Читать книгу Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition) - William Gregory - Страница 32

A term that has appeared in the last few years is late phase studies, referring to the grab bag of requirements that agencies and companies are doing both for registration, evaluating risk, and marketing reasons. They include registries (product, disease, safety), post-marketing observational studies, classic phase IV trials as discussed earlier, clinical effectiveness trials (i.e., real world evidence), OTC trials, community-based trials, health economic and outcomes studies (retrospective, prospective, observational), cost-effectiveness, burden of disease, patient reported outcome (PRO, Quality of Life [QoL], chart review, survey (physicians, patients), health economic piggyback trials, risk management, expanded access, drug safety, and others.

Commercially-driven “Customer Engagement Programs”, e.g., patient support programs, etc., where there is the possibility of two-way communication, are an additional source of AEs after a product is marketed. Patient safety is usually not the focus of such programs, but any safety data that are generated must be evaluated.

Other study designs that merit mention include pragmatic clinical trials and low interventional studies. Pragmatic trials are randomized trials designed to assess how effective a treatment actually is in routine, everyday practice. These studies have limited protocol-driven requirements so that there is minimal impact on the patient’s standard treatment for the condition of interest. Following randomization, follow-up patient care is managed by the healthcare provider(s) according to their normal standard of care. Pragmatic studies address practical questions about risks, benefits, and costs of an intervention as it is used in daily practice under usual circumstances. This type of study can also be used to assess compliance, i.e., whether patients actually follow the instructions as to daily dose, timing of drug intake, avoiding known interactions with foods or other medicines, etc.

In some pragmatic studies, non-standard of care diagnostic or monitoring procedures are included, but these must not pose more than minimal additional risk or burden to the safety of patients compared to normal clinical practice. Secondary data sources (e.g., electronic health records, claims data, safety monitoring databases, etc.) may be used to obtain follow-up information.

Low interventional studies do not involve any protocol-required assignment to an intervention that is expected to impact a clinical outcome. However, they do require non-standard of care diagnostic or monitoring procedures which do not pose more than minimal additional risk or burden to the safety of patients compared to normal clinical practice. Low interventional studies are designed and conducted in real-world healthcare settings to evaluate, for example, epidemiology or natural history of a disease or the safety or effectiveness of an intervention under routine care conditions.