Understanding Issues and Awareness towards Reporting of Adverse Drug Reactions in India from Patients Suffering or have Suffered with Cancers

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 oncology patients 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 oncology patients 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 patients suffering/recovering from cancer. The primary approach involved interviewing patients undergoing treatment for cancer to understand their perception of appropriate ADR reporting 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 survey of patients who had undergone or were undergoing cancer treatment was conducted by involving 390 patients. Among these participants, the majority 287 (73.6%) were between the ages of 46 and 60, and another 84 participants were above the age of 60 years. Only 19 were aged between 31 to 45 years, while there were no participants below 31 years. Among the participants 53% were male and 47% were female.

Regarding ADR, when the patients were asked if they were aware that adverse drug reactions (ADRs) to anticancer medicine can be reported, 88% of the participants responded “No”.  Similarly, when the patients were asked if they had been informed by their oncologist or nurse about reporting ADRs to anticancer medicine, 90% of the patients stated that they hadn’t.

 

Figure 1:  Awareness of ADR reporting among patients participating in the survey

Figure2:  Receipt of information from medical professionals among patients participating in the survey

When the participants were asked, if they knew whom or where to report an ADR in case of experiencing one, 93% of patients stated that they were unaware of the process. Only 26 of the 390 (7%) participants stated that they knew whom to approach in case of experiencing ADR. Next the patients were asked if they had ever reported an ADR to any healthcare provider or a reporting system, the response was overwhelmingly negative at 96%.

 

Figure3:  Awareness of ADR reporting procedures among patients participating in the survey

Figure 4: Incidence of ADR reporting among patients participating in the survey

The participating patients were then asked, if they believed reporting ADRs was important for patients’ safety. To this, the response was more or less equally distributed among the options of ‘Strongly agree’, ‘Agree’, and ‘Neutral’, with 25% of participants (101 of 390) choosing the first option, 31% (122 of 390) opting for the second option and 27% (109 of 390) selecting the third. However, 14% and 0.5% of participants ‘Disagreed’ and ‘Strongly disagreed’ with the notion respectively.    

 

Figure 5: Importance of ADR reporting among patients participating in the survey

When the participants were asked if they would report ADRs in case of experiencing one, the response was majorly positive, with 66% of the respondents choosing ‘yes’. 24% of the patients were unsure about it and 10% responded in negative.

 

Figure 6:  Willingness to report ADR in case of experiencing one among patients participating in the survey

The patients were then required to answer the question, ‘What would motivate you to report an ADR?’, the patients could choose multiple options from the list, so there were overlaps. Most of the participants (70.8%) chose the option of preventing others from experiencing the same reaction, and 50.8% chose that they would do it to help improve drug safety.

 

Figure 7:  Motivation for ADR reporting among patients participating in the survey

The patients were then inquired about the factors that might discourage ADR reporting. 77.2% of the respondents (301 of 390) stated that ‘Lack of knowledge on how to report’ is the major factor that discouraged ADR reporting. ‘Lack of time’ and ‘Fear of legal repercussions’ were other factors that were chosen by the participants.

The patients were then asked if they had received any education or information about ADRs to anticancer drugs from their oncologist or nurse. To which the majority of patients, 66% stated that they had not received any such information, and only 34% stated that they had been provided with such information. When the patients were asked if they felt that they had enough information about ADRs and how to report them, the responses were almost equally divisive. 46% of the patients said that they felt they had enough information, while 54% stated that they did not.  However, 90% of the patients were of the opinion that they were open to receiving more information.

