# The openVA Toolkit for Verbal Autopsies

Verbal autopsy (VA) is a survey-based tool widely used to infer cause of death (COD) in regions without complete-coverage civil registration and vital statistics systems. In such settings, many deaths happen outside of medical facilities and are not officially documented by a medical professional. VA surveys, consisting of signs and symptoms reported by a person close to the decedent, are used to infer the COD for an individual, and to estimate and monitor the COD distribution in the population. Several classification algorithms have been developed and widely used to assign causes of death using VA data. However, the incompatibility between different idiosyncratic model implementations and required data structure makes it difficult to systematically apply and compare different methods. The openVA package provides the first standardized framework for analyzing VA data that is compatible with all openly available methods and data structure. It provides an open-source, R implementation of several most widely used VA methods. It supports different data input and output formats, and customizable information about the associations between causes and symptoms. The paper discusses the relevant algorithms, their implementations in R packages under the openVA suite, and demonstrates the pipeline of model fitting, summary, comparison, and visualization in the R environment.

Zehang Richard Li (University of California, Santa Cruz) , Jason Thomas (The Ohio State University) , Eungang Choi (The Ohio State University) , Tyler H. McCormick (University of Washington) , Samuel J Clark (The Ohio State University)
2023-02-25

# 1 Introduction

Verbal autopsy (VA) is a well-established approach to ascertaining the cause of death (COD) when medical certification and full autopsies are not feasible or practical . After a death is identified, a specially-trained fieldworker interviews the caregivers (usually family members) of the decedent. A typical VA interview includes a set of structured questions with categorical or quantitative responses and a narrative section that records the “story” of the death from the respondent’s point of view . Currently, there are multiple commonly used questionnaires with overlapping, but not identical questions. VAs are routinely used both by researchers in health and demographic surveillance systems and multi-country research projects , and in national-scale surveys in many low- and middle-income countries (LMICs). For a more comprehensive overview of the current use of VA, we refer readers to Chandramohan et al. (2021).

The process of inferring a cause from VA data consists of two components. First, there must be some external information about the relationship between causes and symptoms. In supervised learning problems, the external information is typically derived from training datasets with known labels. In the context of VA, a common practice is to obtain training data using clinically trained, experienced physicians who read a fraction of the interviews and determine causes. To address the fact that physicians frequently do not agree on causes, VA interviews are often read by two physicians, and sometimes three, and the final causes are determined through a consensus mechanism (e.g., Kahn et al. 2012). This process can be extremely time- and resource-intensive. Another means of obtaining this information is directly through expert opinion. For example, one can ask groups of physicians to rate the likelihood of a symptoms occurring, given a particular COD, which can be converted into a set of probabilities of observing a symptom given a particular cause. Such expert knowledge can be highly useful in analyzing VA data when training datasets do not exist.

Secondly, an algorithmic or statistical model is needed to assign the causes of death by extrapolating the relationship between symptoms and causes to the target population. The cause-of-death assignment model is conceptually a separate construct from the symptom-cause information. The current state of the VA literature, however, often does not distinguish between the two. This is in part due to popular VA software that combines a source of symptom-cause information (e.g., a certain training data or a database of expert knowledge) with a specific algorithm, and requires a specific type of survey instrument to be used. This restriction prevents robust comparison between methods and contexts. A health agency in one region may, for example, want to analyze VA data using the same VA algorithm as a neighboring region to ensure estimates are comparable. Unless the agencies used the same survey format, however, this is not possible with existing tools.

The openVA package addresses this issue through an open-source toolkit. The openVA suite comprises a collection of R packages for the analysis of verbal autopsy data. The goal of this package is to provide researchers with an open-source tool that supports flexible data input formats and allows easier data manipulation and model fitting. The openVA suite consists of four core packages that are on CRAN, InterVA4 , InterVA5 , InSilicoVA , and Tariff , and an optional package nbc4va . Each of these packages implements one coding algorithm. For three of these algorithms – namely, InterVA-4, InterVA-5 and Tariff – there are also compiled software programs distributed by the original authors.

The main focus of this paper is to provide a general introduction to the implementation details of the included algorithms both in terms of the underlying methodology, and through case studies. The openVA package has four major contributions:

1. It provides a standardized and user-friendly interface for analysts to fit and evaluate each method on different types of data input using standard syntax. Previously, most of the methods were designed to be used specifically with their own input formats and are usually incompatible with others. The openVA package closes this gap by allowing easier and fair model comparison of multiple algorithms on the same data. This significantly facilitates further research on VA algorithms.
2. It provides a series of functionalities to summarize and visualize results from multiple algorithms, which is helpful for analysts not familiar with data manipulation and visualization in R.
3. It does not directly implement any algorithms for coding VA data, so that it is possible for a research group to maintain their own algorithm implementations callable from the openVA package, while also making it available to general users as a standalone piece of software. For example, the nbc4va was developed and maintained independently by researchers at the Center for Global Health Research in Toronto, but is designed so that it can be seamlessly integrated into the openVA package.
4. It is fully open source, and can be run on multiple platforms. The open-source nature of openVA significantly expands its potential for methodological research and its suitability for integration within a larger data analysis pipeline. Compared to the alternative implementations, the InterVA-4 and InterVA-5 software are distributed as compiled software that can only be run on Windows system. They provide the source codes as an additional code script, which are difficult to modify and re-compile. Tariff, as implemented through the SmartVA-Analyze application , was also primarily distributed as a compiled application that can only be run on Windows system . However, their source codes were recently made available under the open source MIT License on GitHub .

