Postmarketing studies

Clinical development of NCEs is broadly divided into Phases I, II, III, and then IV (postmarketing) studies. 

Hypersensitivity reactions Serious hypersensitivity reactions have been rarely reported. One case of a life-threatening hypersensitivity reaction has been observed in a patient who received a single dose of sodium ferric gluconate complex in a postmarketing study. Three serious hypersensitivity reactions have been reported from the spontaneous reporting system. 

The clinical development of new drugs usually takes place in steps or phases conventionally described as clinical pharmacology phase I), clinical investigation (phase II), clinical trials (phase III), and postmarketing studies (phase IV). Table 1.1 summarizes the four phases of clinical evaluation. 

NDA requires manufacturers to submit product-labeling language, which describes the proper use, benefits, and risks of the product in question. FDA may also require, as a condition of approval of an NDA or BLA application, that postmarketing studies be conducted to monitor and confirm the safety and efficacy of a product as it is used more widely in clinical practice. In addition, all sponsors or manufacturers are required to monitor and report adverse effects, defined as health effects that may or may not be related to the drug in question. For vaccines, adverse events that occur after immunization must be reported to the Vaccine Adverse Event Reporting System. 

Postmarketing study commitments, also called Phase 4 commitments, are studies required of or agreed to by a sponsor that are conducted after the FDA has approved a product for marketing. The FDA uses postmarket-... 

When a manufacturer believes he has adequate evidence to demonstrate the safety and effectiveness of a compound, an NDA is submitted to the FDA. After the NDA has been approved, the drug can be marketed in this country. The term Phase IV is used to denote postmarketing studies that are done to examine the properties of the drug in more widespread or long-term utilization. 

US Food and Drug Administration (USFDA). 2002. Report to Congress. Reports on Postmarketing Studies [FDAMA 130], Washington, DC FDA. 

Changes based on postmarketing study results, including, but not limited to, labeUng changes associated with new indications and usage. Change in, or addition of, pharmacoeconomic claims based on clinical studies. 

Gavin JR 3rd, Kubin R, Choudhri S, Kubitza D, Himmel H, Gross R, Meyer JM. Moxifloxacin and glucose homeostasis a pooled-analysis of the evidence from clinical and postmarketing studies. Drug Saf 2004 27(9) 671-86. 

Clinical data summary and results of statistical analysis Discussion of benefit risk relationship and proposed postmarketing studies... 

Until the new guidelines are released, the FDA is operating under section 103(a) of Title I of the FDA Modernization Act of 1997, final rule on postmarketing study requirements (October 30, 2000 65 FR 64607), which became effective on April 30,2001. 

Under the current final rule, those applicants with a commitment to conduct postmarketing studies must submit an annual report within 60 days of the anniversary of the product approval, and annually thereafter until notified by the Agency that either (a) the study commitment has been met or (b) the study is either no longer feasible or would not provide any additional useful data. 

While all speculation on yet-to-be-released future guidelines is by definition uncertain, it seems likely based upon the Congressional mandate that the new guidance will broaden the pool of products for which postmarketing studies will be required, will expand the duration of those studies, and possibly will increase the level of scrutiny of both studies and patient tracking. 

Currently, the Annual Postmarketing Study Report should include the following ... 

A plan for continued or future postmarketing studies and monitoring... 

The exception is the NDA/ANDA Postmarketing Study Reports, which are evolving and likely to become more structured and more closely scrutinized. Once those new guidelines are released, strict adherence to then-requirements will be mandatory, at the ultimate risk of a withdrawing of drug approval. 

Buncher, C.R. and Tsay, J-Y., 2006b, Phase IV postmarketing studies. In Buncher, C.R. and Tsay, J-Y., (Eds), Statistics in the pharmaceutical industry, 3rd Edition, Chapman Hall/CRC, 303-314. 

Drug discovery requires a host of inputs, new ideas, design and synthesis of substances, evaluation of preclinical toxicity tests in animals, clinical studies in human volunteers, permission to market the drug, postmarketing studies of safety, and comparison with other medicines. Drug development is highly technical and enormously expensive, with a success rate of 1 in 10,000 compounds. 

The FDA may require, at the time of product approval, that the manufacture agree to conduct additional testing on its biological product, called phase 4 studies. These postmarketing studies may further evaluate the product s safety, efficacy, or manufacturing methods. Sponsors that agreed to conduct phase 4 studies as part of their BLA approval must update the FDA annually. 

In response to voluntary reports from physicians to the FDA or the manufacturer, the FDA has issued warnings, made label changes, required manufacturers to conduct postmarketing studies, and ordered product withdrawals that have ultimately prevented patient deaths and suffering. 

I. Discussion of Benefit/Risk Relationship and Proposed Postmarketing Studies... 

Need for postmarketing studies—for duration, for specialty groups (e.g., children or elderly)... 

Mann RD. The safety of risperidone a postmarketing study on 7684 patients. Hum Psychopharmacol... 

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