Analytical Framework for Examining the Value of Antibacterial Products. 3.2.5 Pre-clinical, Clinical, NDA/BLA Submission Success Probabilities

04/15/2014

Table 8 presents the different phase success probabilities (also referred to as phase transition probabilities) reported in the literature and gleaned from discussions with experts and drug sponsors.  Estimates reported in DiMasi et al., (2004) and DiMasi et al., (2010) are applicable to anti-infectives whereas the remaining figures from published studies apply to all pharmaceuticals.  Based on the collective body of information, we use the following success rates by phase in the model:

  • Pre-clinical: Lower bound of 17.5%, upper bound of 69.0%, likely point estimate of 35.2%
  • Phase 1: Lower bound of 25.0%, upper bound of 83.7%, likely point estimate of 33.0%
  • Phase 2: Lower bound of 34.0%, upper bound of 74.0%, likely point estimate of 50.0%
  • Phase 3: Lower bound of 31.4%, upper bound of 78.6%, likely point estimate of 67.0%
  • NDA/BLA Approval: Lower bound of 83.0%, upper bound of 99.0%, likely point estimate of 85.0%

Table 8: Pre-clinical, Clinical, and NDA/BLA Submission Success Probabilities (in %)

Source Pre-clinical Phase 1 Phase 2 Phase 3 NDA/BLA
DiMasi et al., 2003 N/A N/A 71.0% 31.4% N/A
DiMasi et al., 2004 [d] N/A N/A 66.1% 38.2% N/A
DiMasi & Grabowski, 2007 [a] N/A 83.7% 56.3% 64.2% N/A
DiMasi et al., 2010 [d] N/A 58.2% 52.2% 78.6% 100.0%
Adams & Brantner, 2006 [b] 31.0% N/A 74.0% 46.0% N/A
Paul et al., 2010 69.0% 54.0% 34.0% 70.0% 91.0%
Abrantes-Metz et al., 2004 N/A 81.0% 57.0% 57.0% N/A
Hay et al., 2011 N/A 67.0% 41.0% 65.0% 83.0%
ERG 35.2% 33.0% 50.0% 67.0% 85.0%

[a] The figures are applicable to biopharmaceuticals.

[b] The reported figures only include those based on the Pharmaprojects database.

[c] The figure reflects time for an accelerated FDA approval.

[d] The reported figures are specific to anti-infectives.


It should be noted that the average Phase 1 success rate selected for the model is much lower than the figures reported in the literature. According to experts interviewed, this high failure rate is primarily attributable to higher toxicity and tolerance issues for antibacterials compared to other therapeutic areas.  Often, studies require use of high doses of the antibacterial to treat resistant infections resulting in toxicity issues for the trial subjects.  Unlike other therapeutic areas, such as oncology, where the efficacious exposure may not be determined till Phase 3 trials are completed, the efficacious exposures are known early on for antibacterials, leading to early rather than late failures.  Because we did not have any information on how success rates may vary by indication, we apply the same rates across all of the six indications under consideration.

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