The rest of this paper is organized as follows: We first briefly introduce the main component packages and the underlying algorithms. We then demonstrate standard data structures and model fitting steps with the openVA package and functionalities to summarize results. We then discuss how additional information can be incorporated into modeling VA data, and we briefly survey additional packages and software developments built around the openVA package. We end with a discussion of remaining issues and limitations of the existing automated VA algorithms and propose new functionalities to be included in openVA package.

# 2 Structure of the openVA package

The openVA suite of packages currently consists of four standalone packages that are available on CRAN and one optional package hosted on GitHub. In this section, we first provide a brief introduction to these five packages, and we discuss the mathematical details behind each algorithm in the next subsection.

• InterVA4 is an R package that implements the InterVA-4 model . It provides replication of the widely used InterVA software . The standard input of InterVA4 is in the form of a pre-defined set of indicators, based on the 2012 World Health Organization (WHO) VA instrument . The default InterVA-4 algorithm cannot be applied to other data input formats because its internal built-in prior information is specific to a fixed set of indicators and causes. The same restriction is also maintained in the InterVA4 package. However, the mathematical formulation of the InterVA-4 model is completely generalizable to other binary input formats, as described in later sections, and is also implemented in the openVA package.

• InterVA5 is an R package that implements the InterVA-5 model . The InterVA-5 model updates the previous version in several ways. First, the input data must adhere to the format of the 2016 WHO VA instrument . Second, changes have been made to the data processing steps. It is also worth noting that the model outputs have been expanded by the inclusion of the most likely Circumstances Of Mortality CATegory, or COMCAT, among the results – the categories include: culture, emergency, health systems, inevitable, knowledge, resources, or an indeterminant combination of multiple factors (for more details, see D’Ambruoso et al. 2017). Despite these changes, the mathematical formulation of InterVA-5 is identical to that of InterVA-4.

• InSilicoVA is an R package that implements the InSilicoVA algorithm, a Bayesian hierarchical framework for cause-of-death assignment and cause-specific mortality fraction estimation proposed in McCormick et al. (2016). It is originally designed to work with the WHO VA instrument, i.e., the same input data used by the InterVA software, but is also generalizable to other data input formats. It is a fully probabilistic algorithm and can incorporate multiple sources of information, such as known sub-populations in the dataset, and physician coding when such data are available. The Markov Chain Monte Carlo (MCMC) sampler is implemented in Java for improved speed.

• Tariff is an R package that implements the Tariff algorithm . It most closely reflects the description of the Tariff 2.0 method . The Tariff algorithm is developed by the Institute for Health Metrics and Evaluation (IHME) and is officially implemented in the SmartVA-Analyze software . However, as the developers of this R package are not affiliated with the authors of the original algorithm, there are some discrepancies in implementation. The source code of the two versions of Tariff was not publicly available at the time when the Tariff package was created, so the package was developed based solely on the descriptions in the published work. Despite the difference in implementation, Tariff is able to achieve comparable results as the published work as demonstrated in McCormick et al. (2016). More detailed descriptions of the Tariff implementations are also discussed in the supplement of McCormick et al. (2016). The later released Python source codes of SmartVA-Analyze have been incorporated in the web application extension of the openVA package.

• nbc4va is an R package that implements the Naive Bayes Classifier for VA encoding . It calculates the conditional probabilities of symptoms given causes of death from a training dataset, instead of using physician-provided values. nbc4va is developed and maintained by researchers at the Center for Global Health Research in Toronto, but is designed so that it can be seamlessly integrated into openVA. It is an optional package that users can choose to load separately.

We note that there are additional methods and implementations to assign causes of death using VA data that are not included in the openVA implementation . These methods are not widely adopted by VA practitioners and most of these implementations are either not publicly available or require data processing steps that are specific to certain datasets, making them impractical for routine use in general. In addition, while the cause-of-death assignment process is closely related to the generic multi-class classification problem, naive application of off-the-shelf classification algorithms has been shown to perform poorly in the context of VA . Therefore, we focus on the methods that are currently adopted by practitioners. We briefly survey some more recent developments and their implementations at the end of this paper.

The openVA package is hosted on CRAN and can be installed with the following commands. Since posterior inference is carried out using MCMC in the InSilicoVA algorithm, we set the seed for the random number generator to make the paper reproducible. For the analysis in this paper, we also install the nbc4va package separately from GitHub. The versions of the supporting packages can be checked in R using the openVA_status() function.

set.seed(12345)
library(openVA)
openVA_status()

## Overview of VA cause-of-death assignment methods

The common modeling framework for VA data consists of first converting the survey responses into a series of binary variables, and then assigning a COD to each death based on the binary input variables. Typically, the target of inference consists of two parts: the individual cause-of-death assignment, and the population-level cause-specific mortality fractions (CSMF), i.e., the fraction of deaths due to each cause. In this section, we formally compare the modeling approaches utilized by each algorithm for these two targets. We adopt the following notations. Consider $$N$$ deaths, each with $$S$$ binary indicators of symptoms. Let $$s_{ij}$$ denote the indicator for the presence of $$j$$-th symptom in the $$i$$-th death, which can take values 0, 1, or NA (for missing data). We consider a pre-defined set of causes of size $$C$$. For the $$i$$-th death, denote the COD by $$y_i \in \{1, ..., C\}$$ and the probability of dying from cause $$k$$ is denoted by $$P_{ik}$$. For the population, the CSMF of cause $$k$$ is denoted as $$\pi_k$$, with $$\sum_{k=1}^C \pi_k = 1$$.

