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 Table of Contents  
ORIGINAL ARTICLES
Year : 2021  |  Volume : 10  |  Issue : 1  |  Page : 110-117

Incidence and cost of chemotherapy-induced adverse drug reactions among cancer patients in a charitable hospital


1 Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences, Nitte (Deemed to be University), Paneer, Deralakatte, Mangaluru 575018, Karnataka, India
2 Department of Radiation Oncology, K.S. Hegde Medical Academy, Justice K.S. Hegde Charitable Hospital, Nitte (Deemed to be University), Deralakatte, Mangaluru 575018, Karnataka, India

Date of Submission27-May-2020
Date of Acceptance14-Mar-2021
Date of Web Publication31-May-2021

Correspondence Address:
Dr. Uday Venkat Mateti
Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences, Nitte (Deemed to be University), Paneer, Deralakatte, Mangaluru 575018, Karnataka.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jrptps.JRPTPS_68_20

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  Abstract 

Introduction: Chemotherapy-induced adverse drug reactions (ADRs) are one of the major consequences of cancer therapy that affects patients’ quality of life, outcomes of the treatment, morbidity, and mortality and increases the economic burden. The study’s objective was to evaluate the incidence, causality, severity, and preventability and to calculate the direct medical cost of chemotherapy-induced ADRs among cancer patients. Materials and Methods: A prospective observational study was conducted for 8 months in patients above 18 years and receiving chemotherapy. ADRs were evaluated for their causality, severity, and preventability using different ADR assessment scales, and the economic burden for different ADRs was based on their direct medical costs. Results: A total number of 230 patients were enrolled in the study, out of which 84 patients developed 148 ADRs. Patients who received chemotherapy showed a higher incidence of ADRs in 45–55 years of age group (30.95%), females (69.04%), solid tumors (92.85%), stage III (55.95%), and double regimen (61.90%). Paclitaxel and carboplatin were reported to cause most ADRs, such as anemia (14.18%) and leucopenia (6.75%). ADRs were assessed using scales. As per the WHO-UMC scale, 59.4% ADRs were possible, followed by probable (39.2%). The majority of the ADRs were mild (52%) in severity. About 41.9% reactions were probably preventable, and 3.4% were definitely preventable. Conclusion: The overall incidence of ADRs was 36.52%. The direct medical cost incurred for the management of ADRs was 457.23 USD.

Keywords: Causality, costs, incidence, preventability, severity


How to cite this article:
Varghese J, Mateti UV, Shetty J, Philip ML, Naga Raju B. Incidence and cost of chemotherapy-induced adverse drug reactions among cancer patients in a charitable hospital. J Rep Pharma Sci 2021;10:110-7

How to cite this URL:
Varghese J, Mateti UV, Shetty J, Philip ML, Naga Raju B. Incidence and cost of chemotherapy-induced adverse drug reactions among cancer patients in a charitable hospital. J Rep Pharma Sci [serial online] 2021 [cited 2021 Dec 8];10:110-7. Available from: https://www.jrpsjournal.com/text.asp?2021/10/1/110/317252




  Introduction Top


Cancer is the abnormal proliferation of cells, the second leading cause of death after heart diseases.[1] Chemotherapy is a type of treatment that includes single or combination drugs that interfere with the ability of cancer cells to divide and proliferate.[2] Chemotherapy-induced adverse drug reactions (ADRs) are one of the major consequences of cancer therapy that affects patients’ quality of life, outcomes of the treatment, morbidity, mortality, and economic burden.[1]

The severity of the ADRs is determined by the drug use pattern, disease severity, and other co-morbidities. The prevention of chemotherapy-induced ADRs is required to improve drug efficacy and patients’ Quality of Life (QoL).[3] Chemotherapy-induced ADRs are unwanted drug effects that substantially impact the patients, including additional cost requirements for investigations, additional drug therapy, prolonged hospitalization, admission, and emergency hospital visits. They can also lead to disability or required intervention to prevent the damage.[4] The study’s objective was to evaluate the incidence, causality, severity, and preventability and to calculate the direct medical cost of chemotherapy-induced ADRs among cancer patients.


  Materials and Methods Top


Study design and setting

A prospective observational study was conducted for 8 months (September 2017–April 2018). This study was conducted on cancer patients receiving chemotherapy in the Oncology Department, Deralakatte, Mangaluru. This study was approved by the Institutional Ethics Committee (REF: NGSMIPS/IEC/06/2017–18), NGSMIPS, Mangaluru.

Study criteria

The inclusion criteria comprised patients above 18 years of age, either gender, all cancerous patients receiving chemotherapy, and patients on six chemotherapy cycles. Pregnant, lactating women, and patients not willing to participate in the study were excluded.

Data collection

The information was obtained from the patient’s clinical records, including demographics (age, gender, social habits, stage of cancer, tumor type, and chemotherapy regimens) and complaints on admission, and routine laboratory investigations were collected. Demographics of the patients were studied to find out the patterns of ADR. Identification of ADRs was made based on the regular follow-up of the patients by analyzing the subjective findings.

