Structured expert elicitation to inform long-term survival extrapolations using alternative parametric distributions: a case study of CAR T therapy for relapsed/ refractory multiple myeloma
Abstract Background Our aim was to extend traditional parametric models used to extrapolate survival in cost-effectiveness analyses (CEAs) by integrating individual-level patient data (IPD) from a clinical trial with estimates from experts regarding long-term survival. This was illustrated using a c...
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| Format: | Article |
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BMC
2022-10-01
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| Series: | BMC Medical Research Methodology |
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| Online Access: | https://doi.org/10.1186/s12874-022-01745-z |
| _version_ | 1817983876467785728 |
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| author | Dieter Ayers Shannon Cope Kevin Towle Ali Mojebi Thomas Marshall Devender Dhanda |
| author_facet | Dieter Ayers Shannon Cope Kevin Towle Ali Mojebi Thomas Marshall Devender Dhanda |
| author_sort | Dieter Ayers |
| collection | DOAJ |
| description | Abstract Background Our aim was to extend traditional parametric models used to extrapolate survival in cost-effectiveness analyses (CEAs) by integrating individual-level patient data (IPD) from a clinical trial with estimates from experts regarding long-term survival. This was illustrated using a case study evaluating survival of patients with triple-class exposed relapsed/refractory multiple myeloma treated with the chimeric antigen receptor (CAR) T cell therapy idecabtagene vicleucel (ide-cel, bb2121) in KarMMa (a phase 2, single-arm trial). Methods The distribution of patients expected to be alive at 3, 5, and 10 years given the observed survival from KarMMa (13.3 months of follow-up) was elicited from 6 experts using the SHeffield ELicitation Framework. Quantities of interest were elicited from each expert individually, which informed the consensus elicitation including all experts. Estimates for each time point were assumed to follow a truncated normal distribution. These distributions were incorporated into survival models, which constrained the expected survival based on standard survival distributions informed by IPD from KarMMa. Results Models for ide-cel that combined KarMMa data with expert opinion were more consistent in terms of survival as well as mean survival at 10 years (survival point estimates under different parametric models were 29–33% at 3 years, 5–17% at 5 years, and 0–6% at 10 years) versus models with KarMMa data alone (11–39% at 3 years, 0–25% at 5 years, and 0–11% at 10 years). Conclusion This case study demonstrates a transparent approach to integrate IPD from trials with expert opinion using traditional parametric distributions to ensure long-term survival extrapolations are clinically plausible. |
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| format | Article |
| id | doaj.art-e0028cd12f7a4956a091b5cfd66a06a5 |
| institution | Directory Open Access Journal |
| issn | 1471-2288 |
| language | English |
| last_indexed | 2024-04-13T23:38:23Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
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| series | BMC Medical Research Methodology |
| spelling | doaj.art-e0028cd12f7a4956a091b5cfd66a06a52022-12-22T02:24:37ZengBMCBMC Medical Research Methodology1471-22882022-10-0122111110.1186/s12874-022-01745-zStructured expert elicitation to inform long-term survival extrapolations using alternative parametric distributions: a case study of CAR T therapy for relapsed/ refractory multiple myelomaDieter Ayers0Shannon Cope1Kevin Towle2Ali Mojebi3Thomas Marshall4Devender Dhanda5Evidence Synthesis & Decision Modeling, PRECISIONheorEvidence Synthesis & Decision Modeling, PRECISIONheorEvidence Synthesis & Decision Modeling, PRECISIONheorEvidence Synthesis & Decision Modeling, PRECISIONheorBristol Myers SquibbBristol Myers SquibbAbstract Background Our aim was to extend traditional parametric models used to extrapolate survival in cost-effectiveness analyses (CEAs) by integrating individual-level patient data (IPD) from a clinical trial with estimates from experts regarding long-term survival. This was illustrated using a case study evaluating survival of patients with triple-class exposed relapsed/refractory multiple myeloma treated with the chimeric antigen receptor (CAR) T cell therapy idecabtagene vicleucel (ide-cel, bb2121) in KarMMa (a phase 2, single-arm trial). Methods The distribution of patients expected to be alive at 3, 5, and 10 years given the observed survival from KarMMa (13.3 months of follow-up) was elicited from 6 experts using the SHeffield ELicitation Framework. Quantities of interest were elicited from each expert individually, which informed the consensus elicitation including all experts. Estimates for each time point were assumed to follow a truncated normal distribution. These distributions were incorporated into survival models, which constrained the expected survival based on standard survival distributions informed by IPD from KarMMa. Results Models for ide-cel that combined KarMMa data with expert opinion were more consistent in terms of survival as well as mean survival at 10 years (survival point estimates under different parametric models were 29–33% at 3 years, 5–17% at 5 years, and 0–6% at 10 years) versus models with KarMMa data alone (11–39% at 3 years, 0–25% at 5 years, and 0–11% at 10 years). Conclusion This case study demonstrates a transparent approach to integrate IPD from trials with expert opinion using traditional parametric distributions to ensure long-term survival extrapolations are clinically plausible.https://doi.org/10.1186/s12874-022-01745-zRelapsed/refractory multiple myelomaCost-effect analysesExpert opinionLong-term survival models |
| spellingShingle | Dieter Ayers Shannon Cope Kevin Towle Ali Mojebi Thomas Marshall Devender Dhanda Structured expert elicitation to inform long-term survival extrapolations using alternative parametric distributions: a case study of CAR T therapy for relapsed/ refractory multiple myeloma BMC Medical Research Methodology Relapsed/refractory multiple myeloma Cost-effect analyses Expert opinion Long-term survival models |
| title | Structured expert elicitation to inform long-term survival extrapolations using alternative parametric distributions: a case study of CAR T therapy for relapsed/ refractory multiple myeloma |
| title_full | Structured expert elicitation to inform long-term survival extrapolations using alternative parametric distributions: a case study of CAR T therapy for relapsed/ refractory multiple myeloma |
| title_fullStr | Structured expert elicitation to inform long-term survival extrapolations using alternative parametric distributions: a case study of CAR T therapy for relapsed/ refractory multiple myeloma |
| title_full_unstemmed | Structured expert elicitation to inform long-term survival extrapolations using alternative parametric distributions: a case study of CAR T therapy for relapsed/ refractory multiple myeloma |
| title_short | Structured expert elicitation to inform long-term survival extrapolations using alternative parametric distributions: a case study of CAR T therapy for relapsed/ refractory multiple myeloma |
| title_sort | structured expert elicitation to inform long term survival extrapolations using alternative parametric distributions a case study of car t therapy for relapsed refractory multiple myeloma |
| topic | Relapsed/refractory multiple myeloma Cost-effect analyses Expert opinion Long-term survival models |
| url | https://doi.org/10.1186/s12874-022-01745-z |
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