Understanding Issues and Awareness towards Reporting of Adverse Drug Reactions in India amongst Practicing Oncologists

Dr. Shailaja Hanumandla *¹; Dr. Kaushal Kapadia²

1 Texila American University.

2 Clinical Research Professional.

*Correspondence to: Dr. Shailaja Hanumandla, Texila American University.

Copyright

© 2025 Dr. Shailaja Hanumandla. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 27 March 2025

Published: 03 April 2025

ABSTRACT:

Introduction: Adverse drug reactions (ADRs) pose a significant public health challenge, especially in oncology, where high-risk medications are frequently used. Despite the critical role of ADR reporting in safeguarding patient safety, underreporting remains a persistent issue in India. This study aims to explore the factors contributing to the underreporting of ADRs in oncology within India, focusing on the perceptual differences between rural and urban oncologists and patients.

Aim of the Research: The primary objective of this study was to evaluate the perceptions of oncologists regarding ADR reporting in both rural and urban India. The study seeks to identify the factors leading to the underreporting of ADRs in oncology, compare the perceptions of oncologists in rural versus urban settings, and assess their awareness and knowledge about the importance of ADR reporting.

Methodology: This research will utilize a qualitative survey-based approach, involving oncologists and patients from both rural and urban areas. Data collection methods will include questionnaires and interviews, with data analysis conducted using Microsoft Excel.

Conclusion: This study holds significant implications for patient safety and healthcare quality in India. The findings will aid in developing strategies to enhance ADR reporting in oncology, particularly in rural regions. Additionally, the study will inform policy makers and regulatory authorities about the necessity for training and infrastructure improvements to support ADR reporting. Furthermore, it will contribute to the existing body of literature on ADR reporting in low- and middle-income countries, offering insights into the challenges and opportunities for improving patient safety and drug development.

Introduction

Adverse Drug Reactions (ADRs)

Substances that have the potential to be helpful might potentially have unintended or negative side effects. The risk of these side effects varies from zero, as with nystatin and hydroxocobalamin, to significant, as with immunosuppressive or antitumor medications. Any unintended, unpleasant side effect of a medication that arises during routine therapeutic usage is known as an adverse event ADR has most commonly been defined as ‘a response to a drug that is noxious and unintended and occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for modification of physiological function’ (WHO, 1972). The World Health Organization's (WHO) 1972 study on international drug monitoring gave rise to this definition, which has remained mostly constant since then. The Oxford English Dictionary defines "noxious" as "injurious, hurtful, harmful" however, this meaning is ambiguous in its use; for instance, encompasses all negative reactions, regardless of their minimal severity. The existing surveillance techniques would be defeated by such inclusivity. Therefore, several other definitions have been proposed. Laurence, for instance, defines a harmful or significantly unpleasant effect caused by a drug at doses intended for therapeutic effect (or prophylaxis or diagnosis) which warrants reduction of dose or withdrawal of the drug and/or foretells hazard from future administration (Laurence, 1988). This definition expressly excludes minor unwanted reactions. These definitions, however, do not include error as a cause of negative consequences. Additionally, they do not include reactions brought on by impurities or purportedly inactive excipients in a mixture. Others have used the notion of "an injury resulting from medical intervention related to a drug" to adverse occurrences (Bates et al., 1995). However, there are other issues with this definition. For example, there is no reason why an intervention should always be medical in order to have a negative effect, and the terms "injury" and "medical" are unclear. Therefore, an alternative definition of adverse responses was proposed by Edwards and Aronson (2000), “An appreciably 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 dosage regimen, or withdrawal of the product”. 

Adverse Drug Reactions in Cancer Treatment

ADRs appear to be 4th to 6th leading cause of death of patients. The impact of ADRs on patients can lead to a decline in their quality of life, an increase in hospital admissions, financial strain on healthcare management, and a higher mortality rate. Antineoplastic agents with a narrow therapeutic index are more toxic to cells and can harm both healthy and cancerous cells. Patients undergoing anticancer treatment are at an elevated risk of experiencing ADRs due to the use of multiple drugs. Considering the Indian landscape, the prevalence of ADRs from anticancer drugs is estimated to be 10-12%. Elderly and hospitalized patients (16.6%) are more likely to experience ADRs compared to the adult population (4.1%). (Datta et al 2021; Kirthi et al 2014). Monitoring of adverse drug reactions has become crucial in detecting uncommon and potentially serious ADRs, thus ensuring patient safety as these reactions are inevitable. Survival rates have increased due to recent advancements in anticancer agents, but cancer and its treatment can still have a deteriorating impact on patients both physically and psychologically. The adverse effects commonly associated with anticancer treatment include alopecia, bone marrow suppression, nausea and vomiting, infections, and pain among other issues. In addition to physical effects, some patients may also experience depression, anxiety, and sexual dysfunction, leading to a diminished quality of life. Taxanes, platinum compounds, alkylating agents, and anticancer antibiotics are among the common drugs known to cause ADRs. (Datta et al., 2021; Sharma et al., 2018).

