INTRODUCTION

India is also known as ‘the pharmacy of the world’ because of its massive production of generic drugs, therefore, an excellent healthcare system is a must-have, where every healthcare professional knows all possible risks and benefits of a drug, and are well-informed about the importance of monitoring and reporting ADRs to regulate and provide better quality drugs to ensure the safety of every patient [1]. Yet, a study shows that India’s contribution to the global safety database (WHO) is only up to 3%, with a competence score of 0.93 out of 1. The percentage of total admission to hospital due to ADR was 0.7% out of which there is 1.8% death, whereas, in England, 0.9% of total hospital admissions were due to ADR, 1% in Austria, and 3.4-7% in Australia. This report shows that ADR is highly under-reported in India considering its population and status of drug production [2]. However, due to India being a developing country, the importance of implementing Pharmacovigilance services is not well understood by the majority of the people, including healthcare professionals.  Despite its frequent occurrence, ADRs are greatly underreported due to the lack of official culture in its monitoring [3, 4].

Most of the ADRs occur due to medication error, drug interactions, polypharmacy, patient compliance, and sometimes, due to the use of counterfeit or substandard drugs. Unwanted reactions that occur due to deliberate excessive or accidental dosage and maladministration can be considered as adverse events [5, 6]. ADR adversely affects the patient’s quality of life and is believed to occur almost every day in healthcare institutions throughout the country. ADR is one of the leading roots of morbidity, mortality, hospitalization, and increased healthcare costs in many countries [7]. This can be attributed to the lack of a proper Pharmacovigilance system in India. Therefore, robust and pro-active Pharmacovigilance (PV) services are the need of the hour [8].

A formal ADR monitoring was introduced and initiated back in 1986 under the observation of the Drug Controller General of India (DCGI) [3]. They brought a spotlight on the possible adverse impact of prescription medicines and stressed the need for rational prescribing. Thus, after much struggle, the National Programme of Pharmacovigilance (NPP) was established in 2005 which was then changed to the Pharmacovigilance Programme of India (PvPI) in 2010. Currently, there are 250 PvPI established ADR monitoring centers across the country [3, 7]. PvPI aims to protect the health of the Indian people by making sure that the advantages of medicines balance the risks of using them. PV works hard to establish a relationship of trust between the physician and the patients. It not only improves patient safety, but also boosts public confidence in the country's healthcare system and helps discover inferior drugs as well as prescribing, dispensing, and administration problems [9, 10]. However, all of these can be possible only if ADR reporting and monitoring are taken seriously by all; including the healthcare professionals [11, 12]. The information acquired from the research may be valuable in recognizing and reducing unnecessary ADRs, as well as improving healthcare personnel's abilities to control ADRs more effectively in general [13].  Over 20 million Individual Case Safety Reports (ICSRs) have been created and given to WHO-vigibase too far [5]. When we consider that India is home to around 15% of the world's population, this enormous number represents barely 1-2 percent when seen in a global context [7, 8].

The main goal of this study is to strengthen the Pharmacovigilance services in hospitals by undertaking ADR reporting and monitoring by regular passive surveillance of ADR which will create awareness among the healthcare professional of the institution and sensitize them to the importance of ADR detection and monitoring. This will, hopefully, lead to an increase in their engagement and will result not just in the quantification, but also, in an improvement in the ability for precise identification of ADR. The triggered alerts can then be evaluated to guide the kind of clinical interventions required to prevent the emergence of ADR and mitigation of actual ADR.

MATERIALS AND METHODS

Not many reports on incidence of ADRs are available in North Indian hospitals. An Adverse Event Reporting System (AERS) has existed in this tertiary care hospital since 2014 under the supervision of clinical pharmacology department of teaching hospital. The ADR reporting unit of this hospital is one of the state’s ADR monitoring centers (AMC) among 11 centers in the state. This study was conducted for a period of six months from September 2019 to February 2020 at the tertiary care hospital of Haryana state. This is an observational study, based on ADR collected from all the in-patients with suspected adverse drug reactions/side effects from various departments. The study protocol was approved by the Institutional Ethics Committee (IEC) of University with reference no. MMIMSR/IEC/2019 /1561.

