===== "Now, they would say they received important feedback on the trial design that they incorporated, and to be fair, I suspect they did. They are saying they moved forward without signature because they didn't want to wait anymore (and they incorporated the FDA's feedback). They made a call that the risk in moving forward was low relative to the cost of waiting more, if I understand correctly. I understand this argument, but it really does beg the question -- what else is outstanding, i.e., why didn't the FDA just "agree" and "sign" so ABT could then move forward. What's outstanding or incomplete?"
Here's a quote from the FDA's guidance, numbered pages 2/3 or document pages 5/6.
Under new sections 505(b)(4)(B) and (C) of the Act, if a sponsor makes a reasonable written request to meet with the Agency for the purpose of reaching agreement on the design and size of a clinical trial, the Agency will meet with the sponsor. If an agreement is reached, the Agency will reduce the agreement to writing and make it part of the administrative record. An agreement may not be changed by the sponsor or FDA after the trial begins, except (1) with the written agreement of the sponsor and FDA, or (2) if the director of the FDA reviewing division determines that "a substantial scientific issue essential to determining the safety or effectiveness of the drug" was identified after the testing began (section 505(b)(4)(C) of the Act). If a sponsor and the Agency meet regarding the design and size of a clinical trial under section 505(b)(4)(B) of the Act and the parties cannot agree that the trial design is adequate to meet the goals of the sponsor, the Agency will clearly state the reasons for the disagreement in a letter to the sponsor (PDUFA goals at VI.A.2). However, the absence of an articulated disagreement on a particular issue should not be assumed to represent an agreement reached on that issue.
Meetings between the Agency and sponsors are generally helpful in reaching agreement on the design and, in some cases, interpretation of studies submitted in support of marketing applications.4
You can draw your own conclusions from the lack of SPA, but here's my best guess ... put in admittedly idiotic terms. :)
Abbott: We propose that X is sufficient to demonstrate efficacy.
FDA: No, we need X + 7
Maybe Abbott doesn't think they can reach X + 7, but the DO think they can reach X + 5. They certainly wouldn't want to commit to a possibly unreachable X + 7, hence no SPA.
The natural question is ... if the FDA couldn't specifically describe what they wanted, why the hell would a sponsor proceed with the trial? That's called confidence boys and girls.
A) a product?
B) changing attitudes at the FDA?
C) a solid safety profile which could decrease the efficacy requirement?
D) the necessity to gamble sometimes even when you don't have a sure thing?
E) all of the above (and probably more)
Yeah ... you guessed it ... I'm going with E.
===== "The only other issue I wonder about is the mention of confidentiality. I wonder what would be released in the SPA if the FDA had agreed and ABT had announced it. I doubt it, but maybe there was a decision around this issue."
I don't think the contents of SPAs are required to be in the public domain.