• InterVA4 and InterVA5 algorithms calculate the probability of each COD given the observed symptoms using the following formula, $P_{ik} = \frac{\pi_{k}^{(0)} \prod_{j=1}^S P(s_{ij}=1|y_{i}=k) \mathbf{1}_{s_{ij} = 1}} {\sum_{k' = 1}^C \pi_{k'}^{(0)} \prod_{j=1}^S P(s_{ij}=1|y_{i}=k') \mathbf{1}_{s_{ij} = 1}},$ where both the prior distribution of each of the causes, $$\pi_{k}^{(0)}$$ and the conditional probabilities $$P(s_{ij} = 1 | y_i = k)$$ are fixed values provided in the InterVA software. It is worth noting that the formula does not follow the standard Bayes’ rule as it omits the probability that any symptom is absent. A detailed discussion of this modeling choice can be found in McCormick et al. (2016). The conditional probabilities, $$P(s_{ij}=1|y_{i}=k)$$, used in InterVA algorithms are represented as rankings with letter grades instead of numerical values . For example, $$P(s_{ij}=1|y_{i}=k) = A+$$ is translated into $$P(s_{ij}=1|y_{i}=k) = 0.8$$, etc. The standard InterVA software only supports the fixed set of symptoms and causes where such prior information is provided. For a different data input format, this formulation can be easily generalized if training data are available. We include in the openVA package an extension of the algorithm that calculates $$\hat P(s_{ij}=1|y_{i}=k)$$ from the empirical distribution in the training data and then maps to letter grades with different truncation rules. Details of the extended InterVA algorithm can be found in McCormick et al. (2016).

After the individual COD distributions are calculated, InterVA-4 utilizes a series of pre-defined rules to identify up to the top three most likely COD assignments, and truncates the probabilities for the rest of the CODs to 0 and adds an ‘undetermined’ category so that the probabilities sum up to 1 (See the user guide of Byass (2015)). Then the population-level CSMFs are calculated as the aggregation of individual COD distributions, such that $\pi_k = \sum_{i=1}^N P^*_{ik},$ where $$P^*_{ik}$$ denotes the individual COD distribution after introducing the undetermined category.

• Naive Bayes Classifier is very similar to the InterVA algorithm with two major differences. First, instead of considering only symptoms that present, the NBC algorithm also considers symptoms that are absent. Second, the conditional probabilities of symptoms given causes are calculated from training data instead of given by physicians, which is similar to our extension of InterVA discussed above. Similar to InterVA, the NBC method can be written as $P_{ik} = \frac{\pi_{k}^{(0)} \prod_{j=1}^S (P(s_{ij}=1|y_{i}=k) \mathbf{1}_{s_{ij} = 1} + P(s_{ij} \neq 1|y_{i}=k) \mathbf{1}_{s_{ij} \neq 1})} {\sum_{k' = 1}^C \pi_{k'}^{(0)} \prod_{j=1}^S (P(s_{ij}=1|y_{i}=k') \mathbf{1}_{s_{ij} = 1}+ P(s_{ij} \neq 1|y_{i}=k') \mathbf{1}_{s_{ij} \neq 1})},$ and the CSMFs are calculated by $$\pi_k = \sum_{i=1}^N P_{ik}$$.

• InSilicoVA algorithm assumes a generative model that characterizes both the CSMF at the population level, and the COD distributions at the individual level. In short, the core generative process assumes $\begin{eqnarray} s_{ij} | y_i = k &\propto& \mbox{Bernoulli}(P(s_{ij} | y_i = k)), \\ y_i | \pi_1, ..., \pi_C &\propto& \mbox{Categorical}(\pi_1, ..., \pi_C), \\ \pi_k &=& \exp \theta_k / \sum_{k=1}^C \exp \theta_k, \\ \theta_k &\propto& \mbox{Normal}(\mu, \sigma^2). \end{eqnarray}$ Hyperpriors are also placed on $$P(s_{ij} | y_i = k)$$, $$\mu$$, and $$\sigma^2$$. The priors for $$P(s_{ij} | y_i = k)$$ are set by the rankings used in InterVA-4 if the data are prepared into InterVA format, otherwise they are learned from training data. The priors on $$\mu$$ and $$\sigma^2$$ are diffuse uniform priors. Parameter estimation is performed using MCMC, so that a sample of posterior distributions of $$\pi_k$$ can be obtained after the sampler converges.

• Tariff algorithm differs from the other three methods in that it does not calculate an explicit probability distribution of the COD for each death. Instead, for each death $$i$$, a Tariff score is calculated for each COD $$k$$ so that $Score_{ik} = \sum_{j = 1}^{S} \mbox{Tariff}_{kj}\mathbf{1}_{s_{ij}=1},$ where the symptom-specific Tariff score $$\mbox{Tariff}_{kj}$$ is defined as $\mbox{Tariff}_{kj} = \frac{n_{kj} - median(n_{1j}, n_{2j}, ..., n_{Cj})} {IQR(n_{1j}, n_{2j}, ..., n_{Cj})},$ where $$n_{kj}$$ is the count of how many deaths from cause $$k$$ contain symptom $$j$$ in the training data. The Tariff scores are then turned into rankings by comparing them to a reference distribution of scores calculated from re-sampling the training dataset to obtain a uniform COD distribution. It is worth noting that the Tariff algorithm produces the COD distribution for each death in terms of their rankings instead of the probability distributions. And thus the CSMF for each cause $$k$$ is calculated by the fraction of deaths with cause $$k$$ being the highest ranked cause, i.e., $\pi_k = \frac{\sum_{i=1}^N\mathbf{1}_{y_i = k}}{N}.$

In addition to the different model specifications underlying each algorithm, there is also a major conceptual difference in handling missing symptoms across the algorithms. Missing symptoms could arise from different stages of the data collection process. For example, the respondent may not know whether certain symptoms existed or may refuse to answer a question. From a statistical point of view, knowing that a symptom does not exist provides some information to the possible cause assignment, while a missing symptom does not. Although in theory, most of the VA algorithms could benefit from distinguishing ‘missing’ from ‘absence’, InSilicoVA is the only algorithm that has been implemented to acknowledge missing data. Missing indicators are assumed to be equivalent to ‘absence’ in InterVA, NBC, and Tariff.

