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CombiStats: What's new in version 6.0?

CombiStats version 6.0 was released on 01 January 2020. Upgrading from version 5.0 to version 6.0 comes at no extra cost but is mandatory as it implements the change in the formula of the semi-weighted combination of assay results in Chapter 5.3 of the Ph. Eur. 10th Edition.

The software is backward compatible so all your existing datasheets and templates will work as before. However, former passwords will not work for version 6.0. New credentials will be provided as part of the renewal of licence or when ordering the software for the first time.

This is a quick guide to the new and some existing features:

Semi-weighted combination of assay results

CombiStats offers the possibility to combine the results of several assays according to the 3 calculation approaches described in Chapter 5.3 of the European Pharmacopoeia. The datasheet displays the individual potency estimates along with their 95% confidence limits as a start. The p-value of the test of homogeneity of potency estimates is then calculated and tables of results displayed for the unweighted, weighted and semi-weighted combination approaches. Version 6.0 implements the change introduced in the 10th edition of the Ph. Eur. for calculating the between-assay variability involved in the semi-weighted combination approach. Here is an example.

Password protection of templates and datasheets

This is provided via the button with a padlock icon https://www.edqm.eu/sites/default/files/cadenas.png. There are 4 levels of protection and each level can have its own password. Passwords are optional. If you type no password when increasing the level of protection, the user can remove the protection without password. Even if no password is used, this provides an increased safeguard against accidental modification. More information on the 4 levels of protection and the use of passwords is provided in the manual.

Support for equivalence testing

Equivalence testing can be activated in the options wizard’s tab ANOVA. CombiStats shows a table with the slopes of the individual preparations and their 90% confidence interval. If a standard is included, the differences and ratios of the slopes with that of the standard are also shown, again with 90% confidence limits. For slope ratio models, the intercepts are used instead of the slopes and, in that case, no ratios are calculated since this has no meaningful interpretation. The purpose of these statistics is to check whether the complete 90% confidence interval is contained within pre-defined “goal-posts”. If this is the case, the slopes are equivalent, even when there is significant non-parallelism according to the traditional ANOVA approach. Here is an example.

Robust regression to reduce the effect of outliers

Although the European Pharmacopoeia discourages users to apply outlier tests to exclude outliers, many laboratories still apply such a test blindly without looking into an experimental explanation for the occurrence of these values. To encourage these laboratories to abandon this practice in favour of better alternatives, CombiStats offers robust regression by the use of Huber’s weights. This can be activated in the advanced options by specifying a weight of w=h. Here is an example.

Automatic invocation of Spearman/Kärber method

Some assays that are designed to be analysed with probit models (or similar parametric curves), may have insufficient data in the central part to allow for estimation of the slope. Often, an estimate can still be obtained using the Spearman/Kärber method. CombiStats detects when the parametric models cannot be used and automatically invokes the Spearman/Kärber method. A message that this is the case is printed on the output. Here is an example.

5-parameter sigmoid curve regression

It allows for a 5th parameter to model asymmetry of the curves. It can be activated in the options wizard’s tab “transformation” and is available only for quantal models and quantitative sigmoid models. Here is an example.

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