What is Non-Compliance?

Compliance

It is the use of medication according to physician instruction by the patient for the treatment of some illness.

Non-compliance

Failure to obey the instructions of a physician by the patient for the management of illness.

“Lack of compliance with the instructions of the physician by the patient in taking medication, diet, exercise, smoking, and drinking habits.”

Adherence

This term is used to emphasize that patients are free to decide or to adhere to the physician's instructions and in case of non-compliance only the patient is not blamed.

Concordance

This term is used to denote the drug to which the patient and physician agree about the nature of the illness and the need for treatment.

Level of compliance

It is expressed by % compliance.   % compliance = NDP – NME x 100 / NDP

NDP = No of doses prescribed

NME = No medication errors

If the result is less than 90 %, then it is called suboptimal usage of drugs or non-compliance.

Non-compliance not only involves failure to obey physician instructions but also involves the underutilization or overutilization of medication. Therefore non-compliance varies in intensity, extent, and frequency.

Examples:

1. A drug is prescribed three times a day and the patient takes it once a day.
2. Instead of 250 mg prescribed, taking less than 250 mg or more than 250 mg will be non-compliance.
3. Generally, antibiotics are prescribed for 7 days. So taking antibiotics for less or more than seven days will be non-compliance.

Importance of non-compliance

Non-compliance not only produces problems for the patient but also for the physician, lab technician, and even medicines (in the form of resistance). For examples;

1. It is estimated that a significant % of the population does not take a complete duration/course of therapy which may result in resistance to that drug as in the case of antibiotics.
2. Failure to take any single contraceptive pill may lead to unwanted pregnancy.
3. Non-compliance with anticonvulsant drugs results in uncontrolled seizures.
4. Failure to take a single dose of clonidine or insulin will result in fatal consequences.
5. Sometimes the taste or smell of the drug is good and the patient may take more than prescribed. This is over-utilization and may result in toxicity.
6. Less dosage, less dose units, or discontinuation of the drug result in underutilization which ultimately results in overutilization of the drug or re-assessment of the patient.
7. An important outcome of non-compliance is the destruction of the outcomes of clinical trials.
8. Due to non-compliance, there is a wastage of expensive medicines.
9. Non-compliance may also lead to misuse of drugs e.g. taking a double dose after missing a dose.
10. Non-compliance can also result in drug abuse.

Detection of Non-Compliance/Methods of Assessment of Non-Compliance

The methods of assessment of non-compliance can be classified into two categories:

1. Direct methods
2. Indirect methods

1. Direct methods

It includes :

i. Patient self-reports

ii. Pill count

iii. Change in a dose of metered dose inhaler

iv. Computerized compliance monitoring system

v. Observing clinical outcomes

i. Patient self-report/ patient interview/ interrogation method

The patient self-report may be prepared by ;

• Patient interview
• Or interrogation method

During the patient interview, the physician will ask questions in a non-judgmental manner as the interrogation method is used in clinical trials.

In this case, a study questionnaire is prepared and patient data is collected. The questions may include:

• Incidence of side effects.
• The inconvenience of dosage regimen.
• Clarity of label instructions.
• The overall level of comprehension.

The data obtained is subjective and has a notorious effect on the study protocol. This method has ;

• Low cost
• Poor feasibility
• Poor accuracy

ii. Pill count

• It is based upon the difference in the tablets initially made available to the number of tablets remaining at the end of the course of treatment. It is also known as the residual tablet count method.
• This method gives an overestimation of compliance.

iii. Change in weight of metered dose inhaler

• A metered-dose inhaler (MDI) is a device that delivers a specific amount of medication to the lungs at actuation. So in this case, the change in weight of the MDI can be used to assess compliance.

iv. Computerized compliance monitoring system/Medication event monitoring system

In this case, a microprocessor is fixed in a container and it will count each time the container is inverted from this we can assess patient compliance. Anyhow, inversion can occur intentionally and even unintentionally. An example is an automatic eye drop dispenser.

v. Observing outcomes

• In this case, the physician assesses the patient's compliance by asking him for follow-up and seeing the outcome. However, sometimes in cases like diabetes, hypertension etc. the patient has to take medicines throughout life. A patient may obey physician instructions for the ist week. Then he/she may be non-compliant for some days and then, before visiting his/her physician, the patient starts following the physician's instructions in the last week. This is called pre-appointment behavior or tooth-brush behavior. Thus a patient of a controllable disease may avoid precautionary measures which can not be assessed.

vi. Rate of prescription refill methods

• In this method, the patient card is issued and then refilled after a specific time interval. From the prescription refilling, patient compliance is assessed. e.g. in the case of T.B. patient has his/her own patient card which he/she refills at the specified date.

