PharmacoEpi
Introduction
Eelko Hak
15/03/2021
Epidemiology is the science that studies the occurrence of diseases in large populations of people as
a function of determinants. It is an essential science for the conduct of ‘evidence-based medicine’.
Topics of epidemiology:
- Etiology (by nature exposed)
- Intervention/therapy/prevention (therapeutical)
- Diagnosis
- Prognosis
Etiology/intervention deals with causal associations, analytic studies, case-control/RCT, mostly 1
determinant, confounding bias, explanatory statistical model.
Diagnosis/prognosis deals with predictive associations, descriptive studies, cohort design, more
determinants, no confounding bias, predictive statical model.
Dr. Salk mineral oil polio vaccination: safe vaccination.
Cutter incident: vaccination unsafe > polio injected.
Four main reasons for dangerous side effects and withdrawal:
- Clinical trials are not large enough
- ‘Real world’ use of drug differs
- Time plays a role
- Off-label prescribing
E.g., Rofecoxib was withdrawn because of cardiovascular side effects.
Positive side effects:
New indications:
- Finasteride > used for Benign prostatic hyperplasia > increased hair growth
- Statins > less sepsis/COPD exacerbations
- Sildefanil (Viagra) > used for heart-related chest pain > erectile dysfunction
Protective effects:
- Acetylsalicylic acid > protection colorectal cancer
- Bisphosphonates > protection breast cancer
,Phases of drug development
Epidemiological studies
Experimental studies: researcher determines
- Clinical trials
- Community intervention trials (e.g., hospital)
- Field trials
Observational studies:
- Descriptive studies / cross-sectional studies (prognosis/diagnosis)
- Case control studies / cohort studies
General characteristics of clinical drug research: RCT
- Narrow clinical indications
- Homogenous population
- Small number
- Randomized: determinant/exposure
- Controlled: determinant/exposure
- Double blind
- Relatively short-term therapy
Evidence based medicine
Observational post marketing surveillance (PMS) has a large number of patients, has an unlimited
time, and have drug-users in practice. Also influences like smoking, other drugs, and nutrition are
taken into account.
Hard endpoints = hospital disease, mortality
Soft endpoint = QALY
Efficacy = effect in clinical trials or laboratory studies
Effectiveness = effect in daily practice
Efficiency = costs in relation to effects
The institute of medicine requires more transparency in communication about adverse effects to the
public. The black triangle on all newly approved drugs. The ‘direct-to-consumer advertising’’ is
prohibited in the first two years after registration. Also, better monitoring and reporting on drug
safety is needed, and therefore more funding.
Who had interest in PMS (post-marketing surveillance):
- 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 in regard to costs
- Government: registration and safety
- Industry: want a good product
, Information sources for PMS research:
- Spontaneous reporting system LAREB
- Routine (administrative) databases
- Questionnaires/interviews/web-based
- Cohorts/physical testing/lab data
Pharmacy: considerations
- Privacy
- Indication is not available
- Patient data limited
- Self-medication
- Compliance
- Adverse effects
- History
- Good information about medication: dosage, duration, which drug
Patient: considerations
- Labour intensive
- Completeness
- Reliability
- Adverse effects
- Smoking, alcohol
Pharmlines Initiative
Lifelines
- Cohort study patient inclusion 2006-2013
- 167.000 participants
- Aim: healthy aging
- Method: providing population information to researchers
IADB
- Prescription database
- 60 pharmacies (600.000 patients)
- Providing research data to FTEE
Research goals assess concordance Lifeline mediation data (Cohen’s Kappa, sensitivity, specificity,
PVV and NPV) compared with the prescription databases. Base line measurement.
- High agreement: cardiovascular medication
- Low agreement: dermatological, not considered as medication
- ATC G: stigmatization bias
- ATC H, J, P: short usage
See how good the questionnaires represent the prescription database. Depends on medication.
ATC/DDD system: Anatomical Therapeutic Chemical classification
system, developed by the WHO collaborating centre of drug
statistics and methodology.
7 positions, 5 hierarchical levels
1. 1 letter – anatomical main group
2. 2 digits – therapeutic main group
3. 1 letter – therapeutic subgroup
4. 1 letter – therapeutic/chemical subgroup
5. 2 digits – chemical substance
e.g., aspirin N02BA01, diazepam N05BA01
Introduction
Eelko Hak
15/03/2021
Epidemiology is the science that studies the occurrence of diseases in large populations of people as
a function of determinants. It is an essential science for the conduct of ‘evidence-based medicine’.
