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7377 Final Exam Study Guide

Terms in this set (81)

Describe the different phases in the U.S. drug development and approval process.
Phase 1:
- RCTs that consist of small studies of healthy volunteers
- determine basic safety and pharmacological information in humans
- usually short, lasting 6 to 12 months
- may exclude children, women of childbearing age, and other patient groups

Phase 2:
- RCTs conducted in small numbers of subjects who suffer from the indicated condition the drug is intended to treat
o drug is used cautiously to ensure safety before large numbers of people are exposed
- provides safety data and begins to provide some indication of the drug's clinical efficacy

Phase 3:
- drug is used in a larger group of patients who suffer from the indicated disease or condition
- randomized, double-blind, placebo-controlled
- may have several hundred to several thousand patients who have the disease or condition being studied
- the drug sponsor can assess the safety and efficacy of the drug
- typically take one to four years

After completion of these trials, the drug sponsor will seek drug approval from the FDA by submitting a New Drug Application (NDA).

The FDA will then review the NDA to determine whether the drug is safe and efficacious as well as whether the product labeling, marketing, and manufacturing processes are adequate.

The entire process can take between 10 to 15 years and costs range from $200 million to $1.3 billion per drug approved.
Describe the limitations of clinical trials.
- Certain patient groups like children and women of childbearing age may be excluded from clinical trials.
- Phase 3 trials may have a few thousand people enrolled, but not hundreds of thousands or millions. Some adverse events and other safety issues that only occur in one in a million may not be detected.
- Clinical trials have short durations, so the effects of taking a drug for 10+ years is not studied.
Recognize the names and sponsoring agencies of spontaneous adverse event reporting systems in the
United States.
MedWatch Safety Information and Adverse Event Reporting Program
- allows health professional and the public to report voluntarily serious reactions and problems with medications
- FDA uses it to identify and evaluate risk with a specific product, develop interventions to modify the risk, and to communicate the risk to health care professionals and the public

Vaccine Adverse Event Reporting System (VAERS)
- implemented by the FDA and CDC
- collects information about safety issues related to vaccine use


Pharmaceutical companies and other health care organizations also collect and use medication safety information
- pharmaceutical companies have toll-free numbers and websites
- academicians publish case reports about rare events that may be associated with drug use
- many hospitals have process to collect the drug history of patients upon admission and then attempt to identify relationships between drug exposure and reason for hospital admission
Describe the limitations of spontaneous adverse event reporting.
- There is no control group: patients exposed to a drug product cannot be compared to patients not exposed to the product
- It is difficult to know the frequency or the rate at which the drug effect occurs.
- With so many factors involved with each patient, it is difficult to know whether the drug is causing the outcome or if something else is the cause.
- There may be bias from the reporter or other source, and the report may be inaccurate or incomplete.
List the advantages of using secondary databases in pharmacoepidemiology.
- Through these databases, researchers can evaluate the use of a drug in an unstudied population or for an unlabeled use.
- Rare drug-drug interactions, drug-disease interactions, or other adverse drug reactions can be identified.
Datasets with multiple years of patient data enable researchers to study the effect of the drug over an extended period of time. The effect of a prescribing intervention or other quality-improvement initiative can be evaluated using these large datasets.
Differentiate between efficacy and effectiveness.
- Efficacy refers to whether the drug product can produce a specific therapeutic outcome in a controlled environment.
- Efficacy is measured in clinical trials
- Effectiveness refers to the ability of the drug to produce the desired therapeutic outcome in practice where the environment is not controlled (i.e., in the real world).
- Effectiveness of drugs is measured in postmarketing surveillance/pharmacovigilance/Phase IV studies.
Distinguish between association and causation.
- No matter how strong the association between an exposure (e.g., drug or intervention) and an outcome (e.g., adverse event or benefit), we cannot automatically assume causation.
- Associations observed in epidemiologic studies could be due to chance or confounding, but FDA and clinicians are more interested in causal relationships (i.e., whether a treatment or an intervention causes a specific outcome)
Distinguish between prevalence and incidence as key measures of disease frequency.
INCIDENCE:
- Incidence of a disease is defined as the number of new cases that occurs in a population at risk for developing the disease during a specified time period (usually a year).
- The individuals at risk are initially disease free.
- Incidence measures the occurrence of new cases of disease. It measures disease occurrence in persons who did not have the condition before.
- For diseases that can occur more than once during the specified period of time, incidence only measures the first occurrence of the disease.

PREVALENCE:
- The prevalence of disease is defined as the number of existing cases (old and new) in the population (sick, healthy, at risk, and not at risk)
- It focuses on disease status and measures the proportion of the population who has the disease of interest.
Differentiate between cumulative incidence/incidence proportion and incidence rate/incidence density.
CUMULATIVE INCIDENCE:
- Cumulative incidence measures the proportion of the population at risk that develops the disease of interest over a specified period of time.
- Once a patient becomes a case, they are no longer at risk (i.e., they already had the disease)
- Cumulative incidence can be expressed as a percentage or the number of new cases per 1,000 or per 100,000 populations.