2. Direct Methods

These include;

i. Biological markers

ii. Tracer compounds

iii. Drug analysis

i. Biological markers

These are to be detected in biological fluids, especially in urine and blood. If these are present, it means the patient is showing compliance. Special markers are added in the preparation which should be;

• Pharmacologically inactive
• Non-accumulative
• Should Not show physical or chemical interaction or attraction.
• Rapidly and completely excreted in biological fluid.
• The best urine marker is riboflavin (vit-B2).
• Glycosylated hemoglobin in the blood of diabetic patients shows an objective assessment of compliance preceding 3 months.

ii. Tracer compounds

• Tracer compounds are incorporated into the drugs. These should be used in very small quantities but should have greater t½. for example, Phenobarbital and digoxin.

iii. Drug analysis/ Drug assay

• In this method, the drug is directly measured in the sample. In present times, it is a very rapid and quick method due to advanced technology. Examples are rapid chromatographic technique and rapid immunoassay technique.
• This method shows excellent accuracy, however is expensive.

Causes Of Non-Compliance

The causes of non-compliance can be well highlighted under the following headings.

1. Patient-oriented problems
2. Disease state-related problems
3. Therapeutic regimen-related problems
4. Physical limitations
5. Miscellaneous problems
6. Poor labeling
7. Socioeconomic or dimorphic of the patient
8. Deliberate deviation
9. Inappropriate packaging
10. Inappropriate labeling
11. Social isolation
12. Mental reality
13. Patient interaction with a physician

ALSO READ: Medication History Interview

1. Patient-oriented problems

The patient is willing to take the medication but he/she has ;

• Forgetfulness
• Poor eyesight
• Too small writing of the prescription or confusion
• Misprinting
• Language problem
• Misunderstanding
• Illiterate person
• The patient thinks that the drug prescribed by the physician to him is not good for him.
• The patient visits two or more pharmacies or physicians.

2. Disease state-related problems

• Psychiatric diseases make the patient non-cooperative towards the medicine.
• Some diseases that are not related to symptomologies such as hypertension and hypercholesteremia make the patient non-compliant.
• Vomiting associated with the medicines leads to non-compliance.
• There are certain conditions that interfere with the condition of the patient, thus non-compliance results.
• When the symptoms disappear, the patient becomes ready to discontinue the therapy. This is called asymptomatic.
• Compliance is directly proportional to disability. If the disability is greater, a patient will show compliance and vice versa.

3. Therapeutic regimen-related problems

i. Multiple drug therapy

• It is generally agreed that as the number of drugs in a prescription increases, the chance of non-compliance increases e.g. if there are five drugs in a prescription that are to be taken at different intervals, patients may get confused, and thus non-compliance may result then.

ii. Frequency of administration

• Research was conducted on three groups of patients to demonstrate the relation b/w frequency of administration and compliance. The result was as under:

Frequency of administration	Compliance showed
3 times a day	59 %
Two times a day	74 %
Once a day	85%

iii. Duration of Therapy

• If the duration of therapy is less, chances of compliance are more, and vice versa e.g. in T.B. the duration of therapy is long and thus, the chances of compliance are less.

iv. Adverse drug reactions

• Nausea, vomiting, and alopecia associated with the antineoplastic agents create problems for the patient. Similarly, prolonged use of antihypertensive drugs such as β-blockers and antidepressants produces sexual dysfunction. Due to such adverse reactions, the patient may show non-compliance.

v. Cost of the drugs

• Both low-cost and high-cost may be responsible for non-compliance. In the case of low cost, a patient may think that the quality of the drug is of a low standard while in case of too high cost, the patient may not afford the high price of the medicine. Thus both cases may be responsible for non-compliance.

vi. Taste or smell of the drug

• Sometimes a drug may have a bitter taste or bad smell (e.g. potassium chloride solution) and the patient may be reluctant to take that. So in order to improve compliance flavourants are added.

4. Physical limitations

Physical limitations also add to the non-compliance of the patient. For examples;

i. When the pharmacy is at a distance.

ii. When working hours are odd.

iii. Certain dosage forms such as suppositories, enemas, eye drops, ear drops, etc. require specific instructions and some companion.

iv. Inhalers require a relation between the fingers of the patient and the rate of breathing.

All the above-mentioned and other similar factors produce barriers between compliance and patient, either one way or another.

5. Miscellaneous problems

i. Social and psychological beliefs

such as;

• No benefit of medicines
• Fear of ADRs
• Daniel (refuses to take medicines)

ii. Confidence and trust in the doctor

iii. Religious beliefs. 

For examples;

• Muslims do not take alcohol.
• Jeus do not take procaine insulin.
• Hindus do not use gelatin.
• Muslims do not take medicines during fasting.

6. Poor Labeling

• It is estimated that more than 25% of prescriptions do not contain adequate labeling.
• Usually, the prescription contains the label “Take when required”. this sentence is interpreted by different persons in a different manner. This is poor labeling because taking medicine w.r.t time is undefined. Instead, it should be labeled with terms like B.I.d or T.I.D, etc.

7. Socioeconomic / Dimorphic of patient

• Socioeconomic status of the patient is one of the major factors for non-compliance.
• According to a survey, non-compliance is more common in unemployed people as compared to the employed. Similarly in unmarried and divorced patients, non-compliance is more.

8. Deliberate Deviation

• Taking all the medication at one time.
• Not to obey prescriber instructions due to prescriber behavior.
• Using antibiotics without meals.
• Taking antihistamines in day time.
• Taking diuretics at night.

However, sometimes deliberate deviation is advantageous e.g. skipping diuretics in the morning before a long drive.

