| Literature DB >> 35601839 |
Minmin Zhang1, Guihua Wang1, Jun Li2, Wallace J Hopp2, David D Lee3.
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has disrupted normal operating procedures at transplant centers. With the possibility that COVID-19 infection carries an overall 4% mortality rate and potentially a 24% mortality rate among the immunocompromised transplant recipients, many transplant centers considered the possibility of slowing down and even potentially pausing all transplants. Many proposals regarding the need for pausing organ transplants exist; however, much remains unknown. Whereas the impact of the COVID-19 pandemic on the overall healthcare system is unknown, the potential impact of pausing organ transplants over a period can be estimated. This study presents a model for evaluating the impact of pausing liver transplants over a spectrum of model for end-stage liver disease-sodium (MELD-Na) scores. Our model accounts for two potential risks of a pause: (1) the waitlist mortality of all patients who do not receive liver transplants during the pause period, and (2) the impact of a longer waiting list due to the pause of liver transplants and the continuous accrual of new patients. Using over 12 years of liver transplant data from the United Network for Organ Sharing and a system of differential equations, we estimate the threshold probability above which a decision maker should pause liver transplants to reduce the loss of patient life months. We also compare different pause policies to illustrate the value of patient-specific and center-specific approaches. Finally, we analyze how capacity constraints affect the loss of patient life months and the length of the waiting list. The results of this study are useful to decision makers in deciding whether and how to pause organ transplants during a pandemic. The results are also useful to patients (and their care providers) who are waiting for organ transplants.Entities:
Keywords: COVID‐19 pandemic; healthcare operations; organ transplant
Year: 2022 PMID: 35601839 PMCID: PMC9115406 DOI: 10.1111/poms.13697
Source DB: PubMed Journal: Prod Oper Manag ISSN: 1059-1478 Impact factor: 4.638
Description of key parameters
| Parameter | Description | DEs | PLMs | Data |
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| Arrival rate |
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| Transplant rate |
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| Waitlist mortality rate (individual) |
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| Inactivation rate (individual) |
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| Transition rate (individual) |
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| Number of patients on the waiting list at time |
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| Pause policy |
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| Duration of a pause |
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| Extra deaths due to a pause |
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| Extra deteriorations due to a pause |
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| Expected life months without an organ transplant |
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| Expected life months with an organ transplant |
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| Expected life months for a patient who becomes inactive |
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| Expected life months for a patient in category |
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| The first period under consideration |
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| The second period under consideration |
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| Probability of mortality due to the pandemic during |
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| Probability of mortality due to the pandemic during |
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Note: This table describes the key parameters used in this paper. The subscript indicates the category of patients. The last three columns indicate whether a parameter is used in the system of differential equations (DEs), calculation of the loss of patient life months (PLMs), or empirical estimation from the data.
FIGURE 1Illustration of different pause policies Note: This figure depicts different pause policies. Under the complete shutdown policy, the decision maker does not consider the difference between patients and pauses all categories for the same period. Under the tiered shutdown policy, the decision maker considers the difference between patients and pauses categories 1 to for the same period. Under the nation‐guidance policy, the decision maker does not consider the difference between centers and pauses organ transplants in different centers in the same way. Under the center‐specific policy, the decision maker considers the difference between centers and pauses organ transplants in different centers in center‐specific ways.
FIGURE 2Regions defined by United Network for Organ Sharing (UNOS). Note: This figure depicts the regions defined by UNOS for organ procurement and allocation. More details about these regions are available at https://unos.org/community/regions/.
