Bioequivalence and Bioavailability Forum

Dear All,


We are conducting bioequivalence studies on patients, carried out at different clinical sites. As the biostudies are conducted on cancer patients, the dosing is planned [either single (one) or in group] at different clinical sites based on the availability of patients. Even at the same clinical site the dosing is done for different group which is separated by 1- 3 months.

As per FDA guidance, if a crossover study is carried out in two or more groups of subjects (e.g., if for logistical reasons only a limited number of subjects can be studied at one time), the statistical model should be modified to reflect the multi-group nature of the study. Hence we are planning to include ‘group effect' in our statistical model to evaluate whether the group effect is present or not.

We have worked out the following approaches for choosing a ‘group’, which we are mentioning below along with the probable concern that may occur by doing so.

• Approach 1 (group formed as per dosing date): Usually the dosing is being done based on the patient availability. So if we consider the dosing dates for denoting a group, then we may end up in getting more than 10 to15 groups, which will be huge in number.
  
  
• Approach 2 (group formed on the basis of dosing performed within a time interval): Based on the dosing date of the patient within a specified time frame (e.g. 1 or 2 months), one group can be framed. Similarly other groups can be formed based on all the next dosing performed in the subsequent month(s). In this way; we can minimize the number of groups. But we are not sure, whether this time frame for group selection is justifiable.
  
  
• Approach 3 (group formed as per clinical site): all the patients enrolled in a particular clinical site shall be considered as a group for the statistical evaluation.
  In this case, number of groups will be less. But by doing so, will it be misinterpret as 'center effect' rather than 'group effect'? Also in a single clinical site/ center dosing is done for different patients whose doing date is separated by 1- 3 months. Can we consider the data of all the patients as one 'group'?

Kindly suggest which is the most appropriate way for grouping of subject data among above approach and please also let us know if there is any other better option available beside those.

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Edit: Category changed. [Helmut]