Bioequivalence and Bioavailability Forum

Study costs: Replicate vs. 2×2×2 [Regulatives / Guidelines]

posted by M.tareq  – 2017-05-07 23:21 (2876 d 17:42 ago) – Posting: # 17314
Views: 23,491

hi all

from ethical view regarding replicate study vs standard crossover,

first case:

the published data suggest slightly boarder line CV% of 29-31%

the required sample size will be around 42 volunteer without accounting for dropouts
however if it will be replicated whether partially around (33 volunteer) or fully replicate around (22 volunteers) and power maintained at at least 80% without scaling to ref variability

in standard design even though higher number of volunteers will be dosed but only for 2 periods
and in replicate design fewer subjects will be dosed but for longer periods,
my question about the ethical view of such approach vs sponsor risk due to inadequate design?

2nd case

regarding drugs which aren't stated to be HVDP (from previous studies or assessment reports)

suppose the CV was found to be around 20% and the sponsor or cro wishes to go for replicate design for safe planning that the drug might shows high CV just in case or so

whats the regulatory views regarding that matter? in EMA guidelines regarding replicate design and widening of acceptance range for cmax it stated that the drug known to be HVPD CV > 30 and not as a result of outliers

so from ethical point of view ,given the drug isn't HVPD and it's stated in the protocol if the drug CV% was less than 30% the normal acceptance criteria will be applied, why the need for the extra periods/dosing of volunteers from ethical/scientific view?

Thanks in advance

Complete thread:

• Highly Variable Drug BE Justification jag009 2017-03-20 04:42 [Regulatives / Guidelines] 
  • Highly Variable Drug BE Justification ElMaestro 2017-03-20 06:55
    • Study costs: Replicate vs. 2×2×2 Helmut 2017-03-20 13:12
      • Study costs: Replicate seems to be cheaper VStus 2017-03-21 12:49
        • Study costs: Replicate seems to be cheaper Dr_Dan 2017-03-21 13:06
          • Study costs: Replicate seems to be cheaper Helmut 2017-03-21 14:50
            • expected power d_labes 2017-03-21 15:16
            • Doesn't hurt! VStus 2017-03-23 14:24
      • Study costs: Replicate vs. 2×2×2 mahmoud-teaima 2017-03-23 08:17
      • Study costs: Replicate vs. 2×2×2M.tareq 2017-05-07 21:21
        • Replicate vs. 2×2×2 (ethics?) Helmut 2017-05-08 14:21
          • Replicate vs. 2×2×2 (ethics?) nobody 2017-05-08 14:52
            • Applicability of reference-scaling Helmut 2017-05-10 14:10
          • Replicate vs. 2×2×2 M.tareq 2017-05-14 23:04
            • Replicate vs. 2×2×2 Helmut 2017-05-15 19:07
              • Replicate vs. 2×2×2 M.tareq 2017-05-15 21:02
              • Regulators view of HVD drugs DavidManteigas 2017-05-16 12:41
                • Regulators view of HVD drugs Helmut 2017-05-16 15:01
                • What's the problem? ElMaestro 2017-05-17 03:30
                  • What's the problem? nobody 2017-05-17 07:48
                    • What's the problem? nobody 2017-05-17 09:31
                      • What's the problem? DavidManteigas 2017-05-17 11:25
                        • What's the problem? ElMaestro 2017-05-17 12:07
                          • What's the problem? kumarnaidu 2017-07-11 14:43
                            • What's the problem? ElMaestro 2017-07-11 14:56