Topics of epidemiology:
- Etiology (by nature exposed)
- Intervention/therapy/prevention (therapeutical)
- Diagnosis
- Prognosis
Etiology/intervention deals with causal associations, analytic studies, case-control/RCT, mostly 1
determinant, confounding bias, explanatory statistical model.
Diagnosis/prognosis deals with predictive associations, descriptive studies, cohort design, more
determinants, no confounding bias, predictive statical model.
Dr. Salk mineral oil polio vaccination: safe vaccination.
Cutter incident: vaccination unsafe > polio injected.
Four main reasons for dangerous side effects and withdrawal:
- Clinical trials are not large enough
- ‘Real world’ use of drug differs
- Time plays a role
- Off-label prescribing
E.g., Rofecoxib was withdrawn because of cardiovascular side effects.
Positive side effects:
New indications:
- Finasteride > used for Benign prostatic hyperplasia > increased hair growth
- Statins > less sepsis/COPD exacerbations
- Sildefanil (Viagra) > used for heart-related chest pain > erectile dysfunction
Protective effects:
- Acetylsalicylic acid > protection colorectal cancer
- Bisphosphonates > protection breast cancer
,Phases of drug development
Epidemiological studies
Experimental studies: researcher determines
- Clinical trials
- Community intervention trials (e.g., hospital)
- Field trials
Observational studies:
- Descriptive studies / cross-sectional studies (prognosis/diagnosis)
- Case control studies / cohort studies
General characteristics of clinical drug research: RCT
- Narrow clinical indications
- Homogenous population
- Small number
- Randomized: determinant/exposure
- Controlled: determinant/exposure
- Double blind
- Relatively short-term therapy
Evidence based medicine
Observational post marketing surveillance (PMS) has a large number of patients, has an unlimited
time, and have drug-users in practice. Also influences like smoking, other drugs, and nutrition are
taken into account.
Hard endpoints = hospital disease, mortality
Soft endpoint = QALY
Efficacy = effect in clinical trials or laboratory studies
Effectiveness = effect in daily practice
Efficiency = costs in relation to effects
The institute of medicine requires more transparency in communication about adverse effects to the
public. The black triangle on all newly approved drugs. The ‘direct-to-consumer advertising’’ is
prohibited in the first two years after registration. Also, better monitoring and reporting on drug
safety is needed, and therefore more funding.
Who had interest in PMS (post-marketing surveillance):
- 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 in regard to costs
- Government: registration and safety
- Industry: want a good product
, Information sources for PMS research:
- Spontaneous reporting system LAREB
- Routine (administrative) databases
- Questionnaires/interviews/web-based
- Cohorts/physical testing/lab data
Pharmacy: considerations
- Privacy
- Indication is not available
- Patient data limited
- Self-medication
- Compliance
- Adverse effects
- History
- Good information about medication: dosage, duration, which drug
Patient: considerations
- Labour intensive
- Completeness
- Reliability
- Adverse effects
- Smoking, alcohol
Pharmlines Initiative
Lifelines
- Cohort study patient inclusion 2006-2013
- 167.000 participants
- Aim: healthy aging
- Method: providing population information to researchers
IADB
- Prescription database
- 60 pharmacies (600.000 patients)
- Providing research data to FTEE
Research goals assess concordance Lifeline mediation data (Cohen’s Kappa, sensitivity, specificity,
PVV and NPV) compared with the prescription databases. Base line measurement.
- High agreement: cardiovascular medication
- Low agreement: dermatological, not considered as medication
- ATC G: stigmatization bias
- ATC H, J, P: short usage
See how good the questionnaires represent the prescription database. Depends on medication.
ATC/DDD system: Anatomical Therapeutic Chemical classification
system, developed by the WHO collaborating centre of drug
statistics and methodology.
7 positions, 5 hierarchical levels
1. 1 letter – anatomical main group
2. 2 digits – therapeutic main group
3. 1 letter – therapeutic subgroup
4. 1 letter – therapeutic/chemical subgroup
5. 2 digits – chemical substance
e.g., aspirin N02BA01, diazepam N05BA01
