Pharmacoepidemiology, Drug Utilisation Evaluation & Pharmacoeconomics

Pharmacoepidemiology

Definition and Rationale

• Definition: The application of epidemiologic reasoning, methods, and knowledge to the study of the uses and effects (beneficial and adverse) of drugs in human populations.
  • Epidemiology: The research discipline concerned with the distribution and determinants of disease in populations.
• Purpose: To measure the source, diffusion, use, and effects of drugs in large populations and determine the frequency and distribution of drug use outcomes.
• Pharmacist’s Role: Pharmacists must be involved in studying drugs and their effects at the population level to ensure better therapy at the patient level. Pharmacoepidemiology is integral to the pharmacist’s role in society.
• WHO Targets: Ensure quality, safety, and efficacy of drugs in specific patient populations by:
  • Describing drug use patterns and changes over time.
  • Measuring effects of information, education, promotion, and price on drug use.
  • Identifying inappropriate drug use and related problems.
  • Predicting drug needs in disease outbreaks.
  • Planning selection, supply, and distribution of drugs.

Place in Drug Development and Healthcare

• Efficacy vs. Effectiveness:
  • Efficacy: Clinical effect under ideal conditions (e.g., in Randomized Controlled Trials - RCTs).
  • Effectiveness: Use under normal, real-life conditions (e.g., patients with co-morbidities, taking multiple drugs, less than 100% adherence).
  • Role of Pharmacoepidemiology: The only way to study drug effectiveness is through pharmacoepidemiological studies.
• Outcomes:
  • Positive Outcomes: Efficacy or effectiveness.
  • Negative Outcomes (Adverse Drug Events - ADEs): Relationship between drug ingestion and negative outcome, where causation is not certain.
  • Adverse Drug Reaction (ADR): When there is a causal association with the drug.
• Levels of Operation: Pharmacoepidemiology operates on three distinct levels:
  • Macro level: Population level (e.g., drug use patterns, overall net benefit, national/international expenditure, drug policy).
  • Meso level: Groups clustered by a common factor (e.g., age, geography, drug use, disease, service, insurance).
  • Micro level: Individual patient, prescriber, or pharmacist level drug use measurement.

Origins and Evolution

• Early Studies: Investigation into tetanus outbreaks due to contaminated vaccines in 1901-1902 in the USA, leading to the 1902 Biologics Control Act.
• Legislation: Prompted protective legislation after events like 1937 contamination, requiring toxicity and clinical safety data before marketing.
• Development: First textbook in 1986, formation of the International Society of Pharmacoepidemiology (ISPE) in the same year.

Evidence-Based Medicine (EBM) and Pharmacoepidemiology

• EBM Definition: Integration of best research evidence with clinical expertise and patient values.
• Hierarchy of Evidence: Evidence includes information from RCTs and other studies, most of which fall within pharmacoepidemiology.
• Advantages over RCTs:
  • RCTs are ideal for efficacy but may not reflect real-life effectiveness.
  • Pharmacoepidemiological studies complement RCTs by examining safety and effectiveness in the general population using observational methods.
  • RCTs are not designed for detecting new ADRs or new indications.
• Disadvantages (Weakness): A major weakness with observational studies is that causation cannot usually be determined with certainty.

Aims and Applications

• Identify New ADRs and Indications: Through signal generation, often from case reports or patient follow-up studies.
• Qualify Nature of ADRs/Clinical Effects: Identify and describe factors associated with drug’s risk/benefit.
• Quantify Outcomes: Using large patient samples for precision in estimating risks/benefits and quantifying association between exposure and outcome.

Sources of Data on Drug Use

• Institutional medical records and databases (hospital, pharmacy claims).
• System-wide databases (health insurance, pharmaceutical organizations, commercial vendors).
• National databases (surveillance systems, government-sponsored studies like Medical Expenditure Panel Survey, National Ambulatory Medical Care Survey).
• Field data (records from dispensers, sellers, distributors, or small groups).
• Experimental clinical trial data.

