Talk:Dofetilide

DOFETILIDE drug safety
It should be noted that DIAMOND study is the only known case of a death in a clinical trial being reported to the FDA *BEFORE it happened*.

The pharmacovigilance for the DIAMOND study produced more serious adverse event data than all other Pfizer studies combined at the time: SAEs were reported direct to Pfizer Sandwich for the 3000 patients in the cohort for each "Death" being defined for thus "sudden death prevention" study as "cardiac arrhythmia requiring cardioversion or resuscitation" where the patient could have died without intervention, and reported actual death: This meant the cohort produced around a massive 7,000 "deaths", for 3000 patients - all of which needed to be reported to the FDA in an expedited manner. All of this work was managed by *one* person (a contractor)' who also managed any reports arriving from ongoing VIAGRA (Sildenafil) studies worldwide.

An average of 30 *Serious* Adverse Events a day arose from the three year : these reports were often made within hours of the event: This lead to an enquiry and Audit of the Drug Safety operation by Legal Compliance team of the FDA who travelled in a team from the USA to Sandwich, at short notice, certain that errors had been made:  On arrival to a slightly panicked Pfizer they stated that an error *must* have been made because the death of a patient had been reported to the FDA *before it happened*. Luckily the entire DIAMOND safety data load was being managed by the one person (note a contractor *not* a Pfizer employee) who explained the apparent error was due to the time difference between Denmark and The FDA in the USA being 7 hours at the time, and the entire process of 1) patient dying 2) Site investigator reporting to Sandwich by fax 3) fax received, processed and checked and 4) raised as a SAE report to the FDA and 5) submitted had taken less than 6 hours. Accepting this perfectly valid and calmly delivered explanation, the FDA team (who had been booked for several days to investigate) returned to The Bell Hotel in Sandwich.  The next day they had to be educated by the contractor that 20 fluid ounce pints in England as opposed to 16 oz in the USA, combined with drinking 5% alcohol beer as opposed to domestic strength US (3.5%) was probably the reason for their collective hangovers.l despite "only having 4 or 5 beers".

Incidentally, the study was also the first where "continuing ongoing reconciliation" of the separate SAE/FDA reports were reconciled with the AE reports in the study database (recorded on Pfizer in house software PFIZERCLIN, running on VAX/VMS) Somewhat amazingly this was also handled by the *same* contractor as managed the SAE reports *at the same time* by running periodic data comparison routines that *they had worked out themselves* "on the fly".

Pfizer later set up a task group to look at ongoing reconciliation of SAE Vs Study AE databases to compress the long delays at database close out. The working party realised somewhat incredulously that this process had actually already been successfully invented and implemented for the single largest SAE database ever generated, and by one person who was not even a Pfizer employee. The contractor was phoned and asked "...er ... How did you do it?" Rather generously in hindsight, the contractor explained the process in detail, and was then replaced by a team of 6 Pfizer employees, but the work had already largely been done for DIAMOND. It may be noted that the contractor did decline a permanent position employed by Pfizer (at substantial pay CUT) and went on to a successful career in Pharma consulting Business Development, while the site at Sandwich (with new building capital projects paid for mainly from profits of Viagra) was gradually mothballed closed and even demolished, but not before Brad Pitt and Co used the cafeteria and other buildings for "World War Z". Funny old world... Dofetikide (talk) 08:59, 25 June 2024 (UTC)