|Year : 2022 | Volume
| Issue : 1 | Page : 22-27
Adverse drug reaction monitoring through active surveillance in the inpatients of general medicine ward of a tertiary care hospital
Pooja Roy1, Pratibha Nadig2, CA Jayashankar3
1 Senior Medical Safety Advisor, IQVIA, Bengaluru, Karnataka, India
2 Head of Department of Pharmacology, Dr. Chandramma Dayananada Sagar Institute of Medical Education and Research, Bengaluru, Karnataka, India
3 Head of Department of General Medicine, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India
|Date of Submission||23-Jan-2021|
|Date of Decision||03-Jul-2021|
|Date of Acceptance||25-Aug-2021|
|Date of Web Publication||06-Jan-2022|
Dr. Pratibha Nadig
Chandramma Dayanand Sagar Institute of Medical Education and Research, Devarakaggalahalli, NH-209, Kanakapura Road, Ramanagara - 562 112, Karnataka
Source of Support: None, Conflict of Interest: None
Objective: To monitor and analyze the adverse drug reactions (ADRs) by active surveillance in the inpatients of the department of general medicine of a tertiary care hospital. Materials and Methods: This was a cross-sectional study on the patients aged 18–70 years conducted for a period of 6 months. Patients' medical history, any new symptoms after commencing treatment, and their details were obtained after direct interviews. The case report forms were also reviewed. Suspected ADRs were documented in consultation with the attending physicians. Descriptive statistics was used to analyze the data for the occurrence, relatedness to the drug, seriousness, preventability, severity, intensity, and predictability of ADRs. Results: Fifty-three women and 47 men consented to participate, the majority of whom were between the ages of 20 and 30 years. Thirty suspected ADRs were detected in 24 out of 100 patients. The most common indications for which the drugs were prescribed were depression, psychosis, bipolar disorder, atopic dermatitis, and cervical spondylitis. Of the 30 ADRs, 28 were probably related, and 2 were possibly due to the prescribed drugs. Seven ADRs were serious in nature. Four ADRs were definitely preventable, seven were probably preventable, and nineteen were not preventable. Maximum ADRs were caused by immunosuppressants including steroids. Dermatological reactions were the most common manifestations of ADRs followed by that of central nervous system. There were four rare ADRs, namely, escitalopram-induced duodenitis, phenobarbitone-induced pancytopenia, quetiapine-induced thrombocytopenia, and aripiprazole-induced ocular gyrus syndrome. ADRs were mostly mild to moderate in intensity. Conclusion: Monitoring the ADRs through active surveillance is helpful to get a detailed information and to detect rare ADRs.
Keywords: Active surveillance, adverse drug reactions, causality assessment, pharmacovigilance, serious adverse drug reactiona
|How to cite this article:|
Roy P, Nadig P, Jayashankar C A. Adverse drug reaction monitoring through active surveillance in the inpatients of general medicine ward of a tertiary care hospital. APIK J Int Med 2022;10:22-7
|How to cite this URL:|
Roy P, Nadig P, Jayashankar C A. Adverse drug reaction monitoring through active surveillance in the inpatients of general medicine ward of a tertiary care hospital. APIK J Int Med [serial online] 2022 [cited 2022 May 26];10:22-7. Available from: https://www.ajim.in/text.asp?2022/10/1/22/335085
| Introduction|| |
An adverse drug reaction (ADR) is a “harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product, which predicts hazard from future administration and warrants prevention or specific treatment, or alteration of the drug regimen, or withdrawal of the product.” About 70% of the ADRs are preventable and may occur due to medication errors. Monitoring of ADRs helps in prevention. It also helps detect new and unexpected ADRs not detected during clinical trials. Monitoring, detecting (diagnose), understanding, and reporting constitute pharmacovigilance.
Pharmacovigilance encourages the physicians to voluntarily report ADRs that helps the drug regulatory authorities to take the necessary actions for the safe use of medications. However, there is underreporting by the physicians. Active surveillance involves detection of ADRs either by review of the case files or direct patient interviews. This method generates more ADRs and collects a more detailed information. Very few studies can be found in literature, where active surveillance was adopted to monitor ADRs, particularly in India. Hence, this study was undertaken to determine the incidence, the profile, relatedness (causality), the seriousness, and preventability of ADRs in the inpatients of the department of general medicine by active surveillance.
| Materials and Methods|| |
Study design, study population, and setting
This was a cross-sectional, observational study, conducted over a period of 6 months (July 2014 to December 2014). The study commenced after the approval of the institutional ethics committee. Patients above 18 years of age hospitalized in the department of general medicine with any complaint and willing to provide written informed consent for the interview were included in the study.
