Pharmacoepidemiology Overview

Pharmacoepidemiology

• Pharmacoepidemiology is a science focused on evaluating the effects of medications on populations' health.
• It builds on epidemiology, which initially focused on infectious epidemics, to examine drug impacts.
• Pharmacoepidemiology differentiates itself from fundamental pharmacology and comparative clinical pharmacology by analyzing drug effectiveness in real-world settings.

Different Types of Pharmacology

• Fundamental Pharmacology: Analyzes drug mechanisms of action.
• Comparative Clinical Pharmacology: Evaluates drug efficacy via clinical trials, focusing on comparisons between drug groups.
• Pharmacoepidemiology: Assesses drug effectiveness in heterogeneous populations with varying characteristics, considering real-world drug consumption and impact.

Proof and Reasoning in Pharmacoepidemiology

• Logical reasoning and fundamental pharmacology can suggest potential drug effects, but firm proof is required.
• Comparative clinical pharmacology (e.g., clinical trials) provides evidence of efficacy.
• Pharmacoepidemiology can validate or challenge clinical trial outcomes by examining drug effectiveness in the real world.

The CAST Study

• The CAST study (1991) examined the mortality associated with flecainide and encainide.
• The study demonstrated an increased mortality risk when treated with flecainide/encainide compared to placebo, an important finding that informed use recommendations.

Population Differences

• Clinical trials often do not account for important subgroups.
• Key groups such as children, pregnant/breastfeeding women, elderly, and patients with comorbidities are often excluded.
• Differences in drug consumption and usage patterns should be considered.

Objectives of Pharmacoepidemiological Studies

• Describe treated subjects and patterns of drug consumption within the real world.
• Estimate drug safety and effectiveness within a real-world population.

Concept of Risk

• Risk is estimated by incidence rate.
• Risk of events (e.g., adverse effects) varies based on time, place, and individual differences.

Risk and Medication

• Medications can expose individuals to predictable/unpredictable and/or avoidable risks.
• Medications can have effects on individuals, and they should be considered in a variety of contexts.
• Predictable risks are those with known potential effects or properties, while unpredictable risks are those with unknown (unforeseen) effects.

Effectiveness

• Effectiveness refers to the ability of a drug or treatment to achieve intended results in a real-world or heterogeneous population.

Studying Medication Effectiveness

• Authorities, insurers, and hospitals need comparable, comprehensive data to make informed decisions.
• Real-world effectiveness informs whether fundamental pharmacology and clinical pharmacology findings are transferable to practice.

Study Objectives for Effectiveness

• Determine the association between drug use and patient health outcomes.
• Evaluate the effectiveness of multiple medications in treating similar conditions.

Impacts of Pharmacoepidemiological Studies

• Pharmacoepidemiology can impact medication market withdrawal, new indications, and reimbursement decisions.

Bias in Observational Studies

• Bias is an important concern in pharmacoepidemiology.
• Three major types of bias are selection, information, and interpretation bias.

Selection Bias

• This bias occurs due to differences in exposure (e.g., drug use) between sampled individuals.
• Bias results from how participants are selected and recruited.

Information Bias

• Information bias is caused by errors in gathering data due to how researchers collect the information.
• Misclassification of exposure or event is a significant cause of information bias.

Interviewer Bias

• Researchers who conduct the interviews/collection process may be unintentionally predisposed to interpret responses of selected groups differently.
• Researchers may unconsciously influence responses based on their prior knowledge or hypotheses.

Recall Bias

• Patients may misremember their exposure or event occurrences.
• The memory bias may depend on the reason for the assessment.

Admission Bias (Berkson's Bias)

• This bias is often found in case-control studies with hospital settings.
• Patients hospitalized are more likely to use certain medications.

Preventing Selection and Information Bias

• To mitigate bias, researchers must anticipate and address potential biases during study design and data collection.
• Researchers must have meticulous data collection processes.

### Confounding Bias

• In pharmacoepidemiology, this distortion can misrepresent an association between drug usage and health outcome.
• It is essential to control for confounding factors.

Indication Bias

• This bias involves preferential prescription of a drug based on existing patient risk factors.

Protopathic Bias

• This bias suggests that a treatment for early symptoms might be wrongly implicated as causing the disease itself.

Preventing Confounding Bias

• Researchers should strategically apply methods like multivariable analysis to appropriately control for potential confounders.

Conclusion and Further Research

• No pharmacoepidemiological test is fully bias-free.
• Researchers should prepare for potential biases during study protocol design. Also, systematically discuss their biases when presenting results.
• Critical appraisal of published articles should carefully evaluate population differences and possible confounding variables.