Structural zeroes and zero-inflated models

Hua HE*, Wan TANG, Wenjuan WANG, Paul CRITS-CHRISTOPH

?Biostatistics in psychiatry (22)?

Structural zeroes and zero-inflated models

Hua HE1,2,3*, Wan TANG1, Wenjuan WANG1, Paul CRITS-CHRISTOPH4

count response, structural zeroes, random zeroes, zero-inflated models

1. Introduction

Count (or frequency) responses such as number of heart attacks, number of days of alcohol drinking, number of suicide attempts, and number of unprotected sexual encounters during a period of time arise quite often in biomedical and psychosocial research. Poissondistribution based log-linear regression models are widely used when such count variables are treated as the dependent variable in an analysis. One major limitation of the Poisson model is that the mean is identical to the variance. In practice, heterogeneity in study populations due to data clustering or other factors often creates extra variability, resulting in variance that is larger than the mean. This renders the Poisson distribution inappropriate for modeling count data in such instances. Depending on the nature of the heterogeneity, there are different approaches to address this extra variability, oroverdispersion. For example, overdispersion may occur if the length of the observation period varies across the subjects. We can use an offset in the log-linear model to remove the overdispersion if the length of the observation period is available for each subject. Otherwise, we can treat the length as a latent variable, which is equivalent to treating the mean of the Poisson distribution for each subject as a random variable. If such a random effect is modeled using a gamma distribution, this approach yields a negative binomial (NB) distribution.Compared with the Poisson, the NB distribution has an extra parameter to account for the additional variation beyond the Poisson, and hence is able to address the limitations of the Poisson model for over-dispersed count responses. The Poisson and NB log-linear models are implemented in most major statistical software packages such as SAS, SPSS, and Stata.

However, NB cannot address the overdispersion caused by an excessive number of zeroes in the count data, which is quite common in psychosocial and behavioral studies. Excessive zeroes are particularly evident in alcohol and substance abuse research. Forexample, in a substance abuse multicenter intervention study, 50% of patients (n=318) had zero days of drug use during the entire primary outcome phase (weeks 4 to 16).[1]In another multicenter trial involving over 1500 patients at 20 community sites, zero days of drug and alcohol use in the past 7 days was reported by over 80%of patients at each weekly assessment.[2]Moreover, a wide range of other types of alcohol research studies have reported zero-inflated data across various types of alcohol measures.[3-12]Like substance use outcomes,HIV risk behavior measures show excessive zeros. For example, in a HIV risk intervention study[13]with 102 subjects, nearly 50% had scores of zero on the HIV risk measure. Zero-inflated data were also evident in other HIV risk reduction studies.[14,15]Other common examples of zero-inflated data that could serve as outcome measures in intervention or prevention trials include counts of uncommon adverse events,[16]number of hospital stays,[17]number of arrests,[18]and number of traffic accidents.[19]

Excessive zeros when assessing these types of outcome measures are often due to the existence of a subpopulation of subjects who are not at risk for such a behavior during the study period. For example, the number of unprotected sexual occasions over a period of time is an important measure in HIV prevention research. But a specific study population may contain a subgroup of individuals who are not at risk at all of sexual activity and, thus, will always produce a zero outcome in the count variable. Such zeros are calledstructural zeros. On the other hand, subjects who are at risk of the behavior may still produce a zero outcome due to sampling variability; such zeros are calledrandom(orsampling)zeros.

The concept of structural zeros or non-risk groups is very important in psychosocial studies, because the non-risk and at-risk groups may have very different health and demographic characteristics. For example,in alcohol studies days of alcohol use over a week may contain both structural and random zeros: structural zeros that come from the non-risk group who are abstinent from drinking, while random zeros from the at-risk group of subjects who, due to sampling variation,did not drink in the prior week. The two groups of subjects may have different health outcomes such as different rates of depression and anxiety. So it is critical to distinguish the structural zeros from random zeros when modeling a count response with structural zeros.

Neither the Poisson nor the NB has the capability to accommodate the difference between structural and random zeros. When structural zeros are present in a count response, the count response becomes a mixed distribution, a mixture of degenerate zeros from the non-risk group (structural zeros) and responses (positive or random zero outcomes) from the at-risk group. The inherent methodological problems with structural zeros have received a great deal of attention in the statistical literature.[19-25]One popular approach is to use the mixture distribution based on zero-inflated models such as the zero-inflated Poisson (ZIP) model, which has been applied to a diverse range of studies.[26-30]

In this article, we first introduce some basic concepts about the mixture distribution and regression models for zero-inflated Poisson count responses and then use a real study example to illustrate the ZIP model. Sample codes in SAS and Stata and detailed explanations of the codes and output are provided.Finally, we discuss limitations of ZIP and related models and some newly developed methods that address such limitations.

2. Zero-inflated Poisson models

2.1 Zero-inflated Poisson distribution

In biomedical and psychosocial research the distribution of zeros often exceeds the expected frequency of zeros predicted by the Poisson model. Examples from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) study are shown in Figure 1: the distribution scores on the 9-item Patient Health Questionnaire (PHQ-9), a popular screening test for depression; the number of sexual partners in the past year (with 1 subtracted from the original outcome for the married and living-together couples); and the days of heavy drinking per month in the past year. In this example, the presence of excessive zeros reflects a proportion of subjects who were not at risk for the health condition or behavior of interest. For example,in the case of the number of sexual partners in the past year, the non-risk group are individuals who never had extra sexual partners beyond their spouse or significant other; these non-risk individuals substantially inflate the number of zero results beyond what is under the Poisson distribution. The distributions of the results shown in the figure provide support for a mixed population consisting of an at-risk subgroup and a non-risk subgroup for each of the respective outcomes of interest: depression, sexually transmitted diseases, and alcohol-related health problems.

