Exploring the factors influencing the health-related quality of life in patients experiencing adverse drug reactions: a cross-sectional study

Abstract

Background

This study aimed to assess the factors influencing health-related quality of life (HRQoL) in patients experiencing adverse drug reactions (ADRs) at a tertiary care public sector hospital. A cross-sectional study was conducted over a period of 18 months, and included both male and female patients aged 18 years and above. Patients who visited the outpatient and inpatient departments with complaints associated with ADRs were included in this study. HRQoL data were collected using the EuroQol—5 Dimension—5 Level (EQ-5D-5L) questionnaire to assess five dimensions of health on a five-level scale. Descriptive statistics, t-tests, and analysis of variance were used to analyze the data. Multivariate regression analysis was performed to identify the potential determinants of HRQoL.

Results

A total of 316 patients were included in the study among these participants, of which 54% were female, and 65% were from rural areas. The majority (68%) of the patients had moderately severe ADRs, and 63% of the participants had an income < 2.5 lakh Indian rupees (3009 USD). The mean EQ-5D-5L and EuroQoL Visual Analog Scale (EQ VAS) scores of the study participants were 0.714 and 69.73, respectively. The variables ADR severity, income, and age showed a significant difference (p < 0.05) in HRQoL.

Conclusion

This study provides insights into HRQoL among patients with ADRs and identifies the determinants of HRQoL. The findings of this study will contribute to improving patient-centered care and optimizing patient outcomes.

Background

Adverse drug reactions (ADRs) are harmful and unintended effects of medications that occur during regular clinical use, and they can range from minor side effects to life-threatening events [1]. Literature shows 5–10% of ADRs were responsible for hospital admissions [2, 3]. In developed countries, the prevalence of hospital admissions due to ADRs was 6.3% and in developing countries 5.5% [4]. A study from India reported prevalence of ADRs was 3.7% and 0.7% ADRs were responsible for hospitalization [5]. The estimated economic burden incurred due to ADRs in Europe at €79 billion [6] and in US at $30.1 billion [7]. A study from India reported direct and indirect costs associated with ADR management were €3008 and €27,206 respectively [8].

ADRs can significantly impact health-related quality of life (HRQoL), leading to physical, emotional, and social burdens. Patients with ADRs may experience pain, fatigue, swelling, and numbness affecting their ability to perform daily activities which cause physical discomfort [9]. The experience of dealing with skin ADRs affect patients’ self-esteem and impacting emotional health leading to anxiety or depression [9, 10]. The ADRs affecting skin impacts person’s ability to interact with others leading to social avoidance [11]. Additionally, treating ADRs can be costly and time-consuming, leading to further stress and burden on patients and their families [12, 13].

Quality of life (QoL) measures an individual’s perception of their physical, mental, and social well-being concerning their health status and the treatments they receive. HRQoL is affected by various factors, including the severity and duration of illnesses, disabilities, and chronic conditions, including social and environmental factors [14, 15]. Improving HRQoL is a priority for healthcare providers, as it can impact individuals’ overall health outcomes and their ability to participate in daily activities [16]. HRQoL is relevant worldwide and is increasingly being studied and measured around the globe.

HRQoL is often measured using standardised questionnaires or surveys that ask individuals about their ability to perform activities of daily living, their emotional well-being, their social relationships, and their overall satisfaction with their health status and healthcare [17]. These measurements can provide valuable information for healthcare providers, policymakers, and researchers to assess the impact of various interventions and treatments on individuals’ QoL [14, 15].

The availability of ADR-induced QoL data may vary depending on several factors, including the specific drugs and health conditions considered [18]. However, in many countries, including India, there is often a lack of robust and systematic collection of ADR-induced QoL data. In India, the primary focus of pharmacovigilance efforts has been on monitoring and reporting adverse drug reactions rather than specifically assessing their impact on QoL. The Pharmacovigilance Programme of India (PvPI) is a government initiative that aims to collect, analyze, and monitor ADRs under the Indian Pharmacopoeia Commission (IPC) [19]. While the programme helps to identify and document adverse reactions; however, it may not consistently capture data on the impact of these reactions on patients’ QoL.

