The authors have declared that no competing interests exist.
Conceived and designed the experiments: ASB AAE. Performed the experiments: ASB AAE SQJ AS. Analyzed the data: ASB AAE. Contributed reagents/materials/analysis tools: ASB AAE SQJ AS. Wrote the paper: ASB.
Spontaneous or voluntary reporting of suspected adverse drug reactions (ADRs) is one of the vital roles of all health professionals. In India, under-reporting of ADRs by health professionals is recognized as one of the leading causes of poor ADR signal detection. Therefore, reviewing the literature can provide a better understanding of the status of knowledge, attitude and practice (KAP) of Pharmacovigilance (PV) activities by health professionals.
A systematic review was performed through Pubmed, Scopus, Embase and Google Scholar scientific databases. Studies pertaining to KAP of PV and ADR reporting by Indian health professionals between January 2011 and July 2015 were included in a meta-analysis.
A total of 28 studies were included in the systematic review and 18 of them were selected for meta-analysis. Overall, 55.6% (95% CI 44.4–66.9;
There was an enormous gap of KAP towards PV and ADR reporting, particularly PV practice in India. There is therefore an urgent need for educational awareness, simplification of the ADR reporting process, and implementation of imperative measures to practice PV among healthcare professionals. In order to understand the PV status, PvPI should procedurally assess the KAP of health professionals PV activities in India.
India is home to one of the largest drug consuming populations in the world. There are between 60,000–80,000 brands of drugs available in the Indian market that are irrationally prescribed and misused [
The World Health Organization (WHO) defines ADRs as any noxious, unintended, and undesired effect of a drug, which occurs at doses used in humans for prophylaxis, diagnosis, or treatment of the disease [
Pharmacovigilance (PV) is and the sum of activities related to the detection, assessment, understanding, and prevention of ADRs caused by drugs [
Furthermore, it is evident that under-reporting of suspected ADRs by health professionals is a widespread problem in India [
To summarize the existing evidence related to PV activities in India, a systematic review using Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statements was conducted (
Awareness of PvPI
Knowledge about the safety of drugs
Attitude towards reporting ADRs
Knowledge about obtaining ADR forms
Practice of ADR reporting
Availability of ADR forms
Surveys using open answers focused on health professionals
Titles and abstracts were screened by one author (ASB). Studies were selected for inclusion from full-text articles by two researchers (ASB, AAE). The database search fields for titles, abstracts and index terms were searched using the following research string: pharmacovigilance* AND adverse drug reactions reporting* AND health professionals* AND survey* AND India* AND (knowledge OR attitude OR practice).
Two authors (ASB and SQJ) analyzed the search results in collaboration to find potentially eligible studies. Small changes in wording were also overlooked for their exact functional meaning. We excluded duplicates and studies in which data was inadequately reported (
Two researchers independently performed the data extraction and disagreement was resolved by consensus. The extracted data was based on information reported in or calculated from the included studies. Corresponding authors were not contacted for unpublished information. Information including year of execution of the survey, sample size, study location, the method of administration of the questionnaire, and data towards KAP of PV and ADR reporting were retrieved. In particular, we considered six statements that were common to the different studies as outcomes for the meta-analysis:
Respondent is aware of the National Pharmacovigilance Programme in India (percentage of inappropriate answers)
Respondent considers all drugs to be safe (percentage of inappropriate answers)
Respondent is interested in reporting ADRs (percentage of inappropriate answers)
Respondent knows where to obtain ADR forms (percentage of inappropriate answers)
Respondent never reported an ADR (percentage of yes)
Respondent reports non-availability of ADR forms (percentage of yes)
The first two statements assessed the knowledge concerning the national PV programme and safety of drugs, statements three and four assessed the attitude towards ADR reporting, and the last two evaluated the practice of PV activities. Due to differences in the questionnaires administered in different studies, the information suitable to our purpose was extracted for analysis.
Meta-analysis was performed using statistical software StatsDirect 2.8.0 on all the studies that yielded comparable outcomes. Heterogeneity of the studies was evaluated using Cochrane's Q test and the
To address the issue of heterogeneity of the studies, a sensitivity analysis was considered using the following subgroups:
studies of high quality (over 75% of the STROBE checklist)
studies of low quality (under 75% of the STROBE checklist)
Moreover, publication bias was assessed using Egger and Begg tests and graphs representing funnel plots.