# 3 Data preparation

In the openVA package, we consider two main types of standardized questionnaire: the WHO instrument and the IHME questionnaire. In this section, we focus on describing these two data formats and tools to clean and convert data. Pre-processing the raw data collected from the survey instrument (usually with Open Data Toolkit) is usually performed with additional packages and software outside of the analysis pipeline in R. We briefly mention software for data pre-processing towards the end of this paper.

## The WHO standard format

For users familiar with InterVA software and the associated data processing steps, the standard input format from the WHO 2012 and 2016 instruments is usually well understood. For the 2012 instrument, the data expected by the InterVA-4 software are organized into a data frame where each row represents one death and the corresponding VA information is contained in $$246$$ fields, starting from the first item being the ID of the death. The $$245$$ items following the ID each represent one binary variable of symptom/indicator, where ‘presence’ is coded by ‘Y’, and ‘absence’ is coded by an empty cell.

To accommodate updates for the WHO 2016 instrument , the InterVA-5 software accepts a data frame with $$354$$ columns that include $$353$$ columns of symptom/indicators followed by an additional column for the record ID. It should be noted that the R package InterVA5 retains the format with the record ID residing in the first column. Another important update with InterVA-5 is that it acknowledges the difference between “Yes” and “No” (or “Y/y” and “N/n”, which is different from the coding scheme in InterVA-4), both of which are processed as relevant responses, while all other responses are treated as missing values and ignored. With respect to the list of causes of death, InterVA-5 utilizes the WHO 2016 COD categories, which is nearly identical to the WHO 2012 COD categories (used by InterVA-4) except that hemorrhagic fever and dengue fever are two separate categories in the 2016 COD categories.

The same input format is inherited by the openVA package, except for one modification. We further distinguish ‘missing’ and ‘absence’ in the input data frame explicitly. We highly recommend that users pre-process all the raw data so that a ‘missing’ value in the data spreadsheet is coded as a ‘.’ (following the Stata practice familiar to many VA practitioners), and an ‘absence’ value is indicated by an empty cell, as in the standard InterVA-4 software. For WHO 2016 data, both ‘.’ and ‘-’ (following the default coding scheme of InterVA-5 software) are interpreted as missing values. For methods other than InSilicoVA, ‘missing’ and ‘absence’ will be considered the same internally and thus will not introduce a compatibility problem.

## The PHMRC format

The Population Health Metrics Research Consortium (PHMRC) gold standard VA data consist of three datasets corresponding to adult, child, and neonatal deaths, respectively. All deaths occurred in health facilities and gold-standard causes are determined based on laboratory, pathology and medical imaging findings. These datasets can be downloaded directly using the link returned by the function getPHMRC_url(). For example, we can read the adult VA dataset using the following command.

PHMRC_adult <- read.csv(getPHMRC_url("adult"))

Although the data are publicly accessible, a major practical challenge for studies involving the PHMRC gold standard dataset is that the pre-processing steps described from the relevant publications are not clear enough nor easy to implement. The openVA package internally cleans up the PHMRC gold standard data when calling the codeVA() function on the PHMRC data. The procedure follows the steps described in the supplement material of McCormick et al. (2016). Notice that the original PHMRC data are useful for comparing and validating new methods, as well as for using as training data, but the cleaning functions only require that the columns are exactly the same as the PHMRC gold standard datasets, so they could also be used for new data that are pre-processed into the same format.

## Customized format

In addition to the two standard questionnaires discussed previously, researchers might also be interested in including customized dichotomous symptoms in their analysis. The openVA package also supports customized inputs as long as they are dichotomous. In such case, neither the built-in conditional probability matrix of InterVA nor the PHMRC gold standard dataset could be used to learn the relationship between training and testing data, thus different training data with known causes of death are necessary for all three algorithms. The ConvertData() function can be used to convert data with customized coding schemes into the format recognized by the openVA package.

Finally, we note that the openVA package currently does not reformat data from one standardized questionnaire to another. This is because mapping the symptoms collected from one questionnaire to those collected by another questionnaire inevitably creates loss of information. Such mapping tasks can be useful for some applications. For example, a full mapping of a PHMRC dataset into the WHO format enables the use of physician provided conditional probabilities included in the InterVA software on data collected by PHMRC questionnaires. This remains as an important feature to be added to the package in the future.

# 4 Fitting VA cause-of-death assignment models

In this section, we demonstrate the model fitting process in the openVA package using two datasets: (1) a random sample of $$1,000$$ deaths from the ALPHA network without cause-of-death labels collected with the WHO 2012 instrument, and (2) the adult VA records in the PHMRC gold standard data, with the $$1,554$$ records from Andhra Pradesh, India used as a testing set and the rest used as a training dataset. In the first case without gold standard training data, only InterVA and InSilicoVA can be fitted. All four methods can be fitted in the second case.