A resident doctor from the department of pharmacology, associated with the hospital's ADR monitoring center, screened 200 inpatients for eligibility. Direct patient interviews were conducted using a structured questionnaire pertaining to the medical condition, the treatment received, new complaints seen after the initiation of treatment, any previous reactions, concomitant illnesses, coadministered drugs, etc., In addition, the physicians' notes, nurse's notes, and the investigation reports were also reviewed in the case report form. The suspected ADRs were documented in consultation with the attending physicians.
The ADRs were evaluated for the incidence as percentage of reactions. The severity and causality (relatedness to the drug) assessment and whether they were serious or nonserious were analyzed based on the World Health Organization (WHO) guidelines. The reaction was considered as mild if the symptoms did not interfere with the day-to-day activities. It was severe if it had to be managed with intervention and affected the day-to-day activity. Moderate degree was when it was between the two. An ADR was considered serious if it caused or prolonged hospitalization, was life-threatening, or resulted in disability. The WHO categorization of causality assessment was based on several factors such as whether it appeared after the drug started, could be explained by any other alternative causes, and whether such reactions were known in the past with this drug or the class of the drug. Accordingly, the causality is categorized as certain, probable, possible, and unlikely. The ADRs were analyzed for preventability using modified 'Schumock and Thornton scale. Further, predictability was also evaluated using standard literature. ADRs were considered unexpected if they were not as per what was reported in the company product profile and/or not published in the literature.
The data were analyzed as descriptive statistics as means and proportions.
| Results|| |
A total of 200 patients admitted to the department of general medicine were screened. Among them, there were some who were not able to understand the questions and/or unwilling to cooperate (and consent). Hence, a total of 100 patients who consented to participate were interviewed.
Demographics and profile of the participants
Majority of the patients were between 20 and 30 years of age. The mean (standard deviation) age of the patients was 28 ± 5.3 years; the age range of the patients who were interviewed was from 18 to 81 years. Of the 100 patients, 53 were women and 47 were men. There were 56 patients with type 2 diabetes, 18 with hypertensive, 13 with hypercholesterolemia, 7 with chronic kidney disease, 4 with hypothyroid, and 2 with iron-deficiency anemia. The indications (primary diagnosis) for which the suspected drugs causing ADRs were prescribed are summarized in [Figure 1]. Psychiatric disorders (depression, psychosis, and bipolar disorder) were the most common diagnoses.
Incidence of adverse drug reactions
Thirty adverse events suspected to be due to a drug were detected in 24 out of 100 patients, accounting for an incidence of 24%, considering the number of patients as the denominator for calculating the incidence. Among these, 7 were hospitalized for the adverse event itself, whereas the remaining 17 had developed the ADR during the hospital stay.
Causality assessment of adverse drug reactions
[Table 1] gives the comprehensive review of the ADRs observed, suspected drugs involved, the indications for which they were used along with their comorbidities, and the causality assessment. As per the WHO criteria, no reaction was considered “definitely related” to drug as the dechallenge (discontinuation of the drug) and rechallenge (reintroduction of the drug) was not done. Hence, 28 out of 30 reactions were only “probably related” to the suspected drugs. There were 2 ADRs that were “possibly related.” Seven patients who developed ADRs had comorbidities as shown in [Table 1].
|Table 1: Profile of Adverse drug reactions, associated co-morbidities and the causality assessment|
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Seriousness, severity, preventability, and predictability of adverse drug reactions
Seven of 30 ADRs were serious in nature and the remaining were nonserious. 93% (28/30) of ADRs were expected, whereas 7% (2/30) of ADRs were unexpected [Table 1].
