University of Twente Student Theses


Evidence Development and Regulatory Approval of Drugs: A Case Study on Fibrin Sealant

Wang, Haiyan (2013) Evidence Development and Regulatory Approval of Drugs: A Case Study on Fibrin Sealant.

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Abstract:The process of developing and approving drugs has changed in the past decades. Companies have to pass more hurdles, and present more scientific evidence regarding safety, clinical effectiveness and cost-effectiveness. But there are also new opportunities in emerging markets such as China. Because of these changes, we are interested in finding the relation between scientific evidence development and regulatory approval of drugs in existing markets (US, EU), as well as in China. Relevance To understand this relation we used evidence development of fibrin sealant as a case study. In general fibrin sealant is a good case study because there is a lot of information available about it. The first commercial fibrin sealant was available in EU in 1970s, but it took until 1998 for fibrin sealant to be approved by FDA in the US. Thus, there is a lot of evidence and many companies already filed for approval. Over time, new indications have been approved, and there are several off-label indications that might be approved by FDA in the near future. Finally fibrin sealant is also approved in China. Method A systematic review method based on the Cochrane handbook was used to find the evidence development regarding fibrin sealant. The research is limited to the on-label indications of fibrin sealant. No off-label indications were examined, because these cannot be commercially used in the market and our goal is to examine the relation between evidence development of on-label indications and regulatory approval. We investigated different indications of fibrin sealant, the year of publication, and the phases in clinical trials. To find the procedures and requirements of the approval for fibrin sealant in the US, EU, and China, we searched the government website of their regulatory agencies FDA, EMA, and SFDA. We analyzed the relation between evidence development of fibrin sealant and regulatory approval by looking at the relation between publications and approved indications and applications over time. Results It was shown that on-label indications for fibrin sealant (hemostat, colon sealing, adhesive, and face-lift) of fibrin sealant were efficacious and effective. We only found a few studies which showed any negative results of using fibrin sealant. Fibrin sealant for obtaining hemostasis was efficacious to control bleeding for all kinds of surgeries, patients needed less blood transfusion. Fibrin sealant used for colon sealing improved the strength of anastomosis and the survival rate. Adhesive used for burns skin grafting increased the survival rate of grafting skin. Fibrin sealant used for face-lift reduced hematoma rate, and shortened the recovery time. Concerning the drug approval process, this is managed by FDA in US, EMA in EU, and SFDA in China. Generally, the process includes two phases: Clinical Trials (CT) and New Drug Application (NDA) approval process. The processes in US and China are centralized processes. However, in EU there are both centralized and decentralized (national) authorization procedures. Pharmaceutical companies can choose the centralized approval procedures, which is applied to all European countries. Regarding the national approval procedures, the drug can be approved in one or more countries. From 1998 to 2011, there were four indications of fibrin sealant approved by the FDA. Hemostat and colon sealing were the first approved indications by FDA in 1998. Next, adhesive was approved for burn skin grafts in 2008, and then in 2011 face-lift was approved for using in facial rhytidectomy surgery. In EU, hemostasis was approved by EMA for using in cardiovascular surgery in 2004, and in China it was approved for using in general surgery in 2010. Concerning new market opportunities such as China, it is clear that pharmaceutical companies still focus on the US and EU market. Also, most of the studies included in this study came from there. If we look at the relation between evidence development and approval, we found that the cumulative publications of fibrin sealant increased almost in a straight line from 1998 to 2011. Regarding the applications of fibrin sealant, in the first four years after 1998, no new applications were approved, the next four years, two applications were approved, in the four years after that, there were four new applications. The conclusion is that in the first years, the amount of new approved applications is very low, compared to the amount of new publications, but afterwards it goes much faster. Even though fibrin sealant seems to be a very good drug, the regulatory approval takes time to catch up.
Item Type:Essay (Master)
Faculty:BMS: Behavioural, Management and Social Sciences
Subject:88 social and public administration
Programme:Health Sciences MSc (66851)
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