PHARMACOEPIDEMIOLOGY
INTRODUCTION
• What is wrong with the person? → diagnostics
• Cause of the disease? → etiology
• Future of the person? → prognosis
• Best treatment? → intervention/therapy
• How to prevent? → intervention/prevention
• Expensive to prevent? → efficiency/economics
Epidemiology is the science that studies the occurrence of diseases/deaths in large
populations of people as a function of determinants. Epidemiology is an essential
science for the conduct of ‘evidence based medicines’.
Etiology/intervention –
- Causal associations
- Analytic studies
- Case-control/RCT
- Mostly 1 determinant
- Confounding bias
- Explanatory statistical model
Diagnosis/prognosis –
- Predictive associations
- Descriptive studies
- Cohort design
- More determinants
- No confounding bias
- Predictive statistical model
Pharmaco-epidemiology is the scientific field
that studies the contribution of drugs in
disease prevention and therapy in large
populations.
Fields of research in pharmaco-epidemiology:
- What proportion of the population is using the drug/vaccine?
- Which determinants predict the use of the drug/vaccine?
- Does the drug/vaccine lead to a reduction in diseased cases/mortality/increase
in quality of life?
- What type of and how many side effects are caused by the drug/vaccine?
4 main reasons for dangerous side effects and withdrawal of a drug from the
market:
1. Clinical trials are not large (only tested on few people, since it is expensive)
2. Time plays a role (clinical trials are short, so long-term effect not known)
1
, 3. “Real world” use of drug differs (in the clinical trial only healthy people are
used for example. In the “real world”, the people that are sick are using the
drug, and they may have a different reaction to the drug than the people in the
clinical trial)
4. Off-label prescribing may lead to unexpected issues (the drug is prescribed to
a group of people, e.g. children, where the drug is not tested on during the
clinical trial)
Relative risk of coronary heart disease associated
with individual dosing of COX-2 inhibitor –
The recommended dosage (DDD) is 25 mg/day.
From the table it can be seen that it is not the drug
itself that is increasing the risk of heart disease, but it is the dosage taken by the
patient. There is an overuse of the drug, so the patient is making the problem in this
case, not the drug itself.
Drug repurposing – other indication identified for the same drug.
E.g. finasteride is used for benign prostatic hyperplasia, however, it is also found to
increase hair growth. Additionally, salbutamol is found to reduce the cumulative
incidences of Alzheimer disease as repurpose.
Phases in the drug development process –
Typical post-marketing research questions –
Type 1: what is the use of drug X in patient Y and what is the variation between age
and sex?
Type 2: what is the effect of drug X in the treatment of disease Z on outcome Y?
• Outcome
• Study domain
• Determinants
2
,Example of type 2: “To what extent prevents polio vaccination the occurrence of polio
in children?”
In experimental studies, researchers introduce
an intervention or treatment to one group
(experimental group) and compare it to a control
group that does not receive the intervention.
This allows for the assessment of the
intervention's impact. Experimental studies are
typically prospective, meaning that data is
collected over time as the study progresses.
In observational studies, researchers do not intervene or manipulate any variables.
They observe and record existing data. Observational studies can be either
retrospective (looking at past data) or prospective (collecting data as the study
progresses).
Randomized clinical trials (RCT) –
- Limited number of patients
- Limited time
- Homogenous population
- Other variables (e.g. smoking or usage of other drugs) are excluded or
controlled
Observational (post-marketing surveillance/PMS) –
- Large number of patients
- Unlimited time
- Drug-users in practice
- Other influences (e.g. smoking, other drugs, nutrition)
Important clinical information that has to be obtained from PMS research –
- Usage and determinants in practice
- Effects in daily practice
- Adverse effects
- Drug interactions
- Usage of drugs for other indications (off-label)
- New applications
- Applied dosage and duration
- Usage/effect in children, elderly and pregnant woman
- Effect on ‘hard’ endpoints (disease/mortality)
- Effect on population level (if 50% of the population is vaccinated, what is the
effect on the whole population? Are the others also protected?)
- Pharmaco-economics:
- Costs
- Compliance
- Cost-effectiveness of interventions
3
, Efficacy: effect in clinical trials or laboratory studies
Effectiveness: effect in daily practice
Efficiency: cost in relation to effects
Post-marketing surveillance/phase-IV research: monitoring all desirable and
undesirable (adverse-)effects of drugs to human health, after these drugs are
released on the market. The goal is to obtain scientific based data on rational and
safe use of drugs.
Since 2008, it is obligatory for pharmaceutical companies to have a risk management
plan (RMP) for all drugs that are released on the market. In the RMP a company
explains which studies are performed to increase knowledge about the risks of the
drug.
Institute of medicine –
- More transparency in communication about adverse effects to the public
- Black triangle on all newly approved drugs (warning that it is new)
- “Direct-to-consumer advertising” prohibited in the first 2 years after registration
- Better monitoring and reporting on drug safety
Who has interest in PMS?
- Patient – wants an effective and safe drug with reliable information
- Physician/pharmacist – wants reliable and complete information to make a
good decision
- Insurance company – importance of rational prescribing with regard to costs
- Government – registration and safety
- Industry – wants a good product
Which person has the “best” information ?
Lifelines is a cohort study with 167.000 participants. Their aim is healthy aging.
Population information is provided to the researchers, e.g. urine, hair, blood, personal
information, disease, medication.
