Benefit-risk evaluation

Unforfunafely, fhere currenfly is no generally accepted formal approach as to how to assess fhe benefif-risk balance in a quantitative manner. Medical judgment has been the method of choice by regulatory bodies in the past. More recently, the need to switch from implicit to more explicit decisions has been demanded by Eichler et al. (2009) in Europe. This, however, calls for more quanfifafive approaches to risk assessment. Major initiatives were found to systematically evaluate fhese approaches, for example, fhe IMI-Protect project Chapter 15 discusses benefif-risk assessment in depth. Noteworthy, the FDA continues to not support these approaches for the time being (U.S. Food and Drug Administration 2013). There is consensus, though, on the value of fhe use of a formal framework for benefit-risk evaluation. 

Relationship of Signal Detection to Risk Communication, Risk Management, and Benefit-Risk Evaluation Processes... 

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH harmonised tripartite guideline E2C(R2) Periodic benefit-risk evaluation report. ICH, Geneva, Switzerland, December 2012. 

FDA. E2C(R2) Periodic benefit-risk evaluation report. Washington, DC FDA ... 

Benefit Risk Evaluation Global Clinical Safety and Pharmacovigilance GlaxoSmithKline Research Triangle Park, North Carolina... 

This report proposes a standard format and content for a benefit-risk evaluation report and also lays down the principles for good decision-making practices. The proposed structure of the report is as follows ... 

The latter (used only as examples) contemporary decision-theory attempts at benefit-risk evaluation apparently refer back to the above-mentioned efforts, directly comparable, with respect to method, to those of the utilitarian school of the last century enumeration of effective motives (requirements, hazards) in the form of catalogues and statistical, empirical determination of the laws governing their efficacy (arrangement in hierarchies, in scales). 

As a general rule, clinical data are required as evidence to support conformity with the requirements of the Active Implantable Medical Devices (AIMD) and the Medical Device (MD) directives with regards to safety and effectiveness under the normal conditions of use, evaluation of undesirable side effects, and the acceptability of the benefit/risk ratio. Risk analysis should be used to establish key objectives that need to be addressed by clinical data, or alternatively to justify why clinical data are not required (mainly for Class I devices). The risk analysis process should help the manufacturer to identify known (or reasonably foreseeable) hazards associated with the use of the device, and decide how best to investigate and estimate the risks associated with each hazard. The clinical data should then be used to establish the safety and effectiveness of the device under the intended use conditions, and to demonstrate that any of the residual risks are acceptable, when weighed against the benefits derived from use of the device. 

In US, AF products need a registration both at federal and at state level. Registration/regulation of AF paints is governed by the Federal Insecticide, Fungicide, and Rodenticide Act FIFRA (US, 2004) and administered by US Environmental Protection Agency. Extensive data packages need to be submitted by the biocide producers and the paint manufacturers. The decision for approval of products is based upon a risk benefit balance evaluation process. 

It is an element of risk management. Risk Evaluation is synonymous with Risk-Benefit evaluation. 

Gordon AJ, editor. Benefit-risk balance for marketed drugs evaluating safety signals. Report of CIOMS Working Group IV. Geneva WHO Press 1998. 

Approving drugs that have been scientifically evaluated to provide evidence of a satisfactory benefit/risk ratio (the balance between the therapeutic advantages of receiving the drug and possible risks). 

Figure 13-15. A simplified/generic representation of clinical trials involving Phases I (safety and tolerability in healthy participants and/or patients), II (to evalnate effectiveness of the drug in patients), and III (to perform expanded controlled and uncontrolled trials and gather benefit-risk data). About 70-90% of drugs entering Phase III studies successfully complete this phase of evaluation. For more details see the glossary at www.clinicaltrials.gov.

Risk assessment typically begins with a characterization of the risks associated with baseline or current releases. The baseline assessment gives an indication of the potential for human health or ecological risk problems. The predicted changes in emissions and sources are then estimated and the expected risk from the option scenarios is evaluated. The risk evaluation is based on both risk reduction to the most highly exposed individuals and to the exposed population as a whole. Cumulative benefits of risk reduction are estimated by adding the benefits for each risk reduction option. 

It is generally accepted that the bioavailability of most topically applied drugs remains low. Various methods to increase this bioavailability have been used. One of the approaches is the use of absorption enhancers, and over the years, there has been a great interest in new chemical absorption enhancers. An absorption enhancer should be pharmacologically inert, non-toxic, have a rapid and reversible onset of action, be chemically and physically compatible with other formulation compounds, and be cosmetically acceptable. Of course not all absorption enhancers possess all of these characteristics, and a benefit-to-risk evaluation will determine the choice of a molecule as an absorption enhancer. The range of absorption enhancers that has been researched is large. Thus, overview of the most researched compounds is presented. 

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