Analysis of chemotherapy-induced ADRs

In order to assess the likelihood that a drug has caused the reaction, the causality assessment was done using Naranjo and the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) scale.[5],[6] Depending on the severity, ADRs were classified into mild, moderate, and severe reactions using the criteria developed by Hartwig et al.[7] for severity assessment. ADRs were categorized into definitely preventable, probably preventable, and not preventable using the modified Schumock and Thornton scale.[8]

Cost analysis of ADRs

The direct medical costs involved in the management of ADRs were collected from the Hospital Medical Billing System (HMBS). Items included in the cost incurred for the management of ADRs were additional or prolonged hospitalization, additional treatment, clinical investigational charges, additional procedures, and other costs incurred, such as other healthcare professional and nursing charges due to ADRs. The cost data were presented in USD (1USD = 65 INR).

Statistical analysis

The analysis was done using descriptive statistics. χ2 test/Fisher’s exact test was applied to test the association between categorical variables, with P-value less than 0.05 considered statistically significant. Statistical software (SPSS version 20.0) was used to analyze the data.


  Results Top


A total number of 230 patients were enrolled in the study; 84 patients developed 148 ADRs. All the patients underwent six cycles of chemotherapy without any dropouts. The overall incidence of ADRs was 36.52%. During the study, the higher incidences of ADRs were observed in the age group of 45–55 years (30.95%), and the mean age of the patients with ADRs was 53.32±12.99 and without ADRs was 49.17±15.76 years. Female patients had a higher incidence (69.04%) of ADRs when compared with the males. There was no significant association between gender and ADRs. Higher incidence of ADRs was developed in solid tumors (92.85%) than in hematological tumors (7.14%). Out of the 84 patients, the higher incidence of ADRs was observed in stage III (55.95%), followed by stage IV (23.80%). The majority of the patients had prolonged their hospitalization from 1 to 3 days (4.76%) due to ADRs. There was a significant association (P = 0.004) between ADRs and hospital stay. The higher incidences of ADRs were observed in doublet regimens (61.90%), followed by triplet regimens (23.80%). The demographics details of patients are depicted in [Table 1].
Table 1: Demographic details of patients with and without ADRs

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The most commonly observed ADRs were anemia 54 (36.48%), followed by leucopenia 27 (18.24%). The doublet regimen responsible for these ADRs was paclitaxel and carboplatin. The most commonly affected organ system was the hematological system (61.5%), followed by the gastrointestinal (12.8%) system. The chemotherapy regimen, cycles, organ system, and their ADRs are summarized in [Table 2]. According to the WHO probability scale, most of the ADRs were possible (59.4%), followed by probable (39.2%). As per the Naranjo scale, most of the ADRs were possible (53.4%), followed by probable (45.9%). Most of the ADRs were predictable (97.3%), and 2.7% of the ADRs were not predictable. The assessments of ADRs using different scales are depicted in [Table 3].
Table 2: Chemotherapy regimen and their ADRs

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Table 3: Causality, severity, preventability, and predictability of ADRs

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Out of the 148 ADRs, only 64 ADRs (43.24%) incurred the cost for the management. The utmost cost was incurred for the hematological system (226.70 USD), followed by the gastrointestinal system (95.66 USD). The utmost cost was observed in patients presented with leucopenia (135.16 USD), followed by vomiting (83.85 USD). The economic burden was the highest for the moderate type of reactions who had hospitalization due to ADRs (346.06 USD). The cost analysis of different ADRs is summarized in [Table 4].
Table 4: Cost analysis of different ADRs

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  Discussion Top


In the present study, the overall incidence of ADRs was 36.52%, which was consistent with the study conducted by Khandelwal et al.,[3] which reported that ADR in patients receiving chemotherapy was 37.70%. So the present study resembles the previous study in that the overall incidence was 37%.

Out of the 84 ADR patients, higher incidences of ADRs were reported in the age group between 45 and 55 years. The studies conducted by Behera et al.[9] and Rao et al.[10] show that the incidences of ADRs were higher in 41–60 years than the other age groups. This study corresponds with the previous studies in which 40–55 years had a greater number of ADRs.

In the present study, greater incidences of ADRs were observed in females (69.04%) than in males (30.95%). The preceding studies reported that higher incidences of ADRs were in females when compared with males. The present study is in coincidence with the previous studies.[3],[9],[11]

Majority of the patients presented with solid tumors (93.91%) when compared with hematological tumors (6.08%), which resembles the study conducted by Lyman et al.,[12] in which solid tumors (88.15%) were the most commonly observed than hematological tumors (11.84%).

