**3. Adherence measuring**

The concept of adherence or compliance can be measured in many different ways, including multi-item questionnaire scales, individual questionnaire, independent observations from patients and physicians, electronic monitoring devices, etc.

Many methods have been utilized to collect data for measuring medication adherence. Some data collection techniques include directly observing patients consuming medications, monitoring through electronic pill dispensers, and measuring clinical outcomes, such as, serum drug concentration levels. Other methods include clinical data from clinical trials, administrative claims data, electronic pharmacy databases, registries, patient and provider surveys, and paper medical records. There are several methods for measuring medication adherence using data obtained from these techniques that measure the time a patient has access to medication, including the medication possession ratio (MPR = number of days of medication supplied within the refill interval/number of days in refill interval), proportion of days covered (PDC=total days all drugs available/days in follow-up period), missing days, time to discontinuation, persistence rate, medication gaps, or self-reported questionnaires like Composite Adherence Score (CAS), Morisky Medication Adherence Scale (MMAS) with 4/8/9 questions, and Compliance Questionnaire for Rheumatology (CQR) with 5/19 questions.

#### **3.1. Rheumatic diseases**

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

306 Financial Management from an Emerging Market Perspective

In rheumatology clinics, Berry et al. [17] found nonadherence patients who were answering 'no' to the question "Have you taken medicine regularly as prescribed or directed?", more common among new (28%) than follow-up patients (1%). Overall, the patients were more on nonsteroidal anti-inflammatory drug (NSAIDs) than on diseasemodifying antirheumatic drug (DMARDs), also the adherence was better for them, according to the symptoms and directed dose. Another difference measured in adherence is the cultural one, especially because of the economic impact of the treatment, that can lead to big cost problems. The follow-up adherence among patients with lupus depends on the medications prescribed. McElhone et al. [18] discussed that the perfect adherence rate is between 100% for treatment with azathioprine, 94% for oral steroids, and 68% for NSAIDs.

In the case of rheumatoid arthritis (RA), adherence is estimated at similar values. Researchers such as Neame and Hammond [19] found that 90% of the patients with RA are in fact taking their medication according to doctors' recommendations. Adherence rate is also correlated with the type of medication that is prescribed. The overall adherence is approximately 70% for NSAIDs, 50% for sulfasalazine and 80% for methotrexate, according to Klerk et al. [20]. Viewing the results, the weekly treatment with methotrexate may facilitate the enhanced adherence rate. In addition, patients' result are not as dependent on NSAIDs as it is thought, and this can be a good thing for the recent concerns about the cardiovascular risk associated with continuous usage of the high-dose drug.

#### **3.2. Diabetes**

The healthcare costs and the nonadherence to treatment for diabetes are both problems that need to be resolved. The information that is available at this moment regarding patient's adherence in diabetes is very poor. Studies have shown that adherence in diabetes is related more often to insulin (from 19 to 46%) [21], than to oral agents. The complications and the cost-effectiveness of antidiabetic drugs are a serious problem, according to the American Diabetes Association [22]. Inadequate use or poor adherence to insulin results in ketoacidosis that often requires hospitalization and more costs.

For people with diabetes, all-cause medical costs decrease as hypoglycemic drugs' adherence increases.

Sokol et al. [2] demonstrated that costs and hospitalization risk for people with diabetes monotonically decreased as adherence to drug treatment increased (**Table 2**).

Even if drug cost is bigger and medical cost is smaller in the case of adherent patients (adherence level>80), the total cost is the smallest. These savings probably reflect the effects of


**Table 2.** Costs for people with diabetes.

improved glycemic level on related diseases like microvascular disease or neuropathy, reducing the need for medical services.

Balkrishnan et al. [23] found that a 10% increase in medication possession ratios (MPRs) for an antidiabetic medication was associated with an 8.6% reduction in total annual healthcare costs.

