**2. Pharmacoeconomic tools**

life from a chronic disease, and approximately 20% are hospitalized because of it. Another perspective is that they are costly, but in many cases preventable. The main cause is usually lifestyle choices that are hard to change; eating foods that are low in fats, becoming more physically active, and avoiding tobacco can help from developing high-risk conditions and diseases. Patients with multiple chronic diseases struggle with great challenges on their daily lives; also, they experience poor health outcomes and will tend to use health national services more than patients with single chronic disease. Not respecting treatment prescriptions have both personal health impact and health economics consequences. These people are regarded as the highest cost patient populations in the healthcare system [1], with a poor adherence to treatment and medical advices. Worldwide, experts are examining the situation in which health care can be better organized to meet the needs of every patient. It was demonstrated that every dollar spent for improving adherence saves seven dollars in total healthcare costs [2, 3]. The absence of appropriate clinical practice guidelines for patients with multiple chronic diseases is a huge problem, which healthcare providers contend. Furthermore, patientcentered care needs to be supported through the transition of a more oriented approach to

Moreover, not taking the required medication prescribed can have both personal health impact and health economics consequences. Recently, patients have shown increased interest in their own healthcare possibilities, raising the overall rate of adherence to treatment. However, the cost-effectiveness is still a parameter that is often ignored when a medical expert chooses to treat different kinds of conditions. Adherence is defined as "persistence in a practice," so this definition emphasizes the routine that people with chronic disease ideally engage in when

The term first used was "compliance." Charavel et al. [5] described this concept like physician alone makes the treatment decision, while the passive and dependent patient is obliged to comply with it. But the patient is not so silent and the term "adherence" is more used, the

Adherence cannot be defined as an "all or nothing" response in which the patient either follows the prescriber's instruction to the letter (adherence) or deviates from it in some way (nonadherence) [6]. A patient is considered adherent if he/she takes 80% of his/her prescribed medicine(s). In the current era of free and easy access to information, with a higher educational level across the population, the concept of "concordance" seems to win for some diseases, when the patient want to defer decisions entirely to their health professionals or family members. Some patients prefer a collaborative role, whereas others prefer a passive role.

The most common chronic diseases that have a low adherence rate to treatment are asthma, diabetes, heart disease, obesity, rheumatic diseases, eating disorders, chronic obstructive pul-

The estimated rate of adherence is only half of the percentage of the patients with chronic diseases. Ten days after a new prescription has been filled [7], another quarter of the patients have missed one dose of the medication (intentionally or unintentionally). This kind of behavior

help patients prioritize their condition.

302 Financial Management from an Emerging Market Perspective

taking prescription medication [4].

patient is more engaged in taking prescription medication.

monary disease (COPD), and psychotic disorders.

An economic evaluation of adherence consists in assessing the outcomes and costs of intervention designed to improve health. It is like we evaluate a new intervention when the new one is not compared with usual health care, for example the standard intervention, but with no intervention at all. The incremental cost-effectiveness ratio (ICR) is the difference in costs (C) between the drug and no drug divided by the difference in effects (E) between the drug and no drug.

$$\text{LCR} = \frac{\text{C}\_{\text{drug}} - \text{C}\_{\text{no drug}}}{\text{E}\_{\text{drug}} - \text{E}\_{\text{no drug}}} \tag{1}$$

There are four form of economic evaluation of interventions:


A summary of the characteristics of these types of economic evaluation is described in **Table 1**.

The most used techniques are cost-effectiveness analysis (CEA) and cost-utility analysis (CUA). A budget impact analysis (BIA) might be added to the economic evaluation.

#### **2.1. Cost-effectiveness analysis**

A cost-effectiveness analysis of adherence shows effects in naturally occurring units, such as death, illnesses or burns prevented, and the costs in monetary units (Euros, Dollars, etc.). We can use this type of analysis because it provides information about the relative efficiency of alternative interventions that serve the same goal, what happened if the adherence is smaller comparative with a higher value. A cost-effective analysis must contain effect outcomes and the costs for the different values of adherence and should compare them. Cost-effectiveness analysis is the simplest type of economic evaluation to explain the differences in outcomes.

Measuring benefits in natural units is the main advantage and focusing on a single outcome adherence—could be considered a disadvantage.

#### **2.2. Cost-utility analysis**

Cost-utility analysis evaluates the difference in costs relative to the difference in quality adjusted life years (QALYs). Both types of effects—on the life expectancy and on quality of life—are used to justify the costs. QALYs are represented by the number of gained life


**Table 1.** Characteristics of the four types of pharmacoeconomic evaluations [11].

years corrected for quality of life. The QALY is the standard outcome measure existed in health economic evaluations, but there are some countries (Germany, Spain, and USA) that decided to ban the use of QALY in Health Technologies Assessment (HTA), after considering that QALY is methodologically and ethically not robust for health decision making. It is based on the use of subjective parameters, which are less robust than the chemical and biochemical parameters.