A total of 320 studies were retrieved from the four scientific databases (Pubmed, Scopus, Embase and Google Scholar) for analysis. After screening titles and abstracts, for duplicates and irrelevant studies, 270 papers were excluded. Fifty studies were considered for the full text review, of which twenty-two were excluded as they did not meet the inclusion criteria (
All the 28 citations included in the systematic review were cross-section observational surveys using self-administered questionnaires conducted among Indian healthcare professionals and published between January 2011 and July 2015. Of these, one study was a web-based survey of pharmacists [
The sample size of the studies ranged from 42 [
References | Author | Year | Journal | Study design | Study location | Quality assessment |
Sample size | Focusing group | Questionnaire administration | Outcome |
---|---|---|---|---|---|---|---|---|---|---|
[ |
Torwane NA et al | 2015 | J Nat Accred Board Hosp Healthcare Providers | Cross-section observational study | Bhopal, Madhya Pradesh | - | 392 | Doctors, dentists, nursing | Close-ended | Knowledge, attitude and practice regarding ADR reporting |
[ |
Bansoda AA et al | 2015 | J Evolution Med Dent Sci | Cross-section observational study | Solapur, Maharastra | >75% | 150 | Resident doctors | Open and close-ended | Awareness of pharmacovigilance amongst resident doctors |
[ |
Sridevi SA et al. | 2014 | Int J Pharmacol Toxicol | Cross-section observational study | Chennai, Tamil nadu | <75% | 324 | Medical Postgraduates, graduates, doctors, surgeons, dentists | Close-ended | Knowledge, attitude and practice of ADR reporting and pharmacovigilance |
[ |
Kiran LJ et al | 2014 | Sch J App Med Sci | Cross-section observational study | Karnataka | >75% | 120 | Clinicians | Close-ended | Knowledge, attitudes |
[ |
Karelia BN et al | 2014 | Int J Basic Clin Pharmacol | Cross-section observational study | Rajkot, Gujarat | <75% | 332 | Doctors | Open and close-ended | Knowledge, attitudes |
[ |
Chanchu S et al | 2014 | Int J Sci Res | Cross-section observational study | Anantapur, Andhra Pradesh | ~ 75% | 165 | Medical, nursing and pharmacists | Close-ended | Knowledge, attitude and |
[ |
Maharani B et al | 2013 | Nat J Basic Med Sci | Cross-section observational study | Salem, Tamil nadu | >75% | 249 | Medical Practitioners | Self-administered | Knowledge and attitude of Pharmacovigilance reporting system |
[ |
Amrita P et al | 2012 | Indian J Pharm Prac | Cross-section observational study | New Delhi | <75% | 376 | Physician, pharmacists, nurses | Close-ended | Knowledge, attitude and skills of pharmacovigilance and spontaneous reporting of ADRs |
[ |
Kumar MB et al. | 2012 | Indian J Pharm Prac | Cross-section observational study | Karnataka | <75% | 128 | Pharmacists | Close-ended | Knowledge, attitude and behavior of adverse drug reactions reporting |
[ |
Kamtane R et al | 2012 | Asian J Pharm Clin Res | Cross-section observational study | Hyderabad, Telangana | >75% | 94 | Doctors | Open and close-ended | Knowledge, attitude, and practice of ADR reporting |
[ |
Upadhyaya HB et al | 2015 | J Adv Pharm Technol Res | Cross-section observational study | Vadodara, Gujarat | >75% | 101 | Postgraduate Medical students | Open and close-ended | Knowledge, Attitude of Pharmacovigilance and ADRs, and practice towards ADRs |
[ |
Gupta SK et al. | 2015 | Perspect Clin Res | Cross-section observational study | Perambalur, Tamil nadu | <75% | 101 | Doctors, nurses, and pharmacists | Close-ended | Knowledge, Attitude of Pharmacovigilance and ADRs, and practice towards ADRs |
[ |
Ravinadan AP et al | 2015 | Asian J Pharm Clin Res | Cross-section observational study | Davangere, Karnataka | <75% | 102 | Pharmacists | Close-ended | Knowledge, attitude, and practice of pharmacists towards adverse drug reaction (ADR) reporting |
[ |
Panja B et al | 2015 | Indian J Pharmacol | Cross-section observational study | Kishanganj, Bihar | - | 66 | Postgraduate medical students | Open and close-ended | Awareness of pharmacovigilance and ADR reporting |
[ |
Aithal S et al. | 2014 | Int J Pharm Bio Sci | Cross-section observational study | Unspecified | >75% | 42 | Doctors | Open and close-ended | Knowledge, attitude, and practice of ADR reporting |
[ |
Gupta P et al. | 2014 | Mal Res Treat | Cross-section observational study | Assam | <75% | 154 | Health care professional | Close-ended | Knowledge and attitude of Pharmacovigilance Practice |
[ |
Khan SA et al | 2013 | J Nat Sci Biol Med | Cross-section observational study | Indore, Madhya Pradesh | <75% | 68 | Doctors | Open and close-ended | Awareness and knowledge of ADR reporting, attitude and practice of ADR reporting |