INCIDENCE RATE:
- Incidence rate will be used to measure how fast new cases of a disease occur, accounting for the varying observation time for different individuals.
- The numerator is the same as for cumulative incidence.
- The denominator is the sum of the time periods that each person in the population at risk for developing disease has contributed (i.e., does not assume that everyone stayed for the whole study period).
Calculate and interpret cumulative incidence and incidence rate
see attached image

Cumulative Incidence:
- measures the proportion of the population at risk that develops the disease of interest over a specified period of time
- once a patient becomes a case, they are no longer at risk

Incidence Rate:
- used to measure how fast new cases of a disease occur, accounting for the varying observation time for different individuals
Calculate and interpret point prevalence and period prevalence.
see attached image

POINT PREVALENCE:
- Point prevalence is the number of people who have the disease of interest at a single point in time, divided by the number of people in the population at that specific time, for example, on a given day.
- Point prevalence can be thought of as a single snapshot of the population; that is, the calculation of point prevalence is based on a single examination at one point in time, such as a calendar date, or the day of hospital admission.

PERIOD PREVALENCE:
- Period prevalence refers to the number of persons who have the disease at any point during a specified period, divided by the number of persons in the population during that specified period.
- Period prevalence can be calculated for a week, month, year, decade, or any other specified length of time.
Describe the relationship between prevalence, incidence rate, and average duration of disease.
- Incidence and prevalence measures reflect different phases of a disease.
- Incidence and prevalence are influenced by the duration of the disease.
- A short-duration, curable disease, such as common cold, may have a high incidence but low prevalence, because many people get a cold each year, but it lasts for a short time.
- A chronic, incurable disease, such as hypertension may have a high incidence and high prevalence, because many people get diagnosed with hypertension, and the disease is not very fatal, but it cannot be completely cured either.

Prevalence (P) ≈ Incidence Rate (I) x Duration of Disease (D)
Calculate and interpret crude mortality, age-specific mortality, and cause-specific mortality rates.
see attached image

CRUDE MORTALITY:
- Crude mortality rate (also referred to as all-cause mortality) is the total number of deaths from all causes per number of persons in a population during a specified time period divided by the total number of persons in the population during that time period
- Crude mortality rates are influenced by the population's age composition—Using crude mortality rates in examining changes over time or making comparisons between subgroups in a population can often be misleading.

AGE-SPECIFIC MORTALITY:
- Age-specific mortality rate measures the total number of deaths from all causes among individuals in a specific age category.
- Allows comparisons of mortality risks for a particular age group across different subpopulations.
- Age-adjusted mortality rate is used to account for variation in age distribution when comparing crude mortality rates over time or across different segments or geographic locations in the population.
- Age adjustment is a statistical process that allows the comparison of mortality rates and health outcomes across communities with different age structures by removing the confounding caused by age.

CAUSE-SPECIFIC MORTALITY:
- Cause-specific mortality rate measures the total number of deaths from a specific cause or a specific diagnosis.
- The cause of death refers to the single, specific, underlying cause (disease or injury) that initiates the series of events leading to the death—all other reported causes are the non-underlying causes of death. The underlying cause of death is the one used in computing cause-specific mortality rate
- Misclassification and miscoding can affect the accuracy of reported cause-specific mortality rate.
Calculate and interpret case fatality and proportionate mortality.
see attached image
Identify the exposures and outcomes in pharmacoepidemiology studies.
- In epidemiology, association refers to a statistical relationship between two or more variables
- Exposure refers to having any potential causal characteristics, such as a behavior (e.g., smoking) or a treatment (e.g., drug therapy).
- The risk ratio (RR) and odds ratio (OR) are the most commonly used measures of association in epidemiology.
- They measure the magnitude/strength of association between the exposures and outcomes of interest.
- The further away RR or OR are from 1, the stronger the relationship between the exposure and the outcome.
Calculate and interpret the following measure of association between exposures and outcomes:

relative risk/risk ratio (RR)
- Risk ratio (also referred to as relative risk) is the ratio of the risk of developing the event (disease, adverse drug effect, death, or any other outcome) in exposed individuals (Re) to the risk of developing that same event in unexposed individuals (Ru).
- Re is the risk (cumulative incidence) in the exposed group and Ru is the risk (cumulative incidence) in the unexposed group.