Cobden et al. [36] used MPR to assess diabetic patients and found that MPR of 80% or greater was associated with significant reduction in all-cause healthcare costs. MPR of 68% was associated with total mean costs of \$8056, whereas an MPR of 59% had total mean costs of \$8699.

Gilmer et al. [24] estimated that medical care costs increased significantly for each 1% increase in HbA1c (glycosylated hemoglobin) above 7%. For a person with an HbA1c value of 6%, successive 1% increases in HbA1c resulted in cumulative increases in charges of almost 4, 10, 20, and 30%. For adults with diabetes and other diseases the costs are also increased. The most substantial cost increments occurred in individuals who had diabetes in combination with heart disease and hypertension: a 1% improvement in HbA1c level from 10 to 9% was associated with increasing in costs of \$4116. The differences in costs are lower if the HbA1c value is smaller. If the patient isn't adherent to the antidiabetic medicines, the increased HbA1c will rise the costs for healthcare system (**Table 3**).

Nonadherence to oral hypoglycemic medications may partly explain why only 43% of patients with diabetes mellitus have HbA1c below 7% level [21].

#### **3.3. Pulmonary diseases (chronic obstructive pulmonary disease)**

according to the symptoms and directed dose. Another difference measured in adherence is the cultural one, especially because of the economic impact of the treatment, that can lead to big cost problems. The follow-up adherence among patients with lupus depends on the medications prescribed. McElhone et al. [18] discussed that the perfect adherence rate is between 100% for treatment with azathioprine, 94% for oral steroids,

In the case of rheumatoid arthritis (RA), adherence is estimated at similar values. Researchers such as Neame and Hammond [19] found that 90% of the patients with RA are in fact taking their medication according to doctors' recommendations. Adherence rate is also correlated with the type of medication that is prescribed. The overall adherence is approximately 70% for NSAIDs, 50% for sulfasalazine and 80% for methotrexate, according to Klerk et al. [20]. Viewing the results, the weekly treatment with methotrexate may facilitate the enhanced adherence rate. In addition, patients' result are not as dependent on NSAIDs as it is thought, and this can be a good thing for the recent concerns about the cardiovascular risk associated

The healthcare costs and the nonadherence to treatment for diabetes are both problems that need to be resolved. The information that is available at this moment regarding patient's adherence in diabetes is very poor. Studies have shown that adherence in diabetes is related more often to insulin (from 19 to 46%) [21], than to oral agents. The complications and the cost-effectiveness of antidiabetic drugs are a serious problem, according to the American Diabetes Association [22]. Inadequate use or poor adherence to insulin results in ketoacidosis

For people with diabetes, all-cause medical costs decrease as hypoglycemic drugs' adherence

Sokol et al. [2] demonstrated that costs and hospitalization risk for people with diabetes

Even if drug cost is bigger and medical cost is smaller in the case of adherent patients (adherence level>80), the total cost is the smallest. These savings probably reflect the effects of

**Adherence level Medical cost (\$) Drug cost (\$) Total cost (\$) Hospitalization risk** 

**(%)**

monotonically decreased as adherence to drug treatment increased (**Table 2**).

1–19 8812 55 8867 30 20–39 6959 165 7124 26 40–59 6237 285 6522 25 60–79 5887 404 6291 20 80–100 3808 763 4570 13

and 68% for NSAIDs.

**3.2. Diabetes**

increases.

**Table 2.** Costs for people with diabetes.

with continuous usage of the high-dose drug.

308 Financial Management from an Emerging Market Perspective

that often requires hospitalization and more costs.

Chronic obstructive pulmonary disease (COPD) is a chronic limitation hat is usually progressive and not reversible. The main treatment for this condition aims to reduce symptoms, prevent exacerbations and delay the progression of the disease. Although medication has not been shown to modify the long-term of lung disease, various medications are available to prevent and control patients' symptoms, and improve health. Patient adherence to medication for COPD is very poor compared with rates for medicines and other long-terms conditions. Nonadherence to medication is a risk factor for morbidity, hospital admission and increased mortality.