## Modeling data collected with WHO 2012 questionnaire

The randomly sampled VA records from the ALPHA network sites are already included in the openVA package as a dataset RandomVA1 and can be loaded directly.

data(RandomVA1)
dim(RandomVA1)
[1] 1000  246
head(RandomVA1[, 1:10])
  ID elder midage adult child under5 infant neonate male female
1 d1     Y                                             Y
2 d2     Y                                                    Y
3 d3            Y                                      Y
4 d4                  Y                                       Y
5 d5                  Y                                Y
6 d6                  Y                                       Y

The codeVA() function provides a standardized syntax to fit different VA models. Internally, the codeVA() function organizes the input data according to the specified data type, checks for incompatibility of the data and specified model, and calls the corresponding model fitting functions. It returns a classed object of the specified model class. In this example, we use version 4.03 of the InterVA software, which is the latest release of the original software compatible with the WHO 2012 instrument. Any additional model-specific parameters can be passed through the arguments of codeVA(). Here we specify the HIV and malaria prevalence levels required by the InterVA model to be ‘high’. Guidelines on how to set these parameters can be found in Byass et al. (2012).

fit_inter_who <- codeVA(data = RandomVA1, data.type = "WHO2012",
model = "InterVA", version = "4.03",
HIV = "h", Malaria = "h")
summary(fit_inter_who) 
InterVA-4 fitted on 1000 deaths
CSMF calculated using reported causes by InterVA-4 only
The remaining probabilities are assigned to 'Undetermined'

Top 5 CSMFs:
cause                     likelihood
Undetermined              0.154
HIV/AIDS related death    0.122
Stroke                    0.072
Reproductive neoplasms MF 0.058
Pulmonary tuberculosis    0.055     

We can implement InSilicoVA method with similar syntax. We use the default parameters and run the MCMC for $$10,000$$ iterations. Setting the auto.length argument to FALSE specifies that the algorithm does not automatically increase the length of the chain when convergence failed. In practice, we recommend setting this argument to TRUE if the algorithm displays warnings concerning MCMC convergence. The InSilicoVA algorithm is implemented using a Metropolis-Hastings within Gibbs sampler. The acceptance rate is printed as part of the message as the model samples from the posterior distribution.

fit_ins_who <- codeVA(RandomVA1, data.type = "WHO2012", model = "InSilicoVA",
Nsim = 10000, auto.length = FALSE)
summary(fit_ins_who) 
InSilicoVA Call:
1000 death processed
10000 iterations performed, with first 5000 iterations discarded
250 iterations saved after thinning
Fitted with re-estimated conditional probability level table
Data consistency check performed as in InterVA4

Top 10 CSMFs:
Mean Std.Error Lower Median Upper
Other and unspecified infect dis  0.266    0.0168 0.235  0.265 0.301
HIV/AIDS related death            0.102    0.0091 0.085  0.102 0.119
Renal failure                     0.101    0.0108 0.084  0.101 0.123
Other and unspecified neoplasms   0.062    0.0089 0.046  0.061 0.080
Other and unspecified cardiac dis 0.058    0.0076 0.044  0.058 0.075
Digestive neoplasms               0.050    0.0077 0.033  0.050 0.065
Acute resp infect incl pneumonia  0.048    0.0073 0.034  0.049 0.063
Pulmonary tuberculosis            0.039    0.0068 0.025  0.039 0.054
Stroke                            0.038    0.0061 0.027  0.038 0.052
Other and unspecified NCD         0.034    0.0089 0.018  0.034 0.052

## Modeling the PHMRC data

In the second example, we consider a prediction task using the PHMRC adult dataset. We first load the complete PHMRC adult dataset from its on-line repository, and organize it into training and test datasets. We treat all deaths from Andhra Pradesh, India as the test dataset.

PHMRC_adult <- read.csv(getPHMRC_url("adult"))
is.test <- which(PHMRC_adultsite == "AP") test <- PHMRC_adult[is.test, ] train <- PHMRC_adult[-is.test, ] dim(test) [1] 1554 946 dim(train) [1] 6287 946 In order to fit the models on the PHMRC data, we specify data.type = "PHMRC" and phmrc.type = "adult" to indicate the data input is collected using the PHMRC adult questionnaire. We also specify the column of the causes-of-death label in the training data. The rest of the syntax is similar to the previous example. When the input consists of both training and testing data, the InterVA and InSilicoVA algorithms estimate the conditional probabilities of symptoms using the training data, instead of using the built-in values. In such case, the version argument for the InterVA algorithm is suppressed. There are several ways to map the conditional probabilities of symptoms given causes in the training dataset to a letter grade system, specified by the convert.type argument. The convert.type = "quantile" performs the mapping so that the percentile of each rank stays the same as the original $$P_{s|c}$$ matrix in InterVA software. Alternatively we can also use the original fixed values of translation, and assign letter grades closest to each entry in $$\hat{P}_{s|c}$$. This conversion is specified by convert.type = "fixed", and is more closely aligned to the original InterVA and InSilicoVA setting. Finally, we can also directly use the values in the $$\hat{P}_{s|c}$$ without converting them to ranks and re-estimating the values associated with each rank. This can be specified by convert.type = "empirical". In this demonstration, we assume the fixed value conversion. fit_inter <- codeVA(data = test, data.type = "PHMRC", model = "InterVA", data.train = train, causes.train = "gs_text34", phmrc.type = "adult", convert.type = "fixed") fit_ins <- codeVA(data = test, data.type = "PHMRC", model = "InSilicoVA", data.train = train, causes.train = "gs_text34", phmrc.type = "adult", convert.type = "fixed", Nsim=10000, auto.length = FALSE) The NBC and Tariff method can be fit using similar syntax. fit_nbc <- codeVA(data = test, data.type = "PHMRC", model = "NBC", data.train = train, causes.train = "gs_text34", phmrc.type = "adult") fit_tariff <- codeVA(data = test, data.type = "PHMRC", model = "Tariff", data.train = train, causes.train = "gs_text34", phmrc.type = "adult") Notice that we do not need to transform the PHMRC data manually. Data transformations are performed automatically within the codeVA() function. # 5 Summarizing results In this section we demonstrate how to summarize results, extract output, and visualize and compare fitted results. All the fitted object returned by codeVA() are S3 objects, for which a readable summary of model results can be obtained with the summary() function as shown in the previous section. In addition, several other metrics are commonly used to evaluate and compare VA algorithms at either the population or individual levels. In the rest of this section, we show how to easily calculate and visualize some of these metrics with the openVA package. ## CSMF accuracy We can extract the CSMFs directly using the getCSMF() function. The function returns a vector of the point estimates of the CSMFs, or a matrix of posterior summaries of the CSMF for the InSilicoVA algorithm. csmf_inter <- getCSMF(fit_inter) csmf_ins <- getCSMF(fit_ins) csmf_nbc <- getCSMF(fit_nbc) csmf_tariff <- getCSMF(fit_tariff) One commonly used metric to evaluate the CSMF estimates is the so-called CSMF accuracy, defined as $CSMF_{acc} = 1 - \frac{\sum_j^C CSMF_i - CSMF_j^{(true)}}{2(1 - \min CSMF^{(true)})}$ The CSMF accuracy can be readily computed using functions in openVA as the codes below shows. csmf_true <- table(c(testgs_text34, unique(PHMRC_adult\$gs_text34))) - 1
csmf_true <- csmf_true / sum(csmf_true)
c(getCSMF_accuracy(csmf_inter, csmf_true, undet = "Undetermined"),
getCSMF_accuracy(csmf_ins[, "Mean"], csmf_true),
getCSMF_accuracy(csmf_nbc, csmf_true),
getCSMF_accuracy(csmf_tariff, csmf_true))
[1] 0.53 0.74 0.77 0.68

