Bioequivalence and Bioavailability Forum

Dear Detlew,

❝ It was very recreative. And I could practise what I have to do if I will be a rendeer (German Rentier) next time.

❝ Doing nothing the whole blessed day but "Maulaffen feil halten" (to gawk, to sit on one's hands) .

That’s not the worst thing one can do!

❝ ❝ I would not add other argument(s) to power.NTIDFDA(). AFAIK dabigatran is not a NTID.

❝

❝ That astonishes me.

See the linked references I added in the meantime to my previous post.

❝ I had interpreted the sentence "Dabigatran demonstrated a steep exposure response relationship for both efficacy and safety." as some sort of NTID.

Me too. Seems that the innovator (Boehringer Ingelheim) assessed the variabilities in its studies.
This is the first example I’m aware of where the observation “HVDs/HVDPs are safe drugs since they have a flat dose/response-curve” seemingly does not hold.
Another question comes into my mind: How the heck did Boehringer’s formulation “survive” phase III and/or bridging from the formulation used in phase III to the marketed formulation?

A dirty story? Wikipedia:

On July 26, 2014, the British Medical Journal (BMJ) published a series of investigations that accused Boehringer of withholding critical information about the need for monitoring to pro­tect patients from severe bleeding, particularly in the elderly. Review of internal com­mu­nications between Boehringer researchers and employees, the FDA and the EMA revealed that Boehringer researchers found evidence that serum levels of dabigatran vary widely. The BMJ investigation suggested that Boehringer had a financial motive to with­hold this concern from regulatory health agencies because the data conflicted with their extensive marketing of dabigatran as an anticoagulant that does not require mon­i­tor­ing.^1,2

❝ BTW: Do you think this sort of BE evaluation is not an "Eintagsfliege" (nine day wonder, ephemera), specific for dabigatran?

No idea. Let’s ask generic companies to follow the path the innovator walked?

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1. Cohen D. Dabigatran: how the drug company withheld important analyses. BMJ. 2014;349:g4670. doi:10.1136/bmj.g4670.  free resource.
   
2. Moore TJ, Cohen MR, Mattison DR. Dabigatran, bleeding, and the regulators. BMJ. 2014;349:g4517. doi:10.1136/bmj.g4517.