Summary statistics for the liver transplant
| Variable | Description | Mean | Std. dev. |
|---|---|---|---|
| Patient features | |||
| Age | Patient's age at registration | 54.0 | 10.9 |
| Gender female | Patient's gender is female | 0.38 | 0.49 |
| Race Black | Patient's race is Black | 0.08 | 0.28 |
| Blood type AB | Patient's blood type is AB | 0.04 | 0.19 |
| Blood type B | Patient's blood type is B | 0.12 | 0.32 |
| Blood type O | Patient's blood type is O | 0.47 | 0.50 |
| Malignancy all | Patient has known malignancies | 0.11 | 0.32 |
| Private insurance | Patient has private insurance | 0.24 | 0.42 |
| Previous transplant | Patient had a transplant before | 0.02 | 0.15 |
| Diagnoses | |||
| Alcoholic liver disease | Patient has alcoholic liver disease | 0.28 | 0.45 |
| Cholestatic liver disease | Patient has cholestatic liver disease | 0.08 | 0.27 |
| Cirrhosis viral hepatitis | Patient has hepatitis B or C | 0.23 | 0.42 |
| Fatty liver | Patient has fatty liver | 0.13 | 0.33 |
| Malignancy | Patient has known malignancies | 0.06 | 0.24 |
| Metabolic liver disease | Patient has metabolic liver disease | 0.03 | 0.16 |
| Other | Patient has other diagnoses | 0.20 | 0.40 |
| MELD‐Na | |||
| 5–10 | Patient's MELD‐Na score is between 5 and 10 | 0.16 | 0.37 |
| 11–15 | Patient's MELD‐Na score is between 11 and 15 | 0.20 | 0.40 |
| 16–20 | Patient's MELD‐Na score is between 16 and 20 | 0.21 | 0.41 |
| 21–25 | Patient's MELD‐Na score is between 21 and 25 | 0.15 | 0.36 |
| 26–30 | Patient's MELD‐Na score is between 26 and 30 | 0.11 | 0.31 |
| 31–35 | Patient's MELD‐Na score is between 31 and 35 | 0.08 | 0.27 |
| 36–40 | Patient's MELD‐Na score is between 36 and 40 | 0.09 | 0.29 |
| Number of observations | 128,098 | ||
Note: The malignancy in the diagnoses category includes hepatoma and cirrhosis, fibrolamellar, cholangiocarcinoma, hepatoblastoma, hemangioendothelioma, hemangiosarcoma, angiosarcoma, any other specify (e.g., klatskin tumor, leiomyosarcoma), bile duct cancer, and secondary hepatic malignancy.
Basic information at the country level and the center level
| Parameter | Country | Center A | Center B | Center C |
|---|---|---|---|---|
| (1) Arrival rate (per day) | 21.6 | 0.6 | 0.3 | 0.3 |
| (2) Transplant rate (per day) | 8.5 | 0.2 | 0.2 | 0.1 |
| (3) Mortality rate (%) | 0.04 | 0.04 | 0.03 | 0.05 |
| (4) Inactivation rate (%) | 0.08 | 0.04 | 0.10 | 0.08 |
| (5) ELMs with LT (months) | 93.5 | 108.3 | 75.8 | 88.4 |
| (6) ELMs without LT (months) | 30.6 | 26.5 | 17.3 | 53.0 |
Note: Mortality and inactivation rates are for individuals. Center A locates in California and has one of the largest transplant programs in the country for more than 60 years. Center B locates in Pennsylvania and has been a pioneer in organ transplants for more than 50 years. Center C locates in Pennsylvania and is a leader in organ transplants for more than 40 years.
Abbreviations: ELMs, expected life months; LT, liver transplant.
Rates of transition and mortality for individuals at the country level
| MELD‐Na | 6–10 | 11–15 | 16–20 | 21–25 | 26–30 | 31–35 | 36–40 | Death |
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| 6–10 | 99.81 | 0.09 | 0.02 | 0.01 | 0.00 | 0.00 | 0.00 | 0.01 |
| 11–15 | 0.11 | 99.58 | 0.20 | 0.03 | 0.01 | 0.00 | 0.00 | 0.01 |
| 16–20 | 0.03 | 0.24 | 99.24 | 0.30 | 0.05 | 0.01 | 0.00 | 0.03 |
| 21–25 | 0.01 | 0.08 | 0.50 | 98.49 | 0.54 | 0.08 | 0.02 | 0.06 |
| 26–30 | 0.01 | 0.04 | 0.22 | 1.37 | 96.08 | 1.29 | 0.18 | 0.17 |
| 31–35 | 0.00 | 0.01 | 0.09 | 0.43 | 2.45 | 92.01 | 2.50 | 0.43 |
| 36–40 | 0.00 | 0.00 | 0.03 | 0.10 | 0.38 | 1.17 | 90.00 | 1.65 |
Note: All rates are in percentages.
Abbreviation: MELD‐Na, model for end‐stage liver disease‐sodium.
Results from the survival model estimated at the country level
| Variable | Coefficient | Standard error |
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| MELD‐Na | ||
| 5–10 | 3.7383 | 0.0281 |
| 11–15 | 3.2921 | 0.0276 |
| 16–20 | 2.5172 | 0.0268 |
| 21–25 | 1.8862 | 0.0266 |
| 26–30 | 1.1750 | 0.0283 |
| 31–35 | 0.6713 | 0.0296 |
| 36–40 | Control | |
| Transplant | 2.2010 | 0.0360 |
| MELD‐Na | ||
| 5–10 | −2.5112 | 0.0936 |
| 11–15 | −1.9500 | 0.0641 |
| 16–20 | −1.3152 | 0.0492 |
| 21–25 | −1.0328 | 0.0475 |
| 26–30 | −0.6432 | 0.0485 |
| 31–35 | −0.3539 | 0.0510 |
| 36–40 | Control | |
| Patient features | Included | |
| Number of observations | 103,320 | |
| LR | 31,354 | |
Abbreviation: MELD‐Na, model for end‐stage liver disease‐sodium.