INTERPRETING:
- RR = 1 indicates that the risk of the outcome (e.g., drug adverse effect, disease, or death) is equal in the exposed and unexposed groups. There is no association between the exposure and outcome.
- RR > 1 indicates that the exposure is associated with the outcome. The greater the RR, the higher the risk of the outcome in the exposed group compared to unexposed group.
- RR < 1 indicates that the exposure is associated with the outcome. The smaller the RR, the lower the risk of the outcome in the exposed group compared to unexposed group.
- If the confidence interval (CI) for the estimated RR includes 1, this means there is no association between the exposure and outcome.
- If the CI for the estimated RR does not include 1, this means that there is an association between the exposure and outcome (could be an increased or decreased risk of the oucome).
- RR is the measurement of choice for the association between exposure and outcome in cohort studies, but it should not be used in case-control studies.
Calculate and interpret the following measure of association between exposures and outcomes:

odds ratio (OR)
- Odds ratio (OR) is the preferred measure of association between exposures and outcomes in case-control studies, but can also be used in cohort studies.
- For case-control studies, the OR is the ratio of the odds of cases being exposed to the odds of controls being exposed.
- For cohort studies, the OR is the ratio of the odds of developing the outcome in the exposed group to the odds of developing the outcome in the unexposed group.

CASE-CONTROLS:
- OR = 1 indicates that the odds of exposure among cases are the same as the odds of exposure among controls. The exposure is not associated with the disease or outcome.
- OR > 1 indicates that the odds of exposure among cases are greater than the odds of exposure among controls. The exposure might be a risk factor for the disease or outcome.
- OR < 1 indicates that the odds of exposure among cases are lower than the odds of exposure among controls. The exposure might be a protective factor against the disease or outcome.

COHORT STUDIES:
- OR = 1 suggests that the odds of an event is the same in those who are exposed and unexposed.
- OR > 1 suggests that the odds of an event is higher in the exposed group than in the unexposed group.
- OR < 1 suggests that odds of an event is lower in the exposed group than in the unexposed group.

INTERPRETING:
- Statistical significance of OR must be evaluated before any conclusions are made.
- If the CI for the estimated OR includes 1, this means there is no association between the exposure and outcome.
- If the CI for the estimated OR does not include 1, this means that there is an association between the exposure and outcome.
Calculate and interpret the following measure of association between exposures and outcomes:

relative risk reduction/increase (RRR/RRI)
- Relative risk reduction (RRR) measures the extent to which an exposure (e.g., therapy) reduces a risk, in comparison with individuals in the unexposed group (e.g., not receiving therapy).
- Relative risk increase (RRI) measures the extent to which an exposure increases a risk, in comparison with individuals in the unexposed group.
Calculate and interpret the following measure of association between exposures and outcomes:

absolute risk reduction/increase (ARR/ARI)
ARR:
- ARR is the absolute difference in the event rates of the exposed (or treated) and unexposed (or untreated) groups; it is also called risk difference.

ARI:
- When the event rate in the exposed group is greater than that of the unexposed group, the absolute measure of risk difference is referred to as absolute risk increase (ARI).

- Example: A cohort study is conducted to evaluate the rate of palpitations (adverse drug effect) from receiving Drug A (exposed group) compared to control (unexposed group). Out of 1557 patients in the treatment group, 85 had palpitations, compared to 24 out of 781 patients in the control group.
- ARI = |5.5% - 3.1%| = 2.4%; the difference in the risk of palpitations between the treatment and control groups is 2.4%
Calculate and interpret the following measure of association between exposures and outcomes:

number needed to treat/harm (NNT/NNH)
NNT:
- The number needed to treat (NNT) is defined as the number of individuals who would have to receive the treatment for one of them to benefit from the treatment over a specified time period.
- The reciprocal of the ARR (NNT = 1/ARR)
- NNT reflects the likelihood an individual will benefit from a treatment.

INTERPRETING NNT:
- A calculated NNT of 10 indicates that for a given treatment to be beneficial to one person, 10 persons would have to be treated with the therapy.
- When treatment is administered to an individual, an NNT of 10 also indicates that for each person who received the treatment, he or she would have a 1 in 10 chance of benefiting from the treatment.
- If ARR is large, the calculated NNT would be small, which means that only a small number of persons need to be treated for one of them to benefit.
- NNT can only be directly compared when the same outcome is being evaluated.
- NNT values that are not whole numbers should always be rounded up.

NNH:
- The number needed to harm (NNH) is a measure of the number of persons who would have to be treated for one person to experience an adverse event.
- The reciprocal of the ARI (NNH = 1/ARI)
- A large NNH indicates that adverse events are rare, whereas a small NNH suggests adverse events are common.
- NNH values that are not a whole number should be rounded down— Example: If NNH is equal to 50.8, it should be rounded down to 50.
What is the appropriate measure of association between exposures and outcomes in case-control studies?
odds ratio (OR)

CASE-CONTROLS:
- OR = 1 indicates that the odds of exposure among cases are the same as the odds of exposure among controls. The exposure is not associated with the disease or outcome.
- OR > 1 indicates that the odds of exposure among cases are greater than the odds of exposure among controls. The exposure might be a risk factor for the disease or outcome.
- OR < 1 indicates that the odds of exposure among cases are lower than the odds of exposure among controls. The exposure might be a protective factor against the disease or outcome.
Describe recall bias.
- occurs when one study group or subgroup has a differential recall of exposures or events prior to the onset of a disease