4
INTRODUCTION
• What is wrong with the person? → diagnostics
• Cause of the disease? → etiology
• Future of the person? → prognosis
• Best treatment? → intervention/therapy
• How to prevent? → intervention/prevention
• Expensive to prevent? → efficiency/economics
Epidemiology is the science that studies the occurrence of diseases/deaths in large
populations of people as a function of determinants. Epidemiology is an essential
science for the conduct of ‘evidence based medicines’.
Etiology/intervention –
- Causal associations
- Analytic studies
- Case-control/RCT
- Mostly 1 determinant
- Confounding bias
- Explanatory statistical model
Diagnosis/prognosis –
- Predictive associations
- Descriptive studies
- Cohort design
- More determinants
- No confounding bias
- Predictive statistical model
Pharmaco-epidemiology is the scientific field
that studies the contribution of drugs in
disease prevention and therapy in large
populations.
Fields of research in pharmaco-epidemiology:
- What proportion of the population is using the drug/vaccine?
- Which determinants predict the use of the drug/vaccine?
- Does the drug/vaccine lead to a reduction in diseased cases/mortality/increase
in quality of life?
- What type of and how many side effects are caused by the drug/vaccine?
4 main reasons for dangerous side effects and withdrawal of a drug from the
market:
1. Clinical trials are not large (only tested on few people, since it is expensive)
2. Time plays a role (clinical trials are short, so long-term effect not known)
1
, 3. “Real world” use of drug differs (in the clinical trial only healthy people are
used for example. In the “real world”, the people that are sick are using the
drug, and they may have a different reaction to the drug than the people in the
clinical trial)
4. Off-label prescribing may lead to unexpected issues (the drug is prescribed to
a group of people, e.g. children, where the drug is not tested on during the
clinical trial)
Relative risk of coronary heart disease associated
with individual dosing of COX-2 inhibitor –
The recommended dosage (DDD) is 25 mg/day.
From the table it can be seen that it is not the drug
itself that is increasing the risk of heart disease, but it is the dosage taken by the
patient. There is an overuse of the drug, so the patient is making the problem in this
case, not the drug itself.
Drug repurposing – other indication identified for the same drug.
E.g. finasteride is used for benign prostatic hyperplasia, however, it is also found to
increase hair growth. Additionally, salbutamol is found to reduce the cumulative
incidences of Alzheimer disease as repurpose.
Phases in the drug development process –
Typical post-marketing research questions –
Type 1: what is the use of drug X in patient Y and what is the variation between age
and sex?
Type 2: what is the effect of drug X in the treatment of disease Z on outcome Y?
• Outcome
• Study domain
• Determinants
2
,Example of type 2: “To what extent prevents polio vaccination the occurrence of polio
in children?”
In experimental studies, researchers introduce
an intervention or treatment to one group
(experimental group) and compare it to a control
group that does not receive the intervention.
This allows for the assessment of the
intervention's impact. Experimental studies are
typically prospective, meaning that data is
collected over time as the study progresses.
In observational studies, researchers do not intervene or manipulate any variables.
They observe and record existing data. Observational studies can be either
retrospective (looking at past data) or prospective (collecting data as the study
progresses).
Randomized clinical trials (RCT) –
- Limited number of patients
- Limited time
- Homogenous population
- Other variables (e.g. smoking or usage of other drugs) are excluded or
controlled
Observational (post-marketing surveillance/PMS) –
- Large number of patients
- Unlimited time
- Drug-users in practice
- Other influences (e.g. smoking, other drugs, nutrition)
Important clinical information that has to be obtained from PMS research –
- Usage and determinants in practice
- Effects in daily practice
- Adverse effects
- Drug interactions
- Usage of drugs for other indications (off-label)
- New applications
- Applied dosage and duration
- Usage/effect in children, elderly and pregnant woman
- Effect on ‘hard’ endpoints (disease/mortality)
- Effect on population level (if 50% of the population is vaccinated, what is the
effect on the whole population? Are the others also protected?)
- Pharmaco-economics:
- Costs
- Compliance
- Cost-effectiveness of interventions
3
, Efficacy: effect in clinical trials or laboratory studies
Effectiveness: effect in daily practice
Efficiency: cost in relation to effects
Post-marketing surveillance/phase-IV research: monitoring all desirable and
undesirable (adverse-)effects of drugs to human health, after these drugs are
released on the market. The goal is to obtain scientific based data on rational and
safe use of drugs.
Since 2008, it is obligatory for pharmaceutical companies to have a risk management
plan (RMP) for all drugs that are released on the market. In the RMP a company
explains which studies are performed to increase knowledge about the risks of the
drug.
Institute of medicine –
- More transparency in communication about adverse effects to the public
- Black triangle on all newly approved drugs (warning that it is new)
- “Direct-to-consumer advertising” prohibited in the first 2 years after registration
- Better monitoring and reporting on drug safety
Who has interest in PMS?
- Patient – wants an effective and safe drug with reliable information
- Physician/pharmacist – wants reliable and complete information to make a
good decision
- Insurance company – importance of rational prescribing with regard to costs
- Government – registration and safety
- Industry – wants a good product
Which person has the “best” information ?
Lifelines is a cohort study with 167.000 participants. Their aim is healthy aging.
Population information is provided to the researchers, e.g. urine, hair, blood, personal
information, disease, medication.
4