The existing literature highlights a dearth of data on the determinants of HRQoL among individuals with ADRs. Therefore, this study sought to fill this gap by investigating the factors affecting QoL in patients with ADRs. The EuroQol—5 Dimension—5 Level (EQ-5D-5L) questionnaire was used to comprehensively evaluate various QoL dimensions. The EQ-5D-5L is known for its ease of use and the calculation of quality-adjusted life years (QALYs). The QALYs generated from this study results can be used for the cost-effectiveness analysis of any new intervention focusing on ADR management or prevention.

Methods

Study design

A cross-sectional questionnaire-based study was conducted to assess QoL among patients who experienced ADRs at a tertiary care public sector hospital. The study was conducted over 18 months from December 2021 to June 2023.

Study setting and participants

Bihar is located in the eastern part of India with more than 100 million population and is India’s third most populous state. Bihar is classified as a low-income state and is one of India’s less economically developed states [20]. The primary language spoken is Hindi, however, several regional languages and dialects are also prevalent, including Bhojpuri, Maithili, and Magahi. About 11.3% of the population lives in urban areas, indicating a predominantly rural population. According to the NITI Aayog Health Index ranking, Bihar has been ranked last among the large states [21]. The state has inadequate health care infrastructure, including shortage of beds and health care professionals.

This study was conducted at the Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, a tertiary care public sector hospital that provides health services to the people of Bihar and nearby regions. Additionally, IGIMS is an ADR monitoring center (AMC) working under IPC-PvPI. The hospital accommodates 1163 beds and during 2022–2023 a total of 42,529 in-patients and 8,47,493 outpatients treated at IGIMS. More than half of the patients utilising this hospital belong below the poverty line and come from rural areas.

Patients with ADRs attending the inpatient and outpatient departments of IGIMS were identified by health care professionals and referred to the AMC for reporting ADRs to the IPC. Eligible patients were enrolled in the study based on predefined inclusion and exclusion criteria. The study participants included patients of both sexes, aged 18 years and above, who experienced ADRs. Patients with intellectual disabilities, physical handicaps, or ADRs due to intentional drug abuse were excluded from the study. Participants with incomplete information were excluded to ensure the accuracy and integrity of the data. Eligible participants were approached, provided with a detailed explanation of the study, and informed consent was obtained prior to their inclusion in the study.

Ethical considerations

The study adhered to ethical guidelines and obtained the necessary ethical approval from the institutional ethics committee of IGIMS, Patna, Bihar, India (373/IEC/IGIMS/2021). The participants’ privacy, confidentiality, and rights were protected throughout the study. Adequate measures were taken to ensure informed consent, voluntary participation, and the right to withdraw from the study.

Data collection

A trained individual administered the questionnaire through face-to-face interviews or self-administration, depending on the participant’s preference and feasibility. The interviews were conducted the same day after the patients were included in the study. All interviews took place in the hospital, and during the interviews, the patients were accompanied by their caregivers or relatives. A structured questionnaire was used to collect demographic information, medical history, and details of ADRs experienced by the participants. While collecting information regarding medical history sometimes patient caregivers responded on behalf of the patients when the patients found it difficult to recall the necessary details. Based on the Hartwig’s criteria ADRs were classified as mild, moderate or severe. Mild ADRs cause minimal discomfort and are self-limiting in nature. Moderate ADRs have a clinical impact and require treatment to manage them. Severe ADRs have a significant clinical impact and require immediate medical intervention [22].

The EQ-5D-5L Hindi questionnaire was administered to assess the participants’ QoL. The EQ-5D-5L consisted of five dimensions mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension contains five response levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The EuroQol Visual Analog Scale (EQ VAS) is a self-reported measure that assesses an individual’s overall health or quality of life on a continuum from 0 to 100, with 0 indicating the worst imaginable health state and 100 representing the best possible health state [23,24,25]. The QoL assessment using the EQ-5D-5L was performed at a single time point, specifically during the occurrence of the ADR. The EQ-5D-5L questionnaire has been widely used, validated translated and culturally adapted for use across the globe, including India. This study used an Indian value set and algorithm to calculate the utility score [26, 27].