**especially of concern in retrospective case-control studies
Describe the Hawthorne effect.
- observational bias
- involves the mere awareness of being under observation altering the way in which a person behaves
Describe attrition bias.
- occurs when participants invariably drop out of the study for multiple reasons
- results in missing data at random and weakening of the power of the study
- may also introduce systematic bias if the characteristics of study participants who are lost to follow-up differ between the randomized treatment groups or observational study cohorts
Describe misclassification bias.
- produces a systematic error in the information about the exposure and/or disease (outcome)
- bias is more prevalent in one group than the other
- of particular concern in medical research that uses medical information systems and administrative claims databases to determine whether patients have pre-existing medical conditions or have undergone previous procedures
Describe selection bias, including self-selection bias.
- a distortion of the study findings that results from the factors that determine study participation, specifically, the procedure or way in which study subjects are selected
- self-selection bias is another type of selection bias that may occur when participants themselves decide to participate in a study
Describe interviewer bias.
- another form of information bias that occurs when an interviewer treats patients during an interview with more sympathy than the controls, as their status as cases rapidly becomes clear to him during the interview
What are the five methods used to minimize confounding and identify which are applied at the design vs. analysis phase?
Restriction
- defines the eligibility criteria for the study population
- design phase

Matching
- selecting cases and controls that share similar characteristics
- e.g., propensity score matching
- design phase

Stratification
- calculates the estimate for the association between exposure or outcomes within different strata or categories of confounding variables
- analysis phase

Multivariable Regression Models
- building multivariable regression models that provide adjusted parameter estimates for the relationship between exposures and outcomes after controlling for or eliminating the effect of the confounders
- analysis phase

Sensitivity Analysis
- conducted to perform checks by systematically repeating the analysis and varying the assumptions each time
- analysis phase
Define suboptimal medication utilization.
- the point below which the desired therapeutic effect is unlikely to be achieved
- can also be defined as the number of doses not taken or taken incorrectly that places the expected therapeutic outcome in doubt
Define compliance, adherence, concordance, and persistence.
- Compliance/Adherence is the extent to which patients consume their medications according to the prescriber's directions
- more standardized definition: the extent of conformity to the recommendations about day-to-day treatment by a provider with respect to timing, dosage, and frequency
- Concordance is the agreement between the patient and the healthcare professional, reached after negotiation, that respects the beliefs and wishes of the patient in determining whether, when, and how their medication is taken
- it is believed that the patient and healthcare provider agree on all aspects of therapy before its initiation
- Persistence is defined as the act of conforming to a recommended therapy for the prescribed length of time
- compliance is the percentage of doses consumed correctly, persistence is measured by time
Define initial noncompliance, partial compliance, compliance, and hypercompliance.
Initial Noncompliance
- occurs when a patient does not receive the medication prescribed for them due to unpresented or unclaimed prescription

Partial Compliance
- occurs when a patient receives their medication but does not follow the physician's orders on how this medication should be taken or used

Compliance
- the extent to which patients consume their medications according to the prescriber's directions
- more standardized definition: the extent of conformity to the recommendations about day-to-day treatment by a provider with respect to timing, dosage, and frequency

Hypercompliance
- occurs when a patient takes a prescribed medication at a level over and above the recommended dosing interval
Describe social desirability bias and how it can affect medication utilization estimates.
- the tendency of respondents to respond in a manner that will be viewed favorably by others; a common problem in survey research.
Compare direct and indirect methods of measuring medication utilization.
DIRECT:
- directly observed therapy (DOT)
- biological fluids

Examples of BF:
- blood or urine samples
- costly, intrusive, and impractical
- sensitive to pharmacokinetic characteristics
- relatively short time intervals assessed

INDIRECT:
- patient self-report
- provider estimates
- pill counts
- microelectronic medication-monitoring devices
- administrative claims data
Calculate the following measures of medication utilization using prescription-fill information:

A. MPR
B. PDC
C. CMG
D. CMOS
MPR:
days' supply / days in evaluation period

PDC:
(total days supplied / total days evaluated) x 100%

CMG:
total days of treatment gaps / total days to end of observation period

CMOS:
total days of treatment gaps or surplus / total days in observation period
Determine the design of a study based on the study abstract:

I. Case report
II. Case series
III. Cross-sectional
IV. Case-control
V. Retrospective/prospective cohort
VII. Randomized-controlled trial (RCT)
VIII. Systematic review/meta-analysis
Case Report:
- descriptive case study written with a specific area of interest

Case Series
- a group or series of case reports involving patients who were given similar treatment

Cross-Sectional:
- survey a defined population at a single point in time

Case-Control:
- two groups of people selected
- one group with disease, one without
- OUTCOME first, then looking for exposure ("looked back")

Retrospective/Prospective Cohort:
- subjects classified according to a particular exposure
- prospective: outcome hasn't happened yet
- retrospective: outcome has happened (uses databases)

RCT:
- comparison of the group receiving the intervention with a control group
- RANDOMIZED

Systematic Review/Meta-Analysis:
- answers a defined research question by collecting and summarizing all empirical evidence that fits pre-specified eligibility criteria
- a meta-analysis is the use of statistical methods to summarize the results of these studies
Describe the Economic, Clinical, and Humanistic Outcome (ECHO) model and provide examples of each type of outcome in this model.
- The ECHO model provides a framework for comprehensive evaluation out outcomes associated with diseases and their treatments.

