The Role of Uncertainty in Health Technology Assessment in Australia
The Pharmaceutical Benefits Advisory Committee (PBAC) in Australia performs a Health Technology Assessment (HTA) to inform recommendations for listing medicines on the Pharmaceutical Benefits Scheme. Managing decision uncertainty to ensure timely patient access to medicines and avoid healthcare resource loss is important for the Pharmaceutical Benefits Advisory Committee (PBAC). Delayed funding decisions or lack of funding for medicines have been highlighted as major concerns by some consumer organisations and the pharmaceutical industry. However, research on the impact of uncertainty on the PBAC’s decision-making process has been limited.
One potential reason behind delayed or negative recommendations for medicines is the presence of uncertainty in the incremental cost-effectiveness ratio (ICER) based on available information. Chapter 2 developed a framework to characterise four types of uncertainty (i.e., methodological, structural, generalisability and parameter uncertainty) in model-based submissions to the PBAC from 2014 to 2021. The first two were then subcategorised as unparameterisable and parameterisable uncertainty, depending on whether their impact on the ICER can be explored using alternative data inputs and sources. It was found that the PBAC more often raised issues regarding parameter and parameterisable structural uncertainties. Logistic regression results suggested that the PBAC was more likely to recommend a medicine without concerns about parameterisable structural, unparameterisable methodological and generalisability uncertainties.
Another reason behind delayed or lack of funding for medicines may stem from the misalignment between the Therapeutic Goods Administration (TGA, the regulator) and the PBAC on the evidentiary requirements for surrogate outcomes, which are substituted for clinical endpoints as they enable smaller sample sizes, shorter lengths of time required for follow-up, easy measurement, and lower costs of conducting trials. Chapter 3 demonstrated the potential for improved decision efficiency by aligning the different considerations on using and accepting the surrogate outcomes between the bodies. It also revealed that their agreement on accepting surrogate outcomes was fair and the accepted surrogate outcomes had poor quality.
Based on a survival analysis, Chapter 4 found that medicines submitted between 2014 and 2021 with accepted surrogate outcomes were 3.053 times more likely to be recommended than medicines with unaccepted surrogate outcomes after controlling for variables such as unmet clinical need and the types of economic evaluation.
The findings in chapters 3 and 4 highlighted the necessity to investigate the PBAC’s implementation of its guidance for evaluating surrogate outcomes based on the information disclosed to the public. Chapter 5 explored whether the rationale of the unaccepted surrogate outcomes was structurally reported in line with the guidelines. It showed that the Public Summary Documents poorly reported the rationale for unaccepted surrogate outcomes in terms of qualitative and quantitative evidence. This was partly due to the poor practice of the sponsors in not submitting the required evidence.
This thesis identified the uncertainties that significantly influenced PBAC recommendations and investigated the uncertainty around surrogate outcomes used in PBAC’s decision-making. The findings provided empirical evidence for multiple stakeholders to mitigate decision uncertainty by improving collaboration on characterising different types of uncertainty, and fully addressing the uncertainty around surrogate outcomes. This could be helpful for the improvement of decision-making efficiency between the TGA and the PBAC to promote timely access to medicines for Australian patients.
