<p>Economic Evaluation of Single versus Combination Immuno-Oncology Therapies: Application of a Novel Modelling Approach in Metastatic Melanoma</p>
Bibliographic record
Abstract
BACKGROUND: Existing economic model frameworks may not adequately capture the atypical treatment response patterns in immuno-oncology (I-O) compared with conventional therapies and thus may fail to represent the full clinical value associated with disease dynamics and improved survival. OBJECTIVE: A cost-effectiveness analysis (CEA) of the I-O Regimen (nivolumab/ipilimumab) versus ipilimumab alone in advanced melanoma was carried out by applying a 5-state partitioned survival model (PSM) as a case study, to explore the I-O treatment response and clinical outcomes. The findings were compared with those of a conventional 3-state PSM. MATERIALS AND METHODS: The case study extends the conventional 3-state PSM, by separating the pre-progression state into non-responders and responders, and the post-progression state into normal and I-O progression to account for delayed treatment effects preceding clinical response. Model states were populated using patient-level data (where possible), mapping from the best overall response (BOR), and survival analysis with flexible and traditional parametric methods. Survival functions were applied to progression-free survival (PFS) and overall survival (OS) endpoints across treatment arms using the 4-year follow-up data (data available at the time of the research; since then 5-year follow-up data have been published) from the CheckMate 067 trial. Information on BOR was used as a means of differentiating the I-O treatment response in addition to the outcomes of progression-free and progressed disease. A UK National Health Service and personal social services (NHS/PSS) perspective over a lifetime horizon was used with outcomes discounted at 3.5% annually. RESULTS: The 5-state PSM generated an increase in quality adjusted life years (QALYs) in both treatment arms and gave a more granular description of patients' health profiles compared with the traditional 3-state PSM. The incremental QALY increased by 13% (from 2.62 to 2.95 QALYs) and the incremental cost decreased by 12% (£29,125 to £25,678) with the 5-state model. In both models, the Regimen had an incremental cost-effectiveness ratio (ICER) relative to ipilimumab alone within the lower bound of the National Institute for Health and Care Excellence (NICE) reference range (£20,000 per QALY gained). CONCLUSION: A 5-state economic model, incorporating relevant I-O health states, can be more informative to gain insight into treatment response and progression differences that are not commonly captured in existing economic models. Clinical trial endpoints, including those relating to treatment response, which are not directly reported in ongoing I-O trials, can be mapped on to the proposed modelled health states (although assumptions are required to do so). Improvements in reporting treatment response in future I-O clinical trials could help to further validate and improve the proposed model framework.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".