Social and Financial Barriers to Optimum TKI Treatment in Patients with Chronic Myeloid Leukemia- A Knowledge-Attitudes-Practices Study from India
Received: August 7, 2020
Accepted: December 7, 2020
Mediterr J Hematol Infect Dis 2021, 13(1): e2021004 DOI 10.4084/MJHID.2021.004
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Outcomes in chronic myeloid leukemia (CML) have vastly improved after
introducing tyrosine kinase inhibitors. However, patients in low and
middle-income countries (LMICs) face many challenges due to social and
Clinical history and examination findings, along with demographic data and treatment procedures, were recorded. The investigator administered a questionnaire (in the Hindi language); wherein patients were asked about their perceptions of the nature of the disease and its treatment, how imatinib was obtained, drug-taking behavior, the economic and social burden of the treatment. The patient reported nonadherence was recorded by enquiring the percentage of missed doses since the last hospital visit and episodes of treatment interruptions (TIs) of ≥7 days (at any point during treatment).
Categorical variables were presented in number and percentage (%), and continuous variables were presented as mean ± SD and median. The normality of data was tested by the Kolmogorov-Smirnov test. If the normality was rejected, then the non parametric test was used. Quantitative variables were compared using the Kruskal Wallis test for more than two groups. Qualitative variables were correlated using the Chi-Square test. A p-value of <0.05 was considered statistically significant. The data was entered in MS EXCEL spreadsheet, and analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0.
1. Demographic and social data .
Patient awareness about the disease and treatment is described in Table 2. The disease's nature was thought to be a "blood infection" by 23 patients (5.75%). A third of the patients were unaware of the lifelong nature of the treatment. One hundred sixty-seven patients (41.75%) were unaware of the risks of interrupting treatment. Drug-taking practices are mentioned in Table 3. A fixed routine for taking the drug was followed by 94.25% of the patients, and nearly two-thirds preferred to take the drug at bedtime. 27% of the patients relied on reminders from family members to take the drug every day. One hundred eighteen (29.5%) patients felt inconvenienced by the treatment, and that was due to a combination of adverse drug effects, treatment financial burden and to the need for regular lifelong follow-up and treatment.
|Table 2. Knowledge about disease and treatment.|
|Table 3. Drug taking practices.|
Imatinib was obtained through three different means (Table 4). The majority (61.75%) obtained imatinib under the Glivec International Patient Assistance Program (GIPAP). This group of patients received imatinib free of cost from a designated GIPAP center in Delhi. They had to bear the cost of investigations by themselves. The second group (14.25%) of patients obtained imatinib through a cost-reimbursement program which covered all treatment-related expenses. The third group (24%) were self-paying patients who had to bear the entire treatment cost themselves. The GIPAP group received Glivec, and the other two groups of patients received generic imatinib. The median annual treatment related expenditure was highest in the self-paying group of patients, followed by the GIPAP group. The majority of self-paying patients felt that the treatment was a significant financial burden. 44.4% of patients in the GIPAP group also felt the treatment was a financial burden due to the cost of investigations, the expenditure of the commute for the visit, and loss of employment due to hospital visits. Monitoring BCR-ABL IS by quantitative PCR (at any point during follow-up) was done by 76% of patients. Among the three groups, the GIPAP group had the maximum number of patients (30%) who had not tested even once during follow-up.
|Table 4. Financial impact of treatment.
One hundred sixty-five patients (41.25%) reported missing a dose of imatinib since the last hospital visit. The frequency of hospital visits was once in 3 months. Thirty-six patients (9%) had missed more than 10% of doses. Sixty-six patients (16.5%) reported treatment interruptions of 7 days or more (at any time during treatment). The self-paying patients had significantly higher nonadherence rates (15.6%) and treatment interruptions (25%). (Table 4)
Most common treatment-related adverse effects were gastrointestinal (nausea, vomiting, and decreased appetite), followed by skin hypopigmentation and fatigue. (Figure 1)
|Figure 1. Treatment related adverse effects (alone or in combination).