Data analysis

The collected data were entered into the Statistical Package for the Social Science (SPSS) software and descriptive statistical analysis was performed to summarise the demographic characteristics, ADR severity, and QoL scores obtained from the EQ-5D-5L. The distribution of participants across the response levels of the EQ-5D-5L was examined to assess the proportion of patients experiencing problems in each dimension. Descriptive information was presented as frequencies and percentages. To investigate differences in QoL scores between the two groups, Student’s t-test was employed. For the comparisons involving more than two groups, analysis of variance (ANOVA) was performed. Multivariate regression models were employed to identify potential determinants of QoL. A p value of < 0.05 was considered statistically significant. The statistical analyses were conducted using SPSS version 25.

Results

A total of 320 patients were initially enrolled in the study. Four participants were excluded from the analysis due to missing information, resulting in a final sample size of 316 participants.

The mean age of the participants was 41.74 years, with a standard deviation (SD) of 16.83. Among the 316 participants, 54.1% were female. Table 1 presents the sociodemographic and clinical characteristics of the participants. The largest proportion (37%) of the respondents belonged to the 31–50 years age group. In terms of residence, 65.2% of the participants were from rural areas, and 75.3% were married. Regarding education, approximately one-third (34.8%) of the respondents had completed their secondary education. The annual income measured in terms of Indian Rupees (INR) where, one lakh equals to hundred thousand. Over half (55.1%) of the participants fell into the 1–2.5 lakh INR (1203-3009USD) income category. Furthermore, the majority of the ADRs (68.04%) were classified as moderately severe. A large proportion (60.8%) of the participants were from in-patient wards and 33.5% of the ADRs were related to the antibiotic class of drugs. Over 40% of the participants were from the general medicine and medical oncology departments.

Table 1 Participants’ sociodemographic and clinical characteristics

Table 2 represents the distribution of HRQoL across five dimensions and five levels. Most of the participants had no problems with mobility (47.5%) and anxiety/depression (56.3%). Most of the respondents had slight problems with selfcare (44.9%), usual activity (60.4%) and pain/discomfort (44.6%).

Table 2 Descriptive distribution of EQ-5D-5L responses provided by the participants

In Table 3, the association between QoL scores and variables is presented. The mean HRQoL scores for the EQ-5D-5L and EQ VAS were 0.71 and 69.73, respectively. Participants aged over 50 years had significantly (p < 0.001) lower QoL scores than the other age groups. The following variables showed a significant (p < 0.001) association with utility and EQ VAS scores: education, occupation, and ADR severity. Females had a higher utility score (0.73) than males additionally, single participants had a healthier score (0.80) than married individuals. A significant (p < 0.001) difference in EQ VAS scores was observed among respondents with low income.

Table 3 Association between HRQoL scores and sociodemographic and clinical characteristics

All variables were included in the linear regression analysis, and the values are presented in Table 4. The results indicated that both gender and income significantly (p < 0.05) influenced utility and VAS scores. Moreover, the severity of ADRs was found to be a significant (p < 0.01) variable affecting the HRQoL scores.

Table 4 Determinants of HRQoL among patients with ADRs

Discussion

This study investigated the HRQoL among patients with ADRs using the EQ-5D-5L questionnaire. The findings reveal that the mean utility score (0.714 ± 0.270) was lower than the utility score of the Indian general population (0.849 ± 0.212) [26, 28] but higher than the utility score of cancer patients (0.602 ± 0.311) [29]. Additionally, the mean EQ-VAS score (69.73 ± 10.29) was lower than that of both the Indian general population (75.18 ± 16.42) [26, 28] and cancer patients (75 ± 12.3) [29]. These results indicate that patients with ADRs experience a lower level of HRQoL than the general population. Lower scores suggest a burden of health problems and reduced overall well-being among individuals affected by ADRs.

Over half of the respondents reported problems with mobility which is higher (30.3%) than the Indian general population [26]. Two studies from India reported ADRs responsible for decreased physical domain scores [30, 31], another study reported 25% of the patients with ADRs reported diminished general condition [32] and a study showed lower physical component summary patients with ADRs [33]. Patients with ADRs like muscle pain, dizziness, fatigue and numbness lead to mobility issues. The reported lower physical health among patients indicating noticeable mobility impairment leading to overall diminished QoL. Approximately 30.1% of the respondents reported slight problems related to anxiety or depression which is lower (24.8%) than the Indian general population [26]. A study from India reported patients with ADRs reported diminished psychological health [30], and another study reported a quarter of the participants’ mood or enjoyment of life was impacted [32]. A cross-sectional study reported a lower mental component summary among patients with ADRs [33], and a study revealed depression and anxiety prevalence was higher among ADR patients than the general population [34]. A higher reporting of mobility problems and anxiety/depression is consistent among ADR patients. This highlights the significant impact of ADRs on patients’ QoL and the importance of addressing both physical and mental health aspects in ADR management.

