PONE-D-20-00501

Medical Students' Knowledge, Attitude and Perception of Pharmacovigilance: A Systematic Review

PLOS ONE

Dear Dr. Alwhaibi,

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PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: No

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: I Don't Know

Reviewer #3: N/A

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3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: 1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript is technically sound, however this manuscripts aim is not consistent with the outcome of the search and the results. The authors claim to have only included MEDICAL students, however most included articles are NOT about medical students (ie pharmacy, dental or nursing). The conclusion, where you claim knowledge and perceptions about PV in MEDICAL students is insufficient, should therefore be changed.

2. Has the statistical analysis been performed appropriately and rigorously?

The manuscript doesn’t include a section on statistical analysis, although some descriptive statistical tests were probably done.

3. Have the authors made all data underlying the findings in their manuscript fully available?

Yes.

4. Is the manuscript presented in an intelligible fashion and written in standard English?

Yes, most of the manuscript is written in standard English, although many parts should be looked over because of spelling errors or non-fluent sentences (my comments are presented down below).

More specific remarks

Introduction

Page 5, line 8: “Have the above questions adequately… “:This sentence is too complicated and doesn’t flow, please rewrite.

Methods:

Overall: No section was dedicated to the (descriptive) statistical analysis.

Page 5, line 19/20: “Articles search of the four databases was conducted independently by two review authors (MA and NA), the disagreement was resolved by consensus.”: We suggest changing “the disagreement” to “any disagreement”.

Page 5, line 21: “Limits that were applied included selecting studies those published in English from inception until December 2019 …… “: Incorrect grammar. Possible to delete “those”.

Page 6, line 1: “studies that pertaining to the evaluation …..”: Incorrect grammar. Either: use “studies pertaining to” OR “studies that pertained to the ……”

Page 6, line 2/3: “and where the participants are medical schools students but not healthcare professionals”: Too much information, medical students are not healthcare professionals, so choose either “medical school students’ or “not healthcare professionals”.

Page 6, line 13: “This tool covers twenty-two criteria for Study design quality and biases in the study.“ : No need for a capital letter.

Results:

General remarks: Your aim is to analyze MEDICAL students knowledge and perceptions, you have only included the term MEDICAL STUDENT in your search, however have found studies who only include PHARMACY or DENTAL students. Please elaborate on this strange finding. Do you also think PHARMACY and DENTAL students are MEDICAL students. In this case you should clearly state this.

Page 7, line 6/12: Please add more sourceremarks to these lines. E.g. “Twenty studies examined the Pharmacovigilance knowledge and nine evaluated attitudes towards pharmacovigilance and thirteen studies measured the perception of pharmacovigilance”: has no sources.

Page 7, line 19: Wrong word: “Key information form selected articles were extracted and …”, you probably mean “Key information from selected articles were extracted and …”,

Page 8, line 1/3: “The most common questions asked about PV, ADR definitions and the local regulatory body of ADR reporting, while few studies asked about the ADR causality assessment, types of ADR, and the online WHO PV database (Appendix 2).” Incorrect grammar, is missing a verb and is too long.

Page 8, line 11/12: “Attitude towards pharmacovigilance and ADR reporting was measured using multiple-choice response options range from 2 to 5 questions”, should be “ranging”.

Page 8, line 15/16: and 24/1 “The attitude towards PV and ADRs from the included studies was ranging from 25% to 97%”: should be “…. studies ranged from ……”

Discussion

Page 9, line 11/13: ´Moreover, some studies piloted their instrument and some were face and content validated, around 50% measured the reliability, i.e., internal consistency using Cronbach’s Alpha.”:Incorrect grammar and is too long, try making it into two sentences.

Page 9, line 16/19: “This variation could be attributed to the following factors: i) inconsistency in tools/measured used to evaluate KAP between the studies; ii) lacking validated KAP measures, iii) different study setting, and iv) different experience the students have during their education about PV and ADRs reporting.”: point iv) Incorrect grammar. Try “and iv) different PV and ADR reporting experiences during their education.”