Zaniolo et al. [27] made a budget impact study to demonstrate the implications of the adherence to patients with chronic obstructive pulmonary diseases. The target population that they


**Table 3.** Costs for patients with diabetes and other diseases.

examined corresponds to the entire sick population. They simulated that the same target population is managed under the same strategies of medical purpose. The current strategy is defined in order to reproduce the actual pattern of healthcare resource consumption and related costs for COPD management.

Toy et al. [28] had examined in their study the adherence level among patients with inhaled COPD medications. They used the data from real-world clinical practice, as well as the national healthcare database. As a conclusion, it was emphasized that a correct management of COPD can be aided by the frequency which the patient is using the drug. Drugs with fewer daily doses are associated with improved adherence, and as well with lower healthcare resource use and cost. For 1000 COPD patients, a 5% increase in proportion of days covered (PDC) reduced the annual number of inpatient visits with 2.5% and emergency room visits with 1.8%, with a slightly increased outpatient visits (+0.2%) and a net reduction in annual cost of approximately \$300,000. This study suggests that dosing frequency should be an important method in increasing adherence of COPD patients because patients with once-daily dosing frequency had highest adherence levels relative to patients with twice-daily, three times daily and four times daily dosing frequency.

Simoni-Wastila et al. [25] used administrative data with COPD patients, medication continuity and proportion of days covered (PDC) for assessing adherence. COPD patients with higher adherence to prescribed treatments experienced fewer hospitalizations and lower medicare costs than those who presented lower adherence behaviors. Both lack of interruption in drug dispensing and higher adherence were associated with better clinical outcomes.

#### **3.4. Heart diseases**

The costs for heart diseases are creating a burden on the patients' finances. Most commonly they experience acute myocardial infarction, known as heart attack. The costs include ambulance rides, diagnostic test, hospital stays, and also surgery if needed. Employees suffering from heart disease require additional days off, so they are less productive at work, so it is not cost-effective for the economy. Additionally, the premature deaths caused by heart diseases are growing in the United States. In 2010, according to George and Hong [26], \$41.7 billion was lost in potential productivity due to cardiovascular diseases.

To lower the high costs of this condition, patients must make small changes in their lifestyle. These preventive changes include weight lost, exercising, avoiding smoking, eating healthy, also they can monitor their blood pressure and cholesterol levels every month, for lowering the rate of mortality.

Sokol et al. [2] demonstrated that hospitalization risk for people with hypertension monotonically decreased as adherence to drug treatment increased. Differences were significantly higher than the outcome for adherence >80% in the case of low adherence (<60%). We observe higher costs only for adherence in the interval [20].

In the case of congenitive heart failure, the differences in costs were not so obvious like in the case of hypertension. The total costs are the highest in the case of adherent patients (adherence level >80%). Hospitalization risk is significant higher than the outcome for adherent patients with congenitive heart failure in the case of patients with adherence in the interval (**Tables 4** and **5**) [20].

Analysis of Financial Losses due to Poor Adherence of Patients with Chronic Diseases and Their... http://dx.doi.org/10.5772/intechopen.70320 311


examined corresponds to the entire sick population. They simulated that the same target population is managed under the same strategies of medical purpose. The current strategy is defined in order to reproduce the actual pattern of healthcare resource consumption and

Toy et al. [28] had examined in their study the adherence level among patients with inhaled COPD medications. They used the data from real-world clinical practice, as well as the national healthcare database. As a conclusion, it was emphasized that a correct management of COPD can be aided by the frequency which the patient is using the drug. Drugs with fewer daily doses are associated with improved adherence, and as well with lower healthcare resource use and cost. For 1000 COPD patients, a 5% increase in proportion of days covered (PDC) reduced the annual number of inpatient visits with 2.5% and emergency room visits with 1.8%, with a slightly increased outpatient visits (+0.2%) and a net reduction in annual cost of approximately \$300,000. This study suggests that dosing frequency should be an important method in increasing adherence of COPD patients because patients with once-daily dosing frequency had highest adherence levels relative

to patients with twice-daily, three times daily and four times daily dosing frequency.

dispensing and higher adherence were associated with better clinical outcomes.

was lost in potential productivity due to cardiovascular diseases.

higher costs only for adherence in the interval [20].