Study Design and Patient Criteria

All the patients with suspected and reported ADR or side effects in general medicine, pediatrics, psychiatry, gynecology & obstetrics, and surgery departments were included in the study. Patients treated on an outpatient basis and admitted to intensive care units were not included in the research. All the relevant and necessary data was gathered by patients’ case notes, treatment charts, laboratory reports, interviewing the patient or patient’s caretaker(s), or any other relevant source.

Data Analysis

The reported ADRs were defined and categorized as per the operational guidelines framed by National Pharmacovigilance Programme of India (PvPI). The severity of reaction, onset time, predisposing factors, predictability, preventability, and outcome of the reaction were recorded for every suspected ADR. The identified ADRs were assessed by using Naranjo’s Causality Assessment Scale, which categorizes ADRs into four different categories based on their respective scores i.e, doubtful (score=0), possible (score 1-4), probable (score 5-8), definite (score ≥9), [14].

The severity of the ADRs was also determined through the Modified Hartwig Scale, which classified them as extreme, moderate, or mild [15]. The ADRs' preventability was determined using Schumock and Thornton's criteria, and the ADRs were divided into three categories: possibly avoidable, definitely preventable, and preventable [16]. Each ADR was classed into Type A (augmented) or Type B (standard) according to Rawlins and Thompson's classification (bizarre) [17].

Statistical Analysis

Since the study is qualitative, only the mean and standard deviations are implicated for analyzing the data obtained. The methods that were used to present the information gathered were the use of the number, average ± standard error mean, and percentages.

RESULTS AND DISCUSSION

We analyzed more than 250 patients during a period study period in different wards of a tertiary care hospital. Out of which a total of 52 ADRs were noticed, put down, and reported. People between 19 to 60 years of age (60%) are the majority of ADR patients, followed by 0 to 18years (21%) and the age group above 60 with the least (19%) numbers of ADRs reported. The study revealed that more male patients (64%) were affected compared with females (36%). However, gender was not found to be a predisposing factor for the reactions (Table 1).

The analysis showed that the general medicine department reported the highest number of ADRs (55.76%), followed by the respiratory department (21.15%), and the pediatrics department (15.38%). The departments of obstetrics & gynecology, psychiatry, dermatology, and surgery showed the least report which is less than 2% (Table 2).

According to an analysis of the system involved, the skin was the most affected (38.46%), followed by the gastrointestinal system (23.07%). The involvement of the nervous system was less than 20% (19.23%), followed by the endocrine system (9.61%), and respiratory system (5.76%). Muscular system and miscellaneous was found to be the least involved system with less than 2% each (Table 3).

One day of hospitalization was the least amount of time before ADR development, the median time being 51.63 days, and the maximum time was seven years (delayed reaction due to chronic use of the drug). The reactions that were perceived within two weeks of hospitalization constituted 38.46% of total number of adverse reactions identified in this study. In this study, ATT shows the largest number of ADR (9.61%), followed by ceftriaxone and a combination of piperacillin & tazobactam with a percentage of 7.69%, then vancomycin, acetaminophen, phenytoin, and pantoprazole with 3.84% of ADR. The majority of the drugs which cause ADR were found to be from antibiotics (36.53%), followed by analgesic (9.61%), then antihypertensive drugs with less than 4%. All drugs were prescribed by oral route only (Table 4).

^{* 1}Antituberculer treatment, ²Liver function test, ³Gastrointestina, ⁴Stevens-Johnson syndrome

The occurrence of ADR with respect to the organ system in this study was found to be highest in the skin with a total of 20 ADR reports (38.46%), followed by GIT with 12 ADR reports (23.07%), CNS with 10 ADRs (19.23%), endocrine with 5 ADRs (9.61%), respiratory with 3 ADRs (5.76%), muscular with 1 ADR (1.92%), and miscellaneous with 1 ADR (1.92%) (Table 5).

¹Antitubercular treatment; ²Stevens-Johnson syndrome; ³Gastrointestinal tract, ⁴Central nervous system, ⁵Liver function test, ⁶Miscellanous