Reference control group

A maximal concentration of cTnl or cTnl exceeding the decision limit, defined as the 99th percentile of values for a reference control group, on at least one occasion during the first 24 hours after the index clinical event. 

Hydroxypyrene was measured in the urine, and PAH-DNA adducts were measured in white blood cells to demonstrate their relationship to the exposure. Results from these workers were compared to two reference control groups research and development (R D) workers and nickel refinery workers. Mean values of PAH-DNA adducts in the white blood cells from randomly selected participants in the three groups were only marginally different, with the exception of two smokers in the electrode plant, who had the highest levels. Mean PAH-DNA adduct levels were 10.9 adducts per 108 nucleotides for the electrode workers, 10.8 adducts per 10 nucleotides for the R D personnel, and 10.0 adducts per 10 nucleotides for nickel plant workers not occupationally exposed to PAHs. No correlation was found between PAH-DNA adducts and 1-hydroxypyrene in the urine. 

Hydroxypyrene was measured in the urine. Results from these workers were compared to two reference control groups, research and development workers and nickel refinery workers. 

Rabbit litters are notoriously difficult to handle without inducing cannibalism of the pups by the mother and few laboratories have experience of postnatal safety studies in this species. Such studies are possible with accumulated experience, however. Example reference data from the control groups of 15 regulatory studies are presented in Table 2. 

Since teratology studies in mice are far less frequent than in the rat, the amount of recent historical control data may be limited. If little or no recent reference data are available, the size of the concurrent control group should be increased. 

There may be some situations where the test treatment is, in fact, harmful relative to the control treatment in terms of a particular endpoint. In these circumstances it does not make sense to take talk about number needed to treat and we refer instead to number needed to harm (NNH). So, for example, if the survival rate on the test treatment were 72 per cent compared to 84 per cent in the control group then the number needed to harm would be equal to 1 /(0.84 — 0.72) which rounds to eight. 

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. 

Table 6.2. UNIVARIATE SUMMARY STATISTICS (MEAN + S.E.M.) FROM THE SIMULATED DATA ILLUSTRATED IN FIGURE 6.5 CONSISTING OF A CONTROL GROUP AND A TREATMENT GROUP The p values refer to a two-sided r-test with 20 degrees of freedom.

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