Pharmacoepidemiology

PHARMACOEPIDEMIOLOGY

OVERVIEW

Definition Contributions Epidemiological aspects Reasons to perform Pharmacoepidemiology (PEp) Role of Pharmacoepidemiology Sources of data Special applications Goals Conclusion

DEFINITION

Pharmacoepidemiology

Pharmakon - Drug

Epi – upon or among

Demos – People or district

Logos - Study

Study of the uses of and the effects of drugs in a large number of people.

Potential contributions of PEp

(A) Information that supplements premarketing studies information(a) Higher precision (e.g.: Prazosin)(b) In patients not studied prior to marketing, e.g. the elderly, children, pregnant women(c) As modified by other drugs and other illnesses (e.g.: Timolol)(d) Relative to other drugs used for the same indication (standard drug v/s new drug)


(B) New types of information not available from premarketing studies

(1) Discovery of previously undetected adverse and beneficial effects(a) Uncommon effects (e.g.: agranulocytosis) (b) Delayed effects(e.g.: DES)(2) Patterns of drug utilization(3) The effects of drug overdoses(4) The economic implications of drug use


(C) General contributions of pharmacoepidemiology

(1) Reassurances about drug safety(2) Fulfillment of ethical and legal

obligations

Questions that can be answered by PEp

Patterns of use What are patterns of drug utilization How are drug utilized in special population How long do people take this drug e.g.: doxycycline

Safety What is the frequency of drug induced

outcomes Are there drug drug interactions?

Effectiveness What are the clinical benefits of this drug Is drug A more effective than drug B?

Economic evaluation What are the economic consequences of

therapy

Bridging science - PEp

Basics of clinical pharmacology Pk, Pd, Pharmacogenomics, Pharmacovigilance, Pharmacoeconomics etc.

Basics of epidemiology

SCIENTIFIC METHOD

statistical inference

biological inference

Study sample

Conclusion about a population

Conclusion about scientific theory

association

causation

Study designs available for PEp studies

In hierarchical order of progressively harder to perform but more convincing Randomized clinical trials

Cohort studies

Case-control studies

Analysis of secular trends

Case series

Case reports

Reasons to perform PEp studies

1) Regulatory

(a) Required(b) To obtain earlier approval of marketing(c) As a response to question by regulatory agency(d) To assist application for approval for marketing elsewhere

2) Marketing

(1) To assist market penetration by documenting the safety of drug

(2) To increase the name recognition(3) To assist in re positioning the drug(4) To protect the drug from accusations about

adverse effects

3) Legal(1) In anticipation of future product liability litigation

4) Clinical(1) Hypothesis testing

(2) Hypothesis generating

ROLE OF PHARMACOEPIDEMIOLOGY IN VARIOUS SECTORS

Government agencies and health care plans

They use PEp studies to Learn how drug products are used in real

world Provide access to drugs in quality manner, at

an affordable cost, to a variety of population To deal with coverage issues, educational

intervention

E.g.: Sildenafil In 1998 FDA approved Till 2005, 43 cases of NAION

Pharmaceutical industry

They conduct PEp to know How a drug is prescribed Used What are the outcomes – positive and

negative E.g.: Astra Zeneca - to complement the

safety data Rosuvastatin with other statins Contained around 50000 patients

Practitioners

To make informed decisions at both individual patient level and the population level

Attorneys

They use PEp studies As evidence that a drug product did or did

not cause as event E.g.: Sildenafil. A patient sued Pfizer

Importance of monitoring medication use

International users

In 2008, approximately 1/3rd of the reports made to FDA Med watch were reported by other countries outside the U.S.

Countries have their own national databases or national registries that provide much more opportunities to PEp studies

Sources of data

Adverse drug reactions Pharmacovigilance E.g.: Felbamate -1993

Databases – Inpatient record Outpatient record Laboratory tests Radiological tests Prescribed and OTC drugs.

Sources of data contd…

CLAIMS DATABASES MEDICAL DATABASES

Arise from person’s use of health care system, & submission of claims to insurance companies for payment

Arise from increasing use of computerization in medical care

Automated databases


Medical record databases Health maintenance organizations(HMO)

Full text records HMO based research – Arthritis

Cancer CVS

Commercial insurance database


Case control surveillance Large database E.g.: patients with malignancy and without

malignancy Drugs : headache, OCP’s, herbal- dietary

supplements Assess the relation of use of prescription

and non prescription drugs with risk of a wide range of outcomes.

Prescription event monitoring (PEM) PEM v/s Yellow card Common to rare eventsResearchers

Questionnaires

General practitioners

Demography, exposure, risk factors, outcome, patterns of prescription etc.

Analysis

Yellow Card Scheme:- The UK national spontaneous ADR reporting scheme


Registries : Disease or event – Gaucher Product – Implantable cardiac device Service or procedure – Carotid art. stenting

To describe - Special condition Natural history of a disease Patterns of treatmentHealth care utilization

Special applications of PEp

1. Studies of drug utilization: Recommended v/s actual E.g.: Underuse of beta blockers- elderly

2. Evaluating and improving physician prescribing: Use of addictive drugs v/s safer Use of therapy when nothing is required

3. Pharmacoepidemiologic studies of vaccine safety: Events that occur at approximately 1 in

100000 doses E.g: GBS after H1N1 influenza vaccine Oral polio vaccine associated paralytic

polio 4. Epidemiological studies of medical devices:

Utilization and identification of risk for certain outcomes.

5. Studies of drug induced birth defects: With other related disciplines (embryology, teratology)

6. Risk management: Can be from medication error, quality, ADR’s E.g: Eculizumab- meningococcal infection

7. Pharmaceutical reimbursement policy: Whether or not the product should be reimbursed by drug benefit policy

Special methodological issues in PEp

(1) Assessing causality of case reports of suspected adverse events

(2) Bioethical issues in pharmacoepidemiology Taking consent, confidentiality

maintenance Studies using electronic databases, records

increases probability of answering drug safety questions

(3) Using quality of life measurements: E.g.: Quadriplegic woman

(4) The use of meta analysis: Issues :- from part of the reader - from lack of clarity of presentation of material in original article - observer bias

(5) Study of medication adherence: Tracking is burdensome

(6) Studying effects of antibiotics: How far back should be assessed How antibiotic agents are grouped

(7) Controlling confounding: Study is large-> data sources ->

confounding

Goals

To assist researchers in adhering to good pharmacoepidemiologic

research principles, including the use of pharmacoepidemiologic

studies for risk management activities and CER (comparative

effective research)

To promote sound pharmacoepidemiologic research by encouraging rigorous data collection, analysis, and reporting.

To provide a framework for conducting and evaluating pharmacoepidemiologic studies.

To facilitate the appropriate utilization of technical resources by promoting careful study design and planning of study conduct.

To facilitate transparency and ethical integrity in research conduct.

There are no really SAFE biologically active drugsthere are only SAFE physicians

- Harold A Kaminetzsky

All drugs have adverse effects PEp will never succeed in preventing them It can only detect them, hopefully early and thereby educate health care providers and public which will lead to better medication…

Pharmacoepidemiology

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