Event rate in the control group

For the test we need to know the success/event rate in the control group and as usual some measure of the treatment difference we are looking to detect. 

The standard deviations referred to above often provide the biggest challenge. The information for this will come from previous data for that same endpoint, from a similar population/sample of patients, treated for the same period of time etc., similarly for the success/event rate in the control group for binary data. We should try and match as closely as possible the conditions of the historical data with those pertaining to the trial being planned. 

Estimates of the basic quantities needed for the calculation such as the standard deviation or the event rate in the control group and the sources of those estimates. 

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. 

Relative risk reduction—The amount of risk reduced when compared to a control. When one sees a 5% event rate in the control group and a 4% event rate in the treatment group, the relative risk reduction is 20%. The absolute risk reduction is 1%. 

PAPWORTH 255 postmenopausal women with coronary heart disease Transdermal 17 S-estradiol 80 mcg/day alone for women with hysterectomy transdermal 17 S-estradiol, 80 mcg/day plus cyclic transdermal norethisterone 120 mcg/day for 14 days or placebo No reduction in the incidence of acute coronary events (coronary disease death, myocardial infarction, unstable angina) among women in the hormone therapy group During the first 2 years of follow-up, the hormone-therapy group had a higher acute coronary event rate than the control group. 

Increased rate of bacterial pneumonia was observed in subjects treated with enfuvirtide in clinical trials (4.68 pneumonia events per 100 patient-years in the treatment group versus 0.61 events per 100 patient-years in the control group)... 

Using the risk ratio is a particularly challenging way to show noninferiority when event rates are very low due to the mathematics defining the variability of a risk ratio. When there are few events in the control group, the Cl for fhe control rate is wide and contains very small values—values in the denominator of the risk ratio—and therefore, the Cl for the ratio may contain extremely large values even if the observed rates are similar. 

The incidence rates for six categories of adverse events of antipsychotic drug use have been compared in a retrospective cohort study of 4140 children and adolescents (mean age 10 years) and 4500 children (mean age 7.2 years) with similar service encounters but not treated with psychotropic drugs /(5 7- Six atypical and two conventional antipsychotic drugs were studied. The overall incidence/prevalence rates in the control and treated groups differed dramatically in obesity/weight gain (8.6% versus 20%), type 2 diabetes (1.9% versus... 

A systematic review of quetiapine included 12 studies [69]. The attrition rate in the four placebo-controlled studies was almost as high as in the olanzapine studies (quetiapine -53%, placebo -60%), the RR being 0.84 (Cl 0.7-0.9 NNT 11 Cl 7-55) thus, it is rather difficult to interpret the data with such Cl-values. [RR = relative risk in randomized controlled trials, the ratio of rate of negative events in the exposed group to the rate in controls.]... 

The safety and tolerability of once-daily oral metrifonate has been evaluated in patients with probable mild to moderate Alzheimer s disease in a randomized, doubleblind, placebo-controlled, parallel-group study (9). Metrifonate was given to 29 patients as a loading dose (2.5 mg/kg) for 2 weeks, followed by maintenance dose (1 mg/kg) for 4 weeks 10 patients received placebo. The proportion of patients who had at least one adverse event was comparable in the two groups metrifonate 76%, placebo 80%. Selected adverse events, defined as those for which the incidence in the metrifonate and placebo group differed by at least 10%, were diarrhea, nausea, leg cramps, and accidental injury. The adverse events were predominantly mild and transient. Those who took metrifonate had a significantly lower heart rate. Metrifonate had no clinically important effect on laboratory tests, such as liver function tests, and did not affect exercise tolerance or pulmonary function. 

In Irian Jay a, a randomized, controlled trial (n = 105 88 children) of oral artesunate (4 mg/kg od for 3 days) with pyrimethamine (1.25 mg/kg) + sulfadoxine or pyrimethamine + sulfadoxine alone (same dose) showed reduced gametocyte carriage and reduced treatment failure rates (RR = 0.3 95% Cl = 0.1, 1.3) in the combination group (16). Self-limiting adverse events of combination treatment were mild diarrhea (2.1%), rashes (4.3%), and itching (2.1%). 

There has been a multicenter, randomized, placebo-controlled, double-blind comparison of aprindine and digoxin in the prevention of atrial fibrillation and its recurrence in 141 patients with symptomatic paroxysmal or persistent atrial fibrillation who had converted to sinus rhjdhm (63). They were randomized in equal numbers to aprindine 40 mg/day, digoxin 0.25 mg/day, or placebo, and were followed every 2 weeks for 6 months. After 6 months the Kaplan-Meier estimates of the numbers of patients who had no recurrences while taking aprindine, digoxin, and placebo were 33%, 29%, and 22% respectively. The rates of adverse events were similar in the three groups. This confirms that digoxin does not prevent relapse of sjmptomatic atrial fibrillation after conversion to sinus rhjdhm. 

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