Estimating and Evaluating Clinical Risk

In previous chapters the focus has been on risk identification and the systematic methods used to characterise hazards. Our next task is to exanune the practicalities of evaluating risk - studying the properties of hazards and their causes to establish the degree of risk and therefore its acceptability. Doing so allows us to prioritise those hazards which require further risk nutigation. 

Note that some authors use the term estimation for determining the degree of risk and reserve evaluation for the process of determining whether or not the established risk is acceptable. In this text the term evalnation will collectively refer to these activities combined. 

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The risk associated with the issue should be estimated and evaluated in the usual way as outlined in previous chapters. Attention should be paid to the key factors mentioned earlier which influence risk clinical dependency, detectability, presence of workarounds, etc. (see Sect. 14.1). There may however be some thought required when it comes to ascertaining the likelihood component of risk. The question is this, if an issue has already occurred is the likelihood not 100 % This seems a reasonable chain of logic to begin with but it suffers from a couple of complexities. 

Gastrointestinal A systematic search for case reports, case series, and clinical studies of the association between isotretinoin and inflammatory bowel disease yielded 12 case reports and one case series of such an association, to which the Bradford Hill guidelines to evaluate causality [36 ] were applied [37 ]. The cases occurred in seven countries over 23 years and differed with respect to isotretinoin dose, duration of treatment before development of the disease, whether the disease developed on or off medication, and the clinical presentation. There have been no prospective or retrospective studies. An estimated 59 coincident cases of inflammatory bowel disease would be expected in isotretinoin users each year, assuming no increased risk. The current evidence is insufficient to confirm or refute a causal association. 

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. 

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