ECONOMIC:
- direct medical costs
- direct non-medical costs
- indirect costs
- intangible costs

CLINICAL:
- medical events that occur as a result of treatment or intervention

Examples:
- adverse drug reactions
- treatment failure
- hospital readmission
- emergency room visits
- death

HUMANISTIC:
- consequences of the treatment reported by the patient or their caregiver

Examples:
- patient satisfaction
- functional status
- health-related quality of life
Match different examples of costs with the correct cost category:

I. Direct medical costs
II. Direct nonmedical costs
III. Indirect/Productivity costs
IV. Intangible costs
DIRECT MEDICAL COSTS:
- most obvious costs to measure
- medically-related inputs used directly to provide the treatment

Examples:
- pharmaceutical costs
- diagnostic tests
- physician visits
- pharmacy visits
- emergency department visits
- hospitalizations

DIRECT NON-MEDICAL COSTS:
- costs to patients and their families that are directly associated with treatment but are not medical in nature

Examples:
- cost of traveling to and from the physician's office, clinic, or hospital
- childcare services
- food and lodging required for the patients and their families during out-of-town treatment

INDIRECT/PRODUCTIVITY COSTS:
- costs experienced by a patient, the patient's family, or society resulting from the loss of earnings or productivity due to the patient's illness or death

Examples:
- lost productivity to the patient
- lost productivity for an unpaid caregiver
- lost productivity because of a patient's premature mortality

INTANGIBLE COSTS:
- include the costs of pain, suffering, anxiety, or fatigue that occur because of an illness or the treatment of an illness
- difficult to measure and quantify in monetary units

Example:
- nausea and fatigue in patients receiving chemotherapy
Compare different medication pricing methods:

I. Wholesale Acquisition Cost (WAC)
II. Average Manufacturer's Price (AMP)
III. Average Wholesale Price (AWP)
WAC:
- estimates of costs to wholesalers from manufacturers
- these estimates do not include discounts

AMP:
- average amount paid to manufacturers by wholesalers after discounts are included
- more precise estimate of what pharmacies pay for medications, but are proprietary and not available to the general public

AWP:
- often used when calculating the cost of pharmaceutical products
- considered the "list price" or "sticker price" or medications
- higher than what pharmacies, institutions, or third-party payers pay for medications
- least precise of the three
Rank medication pricing methods according to their precision.
Least-to-Most Precise:
- AWP
- WAC
- AMP
Describe the methods used to estimate hospital costs.
Per Diem:
- for each day that a patient is in a hospital setting, an average cost per day for all types of hospitalizations is used as a multiplier

Disease-Specific Per Diem:
- a more precise method that estimates costs per day for specific diseases

Diagnosis-Related Group (DRG):
- this method is used to classify clinically cohesive diagnoses and procedures that use similar resources
- each patient is assigned one of more than 500 DRGs based on factors such as principal diagnosis, specific procedures involved, secondary diagnoses, age, sex, treatment received, comorbidities, complications, length of hospital stay, and discharge status
- in general, a DRG payment covers all charges associated with an inpatient stay from the time of admission to discharge
- the average reimbursement for each DRG can be used to approximate the cost to the payer (i.e., the reimbursements for resources used by a "typical" patient within the DRG group)

Micro-Costing:
- the most precise method of estimating hospital costs
- involves collecting information on resource use for each component of an intervention or hospitalization
- it is used to determine what specific services (e.g., medications, laboratory services, procedures) were used and to assign a cost to each service
Rank the methods used to estimate hospital costs according to their precision.
Least-to-Most Precise:
- per diem
- disease-specific per diem
- diagnosis-related group (DRG)
- micro-costing
Identify the appropriate source for obtaining different types of cost data (AWP and reimbursement rates).
- AWP can be found in Red Book
- reimbursement rates can be found in the Physician's Fee Reference database
Determine the perspective of pharmacoeconomic studies (e.g., patient, third-party payer, hospital,
government, society).
- the perspective tells the readers whose costs are measured
- it is important to identify from whose perspective the analysis will be conducted because this determines the costs to be evaluated
Recognize when adjustment or discounting of costs in a study would be necessary.
- If retrospective data are used to assess the cost of resources used over several years back (more than one year in the past), these costs should be adjusted, or valued at one point in time; which is referred to as adjustment or standardization of costs
- If one assumes that the expenses occur at the beginning of each year, then first-year costs are not discounted.
- It is equally acceptable to assume that expenses occur at the end of the first year (12 months later), and therefore, they are discounted.

