Post-marketing safety

IV Post-marketing safety surveillance undertaken for some drugs that are administered over particularly long periods of time (number of patients varies) Several... 

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 fulfill all the requirements for post-marketing 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. 

The need for a more structured monitoring of the post-marketing safety of products approved by centralised and mutual recognition routes, and for a very interactive relationship with other regions and principles for providing the WHO with pharmacovigilance information, has been set out in the following papers ... 

Post-marketing safety studies are considered in their own chapter of this book. However, it should be noted here that patient registries have been associated with grave jeopardy of litigation in the United States, and not necessarily on a sound scientific basis. On more than one occasion, pharmaceutical companies have been deterred from marketing new drugs when FDA has required a patient registry as a condition of NDA approval. 

The greater control over promotional practice, under the accelerated approval process, usually places less burden on an ethical company than the post-marketing safety requirements. Promotional materials must be submitted for review before NDA approval, with the obviously desirable intention that promotion should not be any broader than the approved indication, which under these special circumstances is likely to be narrower than usual. Furthermore, the package insert should usually quantitate how narrow or broad the tolerability experience with the drug might be frequent labeling revisions and NDA supplements should be planned for. 

The major criterion for filing a report is belief or evidence that a serious adverse reaction has occurred (Henkel, 1999). Generally, the type of reaction to report is one that was not evident during initial drug trials and was not expected to be a common side effect and, therefore, does not appear in the product handout. The reporter is not required to demonstrate or substantiate an actual reaction, yet the reporter needs to believe it has occurred and that future incidents are possible. Since the FDA will probably ask for technical follow-up information on each of these reports, it prefers that a trained health care professional, rather than a client, make the actual reports. A post-marketing safety evaluator examines information from MedWatch reports, and according to Henkel (1999) once the adverse effect has been identified the FDA can take the following actions ... 

Additional, more systematic methods of studying post-marketing safety are needed. 

Zhu X, Kruhlak NL (2014) Construction and analysis of a human hepatotoxicity database suitable for QSAR modeling using post-market safety data. Toxicology 321, 62-72. 

Gonzdlez V, Salgueiro E, Jimeno FJ, Hidalgo A, Rubio T, Manso G. Post-marketing safety of antineoplasic monoclonal antibodies rituximab and trastuzumab. Pharmacoepidemiol Drug Saf 2008 17 714-21. 

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