Cost-effectiveness of invasive devices versus non-invasive devices for screening of anemia in field settings in India: A study protocol

Background

Anemia is a public health problem that affects women and children, especially in low- and middle-income countries (LMICs). It affects nearly 53% of women and 58% of children in India¹. The most commonly used parameter to diagnose and detect anemia is by measuring hemoglobin (Hb). Several methods have been tested to ascertain an accurate value of Hb that can guide the course of management.

In India, Sahli’s hemoglobinometer has been in use extensively in public health settings. Its accuracy is being questioned, and hence there is a felt need to replace this device by a more accurate and easier-to-use method. Currently, several invasive and non-invasive devices are available for detecting anemia. These have been evaluated in diverse settings and population groups with mixed findings^2–4. In the absence of a concrete evidence, there is a need to examine the devices that have the potential to be included in public health programs. Given the fact that most of the screening happens in community and outreach settings where provision for a laboratory support seems difficult, the device ought to be tested in field settings with health workers (Auxillary Nurse Midwives or ANMs) as end users.

Currently four such devices have been identified that have the potential to be used in public health settings, namely, digital hemoglobinometers (True Hb and Hemocue), and non-invasive devices, i.e. Masimo Pulse Oximetry test and AJO spectroscopic device test⁵. There is a need to evaluate them in order to identify the most cost-effective device suitable for use in Indian and similar settings.

Methods

Study participants

The study population will include consecutive adult patients attending the outpatient departments (OPD) of urban and rural field practice areas attached to the select Medical Colleges. Children, pregnant women and patients suffering from bleeding disorders will be excluded from the study. All the patients will be recruited face to face at the clinics. Only those patients who are advised Hb estimation as part of the routine investigations will be screened for their eligibility for the study. They will undergo the reference (Gold standard) test. In addition, each patient will be subjected to one or two index tests. Allocation of participants to different index tests will be based on a predefined weekly schedule⁵.

A sample of size of 600 is required to assess the diagnostic accuracy of each device based on a 50% prevalence of anemia, sensitivity = 82% (TrueHb) and 82% (HemoCue, at 5% level of significance. Details of the calculation have been mentioned elsewhere⁵.

Data collection

Individual level data on Hb readings of autoanalyzer and other devices will be collected electronically. Data from field workers will be collected on paper forms. Data pertaining to every participant will be linked using a unique identification number given at the time of recruitment. Blinding will be ensured by allowing users to upload the data real time that will be merged at the central level using unique identification number. This will help maintain the validity of the study⁵. Missing data or indeterminant data of the index test or reference standards will be excluded from the analysis.

Cost assessment

We will capture the costs using a step-down costing methodology on paper forms, that will be transferred to a customized tool created in MS Excel, available as Extended data¹⁰.

Unit costs of all resources used in the different activities occurring in the in OPDs for the purpose of screening will be collected. The cost of ANM time will be calculated based on the time they would devote for testing for anemia including noting down patient details and test results. The costs will include full salary including fringe benefits.

The life-cycle of each medical device, considered as capital equipment in the study, will be 2.5 years. Annual maintenance cost of all diagnostic equipment will be assumed to be 10% of the annual rental value. Costs of other equipment such as syringe, needle, cotton swab and other consumables for conducting each test will also be accounted for.

The rental value of clinics (urban and rural health centers) will be captured based on present value as per the local information. Contribution of rental values of clinics and capital equipment towards each test will be calculated based on the time required to perform the test¹¹.

To determine the examination cost, we will prepare the list of equipment needed to conduct each test. At the hospital, the examination cost will include both direct and overhead costs. Direct costs will include labor, capital and material costs. Labor cost will be the cost of ANM time, calculated based on the time they would devote for testing for anemia including noting down patient details and test results. Average time taken by ANMs to perform the test based on real-time observations of at least 30 patients would be captured. The costs will include full salary including fringe benefits. Capital costs will include annualised discounted depreciation cost of furniture, equipment and instruments used in the OPDs for screening. The material costs will include the actual usage of drugs, medical supplies, and office supplies for performing each test. Any wastage of resources incurred in the process will be accounted for. These costs to the public health system will be elicited from the records/ publications.

Overhead costs will not be considered as both the facilities being large public hospitals, are managed through government funding; it will be difficult to identify budgetary allocations, and expenditure heads for allocation towards examination cost for each test.

The cost data will be collected in a MS-Excel divided into eight sections named as under:

i. Information about the facility: basic details of the facility will be collected.

ii. General information: which include data about working hours of the health facility

iii. Salary structure of the ANM as reported

iv. Details of Equipment: The cost of devices will be directly obtained from the manufacturers in the prescribed format. The format will include name of the device, unit price and expected life of the equipment. This data will be collected across the sites in Kolkata and Puducherry. The prices provided by the manufacturer will be considered for cost of screening.

v. Consumables: Under this section, details of consumables which includes materials and supplies issued, consumed, quantity used per test, and price per unit for every device will be collected in the facility.

vi. Details of the physical infrastructure: Under this section area, monthly rental price of 100 square feet place where the center is located and expenditure (if any) on renovation or construction of accessory items will be collected.

vii. Details about non-medical items: Name and quantity of functional non-medical items in each room will be physically observed by the researcher and reported.

viii. Activity time: Under this the respondents will be asked to report the activities which they perform and the time they spend routinely for the same. At both the sites the time which the ANM take for conducting the test will be estimated.