**formula for the discount factor is 1/(1+r)²
Determine the type of pharmacoeconomic or cost analysis described in a study:

a. Cost-minimization analysis (CMA)
b. Cost-effectiveness analysis (CEA)
c. Cost-benefit analysis (CBA)
d. Cost-utility analysis (CUA)
e. Cost-consequence analysis (CCA)
f. Cost-of-illness analysis (COI)
Cost-Minimization Analysis (CMA)
- used to choose the least costly option among alternative interventions that are assumed to produce equivalent health outcomes

Cost-Effectiveness Analysis (CEA)
- measures outcomes in natural units (e.g., mmHg, cholesterol levels, symptom-free days [SFDs], years of life saved)

Cost-Benefit Analysis (CBA)
- unique in that both costs and outcomes (benefits) are valued in monetary terms

Cost-Utility Analysis (CUA)
- measures outcomes based on years of life that are adjusted by 'utility' weights, which range from 1 for 'perfect
health' to 0 for 'dead'. These utility weights incorporate patient or society preferences for specific health states

Cost-Consequence Analysis (CCA)
- only a simple list of costs and a list of consequences (outcomes) of the products being compared are presented separately, with no direct calculations or comparisons

Cost-of-Illness Analysis (COI)
measures the total economic burden of a particular disease, injury, or risk factor on society, including medical costs, non-medical costs, and productivity losses
What are societal costs and what are the most common perspectives in pharmacoeconomic studies?
- Societal costs include costs to the insurance company, costs to the patient, costs to the provider/institution, other sector costs, and indirect costs because of the loss of productivity.
- The most common perspectives used in pharmacoeconomic studies are the perspective of the institution or provider (e.g., hospital or clinic) or the payer (e.g., Medicare/Medicaid or private insurance plan) because these may be more pragmatic.
Distinguish cost-minimization analysis (CMA) from other types of pharmacoeconomic analyses.
- used to choose the least costly option among alternative interventions that are assumed to produce equivalent health outcomes
List the advantages and limitations of CMA.
Advantages:
- the simplest type of pharmacoeconomic analysis to conduct because the outcomes are assumed to be equivalent
- only the costs of interventions are compared

Disadvantages:
- interventions with different types of outcomes cannot be compared
- can only be used when there is reliable evidence that the interventions being compared have demonstrated equivalent therapeutic outcomes
Distinguish cost-effectiveness analysis (CEA) from other types of pharmacoeconomic analyses.
- measures outcomes in natural units (e.g., mmHg, cholesterol levels, symptom-free days [SFDs], years of life saved)
- measures costs in dollars or monetary value
List the advantages and disadvantages of CEA.
Advantages:
- outcomes are easier to quantify when compared with CBAs or CUAs
- clinicians are familiar with measuring these types of health outcomes because they are routinely collected in clinical trials and clinical practice

Disadvantages:
- alternatives used in the comparison must have outcomes that are measured in the same clinical units
- difficult to collapse different outcomes into one unit of measurement
Distinguish between intermediate/surrogate and primary/final outcomes.
- primary/final outcomes (e.g., cure of a disease, eradication of infection, or life years saved) are preferred units of measurement
- when it is not feasible to collect primary outcomes because of time or monetary resources, intermediate or surrogate outcomes (e.g., laboratory measures or disease markers) are used as proxies or surrogate endpoints
- the limitation of using intermediate outcomes is reduced as the strength of the association between the intermediate and primary outcome measures increases
Compare 'cost-efficacy' and 'cost-effectiveness' analyses.
- pharmacoeconomic studies that use data from RCTs are referred to as cost-efficacy analyses
- pharmacoeconomic studies that use data from the "real world" or routine clinical practice are referred to as cost-effectiveness analyses
Describe the limitations of using costs and outcomes from randomized-controlled trials in CEA.
- patients in RCTs are routinely monitored more closely, so they are likely to be more adherent to medications
- RCTs capture data for a short time period, even for chronic conditions
- off-label drug us is not captured in RCTs
- the underlying subjectivity as to whether the added benefit is worth the added cost provides another disadvantage
Calculate and interpret the average cost-effectiveness ratio (CER) for one treatment option.
- The cost-effectiveness ratio (CER) is the ratio of resources used per unit of clinical benefit, and it implies that this calculation has been made in relation to "doing nothing" or no treatment.

CER = net cost / changes in health outcomes
Calculate and interpret the incremental cost-effectiveness ratio (ICER) for two treatment options.
- The ICER is the ratio of the difference in costs divided by the difference in outcomes between two alternatives.
- If incremental calculations produce negative numbers, this indicates that one treatment, the dominant option, is both more effective and less expensive than the other, dominated option.
- When one of the alternatives is both more expensive and more effective than another, the ICER is used to determine the magnitude of the added cost for each unit in health improvement (tradeoff).
- The underlying subjectivity as to whether the added benefit is worth the added cost is another disadvantage of CEA.

