An evaluation of the replicability of analyses using synthetic health data
- PMID: 38521806
- PMCID: PMC10960851
- DOI: 10.1038/s41598-024-57207-7
An evaluation of the replicability of analyses using synthetic health data
Abstract
Synthetic data generation is being increasingly used as a privacy preserving approach for sharing health data. In addition to protecting privacy, it is important to ensure that generated data has high utility. A common way to assess utility is the ability of synthetic data to replicate results from the real data. Replicability has been defined using two criteria: (a) replicate the results of the analyses on real data, and (b) ensure valid population inferences from the synthetic data. A simulation study using three heterogeneous real-world datasets evaluated the replicability of logistic regression workloads. Eight replicability metrics were evaluated: decision agreement, estimate agreement, standardized difference, confidence interval overlap, bias, confidence interval coverage, statistical power, and precision (empirical SE). The analysis of synthetic data used a multiple imputation approach whereby up to 20 datasets were generated and the fitted logistic regression models were combined using combining rules for fully synthetic datasets. The effects of synthetic data amplification were evaluated, and two types of generative models were used: sequential synthesis using boosted decision trees and a generative adversarial network (GAN). Privacy risk was evaluated using a membership disclosure metric. For sequential synthesis, adjusted model parameters after combining at least ten synthetic datasets gave high decision and estimate agreement, low standardized difference, as well as high confidence interval overlap, low bias, the confidence interval had nominal coverage, and power close to the nominal level. Amplification had only a marginal benefit. Confidence interval coverage from a single synthetic dataset without applying combining rules were erroneous, and statistical power, as expected, was artificially inflated when amplification was used. Sequential synthesis performed considerably better than the GAN across multiple datasets. Membership disclosure risk was low for all datasets and models. For replicable results, the statistical analysis of fully synthetic data should be based on at least ten generated datasets of the same size as the original whose analyses results are combined. Analysis results from synthetic data without applying combining rules can be misleading. Replicability results are dependent on the type of generative model used, with our study suggesting that sequential synthesis has good replicability characteristics for common health research workloads.
© 2024. The Author(s).
Conflict of interest statement
This work was performed in collaboration with Replica Analytics Ltd. This company is a spin-off from the Children’s Hospital of Eastern Ontario Research Institute. KEE is co-founder and has equity in this company. LM and XF are data scientists employed by Replica Analytics Ltd. AAH has no competing interests.
Figures






Similar articles
-
Augmenting Insufficiently Accruing Oncology Clinical Trials Using Generative Models: Validation Study.J Med Internet Res. 2025 Mar 5;27:e66821. doi: 10.2196/66821. J Med Internet Res. 2025. PMID: 40053790 Free PMC article.
-
Validating a membership disclosure metric for synthetic health data.JAMIA Open. 2022 Oct 11;5(4):ooac083. doi: 10.1093/jamiaopen/ooac083. eCollection 2022 Dec. JAMIA Open. 2022. PMID: 36238080 Free PMC article.
-
Evaluating the Utility and Privacy of Synthetic Breast Cancer Clinical Trial Data Sets.JCO Clin Cancer Inform. 2023 Sep;7:e2300116. doi: 10.1200/CCI.23.00116. JCO Clin Cancer Inform. 2023. PMID: 38011617 Free PMC article.
-
Validation Assessment of Privacy-Preserving Synthetic Electronic Health Record Data: Comparison of Original Versus Synthetic Data on Real-World COVID-19 Vaccine Effectiveness.Pharmacoepidemiol Drug Saf. 2024 Oct;33(10):e70019. doi: 10.1002/pds.70019. Pharmacoepidemiol Drug Saf. 2024. PMID: 39375947
-
Federated learning for generating synthetic data: a scoping review.Int J Popul Data Sci. 2023 Oct 31;8(1):2158. doi: 10.23889/ijpds.v8i1.2158. eCollection 2023. Int J Popul Data Sci. 2023. PMID: 38414544 Free PMC article.
Cited by
-
Augmenting Insufficiently Accruing Oncology Clinical Trials Using Generative Models: Validation Study.J Med Internet Res. 2025 Mar 5;27:e66821. doi: 10.2196/66821. J Med Internet Res. 2025. PMID: 40053790 Free PMC article.
-
Synthetic Data in Healthcare and Drug Development: Definitions, Regulatory Frameworks, Issues.CPT Pharmacometrics Syst Pharmacol. 2025 May;14(5):840-852. doi: 10.1002/psp4.70021. Epub 2025 Apr 7. CPT Pharmacometrics Syst Pharmacol. 2025. PMID: 40193292 Free PMC article. Review.
-
Semisynthetic simulation for microbiome data analysis.Brief Bioinform. 2024 Nov 22;26(1):bbaf051. doi: 10.1093/bib/bbaf051. Brief Bioinform. 2024. PMID: 39927858 Free PMC article. Review.
-
Synthetic data generation methods in healthcare: A review on open-source tools and methods.Comput Struct Biotechnol J. 2024 Jul 9;23:2892-2910. doi: 10.1016/j.csbj.2024.07.005. eCollection 2024 Dec. Comput Struct Biotechnol J. 2024. PMID: 39108677 Free PMC article. Review.
-
To be or not to be, when synthetic data meet clinical pharmacology: A focused study on pharmacogenetics.CPT Pharmacometrics Syst Pharmacol. 2025 Jan;14(1):82-94. doi: 10.1002/psp4.13240. Epub 2024 Oct 16. CPT Pharmacometrics Syst Pharmacol. 2025. PMID: 39412034 Free PMC article.
References
-
- Wang, Z., Myles, P. & Tucker, A. Generating and evaluating synthetic UK primary care data: Preserving data utility patient privacy. In 2019 IEEE 32nd International Symposium on Computer-Based Medical Systems (CBMS), Cordoba. 126–31. 10.1109/CBMS.2019.00036 (2019).
-
- Wang Z, Myles P, Tucker A. Generating and evaluating cross-sectional synthetic electronic healthcare data: Preserving data utility and patient privacy. Comput. Intell. 2021;37:819–851. doi: 10.1111/coin.12427. - DOI
MeSH terms
Grants and funding
LinkOut - more resources
Full Text Sources