TY - JOUR
T1 - External validation of existing dementia prediction models on observational health data
AU - John, Luis H.
AU - Kors, Jan A.
AU - Fridgeirsson, Egill A.
AU - Reps, Jenna M.
AU - Rijnbeek, Peter R.
N1 - Funding Information: Jenna M. Reps is an employee of Janssen Research & Development and shareholder of Johnson & Johnson. Peter R. Rijnbeek, Egill A. Fridgeirsson, Luis H. John, Jan A. Kors work for a research group who received unconditional research grants from Boehringer-Ingelheim, GSK, Janssen Research & Development, Novartis, Pfizer, Yamanouchi, Servier. None of these grants result in a conflict of interest to the content of this paper. Funding Information: This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 806968. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. Publisher Copyright: © 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Background: Many dementia prediction models have been developed, but only few have been externally validated, which hinders clinical uptake and may pose a risk if models are applied to actual patients regardless. Externally validating an existing prediction model is a difficult task, where we mostly rely on the completeness of model reporting in a published article. In this study, we aim to externally validate existing dementia prediction models. To that end, we define model reporting criteria, review published studies, and externally validate three well reported models using routinely collected health data from administrative claims and electronic health records. Methods: We identified dementia prediction models that were developed between 2011 and 2020 and assessed if they could be externally validated given a set of model criteria. In addition, we externally validated three of these models (Walters’ Dementia Risk Score, Mehta’s RxDx-Dementia Risk Index, and Nori’s ADRD dementia prediction model) on a network of six observational health databases from the United States, United Kingdom, Germany and the Netherlands, including the original development databases of the models. Results: We reviewed 59 dementia prediction models. All models reported the prediction method, development database, and target and outcome definitions. Less frequently reported by these 59 prediction models were predictor definitions (52 models) including the time window in which a predictor is assessed (21 models), predictor coefficients (20 models), and the time-at-risk (42 models). The validation of the model by Walters (development c-statistic: 0.84) showed moderate transportability (0.67–0.76 c-statistic). The Mehta model (development c-statistic: 0.81) transported well to some of the external databases (0.69–0.79 c-statistic). The Nori model (development AUROC: 0.69) transported well (0.62–0.68 AUROC) but performed modestly overall. Recalibration showed improvements for the Walters and Nori models, while recalibration could not be assessed for the Mehta model due to unreported baseline hazard. Conclusion: We observed that reporting is mostly insufficient to fully externally validate published dementia prediction models, and therefore, it is uncertain how well these models would work in other clinical settings. We emphasize the importance of following established guidelines for reporting clinical prediction models. We recommend that reporting should be more explicit and have external validation in mind if the model is meant to be applied in different settings.
AB - Background: Many dementia prediction models have been developed, but only few have been externally validated, which hinders clinical uptake and may pose a risk if models are applied to actual patients regardless. Externally validating an existing prediction model is a difficult task, where we mostly rely on the completeness of model reporting in a published article. In this study, we aim to externally validate existing dementia prediction models. To that end, we define model reporting criteria, review published studies, and externally validate three well reported models using routinely collected health data from administrative claims and electronic health records. Methods: We identified dementia prediction models that were developed between 2011 and 2020 and assessed if they could be externally validated given a set of model criteria. In addition, we externally validated three of these models (Walters’ Dementia Risk Score, Mehta’s RxDx-Dementia Risk Index, and Nori’s ADRD dementia prediction model) on a network of six observational health databases from the United States, United Kingdom, Germany and the Netherlands, including the original development databases of the models. Results: We reviewed 59 dementia prediction models. All models reported the prediction method, development database, and target and outcome definitions. Less frequently reported by these 59 prediction models were predictor definitions (52 models) including the time window in which a predictor is assessed (21 models), predictor coefficients (20 models), and the time-at-risk (42 models). The validation of the model by Walters (development c-statistic: 0.84) showed moderate transportability (0.67–0.76 c-statistic). The Mehta model (development c-statistic: 0.81) transported well to some of the external databases (0.69–0.79 c-statistic). The Nori model (development AUROC: 0.69) transported well (0.62–0.68 AUROC) but performed modestly overall. Recalibration showed improvements for the Walters and Nori models, while recalibration could not be assessed for the Mehta model due to unreported baseline hazard. Conclusion: We observed that reporting is mostly insufficient to fully externally validate published dementia prediction models, and therefore, it is uncertain how well these models would work in other clinical settings. We emphasize the importance of following established guidelines for reporting clinical prediction models. We recommend that reporting should be more explicit and have external validation in mind if the model is meant to be applied in different settings.
KW - Alzheimer
KW - Dementia
KW - External validation
KW - Patient-level prediction
KW - Prognostic model
KW - Transportability
UR - http://www.scopus.com/inward/record.url?scp=85143372891&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s12874-022-01793-5
DO - https://doi.org/10.1186/s12874-022-01793-5
M3 - Article
C2 - 36471238
SN - 1471-2288
VL - 22
JO - BMC medical research methodology
JF - BMC medical research methodology
IS - 1
M1 - 311
ER -