Underreporting of ADRs

In the past few years, developments and advancements have been rapid in the field of ADR monitoring at the global level. PvPI provides a continuous monitoring system to collate post-marketing monitoring data and use the inferences to provide regulatory procedural recommendations and spread awareness to healthcare professionals (HCPs) and the public. Despite releasing periodically updated detailed guidance documents for pharmacovigilance and active and passive reporting including spontaneous reporting processes under the PvPI, underreporting of ADRs is a major problem in India (Mulchandani et al., 2018). In the 2020 review by Dutta et al. the leading causes of underreporting have been underlined.

The factors listed below were highlighted:

a. Lack of proper knowledge of pharmacovigilance such as the difference between an ADR and a side effect (adverse event).

b. Unawareness of regional reporting centers and contact information.

c. Unavailability of reporting forms at the treatment site viz. hospital, nursing home, health center, specialty clinic, etc.

d. Identifying an ADR and determining the suspected drug while distinguishing the influence of other drugs and disease processes posed a challenge.

e. Unpreparedness of systems such as passive monitoring systems based on regulations do not offer practical support in interpreting potential adverse drug reactions, leading to many cases being overlooked.

f. Personal aspiration Factors: Physicians may choose not to report ADRs due to a lack of incentives or they prefer to collect the data and publish it themselves.

g. Fear factors: Doctors acknowledged that they sometimes fail to report adverse reactions out of concern for legal repercussions, potential labeling as negligent, and fear of admitting to causing harm to patients.

h. Complacency factor: There is a perception among healthcare professionals that only safe drugs are available in the market, and therefore, a single report of an adverse effect would not make a significant impact.

i. Lack of time: Healthcare professionals have mentioned that the ADR reporting forms are often complex, making the reporting process time-consuming.

j. Expectation of incentives was also seen as a causative factor in the underreporting of ADRs among a few clinicians.

k. Patients and/or caregivers often lack awareness about the drug safety system and feel uncertain about how and where to report adverse events. Multiple companies have begun utilizing social media platforms to gather information on adverse events disclosed by consumers. Yet, social media is not a recognized source for reporting ADRs.

l. Lack of understanding in patients about the significance of ADR reporting and its potential impact on their well-being, while they are they are typically more focused on receiving treatment for the ADRs rather than reporting them.

According to the recent turn of events in the country, regulatory clearance for selling pharmaceutical products in India is now possible for companies if their new drugs provide a "significant therapeutic advance over the current standard of care", though the scientific evidence did not suggest a potential difference of tolerance in Indian population, and have been approved by regulators in any of the specified six countries or regions. (Report by Dutt Anonna, 2024) The United States of America, United Kingdom, Japan, Australia, Canada, and the European Union, are the mentioned countries, in the order passed by the Drug Controller General of India (DCGI) on 7th August 2024, all of which are recognized for their stringent regulatory approval processes. However, it is important to note that Phase IV clinical trials will be required for these medicines. These trials will assess any side effects that were not observed in earlier trials and might also evaluate the long-term effectiveness of the new treatments. Although the move is meant to ensure early access to tested cutting-edge therapies for rare diseases and cancers with specific genetic markers, it buttresses the need to reinforce the ADR reporting practice.

