Bioequivalence and Bioavailability Forum

Dear ElMaestro!

❝ The first option can be difficult in practice ...

I didn’t say it's easy.
These were just some desultory thoughts for consideration.

❝ ... because it might need a validation of the methods for 1. assessing the actual caloric consumption and composition of the eaten part of the meal.

To be honest, I have only very rarely seen a caloric breakdown of meals in a BE study – except of the breakfast. Validation? Come on! I even have no clue where the FDA got the caloric breakdown and composition of their standard high-calory high-fat breakfast from. OK, cal should read kcal (I know, I know), but

• 2 eggs fried in butter (How much butter? Do you consume the melted butter or does it go to the waste bin?)
  
• 2 strips of bacon (Weight?)
  
• Two slices of toast with butter (Weight? How much butter?)
  
• Hash brown potatoes (4 ounces – great; the first component without ambiguities)
  
• Whole milk (8 fl. ounces - hurrah!)

After consulting two nutritionists, chewing the Geigy-tables, and trying to solve a system of linear equations (3 variables: butter, bacon, toast; 4 constants: three percentages of energy content and total kcal) we assumed 1 slice of toast = 37.5 g, 1 strip of bacon = 3 g, and two servings of butter à 20 g. This gave:
                              #  protein  carbohydrate   fat    total
eggs fried in butter          2    49.2        3.3      102.3    154.8
strips of bacon               2     2.2        0.0       36.3     38.5
toast                         2    30.8      135.3       22.3    188.4
hash brown potatoes (ounces)  4    13.5      122.7       84.4    220.6
whole milk (fl. ounces)       8    32.0       46.0       83.9    161.9
butter (servings)             2     0.0        1.1      301.3    302.5
        total energy [kcal]       128        308        631     1067
        of total                   12%        29%        59%
        FDA's target [kcal]        15%        25%      50-60%  800-1000
Everybody is welcome to come up with a better match (Hints: 1 g protein or carbohydrate = 4.1 kcal, 1 g fat = 9.3 kcal; amount of butter is the main problem).

❝ 2. matching pt. 1 on the next plate (this involves setting a kind of specification, and FDA needs a justification for specifications…

Given the above I don’t think it is sooo complicated. Just record what was left in period 1 and reduce the serving in period 2. It makes sense to exclude a subject in food-effect study or a study in fed state, if the breakfast was not consumed entirely – but the other meal(s)? Another story is the ominous 4 hour interval between administration and lunch. Unfortunately many guideline-believers are nonprofessional in reading. Guidelines state “at least [sic!] 4 hours”. Especially after a high-calory high-fat breakfast the interval should be longer – and a smaller meal considered for females.

❝ ... Very hard)

Hard is hard, and
soft is soft, but
always soft
is also hard. (Austrian proverb)