Assessing the International Transferability of a Machine Learning Model for Detecting Medication Error in the General Internal Medicine Clinic: Multicenter Preliminary Validation Study
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Previously, we had developed a machine learning (ML) model based on Taiwan’s local databases (TLD) to address this issue. However, the international transferability of this model is unclear. This study examines the international transferability of a machine learning model for detecting medication errors and whether the federated learning approach could further improve the accuracy of the model. |
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Medication errors are a major contributor to morbidity and mortality. Although the exact number of deaths related to medical errors is still under debate, the To Err Is Human report estimated that the figure might be approximately 44,000 to 98,000 per year in the United States alone. Medication errors also result in excess health care–related costs, which are estimated at more than US $20 billion per year in the United States.
Preventable adverse drug events (ADEs) also appear to be common not only in the hospital but also in the ambulatory setting, with one estimate amounting to US $1.8 billion annually for treating them. Reducing medication errors is crucial to enhance health care quality and improve patient safety. However, considering the time and cost needed, it is impossible for hospitals to double-check every prescription made by every physician in real time.
To combat this problem, studies have shown that health information technology (IT) presents a viable solution . Among all IT tools, clinical decision support systems that can provide real-time alerts have demonstrated perhaps more effective in helping physicians to prevent medication errors. However, the impact of these applications has been variable. In addition, the vast majority of the currently deployed alert systems are rule based, which means that they have explicitly coded logic written to identify medication errors. However, these rule-based systems are generally set to go off too frequently because of the lack of adaptability in clinical practice, leading to alert fatigue, which in turn can increase ADE rates.
Machine learning (ML) has shown promising results in medicine and health care, especially in relation to clinical documentation and prescription prediction. Unsupervised learning, which is a type of ML algorithm used to establish relationships within data sets without labels, combined with a well-curated and large data set of prescriptions has the potential to generate algorithmic models to minimize prescription errors. Previously, we had presented an ML model that evaluated whether a prescription was explicitly substantiated (by way of diagnosis or other medications) and prevented medication errors from occurring. The model was named as the appropriateness of prescription (AOP) model. It contained disease-medication (D-M) associations and medication-medication (M-M) associations that were identified through unsupervised association rule learning.
These associations were generated based on prescription data from Taiwan’s local databases (TLD), which had collected health information from nearly the entire Taiwanese population (about 23 million people) for over 20 years. The AOP model has been validated in 5 Taiwanese hospitals and continues to have high accuracy (over 80%) and high sensitivity (80%-96%), highlighting the model’s potential to have a true clinical impact.
As physicians in Taiwan are educated with the same evidence-based guidelines as physicians in the United States, in theory, the experience-based ML model generated from TLD could be transferable to US clinical practice. However, there is no validation study that examines the transferability of the TLD-developed ML model in US health care systems. Although there are a few research studies demonstrating the feasibility of transferring ML models across health care institutions, one of the major challenges to the transferability of ML models in health care is that most of these models are trained using single-site data sets that may be insufficiently large or diverse.
Recently, federated learning has become an emerging technique to address the issues of isolated data islands and privacy, in which each distinct data federate trains their own model with their own data before all the federates aggregate their results. In our study, we undertook a cross-national multicenter study to validate the performance of the AOP model in detecting the explicit substantiation of prescriptions using an enriched data set from the electronic health record (EHR) system of Brigham Women’s Hospital (BWH) and Massachusetts General Hospital (MGH). Both are Harvard Medical School teaching hospitals. To the best of our knowledge, this is the first cross-national multicenter study to examine the transferability of an ML model for the detection of medication errors. Detailed analyses were conducted to evaluate the effectiveness of the AOP model, and a federated learning approach was applied to explore the potential to construct a model with better performance using cross-national data sets.