ICER = difference in costs / difference in outcomes

[Cost(experimental) - Cost (control)] / [QALY(experimental) - QALY(control)]
Identify the dominant and dominated options when comparing two alternatives in CEA.
- If incremental calculations produce negative numbers, this indicates that one treatment, the dominant option, is both more effective and less expensive than the other, dominated option.
Calculate and interpret the incremental net benefit (INB) for two treatment alternatives to determine the more cost-effective alternative.
INB = (λ x Δeffects) - Δcosts

λ = willing-to-pay
Δeffects = change in outcome (% success)
Δcosts = change in initial cost
Distinguish cost-utility analysis (CUA) from other types of pharmacoeconomic analyses.
- some consider CUAs a subset of CEAs because the outcomes are assessed using a special type of clinical outcome measure, usually the QALY
- a CUA takes patient preferences (utilities) into account when measuring health consequences
- some researchers prefer to use other terms such as preference weight or preference value in place of the word "utility"
- the most common outcome unit used in a CUA is QALY, which incorporates both quality (morbidity) and quantity (mortality) or life
Describe the advantages and disadvantages of CUA.
Advantages:
- different types of health outcomes can be combined and compared
- health benefits of a particular treatment/intervention incorporate both quantity and quality of life
- comparison of health benefits across different health interventions and healthcare settings is possible

Disadvantages:
- difficult to determine an accurate utility or preference weight for outcomes since QOL measures are more subjective than clinical measures
Define the term 'utility' and the possible range of values for utility weights.
- utilities are patient preferences that determine QOL
- perfect health is assigned a value of 1.0 utility per year
- death is assigned a value of 0 utility per year
- if a person's health is diminished by disease or treatment, a one year of life in this state is valued somewhere between 0 and 1.0
- some researchers point out that there are disease states worse than death, so negative utility weights may be needed to depict these values
List the steps involved in measuring and calculating utility-based outcomes.
- develop a description of each disease state or condition of interest
- choose a method for determining utilities
- choose subjects who will determine utilities
- multiply utilities by the length of life for each option to obtain QALYs
Describe different methods used in estimating utilities.
Direct:
- rating scale (RS)
- standard gamble (SG)
- time tradeoff (TTO)

Indirect:
- EQ-5D instruments
- SF-6D questionnaire

Rating Scale:
- line on a page with scaled markings (like a thermometer)

Standard Gamble:
- the respondent is asked to think about being in a chronic health state and then told that her or she could gamble on an intervention that could either cure the condition (probability = p) or die from it (probability = 1 - p)
- a base probability is given, and the respondent is asked whether he or she would have the intervention or live with the chronic condition
- this probability is varied until the respondent is indifferent
- the probability at this indifference point is the utility associated with the condition

Time Tradeoff:
- the respondent makes a choice about trading off years of life for better health for a shorter period of time
- the respondent is given the choice of living a full life (to time t) with a specific condition or living healthy for fewer years (to time x) without the condition
- the time of living healthy is varied until the respondent is indifferent between living in full health x years and living with the condition for t years
- the utility for the condition is x/t

EQ-5D Instruments:
- family of instruments to describe and value health that have been used in clinical trials, population studies, and real-world settings for over 30 years
- a formula is used to calculate a unique index value (utility) using standardized weights for the five domains

SF-6D Questionnaire:
- abbreviated version of SF-36
- the most widely used health-related quality of life evaluation tool by MCOs and Medicare for routine monitoring and assessment of patient care outcomes
- provides a means for using SF-36 in economic evaluation by using an algorithm to estimate a preference-based single index measure for health from this data (allows analysts to obtain QUALYs from the SF-36 for use in CUAs)
Recognize the "rule of thumb" for the U.S. dollar value per quality-adjusted life years (QALY).
$50,000 per QALY
Calculate incremental cost per quality unit (e.g., QALY or QALD) for two treatment options.
INB = (λ x ΔQALYs) - Δcosts
Distinguish cost-benefit analysis (CBA) from other types of pharmacoeconomic analyses.
- compares both costs and benefits in monetary units (CEAs measure outcomes in natural units)
- while a CEA calculates the cost per unit of effect, a CBA calculates the ratio of all costs to all benefits of a program
Describe the advantages and disadvantages of CBA.
Advantages:
- many different outcomes can be compared as long as the outcomes measured are valued in monetary units

Disadvantages:
- placing economic values on medical outcomes is not an easy task and there is not universal agreement on one standard method for accomplishing this
Recognize which methods are used for measuring indirect and/or intangible benefits.
Indirect:
- Human Capital (HC)
- Willingness-to-Pay (WTP) approaches

Intangible:
- Willingness-to-Pay (WTP) approach only
Describe the advantages and disadvantages of the HC and WTP approaches.
HUMAN CAPITAL:
Advantages:
- fairly straightforward and easy to measure
- income estimates can be obtained or estimated from publicly available sources
- days lost from illness can be readily obtained from the patient or another secondary source

Disadvantages:
- may be biased against specific groups of people, namely unemployed individuals, children, and the retired elderly
- the assumption that the value of health benefits equals the economic productivity they permit may also be biased
- the HC method does not incorporate values for pain and suffering if these values do not impact productivity even if they do have an impact on a person's health-related quality of life