QALYs are determined with the aid of generic measurement instruments like EQ-5D [12], SF-6D (Short Form 6D), DCE (discrete-choice experiment), or MCDA (multi-criteria decision analysis). Another examples of generic instruments are Nottingham Health Profile (NHP), quality of well-being scale (QWB), sickness impact profile (SIP), and Health Utilities Index (HUI) Mark III.

EQ-5D is one of the most commonly used questionnaires to measure health-related quality of life (HRQOL). It consists of a questionnaire about five directions of current health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a visual analogue scale (EQ-VAS). It was developed for adults, but a new version has been recently developed for children aged 8–18 years old (EQ-5D-Y) and the five dimensions are: walking about, look-after myself, doing usual activities, having pain or discomfort, feeling worried, sad or unhappy.

Nottingham Health Profile (NHP) [13] includes two parts: Part I about distress within the following domains: emotions, sleep, social isolation, energy, pain, and mobility and Part II about health-related problems within the domains: occupation, housework, social life, home life, sex life, hobbies, and holidays.

Quality of Well-Being Scale (QWB) [14] includes questions about symptoms/problems, mobility, physical activity, and social activity.

Sickness impact profile (SIP) [15] includes questions about sleep/rest, eating, work, ambulation, mobility, communication, home management, recreation and pastimes, body care and movement, alertness behavior, emotional behavior, and social interaction.

Health Utilities Index (HUI) Mark III [16] includes questions about vision, hearing, speech, ambulation, dexterity, cognition, pain and discomfort, and emotion **(Figure 1**).

The complexity of assessing outcomes in cost-utility analysis is a disadvantage, even if this analysis can decide the best way of spending a given treatment budget or the healthcare budget as a whole.

#### **2.3. Cost-benefit analysis**

There are four form of economic evaluation of interventions:

A summary of the characteristics of these types of economic evaluation is described in **Table 1**. The most used techniques are cost-effectiveness analysis (CEA) and cost-utility analysis

A cost-effectiveness analysis of adherence shows effects in naturally occurring units, such as death, illnesses or burns prevented, and the costs in monetary units (Euros, Dollars, etc.). We can use this type of analysis because it provides information about the relative efficiency of alternative interventions that serve the same goal, what happened if the adherence is smaller comparative with a higher value. A cost-effective analysis must contain effect outcomes and the costs for the different values of adherence and should compare them. Cost-effectiveness analysis is the simplest type of economic evaluation to explain the differences in outcomes. Measuring benefits in natural units is the main advantage and focusing on a single outcome—

Cost-utility analysis evaluates the difference in costs relative to the difference in quality adjusted life years (QALYs). Both types of effects—on the life expectancy and on quality of life—are used to justify the costs. QALYs are represented by the number of gained life

**Methods Costs Effects Evaluation question**

Cost-utility analysis (CUA) Monetary units Utility and QALY (quality-adjusted

**Table 1.** Characteristics of the four types of pharmacoeconomic evaluations [11].

Monetary units Natural units (life-years gained,

burns prevented, etc.)

adjusted life-year)

Monetary units The effects are not measured, since

life-year) or DALY (disability-

they are considered to be equal

Monetary units Monetary units Are the benefits worth the

Comparisons of interventions with same

Comparison of

interventions with different

Least-cost comparisons of programs with the same

objective

objectives

costs?

outcome

(CUA). A budget impact analysis (BIA) might be added to the economic evaluation.

• Cost-effectiveness analysis

304 Financial Management from an Emerging Market Perspective

• Cost-minimization analysis

**2.1. Cost-effectiveness analysis**

**2.2. Cost-utility analysis**

Cost-effectiveness analysis

Cost-benefits analysis

Cost-minimization analysis

(CEA)

(CBA)

(CMA)

adherence—could be considered a disadvantage.

• Cost-utility analysis • Cost-benefit analysis

> Cost-benefit analysis evaluates the difference in costs relative to the difference in benefits, with the benefits expressed in monetary units. This is the only pharmacoeconomic analysis that could determine how much more or less of society's resources could be allocated to pursuing increasing patient adherence.


**Figure 1.** EQ-5D health questionnaire.

Measuring benefits in monetary units is a disadvantage because it is a problem to valuate benefits, including death and disease, in money units.

#### **2.4. Cost-minimization analysis**

This analysis is performed when two health alternatives are equal, but few interventions are actually equally effective. Some evidence must support the assertion that outcomes are the same.

Cost-minimization analysis is not an appropriate method of analysis adherence costs.

In order to estimate costs, studies must include costs for hospitalization, outpatient services, hospital stays, emergency care, clinical visits, laboratory tests, professional services, pharmaceuticals, and medical devices. Patients' copayments and deductibles must not be included in costs assessment. Indirect costs (cost to society due to illness) and direct nonmedical costs (costs to the patient such as travel) could have a significant impact on total costs.
