It can identify factors that contribute to non-adherence, such as patient characteristics, treatment complexity, or lack of access to healthcare.

By understanding the causes of non-adherence, pharmacoepidemiology can help develop strategies to improve medication adherence and patient outcomes.

It can also assess the impact of drug-drug interactions on patient outcomes.

It can also assess the impact of non-adherence on health outcomes and healthcare costs

1.2. Applications and contributions of pharmacoepidemiology Some examples of applications and contributions of pharmacoepidemiology are:  Prediction of the ()frequency and size) of the likely effects of the medicine, both intended and unintended.

 Development of() scales to capture patient-reported outcomes (PRO) that are linked to efficacy and safety measures.

 () of clinical efficacy trials.

 Development of an expected () profile.

 Development of ()plans and post-marketing safety studies.

 () about medicines safety

 Supplementing the ()available from premarketing studies – better quantitation of the incidence of known adverse and beneficial effects, e.g., in patients not studied prior to marketing (e.g., the elderly, pregnant women); as modified by other medicines and other illnesses; relative to other medicines used for the same indication

 New() of information not available from premarketing studies discovery of previously undetected adverse and beneficial effects (e.g., uncommon, delayed, or rare effects)

 formulation of () guidelines finding material for possible new indications understanding how the medicine is being utilized in routine clinical practice describe the characteristics of patients who receive the medicine patterns of medicines prescribing (the appropriateness of use)

 medication adherence and persistence patterns as () of predictors for medication use.

 evaluation of effects of medicines () in everyday use determine the frequency and distribution of medicines use outcomes in a population (“Real-world data” (RWD) and “Real-world evidence” (RWE), focusing on what is being used (assessment of specific medicines being used in certain situations) how it is being used (assessment of the patterns of use, including how much, where and when, and by whom); why it is being used (assessment of the reasons for medicines-taking behaviours and the functions that medicines serve in society)

The drug approval process for new products authorized in Canada, and elsewhere, essentially involves a comprehensive analysis of nonclinical and clinical studies. However, the management of adverse effects associated with these new health products does not end on granting market authorization. Rather, these surveillance activities continue throughout the entire drug's ()and this is made possible essentially through the passive and active surveillance of adverse drug reactions in the postmarket setting.

As mentioned in Chapter 2, passive or active surveillance of adverse drug reactions includes pharmacoepidemiologic studies.2 () studies can be used to identify unexpected or rare safety issues and detect changes in frequency of expected adverse events, and this leads to the reevaluation of a product's benefit–risk ratio.

() is important for the industry because they can use this data to submit future amendments to the approved indications for their products and demonstrate the safety and effectiveness of their products, especially compared to others. ()is especially an important tool for regulatory agencies and the physicians/patients using the products. When a regulator grants authorization for a drug, it is largely a result of the data obtained from ()

These RCTs are designed with the purpose of demonstrating () (not safety): () sample sizes are used, length of follow-up is (), and ()t inclusion/exclusion criteria are used

A () sample size means the study will not have enough power to detect small changes in frequency for commonly reported adverse events or to detect rare, but serious, adverse drug reactions

A ()follow-up period means that serious adverse reactions may not be identified because they do not develop immediately. A ()inclusion/exclusion criteria means the population used in the study is likely healthier, excludes children, elderly and pregnant or breast feeding women, uses no/limited concomitant medications, and has a less complicated medical history than the general population that will actually end up using the medication.

These criteria are made restrictive to increase the() of the results to produce an accurate and unbiased estimate of efficacy. However, the tradeoff is that RCTs have low (); this means the results cannot be generalized to the heterogeneous population that will actually end up using the drug including patients with several concomitant medications, complex medical histories, and increased severity of illness and pregnant women, children, and the elderly.3– 5 The safety profile might then change once the drug is approved, which may require a reevaluation of the benefit–risk profile for the product.

Thus, there is a clear need for()pharmacoepidemiology research in the postmarket setting for the timely identification of any significant safety issues that arise when used in the real world (i.e., uncontrolled setting) to protect the health of patients.

() is a dopamine antagonist with pro-kinetic, and antiemetic properties. This drug product may be dispensed either by its classification, prescription or Over-the-Counter (OTC) drug. OTC drug products are accessible to the general public as these drugs are sold without physician’s prescription. The FDA conducted a literature review to assess the safety of Domperidone considering regulatory actions made by other countries in response to an epidemiological study showing that this drug is associated with an increased risk of serious ventricular arrhythmias or sudden cardiac death. A higher risk was observed in patients older than 60 years, patients taking daily doses greater than 30 mg, and patients concurrently taking QT-prolonging drugs (e.g. disopyramide, quinidine, amiodarone, dofetilide, dronedarone, ibutilide, sotalol, haloperidol, pimozide, sertindole, citalopram, escitalopram) or CYP3A4 inhibitors (e.g. clarithromycin, erythromycin, itraconazole, oral ketoconazole, posaconazole, ritonavir, saquinavir, telithromycin, telaprevir and voriconazole).

Dose-related

Non Dose-related

Dose-related and time-related

Time-related