Measurement of Outcomes in PEY

The outcome measures include the studies on,

1. Functional status (level of functioning, Supervision required, ability to

work)
2. Symptom status (days free of pain / an event)
3. Patient satisfaction with various aspects of care (delivery of care, effects
on daily activities or life satisfaction) and
4. QOL studies
 The therapeutic outcomes may be classified as cure, improvement, no
change or deterioration.
 On the other hand they can also be classified as success or failure.
 In any event, clinical judgment is required in establishing outcomes.
Morbidity & mortality are the most commonly used measures of out
come
 Morbidity is measured as the number of cases of disease or events that
occur per unit of population (per 100), unit of time (per year) or both
(events/100/year)
 Other measures of morbidity are,
The number of hospitalisations resulting from drug use or prevented by
drug use or days of hospitalisation (or days avoided) and deaths due to
or prevented by the use of drugs

The measurement of outcomes in PEY can be done by two approaches:

1. Outcome measures
2. Drug use measures

Out come measures

The occurrence of pharmacoepidemiological outcomes is commonly

expressed by measurements such as,
a. Prevalence
b. Cummulative incidence and
 c. Incidence rate

 Prevalence
 It is concerned with the disease status
 It is the proportion of people affected with a disease or exposed to a
particular drug in a population at a given time
 It is usually determined by surveying the population of interest
 Prevalence varies between 0-1, it can also be expressed as a
percentage
Ex. The prevalence of schizophrenia is 1% in Europe.
 Mathematically,
Prevance = a/b
a- number of population with disease at a given time
b- total number of population at a given time

Ex. In the year 2003, among 7.8 lac population of Mysore city, 1.2 lac
suffered from chikungunya.
What is the prevalence of Chikungunya in Mysore in the year
2003?
P= 0.15 or 15%

Incidence:

• It is a measure of the risk of developing some new condition with in a

specified period of time
• it is better expressed as a proportion or as a rate.

Cummulative incidence (incidence proportion):

• It is the number of new cases with in a specified time period divided by the
size of the population initially at risk
Ex. if a population initially contains 1,000 non-diseased
persons and 28 develop a condition over two years of observation, the
incidence proportion is 28 cases per 1,000 persons, i.e. 2.8%.
Incidence rate:

• it is the number of new cases per unit of person-time at risk.

• It describes the probability of a new case occurring during a given time
interval

What is person-time?

• It is an estimate of the actual time-at-risk in years, months or days that all

persons contributed to study.
• In certain studies people are followed for different lengths of time as some
will remain disease-free longer than others.
• A subject is eligible to contribute person-time to the study only so long as
that person remains disease-free and therefore, still at risk of developing
the disease of interest.
• By knowing the number of new cases of disease and the person-time-at-
risk contributed to the study, an investigator can calculate incidence rate.
• IR= the no. of new cases of disease during a period of time/the person-
time-at-risk.
• The denominator for IR (person-time) is a more exact expression of the
population at risk during the period of time when the change from non-
disease to disease is being measured .
• The denominator for IR changes as persons originally at risk develop
disease during the observation period and are removed from the
denominator

calculating person-time:

 An investigator is conducting a study of the incidence of second MI. He

follows 5 subjects from baseline (after first MI) for up to 10 weeks.
Solun:
As we know, person-time is the sum of total time contributed by all
subjects (days each subject remained as non-case from baseline)
Subject A: 53 days Subject B: 70 days
Subject C: 24 days Subject D: 70 days
 Subject E: 19 day
o Total person-days = 236 person-days
o Now, 236 p-d becomes denominator in measuring IR
o The total no. Of subjects becoming cases (A,C,E) is the
numerator
o Therefore,
The IR of [Link] is 3/ 236 p-d = 0.0127 cases per person-day.
(1.27 cases/ 100 person-days or 12.7 cases/1000 person-days
• Person-days, can be converted into any interval appropriate to the disease
being studied.
o [Link] may be expressed in cases per person-year by:
1.127 cases/p-d) X (365 p-d/1 p-y) = 4.6 cases/p-y

Drug use measures

1. Monetary units
2. Numbers of prescription
3. Units of drug dispensed
4. Defined daily doses
5. Prescribed daily doses
6. Medication adherence measurement

1. Monetary units
• Drug use has been measured in monetary units to quantify the amounts
being consumed by population
• It can indicate the burden on a society from drug use
• Monetary units are convenient & can be converted to a common unit,
which then allows for comparison
• The disadvantage is quantities of drugs actually consumed are not known &
prices may vary widely

2. Number of prescriptions.
 • It has been used in research due to the availability & ease
• The disadv is, quantities dispensed vary greatly as duration of treatment
Ex: Treatment with antibiotics, provide a fairly good estimate
of the no. Of people exposed & of the no. Of treatment episodes .

