Direct-To-Patient Study Designs For Pharmacovigilance

Post-marketing non-interventional safety studies typically enroll patients at sites where patients receive care. During patient follow-up the occurrence of safety events of interest is recorded by site personnel based on information obtained from the patient during standard-of-care visits. Although this is the traditional approach for assessing the occurrence of safety events in the post marketing setting, it has several practical shortcomings, including; high cost associated with site start up, management, and data collection; infrequent or irregular standard-of-care visits; patients switching health care providers; transient nature of some safety events; treatment at non-study sites, and the lack of care-seeking for the safety events. A design alternative that overcomes several of these short comings includes direct-to-patient contact and follow-up. In this approach, enrolled patients are regularly contacted via phone during follow-up and interviewed regarding the occurrence of safety events or potential signs and symptoms associated with the safety events. If either is reported by the patient, trained personnel follow up with the patient’s treating physician for further evaluation through phone interview and/or written confirmation of the safety event. We will present three examples of studies that make use of this direct-to-patient approach to capturing safety data. These studies comprise large multi-national and national studies with sample sizes ranging between 2000 to over 10,000 patients. In one study, the safety events include thromboembolotic and bleeding events in patients discharged from hospitalization for acute coronary syndrome. In two others, safety events comprise anaphylaxis, encephalitis, Bell’s palsy, neuritis, etc. associated with influenza vaccines. For each study, we will present specific design characteristics; procedures for patient contact, follow-up, and interviews; and procedures for confirming the occurrence of safety events. Strengths and weaknesses of the direct-to-patient approach will be discussed and recommendations regarding appropriate indications and safety events best suited to this novel methodology will be presented.