Seventy percent (21/30) of ADRs were mild and 27% (8/30) were moderate in intensity and there was one (3%) severe ADR. Four of the 30 ADRs (13.3%) were definitely preventable, 23% (7/30) were probably preventable, and 77% (19/30) were not preventable. Fifty-seven percent (17/30) of ADRs were predictable. [Table 2] indicates the profile of ADRs in terms of intensity, preventability, and predictability.
|Table 2: Intensity, Preventability and predictability of adverse drug reactions|
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Causative suspected drugs
It was observed that of the 30 ADRs, maximum numbers were caused by immunosuppressants including steroids (26.26%), followed by chemotherapeutic agents, including antitubercular drugs (20%) [Figure 2]. The least number of ADRs were caused by antihypertensive and nonsteroidal anti-inflammatory drugs (NSAIDs) (6.66% each). The most commonly affected organs/organ systems were skin followed by the nervous system.
|Figure 2: Pharmacological classes of suspected drugs implicated in adverse drug reactions|
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Twenty-six ADRs were already diagnosed and recorded in the patient's case report form, but only 20 were reported. Four rare ADRs were detected by active surveillance in consultation with the treating physician. These were escitalopram-induced duodenitis, phenobarbitone-induced pancytopenia, quetiapine-induced thrombocytopenia, and aripiprazole-induced ocular gyrus syndrome [Table 1]. Out of these, escitalopram-induced duodenitis and oral prednisolone-induced depigmentation were considered as unexpected reactions.
Escitalopram-induced duodenitis was observed in a young male patient aged 40 years who had recurrent pain abdomen for 3 years. He was managed by pantoprazole. His endoscopy revealed duodenitis. On enquiry, we found that all the symptoms had started after he started consuming escitalopram before which he was normal. He was a nonalcoholic and a nonsmoker. The dose of escitalopram was gradually tapered after which there was an improvement in his symptoms. Therefore, it was suspected to be duodenitis and “probably related” to escitalopram. We could not consider this as “definitely related” to the drug as no rechallenge was done.
| Discussion|| |
It is not possible to detect the adverse effects of any medication at the time of introducing it in the market even after rigorous premarketing clinical evaluation, as the trial may either not include a large enough population missing out on the rare ADRs or the trial may not be of sufficient duration (delayed ADRs remain undetected). Hence, there is a need for continued monitoring of the ADRs for the prescribed drugs. This can be achieved by active and passive surveillance, stimulated reporting, conducting comparative observational studies, and randomized controlled clinical trials. The Pharmacovigilance Programme of India, under WHO and the Ministry of Health and Family Welfare, Government of India, encourages voluntary reporting of ADRs by the health-care professionals. The reports are analyzed to take certain regulatory actions such as change in the labeling, withdrawal, or banning the drugs. However, the rate of voluntary reporting is very low because both the physicians and patients may not be aware that a particular symptom could be an ADR. Hence, active surveillance methods are found to be useful.
Further, there is a need to bring awareness on ADR monitoring per se. Many of the ADRs go unnoticed if they are not actively enquired into. In this study, since every patient was monitored individually and in detail, we were able to detect more number of reactions as well as the rare and unexpected reactions. Through this exploratory study, we emphasized the need to include ADR monitoring through questioning as a part of clinical management process.
Successful implementation of active ADR surveillance was achieved through the present study. ADRs were reported in 24% of patients. In the previous studies, the results of stimulated spontaneous or voluntary reporting showed an incidence of ADRs approximately as 15%, which is lower than that reported in our study. Our own experience with stimulated spontaneous reporting has shown an incidence of <1% over 6 months of time. It is a known fact that spontaneous or even intensified spontaneous reporting can detect less number of ADRs as compared to active surveillance programs. Various probable reasons for this disparity could be lack of awareness among the physicians, lack of willingness to report, or even poor communication by the patient in explaining their symptoms. Our study showed thirty ADRs in 24 patients; 17 patients had developed ADR during hospitalization, while seven patients were admitted due to the ADR itself. A similar study reporting ADRs in medical ward, by Wu et al., had reported 41 ADRs in 38 patients. In contrast to our study, they reported that 18/41 ADRs had occurred during hospitalization, and 23/41 (majority) ADRs were the reason for hospitalization.