WILLINGNESS-TO-PAY:
Advantages:
- places a dollar value on intangible benefits
- embodies patient preferences and choice

Disadvantages:
- many critics question the validity of the WTP responses because of the various methods used to elicit dollar values
- it is difficult for people to place a dollar value on a health benefit or an increase in HRQoL or satisfaction
- compliance bias occurs when respondents want to "please" the interviewer and may overstate their WTP values
- strategic bias occurs when respondents overstate or understate their WTP values to strategically impact the outcome
- other biases with the bidding vehicles
Describe the advantages and disadvantages of different methods used to elicit WTP values.
Open-Ended Questions:
- simply ask respondents how much they would be willing to pay for the program/intervention
- used the least because it results in WTP values that vary widely

Closed-Ended Questions:
- also called "take-it-or-leave-it" or dichotomous choice questions
- respondents are asked whether they will pay a specified dollar amount for the program/intervention
- drawback is only one question is asked, so only one WTP value can be elicited from a respondent

Bidding Game:
- resembles an auction
- before soliciting a second response, the bids are adjusted based on the first response (suggested that three times is optimal)
- time consuming and best conducted via face-to-face interview or over the internet
- the WTP values can be biased depending on how high or low the first bid is
- requires a large sample size

Payment Card:
- provides the respondent with a list of possible WTP amounts
- easy to use and provided respondents with a range of values to choose from
- providing respondents with a range of values can bias their WTP values
- the range provided can suggest the value of the intervention and can influence what respondents say (range bias)
Calculate the net benefit or net cost of an intervention or project.
Net Benefit = total benefits - total costs

Net Cost = total costs - total benefits
Calculate the benefit-to-cost ratio or cost-to-benefit ratio of an intervention or project.
Benefit-to-Cost Ratio = total benefits / total costs

Cost-to-Benefit Ratio = total costs / total benefits
Determine which alternative is more cost-beneficial based on the net benefit or benefit-to-cost ratio.
Net Benefit:
- interventions would be considered cost-beneficial if one of the following is true: net benefit > 0; net cost <0

Benefit-to-Cost Ratio:
- interventions would be considered cost-beneficial if one of the following is true: benefit-to-cost ratio > 1; cost-to-benefit ratio < 1
Describe the standard equation used to calculate the number of days worked per year.
(365 days in a year) - (number of weekend days) - (number of vacation days) - (number of sick-leave days) = days worked
Calculate the cost savings from implementing an intervention using the human capital approach.
- two basic components to calculating HC: wage rate and missed time (days or years) because of illness
- a yearly wage rate (income per year) would be calculated for a program or intervention that would reduce long-term disability or death
- a daily wage rate (income per year divided by number of days worked per year) may be calculated for a program or intervention targeted at an acute or chronic illness with short-term disability
- missed time (days or years) because of illness can be obtained by self-report

**if a yearly wage rate is calculated, then assessment of the number of years lost because of a disease or illness must be made. If a daily wage rate is calculated, an assessment of the number of missed days because of illness must be calculated

EXAMPLE:
- Assume that the population served by the asthma clinic is made up of adults with an average income (including fringe benefits) of $40,000 and 240 days worked per year.
- The daily wage rate (average income/number of days worked per year) would be $40,000/240 = $167/day.
- An average of 20 days a year were missed from work before participating in the asthma clinic, and an average of 7 days a year were missed from work after participating in the asthma clinic.
- The cost savings or the indirect benefit resulting from the program or intervention = ($167 x 20) - ($167 x 7) = ($167 x 13) = $2,171.
Describe the purpose of decision analysis.
- the application of an analytical method for systematically comparing different decision options when the decision is complex and there is uncertainty about some of the information
- assists with selecting the best or most cost-effective alternative by graphically displaying choices and facilitating the calculation of values needed to compare these options
List the steps for performing decision analysis.
1. Identify the specific decision.
2. Specify alternatives.
3. Draw the decision analysis structure.
4. Specify possible costs, outcomes, and probabilities.
5. Perform calculations.
6. Conduct a sensitivity analysis.
Distinguish between choice nodes, chance nodes, and terminal nodes in a decision tree.
- Choice Node: a choice is allowed
- Chance Node: chance comes into the equation
- Terminal Node: the final outcome of interest for each option in the decision is represented
Compare one-way and two-way sensitivity analyses.
The difference between one-way and two-way sensitivity analyses is the number of independent parameters.
Describe the use of tornado diagrams in decision analysis.
- in economic evaluations, tornado diagrams are used to present the result of multiple one-way sensitivity analyses in a single graph
Use a Tornado diagram to determine which variable has the largest impact on the results of a study.
The largest bar at the top has the largest impact on the results of a study.
Use threshold analysis to determine whether the study results are sensitive or robust to the variation of a particular study variable.
If the bars cross, then the analysis results are sensitive or robus.
Sets found in the same folder