Pharmacoepidemiology is being used increasingly to evaluate health care systems, interventions, and health-related behaviors. Pharmacoepidemiology is the scientific backbone of therapeutic risk management—the process of assessing a product’s benefits and risks, and developing, implementing, and evaluating strategies to enhance the overall balance of such benefits and risks. Pharmacoepidemiology is also the scientific backbone of comparative effectiveness research (CER). These guidelines are intended to address these activities and other pharmacoepidemiologic studies. Pharmacoepidemiology is the core science of risk assessment and the evaluation of the effectiveness of risk minimization interventions. Therefore, the GPP also support risk management activities.

The GPP addresses the following areas:

• protocol development,
• responsibilities, personnel, facilities, resource commitment, and contractors,
• study conduct,
• communication,
• adverse event reporting, and
• archiving

The GPP have the following specific goals:

1. to assist researchers in adhering to good pharmacoepidemiologic research principles, including the use of pharmacoepidemiologic studies for risk management activities and CER;
2. to promote sound pharmacoepidemiologic research by encouraging rigorous data collection, analysis, and reporting;
3. to provide a framework for conducting and evaluating pharmacoepidemiologic studies;
4. to facilitate the appropriate utilization of technical resources by promoting careful study design and planning of study conduct; and
5. to facilitate transparency and ethical integrity in research conduct.

The International Society for Pharmacoepidemiology’s (ISPE’s) Guidelines for Good Pharmacoepidemiology Practices (GPP) recommends that all pharmacoepidemiologic studies address the following:

• Providing a written protocol, with dated amendments and justifications;
• Performing a critical review of the literature to facilitate the identification of knowledge
• gaps in the current evidence base for safety issue(s) of interest and how the current or
• proposed study contributes to this evidence base;
• Ensuring human subject protection; FDA considers the investigator to be responsible for
• ensuring that the data are Health Insurance Portability and Accountability Act (HIPAA)
• compliant and that all research performed complies with standards of privacy of
• individually identifiable health information and protects the rights of human subjects in
• research;
• Providing confidence intervals about estimates of risk in addition to p-values; although pvalues address the issue of statistical significance, confidence intervals quantify the
• precision of the risk estimates;
• Including both absolute and relative risk estimates to assist in the interpretation of the
• public health impact of the findings; and
• Archiving of relevant study documents and data.

Pharmacoepidemiologic studies are usually designed to assess the relation between certain exposures and health events based on comparisons of the event frequency in groups with and without the exposure of interest via statistical analyses (i.e., analytic studies). The primary goal of these analytic studies is to determine whether a drug exposure increases the risk of an adverse event or provides protection against it. Therefore, causality assessment and reporting of individual exposed cases offers little, if any, scientific value to this goal.

For primary data collection studies, reporting of adverse events is required by law in most countries. Since information on suspected adverse events may be identified during the course of a study, but not as a formal part of the protocol-defined study objectives, procedures for follow-up and reporting of safety information in the study should be defined by the sponsor and research team at the time of protocol development. For specific requirements, relevant regulatory guidance documents should be consulted. As requirements change repeatedly, the latest versions of regulatory guidance should be consulted prior to study commencement.