Challenge
A therapy developed for a rare and severe genetic disease required robust comparative evidence to support evaluation within an HTA process and inform reimbursement decision-making.
However, the available evidence was derived from trials with heterogeneous patient populations and varying treatment durations, thereby limiting the validity of conventional cross-trial comparisons.
Solution
A stepwise analytical approach was implemented to ensure robust relative effectiveness evidence aligned with the HTA authority-defined PICO.
The initial stage consolidated the available evidence, including:
- A pivotal phase 3 randomized controlled trial.
- A systematic literature review (SLR) of available therapies.
- Indirect treatment comparisons (ITCs) using the Bucher method versus relevant comparators.
During the methodological assessment of the evidence base, important cross-trial differences were identified among the studies included in the ITCs, including variations in baseline patient characteristics, treatment duration, and outcome assessment timepoints. To address these challenges, Clevidence implemented population-adjusted indirect treatment comparisons, including:
- Matching-Adjusted Indirect Comparisons (MAICs), and
- Simulated Treatment Comparisons (STCs).
These methods allowed adjustment for cross-trial heterogeneity and alignment of outcome assessment across studies.
Impact
This analytical framework generated robust estimates of relative treatment effectiveness, strengthening the comparative evidence package and supporting the assessment of the therapy’s clinical value within the HTA evaluation process.