Drug Classification and Measurement

• Anatomical Therapeutic Chemical (ATC) Classification System:
  • Developed by WHO.
  • Classifies drugs by Anatomic system, Therapeutic use, and Chemical class.
  • Each drug has a unique identifying number (e.g., omeprazole A02BC01).
• Units of Use:
  • Monetary: Dollars, pounds, rupees. Universal, flexible, but does not measure actual drug use or quantity consumed.
  • Prescriptions: Straightforward and easily understood, but quantity, strength, and duration vary.
  • Number of Units: (e.g., tablets, capsules) dispensed. Varies with patient characteristics and drug forms.
  • Defined Daily Doses (DDDs): Technical unit, average daily dose for major indication in adults. Uniform concept for comparing utilisation between regions/countries/time.
    • Expressed as DDD/1000 inhabitants or DDD/100 bed-days in hospitals.
    • Disadvantages: Not available for all drugs or paediatric use, multiple indications for a drug.

Outcome Measures of Drug Use

• Prevalence: Proportion of people affected by or exposed to a drug at a given time. A cross-sectional statistic, usually from a survey.
• Cumulative Incidence: (Not explicitly defined in the provided text, but mentioned as a classic measure).
• Incidence Rate: (Not explicitly defined in the provided text, but mentioned as a classic measure).

Trend Analysis and Ecological Correlation

• Trend Analysis: Plotting data over time to identify patterns; shifts in trend lines suggest impact of changes (e.g., new pharmacy law).
• Ecological Correlation: When two separate data sets displayed together show a consistent pattern (e.g., antibiotic use and resistant bacterial strains).

Major Pharmacoepidemiological Study Designs

• Observational Studies: Most pharmacoepidemiological studies are observational.
• Cohort Study: (Not explicitly detailed in the provided text, but mentioned as a main type).
• Case-Control Study: Identifies patients with an outcome of interest and compares them to a matched group without the outcome.
  • Example: Chan and co-workers studied hospital admissions for GI haemorrhage, comparing NSAID exposure rates.

Statistical Measures

• Odds Ratio (OR): A common statistical measure used to describe the relationship between drug exposure and outcome. (Example given in case-control study with OR of 14.0 for non-exposed controls for GI hemorrhage).
• Confidence Interval (CI): Used for the odds ratio. For example, 95% CI around the OR indicates the range within which the true OR is likely to fall. (Calculation of CI for relative risks/odds ratios is mentioned by Morris and Gardner, 1988).

Drug Utilisation Evaluation (DUE)

Definition and Terminology

• Definition: An ongoing, authorised, and systematic quality improvement process designed to review drug use, provide feedback, develop criteria/standards, and promote appropriate drug use through education and interventions.
• Evolution of Terms:
  • Originally Drug Utilisation Review (DUR) in the 1970s and early ’80s.
  • Drug Use Evaluation (DUE) and DUR are interchangeable.
  • Medication Use Evaluation (MUE): Another term used since 1994, similar to DUE but more patient outcome-oriented, emphasising clinical outcomes and health-related quality of life (HRQOL).
• Main Aim: To promote rational drug use.

Objectives/Aims of DUE

• Reduce drug- and health-related treatment costs.
• Improve health-related quality of life.
• Improve quality of medical treatment and coordinated healthcare.
• Decrease medication-related problems and errors.
• Decrease hospital admissions.
• Improve prescriber awareness and practice towards appropriate prescribing.

Types of DUE Studies

• Drug-focused: Examines the use of a single drug (e.g., amikacin) or class (e.g., third-generation cephalosporins).
• Indication-focused: Examines the use of a drug or drugs for a specific indication (e.g., intravenous omeprazole for bleeding peptic ulcers).
• Quantitative Studies: Collects, organises, and displays estimates or measurements of drug use. Used for purchasing decisions or financial activities (e.g., preparing drug budgets). Data is suggestive, not conclusive, of quality.
• Qualitative Studies: Multidisciplinary operations that collect, organise, analyse, and report information on actual drug use. Usually one-off examinations of narrowly defined areas. Include concept of predetermined criteria.
• Combined Studies: Possible to combine quantitative and qualitative for information on patterns, amount, and quality of drug use.
• Based on Timing of Data Collection:
  • Prospective Review: Evaluates planned drug therapy before administration. Interventions provided if necessary.
  • Concurrent Review: Data collection and evaluation occur during drug therapy.
  • Retrospective Review: Uses data available from the past.

DUE Committee

• Composition: Physicians, pharmacists, and other relevant healthcare professionals with an interest in improving drug therapy. Usually includes Pharmacy department representation.
• Relationship: May be the hospital’s Drug and Therapeutics Committee (DTC) or a specific DUE Committee.
• Functions:
  • Draft and approve policies and procedures.
  • Establish communication with hospital administration and other committees.
  • Prepare a schedule for meetings (planning, criteria approval, data evaluation, intervention design, review).

