Clinical impact of a modified lung allocation score that mitigates selection bias

https://doi.org/10.1016/j.healun.2022.08.003Get rights and content

Background

The Lung Allocation Score (LAS) is used in the U.S. to prioritize lung transplant candidates. Selection bias, induced by dependent censoring of waitlisted candidates and prediction of posttransplant survival among surviving, transplanted patients only, is only partially addressed by the LAS. Recently, a modified LAS (mLAS) was designed to mitigate such bias. Here, we estimate the clinical impact of replacing the LAS with the mLAS.

Methods

We considered lung transplant candidates waitlisted during 2016 and 2017. LAS and mLAS scores were computed for each registrant at each observed organ offer date; individuals were ranked accordingly. Patient characteristics associated with better priority under the mLAS were investigated via logistic regression and generalized linear mixed models. We also determined whether differences in rank were explained more by changes in predicted pre- or posttransplant survival. Simulations examined how 1-year waitlist, posttransplant, and overall survival might change under the mLAS.

Results

Diagnosis group, 6-minute walk distance, continuous mechanical ventilation, functional status, and age demonstrated the highest impact on differential allocation. Differences in rank were explained more by changes in predicted pretransplant survival than changes in predicted posttransplant survival, suggesting that selection bias has more impact on estimates of waitlist urgency. Simulations suggest that for every 1000 waitlisted individuals, 12.8 (interquartile range: 5.2-24.3) fewer waitlist deaths per year would occur under the mLAS, without compromising posttransplant and overall survival.

Conclusions

Implementing a mLAS that mitigates selection bias into clinical practice can lead to important differences in allocation and possibly modest improvement in waitlist survival.

Section snippets

Methods

This study utilizes pre- and postlung transplant data from the United Network for Organ Sharing (UNOS). Our cohort consisted of all patients 18 years or older who were listed for single or bi-lateral lung transplantation in the United States between January 1, 2016 and December 31, 2017. This cohort is consistent with the testing cohort used in Schnellinger et al (2021),4 and ensures that enough follow-up time accrued among transplanted patients to evaluate 1-year posttransplant survival.

We

Observed analyses

Table 1 summarizes the demographic and clinical characteristics of the complete waiting list population as well as the subset of individuals who received transplant. In the full waitlist population, covariates were measured at the time of waitlist registration; among the subset of transplanted individuals, covariates are shown both at the time of waitlist registration and at the time of transplantation. In the full waitlist population, the median waiting time was 57 days (interquartile range,

Discussion

In this study, we used observed and simulated data to examine the clinical impact of a mLAS score designed to mitigate selection bias. We found that changes in prioritization were more pronounced for patients with certain demographic and clinical characteristics, such as diagnosis group (individuals with restrictive lung disease were more likely to receive better priority), 6-minute walk distance (individuals in the third quartile of walk distance had the highest probability of receiving better

Ethics approval and consent to participate

The study protocol was reviewed by University of Pennsylvania's Institutional Review Board (IRB Protocol #833089) and determined to not meet the definition of human subjects research.

Consent for publication

This manuscript has not been published and is not under consideration for publication elsewhere.

Availability of data and materials

The data that support the findings of this study are available from the United Network for Organ Sharing (UNOS). The authors do not have the authority to share UNOS data; researchers interested in accessing this data must submit a request to UNOS directly. All code is available upon request to the corresponding author, Ms. Erin M. Schnellinger.

Authors’ contributions

All authors contributed to the study's conception and design. Ms. Schnellinger carried out the statistical analyses, and drafted the initial manuscript and revised it based on the critical review and scientific input of Drs Cantu, Schaubel, Kimmel, and Stephens-Shields.

Disclosure statement

The authors have no conflicts of interest to declare.

The authors thank the Editors and Referees for their helpful feedback, which strengthened the manuscript.

This work was funded by the NIH F31HL194338 from the National Heart, Lung, and Blood Institute (NHLBI). DES was partly supported by NIH R01-DK070869 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The funder had no role in the design of the study or the collection, the analysis, and interpretation of the

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