Page 9, line 21/22: You mention that the previous published review investigates all healthcare students (these include medical, pharmacy, dental and nursing). This review also covers these “healthcare students” and mostly focusses on pharmacy students in the text.

Page 10, line 2/5: “In addition, many educational interventions have been implemented among medical schools students to improve PV knowledge to enhance perception and positive attitude toward PV such as; short lecture, multiple training workshops, clinical experience in ADR reporting and assessment [3].”: Last example has incorrect grammar.

Page 10, line 5/7: “These interventions improved students PV knowledge and competences to a different extent, however, due to variation in questions or grouped outcomes scores been used the authors were not able to conclude which intervention was the best.”: Incorrect grammar.

Page 10, line 8/10: “In our review, students satisfaction toward PV coverage in their curriculum was vary from 21 to 85% , which indicates variation in PV integration between different medical schools, highlight the need for uniform PV educational intervention.”: it should be: “student satisfaction towards PV”, it should be: “in their curriculum varied from ….”. Also please make two sentences! Please rewrite the second part of the scentence, it doesn’t flow.

Page 10, line 11: There is a WHO-ISoP core curriculum for pharmacovigilance! Jurgen Backmann et all. Teaching Pharmacovigilance: the WHO-ISoP Core Elements of a Comprehensive Modular Curriculum 2014, drug safety.

Page 10, line 11/14: Too long and malformed sentence. Please rewrite.

Page 10, line 18/19: “This review has helped us gather evidence about the lacking of standardized validated measure to evaluate the KAP of PV and ADR reporting of any medical school students.”: Stange word option ( the lacking), maybe change it for “the absence”

Page 10, line 22/23: “The main limitation in our review is the heterogeneity of assessment measures used between different included studies, which band us from conducting a Meta-analysis.”: change word option (band us), maybe use “made a meta-analysis impossible”.

Conclusion

You argue that this review demonstrated the lack of PV knowledge among MEDICAL students, however you have only 5-6 studies on medical students however include a larger amount of studies with dental, pharmacy and nursing students.

Table 1

- It is surprising that you haven’t included any articles form 2019. I already know of a study by Katyal et al 2019, which should fit your search.

- Please elaborate on the difference between a cross-sectional study and a pilot study. I thought you only included cross-sectional studies? If not so, you missed a lot of interventional studies who also published cross-sectional results (ie pre- or post-interventional results).

Reviewer #2: Dear authors: I'm going to stick to the search strategy:

1. The databases searched are appropriate for a systematic review on medical education (MEDLINE & ERIC especially). I typically expect Embase to be included as well for the international literature. Is there a reason this was not included?

2. MedLine should be MEDLINE (in abstract, design & search strategy, and anywhere else mentioned)

3. Please list the platform used for the search of ERIC.

4. I have some concerns about the low numbers of results (~330). For instance, here is how I interpret the PubMed search based on the search description in the methods,

(knowledge OR attitude OR perception) AND medical students AND (pharmacovigilance OR adverse drug reactions reporting)

There are only ~30 results with that search in the version of PubMed that would've been used for this project. While it may have contained every relevant article, it seems far too narrow, especially when I run a more typical search that gets 3x as many:

(medical students[mh] or student*[tiab]) and (pharmacovigilance[mh] or pharmacovigilance[tiab] or pharmaco-vigilance[tiab] or Adverse Drug Reaction Reporting Systems[mh])

I don't mean to say that this is a perfect search, but that it brings in more suggests to me that there may be some missing in your analysis.

5. It's expected for systematic review searches to explicitly include controlled terms (MeSH in the case of PubMed) and more text word variations. For example, plurals (attitudes), other forms (perceive), other words (beliefs, residents, fellows). These are not called out in the methods at all.

6. I applaud the authors for their manual search.

I fear that the search undertaken wasn't comprehensive enough to support the review.