Preventable adverse drug events (ADEs) also appear to be common not only in the hospital but also in the ambulatory setting, with one estimate amounting to US $1.8 billion annually for treating them. Reducing medication errors is crucial to enhance health care quality and improve patient safety. However, considering the time and cost needed, it is impossible for hospitals to double-check every prescription made by every physician in real time.
To combat this problem, studies have shown that health information technology (IT) presents a viable solution . Among all IT tools, clinical decision support systems that can provide real-time alerts have demonstrated perhaps more effective in helping physicians to prevent medication errors. However, the impact of these applications has been variable. In addition, the vast majority of the currently deployed alert systems are rule based, which means that they have explicitly coded logic written to identify medication errors. However, these rule-based systems are generally set to go off too frequently because of the lack of adaptability in clinical practice, leading to alert fatigue, which in turn can increase ADE rates.
Machine learning (ML) has shown promising results in medicine and health care, especially in relation to clinical documentation and prescription prediction. Unsupervised learning, which is a type of ML algorithm used to establish relationships within data sets without labels, combined with a well-curated and large data set of prescriptions has the potential to generate algorithmic models to minimize prescription errors. Previously, we had presented an ML model that evaluated whether a prescription was explicitly substantiated (by way of diagnosis or other medications) and prevented medication errors from occurring. The model was named as the appropriateness of prescription (AOP) model. It contained disease-medication (D-M) associations and medication-medication (M-M) associations that were identified through unsupervised association rule learning.
These associations were generated based on prescription data from Taiwan’s local databases (TLD), which had collected health information from nearly the entire Taiwanese population (about 23 million people) for over 20 years. The AOP model has been validated in 5 Taiwanese hospitals and continues to have high accuracy (over 80%) and high sensitivity (80%-96%), highlighting the model’s potential to have a true clinical impact.
As physicians in Taiwan are educated with the same evidence-based guidelines as physicians in the United States, in theory, the experience-based ML model generated from TLD could be transferable to US clinical practice. However, there is no validation study that examines the transferability of the TLD-developed ML model in US health care systems. Although there are a few research studies demonstrating the feasibility of transferring ML models across health care institutions, one of the major challenges to the transferability of ML models in health care is that most of these models are trained using single-site data sets that may be insufficiently large or diverse.
Recently, federated learning has become an emerging technique to address the issues of isolated data islands and privacy, in which each distinct data federate trains their own model with their own data before all the federates aggregate their results. In our study, we undertook a cross-national multicenter study to validate the performance of the AOP model in detecting the explicit substantiation of prescriptions using an enriched data set from the electronic health record (EHR) system of Brigham Women’s Hospital (BWH) and Massachusetts General Hospital (MGH). Both are Harvard Medical School teaching hospitals. To the best of our knowledge, this is the first cross-national multicenter study to examine the transferability of an ML model for the detection of medication errors. Detailed analyses were conducted to evaluate the effectiveness of the AOP model, and a federated learning approach was applied to explore the potential to construct a model with better performance using cross-national data sets.
Chin YPH, Song W, Lien CE, Yoon CH, Wang W, Liu J, Nguyen PA, Feng YT, Zhou L, Li YCJ, Bates DW
Assessing the International Transferability of a Machine Learning Model for Detecting Medication Error in the General Internal Medicine Clinic: Multicenter Preliminary Validation Study. JMIR Med Inform 2021;9(1):e23454
doi: 10.2196/23454
PMID: 33502331
Assessing the International Transferability of a Machine Learning Model for Detecting Medication Error in the General Internal Medicine Clinic: Multicenter Preliminary Validation Study. JMIR Med Inform 2021;9(1):e23454
doi: 10.2196/23454
PMID: 33502331
A Probabilistic Model for Reducing Medication Errors: A Sensitivity Analysis using data in Electronic Health Records
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Succeeded performing the analysis of a probabilistic model for reducing medication errors with various thresholds. Picking the optimal threshold is both an art and a science — it should be done with careful reference to both specialties and the purpose of the application. The AESOP model was observed over 80% accurate (accuracy) for overall departments. Inappropriate prescriptions were determined with a lower rate (i.e. 1%–3%) and the positive predictive value (PPV) ranged from 40%−60%. |
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Medication-related clinical decision support systems have already been considered as a sophisticated method to improve healthcare quality, however, its importance has not been fully recognized. This paper’s aim was to validate an existing probabilistic model that can automatically identify medication errors by performing a sensitivity analysis from electronic medical record data.