Patient awareness regarding disease and treatment has been suboptimal in studies from India and Brazil, whereas it was much better in studies from Europe.[2,5] We observed low patient awareness regarding the nature of the disease and treatment, particularly regarding treatment duration. This poor information is a peculiar challenge faced during the treatment of CML in low and middle-income nations, particularly in the public sector, where many patients belong to the lower socioeconomic strata and are less educated. Patient awareness is a critical component in ensuring optimum treatment as lack of adequate knowledge about the disease adds to patient anxiety, hampers adherence to treatment, and creates a trust deficit between the patient and the physician. These findings reiterate the need for focused and easy-to-understand counseling at diagnosis and its repeated reinforcement during subsequent visits.
Patients tend to adopt various practices to make the daily intake of drugs regular and convenient. We observed that most patients followed a regular routine, and many relied on reminders from family members. Similar practices have been reported previously as well.[2,7] Studies from India have reported a lower incidence of comorbid ailments than what is observed in developed nations. and that can be attributed to a younger CML patient population in India.
Many of our patients reported that the treatment caused them inconvenience due to a combination of various factors-adverse drug effects, the financial burden of treatment, and the need for regular lifelong follow-up and treatment. This vital issue can get these patients demotivated and may induce them to discontinue treatment.
The financial impact of cancer treatment is immense, and it remains one of the most important issues that patients have to take into consideration while going for treatment. The GIPAP program, launched in 2001, provides free of cost Glivec to thousands of patients across the globe. It has been a boon for patients of CML in low-income countries. The greatest beneficiaries of the program have been from India. New patients were being enrolled in the program till 2016, and almost all CML patients at our center prior to this got their drug through GIPAP. This group comprises the major bulk of CML patients at our center and it is reflected in the study population with 62% enrolled under GIPAP. We observed that treatment led to a substantial financial burden in our study group. The median annual treatment related expenditure was highest in the self-paying patients, for whom the cost of imatinib made up the bulk of the treatment expenditure. A large number of GIPAP patients also felt financially burdened by the treatment accessories related to the cost of investigations, travel and accommodation for the hospital visit, and loss of employment. The expenses are comparatively lower than other countries but still substantial for a country with an average annual per capita income of INR 92,565.
The cost of BCR-ABL quantitative estimation by PCR is around INR 6,000-7,000. This is almost two times the cost of monthly generic imatinib. The unaffordability of repeated BCR-ABL estimations is reflected by the high number of patients who did not get even a single estimation done in the follow-up. This tendency is true even in developed countries, and regular disease assessment either by cytogenetics or molecular methods is infrequently seen outside the setting of clinical trials.[13,14]
Nonadherence to TKI therapy is a major hindrance to obtaining favorable long term outcomes in patients with CML.[15,16] The nonadherence patient-reported is a less sensitive methodology for assessing nonadherence as it may underestimate the actual prevalence. Despite this, we observed that a large number of patients were non-adherent to imatinib, and also that many patients reported lengthy treatment interruptions. Previous studies from India have observed nonadherence rates of 25% to 55%.[1,8,15] The proportion of nonadherence >10% and TIs was significantly higher in the self-paying patients, concerning the financial difficulties faced by these patients.
Managing CML in low and middle-income countries requires careful titration of the treatment according to the patients' socioeconomic status. All avenues of financial support from both government and non-government schemes must be pursued to ensure uninterrupted treatment. The excellent survival rates of patients under the GIPAP program are a testament to the fact that by improving accessibility to TKIs in LMICs, we can produce results comparable to high-income countries. The availability of TKIs must be coupled with better penetrance of hematology/oncology services to smaller towns and cities and an emphasis on better patient education and treatment adherence.
Our study has several limitations. Patients were assessed at only a single time point without follow up. The disease's awareness would depend upon the initial patient counselling and education that might not be uniform for all patients. The patient-reported nonadherence was assessed over a 3-month duration, which is a less sensitive method and underestimates the actual nonadherence.
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