Pharmaco-economic variables, safety and adherence of Bedaquiline(BDQ) based regimen in drug resistant tuberculosis

Observational prospective study designed as per STROBE guidelines and will be started after approval of IEC (institutional ethics committee) taking treatment at government medical college and new civil hospital.

Convenient type of non-probability sampling.

Case: Data of DR-TB patients on BDQ-based regimen

Controls: Data of DR-TB patients on other than BDQ-based regimen

Sample size: 100 cases and controls each

Participants will be selected as per definition and Inclusion/Exclusion criteria and verbal and written informed consent from the participants will be taken. Data will be collected for the pharmacoeconomic analysis. Following 4 pharmacoeconomic parameters: cost effectiveness analysis, cost minimization analysis, cost utility analysis and cost benefit analysis will be done as mentioned below.

1) Cost effectiveness Analysis: In CEA only drug acquisition cost will be considered.

Table 1: Cost Effectiveness Analysis (CEA)

Cost of therapy (INR)

Effectiveness

CEA(INR)

|BDQ-based regimen

    |Another regimen

Total Cost of a Treatment Option

= Mean Cost per Defined Daily Dosage (DDD)×Duration of Therapy

Mean cost /DDD of treatment option available at NCH will be use.

The effectiveness measure involved theoretical framework by analysis of positive and negative outcome of each treatment option from review of literature as in Table 2 for effectiveness of Drug Resistant Anti TB regimen options.

Table 2: Effectiveness rating

Criteria

BDQ-based regimen

Value

Another regimen

Value

|Efficacy

     |Adverse Drug Reaction

     |Frequency of administration

     |Bioavailability

Efficacy and Bioavailability will be taken by reviewing various scientific literature.

Effectiveness of a treatment option (in natural unit) =Sum of all criterion rating, where Criterion Rating= Criterion Value× Assigned Weight.

Table 3: Decision Analysis of effectiveness of Drug Resistant Anti TB Drug:

BDQ-based regimen

Another regimen

|Criteria

Value

Assigned weight

Criteria rating

Value

Assigned weight

Criteria rating

|Efficacy

       |Tolerability

       |Frequency of administration

       |Bioavailability

       |Sum of criteria rating

(effectiveness)

The criteria value and assign weight which determines the criteria rating is somewhat arbitrary hence fairly subjective. However, each option being considered was treated identically with respect to the assigned weight to limit the subjectivity.

2. Cost Minimization Analysis: The costs to be included in the analysis include medicine costs, along with other health service costs (e.g., hospital cost, medical staff cost), equipment costs (e.g., syringes, needles, IV sets, sterile water for dilution).

Table 4: Cost Minimization Analysis

Cost categories

BDQ-based regimen

Another regimen

|Acquisition price

   |Doses per Day

   |Prices per Day

   |Health service cost per Day

   |Supplies (to administer medicine)

   |Cost of ADR

   |Cost of laboratory tests

   |Total cost

Cost will be provided by District Tuberculosis Centre and Central Drug Store.

3) Cost Utility Analysis: It is a special type of cost effectiveness analysis, in which the outcome is expressed as a utility measure (e.g., Quality Adjusted Life Year (QALY)

• If an individual has perfect health for a period of 1 year, they will be said to have 1 QALY

• If an individual lives in perfect health but only for half a year, that individual will have 0.5 QALY

• If an individual lives for 1 year in a situation with 0.5 utility (half of perfect health) that individual will have 0.5 QALY

4) Cost Benefit Analysis: It is an economic evaluation that measures both the costs and benefits of treatment alternatives in monetary amounts. The results of cost benefit analysis can be stated as a ratio of benefits to costs or as a simple difference representing the net benefit or alternative over another. Results of such analysis are expressed as benefit- to – cost ratios.[12] It is done by calculating Disability Adjusted Life Year (DALY).

DALY=Years of Life Lost (YLL) + Years Lost due to Disability (YLD)

YLL= Number of deaths × Standard life expectancy at age of death in years.

YLD = Number of prevalent cases × Disability weight

Disability weight is a weight factor that reflects the severity of the disease on scale from 0 (perfect health) to 1 (equivalent to death).

Required data will be recorded in case record form (CRF).

Details regarding the safety of the patient (ADR data) will be recorded in ADR reporting form 1.4 version.

Details regarding the adherence of the medication will be recorded in prevalidated questionnaire.

The assessment of causality, preventability and severity of ADRs will be done by using WHO-UMC causality assessment criteria, Modified Schumock and Thornton scale and Modified Hartwig and Seigel scale respectively.

Data will be analyzed by descriptive statistics and appropriate tests with SPSS software’s 20th version (which is freely available)