Steps in the DUE Cycle

1. Identify drugs or therapeutic areas for inclusion: Prioritise based on clinical impact.
   • Sources: Medication error reports, ADR reports, feedback from prescribers/pharmacists, microbiological data, medical/pharmaceutical literature.
   • ABC/VEN Analysis: Tool to identify high priority drugs.
     • ABC Analysis: Divides drugs by annual usage value (A=75-80% value, B=15-20%, C=5-10%).
     • VEN Analysis: Classifies drugs as Vital (V), Essential (E), Non-essential (N).
2. Design of study: Common methods include observational, cross-sectional, and pre-post designs. Categorised as prospective, concurrent, or retrospective.
3. Define criteria and standards:
   • Literature Review: Exhaustive search, critical evaluation of original papers, summarising key findings, deriving evidence-based criteria.
   • Criteria: Must be scientifically based, valid, unambiguous, realistic, easily measured, and outcome-oriented. Developed with specialist input and medical staff consensus for local agreement.
4. Design the data collection form: Limit data collection to most important and relevant aspects due to time/staff constraints.
   • Common aspects surveyed: Patient demographics, drug/disease specifics, appropriateness of use, DRPs, monitoring, patient education, cost.
   • Data sources: Patient treatment charts, admission records, pathology records, microbiological data, medication charts, medical notes, patient/nursing interviews, administrative data.
   • Pilot audit: Recommended to test the form.
5. Develop and implement interventions: If problems identified, address them through educational or operational interventions.
   • Educational: Meetings, academic detailing, protocols, study results feedback, newsletters, posters, guidelines.
   • Operational: Drug order form modification, reminders (manual/computerised), prescribing restrictions, formulary changes, automatic stop orders, staff reallocation.
   • Effective interventions: Academic detailing, routine reminders, prescribing restrictions, structured prescription forms, interactive educational meetings.
6. Re-evaluate to determine if drug use has improved: Typically 3-12 months after intervention, collecting the same data.

Resources and Tools Required for DUE

• Human Resources: Pharmacists, physicians, other healthcare professionals.
• Criteria Development Resources: Professional literature, reference texts, local/national/international guidelines, published consensus statements/protocols.
• Quality Measurement Tools: Indicators (e.g., JCAHO).
• Documentation, Management, Evaluation, and Reporting Resources: Computer databases, specially designed DUE software programs.

Pharmacist’s Role in DUE

• Key role due to experience in pharmaceutical care.
• Identifies prescribing trends and initiates action to improve drug therapy.
• Responsibilities: Planning/organising/implementing DUE programmes, educating staff, promoting goals, developing/reviewing audit criteria, data collection/analysis/reporting, documenting outcomes, participation in quality assurance committees, presenting/publishing results.

Pharmacoeconomics

Need for Pharmacoeconomics

• Resource Constraints: Assists in decision-making under limited resources, tight budgets, and competing programmes.
• Clinical Settings: Consider therapeutic effectiveness, impact of cost on hospital pharmacy budget (nursing/lab costs), and quality of life.
• Indian Context: Important for globalisation of Indian pharmaceutical firms, advent of PharmD curricula (evidence-based pharmacotherapy), and providing affordable lifesaving medications. Required to evaluate objectives of “Vision 2010” statement for “Healthy India”.
• Decision-Making Aid: Helps evaluate affordability/access to the right medication, compare drugs in the same class, establish manufacturer accountability, decide formulary inclusion, determine net positive benefits for patient groups, and assess quality-of-life improvement vs. side effects.

Definition of Pharmacoeconomics

• Economics: Study of allocating limited resources among alternative uses to satisfy unlimited wants. Elements: identification/choice among alternatives, assessment of costs/consequences, decision-making within limited budgets.
• Health Economics (ISPOR Definition): Evaluates the behaviour of individuals, firms, and markets in healthcare, focusing on costs (inputs) and consequences (outcomes) of healthcare interventions.
• Pharmacoeconomics (ISPOR Definition): Evaluates the behaviour of individuals, firms, and markets relevant to pharmaceutical products/services/programs, focusing on costs and consequences of their use.
• Operational Definition: Compares outcomes (clinical, economic, humanistic) and costs (resource consumption) of pharmaceutical products/programmes/services to next best alternatives from selected perspectives.
• Discipline Draws From: Economics, epidemiology, medicine, pharmacy, social sciences.

