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Dinutuximab Beta for Treating Neuroblastoma: An Evidence Review Group and Decision Support Unit Perspective of a NICE Single Technology Appraisal

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Abstract

As part of its Single Technology Appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer (EUSA Pharma) of dinutuximab beta (Qarziba®) to submit evidence of its clinical and cost effectiveness for treating neuroblastoma. The BMJ Technology Assessment Group (BMJ-TAG) was commissioned to act as the Evidence Review Group (ERG), reviewing the submission from the company. The Decision Support Unit (DSU) was commissioned to review additional evidence submitted by the company and to undertake further analyses. This article presents the critical review of the company’s submissions by the ERG and DSU, further analyses undertaken by the DSU, and the outcome of the NICE guidance. The clinical effectiveness for dinutuximab beta was derived from a phase III randomised controlled trial (RCT) that assessed the safety and efficacy of the addition of interleukin (IL)-2 to dinutuximab beta plus isotretinoin. This trial did not inform the relative effectiveness of dinutuximab beta versus isotretinoin alone, which was established practice in the UK for maintenance treatment. In the absence of direct evidence, the company initially conducted a naïve indirect treatment comparison against a historical control, and later performed a matching-adjusted indirect comparison (MAIC) against the isotretinoin arm of an RCT comparing dinutuximab alpha and isotretinoin. The company submitted a partitioned survival analysis model that calculated the incremental cost effectiveness of dinutuximab beta versus isotretinoin. The company’s original incremental cost-effectiveness ratio (ICER) was £22,338 per quality-adjusted life-year (QALY) gained. However, the ERG were concerned that the company’s ICER was not suitable for decision making, and thus carried out initial exploratory analysis as a first step to overcome the naïve estimation of treatment effectiveness in the model. The ERG’s analysis estimated an ICER of £111,858 per QALY gained. In their revised analysis incorporating the MAIC and other changes as requested by the appraisal committee, the company’s ICER was £24,661 per QALY gained. When the DSU incorporated longer-term isotretinoin data and made corrections to the model, the ICER increased to between £62,886 and £87,164 per QALY gained depending on the choice of survival model. A confidential Patient Access Scheme (PAS) decreased the ICERs. The ICERs with the PAS were over £40,000 per QALY gained, but the NICE committee additionally considered the patient population and its size, the disease severity, the potential for significant survival benefit and uncaptured health benefits, and recommended dinutuximab beta as a treatment option, subject to the company providing the agreed discount in the PAS.

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Acknowledgements

This summary of the DSU and ERG report was compiled after NICE issued the FAD. All authors have commented on the submitted manuscript and have given their approval for the final version to be published. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of NICE or the Department of Health. Any errors are the responsibility of the authors. The authors would like to thank Nwamaka Umeweni and Anna Brett for their support throughout the appraisal and for reviewing this article.

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Authors and Affiliations

  1. School of Health and Related Research, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, UK

    Becky Pennington & Shije Ren

  2. BMJ Technology Assessment Group, BMA House, Tavistock Square, London, WC1H 9JR, UK

    Samantha Barton, Mariana Bacelar & Steven J. Edwards

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  1. Becky Pennington
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Contributions

BP and SR were members of the DSU who reviewed the company’s additional analyses and wrote the DSU reports. BP critiqued the economic modelling and undertook new economic analyses. SR critiqued the statistical analyses and performed the MAIC and survival analyses. SB, MB and SE were members of the ERG who reviewed the company’s submission and wrote the ERG report. SB critically appraised the company’s submission, critically appraised the clinical evidence and cross-checked the company’s search strategies. MB critically appraised the company’s submission and economic model, cross-checked the company’s search strategies, critically appraised the economic evidence and carried out economic analyses. SE critically appraised the company’s submission and validated the statistical analyses. All authors were involved in drafting and commenting on this document. This summary has not been externally reviewed by PharmacoEconomics.

Corresponding author

Correspondence to Becky Pennington.

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Funding

The ERG were funded by the National Institute for Health Research (NIHR) Health Technology Assessment Programme (Project number 15/194/02). Visit the HTA programme website for further project information (http://www.nihr.ac.uk). The DSU were funded by the NICE DSU Grant. Visit the DSU website for further project information (http://nicedsu.org.uk/).

Conflict of interest

Becky Pennington, Shije Ren, Samantha Barton, Mariana Bacelar and Steven J. Edwards report no conflicts of interest.

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Pennington, B., Ren, S., Barton, S. et al. Dinutuximab Beta for Treating Neuroblastoma: An Evidence Review Group and Decision Support Unit Perspective of a NICE Single Technology Appraisal. PharmacoEconomics 37, 985–993 (2019). https://doi.org/10.1007/s40273-018-0744-0

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  • DOI: https://doi.org/10.1007/s40273-018-0744-0

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