One major instrument for tackling such ADRs has to be spontaneous reporting of such incidents. One of the best ways to generate signals about unexpected and uncommon ADRs is for health professionals to spontaneously report suspected ADRs, evaluate them, and then add them to databases. This allows for continuous determination of the benefit-risk ratio of a particular medication. However, since only 6% of all adverse reactions are thought to be reported, underreporting is a significant drawback of spontaneous reporting systems (Hazell & Shakir 2006). This high percentage of underreporting has two effects: on the one hand, it makes it impossible to quantify risk; on the other hand, it causes an undue delay in the triggering of alert signals, which has consequences for public health. Such consequences can have larger impacts in the case of patients undergoing chemotherapy.  To help patients and physicians be vigilant before and throughout treatment, certain ADRs associated with chemotherapy are thoroughly defined, categorized, and risk-stratified. Less research has been done on the prevalence and effects of polypharmacy, multimorbidity, and non Systemic Anti-Cancer Therapy (SACT) related ADRs in cancer patients, especially as variables that contribute to acute hospitalization. Thus, there is a substantial knowledge gap regarding (a) the frequency of medication use and multimorbidity in patients who are seen at a specialty cancer center and (b) the frequency, causality, predictability, and preventability of ADRs that result in or contribute to hospitalization. The thesis work presented here delves deep into the problem and attempts to gain significant insight to better understand the instances of oncological ADR underreporting and the factors behind such cases.

Methodology

The research project was carried out using a survey-based model. Initial data collection was done using a validated questionnaire for the clinical experts in oncology. The primary approach involved interviewing oncologists using an objective multiple-choice qualitative questionnaire regarding the attitude and practice-related areas of reporting of ADRs to anti-cancer drugs as per PvPI guidelines using objective multiple-choice qualitative questions. The questionnaires were developed by using the literature review performed and in adherence to the 5-point Likert scale type rating system. The main focus of the questionnaire was to understand factors contributing to the underreporting of ADRs in oncology in urban and rural India.

The collected data was tabulated and graphically presented. Percentage comparison was used as the basis of analysis of the responses in both sets of participants. The tool used to conduct the percentage comparison in both sets of data was Microsoft Excel version 2016. The charts were directly created from the graduated (statistically compared) data in Microsoft Excel.

For hypothesis testing between the two different groups of doctors coming from urban and rural regions, a two-tailed type 3 t-test was performed. In order to do the test the percentage composition values were used to remove any bias due to sample size. As it was a survey, only the value for the option having the highest percentage of responses was chosen from the list of options available for each question.

Results

The conducted survey included a total of 96 oncologists; 48 each from urban and rural centres of cancer treatments. The survey questionnaire was designed to check their awareness of ADR reporting procedures in India, the first question of the survey asked if they were aware of the Pharmacovigilance Programme of India (PvPI). The response was majorly negative, with 66.7 % of urban oncologists saying ‘no’, and 85.4% of rural oncologists saying the same.

Figure 1:  Awareness of the PvPI program among oncologists from (a) urban and (b) rural areas

In the second question, the participating oncologists were asked, if they had ever reported any ADR to PvPI, 70.8% of urban practitioners responded in negative, while 81.2% of rural doctors chose the same. When the doctors were asked if they believed in the importance of ADR reporting as a tool to ensure patient safety, majority of urban (56.2%) and rural (60.4%) participants agreed to the statement, along with oncologists who chose to ‘strongly agree’ to it.

Figure 2:  Previous experience of reporting ADRs to the PvPI program among oncologists from (a) urban and (b) rural areas

Figure 3:   Importance of ADR reporting among oncologists from (a) urban and (b) rural areas

When the doctors were asked, if they had received proper training for ADR reporting, only 12.5 % of urban doctors said ‘yes’, while not a single oncologist practicing in rural India stated that they had been given any training for that. However, when they were asked if they were confident in their own ability to report ADR, all urban doctors stated that they were. The responses from rural doctors were more divisive with 43.7% stating ‘yes’ and 56.2% stating ‘no’.

Figure 4:  Received training for ADR reporting among oncologists from (a) urban and (b) rural areas

Figure 5:  Confidence in reporting ADRs among oncologists from (a) urban and (b) rural areas

The participating doctors were then asked if they thought sufficient time was allocated for ADR reporting. There was a clear difference of opinion between urban and rural doctors. 60.4% of urban doctors stated that the time was not sufficient, while all rural doctors stated that there was enough time on hand.  When the oncologists were asked if they had faced any barriers while reporting ADRs from cancer patients, the majority of the doctors from both urban (83.3%) and rural (100%) stated that they had not faced any such barriers.

Figure 6: Availability of Time for ADR reporting among oncologists from (a) urban and (b) rural areas 

Figure 7: Facing Barriers to reporting ADRs among oncologists from (a) urban and (b) rural areas

The doctors were then asked to select the barriers that they had faced while reporting ADRs. The most popular option chosen by both urban (58.3%) and rural (100%) doctors was the complexity of reporting forms. Among urban doctors, this was followed by ‘Lack of feedback from reporting authorities’ (43.7%) and ‘Lack of time’ (37.5%). In the case of rural doctors, the second most chosen option was, ‘Lack of knowledge on how to report’ (100%) and Lack of institutional support (81.2%).

