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1. Type I error. A type I error occurs if the null hypothesis is rejected i.e. a
significant result is obtained, when the null hypothesis is in fact true. A type I error is a false positive result. The probability of making a type 1 error is denoted as .
2. Type II error.
insignificant result is obtained, when the null hypothesis is in fact not true (the alternative hypothesis is true). A type II error is a false negative result. The probability of making a type II error is denoted as .
clinically worthwhile difference to be detected, standard deviation of the variable and the nominated significance level. These factors are interdependent so that it is possible to calculate any one of them given the others.
detect as statistically significant a real difference of a given magnitude. It is generally recommended that the power of a clinical trial
should be at least 80% - 90%. A high power means that there is a high chance of detecting a
significant difference, if there is one, and a low chance of making a type II error. With a high power, if a result is non-significant, one can be reasonably sure, though not certain, that it is valid to accept the null hypothesis. Since the probability of not detecting a real difference between
study groups is (i.e. the probability of a type II error), the probability of detecting a real difference (the power) is 1-.
2. Minimum clinically worthwhile difference. (a). Hypothesised difference and sample size.
small samples are likely to produce a significant result. If the difference between treatments is small then much larger numbers are required. (b). Statistical significance and clinical difference. When differences are expected to be small, it becomes
important to distinguish between statistical significance and clinical significance. The investigator needs to define the minimum difference
between the groups that he is going to consider clinically relevant. For example, suppose that a new bronchodilator is believed to cause a real increase in tidal volume of 10 ml in patients with chronic bronchitis. The standard deviation of tidal volume in this population is likely to be considerably higher than this figure. It would be possible, however, given a huge sample, to demonstrate the real increase, but the exercise would be very expensive and very pointless because with such a small (but statistically significant) difference, the drug would be of little clinical consequence. Given a large enough sample, any difference, no matter how
small and trivial, can be made statistically significant. Hence, experience and judgement are needed when deciding
and which therefore justifies the time, effort and finance required to investigate it.
3. Standard deviation. The larger the standard deviations of the two groups relative to
the minimal clinically important difference to be detected, the larger the sample size that is going to be required; the smaller the standard deviations, the smaller the sample size required. The ratio of the minimal clinically important difference to the
standard deviation is referred to as the standardised difference and is used in the Altman normogram. The estimated SD. At the start of many investigations, an estimate of the standard deviation may not be readily available. There are several approaches to this problem: Perform a pilot study. Start the trial with the intention of estimating the likely standard
deviation from the first patients Use the standard deviation found in the investigators own
previous trials of a similar kind. Use the standard deviation quoted in similar trials or in similar
sample size required. If the significance level is 0.01 rather than 0.05, a much larger sample size will be required to avoid a error, whereas if is 0.1 then a much smaller sample size will be adequate, though there is then an increased risk of making a type I error. There is a reciprocal relationship between and - as the
nominated decreases the chances of a error increases and vice versa. In other words, for a given sample size, if is 0.01 rather than 0.05, there is a smaller probability of making a type I error but greater probability of making type II error. An value of 0.05 implies that 1 trial in 20 will produce a type I error purely by chance. As a rule of thumb the probability of a type II error of a study
should be approximately 4 times the significance level chosen. For example, if the significance level is 5%, the power should be at least 80%. If the significance level is 1%, the power should be 95%.
more groups, paired and unpaired samples, groups of equal or unequal sizes. However, the formulae used are complex and for many investigator, the guidance of a statistician would be essential.
Two alternative approaches are available for medical investigators with limited mathematical knowledge. 1. The Altman normogram. (a). Advantages. The Nomogram is a simple and elegant idea that can be applied to categorical and continuous data including paired and unpaired samples and groups of unequal sizes. (b). Using the normogram. Figure 1 shows the normogram. It relates standardized
difference (left scale), significance level (middle scale) and power (right scale). In the next section, the normogram will be used to find the sample size required for a two independent group comparison of a continuous measurement. Let the standardized difference (smallest clinically worthwhile
difference/SD) = 1.1, the significance level = 0.05 and the power = 0.85. A straight line is drawn between 1.1 on the standardized difference scale and 0.85 on the power scale. The line passes through N = 30 on the 0.05 significance scale. Therefore, 15 patients in each group will be sufficient to detect the smallest
clinically important difference between the two groups with power of 0.85 at a significance level of 0.05. 2. Computers. Investigator-friendly computer software programs are available
that can calculate sample sizes quickly and automatically. Also, several pages on the world wide web are dedicated to
Table 1. The types of errors associated with hypothesis tests: Decision to accept H0 Decision to reject H0 Type I error (false positive) Probability
H0 true
Correct decision
H0 false
Right decision