We use the empirical distribution in the test data to calculate the true CSMF distribution, i.e., $$CSMF_j^{(true)} = \frac{1}{n}\sum_{i=1}^n {1}_{y_i = j}$$. Then we evaluate the CSMF accuracy using the getCSMF_accuracy() function. As discussed previously, the default CSMF calculation is slightly different for diCfferent methods. For example, the InterVA algorithm creates the additional category of Undetermined by default, which is not in the true CSMF categories and needs to be specified. The creation of the undetermined category can also be suppressed by interVA.rule = FALSE in the getCSMF() function call. For the InSilicoVA algorithm, we use the posterior mean to calculate the point estimates of the CSMF accuracy.

## Individual COD summary

At the individual level, we can extract the most likely cause-of-death assignment from the fitted object using the getTopCOD() function.

cod_inter <- getTopCOD(fit_inter)
cod_ins <- getTopCOD(fit_ins)
cod_nbc <- getTopCOD(fit_nbc)
cod_tariff <- getTopCOD(fit_tariff)

With the most likely COD assignment, other types of metrics based on individual COD assignment accuracy can be similarly constructed by users. The summary methods can also be called for each death ID. For example, using the Tariff method, we can extract the fitted rankings of causes for the death with ID 6288 by

summary(fit_inter, id = "6288")
InterVA-4 fitted top 5 causes for death ID: 6288

Cause                     Likelihood
Stroke                    0.509
Pneumonia                 0.318
COPD                      0.081
Other Infectious Diseases 0.064
Renal Failure             0.013     

The summary() function for InSilcoVA does not provide uncertainty estimates for individual COD assignments by default. This is because, in practice, the calculation of individual posterior probabilities of COD distribution can be memory-intensive when the dataset is large. To obtain individual-level uncertainty measurements, we can either run the MCMC chain with the additional argument indiv.CI = 0.95 when calling codeVA(), or update the fitted object directly with the saved posterior draws.

fit_ins <- updateIndiv(fit_ins, CI = 0.95)
summary(fit_ins, id = "6288")
InSilicoVA fitted top  causes for death ID: 6288
Credible intervals shown: 95%
Mean  Lower Median  Upper
Stroke                      0.5043 0.3485 0.5083 0.6361
Pneumonia                   0.4116 0.2615 0.4083 0.5834
Other Infectious Diseases   0.0660 0.0411 0.0642 0.0966
Epilepsy                    0.0099 0.0064 0.0097 0.0142
COPD                        0.0053 0.0031 0.0052 0.0079
Malaria                     0.0007 0.0005 0.0007 0.0011
Diabetes                    0.0005 0.0003 0.0005 0.0009
Acute Myocardial Infarction 0.0004 0.0003 0.0004 0.0006
Falls                       0.0004 0.0001 0.0004 0.0013
Renal Failure               0.0004 0.0002 0.0003 0.0005

For $$N$$ deaths, $$C$$ causes, the posterior mean of individual COD distributions returned by the InSilicoVA model, along with median and with credible intervals can be represented by a $$(N \times C \times 4)$$-dimensional array. The function getIndivProb() extracts this summary in the form of a list of $$4$$ matrices of dimension $$N$$ by $$C$$, which can then be saved to other formats to facilitate further analysis. For other methods, the point estimates of individual COD distribution are returned as the $$N$$ by $$C$$ matrix.

fit_prob <- getIndivProb(fit_inter)
dim(fit_prob)
[1] 1554   34

## Visualization

The previous sections discuss how results could be extracted and examined in R. In this subsection, we show some visualization tools provided in the openVA package for presenting these results. The fitted CSMFs for the top causes can be easily visualized by the plotVA() function. The default graph components are specific to each algorithm and individual package implementations, with options for further customization. For example, Figure[1] shows the estimated CSMF from the InterVA algorithm in the PHMRC data example.

plotVA(fit_inter, title = "InterVA")