773.4 million prescriptions were employed to compute the disease-medication and medication-medication associations. We built a knowledge base that consisted of 2.22 million disease-medication (DM) and 0.78 million medication-medication (MM) associations.
We collected 626,710 prescriptions from outpatient visit prescriptions from six departments (Cardiovascular, Neurology, Metabolism, Gastroenterology, Ophthalmology, and Urology department) across five hospitals in Taiwan.
We implemented the AESOP model for all 625,710 prescriptions using various threshold (α); the α is ranged from 0.5 to 1.5. Subsequently, 400 prescriptions with their default threshold of 1 that were randomly selected from each department, were evaluated by three certified physicians by their specialty. In total, 2400 prescriptions (400 per department) were evaluated by 18 physicians (three physicians per department) in our study.
Validation against the gold standard showed a high accuracy (over 80%), sensitivity (80–96%), and positive predictive value (over 85%). The negative predictive values ranged from 45 to 75%. PPV (positive predictive values) means both AESOP model prediction and experts evaluate the prescription as appropriate. NPV (negative predictive values) means both AESOP model prediction and experts evaluate the prescription as inappropriate.
We performed sensitivity analysis and validated the AESOP model at different hospital sites. Our findings show that picking up the optimal threshold of the model would be different in departments and depends on the purpose of the applications. Building an innovative system for detecting medication errors has many potential benefits for patient safety, improving quality healthcare, and conducting research.
773.4 million prescriptions were employed to compute the disease-medication and medication-medication associations. We built a knowledge base that consisted of 2.22 million disease-medication (DM) and 0.78 million medication-medication (MM) associations.
We collected 626,710 prescriptions from outpatient visit prescriptions from six departments (Cardiovascular, Neurology, Metabolism, Gastroenterology, Ophthalmology, and Urology department) across five hospitals in Taiwan.
We implemented the AESOP model for all 625,710 prescriptions using various threshold (α); the α is ranged from 0.5 to 1.5. Subsequently, 400 prescriptions with their default threshold of 1 that were randomly selected from each department, were evaluated by three certified physicians by their specialty. In total, 2400 prescriptions (400 per department) were evaluated by 18 physicians (three physicians per department) in our study.
Validation against the gold standard showed a high accuracy (over 80%), sensitivity (80–96%), and positive predictive value (over 85%). The negative predictive values ranged from 45 to 75%. PPV (positive predictive values) means both AESOP model prediction and experts evaluate the prescription as appropriate. NPV (negative predictive values) means both AESOP model prediction and experts evaluate the prescription as inappropriate.
We performed sensitivity analysis and validated the AESOP model at different hospital sites. Our findings show that picking up the optimal threshold of the model would be different in departments and depends on the purpose of the applications. Building an innovative system for detecting medication errors has many potential benefits for patient safety, improving quality healthcare, and conducting research.
Huang, C. Y., Nguyen, P. A., Yang, H. C., Islam, M. M., Liang, C. W., Lee, F. P., & Li, Y. C. (2019). A probabilistic model for reducing medication errors: A sensitivity analysis using Electronic Health Records data. Computer Methods and Programs in Biomedicine, 170, 31-38.
doi:10.1016/j.cmpb.2018.12.033
doi:10.1016/j.cmpb.2018.12.033
A Probabilistic Model for Reducing Medication Errors.