The costs will be presented as average values across each medical device. The proportion of cost distribution across human resources (ANM), equipment (device, charger and adapter), accessories (microcuvettes/strips), consumables (items used in the test), non-medical (items in examination room) and examination room (rental value) will also be presented.

Measurement of cost-effectiveness

Cost-effectiveness analysis will assess the relative efficiency of the invasive and non-invasive methods for detecting anemia. Standard protocols for conducting such evaluation of diagnostic tests would be used¹². This will be reported as ‘correct diagnosis’ as the outcome measure. Correct diagnosis would be defined as ‘agreement of the result of the particular diagnostic method with the gold standard’ or detection rate⁵. The detection rate will be the sensitivity of the devices i.e. ability of the devices to identify true positives. Since the priority of the national program is detection of severe anemia, we will consider the detection rates of anemia and severe anemia to calculate effectiveness.

The health-related quality of life (HRQoL) of patients will be measured at the time of enrolment into the study using the EQ- 5D-5L questionnaire¹³.

Additionally, the user friendliness across key attributes (ease of use, efficiency in daylight, scope of subjective errors, portability, convenience to patient, interpretation of Hb results, need for power/battery, average time taken for performing one test, and expertise required) will also be analyzed.

General principles of cost-effectiveness will be applied to the results of costs and detection rate of each device¹⁴. The device with best accuracy results (sensitivity in this case) will be taken as the reference. Then it will be determined if this device was dominated by other devices. A dominated device is more costly, but less effective than another device. For non-dominated devices, the cost-effectiveness analysis will combine the unit costs per detection rate, i.e. the incremental cost effectiveness ratio (ICER).

The ICER will be calculated as: [(Mean cost per test) device A − (Mean cost per test) device B] / [(Detection rate) device A − (Detection rate) device B].

ICER values will be presented using costs and detection rates of each device, and separately for detection of anemia and severe anemia.

The results of cost-effectiveness analysis would be presented as incremental cost per detection rate of one method compared to the other. Results would be presented in a manner enabling easy comparison between all diagnostic techniques to assess relative efficiency.

Long-term benefits of anemia screening

The long-term benefits and cost-effectiveness of early detection of anemia comparing invasive and non-invasive methods will be analysed using decision analytical model, by quantifying the contribution of screening in preventing morbidities using data from Indian studies.

Assessment of health-related quality of life (HRQoL)

HRQoL will be assessed using a standardized method. Five domains, namely mobility, self-care, usual activities, pain/discomfort, anxiety/depression will be considered. Each one will be given a score ranging from 1 to 5, with 1 being the worst and 5 the best. The response of five questions of EQ-5D-5L questionnaire will be converted into a single index value as described in the methodology of the questionnaire¹³.

User friendliness

Laboratory technicians and ANMs will independently rate each of the following criteria: ease of use, efficiency in daylight, scope of subjective errors, portability, convenience to patient, interpretation of Hb results, need for power/battery, average time taken for performing one test, and expertise required, on a scale of 1 (very poor) to 5 (excellent) for each device method. The total score across each of these parameters for laboratory technicians and ANMs will be used to identify user friendliness for each method (maximum score for each method.

Sensitivity analysis

One-way and probabilistic sensitivity analysis will be conducted using lower and upper bound of sensitivity values of each device, and other cost parameters (e.g. accessories, consumables etc.). Sequential tornado analysis will be presented using ICER values from the sensitivity analysis in order to rank-order the different variables that influence the cost per detection rate values¹⁵. Scenario analysis will be conducted for detailing the annual costs conducted by 1 ANM in a health facility for detecting anemia and severe anemia.

Reporting of results will be based on Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guidelines for reporting health economic evaluation studies¹⁶.

Annexure 2, available as Extended data, provides details the parameters of the proposed data analysis¹⁰.

Ethical approval

Data collection will be started after obtaining ethics clearance from the Institutional Ethics Committee of the Indian Institute of Public Health, Delhi (IIPHD), All India Institute of Medical sciences (AIIMS), New Delhi and two recruiting sites (JIPMER, Calcutta Medical College). Written informed consent will be obtained from every eligible participant. Information collected will not have access to anyone else other than the research team. The treatment of patients will be based on the readings of the reference test and will in no way influence the results of the index test.

Conclusion

This paper constitutes a protocol for the costs and cost effectiveness of medical devices in a LMIC. The evidence generated will contribute significantly by lending evidence on the use of cost effectiveness to influence decisions.

Data availability