Recommendations for economic evaluations of cell and gene therapies: a systematic literature review with critical appraisal

ABSTRACT

Objective

No consensus exists on the ideal methodology to evaluate the economic impact and value of new, potentially curative gene therapies. We aimed to identify and describe published methodologic recommendations for the economic evaluation of gene therapies and assess whether these recommendations have been applied in published evaluations.

Methods

This study was conducted in three stages: a systematic literature review of methodologic recommendations for economic evaluation of gene therapies; an assessment of the appropriateness of recommendations; and a review to assess the degree to which the recommendations were applied in published evaluations.

Results

A total of 2,888 references were screened, 83 articles were reviewed to assess eligibility, and 20 papers were included. Fifty recommendations were identified, and 21 reached consensus thresholds. Most evaluations were based on naive treatment comparisons and did not apply consensus recommendations. Innovative payment mechanisms for gene therapies were rarely considered. The only widely applied recommendations related to modeling choices and methods.

Conclusions

Methodological recommendations for economic evaluations of gene therapies are generally not being followed. Assessing the applicability and impact of the recommendations from this study may facilitate the implementation of consensus recommendations in future evaluations.

KEYWORDS:

• Cost-effectiveness analysis
• economic evaluation
• gene therapy
• health technology assessments
• health-related quality of life
• onasemnogene abeparvovec
• spinal muscular atrophy
• systematic literature review

Article highlights

• Currently, no consensus exists on the ideal methodology to evaluate the economic impact and benefits of new, potentially curative gene therapies, so novel approaches for economic evaluations of gene therapies are needed.

• Fifty methodologic recommendations for the economic evaluation of gene therapies were identified in the published literature, summarized, and critically appraised, with 21 recommendations reaching consensus thresholds and then assessed for applicability and impact in the published economic evaluations.

• Our study found that most evaluations were based on naive treatment comparisons and did not apply consensus recommendations, innovative payment mechanisms for gene therapies were rarely considered, and the only widely applied recommendations related to modeling choices and methods.

• Although analysts conducting economic evaluations of gene therapies have access to many publications that provide methodologic recommendations and guidelines, these published recommendations are generally not being followed.

• Assessing the applicability and impact of the recommendations from this study may facilitate the implementation of consensus recommendations in future economic evaluations of gene therapies to assist with reimbursement and funding challenges for existing healthcare payment structures.

Acknowledgments

Editorial support was provided by Wynne Dillon, MS, of Kay Square Scientific. This support was funded by Novartis Gene Therapies, Inc.

Declaration of interest

M Toumi and S Aballea are former employees of Creativ-Ceutical and consultants for Novartis Gene Therapies, Inc. (NGT). O Dabbous is an employee of NGT and owns stock/other equities. S Sullivan is a consultant for AbbVie, Bayer, Incyte, Nanoscope, Neurocrine, NGT, Novo Nordisk, and Spark Therapeutics. P Neumann served on advisory boards/as a consultant for AbbVie, Amgen, Bayer, the Congressional Budget Office, Janssen, Merck, NGT, Novartis, Novo Nordisk, Vertex, and Curta Inc., and received research grants from the Alzheimer’s Association, Amgen, the Bill and Melinda Gates Foundation, Lundbeck, the National Institutes of Health, and the National Pharmaceutical Council. J-M Graf von der Schulenburg and M Drummond are consultants for NGT. S Tunis has received honoraria from NGT and served on advisory boards for BioMarin and UCB Pharma. D Malone has served as a consultant for Novartis, NGT, Sarepta, Pharmacyclics, Currax, and Seres, and served on advisory boards for BioMarin and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Manuscript concept and design: all. Drafting of manuscript: all. Critical reviews: all. All authors approved and agreed for the final version of the manuscript to be published.

Additional information

Funding

This study was funded by Novartis Gene Therapies, Inc.