The study findings revealed a significant association (p < 0.001) between HRQoL scores and age, indicating that older age is a contributing factor to impaired QoL. Specifically, the HRQoL scores decreased with increasing age, which is consistent with previous studies conducted in India [26, 28, 35], as well as studies conducted in other countries [36, 37]. The consistent findings across different studies and countries further support the robustness and generalisability of the age-related impact on HRQoL. Indeed, the older age group is more susceptible to having multiple diseases and a higher prevalence of mental health issues. Furthermore, mental health issues, such as depression, anxiety, and cognitive decline are more prevalent among older adults [38]. These conditions may further compound the impact of ADRs on the individual’s overall QoL and well-being. Tailored interventions, including medication management, mental health support, and comprehensive care, may help mitigate the impact of ADRs and enhance the overall QoL in this population.

The study findings demonstrated a significant (p < 0.05) impact of participants’ income on HRQoL. These results align with previous studies that have also investigated the influence of income on QoL [39, 40]. Indeed, studies have demonstrated a significant association between insufficient income and high anxiety levels [41, 42]. Specifically, the findings indicate that individuals with lower incomes tend to experience a low level of QoL. Low income could pose various challenges and limitations that may negatively affect multiple aspects of a person’s life, including access to healthcare, living conditions, and social support. These factors might collectively contribute to a diminished quality of life.

The study findings indicate that the severity of ADRs significantly (p < 0.001) influences HRQoL. These results are consistent with previous studies conducted on various diseases, which have consistently shown that disease severity is associated with QoL [43,44,45]. When ADRs are more severe, they may have a greater impact on an individual’s physical and psychological well-being, resulting in a lower HRQoL. Higher levels of symptom burden, functional impairment, pain, and discomfort associated with severe ADRs can adversely affect different dimensions of a person’s quality of life. Understanding the impact of ADR severity on HRQoL is essential for healthcare professionals to accurately assess the consequences of adverse reactions and tailor appropriate interventions. By considering the severity of ADRs and their association with QoL, healthcare providers can prioritise effective management strategies, minimise the impact of ADRs on patients’ well-being, and optimise their overall treatment outcomes.

The study results might be useful in developing patient-centred interventions and policy guidelines to improve patient-reported outcomes. The study highlights the importance of considering individual demographics of patients, such as age, income and ADR severity along with treatment plans to provide a personalised approach that may improve patient outcomes. The study results may enable more patient-centred care, improved treatment decision-making, and enhanced drug safety monitoring, ultimately leading to improved healthcare outcomes and better QoL for affected individuals.

The study results were reliable and replicable; however, the study has some limitations. The study was conducted at a public sector hospital, where most of the population came from rural areas. This could impact the QoL scores as access to health care diminished and patients may have had to travel long hours to reach the hospital. The reliance on self-reported measures may have introduced response bias and subjectivity in QoL assessments. Collecting QoL data only once during the occurrence of the ADR may not have captured long-term or post resolution QoL changes. The EQ-5D-5L is a generic scale and may not capture all disease-specific or condition-specific variables. Differences in understanding and interpreting the questionnaire items can lead to variability in responses. This is particularly relevant in populations with varying levels of health literacy and education. Being in a hospital setting can cause stress and anxiety for patients, which might influence their responses to the survey. The presence of caregivers or relatives might influence patients’ responses.

Conclusion

These findings emphasise the need for interventions and support measures to address the specific challenges faced by the patients and improve their HRQoL. Strategies to improve HRQoL include addressing underlying health conditions, improving access to healthcare, providing social and emotional support, and addressing environmental factors that may impact individuals’ health and well-being. Therefore, healthcare providers need to identify and manage ADRs promptly to improve the QoL of patients and promote better health outcomes.