In estimating the economic burden of diseases, two main methods are used, including "prevalence-based" and "incidence-based". In the incidence-based method, the patient's costs are calculated from the time of diagnosis to a specific time, for example, one year after diagnosis or the final stage of the disease leads to death or recovery. In the prevalence-based approach, the costs of the disease are calculated over a period of time, for example over a one-year period. This procedure is an appropriate method for evaluating the economic burden of disease . In the present study, the economic burden of AML in Iran for 2020 is estimated from a social perspective using the prevalence-based method. Cost analysis included direct medical, non-medical, and indirect costs.
Estimating the prevalence of AML in Iran
The Cancer Registration Program in Iran was established in 2003 and its reports have been published annually. Therefore, these national data were used to calculate the incidence and prevalence of AML in Iran. Then, by modifying the incidence and mortality rates from their underestimating data, we estimate the prevalence of AML in Iran based on registry system data using the annual percentage change (APC) and survival rate in 2019. Finally, the AML survival rate was achieved from published reports .
Data were collected from inpatients or outpatients at Shariati Hospital, one of the most prestigious medical, research, and educational centers in Tehran, Iran. This Center is the largest referral center for AML patients in Iran and under the supervision of the Tehran University of Medical Sciences.
Leukemia patients need more outpatient care services due to frequent referrals for treatment and recurrence. This Hospital annually provides medical services for more than 190,000 outpatients, more than 305,000 clinical outpatients, and approximately 19,800 emergency cares and is one of the top 4 stem cell and bone marrow transplant centers in the world.
To extract direct medical costs, patient records, demographic and pathological data (for disease staging) were used. Data on direct non-medical and indirect costs were obtained from telephone interviews with patients or their families. Other information was collected using a standard questionnaire [14, 15]. To access patients' records, the necessary authorization was obtained from the Vice-Chancellor of Research and Technology of Iran University of Medical Sciences. And also, the purpose of the study was explained in a telephone interview and the verbal consent of the interviewees was obtained.
Direct medical costs
Progress in AML treatment has increased recovery rates to 15% and 40% in patients over 60 and under 60, respectively [4, 16]. Therapeutic approaches in AML are different based on patients’ risk-stratification like patient’s age, blast percentage, cytogenetic and molecular studies. These therapeutic methods include chemotherapy regimens (induction and consolidation steps), and an autologous or allogeneic hematopoietic stem cell transplantation .
We calculated direct costs for Induction therapy, salvage chemotherapy, Consolidation chemotherapy, and hematopoietic stem cell transplantation.
Induction therapy has 7 + 3 protocol chemotherapy, evaluation of response to treatment at +14 and +28 days of the protocol with bone marrow study and flow cytometry and supportive care treatments. Patients who had no response to induction protocol or relapse after the first remission and who contains high-dose chemotherapy (FLANG, FLAG, CLANG, and CLAG protocols) were candidates for receiving salvage chemotherapy. Evaluation of response to the therapy at +14 and +28 days of the protocol with bone marrow study and flow cytometry, and supportive care treatments [17,18].
Consolidation chemotherapy depends on risk stratification after the first remission. If the risk is low, the patient treats with HIDAC or 5+2 chemotherapy protocols and if the risk is moderate or high, the patient treats with allogeneic hematopoietic stem cell transplantation (Allo-HSCT). Allo HSCT cost includes pre-transplant evaluation tests, CT-scans, and consultations, cell separation, transplant chemotherapy protocol, and basic supportive care treatments [17,18].
Finally, patient records were used to extract the average cost of each diagnostic and therapeutic scale at different stages of the disease. The average cost per patient was calculated . To optimize Iran's Medical tariff in 2020 that are obligated from the ministry of health and estimates the costs of medical services, expert opinions were also used .
Direct non-medical costs
Although there were no non-medical cost studies or data from cancer patients such as AML cancer patients, transportation costs and home care costs were estimated. A questionnaire was used to assess non-medical direct costs. Information was obtained through telephone interviews with patients or their families .
Indirect costs of AML include loss of productivity due to disability, job loss, and early death. The indirect costs were calculated by using the human capital approach, assuming that the monetary value of the production loss due to a disability or untimely death of the patient is equal to the patient's wages before disability and death.
To calculate the cost of productivity lost due to disability, the number of days of disability due to AML was extracted by interviewing patients and their families. The average number of days lost is then multiplied by the patient's average daily wage. Different daily wages were used for employed and unemployed patients.
The minimum daily wage approved by the Ministry of Labor Cooperation and Social Welfare of Iran in 2019 was considered for unemployed patients . Because usually a family member accompanies the patient at the time of referral. Therefore, these time costs were estimated for a family member as a patient, and assuming that family members are unemployed, the minimum wage rate was considered.
To estimate the cost of productivity lost due to early death in AML, the number of deaths due to AML was calculated and adjusted based on age groups and gender from data obtained from the Ministry of Health [23, 24]. Then, the number of years lost in each age group was provided by subtracting the average age group from the life expectancy rate in 2019, published in the World Health Organization (WHO) database .
Finally, the years lost in different age groups were calculated by multiplying the number of deaths in the age groups by the corresponding life expectancy. The minimum annual cost and the average annual cost were used for employed and unemployed patients, respectively. Information on the employment rate in each age group based on gender, as well as the average annual wage and the minimum annual wage was obtained from the Ministry of Labor Cooperation and Social Welfare of Iran . All costs were calculated using the average annual exchange rate of 2020 in US dollars.