[ |
Ahmad A et al | 2013 | Perspect Clin Res | Cross-sectional web-based survey | Unspecified | <75% | 400 | Pharmacists | Open and close-ended | Knowledge, attitude, and practice of ADR reporting |
[ |
Thomas TM et al | 2013 | Int J Pharmacol Clin Sci | Cross-section observational study | Manglore, Karanataka | - | 60 | Doctors | Close ended | Knowledge, attitude, and practice of ADR reporting |
[ |
Choudary AK et al. | 2013 | Internet J Pharmacol | Cross-section observational study | Trichy, Tamil nadu | >75% | 121 | Doctors, nurses, pharmacists | Open and close-ended | Knowledge, attitude and practice of ADR reporting |
[ |
Hardeep L et al | 2013 | J Clin Diagnos Res | Cross-section observational study | Jalandhar, Punjab | <75% | 61 | Doctors | Open and close-ended | Awareness of pharmacovigilance |
[ |
Prakasam A et al | 2012 | Pharm Prac | Cross-section observational study | Hyderabad, Telangana | <75% | 347 | Community Pharmacy | Close-ended | Knowledge about Pharmacovigilance, Perception and practice towards ADR reporting |
[ |
Rehan HS et al | 2012 | Indian J Pharmacol | Cross-section observational study | New Delhi | >75% | 200 | Resident doctors and Nurses | Open and close-ended | Knowledge of adverse drug reactions, attitude and practice of ADR monitoring and reporting |
[ |
Pimpalkhute SA et al | 2012 | Indian J Med Sci | Cross-section observational study | Unspecified | >75% | 84 | Resident doctors | Open and close-ended | Knowledge and attitude towards ADR reporting |
[ |
Kharkar M et al. | 2012 | Perspect Clin Res | Cross-section observational study | Mumbai, Maharastra | >75% | 870 | Medical Practitioners | Open and close-ended | Knowledge, attitude and practice of ADR reporting |
[ |
Upadhaya P et al. | 2012 | Ther Clin Risk | Cross-section observational study | Jaipur, Rajasthan | - | 50 | Postgraduate doctors | Open and close-ended | Knowledge of ADR reporting |
[ |
Desai CK et al. | 2011 | Perspect Clin Res | Cross-section observational study | Ahmadabad, Gujarat | <75% | 260 | Consultants, postgraduates, resident doctors | Open and close-ended | Knowledge regarding ADR reporting system, Attitude and Practice of ADR reporting. |
[ |
Chopra D et al | 2011 | Int J Risk Saf Med | Cross-section observational study | New Delhi | - | 100 | Doctors | Open and close-ended | Knowledge, attitude and practice of ADR reporting and Pharmacovigilance |
Systematic review includes 28 studies, N = 5517; Meta-analysis -18 studies, N = 3187.
* Quality of the study assessed using the "STROBE Statement checklist".
J Nat Accred Board Hosp Healthcare Providers- The Journal of National Accreditation Board for Hospitals & Healthcare Providers; J Evolution Med Dent Sci- Journal of Evolution of Medical and Dental Sciences; Int J Pharmacol Toxicol-International Journal of Pharmacology and Toxicology; Sch J App Med Sci- Scholars Journal of Applied Medical Sciences; Int J Basic Clin Pharmacol- International Journal of Basic and Clinical Pharmacology; Int J Sci Res- International Journal of Science and Research; Nat J Basic Med Sci- National Journal of Basic Medical Sciences; Indian J Pharm Prac-Indian Journal of Pharmacy Practice; Asian J Pharm Clin Res- Asian Journal of Pharmaceutical and Clinical Research; J Adv Pharm Technol Res- Journal of Advanced Pharmaceutical Technology and Research; Perspect Clin Res- Perspectives in Clinical Research; Indian J Pharmacol- Indian Journal of Pharmacology; Int J Pharm Bio Sci- International Journal of Pharma and Bio Sciences; Mal Res Treat- Malaria Research and Treatment; J Nat Sci Biol Med- Journal of Natural Science, Biology and Medicine; Int J Pharmacol Clin Sci- International Journal of Pharmacology and Clinical Sciences; Internet J Pharmacol- Internet Journal of Pharmacology; J Clin Diagnos Res- Journal of Clinical and Diagnostic Research; Pharm Prac- Pharmacy Practice (Granada); Indian J Med Sci- Indian Journal of Medical Sciences.
The number of inappropriate responses was considered for each statement regarding KAP of PV and ADR reporting.
Two statements were used in the assessment of knowledge regarding the awareness of existing PvPI and safety of drugs. Overall, 55.6% (95% CI 44.4–66.9;
Attitude towards reporting ADRs were assessed using two statements. 28.7% (95% CI 16.4–40.9;
To the statement "Had you ever reported an ADR to a PV center" nearly three-quarters (74.5%, 95% CI 67.9–81.9;
Publication bias was not highlighted in any of the 18 studies analyzed. Based on Egger and Begg tests graph confirmed by the funnel plot.