3. Units of drug dispensed

• Units of drug dispensed like tablets, vials is easy to obtain & can be used to
compare usage trends within population
• The disadv is that no information is available on the quantities actually
taken by the patient
• Hence difficult to determine the actual no. Of patients exposed to the drug

4. Defined daily doses

• It is the estimated avg. Maintenance dose per day of a drug when used in
its major indication
• It is normally expressed as DDD/1000 ptns/day or DDD/100 bed/day
• It is helpful in describing & comparing patterns of DU & provides
denominator data for estimation of ADR rates
• Adv
 its usefulness for working with readily available drug statistics
 It allows comparisons b/n drugs in the same therapeutic class
• Disadv is problems arises when doses vary widely like with antibiotics or if
the drug has more than 1 major indication
Ex: ASA low dose- avoid cardiac events
moderate dose-pain management
high dose- for inflammatory condition

Prescribed daily doses

• It is the avg daily dose of a drug that has actually been prescribed
• Calculated from representative sample of prescriptions.
• Disadv is that it does not indicate no. Of population exposed to drug.
 • However, it provides estimate of no of person-days of exposure.

Medication adherence measurements

I. Biological Assays
• Biological assays measure the concentration of a drug, its metabolites, or
tracer compounds in the blood or urine of a patient. 
• These measures are intrusive and often costly to administer. 
• Patients who know that they will be tested may conciously take medication
that they had been skipping so the tests will not detect individuals who
have been nonadherent.
• Drug or food interactions, physiological differences, dosing schedules, and
the half-life of the drugs may influence the results
• Biological tracers that have known half lives and do not interfere with the
medication may be used, but there are ethical concerns
• All of these methods have high costs for the assays that limit the feasibility
of these techniques

II. Pill Counts.

• Counting the number of pills remaining in a patient's supply and calculating
the number of pills that the patient has taken since filling the prescription is
the easiest method for calculating patient medication adherence
• Some data indicate that this technique may underestimate adherence in
older populations
• Patterns of non-adherence are often difficult to discern with a simple count
of pills on a certain date weeks to months after the prescription was filled

III. Weight of Topical Medications

• The weight of a topical medication remaining in a tube is used as a measure
of adherence. 
• When compared with patient log books of daily medication use, weight
estimates of adherence were considerably lower than patient log
estimates. 
 • In the clinical trials involving topical applications incorporate medication
weights as the primary measure of adherence. 
• In a comparison of methods to measure adherence, found that estimates
calculated from medication logs and medication weights were consistently
higher than those of electronic monitors

IV. Electronic Monitoring

• The Medication Event Monitoring System (MEMS) manufactured by Aardex
corporation allows the assessment of the number of pills missed during a
period as well as adherence to a dosing schedule
• The system electronically monitors when the pill bottle is opened, and the
researcher can periodically download the information to a computer
• The availability and cost of this system could limit the feasibility of its use
 
V. Pharmacy Records and Prescription Claims
• This method can be used primarily for medications that are taken for
chronic illnesses (such as hypertension)
• These records provide only an indirect measure of drugs consumed. 
• Patterns of over and under consumption for periods less than that between
refills cannot be assessed
VI. Patient Interviews
• Studies have consistently shown that third-party assessments of medication
adherence by healthcare providers tend to overestimate patients'
adherence
• Interviewing patients to assess their knowledge of the medications they
have been prescribed and the dosing schedule provide little information as
to whether the patient is adherent with the actual dosing schedule. 
• Subjective assessments by interviewers can bias adherence estimates. 
• This method is rarely used in medical research to assess adherence
VII. Patient Estimates of Adherence
• Direct questioning of patients to assess adherence can be an effective
method. 
• However, patients who claim adherence may be underreporting their
nonadherence to avoid caregiver disapproval

• Other methods may need to be employed to detect these patients

 Scaled Questionnaire

 Morisky et al. (1986) developed a 4-item scaled questionnaire to assess

adherence with antihypertensive treatment.
 Li et al. (2005) developed four instruments to measure antihypertensive
medication adherence in a population of Chinese immigrants in the US
 The Hill-Bone Compliance to High Blood Pressure Therapy Scale includes 14
items, 8 of which are directed at assessing medication taking behavior in
hypertensive patients
 Not only is this method relatively simple and economically feasible to use,
but it has the added advantage of soliciting information regarding
situational factors that interfere with medication adherence (e.g.
forgetfulness, remembering to bring medications along when out of town)
 The Compliance-Questionnaire-Rheumatology (CQR) is a 19-item
questionnaire that has been favorably compared with electronic
medication event monitoring (de Klerk et al. 2003).  This instrument has
good validity and reliability.