Postmarketing safety evaluation

POSTMARKETING SAFETY EVALUATION MONITORING, ASSESSING, AND REPORTING OF ADVERSE DRUG RESPONSES (ADRs)... 

Each group of methods will be considered in some detail in order to identify their strengths and weaknesses, and to determine those circumstances in which their use is most appropriate. There has in the past been a hope that some new method - a holy grail - might be discovered that would fulfil all the requirements for postmarketing safety evaluation but, not surprisingly, this has not been realised, and it is now accepted that each situation has different needs and the most appropriate method or methods have to be determined according to the circumstances. 

Device Change Information. ODE or OIVD, in consultation with other Offices within CDRH, as appropriate, will evaluate your summary of the changes made to your device. As appropriate, we also plan to search the MAUDE database and review other FDA records to assess the postmarket safety profile of your device. 

With the transfer of most biopharmaceutical INDs from CBER to CDER in 2003, there has been an increased tendency to apply the small-molecule paradigm for evaluation of QT liability to biopharmaceutical product candidates, and to request information on hERG assays or plans for definitive clinical QT studies. This does not seem reasonable based on the postmarketing safety data for biopharmaceuticals, nor on scientific grounds as discussed above. If these investigations become routinely required, they will only add significant time and costs to the process of biopharmaceutical product evaluation and have little ultimate impact on patient safety. 

There is no doubt that the continuing evaluation of the safety of medicines into the postmarketing period is an expanding and still developing area of research. Matters relating to safety spread over into efficacy, which together imply risks and benefits which, in the present international climate of healthcare provision, have consequences for outcomes and costs. A whole new field of research - pharmacoeconomics - is in the process of development and it is to be anticipated that many of the methods used for safety evaluation will be modified and applied in this area. 

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. 

In the evaluation of safety in the postmarketing phase, regulatory agencies are greatly more restricted in their enthusiasm for data derived from some of the methods available than from others. Indeed, the EC national agencies separately and the CPMP collectively have developed a legislative framework that is predominantly concerned with spontaneous adverse event monitoring and which is, for all practical purposes, silent on the matter of safety data collected by other methods. 

HiU PL, Bridgman KM. A multicentre postmarketing surveillance study to evaluate the safety of bisoprolol in the treatment of hypertension and ischaemic heart disease. Br ] Clin Res 1992 3 85-98. 

Postmarketing Reporting of Adverse Drug Experiences, March 1,1992. Center for Drug Evaluation and Research (CDER). Guidance for Industry. Conducting a Clinical Safety Review of a New Product Application and Preparing a Report on the Review, Nov. 1,1992. 

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. 

Phase IV trials are conducted as postmarketing efforts to further evaluate the characteristics of the new drug with regard to safety, efficacy, new indications for additional patient populations, and new formulations. Phase IV is generally used to characterize all post-NDA/BLA clinical development programs. However, some organizations use Phase IV to describe only FDA-requested clinical trials and use Phase V to describe internally motivated market expansion trials (e.g., new indications, new formulations, updated safety databases). 

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