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Description of scenarios and policies to pause organ transplants
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| Nation/tiered | Center/tiered |
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| 1 | 15 | 350 | {0.4, 0.4, | 0.5 | {1} | {1} |
| 2 | 15 | 350 | {0.4, 0.4, | 1.0 | {1, 2} | {1} |
| 3 | 30 | 335 | {0.4, 0.4, | 0.5 | {1, 2} | {1} |
| 4 | 15 | 350 | {0.2, 0.2, | 0.5 | {1} |
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Note: The left part of this table describes different scenarios, in which and indicate the periods under consideration, and and indicate the probabilities of mortality due to the pandemic over the periods. The right part of the table summarizes different policies, in which the numbers in the bracket indicate the categories to be paused. The duration of the pause is 30 days for all scenarios. The center‐specific tiered shutdown policy is calculated based on the data of center A.
Comparison between different pause policies for country and center
| Country‐level analysis | Center‐level analysis | |||
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| Loss of life months | Nation/complete | Nation/tiered | Nation/tiered | Center/tiered |
| Scenario 1 | {1, | {1} | {1} | {1} |
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| 62203.8 | 54653.0 | 1320.4 | 1320.4 |
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| 54711.3 | 54711.3 | 1322.0 | 1322.0 |
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| 7492.5 | −58.3 | −1.6 | −1.6 |
| Scenario 2 | {1, | {1, 2} | {1, 2} | {1} |
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| 110436.1 | 104960.6 | 2538.5 | 2536.4 |
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| 105103.3 | 105103.3 | 2539.6 | 2539.6 |
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| 5332.8 | −142.7 | −1.1 | −3.2 |
| Scenario 3 | {1, | {1, 2} | {1, 2} | {1} |
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| 62203.8 | 56728.2 | 1373.1 | 1371.0 |
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| 56871.0 | 56871.0 | 1374.2 | 1374.2 |
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| 5332.8 | −142.8 | −1.1 | −3.2 |
| Scenario 4 | {1, | {1} | {1} |
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| 38087.6 | 27336.3 | 661.9 | 661.0 |
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| 27355.7 | 27355.7 | 661.0 | 661.0 |
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| 10731.9 | −19.4 | 0.9 | 0.0 |
Note: This table compares (all units are in months) across different pause policies. In scenario 1, we let , , , and . In scenario 2, we let . In scenario 3, we let and . In scenario 4, we let = .
Threshold probability under nation‐guidance tiered shutdown policy
| MELD‐Na | Threshold probability |
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| 6–10 | 0.075 |
| 11–15 | 0.236 |
| 16–20 | 0.449 |
| 21–25 | 0.567 |
| 26–30 | 0.651 |
| 31–35 | 0.683 |
| 36–40 | 0.647 |
Note: This table shows the threshold probability above which a country‐level decision maker should pause transplants. For example, a decision maker should not pause any transplant if the probability of mortality is lower than 0.075, and should pause transplants for only patients with MELD‐Na scores below 11 if the probability of mortality is higher than or equal to 0.075 but lower than 0.236.
Abbreviation: MELD‐Na, model for end‐stage liver disease‐sodium.
Threshold probability under center‐specific tiered shutdown policy
| MELD‐Na | Center A | Center B | Center C |
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| 6–10 | 0.205 | 0.209 | 0.183 |
| 11–15 | 0.377 | 0.392 | 0.294 |
| 16–20 | 0.584 | 0.573 | 0.422 |
| 21–25 | 0.680 | 0.734 | 0.521 |
| 26–30 | 0.746 | 0.861 | 0.579 |
| 31–35 | 0.803 | 0.861 | 0.635 |
| 36–40 | 0.778 | 0.898 | 0.658 |
Note: This table shows the threshold probability above which a center‐level decision maker should pause transplants.
Abbreviation: MELD‐Na, model for end‐stage liver disease‐sodium.
FIGURE 3Impact of overall‐capacity constraints on the loss of patient life months. Note: This figure depicts the impact of overall‐capacity constraints on the loss of patient life months. The results are estimated based on scenario 1 (see Table 6) and the nation‐guidance tiered shutdown policy.
FIGURE 4Impact of the overall‐capacity constraints on waitlist length. Note: This figure depicts the impact of overall‐capacity constraints on the average number of extra patients on the waiting list. The results are estimated based on scenario 1 (see Table 6) and the nation‐guidance tiered shutdown policy.