21 September 2020 - We all know that the PBAC goes to great lengths to ensure its decision-making is consistent. This is to be expected and is not in dispute.

Issues have arisen from time to time when the PBAC breaks new ground in its decision-making. We have seen this lately with the PBAC’s seemingly increasing use of a comparison with the lowest/least cost alternative. The Committee’s justification for doing this is that it is consistent with the legislation that underpins its operations (National Health Act 1953).

But what if the PBAC breaks new ground on an issue that is not covered by the National Health Act (or any other legislation for that matter) or is not well established in the scientific arena? In recent times, we have seen the PBAC introduce a new test for its acceptance of a claim of clinical superiority.

At its meeting in November 2019, the PBAC considered that AbbVie’s claim of the clinical superiority of upadacitinib monohydrate over adalimumab was not fully supported by the evidence. The Committee noted that the claim was based on ACR50 results in the SELECT-COMPARE trial meeting the pre-specified tests for non-inferiority and then superiority of upadacitinib monohydrate versus adalimumab. That is, the lower bound of the 95% confidence interval for the risk difference was larger than the nominated non-inferiority margin of -10%, and then larger than 0% (i.e. statistically significant) in accordance with the sequential testing procedure.

The upadacitinib monohydrate example is not a PBAC first. The PBAC recalled in November 2019 it had previously rejected a superior efficacy claim made by Eli Lilly for baricitinib versus adalimumab based on similar evidence, and suggested using the inverse of the non-inferiority margin to establish superiority rather than statistical significance (PBAC Public Summary Document for baricitinib, July 2017). There is no evidence in the public domain to indicate that Eli Lilly has challenged the PBAC on this.

The PBAC’s use of a new, unestablished method to assess a claim of clinical superiority may well become a precedent if AbbVie’s challenge is unsuccessful. The apparent failure of Eli Lilly to challenge the use of this method has not helped. The continued use of the ‘inverse of the non-inferiority margin’ method by the PBAC will have profound effects on the listing of new medicines on the PBS in the future. This will be discussed in more detail in future issues of MAESTrO Daily.