Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence indicates that both avatrombopag and lusutrombopag reduce the need for platelet transfusions compared to placebo, but there is no evidence demonstrating that they improve survival compared to standard care (platelet transfusions). The trials did not measure survival as an outcome, and the committee concluded that there is no evidence that either drug is more effective than the other. This strengthens the market access risk assessment and overall reimbursement probability.
Cost effectiveness
The economic modeling indicated that while lusutrombopag is likely to save the Healthcare money when considering broader service delivery benefits, the ICER was very high at £3.4 million per QALY gained, indicating low cost-effectiveness without a clear justification for the high cost. This informs pricing and reimbursement risk and pharmaceutical reimbursement forecasting.
Quality of life
The committee acknowledged that the oral administration of lusutrombopag and avatrombopag could reduce the burden of hospital visits for transfusions, which is a significant quality-of-life improvement for patients. However, the evidence for direct HRQoL improvements was not robustly quantified in the trials. These outcomes align with HTA decision predictors and support pricing and reimbursement assessment.
Supporting Domains
Safety and Adverse Effects
The safety profile of both drugs was considered acceptable, with no significant differences in adverse events compared to placebo. The committee noted that while there is a risk of thromboembolic events, the short-term trial results did not show a difference in these events between the treatments and placebo. This profile reduces payer uncertainty and supports access risk forecasting.
Comparator Selection
The trials compared the new treatments against placebo rather than the standard of care (platelet transfusions). While this is acceptable for initial efficacy assessment, it limits the relevance of the findings to real-world clinical practice where transfusions are the standard. This aligns with HTA comparator analysis and strengthens the market access submission.
Patient Population and Subgroups
The trials included patients with chronic liver disease and thrombocytopenia, which is representative of the intended population. However, there were concerns about the generalizability of the results due to the exclusion of patients with more severe disease (Child-Pugh C). This enhances reimbursement likelihood rating and payer relevance.
Care Pathway Integration
The oral administration of the drugs allows for easier integration into existing care pathways, reducing the need for hospital visits for transfusions. The committee noted that coordination with GPs for monitoring platelet levels would be manageable. This supports budget impact analysis and facilitates market access feasibility.
Resource Use and Cost Implications
While the drugs are expected to reduce the need for transfusions and associated hospital stays, the economic models did not fully account for all relevant costs, leading to uncertainty about the overall resource implications. This supports pricing model stress-testing and payer evidence expectations.
Evidence Quality and Robustness
The evidence base is supported by randomized controlled trials, although there are limitations regarding the follow-up duration and the lack of survival data. The committee found the trial evidence appropriate for decision-making despite these limitations. These outcomes align with HTA decision predictors and support pricing and reimbursement assessment.
Uncertainty, Sensitivity, and Broader Impacts
The committee acknowledged some uncertainty regarding the long-term outcomes and cost-effectiveness but noted that the innovative nature of the treatments and their potential benefits could mitigate some of these concerns. These factors elevate access risk forecasting within HTA evaluation frameworks.
