towards the reporting of suspected
22. Stoynova V, Getov IN, Naseva EK, Lebanova HV, Grigorov adverse drug reactions in Norway. Pharmacoepidemiol Drug Saf.
EE. Physicians’ knowledge and attitude towards adverse event 2007;16:429–34.
reporting system and result to intervention randomized nested 39. Johansson ML, Brunlöf G, Edward C, Wallerstedt SM. Effects of
trial among Bulgarian physicians. Med Glas. 2013;10:365–72. e-mails containing ADR information and a current case report on
23. Gonzalez-Gonzalez C, Lopez-Gonzalez E, Herdeiro MT, Figue- ADR reporting rate and quality of reports. Eur J Clin Pharmacol.
iras A. Strategies to improve adverse drug reaction reporting: 2009;65:511–4.
a critical and systematic review. Drug Saf. 2013;36:317–28. 40. Bañeres J, Cavero E, López L, Orrego C, Suñol R. Sistemas de
https://doi.org/10.1007/s40264-013-0058-2. registro y notificación de incidentes y eventos adversos. Ministerio
24. Sanghavi DR, Dhande PP, Pandit VA. Perception of pharma- de Sanidad y Consumo. Madrid. https://seguridaddelpaciente.es/
covigilance among doctors in a tertiary care hospital: influence resources/documentos/sistemasregistronotificacionincidentesea.
of an interventional lecture. Int J Risk Saf Med. 2013;25:197– pdf. Accessed 15 Oct 2022
204. https://doi.org/10.3233/JRS-130598. 41. Dave D, O´Brien MA, Freemantle N, Wolf FM, Mazmanian P,
25. Ribeiro-Vaz I, Herdeiro T, Figueiras A, Polónia J. Strategies for Taylor-Vaisey A. Impact of formal continuing medical education
increasing spontaneous adverse drug reaction reporting rates do conferences, workshops, rounds, and other traditional continu-
among Portuguese pharmacists. Eur J Integr Med. 2009;1:250– ing education activities change physician behavior or health care
1. https://doi.org/10.1016/j.eujim.2009.08.053. outcomes? JAMA.1999;282:867–74.
26. Rosenbaum SE, Thacher-Renshaw A, Green M, Waters WJ. 42. Pagotto C, Varallo F, Mastroianni P. Impact of educational inter-
Interventions to increase physician participation in a volun- ventions on adverse drug events reporting. Int J Technol Assess
tary reporting system: the Rhode Island adverse drug reaction Health Care. 2013;29:410–7.
reporting project. Clin Res Reg Affairs. 1992;9:261–75. https:// 43. Forsetlund L, Bjørndal A, Rashidian A, Jamtvedt G, O’Brien
doi.org/10.3109/10601339209005340. MA, Wolf F, Davis D, Odgaard-Jensen J, Oxman AD. Continu-
27. Herdeiro MT, Ribeiro-Vaz I, Ferreira M, Polónia J, Figueiras A. ing education meetings and workshops: effects on professional
Improving adverse drug reaction reporting through workshops and practice and health care outcomes. Cochrane Database Syst Rev.
telephone education: Cluster Randomized Trial among Portuguese 2009;2009(2):CD003030. https://doi.org/10.1002/14651858.
physicians. Basic Clin Pharmacol Toxicol. 2011;109(s1):56–164. CD003030.pub2.
https://doi.org/10.1111/j.1742-7843.2011.00722.x. 44. Giguère A, Légaré F, Grimshaw J, Turcotte S, Fiander M, Grudniewicz
28. Jha N, Rathore DS, Shankar PR, Gyawali S, Alshakka M, A, Makosso-Kallyth S, Wolf FM, Farmer AP, Gagnon MP. Printed
Bhandary S. An educational intervention’s effect on healthcare educational materials: effects on professional practice and healthcare
professionals’ attitudes towards pharmacovigilance. Australas outcomes. Cochrane Database Syst Rev. 2012;10:CD004398.
Med J. 2014;7:478–89. https://doi.org/10.4066/AMJ.2014.2235. 45. Biagi C, Montanaro N, Buccellato E, Roberto G, Vaccheri A,
29. Potlog SM, Goldstein LH, Arcavi L, Shihmanter R, Berkovitch Motola D. Underreporting in pharmacovigilance: an intervention
M, Levy A. Increasing adverse drug reaction reporting-how can for Italian GPs (Emilia-Romagna region). Eur J Clin Pharmacol.
we do better? PLoS ONE. 2020;15:1–15. 2013;69:237–44.
46. Srba J, Descikova V, Vlcek J. Adverse drug reactions: analysis of 51. Manjhi PK, Kumar M, Dikshit H, Mohan L, Mishra H. A survey
spontaneous reporting system in Europe in 2007–2009. Eur J Clin on knowledge, attitude and practice of pharmacovigilance and
Pharmacol. 2012;68:1057–63. adverse drug reaction reporting among healthcare professionals in
47. Ali S, Egunsola O, Al-Dossari DS, Al-Zaagi IA. Adverse drug reac- a tertiary care hospital of Bihar, India. Int J Basic Clin Pharmacol.
tion reporting in a large tertiary hospital in Saudi Arabia: results of 2016;5:2566–71.
an incentive strategy. Ther Adv Drug Saf. 2018;9:585–90. 52. Herdeiro MT, Figueiras A, Polónia J, Gestal-Otero JJ. Physicians’
48. Salehi T, Seyedfatemi N, Mirzaee MS, Maleki M, Mardani A. attitudes and adverse drug reaction reporting a case-control study
Nurses’ knowledge, attitudes, and practice in relation to phar- in Portugal. Drug Saf. 2005;28:825–33.
macovigilance and adverse drug reaction reporting: a systematic 53. Hardeep, Bajaj JK, Rakesh K. A survey on the knowledge, attitude
review. Biomed Res Int. 2021;2021:6630404. https://doi.org/10. and the practice of pharmacovigilance among the health care pro-
1155/2021/6630404. fessionals in a teaching hospital in northern India. J Clin Diagn
49. Alshammari TM, Alamri KK, Ghawa YA, Alohali NF, Abualkol Res. 2013;7:97–9.
SA, Aljadhey HS. Knowledge and attitude of health-care profes- 54. Gautier S, Bachelet H, Bordet R, Caron J. The cost of adverse drug
sionals in hospitals towards pharmacovigilance in Saudi Arabia. reactions. Expert Opin Pharmacother. 2003;4:319–26.
Int J Clin Pharm. 2015;37:1104–10.
50. Hussain R, Hassali MA, Hashmi F, Akram T. Exploring health- Publisher’s Note Springer Nature remains neutral with regard to
care professionals’ knowledge, attitude, and practices towards jurisdictional claims in published maps and institutional affiliations.
pharmacovigilance: a cross-sectional survey. J Pharm Policy
Pract. 2021. https://doi.org/10.1186/s40545-020-00287-3.

Article

Uploaded by

Copyright:

Available Formats

Article

Uploaded by

Document Information

Original Description:

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Article

Uploaded by

Copyright:

Available Formats

DARU Journal of Pharmaceutical Sciences

Educational interventions in pharmacovigilance to improve

Received: 22 December 2022 / Accepted: 15 February 2024

Introduction not limited by years or language. The strategy search was

Data analysis Results

The score of “knowledge

to 19.16], p = 0.001; report

combined interventions, telephone-based interventions, let- References

You might also like