A two-tailed, type 3 t-test was performed to check for significant differences between the urban and rural oncologists with respect to their responses to the survey questionnaire. The calculated p-value was 0.54, which was greater than the 95% level of significance (p ≥ 0.05). Hence, based on this statistical test the null hypothesis is accepted. There was no significant gap in perception of the underreporting of ADRs to anti-cancer drugs among oncologists practicing in rural areas and oncologists practicing in urban areas

Discussions

When surveying the responses of oncologists from rural and urban regions of India, one can see the subtle difference in the knowledge based on the location of their medical facilities. Although the statistical testing in the present survey failed to identify any significant difference between the urban and the rural oncologists, yet there were subtle differences among their responses that cannot be overlooked. In this section, the discussion focuses on such differences that were apparent by observing the survey responses. This was evident in their awareness of ADR reporting procedures in India as well. In the present survey, the majority of the specialists across urban and rural centers stated that they were unaware of the ADR reporting procedures to the PvPI. The number of negative responses from rural oncologists was far greater than their urban counterparts in this respect. The pharmacovigilance program of India (PvPI) was designed to provide a robust nationwide platform for ADR reporting. However, its effectiveness is dependent on the willingness of the doctors working in the field to report ADRs. In the current investigation, it was revealed that the number of ADR reporting through PvPI was more in urban practitioners when compared to their rural counterparts. In a previous survey carried out by Bhatia et al. back in 2005 of the doctors residing in the urban heartland of Delhi, a similar lack of awareness was noted. Therefore, it cannot be stated that the condition has improved much in the last twenty years. 

The more perplexing insight that was revealed during the present study was when the doctors were asked - if they believed that ADR reporting was important for patient safety, just above 50% of the participating urban doctors and 60% of the rural doctors believed this to be important, which is much below what can be expected from the medical fraternity. This lack of awareness regarding ADR and its importance points towards the lack of knowledge regarding the issue among practitioners. The doctors themselves admitted to the lack of proper training.  Only about 12% of urban doctors said that they had received some sort of training for reporting ADRs, but no such training was made available to rural practitioners as per their response. Despite the lack of training, all urban doctors were highly confident in their ability to report ADRs. This confidence was, however, lacking in the case of rural practitioners. The lack of training combined with a misplaced sense of confidence on the grassroots level can in the future affect the success of the PvPI program. So care must be undertaken to ensure that proper training is provided to all medical practitioners, irrespective of urban or rural location.

While considering the role of doctors in ADR reporting, one should not overlook the busy schedule that doctors go through each day. India is the world's largest population bearing country. Therefore, often there is immense pressure on doctors, irrespective of whether they provide their services in rural or urban areas. Therefore, any reporting activity often becomes a question of time availability. In the present study, when the doctors were asked if they thought that there was sufficient time allocated for ADR reporting, there was a clear difference of opinion between urban and rural doctors. The majority of urban doctors believed that they did not have enough time to conduct such additional tasks, while the majority of the rural doctors stated that time was sufficient. This difference regarding the availability of time can stem from the difference in patient care available in the two types of centers. As discussed previously patients from rural areas often preferred urban centers for their treatment. This can be a causative factor behind the higher patient load in urban medical facilities. The tendency of rural health centers to refer patients to urban centers can also play a major part in this respect. Such practices can limit the time available to urban doctors for additional duties and act as a barrier to ADR reporting.

Conclusion

The present study was undertaken to understand the perception difference in ADR reporting among oncologists in urban and rural India. The study also aimed to understand the factors influencing ADR underreporting and to address the present knowledge gap. The research problem focused on understanding the perspectives, and practical barriers that lead to underreporting of ADRs to anti-cancer drugs in urban and rural clinical setups. The investigation explored the challenges, limitations, and potential areas of improvement in methods, willingness, feasibility, and facilities of ADR reporting in an appropriate manner and frequency. The study comprised of a multiple-choice qualitative questions which were asked to the oncologists on the current knowledge, attitude, and practice related areas of reporting of ADRs to anti-cancer drugs as per PvPI guidelines and perception of appropriate ADR reporting.

The investigational questions were categorized into different sections to understand the various aspects of ADR reporting; awareness of the ADR process, awareness of the current regulations and requirements, experience of ADR reporting, institutional training and support, and individual perceptions and beliefs.