The CSMFs can also be aggregated for easier visualization of groups of causes. For the InterVA-4 cause list, we included an example grouping built into the package, so the aggregated CSMFs can be compared directly. In practice, the grouping of causes of deaths often needs to be determined according to context and the research question of interest. Changing the grouping can be easily achieved by modifying the grouping argument in the stackplotVA() function. For example, to facilitate the new category of Undetermined returned by InterVA, we first modify the grouping matrix to include it as a new cause and visualize the aggregated CSMF estimates in Figure [2].

data(SampleCategory)
grouping <- SampleCategory
grouping[,1] <- as.character(grouping[,1])
grouping <- rbind(grouping, c("Undetermined", "Undetermined"))
compare <- list(InterVA4 = fit_inter_who,
InSilicoVA = fit_ins_who)
stackplotVA(compare, xlab = "", angle = 0,  grouping = grouping)

The ordering of the stacked bars can also be changed to reflect the structures within the aggregated causes, as demonstrated in Figure [3].

group_order <- c("TB/AIDS",  "Communicable", "NCD", "External", "Maternal",
"causes specific to infancy", "Undetermined")
stackplotVA(compare, xlab = "", angle = 0, grouping = grouping,
group_order = group_order)

Among the VA methods discussed in this paper, the InSilicoVA algorithm allows for more flexible modifications to the Bayesian hierarchical model structure when additional information is available. In this section, we illustrate two features unique to the InSilicoVA method: jointly estimating CSMFs from multiple populations, and incorporating partial and potentially noisy physician coding into the algorithm.

## Sub-population specific CSMFs

In practice researchers may want to estimate and compare CSMFs for different regions, time periods, or demographic groups in the population. Running separate models on subsets of data can be inefficient and does not allow parameter estimation to borrow information across different groups. The generative framework adopted by InSilicoVA allows the specification of sub-populations in analyzing VA data. Consider an input dataset with $$G$$ different sub-populations. We can estimate different CSMFs $$\pi^{(g)}$$ for $$g = 1, ..., G$$ for each sub-population, while assuming the same conditional probability matrix, $$P_{s|c}$$ and other hyperpriors. As an example, we show how to estimate different CSMFs for sub-populations specified by sex and age groups, using a randomly sampled ALPHA dataset with additional columns specifying the sub-population each death belongs to.

data(RandomVA2)
head(RandomVA2[, 244:248])
  stradm smobph scosts   sex age
1      .      .      .   Men 60+
2      .      .      . Women 60-
3      .      .      . Women 60-
4      .      .      . Women 60+
5      .      .      . Women 60-
6      .      .      . Women 60-

Then we can fit the model with one or multiple additional columns specifying sub-population membership for each observation.

fit_sub <- codeVA(RandomVA2, model = "InSilicoVA",
subpop = list("sex", "age"),  indiv.CI = 0.95,
Nsim = 10000, auto.length = FALSE)

Functions discussed in the previous sections work in the same way for the fitted object with multiple sub-populations. Additional visualization tools are also available. Figure [4] plots the CSMFs for two sub-populations on the same plot by specify type = "compare".

plotVA(fit_sub, type = "compare", title = "Comparing CSMFs", top = 3)

By default, the comparison plots will select all the CODs that are included in the top causes (specified by the top argument) for each of the sub-populations. We can also plot only subsets of them by specifying the causes of interest, as shown in Figure [5].

plotVA(fit_sub, type = "compare", title = "Comparing CSMFs",
causelist = c("HIV/AIDS related death",
"Pulmonary tuberculosis",
"Other and unspecified infect dis",
"Other and unspecified NCD"))

Figure [6] shows the visualization of the top CSMFs for a chosen sub-population using the which.sub argument.

plotVA(fit_sub, which.sub = "Women 60-", title = "Women 60-")

Similar to before, the stackplotVA() function can also be used to compare different sub-populations in aggregated cause groups, as shown in Figure [7].

stackplotVA(fit_sub)
stackplotVA(fit_sub, type = "dodge")

## Physician coding

When physician-coded causes of death are available for all or a subset of the deaths, we can incorporate such information in the InSilicoVA model. The physician-coded causes can be either the same as the CODs used for the final algorithm, or consist of causes at a higher level of aggregation. When there is more than one physician code for each death and the physician identity is known, we can first de-bias the multiple codes provided from different physicians using the process described in McCormick et al. (2016). For the purpose of implementation, we only need to specify which columns are physician IDs, and which are their coded causes, respectively.

data(SampleCategory)
data(RandomPhysician)
head(RandomPhysician[, 245:250])
  smobph scosts        code1 rev1        code2 rev2
1      .      .          NCD doc9          NCD doc6
2      .      .          NCD doc4          NCD doc3
3      .      .          NCD doc1          NCD doc5
4      .      .      TB/AIDS doc4      TB/AIDS doc7
5      .      .      TB/AIDS doc5      TB/AIDS doc9
6      .      . Communicable doc9 Communicable <NA>
doctors <- paste0("doc", c(1:15))
causelist <- c("Communicable", "TB/AIDS", "Maternal",
"NCD", "External", "Unknown")
phydebias <- physician_debias(RandomPhysician,
phy.id = c("rev1", "rev2"), phy.code = c("code1", "code2"),
phylist = doctors, causelist = causelist, tol = 0.0001, max.itr = 100)

The de-biased step essentially creates a prior probability distribution for each death over the broader categories of causes. Then to run InSilicoVA with the de-biased physician coding, we can simply pass the fitted object from the previous step to the model. Additional arguments are needed to specify both the external cause category, since external causes are handled by separate heuristics, and the unknown category, which is equivalent to a uniform probability distribution over all other categories, i.e., the same as the case where no physician coding exists.

