1.0 DRUG UTILIZATION STUDY
1.1 Drug utilization research was defined by WHO in 1977 as “the marketing, distribution, prescription, and use of drug in a society, with special emphasis on the resulting medical, social and economic consequences”.
1.2 Why drug utilization research?
The principle aim of the drug utilization research is to facilitate rationale use of drugs in populations. For the individual patients rationale use of a drug implies the prescription of a well-documented drug in an optimal dose in a right indication, with the correct information and at an affordable price. Without knowledge on how drug are being prescribe and used, it is difficult to initiate discussion on rationale drug use and to suggest measure to change prescribing habits for the better. Information on the past performance of prescribers is the linchpin of any auditing system. Drug utilization research in itself does not necessarily provide answers, but it contributes to rationale drug use in three important ways:
- Description of drug used pattern.
- Early signal of irrational use of drugs.
- Intervention to improve drug use – follow-up.
1.3 Types of Drug utilization review:-
Drug utilization studies have also been described as either quantitative or qualitative.
1.3.1 Quantitative studies involve the collection, organization and display of estimates or measurements of drug use.
1.3.2 Qualitative studies are multidisciplinary operation, which collect, organize, analyze and report information on actual drug use.
The major difference between qualitative and quantitative drug utilization evaluation studies is that qualitative drug utilization studies include the concept of criteria.
Prescription and dispensing data are useful for determining some of the quality indicator of drug used recommended by WHO. These include:
- Average number of drug per prescription (encounter)
- Percentage of drug prescribed by generic name
- Percentage of encounters with an injection prescribe
- Percentage of encounters with an antibiotic
- Percentage of drug prescribe from essential drug list or formulary
- Average drug cost per encounter
1.4 Drug use evaluation
Drug use evaluation, sometimes referred to as drug utilization review, is a system of continuous, systematic, criteria-based drug evaluation that ensures the appropriate use of drugs. It is a method of obtaining information to identify problems related to drug use and if properly developed, it also provides a means of correcting the problem and thereby contributes to rationale drug therapy.
1.4.1 The objective of drug used evaluation includes:
Ø Ensuring the drug therapy meets current standard of care
Ø Controlling drug cost
Ø Preventing problems related to medication
Ø Evaluating the effectiveness of drug therapy
Ø Identification of areas of practice that require further education of practioners.
Drug use evaluation may be based on data collected:
1.4.2 Prospectively (as the drug is being dispensed or administered)
1.4.3 Retrospectively based on( chart review or other data sources).
1.4.4 Concurrent DUR study evaluates dispensing, prescribing and/or patient use data at a point in time or intervals through acute or ongoing therapy and includes a timeframe from the onset
Typical criteria reviewed in prospective studies include the following:
Ø Drug selection
Ø Dosage prescribed
Ø Dosage form and route of administration
Ø Duration of therapy
Ø Therapeutic duplication
Ø Quantity dispensed
Ø Therapeutic outcome
Ø Adverse drug reaction, and
Ø Drug interactions
In Retrospective studies, the criteria include:
Ø Evaluation of indication
Ø Monitoring use of high-cost medicines
Ø Comparison of prescribing between physicians
Ø Cost of patients
Ø Adverse drug reactions, and
Ø Drug interactions
In Concurrent drug utilization studies:
Most commonly it is used to assess long term or maintenance drug therapy at regular, periodic intervals but can also be used during acute therapy. They can influence the course of drug therapy2.
2.0 ADVERSE DRUG REACTION MONITORING (PHARMACOVIGILANCE)
WHO defines “Pharmacovigilance” (ADR monitoring) as the science and activities relating to the detection, assessment, understanding and prevention of ADRs or any other medicines related problems.12 The overall purpose of pharmacovigilance is improvement in the safety of medicine.
2.1 Definitions of Adverse Drug Reactions (ADR)
1. According to WHO “ADR is any response to a drug which is noxious and unintended and occurs at doses normally used in man for prophylaxis, diagnosis or therapy of disease or the modification of physiological function’’.This definition excludes therapeutic failures, intentional and accidental poisoning and drug abuse.13
2. ‘ASHP’ (American society of hospital pharmacists) defines “a significant adverse drug reaction as an unexpected, unintended, undesired, or excessive response to a drug that,
- Requires discontinuing the drug (therapeutic or diagnostic)
- Requires changing drug therapy
- Requires modifying the dose (except for minor dosage adjustments)
- Necessitates admission to a hospital
- Prolong stay in health care facility
- Necessitates supportive treatment
- Significantly complicates diagnosis
- Negatively affects prognosis or
- Results in temporary or permanent harm, disability or death.
3. FDA defines a serious adverse events as one in which the patient outcome is death, or life threatening, hospitalization, disability congenital anomaly or required intervention to prevent permanent impairment or damage.
4. The Joint Commission on the Accredition of Healthcare Organizations (JCAHO) defines an adverse drug reaction as “an undesirable effect of a medication that either, increases toxicity, decrease desired therapeutic effect, or both.”
5. Laurence defines ADR as “A harmful or significantly unpleasant effect caused by a drug at doses intended for therapeutic affect (or prophylaxis or diagnosis) which warrants reduction of dose or withdrawal of the drug and/or foretells hazard from future administration’’.
6. The Uppsala monitoring centre defines ADR as “an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal products which predicts hazard from future administration, and warrants prevention or specific treatment, or alteration of the dosage regimen, or withdrawal of the product’’.
7. “An ADR is an injury resulting from medical intervention related to a drug”.
8. According to Karch and Lasagna “An ADR is any response to a drug that is noxious or unintended that occurs at doses in humans for prophylaxis, diagnosis or therapy excluding failure to accomplish the intended purpose”.
2.2 TABLE 2: CLASSIFICATION OF ADR
|Types of reaction||Mnemonic||Features|
|A: Dose related||Augmented||
|B: Non-dose related||Bizarre||
|C: Dose related and time related||Chronic||
|D: Only Time related||Delayed||
|E: Withdrawal||Due to end of use||
|F: Unexpected failure of therapy||Failure||
2.3 TABLE 3: Surveillance methods for ADR
|1||Anecdotal reports||Simple; cheap||Relies on individual vigilance ;only detects relatively common effects|
|2||Voluntary organized||Simple||Under-reporting; reporting bias by ‘bandwagon’ effect|
|Easily organized||Selected population studied for a short time|
|4||Cohort studies||Can be prospective;
good at detecting
|Very large numbers required;
for validation and
|Will not detect new effects ;
|6||Case-cohort studies||Good for study
in rare effects
with high power
|As for Cohort and Case-control;
|7||Population statistics||Large number can
|Difficult to coordinate; quality of
information may be poor
|Time consuming; expensive;
Retrospective; relies on accurate
|9||Meta-analysis||Uses data that have
already been obtained
|Heterogeneity of different
2.4 Methods for estimating the probability of ADR
The estimation of the probability that a drug caused an adverse clinical event is usually based on clinical judgment. Using the conventional categories and definitions of definite, probable, possible and doubtful ADRs generates wide variability in assessment of the exact nature of ADR.
Different scales categorize the causality relationship in different ways. For example, the WHO scale categorizes the causality relationship into certain, probable, possible, and unassessable / unclassifiable, unlikely, conditional / unclassified. The Naranjo scale categorizes the reaction as definite, probable, possible or unlikely. The WHO ADR probability scale will be used during the study to estimate the probability of adverse drug reactions.
2.4.1 TABLE 4: WHO CAUSALITY ASSESSMENT SCALES
to drug intake
a relationship improbable (but not impossible)