Four Es of Health Programme Evaluation

1. Efficacy: Can it work? (under ideal conditions).
2. Effectiveness: Does it work? (under realistic conditions).
3. Equity: Is it reaching those who need it? Who gains/loses?.
4. Efficiency: Is it worth doing?.
   • Economic evaluations primarily assess efficiency, but should be preceded by studies on the other three objectives.

Misperceptions about Pharmacoeconomics

• PE = Cost containment: Not only goal; considers clinical, economic, humanistic outcomes.
• PE = Cost effectiveness: CEA is only one tool of PE analysis.
• PE = Medication Utilisation Evaluation (MUE): MUE assesses appropriateness of drug use; PE links costs and outcomes.
• PE = Outcomes research: Outcomes research is broad; PE is a tool within it.

Types of Pharmacoeconomic Evaluations

Full economic evaluations compare two or more alternatives and link both costs and effects.

1. Cost Minimisation Analysis (CMA): Outcomes are assumed to be the same; compares costs only.
2. Cost-Benefit Analysis (CBA): Both costs and consequences are measured in monetary terms.
3. Cost-Effectiveness Analysis (CEA): Consequences are in natural units (e.g., mmHg, life-years gained).
4. Cost-Utility Analysis (CUA): Consequences incorporate quantity and quality of life (e.g., Quality-Adjusted Life Years - QALYs).
5. Cost-Consequences Analysis (CCA): Lists all relevant parameters in an array format; decision criteria are specific to each decision-maker for combining measures of costs and effectiveness.

Types of Costs and Outcomes

• Inputs (Costs/Resource Utilisation):
  • Healthcare Sector (C1): Organising/operating costs, continuing care, direct costs (overhead, capital, variable), drug costs, lab tests, physician visits.
  • Patient and Family (C2): Out-of-pocket expenses.
  • External Costs (C3): Costs to other sectors (e.g., social services).
  • Productivity Losses (C4): Due to illness, disability, premature death.
  • Economic Cost: Includes opportunity costs (health outcomes forgone).
• Outputs (ECHO - Economic, Clinical, Humanistic Outcomes):
  • Economic Outcomes (Monetary): Reduction in resource use or savings (S1-S4: Healthcare sector, patient/family, non-health sector, productivity gains).
  • Clinical Outcomes: (e.g., reduction in total cholesterol level).
  • Humanistic Outcomes: Quality of life, patient satisfaction.
• Perspective: Crucial, as it dictates data collection and analysis. Four types: patient/consumer, provider/institution, payer/insurance company, and society (preferred).

Guidelines for Conducting or Evaluating a Pharmacoeconomic Evaluation

• Prerequisites: Advanced knowledge of research methods, biostatistics, basic understanding of economics/finance, grounding in psychometric analysis.
• Basic Steps:
  1. Definition of the study question: Purpose, perspective (patient, provider, payer, society).
  2. Identification, measurement, and valuation of costs and consequences: Types of costs, enumeration, valuation, sources.
  3. Study design and data collection: (Not explicitly detailed as a separate step but implicit in the evaluation process).
  4. Selection of decision criteria: (Implicit in evaluation).
  5. Presentation of results: (Implicit in evaluation).

Translating Pharmacoeconomic Strategies to Practice

• Approaches:
  1. Evaluating, interpreting, and using results of published studies (simple, inexpensive, quick access, peer-reviewed, but data may not be applicable locally).
  2. Using economic modelling and/or simulation studies.
  3. Conducting pharmacoeconomic studies specific to the institution/scenario using retrospective or prospective data (advantageous for local reality, data quality, but costly in time/resources).
• Population-based Pharmacoeconomics: Contrasts with patient-level (incidence-based) evaluation; considers externalities, phasing-in effects, community effectiveness, capacity issues, and different time perspectives.

Budget Preparation and Implementation

• Relevance: Budget preparation and implementation are integral to pharmacoeconomics, as economic analyses aid in the allocation of limited resources and influence financial planning for pharmaceutical products, programmes, and services.
• Syllabus Inclusion: This topic is explicitly listed in the syllabus under Unit IV. While specific detailed steps for budget preparation are not provided in the sources, the principles of pharmacoeconomics directly inform these activities by evaluating costs and consequences to make efficient spending decisions. This ensures that the acquisition and deployment of pharmaceutical resources align with therapeutic goals and financial constraints.