Medical Dead-ends and Learning to Identify High-risk States and Treatments

Machine learning has successfully framed many sequential decision making problems as either supervised prediction, or optimal decision-making policy identification via reinforcement learning. In data-constrained offline settings, both approaches may fail as they assume fully optimal behavior or rely on exploring alternatives that may not exist. Even if optimality is not attainable in such constrained cases, negative outcomes in data can be used to identify behaviors to avoid, thereby guarding against overoptimistic decisions in safety-critical domains that may be significantly biased due to reduced data availability. Along these lines we introduce an approach that identifies possible "dead-ends" of a state space. We focus on the condition of patients in the intensive care unit, where a "medical dead-end" indicates that a patient will expire, regardless of all potential future treatment sequence. We frame the discovery of these dead-ends as an RL problem, training three independent deep neural models for automated state construction, dead-end discovery and confirmation.

In this repository, we provide the code used develop a novel RL-based method, Dead-end Discovery (DeD), presented in the paper "Medical Dead-ends and Learning to Identify High-risk States and Treatments" published at NeurIPS 2021. DeD focuses on identifying treatments to avoid as opposed to what treatment to select as is typical in RL-based approaches to sequential decision making in healthcare. Our goal in publishing this code is to facilitate reproducibility of our paper in hopes of motivating further research utilizing the DeD framework in safety-critical domains.

Paper

If you use this code in your research please cite the following publication:

@article{fatemi2021medical,
  title={Medical Dead-ends and Learning to Identify High-risk States and Treatments},
  author={Fatemi, Mehdi and Killian, Taylor W and Subramanian, Jayakumar and Ghassemi, Marzyeh},
  journal={Advances in Neural Information Processing Systems},
  volume={34},
  year={2021}
}

This paper can also be found on arXiv at 2110.04186.

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LICENSE

Microsoft Open Source Code of Conduct

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Responsible AI Transparency Information

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Use of this code

Our goal in publishing this code is to facilitate reproducibility of our paper in hopes of motivating further research utilizing the DeD framework in safety-critical domains. This code should not be used in clinical settings to influence treatment decisions.

Project data

This project uses a generated cohort from the publicly available MIMIC III (version 1.4) dataset. The main data is available at physionet.org and all the details and the code for generating the cohort is available at Sepsis Cohort. For more information see Step 0 from the How to use section bellow.

Fairness and Responsible AI testing

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When systems are deployed, Responsible AI testing should be performed to ensure safe and fair operation for the specific use case. No Responsible AI testing has been done to evaluate this method including validating fair outcomes across different groups of people. Responsible AI testing should be done before using this code in any production scenario.

Note: The documentation included in this ReadMe file is for informational purposes only and is not intended to supersede the applicable license terms.

Contributing

This code has been developed as part of the RL4H initiative at MSR Montreal. Most of the core work has been done by

• Mehdi Fatemi (mehdi.fatemi@microsoft.com), Senior Researcher, MSR Montreal

with contributions by

• Taylor Killian (twkillian@cs.toronto.edu), Ph.D. Student, University of Toronto

• Jayakumar Subramanian (jayakumar.subramanian@gmail.com), Intern (Summer 2019), MSR Montreal

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This project welcomes contributions and suggestions. Most contributions require you to agree to a Contributor License Agreement (CLA) declaring that you have the right to, and actually do, grant us the rights to use your contribution. For details, visit https://cla.opensource.microsoft.com.

When you submit a pull request, a CLA bot will automatically determine whether you need to provide a CLA and decorate the PR appropriately (e.g., status check, comment). Simply follow the instructions provided by the bot. You will only need to do this once across all repos using our CLA.

This project has adopted the Microsoft Open Source Code of Conduct. For more information see the Code of Conduct FAQ or contact opencode@microsoft.com with any additional questions or comments.

Requirements

We recommend using the Anaconda distribution for python dependencies. The code should work will any recent version. In addition, the following packages are required:

• Pytorch (https://pytorch.org/) -> All recent versions should work. Tested on 1.8 and newers.
• Click (pip install click) -> All recent versions should work. Tested on 6.5 and newers.
• Pyprind (pip install PyPrind) -> All versions should work.

How to use

Step 0) Data Preparation:

Part 1: MIMIC-III Sepsis Cohort

The code used to define, extract and preprocess the patient cohort from MIMIC-III can be found at https://github.com/microsoft/mimic_sepsis. This code produces two CSV files sepsis_final_data_withTimes.csv and sepsis_final_data_RAW_withTimes.csv.

To replicate the results presented in our paper, it is expected that these two files are accessible via the directory ./data/sepsis_mimiciii/.

Then from the root directory, run the following steps (tested on Windows and Linux). All steps depend on the configuration file config_sepsis.yaml which is used to define experiment specific parameters as well as the directories where data can be found, artifacts of training and, results are stored. As a default (for illustrative purposes) we name the base experiment as "run1" which is used to create a subfolder.

Part 2: Preprocess the extracted trajectories

Run ipython ./data_process.py

The patient cohort provided in part 1 is extracted for general purposes. This script places the extracted trajectories into a more convenient format for the DeD learning processes and also constructs independent training, validation and test datasets. It also removes the raw-input columns from the observations (o:input_total, o:input_4hourly, and o:max_dose_vaso), if they are included by the the cohort generator.

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Step 1) Train the State Construction (SC-) Network

Run ipython ./train_sc_network.py

Following Killian, et al. we form state representations by processing a sequence of observations, using AIS prior to and including any time t as well as the last selected treatment to form the state s_t. The SC-Network is trained to predict the next observation, by reconstructing the latent state representation created via a recurrent encoding module.

Note: Depending on the architecture, this step can take many hours to completion.

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Step 2) Train the Dead-end (D-) and Recovery (R-) Networks

Run ipython ./train_rl.py -- -f "./results/run1"

Based on the MDP formulation introduced in the paper, we train two independent DQN models to discover and confirm dead-ends and identify treatments that may leave a patient toward these unfavorable states. The networks are trained using the DDQN approach introduced by van Hasselt, et al which can be replaced by any appropriate offline RL method. Following Fatemi, et al. we also use bootstrap clipping to mitigate value overflow.

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Step 3) Aggregate and Analyze the Results

Part 1) Results aggregation

Run ipython ./stats/make_plot_data.py

This script takes the trained D- and R-Networks with the embedded states of the test set to aggregate results and identify potentially high-risk states and treatments. In a generated ./plots folder two results artifacts are saved:

• flag_data.pkl contains information about states along a patient trajectory that are flagged as medium or high-risk.
• data_value.pkl contains information about the values of the D- and R- Networks along the step-by-step patient trajectories.

Part 2) Generate Figures

• Run ipython ./stats/circular_hist.py to produce the circular histogram in Figure 2.
• Run ipython ./stats/base_analysis.py to aggregate trends of the features and D- + R-Networks, as done in Figure 3.
• Run ipython ./stats/make_hist.py to create the Appendix Figs. A5 and A6 + a raw version of Figure 2.
• Run ipython ./stats/tsne.py to reproduce the T-SNE plots in the Appendix and also generates a list of informative negative trajectories saved to ./plots/good_neg_trajs.yaml

All following scripts depend on the list of informative negative trajectories: ./plots/good_neg_trajs.yaml:

• Run ipython ./stats/colour_maps.py to reproduce the colour-maps of Figure 4 and any other desired trajectory from good_neg_trajs.
• Run ipython ./stats/patients_obs.py to reproduce the top panel of Figure 4 and any other desired trajectory from good_neg_trajs.
• Run ipython ./stats/prediction.py to reproduce the tables found in the appendix (produced in LaTeX format)