Surveillance, postmarketing

Postmarketing surveillance is conducted once the approved drug is in widespread use to examine safety in a more comprehensive 

1 The Art of Defining a Study Population in Preapproval Clinical Trials 

It is somewhat of an art, albeit a very important one, to carefully define a study population so that a new treatment can be shown to be effective but not so carefully that the treatment effects are not applicable to more heterogeneous populations. It is a balancing act to optimize design in early studies to demonstrate an effect but to make sure that later studies are not so optimized that their results do not generalize well (see Friedman et al., 2006, for additional discussion of generalization). 

A cohort study is a nonexperimental study (recall Section 5.5 for discussion of experimental and nonexperimental studies) that collects information from an identified group of individuals in an overall population. Cohort studies are used widely in epidemiology and clinical epidemiology, and, as Haynes et al. (2006) noted, evidence from cohort studies (also known as cohort analytical studies) is the next most powerful method after the controlled trial (see also Fletcher and Fletcher, 2005 Webb et al, 2005 Woodward, 2005). 

Relatedly, once a drug has been marketed and has proved to be successful (clinically successful as indicated in published clinical communications and likely commercially successful as evidenced by annual sales reports), other companies may wish to develop similar products that they feel will have a clinical (and commercial) advantage. This process involves the development of an analog of the established drug (see Fischer and Ganellin, 2006). 

Pharmacovigilance is a search for the unexpected, and its ultimate goal is the promotion of rational and safe use of medicines (Olsson and Meyboom, 2006). This goal is facilitated by various activities, including  

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SEC. 521 STATE AND LOCAL REQUIREMENTS RESPECTING DEVICES SEC. 522. POSTMARKET SURVEILLANCE SEC. 523. ACCREDITED PERSONS. 

Kopp AF, Mortele KJ, Cho YD, et al Prevalence of acute reactions to iopromide postmarketing surveillance study of74,717 patients. Acta Radiol 2008 49 902-911. 

Contracting out of activities previously only conducted in-house is already becoming quite common and will probably continue to develop. In the past a so-called full-service pharmaceutical company took direct responsibility for all the activities required for the formulation, manufacture, quality control, and regulatory approval of its drug products. Nowadays the use of specialist contract houses to perform activities such as formulation, analytical methods development, manufacture of clinical trials supplies, supervision of the assembly of an NDA, postmarketing surveillance, and even troubleshooting may be contracted for even by some of the largest companies. 

The excellent safety profile observed in clinical trials has been confirmed by the postmarketing surveillance program [117]. More than 8.5 million patients have been treated in Italy and abroad with rifaximin since its introduction to the market. During the overall postmarketing... 

Postmarketing surveillance is critical to ensuring the safety of medications because of the limitations of Phase 2 and 3 studies to identify rare, serious adverse events. Typically, these studies are too short and the study population is fairly healthy. Once a drug is marketed, the population of patients using the drug expands to include sicker patients, older patients, and other populations. 

Noah, B.A. and D.B. Brushwood, "Adverse Drug Reactions in Elderly Patients Alternative Approaches to Postmarket Surveillance," /. Hlth. Law, 33, 383-454 (2000). 

Center for Drug Evaluation and Research (CEDR) Postmarketing Surveillance Programs, www.fda.gov/cder/regulatory/applications/postmarketing/ surveillancepost.htm (accessed May 24, 2002). 

Populations, gene flow between, 55-56 Population structure, 55-56 Positional cloning, 35, 36 Positive drug response, 262 Positive predictive value (PPV), 169-171 Postmarketing surveillance, 94—95, 324-325... 

F. Premarket Notification, Investigational Device exemptions including Humanitarian Exemptions, Premarket Approval, Product Development Protocols, Classification, Device Tracking, Petitions for Reclassification, postmarket surveillance under Sections 510(k), 513, 515, 519, 520(g) and (m), and 522, and the advisory committees necessary to support these activities. 

From 1978 through 1990, the Centers for Disease Control and Prevention (CDC) and the Food and Drag Administration divided the responsibility for postmarketing surveillance of vaccines in the United States. FDA received reports of adverse events after vaccines were administered in the private sector events occurring after the administration of vaccines purchased with public funds were reported to the Monitoring System for Adverse Events Following Immunization. 

Postmarketing Surveillance Studies. Any surveillance of safety of a drug after marketing is postmarketing surveillance (PMS) (now often referred to as a postauthorization safety study). In practice the distinction between Phase TV studies and PMS is blurred (e.g., German drug experience studies). 

Brewer, T. and Colditz, G.A. (1999). Postmarketing surveillance and adverse drug reactions Current perspectives and future needs. JAMA 281 824-829. 

Phase IV. Studies or trials conducted after a medicine is marketed to provide additional details about the medicine s efficacy or safety profile. Different formulations, dosages, durations of treatment, medicine interactions, and other medicine comparisons may be evaluated. New age groups, races, and other types of patients can be studied. Detection and definition of previously unknown or inadequately quantified adverse reactions and related risk factors are an important aspect of many Phase IV studies. If a marketed medicine is to be evaluated for another (i.e., new) indication, then those clinical trials are considered Phase II clinical trials. The term postmarketing surveillance is frequently used to describe those clinical studies in Phase IV (i.e., the period following marketing) that are primarily observational or nonexperimental in nature, to distinguish them from well-controlled Phase IV clinical trials or marketing studies. 

Graham, G.K. (2002) Postmarketing surveillance and black box warnings (To the Editor). The Journal of the American Medical Association, 288, 955-956. 

The Food Additives Amendment to the Federal Food, Drag, and Cosmetic Act of 1938, which was adopted in 1958, requires that proof of safety of a new food additive be furnished by the manufacturer based on extensive scientific research. Since it is impossible to conclusively prove the safety of a new food additive through animal and clinical trials, manufacturers routinely conduct postmarketing surveillance and long-term follow-up studies to monitor adverse events. 

Class II devices are those for which general controls alone are insufficient to provide reasonable assurance of safety and effectiveness and for which sufficient information is available to establish special controls to provide this assurance. Special controls may include performance standards, postmarket surveillance, and guidance for analytical/clinical data. Examples of class II IVDs are automated differential cell counters, fetal hemoglobin test systems, sickle-cell tests, and Toxoplasma gondii serological reagents. 

The astute individual healthcare practitioner is the critical link in the postmarketing surveillance of medical products. One reporter can indeed make a difference in a newly approved drug s postmarketing phase. Only through the diligence of individual practitioners, such as pharmacists, can FDA hope to monitor the adverse events associated with newly marketed products and determine their safety for patient use. 

Postmarketing surveillance Risk-benefit ratio Safety... 

The Safe Medical Devices Act requires reporting of medical devices that probably caused the death, serious filness, or injury of a patient. Postmarket surveillance on permanently implanted devices required with methods for tracing and locating patients depending on such devices. FDA is authorized to recall device product. 

The FDA s postmarketing surveillance of drug safety in FY 2003 includes a new database on prescribed drug use (with patient idenhhes removed). The agency uses this database of marketed drugs to "make risk assessments and decisions about the most appropriate way to manage any new risk or new perspective on a previously known... 

Warden, W.M., Tsianco, M.C., Anavekar, S.N., and Davis, H.T., Postmarketing Surveillance of New Drugs II, Case Study, /. Clin. Pharm., April 1979. 

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