Simoni-Wastila et al. [25] used administrative data with COPD patients, medication continuity and proportion of days covered (PDC) for assessing adherence. COPD patients with higher adherence to prescribed treatments experienced fewer hospitalizations and lower medicare costs than those who presented lower adherence behaviors. Both lack of interruption in drug

The costs for heart diseases are creating a burden on the patients' finances. Most commonly they experience acute myocardial infarction, known as heart attack. The costs include ambulance rides, diagnostic test, hospital stays, and also surgery if needed. Employees suffering from heart disease require additional days off, so they are less productive at work, so it is not cost-effective for the economy. Additionally, the premature deaths caused by heart diseases are growing in the United States. In 2010, according to George and Hong [26], \$41.7 billion

To lower the high costs of this condition, patients must make small changes in their lifestyle. These preventive changes include weight lost, exercising, avoiding smoking, eating healthy, also they can monitor their blood pressure and cholesterol levels every month, for lowering

Sokol et al. [2] demonstrated that hospitalization risk for people with hypertension monotonically decreased as adherence to drug treatment increased. Differences were significantly higher than the outcome for adherence >80% in the case of low adherence (<60%). We observe

In the case of congenitive heart failure, the differences in costs were not so obvious like in the case of hypertension. The total costs are the highest in the case of adherent patients (adherence level >80%). Hospitalization risk is significant higher than the outcome for adherent patients with congenitive heart failure in the case of patients with adherence in the interval (**Tables 4** and **5**) [20].

related costs for COPD management.

310 Financial Management from an Emerging Market Perspective

**3.4. Heart diseases**

the rate of mortality.

**Table 4.** Healthcare costs and hospitalization risk at different levels of adherence for patients with hypertension.


**Table 5.** Healthcare costs and hospitalization risk at different levels of adherence for patients with congenitive heart failure.

Similarly, for hypertensive patients, the total costs are the smallest even if the drug cost is higher. These values reflect the impact of related conditions like, for example, renal disease.

Levine et al. [29] estimated for cardiology patients in USA that 125,000 deaths per year lead to a societal cost of 20 million lost work days and \$1.5 billion lost earnings.

McCombs et al. [30] used individual patient inpatient and outpatient claims data to identify increased health service costs associated with interruptions in therapy. The medicines costs were lower with \$281, but the healthcare costs were higher with \$873 (\$637 due to increased hospitalization).

#### **3.5. Barriers to chronic disease treatment and management**

Morbidity from nonadherence to medications is a major public health problem in many therapeutic areas [31]. About one in four people do not adhere well to prescribe drug therapy. Poor adherence is considered a critical barrier to treatment success and remains one of the challenges to healthcare professionals [32]. Combining adherence to drug therapy with adherence to other interventions limits the ability to examine the relation between adherence to drug therapy and health outcomes. The effect of adherence should be measured on an objective health outcome, such as mortality. Individual studies have reported that good adherence was associated with a lower risk of mortality. The association between adherence to harmful therapy and mortality is a very important subject in the light of recent issues of the safety of patients and postmarket drug surveillance.

The correlations between the mortality/morbidity rates for most chronic diseases are shown in **Table 6**.

Most nonadherence is intentional. Patients make the decision to not take their medicines based on some reasons:


The costs of new drugs often exceed the costs of existing drugs. Such increased costs can be compensated by savings in other areas of health system (costs-offsets). For example, a new drug has fewer side effects and fewer costs to cure them. But, the first step is the patient to be adherent and to respect the prescription.