fit_ins_phy <- codeVA(RandomVA1, model = "InSilicoVA",
phy.debias = phydebias, phy.cat = SampleCategory,
phy.external = "External", phy.unknown = "Unknown",
Nsim = 10000, auto.length = FALSE) 

Figure [8] compares the previous results without including physicians codes.

plotVA(fit_ins_who, title = "Without physician coding")
plotVA(fit_ins_phy, title = "With physician coding")

## Removal of physically impossible causes

The originally proposed InSilicoVA assumes all causes of death are possible for each observation. The impact from such an assumption is mild when data are abundant, but could be problematic when either the sample size is small or the proportion of missing data is high. In both cases, physically impossible causes might get assigned with non-ignorable posterior mass. Since version 1.1.5 of InSilicoVA, when the input is in the WHO format, the algorithm automatically checks and removes impossible causes before fitting the model. The $$k$$-th cause is defined as physically impossible for the $$i$$-th death if $$P(s_{ij}=1 | y_{i}=k) = 0$$ where $$s_{ij}$$ is an indicator that the decedent belongs to a particular sex or age group. We then consider a cause to be physically impossible for the underlying population if it is impossible for all the observations in the input data. For example, with the new implementation, CSMF for pregnancy-related causes will not be estimated if the input data consist of only male deaths.

# 7 Other related software packages

Since the release of the openVA package on CRAN, there have been several new developments in both methodology and software that build on the openVA suite of packages and further extend its functionalities. Here we briefly survey some of the related methods, software packages, and ongoing work in the VA community that are related to openVA.

First, the ability to easily fit and compare existing methods using the openVA package facilitated the development of several new VA methods in the last several years. Most of the development focuses on building statistical models to relax the conditional independence assumption of symptoms given a cause of death . These methods tend to be computationally more demanding compared to the algorithms currently included in the openVA package, but usually provide improved inference. It is future work to include some of these latest developments in the openVA package for routine use. Most of these methods have publicly available implementations, such as the farva package on GitHub. In another direction of research, a class of transfer learning methods focuses on building models to correct for bias in existing methods when predicting out of domain. These methods take the predicted cause of death assignments and distributions obtained with the openVA package and learn an ensemble of the predictions calibrated to the target population . The calibratedVA package is available to implement these models.

Outside of research community that develops new VA algorithms, openVA has also been used extensively by governments and health care organizations, particularly in locations that lack a strong vital registration system and use VA data to identify the leading causes of death. To facilitate the work of these users, openVA has been wrapped into a web application, the openVA App , using the shiny package . The open source openVA App is available on GitHub and provides an intuitive interface to openVA that does not require one to learn R, but provides visual and tabular output produced by the different VA algorithms. It also runs the official Tariff algorithm by calling the Python source code of SmartVA-Analyze and processing the output to be consistent with the other algorithms. The openVA R package has also been a key component in a larger data analysis pipeline that pulls VA data from an Open Data Kit (ODK) Collect server and deposits the assigned causes of death to another server running the District Health Information Software 2 (DHIS2), which is a common information management system used in low and middle-income countries. This open-source software is implemented as a Python package, openva-pipeline, and is available on GitHub and the Python Package Index . Finally, the R package CrossVA and the Python package pyCrossVA provide additional toolkits to convert raw VA data from its original format from the ODK server to the standardized formats discussed before. Both packages are open source and available on GitHub. The pyCrossVA package is also available on the Python Package Index.

# 8 Conclusion

In this paper, we introduce the openVA package. This is the first open-source software that implements and compares the major VA methods. The openVA package allows researchers to easily access the most recent tools that were previously difficult to work with or unavailable. It also enables the compatibility of multiple data input formats and significantly reduces the tedious work to pre-process different data formats specific to each algorithm. The software framework of the openVA package allows for the integration of new methods developed in the future. The openVA package makes all the steps involved in analyzing VA data – i.e., data processing, model tuning and fitting, summarizing results, and evaluation metrics – transparent and reproducible. This contributes significantly to the public health community using VA.

Finally, we make note of several features that will be helpful for future development. First, many users of the openVA package may not be familiar with the command line tools or do not have access to R on their local machines. A well designed graphical user interface can be very useful in such settings. The work on the shiny web application, openVA app, is a first step towards making the package more accessible. The authors intend to extend it to a better front end hosted on secure centralized servers. Second, although we aim to provide users with all the available methods for assigning causes of death, there is a lack of tools for comparing the accuracy and robustness between algorithms. Thus, much future work is needed to systematically assess, compare, and combine these methods in a better analytic framework. Finally, the development of VA algorithms is still an active area of research and it would be possible to extend the openVA suite to incorporate better VA algorithms and new types of data such as free-text narratives.

# 9 Acknowledgement

This work was supported by grants K01HD078452, R01HD086227, and R21HD095451 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Funding was also received from the Data for Health Initiative, a joint project of Vital Strategies, the CDC Foundation and Bloomberg Philanthropies, through Vital Strategies. The views expressed are not necessarily those of the initiative.

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### Reuse

Text and figures are licensed under Creative Commons Attribution CC BY 4.0. The figures that have been reused from other sources don't fall under this license and can be recognized by a note in their caption: "Figure from ...".

### Citation

Li, et al., "The R Journal: The openVA Toolkit for Verbal Autopsies", The R Journal, 2023

BibTeX citation

@article{openVA-RJ-R1,
author = {Li, Zehang Richard and Thomas, Jason and Choi, Eungang and McCormick, Tyler H. and Clark, Samuel J},
title = {The R Journal: The openVA Toolkit for Verbal Autopsies},
journal = {The R Journal},
year = {2023},
note = {https://journal.r-project.org/articles/RJ-2023-020/},
issn = {2073-4859},
pages = {1}
}