 

Figure 8:  Received training/education from clinicians about ADR to anti-cancer drugs among patients participating in the survey

 

Figure 9:  Confidence regarding having adequate information on ADR among patients participating in the survey

 

Figure 10:  Openness to receive ADR information among patients participating in the survey

Please view attached pdf to view all figures

Discussions

Based on this background, the objective of the present investigation focused on understanding the perspectives, and practical barriers that lead to underreporting of ADRs to anti-cancer drugs in urban and rural setups. The research tried to explore the challenges, limitations, and potential areas of improvement in methods, willingness, feasibility, and facilities of ADR reporting in an appropriate manner and frequency. The first phase of the investigation explored the level of awareness regarding ADRs and ADR reporting among the patients who are presently undergoing or have undergone chemotherapeutic treatment. During the initial conceptualization of the present investigation, there were plans to separately categorize the patients into rural and urban groups based on their residential addresses. However, while conducting the survey it came to light that many of these patients were actually getting their treatment from urban facilities despite residing in rural areas.  They often undertook long and tedious journeys to receive proper medical care, which they believe may be lacking in rural facilities. In the case of certain patients, there were instances where they had initially started their treatments in rural medical centers, but had later been referred to urban centers for more advanced care. Upon coming across such overlaps, a decision was taken to not categorize the patient responses into urban and rural groups, as that would have led to erroneous representation.

 The lack of awareness regarding ADRs was quite evident in almost 90% of the patients stating that they were unaware of ADR reporting associated with their treatment and that they had not been informed by their healthcare providers. Lack of awareness among patients has always been a major barrier in ADR reporting. A detailed review of the effect of lack of awareness on ADR reporting had been carried out by Al Dweik et al. (2017). In their review, it was revealed that across 29 studies undertaken internationally, 44.1% to 93.8% of patients were unaware of available ADR reporting systems. The percentage reported by the present investigation was within this previously documented range. If patients are unaware of the ADR progress, then it becomes almost impossible for them to report them.   This lack of awareness among patients meant that they were oblivious to the procedural complexities associated with ADR reporting. This was true, as the majority of the patients as revealed in the present investigation were unaware of how to report ADRs to the PvPI database. This obviously contributed to a lack of ADR reporting from the patient’s side. The lack of ADR reporting has also been recorded in urban patients (Dutta et al., 2020).

In the current investigation, 96% of the participants stated that they had never reported any ADR to their medical care providers, despite the fact that all of them revealed that they had encountered ADRs during their treatment period. The most common ADRs experienced by patients during their cancer treatment were dizziness, nausea or vomiting, hair loss, fatigue etc. This was very similar to ADRs experienced by patients globally in response to chemotherapeutic treatment (Chopra et al., 2021).

This trend of underreporting ADRs cannot be overcome solely based on a top-down approach. The introduction of strong legislation, building of infrastructure, and providing training to healthcare providers on ADR reporting, can only be effective to a certain level. However, a major onus still lies with the patient regarding what he or she might be experiencing and reporting. The importance of ADR reporting is still valid in the patient's opinion, as the investigation revealed that most of them either ‘agreed’ or ‘strongly agreed’ to its importance for patient safety and almost two-thirds of participants were open to reporting ADRs. An altruistic attitude towards society was found to be the major factor encouraging patients to report ADRs. Most of the participants chose the option of helping others by preventing others from experiencing the same reaction, and improving drug safety. Once again the importance of knowledge in ADR reporting gets highlighted, as patients pointed out that lack of knowledge on the procedural complexities is the major discouraging factor behind ADR underreporting. However, it is also a matter of concern what source of information is available to patients. In today’s day and age, finding a reliable source of medical information has emerged as a major challenge. Therefore, it was no surprise when more than 90% of the patients were of the opinion that the best source of information regarding ADR reporting would be through verbal communication by the oncologists, nurses, and social workers. Most of the patients were open to receiving additional information and training on ADR reporting.  This highlights the trust that patients have in their medical care providers and provides a strong indication of possible paths toward better information sharing. 

Conclusion

The present study was undertaken to understand the perception difference in ADR reporting among patients 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 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 patients revealed that there is a general lack of awareness and lack of understanding of ADR reporting, both in urban and rural India. There were different types of challenges listed by the patients, 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 patients. 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 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.

 

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