The data collected from the oncologists revealed that there is a general lack of awareness and lack of understanding of ADR reporting, both in urban and rural India. It was appalling to see even a majority of the oncologists who are the healthcare experts, were oblivious of ADR reporting requirements and the process. The percentage of lack of awareness was higher among rural oncologists, which could be due to a lack of training, resources, facilities, and infrastructure to support them. There were different types of challenges listed by the oncologist, which contributed to the underreporting of the ADRs.  For India’s PvPI program to be successful, these issues must be dealt with as soon as possible.

The survey provided core information about gaps in the understanding and awareness of ADR reporting according to the current guidelines and regulations among oncologists. In the future, further aid in identifying these barriers that help in enforcing standardization of reporting, enhancing the facilities to improve reporting practice in rural and urban clinical setups, and implementing its importance to the Regulatory Authorities (CDSCO) is necessary.

The current study increased the awareness of identifying further bottlenecks and limitations of the current industry practices. It has opened the arena to explore different methods to increase awareness among the medical fraternity and the general public, and also look into possibilities of providing effective customized training. The current process of ADR training is not fully effective; one blanket approach to training of ADR reporting is not working due to various factors that affect the perception and understanding of individuals. It is encouraging to see both oncologists' and patients' willingness to get trained and informed about the drugs, their side effects, and the reporting process so they can help others.

This study holds significant implications for patient safety and healthcare quality in India. The findings will aid in developing strategies to enhance ADR reporting in oncology, particularly in rural regions. Additionally, the study will inform policymakers and regulatory authorities about the necessity for training and infrastructure improvements to support ADR reporting. Furthermore, it will contribute to the existing body of literature on ADR reporting in low- and middle-income countries, offering insights into the challenges and opportunities for improving patient safety and drug development.

To conclude, these changes will benefit the patients as well as the pharmaceutical industry in the coming times.

References

1. World Health Organisation. International drug monitoring: role of national centres. Technical Report Series No. 498. Geneva: World Health Organisation, 1972: 1–25.

2. Laurence DR, Carpenter J. A dictionary of pharmacology and allied topics. (No Title). 1998 Jul.

3. Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi D, Laffel G, Sweitzer BJ, Shea BF, Hallisey R, Vander Vliet M. Incidence of adverse drug events and potential adverse drug events: implications for prevention. Jama. 1995 Jul 5;274(1):29-34.

4. Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. The lancet. 2000 Oct 7;356(9237):1255-9.

5. Datta S., Zosangpuii, C., Ningthoujam, G., Paonam, S.D., Leisangthem, T.D., Nameirakpam, M.D., & Nameirakpam, S.S. A Retrospective Study on Adverse Drug Reactions of Anticancer Drugs in a Tertiary Care Hospital in Northeast India. Journal of Clinical and Diagnostic Research. 2021; Nov, Vol-15(11): FC01-FC05.

6. Kirthi C, Afzal A, Reddy M, Ali SA, Yerramilli A, Sharma S. A study on the adverse effects of anticancer drugs in an oncology center of a tertiary care hospital. Int J Pharm Pharm Sci. 2014;6(2):580-3.

7. Sharma, P.K., Misra, A.K., Gupta, A., Singh, S., Dhamija, P., & Pareek, P. A retrospective analysis of reporting of adverse drug reactions to oncology drugs: An experience from a national center of clinical excellence. Indian Journal of Pharmacology. 2018; 50(5), 273 - 278.

8. Mulchandani, R., Kakkar, A.K.. Reporting of adverse drug reactions in India: A review of the current scenario, obstacles and possible solutions. The International journal of risk & safety in medicine, 2018;30 1, 33-44.

9. Dutt Anonna. India’s regulator allows faster access to drugs approved globally: Why this can bring down cost, get you closer to emerging therapies. Indian Express: India Edition Online. 12 August 2024. Available from: https://indianexpress.com/article/health-wellness/new-drugs-cancer-weight-loss-alzheimer-faster-globally-9503358/. Last accessed: 15 September 2024.

10. Hazell L, Shakir SA. Under-reporting of adverse drug reactions. Drug safety. 2006 May;29(5):385-96.

11. Bhatia A, Kapoor U, Tayal G. A survey of issues regarding ADR and ADR reporting amongst doctors in Delhi. International Journal of Risk & Safety in Medicine. 2005 Feb;17(1-2):39-46.