Out of the 230 patients, most of the patients received doublet regimen in which the frequently prescribed doublet regimens that had caused the majority of the ADRs were paclitaxel and carboplatin (31.7%), followed by doxorubicin and cyclophosphamide (10.77%); these findings correspond to the study conducted by Khandelwal et al.,[3] in which higher incidence of ADRs was observed in patients who received paclitaxel and carboplatin (11.8%), followed by doxorubicin and cyclophosphamide (9.62%). The most commonly affected organ system by chemotherapy was the hematological system (61.5%), followed by the gastrointestinal system (12.8%) and skin and appendages (10.1%), which is in correspondence with the studies conducted by Khandelwal et al.[3] and Behera et al.,[9] in which the hematological system (39.86% and 24.22%) was mostly affected by different ADRs followed by skin and appendages (23.88% and 16.57%), respectively. The present study is consistent with the previous study in which the hematological system is commonly affected but varied in other organ systems.

In the study, frequently occurring ADRs were anemia (36.5%), followed by leucopenia (18.2%), alopecia (8.1%), and anorexia (6.1%), whereas in the studies conducted by Behera et al.[9] and Shrestha et al.,[11] it was reported that anemia had occurred in the majority of the patients, followed by neutropenia, neuropathy, muscular weakness, and thrombocytopenia. The current study findings correspond to the previous study in which the most occurring ADR was anemia, and other ADRs did not have resemblance with the earlier studies.[9]

According to the WHO-UMC scale and Naranjo scale for assessing causality, most of the ADRs were possible (59.4% and 53.4%), followed by probable (39.2% and 45.9%). The studies conducted by Swathi et al.[10] and Rao et al.[13] reported that the WHO probability scale and Naranjo scale were used during the causality assessment, and most of the ADRs were possible followed by probable.

Severity assessment by the Hartwig scale exhibited that most of the ADRs were mild, followed by moderate. There were no deaths due to ADRs that resembled the studies conducted by Wahlang et al.[14] and Chopra et al.,[15] who reported that most of the ADRs were mild followed by moderate and severe without any deaths being observed.

The hematological system had the highest total cost (226.70 USD) followed by the gastrointestinal system (95.66 USD), and the highest total cost was observed in patients who presented with leukopenia (135.16 USD) followed by vomiting (83.85 USD). A study conducted by Rajakannan et al.[16] reported that the hepatic system (7520.09 USD) had the highest total cost, followed by skin and appendages (5176.26 USD). Hepatocellular damage (7520 USD) had the highest cost incurred, followed by nephropathy (2436 USD). The present study was conducted in the oncology department, whereas the previous study was conducted in general medicine.

In the present study, the utmost cost incurred for the ADRs was in a moderate level of severity (Level 4b = 346.06 USD). Rajakannan et al.[16] reported that a moderate level of severity (Level 4a = 12629.63 USD) of ADRs had incurred the utmost cost. This resembles the previous study, in which the cost incurred at a moderate level was higher than that of the present study.

Limitations

The study’s main limitations include that the duration is less, single centric, and the only direct cost was calculated.


  Conclusion Top


The overall incidence of ADRs was found to be 36.52%. Paclitaxel and carboplatin were reported to cause most ADRs, such as anemia (14.18%) followed by leucopenia (6.75%). The direct medical cost incurred for the management of ADRs was 457.233 USD. Regular detection, monitoring, evaluating, and preventing ADRs can minimize the economic burden of treating the ADRs.

Acknowledgements

We would like to thank the NGSM Institute of Pharmaceutical Sciences, Nitte (Deemed to be University), Deralakatte, Mangaluru, Karnataka, India, for providing the research facilities for conducting this study. Dr Vijith Shetty, Associate Professor, Department of Medical Oncology, Justice K.S. Hegde Charitable Hospital, Deralakatte, Mangaluru is acknowledged.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Hartwig SC, Siegel J, Schneider PJ. Preventability and severity assessment in reporting adverse drug reactions. Am J Hosp Pharm 1992;49:2229-32.  Back to cited text no. 7
    
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Lyman GH, Berndt ER, Kallich JD, Erder MH, Crown WH, Long SR, et al. The economic burden of anemia in cancer patients receiving chemotherapy. Value Health 2005;8:149-56.  Back to cited text no. 12
    
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Swathi B, Bhavika D, Begum N. Adverse drug reactions profiles of commonly used platinum compounds in cancer chemotherapy. Int J Basic Clin Pharmacol 2015;4:284-8.  Back to cited text no. 13
    
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Wahlang JB, Laishram PD, Brahma DK, Sarkar C, Lahon J, Nongkynrih BS. Adverse drug reactions due to cancer chemotherapy in a tertiary care teaching hospital. Ther Adv Drug Saf 2017;8:61-6.  Back to cited text no. 14
    
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Rajakannan T, Mallayasamy S, Guddattu V, Kamath A, Vilakkthala R, Rao PG, et al. Cost of adverse drug reactions in a South Indian tertiary care teaching hospital. J Clin Pharmacol 2012;52:559-65.  Back to cited text no. 16
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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