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The AOP model has a variety of applications. It can be used to alert physicians if medication errors are detected while prescribing medications using the CPOE system. Additionally, the model could be used to reduce the size of medication list in the CPOE for a given diagnosis. An automated medication listing systems and clinical decision support system (CDSS) can also be developed by using the AOP model. |
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We developed a model to detect uncommon or rare medication for a given disease when ordering prescriptions based on disease-medication associations.
This study focuses on medication-disease relationships by applying the association rule mining, and using statistical methods to detect medication errors in the computerized physician order entry (CPOE) systems in order to improve patient’s safety. 103.5 million prescriptions with 204.5 million diagnosis ICD9-CM (International Classification of Disease v.9-Clinical Modification) codes and 347.7 million medications with the Taiwan NHI codes were used in the analysis.
We use Q values to compute association for Disease-medication (DM) and Medication-medication (MM). Q value is the ratio between the joint probability of disease-medication and medication-medication with respect to their expected probability under the independent assumption known as lift (interest) and relative risk (RR) in similar studies dealing with associations. A total of 1.34 million DM and 0.65 million MM pairs with their Q values were computed from 103.5 million prescriptions.
Then we develop a model that can automatically evaluate the Appropriateness of a Prescription (AOP) which is developed based upon following rules:
Finally, we test the model for 100,000 randomly selected prescriptions, and then validating the results using seven human experts. The results showed 96% accuracy for appropriate and 45% accuracy for inappropriate prescriptions, with a sensitivity and specificity of 75.9% and 89.5%, respectively.
We successfully developed, tested, and validated the AOP model, which is able to predict and identify the appropriateness of the prescriptions. The AOP model developed in this study is able to detect accurately the inappropriate medications prescribed via COPE system. Thus, the PPV of the validation results from both physicians and pharmacists were accurate for the appropriate prescriptions. Moreover, this model could be applied in clinical practice to aid in improving prescription appropriateness, accuracy, patient safety, and patient care.
This study focuses on medication-disease relationships by applying the association rule mining, and using statistical methods to detect medication errors in the computerized physician order entry (CPOE) systems in order to improve patient’s safety. 103.5 million prescriptions with 204.5 million diagnosis ICD9-CM (International Classification of Disease v.9-Clinical Modification) codes and 347.7 million medications with the Taiwan NHI codes were used in the analysis.
We use Q values to compute association for Disease-medication (DM) and Medication-medication (MM). Q value is the ratio between the joint probability of disease-medication and medication-medication with respect to their expected probability under the independent assumption known as lift (interest) and relative risk (RR) in similar studies dealing with associations. A total of 1.34 million DM and 0.65 million MM pairs with their Q values were computed from 103.5 million prescriptions.
Then we develop a model that can automatically evaluate the Appropriateness of a Prescription (AOP) which is developed based upon following rules:
- The number of positive DMQs and positive MMQs should be greater than or equal to the number of medications.
- All diagnoses should have at least one positive DMQ.
- Each medication should have at least one positive DMQ or positive MMQ.
Finally, we test the model for 100,000 randomly selected prescriptions, and then validating the results using seven human experts. The results showed 96% accuracy for appropriate and 45% accuracy for inappropriate prescriptions, with a sensitivity and specificity of 75.9% and 89.5%, respectively.
We successfully developed, tested, and validated the AOP model, which is able to predict and identify the appropriateness of the prescriptions. The AOP model developed in this study is able to detect accurately the inappropriate medications prescribed via COPE system. Thus, the PPV of the validation results from both physicians and pharmacists were accurate for the appropriate prescriptions. Moreover, this model could be applied in clinical practice to aid in improving prescription appropriateness, accuracy, patient safety, and patient care.
Nguyen, P. A., Syed-Abdul, S., Iqbal, U., Hsu, M. H., Huang, C. L., Li, H. C., Li, Y. C. J. (2013). A Probabilistic Model for Reducing Medication Errors. PloS one, 8(12).
doi:10.1371/journal.pone.0082401
doi:10.1371/journal.pone.0082401
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