Our study also showed that maximum ADRs were seen with the use of immunosuppressants including steroids (26.26%) followed by antimicrobial chemotherapeutic agents (20%), whereas NSAIDs and antihypertensive caused the least number of adverse reactions. This cannot be generalized because the offending drugs and reactions caused by them depends on the time of data collection which is subject to change. A study by Yun et al. has stated chemotherapeutic agents as the most common causative agents for ADRs reported by active surveillance, while opioids, antimicrobial chemotherapy, and contrast media were implicated as the most common drugs causing ADR in spontaneous (voluntary) reporting. Swamy et al. and Bhabhor et al. have also reported antimicrobials to be the most common agents causing adverse reactions in the voluntary reporting system.,
Skin was the most commonly affected organ system (25%), which was comparable to the study carried out by other studies too.,, The WHO causality scale was used to find the causal relationship between the drugs and the observed ADRs, of which 28 were probably related (85.4%) and two were possibly related (6.67%). Some were close to be termed as definitely related such as pancytopenia with phenobarbitone because the reaction reversed on stopping the medication. However, since reintroducing the drug was not possible due to ethical reasons, we could not classify under “definitely” related to the drug. Different proportions have been reported in literature, including Patidar et al. who reported 3.12% of reactions as definitely related; 50%, probably related; and 46.87%, possibly related. Similarly, Swamy et al. reported 51% reactions, probably related, and 49% reactions, possibly related.
Evaluation of the ADR seriousness was done with the help of WHO scale. Our study reported more number of serious reactions compared to the voluntary reporting by Swamy et al. However, Yun et al. after comparing the active surveillance program to spontaneous reporting have reported that active surveillance programs are able to detect additional serious adverse reactions.
Majority of the reactions in our study were nonpreventable similar to Bhabhor et al., who reported a minor percentage of ADRs (8.10%) as preventable. Two-thirds (63.33%) of the reactions were predictable, similar to Roy et al. who reported 90% of spontaneously reported ADRs to be predictable. As reported by others, majority of the ADRs (70%) were mild to moderate in severity.
The study helped detect some of the rare and unexpected ADRs such as escitalopram-induced duodenitis and oral prednisolone-induced skin depigmentation. There are reports that the use of selective serotonin reuptake inhibitors increases the risk of upper gastrointestinal bleeding. However, we did not find the report of escitalopram-induced duodenitis. Hence, it is an unexpected reaction. Similarly, oral steroids are used to treat vitiligo and are rarely reported to induce depigmentation. In this study, oral prednisolone was used to treat atopic dermatitis-produced depigmentation. This was another finding in our study. The rationale for the use of prednisolone in this condition was immunosuppression. Further exploration is required to evaluate the mechanisms of depigmentation caused by oral steroids.
Active surveillance, thus, appears to be a powerful tool for the detection of ADRs in the current scenario as gross underreporting is observed by voluntary reporting system in majority of hospitals. It enables for the compilation of standardized, detailed, and quality data pertaining to ADR reporting, which is considered to be critical for the assessment of risk and benefit associated with the suspected drug entity. Thus, specific drug safety information can be obtained very efficiently and in a relatively short span of time.
Although our results are more or less similar to published analysis of spontaneously or actively reported ADRs, in conjunction with active surveillance reports, our surveillance was able to detect more number of ADRs, serious ADRs, and unexpected rare ADRs as compared to spontaneously reported ADRs. Unexpected ADRs are the ones which are not described under the summary of product characteristics by the company or the drug regulatory authority and rare reactions are those which occur in less than one in one thousand population. This emphasizes the significance of this study. However, this method requires manpower and financial support. At times, there is a difference of opinion in suspicion of an ADR between the pharmacologist and the physician.
Despite the above limitations, the authors recommend active surveillance as a better method for reporting for the advantages mentioned earlier. There is a need to bring awareness on ADR monitoring per se among the treating physicians as many ADRs go unnoticed. Through this exploratory study, we have intended to emphasize the need to include ADR monitoring through questioning as a part of clinical management.
| Conclusion|| |
Adverse drug reactions occur quite commonly. They must be given due importance in the clinical management of any disease. Physicians must enquire for known and unknown reactions. If detected they should be reported with all the details to the Pharmacovigilance centres. Such an activity will help to prevent the ADRs further.
It was a broad-based generic exploratory study including patients of all categories and indications. The outcomes were analyzed using descriptive statistics. However, the study leads to development of some research hypothesis that can be studied.
There was no follow-up till the ADR resolution. Disease-specific or drug-specific active surveillance could yield more information that will be statistically more relevant.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]