Reviewer #3: There are several issues with the methods of with this review

* Reviewers write that they the review was conducted according to PRISMA, However, PRISMA is about reporting not conducting. For example PRISMA says you must describe all resources searched, but Cochrane Collaboration MECIR lists which databases must be searched.

* The eligibility criteria of included studies was not clearly described. "studies pertaining to the evaluation of...". What types of studies? Were intervention studies going to be included?

*The description of the search is inadequate, and if this was the exact search it is not comprehensive enough to have retrieved all possible articles. Medline, CINAHL, and ERIC all have elaborate thesaurus terms which were not used in the searches. If the databases were searched at the same time, this is also not appropriate as this does not allow the use of thesaurus terms.

*The description of study selection does not provide information required by PRISMA. How many screeners? Was the screening done independently.

*Quality assessment used a reporting standard (STROBE) not an assessment of risk of bias in the methods. Giving the percentage of points received by each article according to strobe does not give me any information about the potential risk of bias across these studies as a whole.

*Figure 1, PRISMA flowchart, belongs in the results section, not the methods section

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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PONE-D-20-00501R1

Healthcare Students' Knowledge, Attitude and Perception of Pharmacovigilance: A Systematic Review

PLOS ONE

Dear Dr. Alwhaibi,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

We would appreciate receiving your revised manuscript by May 23 2020 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Lisa Susan Wieland

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

The manuscript is improved, however some of the reviewer comments have not yet been adequately addressed. See comments here:

1) The search strategy is improved. However, if you did not have the searches developed and carried out in collaboration with a trained information specialist please add this to the limitations of the study, as you cannot be certain that there were not additional studies that you did not retrieve. Also, did you search the Cochrane Database of Systematic Reviews or was it the Cochrane Library? If you were searching for systematic reviews it was probably the Cochrane Database of Systematic Reviews but if you were searching for individual controlled trials it was probably the Cochrane Central Register of Controlled Trials. Both of these databases are in the Cochrane Library.

2) The rationale for including a ‘pilot study’ in which pre and post tests were administered and excluding studies reporting KAP measures pre- and post- some intervention is unclear. What is the difference between assessing the results of an intervention and testing the effects of usual education? This needs to be clarified. The inclusion of cross-sectional studies is clear, but the cohort studies could mean anything from a single group tested at multiple time points to a randomized controlled trial.

3) The reviewer is correct that STROBE is a reporting guideline. The authors of the article you cite say that STROBE was referred to in many of the assessment instruments because many STROBE items may have been selected because of presumed association with risk of bias. However the authors do not suggest that STROBE should be used as a risk of bias assessment tool. The authors state that ‘Just under three-quarters of all tools were proposed as being suitable for future use, including all of the critical appraisal tools and generic systematic review tools and six of the tools originally designed for use in a specific systematic review.’ Look in Tables 5-7 for the tools that meet the important criteria identified by the authors (selection of participants, measurement of variables, and control of confounding). These are the tools that the authors judge as appropriate.

A more recent and more targeted approach to risk of bias for surveys may be found in https://www.evidencepartners.com/wp-content/uploads/2017/09/Risk-of-Bias-Instrument-for-Cross-Sectional-Surveys-of-Attitudes-and-Practices.pdf. See https://www.evidencepartners.com/wp-content/uploads/2017/04/Methods-Commentary-Risk-of-Bias-in-cross-sectional-surveys-of-attitude....pdf for comments and further guidance on this tool.

For the pre-post surveys, you might have to look further for a suitable tool, or you could decide to assess the risk of bias based on either the pretest or the posttest survey if you are not interested in the effects of the education intervention. However, as I mentioned above, the inclusion of pretest/posttest pilot studies but the exclusion of other interventional studies lacks a rationale and this needs to be addressed.

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Reviewers' comments:

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Healthcare Students' Knowledge, Attitude and Perception of Pharmacovigilance: A Systematic Review

PONE-D-20-00501R2

Dear Dr. Alwhaibi,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

Lisa Susan Wieland

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: