Absolute risk increase

To calculate the number needed to harm (NNH), first calculate the absolute risk increase (ARI). This is the absolute difference between the event rate in the experimental group (EER) minus the event rate in the control group (CER). The NNH is the inverse of the ARI. 

Control Event Rate Experimental Event Rate ARI (Absolute Risk Increase) NNH... 

In the past, qualitative approaches for hazard evaluation and risk analysis have been able to satisfy the majority of decision makers needs. In the future, there will be an increasing motivation to use QRA. For the special situations that appear to demand quantitative support for safety-related decisions, QRA can be effective in increasing the manager s understanding of the level of risk associated with a company activity. Whenever possible, decision makers should design QRA studies to produce relative results that support their information requirements. QRA studies used in this way are not subject to nearly as many of the numbers problems and limitations to which absolute risk studies are subject, and the results are less likely to be misused. 

Increased patient survival from 10% to 5% Absolute risk reduction From 10% to 5%... 

Intakes that exceed the ADI will not necessarily result in any adverse effect because the uncertainty factors are designed to be conservative. In practice it is probable that most people could exceed the ADI by a considerable margin before suffering any harm. Nevertheless, the probability that an individual will suffer harm (risk) increases once the ADI is exceeded and so this must be balanced against the costs of control. Conversely, the level of risk below the ADI is never quite zero because there is always a residual risk that relates to the lack of absolute certainty in the methods used for toxicological testing. In some cases no adverse end-point can be identified, such as for many naturally-occurring compounds that are widespread in foods. In such cases an ADI Not Specified (ADI NS) is allocated. 

The importance of this effort is illustrated in the following hypothetical example. A new therapy is under development that reduces the absolute risk of dying from a chronic disease by 50% as measured in a one-year trial. However, this therapy is not curative. A four-year trial was initiated at the same time as the one-year trial. The first-year results were the same in both the four-year trial and the one-year trial. However, there was an increased risk of death for treatment patients in the second and third year of the four-year trial, and by the end of the third year of the trial the survival rate was identical in the treatment and control arms of the four-year trial. While there was a clear benefit to the new therapy in terms of postponing events from the first year of treatment to later years, the economic assessment of the therapy would suggest a greatly reduced treatment benefit from the four-year trial as compared with the one-year trial. 

The absolute risk of bone cancer estimated from the BEIR report would be 3 per million man-rem per year. The relative risk of bone cancers expected on the basis of the percent increase in the exposed population was also derived from the BEIR report as 17 per million man-rem per year. This estimate was based on an assumption that bone cancers contributed 4% of the relative risk from total body exposure (excluding leukemia). 

An extensive literature review has provided a useful assessment of the benefit to harm balance of raloxifene (20). The findings were reassuring. One large fracture prevention trial provided the best evidence that raloxifene 60 mg/day for 3 years reduced the relative risk of vertebral fractures by 30-50% in women with prevalent fractures or osteoporosis. The extraskeletal effects of raloxifene include a reduction in total cholesterol and low density lipoprotein cholesterol concentrations. Raloxifene was not associated with endometrial hyperplasia, and there was a 72% reduction in the incidence of invasive breast cancer. Adverse events associated with raloxifene included an increase in the absolute risk of venous thromboembolism and increased risks of hot... 

Older primary prevention trials had often been undertaken in cohorts at low absolute risk of CHD events. The initial secondary prevention studies had typically involved patients with elevated cholesterol levels. In addition, these older trials had tested diet and previous lipid-lowering agents, which only lowered cholesterol by an average of approximately 10% (5). As a consequence, these trials were typically underpowered and had not shown a clear reduction in all-cause mortality. There had been good evidence that lipid-modifying therapy could prevent fatal and nonfatal CHD events (5). However, there were some concerns that noncardiovascular events particularly related to cancers and violence or trauma could be increased. In summary, there was considerable uncertainty about the overall effects of treatment. 

The baseline absolute risk of an Ml during normal daily life is low—one chance in a million per hour for a healthy adult, and 10 chances in a million per hour for a patient with documented cardiac disease. Therefore, during the two hours post-sex, the risk increases to 2.5 in a million for a healthy adult and 25 in a million for a patient with documented cardiac disease, but, importantly, there is no risk... 

The Radiation Effects Research Foundation s Life Span Study of atomic bomb survivors has reported that for all solid tumours combined, there is clear evidence of a radiation dose-response relationship. Both excess relative risk and excess absolute risk are larger for individuals exposed as children than for those exposed as adults, and solid tumour risk continues to increase in later years (Kodama et al., 2003). Survivors of the atomic bombs also have increased risk of all kinds of solid tumours, including those of adult life, although the degree of susceptibility varies with age at the time of the bombings and is generally highest early in life. 

Finally, the RUTH study (Raloxifene Use for the Heart)38 was a placebo-controlled clinical trial following over 10,000 postmenopausal women with coronary heart disease (CHD) or with multiple risk factors for CHD.44 16 This trial demonstrated 44% reduced incidence of invasive breast cancer versus placebo, with 0.6% absolute risk reduction,47 thus confirming the findings from MORE and CORE, while also demonstrating that raloxifene did not increase or decrease risk for coronary events or stroke. However, there was an increase in stroke mortality and incidence of venous thromboembolic events (VTEs) as compared to placebo, already seen in MORE, which resulted in a recommendation that raloxifene should not be used for the prevention or reduction of the risk of cardiovascular disease.21... 

HDL-cholesterol levels are increased by 4—8% (Maron et al., 2000). These changes in plasma lipids are claimed to reduce the risk of major coronary events by around 30%. However, this value is misleading because it refers to the relative risk of CHD the absolute risk reduction is only about 2%. 

The cardiovascular teratogenicity of lithium has been summarized in a review of managing bipolar disorder during pregnancy and postpartum (473). While the risk of Ebstein s anomaly is increased, likely 10-20 times more than in the general population, the absolute risk (0.05-0.10%) is small. Fetal ultrasonography was advised at 18-20 weeks of gestation in cases of first trimester lithium exposure (488). 

The strength of the association between blood pressure and stroke is attenuated with increasing age, although the absolute risk of stroke in the elderly is far higher than in the young (Lewington et al. 2002). Nevertheless, hypertension is still a risk factor in the very... 

One particular variation, eversion endarterectomy, is becoming increasingly popular (Loftus and Quest 1987 Darling et al. 1996 Cao et al. 1998 Brothers 2005). A systematic review of five randomized controlled trials (2590 operations) compared eversion endarterectomy versus conventional endarterectomy performed either with primary closure or patch angioplasty (Cao et al. 2004). Overall, there was no significant difference in the rates of perioperative stroke, stroke or death, and local complication rates, but the absolute risks were rather low (risk of stroke or death was 1.7% with eversion and 2.6% with conventional endarterectomy). 

The list of factors that come into play is indicative of the complexity. For example, the absolute risks of different trials ranges from no improvement while on the drug to actual increased mortality. The length of trials is different antibiotics, 14 days, an Alzheimer drug, at least 24 months, and an osteoporosis drug is 36 to 48 months. The size of trials depends on the improvement one wishes to demonstrate and the natural rate of disease progression. One might only need 30 to 40 patients for a trial on some rare tumor disease, in stroke or sepsis, from 60 to 200 patients, but in cardiovascular medicine or obesity, one needs 2,000 to 10,000 patients to have some idea of efficacy. As a reminder, the key for these clinical trials is Is there a sufficient number of patients who are well characterized and who could enter the trial so that we will have the statistical power to... 

Any benefits of treatment with GP Ilb/IHa inhibitors must be weighed against the risks. Several studies have found an increased risk of major bleeding, which is likely to be of particular importance in patients whose absolute risk of bleeding is high, such as those receiving fibrinolytic therapy (see below for further discussion). A small excess risk of thrombocytopenia has also l n reported in some trials (37). 

Overall, antiplatelet therapy produced a 13% (95% Cl 5-20%) proportional reduction in the odds of a vascular event, corre onding to an absolute risk reduction of only about one vascular event avoided per 1000 patients treated per year (Table 24.2 (a)). As in the ofiier low risk trials, the risk of MI was reduced in both TPT and HOT in TPT the rate of all (i.e. fotal or non-fetal) ischemic heart disease was reduced by 20% (95% Cl 1 -35%) and in HOT the rate of all MI was reduced by 36% (95% Cl 15-51%). But, alfiiough antiplatelet therapy appeared to reduce the risk of ischemic stroke, it also appeared to increase the risk of hemonhagic stroke overall in TPT there was a non-significant 3% (95% Cl -45-35%) reduction in the rate of all stroke and in HOT there was a nonsignificant 2% (95% Cl -24-22%) reduction in the rate of all stroke. As in the other low risk trials, there was no overall effect on vascular death or on all-cause mortality (52,53). 

Relative risk refers to the increased likelihood of a patient having a complication compared to a normotensive patient of the same age and gender. Absolute risk refers to the number of patients out of 100, with the same age, gender and blood pressure, predicted to have a complication of the next 10 years. 

Benign liver tumours may develop when synthetic C17-a-substituted gonadal steroids (e.g. anabolic steroids usually in high dose, and oral contraceptives) are used for more than 5 years there is also increased risk of hepatocellular carcinoma, although the absolute risk of either complication is very low. These liver tumours are highly vascular and may cause recurrent or acute abdominal pain if they rupture and bleed. 

Carcinoma of the endometrium is associated only with unopposed oestrogens, which increase risk by 2-fold during 5 years rising to 7-fold with longer treatment. Because endometrial cancer is uncommon, the absolute risk is about one-tenth that of thromboembolic disease the risk reduces over 5-10 years after stopping treatment. 

In 1996, in a case-control study, 95 patients from 35 centers in France, Belgium, the UK, and the Netherlands were compared with 355 age- and sex-matched controls (14). The use of anorexic drugs (mainly derivatives of fenfluramine) was associated with an increased risk of primary pulmonary hypertension. Association with recognized risk factors such as a family history of primary pulmonary hypertension, infection with HIV, or the use of intravenous drugs was also confirmed. The absolute risk for obese patients who took anorexic agents for more than 3 months was 30 times higher than in non-users. 

Hb Ale) and the risk of complications. The absolute risks of retinopathy and nephropathy were directly proportional to the mean Hb Ai. The risk of retinopathy increased continuously with increasing HbAi and a single measure of Hb Ale predicted the progression of retinopathy 4 years later. In fact, subsequent analysis revealed that the mean Hb Aic was the dominant predictor of retinopathy progression, and a 10% lower Hb Aic concentration was associated with a 45% lower risk. The risk of microvascular complications varies continuously with Hb Ai and there is not an Hb Ai concentration below which the risk is eliminated. 

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