Meta-analysis was stratified based on the quality of the studies (high and low quality) to reveal the KAP concerning PV activities in India. For the statement "Are you aware of the existence of PvPI" the percentage of high-quality studies incorrectly answered 55.3% (95%CI 39.2–71.2) compared to 53.5% (95%CI 37.8–69.1) low-quality studies. Furthermore, sensitivity analysis of the low-quality studies showed a negative attitude of 30.8% (95%CI 10.5–51.1) towards reporting ADRs as compared to the non-stratified groups. However, failure to report ADRs among health professionals was 76.7% (95%CI 64.0–89.3), higher than in the main analysis in high-quality studies.
This systematic review was aimed at assessing the KAP towards PV and ADR reporting in studies conducted in India during January 2011 to July 2015. To the best of our knowledge, this is the first systematic review and meta-analysis on this topic. In 2009, two reviews focused on under-reporting of ADRs [
Our study is the first to execute the KAP of PV activities in India by including 18 studies in meta-analysis. This has helped us gather and strengthen the combination of each study results, providing stronger evidence about ongoing PV activities among Indian health professionals. Our search strategy was comprehensive, including studies published in English, and research using standard questionnaires conducted in India.
We found that more than 50% of the sample were not aware of PvPI and around 32% thought that all drugs available in market were safe (allopathic, herbal/traditional, blood products, biological and medical devices). Although 71.3% were interested in reporting suspected ADRs, 67% did not know where to obtain ADR reporting forms. Indeed, three-quarters of the sample never reported an ADR to any PV centers. Additionally, 40.8% declared that ADR reporting forms were not readily available at their sites to enable ADRs reporting. Overall, we found that more than 40% of the sample have demonstrated inadequate knowledge, attitude and more than half never actually reported an ADR to the PV centers.
The findings of our review identified the lack of knowledge regarding PV and drug safety in India. For instance, nearly 55% of the population answered incorrectly regarding the existence of PvPI in India. This is in agreement with the recent research conducted on 90 ADR monitoring centers working under PvPI which highlighted that 68% of the doctors, 80% of nurses and 81% of the pharmacists are unaware of PvPI in India [
The health professionals’ lack of knowledge regarding safety of marketed drugs could lead to serious drug reactions in patients. Remedies such as allopathic, ayurveda, homeopathy, unani, and other therapies are widely practiced in India. In 2012, the South Asian Association for Regional Cooperation (SAARC) reported that there are more than 4246 herbal drugs registered and available as over-the-counter without restrictions in India [
Further, it was clearly observed that a part of the health professionals (28.7%) were not interested in reporting suspected ADRs. This attitude showcases the passive perception of some of the health professionals ignoring the importance of reporting ADRs. Evidence from various national and international studies suggested that lethargy, diffidence, insecurity and overwork were some of the factors for under-reporting of ADRs by health professionals [
Practice of PV is crucial for generating a national safety database of drugs. Our meta-analysis identified that a majority of the health professionals never reported any ADR encountered during their practice. The average Individual Case Safety reports (ISCRs) received per month by Vigiflow from 12 PV centers during the period of 2011 to 2013 was 48.3 and the rate of spontaneous reporting was only 33.8%. There are manifold hindering factors that need further investigation to understand the barriers influencing the practice of PV. Indeed, it is a difficult task to foster PV practice culture without proper knowledge and attitude. Possible solutions for improving PV practice in India might be implementing strong regulations to report ADRs after providing sufficient training to the health professionals and simplifying the process of ADR reporting using electronic system by giving some amount of financial incentives to health professionals.
This study has some limitations that should be considered. Our meta-analysis showed some heterogeneity with a consistent lack of homogeneity of the responses. This heterogeneity could be due to sociodemographic, inter-professional, and cultural variations among the health professionals across India. Moreover, there were differences in sample selection and the way questionnaires were administered that may lead to selection bias. In addition, questionnaires administered in all studies were open and closed-ended and the population studied may have overestimated or underestimated when responding which may have led to recall bias. Quality assessment and stratification of quality and geographic criteria have allowed the evaluation of the presence of potential bias and confounding. For instance, poor quality could influence the KAP regarding the real function of PV in India.
Our results identified a huge-gap pertaining to KAP towards PV activities in India. The fact that more than 75% of the health professionals never reported an ADR, raises questions on PV activities in India. Educational campaigns and training to improve the knowledge; financial incentives and simplifying the reporting process might change the attitudes. Further, making ADR reporting mandatory can make health professionals aware of the importance of PV in India. In order to better understand the PV progress, PvPI should periodically assess the KAP of health professionals PV activities in India.
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We thank Dr. Raessa Gupte, Ph.D and Dr. Shiri Diskin, Ph.D for their assistance in manuscript editing.