9. Inappropriate Packaging

• It is stated that inappropriate packaging has a negative impact on patient compliance e.g. use of the child-resistant container for geriatric patients. Similarly, in the case of Parkinsonism fine finger movements are missing, so the patient feels difficulty in opening the container, leading to non-compliance.
• Arthritic patients may feel difficulty in opening the container.

10. Inappropriate Labeling

• It is also known as a poor understanding of label instructions. For some drugs such as tetracycline, auxiliary labels are not available which results in a poor understanding of the patient's drug use. Similarly, the Diltiazem-SR cap should be labeled with clear instructions “Swallow with water”. If they are inappropriately labeled, the patient may chew them, causing the death of the patient.

11. Social Isolation

• Social isolation is one of the important causes of non-compliance. It is common, especially in geriatric patients. So they need a loyal companion for the administration of drugs.

12. Mental Friality

• Sometimes if the patient forgets to take a single dose, it may make no difference at all. But if the patient continues to repeat doing so, surely it will cause problems.
• In the case of psychiatric patients, they may mix the medicines or may take frequent doses, leading to non-compliance.

13. Interaction with the Physician

The patient needs pure attention. So generally patients may show more incline to the physician who gives proper consultation time and thus, he/she will give more attention to the instructions and will show compliance. In most cases, when the physician does not show interaction with the patient, the patient shows non-compliance.

Extent of Non-Compliance

As far as the extent of non-compliance is concerned, different methods are available to reveal the extent of non-compliance.

According to one review, 25-60 % of geriatric patient shows non-compliance up to such an extent that they can produce harmful effects as well as affect interventions and financial conditions.

Strategies To Improve Compliance

Compliance can be improved by using the following strategies.

1. High standards of dispensing practice
2. Supplementary labeling
3. Development of patient medication packaging
4. Simplicity of therapeutic regimen
5. Patient Education

1. High standards of dispensing practice

• For the selection of a container, a highly effective container, rather than cost should be the main criteria.
• Preferably a palm-sized transparent size container should be used, provided that the product is not light-sensitive.
• Discretion (patient judgment) should be made when child-resistant containers are used for elderly patients.
• The size of the container depends upon the label specifications. Label instructions must be simple, explicit, and comprehensive.
• In the case of hospitalized patients, Unit Dose Dispensing is adopted. However alternative methods may be used by the pharmacist in case of genuine problems.
• If “Take as necessary/required”, then mention the total number of doses required per 24 hrs.
• The containers of the pharmaceutical industry should not be reused.
• Any prescription leaving the pharmacy bearing the instruction “Take as formerly” must be prevented by the pharmacist and should tell the patient about the appropriate dose of medicines.

2. Supplementary Labeling

In order to improve compliance, some additional information may also be fruitful. e.g.

• Personal use of the patient reduces the non-compliance.
• Description of drug action in lay terminologies also improves compliance.
• The use of symbols and graphics also improves compliance.

3. Simplicity of therapeutic regimen

• Complexity of the regimen is also one of the major causes of non-compliance where simplicity of the regimen can greatly improve patient compliance. e.g. once daily dose (odd) of propranolol and phenytoin shows compliance and effectiveness as compared to the same drug administered in a divided dose.
• Sustained release and long-acting preparation also improve compliance.
• Both physician and pharmacist can improve compliance of the patient by decreasing the complexity of the regimen.
• A combination of drugs also improves compliance e.g. Myrin-P, Septran, etc.
• Taking of dose in the evening for sedative drugs also improves compliance and reduces the chances of non-compliance.

4. Development of patient medication packaging methods

• UDD: The use of unit dose dispensing improves compliance as compared to loose packaging.
• Mediaset: It is divided into segments corresponding to the number of days in a week and each day is further subdivided into four portions. This device is known as Mediset.
• Calendar packing: Calendar packing also improves compliance e.g. Tenormin.
• Medication event monitoring system: In this case, a microprocessor is fixed in a container and it will count each time the container is inverted and from this, we can assess patient compliance. An example is an automatic eye drop dispenser.

5. Patient education

Patient education is also known as patient-pharmacist interaction. It is one of the most important tools to improve patient compliance. Patient education can be done in one of the following ways.

i. Verbal counseling

It is nearly impossible to counsel all the patients verbally. However, priority should be given to give verbal counseling :

• For prophylactic use of drugs.
• For drugs having serious withdrawal effects.
• For drugs used for long-term therapy.
• Premature discontinuation of drugs produces fatal consequences.

The pharmacist should tell the patient about side effects i.e.

• It may disappear
• Either the patient has to tolerate the side effects.
• Or the situation requires medical emergencies.

Counseling should be in simple language, preferably in the inpatient's mother language.

ii. Imprinted information

These include warning cards, individualized patient medication cards, package inserts, etc.

iii. In-patient training program

The patient is given proper training during his/her stay in the hospital so that after discharge the patient shows improved compliance.

iv. Compliance clinic

The physician refers the patient to the pharmacist in the compliance clinic and the pharmacist will try to improve patient compliance.

ALSO READ: Therapeutic Drug Monitoring (TDM)