Clinical risk definition

A consensus-derived definition and classification system for ARF has been proposed and is being validated (Fig. 75-1). Components of the system include both GFR and UOP plus two clinical outcomes. Definitions of risk of dysfunction, injury to and /ail ure of the kidney, loss of function, and end-stage kidney disease are included in the RIFLE acronym. 

The Oxford English Dictionary defines risk as [Exposure to] the possibility of loss, injury, or other adverse or unwelcome circumstance a chance or situation involving such a possibility [4]. The focus here, as with a number of other definitions is that risk involves the loss of something we value. In the context of Clinical Risk Management (CRM) this is likely to be our health, wellbeing or indeed our... 

For those tasked with evaluating clinical risk alone, consequences unrelated to safety need to be consciously removed from the equation and not bias the analysis. As we will go on to discuss, objectivity is paramount in CRM and a tight definition of what constitutes clinical risk versus other types of risk is essential. 

We can therefore see that the concept of risk begins to emerge when we combine the likelihood of a hazard occurring with the severity of its impact. It is therefore proposed that a potential definition of clinical risk in the context of CRM could be the chance of a patient being harmed to a stipulated extent the chance component is defined through the hazard s likelihood whilst the stipulated extent is defined by the severity. In other words ... 

In defining clinical risk it should also be pointed out that the term varies its meaning depending on whether the definite or indefinite article precedes it. The definition presented above holds true when one talks about the clinical risk but from time to time we use the phrase a clinical risk to describe something which could give rise to harm. For example, We believe that the incorrect information on this screen represents a clinical risk . In most cases a more correct term would be hazard (i.e. a potential source of harm ). Nevertheless clinical risk is used so frequently in this way that to deem it incorrect invariably elicits an accusation of pedantry. Still, hazard is a preferable term in formal text to avoid any ambiguity especially when faced with awkward phrases such as the clinical risk of the clinical risk is low . 

Once financial, environmental and reputational forms of risk are excluded one might expect that what is left is a fairly tight definition of the factors which constitute clinical risk. Experience has shown however that there are many boundary cases that can be subject to debate. Clinical risk arises from the manifestation of one or more hazards. Hazards have an intrinsic relationship with harm but it is often in the definition of what constitutes harm where debate arises. 

Risk management is formally carried out in all phases of an approved project. Review of the concept definition document includes analysis of clinical risks, both derived from functionality and from technology. As soon as concept definition phase has been concluded, a risk analysis document is drafted. 

The overall objective of clinical trials is to establish a drug therapy that is safe and effective in humans, to the extent that the risk-benefit relationship is acceptable. The ICH process has developed an internationally accepted definition of a clinical trial as Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of one or more investigational medicinal product(s), and/or to identify any adverse reactions to one or more investigational medicinal product(s) and/or to study absorption, distribution, metabolism and excretion of one or more investigational medicinal product(s) with the object of ascertaining its (their) safety and/or efficacy. ... 

Interferon-a2b has diverse mechanisms of action, including antiviral activity, impact on cellular metabolism and differentiation, and antitumor activity.42 The antitumor activity is due to a combination of direct antiproliferative effect on tumor cells and indirect immune-mediated effects.42 Interferon-a2b is currently approved by the Food and Drug Administration (FDA) as adjuvant therapy for patients who are free of disease after curative surgical resection but are at high risk of MM recurrence. This includes patients with bulky disease or regional lymph node involvement such as stage IIB, IIC, or III disease.43 It is controversial if interferon-a2b (IFN) should be offered as adjuvant therapy for every high-risk MM patient. The reason is because clinical trials with different doses of IFN have not proved definitively that IFN improves overall patient survival. 

In summary, while only the NEI initiated AREDS II study is a large enough RCT to have the potential to provide definitive evidence as to whether the macular xanthophylls can indeed reduce the risk of AMD, the evidence available to date that lutein and zeaxanthin could contribute to this is not only biologically plausible but also supported by various experimental, epidemiological, and small-scale clinical studies. Although the benefits of lutein and zeaxanthin in this respect may be moderate to small, their safety is well documented. 

Without regard to therapy, potentially valuable diagnostic tests are available for presymptomatic evaluation of risk of breast cancer due to predisposition from BRCA 1 or BRCA 2 and of colon cancer related to familial adenomatous polyposis (APC gene) or hereditary nonpolyposis mismatch repair genes (MSH 2). Genetic predisposition to Alzheimer disease associated with ApoE4 is neither sufficient nor necessary to lead to the clinical condition, and no definitive therapy is available. 

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. 

To ensure that the rights and welfare of human research participants are protected, the IRB takes on the task of performing a risk vs. benefit analysis. Before a clinical trial can be initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the trial participant and for society (Section 22.2). Risks associated with participation in research should be justified by the anticipated benefits only then, can the trial be initiated. Because this requirement is clearly stated in the federal regulations, it is, therefore, one of the major responsibilities of fhe IRB to assess fhe risks and benefits associated with proposed research. Definitions of fhe terms fhaf fhe IRB uses to assess risk include the following ... 

Even with this somewhat stricter definition, there is room for discretion. A sportsman who takes an occasional puff of a bronchodilator for exercise-induced asthma but is otherwise asymptomatic may be considered eligible by some. Individuals who have undergone surgery for a congenital condition and are in excellent health may or may not be suitable. Thus, an asymptomatic patient with a hip prosthesis who is taking no medication may be acceptable whereas an equally healthy individual with a prosthetic heart valve should be excluded from a study involving a cannula because of the risk, however remote, of endocarditis. Clearly, whatever definition of a healthy volunteer is used, sensible clinical judgement is still required. 

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