We cannot say that nonadherence always leads to financial losses. Nonadherence is not always bad for the patient. Nonadherence is protective if the prescription is inappropriate or has adverse reactions. It is not useful to pay for an inefficient drug. New undesired costs will appear if side effects occur. Savings associated with undercompliance with overprescribed medications are positive economic effects. We must highlight the fact that the doctor, the pharmacist and the patient carry mutual responsibility for the outcome of the treatment. Further work is needed to develop optimal adherence patterns for individual patients and treatments. Important policy decisions need to be made about increasing nonadherence.

Physicians play a key role in medication adherence. Trust and communication are two elements critical in optimizing adherence. Various studies have shown that physicians trust is more important than treatment satisfaction in predicting adherence to prescribed therapy. In consequence, physicians trust correlates positively with the acceptance of new medication, and improves the self-reported health status. A recent meta-analysis of physician communication and patient adherence to treatment found that there is a 19% higher risk of nonadherence among patients whose physician communicates poorly than among patients whose physician communicates well [34].

The correlations between the mortality/morbidity rates for most chronic diseases are shown

Most nonadherence is intentional. Patients make the decision to not take their medicines

• Fear: Patients may be scared of potential side effects or side effects they had previously

• Misunderstanding: Patients do not understand the need for medicine, the side effects or the

• Too many medications: The greater the number of different medicines prescribed and the

• Lack of symptoms: Patients who do not feel any differences when they start or stop to take

• Depression: Patients who are depressed are less likely to take their medications as

• Mistrust: Patients may be suspicious of their doctor's motives for prescribing certain medications, for example because of the marketing efforts of pharmaceutical companies to influ-

The costs of new drugs often exceed the costs of existing drugs. Such increased costs can be compensated by savings in other areas of health system (costs-offsets). For example, a new drug has fewer side effects and fewer costs to cure them. But, the first step is the patient to be

We cannot say that nonadherence always leads to financial losses. Nonadherence is not always bad for the patient. Nonadherence is protective if the prescription is inappropriate or has adverse reactions. It is not useful to pay for an inefficient drug. New undesired costs will appear if side effects occur. Savings associated with undercompliance with overprescribed medications are positive economic effects. We must highlight the fact that the doctor, the pharmacist and the patient carry mutual responsibility for the outcome of the treatment. Further work is needed to develop optimal adherence patterns for individual patients and treatments. Important policy decisions need to be made about increasing

Physicians play a key role in medication adherence. Trust and communication are two elements critical in optimizing adherence. Various studies have shown that physicians trust is more important than treatment satisfaction in predicting adherence to prescribed therapy. In consequence, physicians trust correlates positively with the acceptance of new medication, and improves the self-reported health status. A recent meta-analysis of physician communication and patient adherence to treatment found that there is a 19% higher risk of

• Worry: Concerns about becoming dependent on a medicine leads to nonadherence.

higher the dosing frequency, the more likely a patient is nonadherent.

in **Table 6**.

based on some reasons:

prescribed.

nonadherence.

with the same or similar medication.

312 Financial Management from an Emerging Market Perspective

expected time it will take to see some results.

their medicines may see no reason to take it.

ence some prescribing patterns.

adherent and to respect the prescription.

• Cost: The prices of medicine can be a barrier to adherence.

Healthcare providers play an unique role in assisting patients to carry out healthy behaviors and also to change patient's beliefs about the risks and benefits of new medication. Another factor is concordance, in which patients and their providers (and physicians) agree whether


**Table 6.** Morbidity and mortality rates for chronic diseases [33].

and how a medication should be taken. Adherence requires the patient to believe there is a benefit to the medicine being prescribed and agree with the instructions on how to take it. Building trust and developing skills for successful communication between the patients and their provider, demands time, effort, knowledge, and practice.

Even those patients who fill and refill their prescriptions appropriately may have lapses in the continuity of their doses. One in five patients who receives a prescription medication cannot read the label.

Elliot et al. [35] concluded there is not possible to make definitive conclusions about the costeffectiveness of Adherence-Enhancing Interventions (AEIs) due to the heterogeneity of the reported studies: unclear reported adherence and outcomes, poorer quality of costs data, and omitted some cost elements.