Figure 1. Frequencies of scores on the 9-item Patient Health Questionnaire (PHQ-9), sexual partners in past year, and heavy drinking days per month

We use mixture distributions to model count responses with structural zeros. Within the current context, the mixture distribution is a mixture of two distributions, with one for the at-risk subgroup and other for the non-risk subgroup.

LetfR(y) be the distribution of the at-risk subpopulation, andf0(y) be a degenerate di≠stribution at 0, [i.e.,f0(y)=1 if y=0 andf0(y)=0 ify 0] for the non-risk subpopulation. Suppose the mixture probabilities for the structural zeros(non-risk subgroup) and the at-risk subgroup areρa(bǔ)nd 1-ρ. Then the mixture distribution can be expressed as

When a Poisson distribution with meanμ,fP(y|μ),is applied to the at-risk subpopulation, we obtain the following zero-inflated Poisson (ZIP)distribution

More precisely, the distribution can be also expressed as

So, the probability of being zero, Pr(y=0),is inflated fromfP(0|μ) under the Poisson distribution byρto account for structural zeros.The mean and variance offZIP(y|ρ,μ) are (1-ρ)μand (1-ρ)μ+(1-ρ)ρμ2, respectively.

Thus, the variance is larger than the mean, confirming that overdispersion may occur if a Poisson distribution is applied in place of ZIP.

Depending on the nature of the data, other distributions may be more appropriate for the at-risk subpopulation. For example, if there is still overdispersion in the at-risk subgroup due to data clustering, we may use NB instead of Poisson for this group, and obtain a zero-inflated NB (ZINB) distribution.[20]For variables where the outcome is the sum of a very limited number of repeated trials, such as the number of days of any drinking over the last week, a binomial-like distribution may be a natural choice for the at-risk subgroup, which results in a zero-inflated binomial distribution.[22,23]In this paper, we restrict our considerations to ZIP and ZINB as these distributions are available in SAS and Stata.

2.2 Zero-inflated Poisson regression models

It is both conceptually and theoretically reasonable to model the outcomes from the two groups of subjects separately due to the heterogeneity of the study sample.The ZIP model has two components, one component is to model the probability of being the structural zerosρusing the logistic regression and the other component is to model the Poisson meanμ. Specifically we have the ZIP model:

where the subscript i indicates the ithsubject, U and V (which may overlap) represent two sets of explanatory variables that will be linked to ρ and μ, respectively, in the ZIP model, andβUandβVare the vectors of parameters for the logistic and Poisson components.

In (4), the logit link function is used to model the likelihood of structural zeros; we can also use other link functions such as probit and complementary loglog. Thus, the presence of structural zeros gives rise not only to a more complex distribution, but also creates an additional link function for modeling the effect of explanatory variables for the occurrence of such zeros.In other words, the ZIP model enables us to better understand the effect of covariates by distinguishing the effects of each specific covariate on structural zeros (likelihood for being non-risk) and on the count response (mean of Poisson for the at-risk subgroup).While the fact that the presence of excessive zeros itself is sufficient to justify the use of zero-inflated models,Vuong has developed a test to formally test whether a ZIP is superior to a Poisson regression.[31]

When there is still dispersion in the at-risk subgroup,we may use the ZINB model, which is identical to ZIP,except that the NB replaces the Poisson to account for overdispersion for modeling the count response from the at-risk subpopulation. Thus a ZINB regression model has one logistic regression for structural zeros and one NB log-linear for the count response for the at-risk subgroup, with the additional dispersion parameter α from the NB to account for overdispersion.

3. Example

We use a study of sexual behavior among adolescent girls to illustrate the application of zero-inflated models.In this controlled randomized study, 640 girls were randomized into either the intervention or a control condition (containing only nutritional materials) to evaluate the short and longer-term efficacy of a Human Immunodeficiency Virus (HIV) -prevention intervention for adolescent girls residing in a high-risk urban environment.[32]A primary outcome is the number of vaginal sex encounters using condoms (VCD) reported over the past 3-month period, which was assessed at 3, 6 and 12 months following the intervention in this longitudinal study. Since we restrict ourselves to crosssectional analysis in the paper, we illustrate the models using this outcome from the 3-month assessment.The data can be downloaded from http://www.urmc.rochester.edu/biostat/people/faculty/Tang-He-Tu-Categorical-Book/sas5.html

Figure 2 presents the distribution of the frequency of VCD at the 3-month assessment. It is clear that there are excessive zeros in the distribution. The structural zeros represent those who were sexually abstinent.Since the status of structural zeros is not available, we apply zero-inflated models to analyze the data. For illustration purposes, we only present a simple model to examine the relationship between this outcome at 3 months and three potential covariates: score on the HIV Knowledge Questionnaire (HIVKQ, higher score means more informed about HIV knowledge), score on the Center for Epidemiological Depression scale (CESD,higher score means more depressed), and baseline number of vaginal sex encounters using condoms in the 3 months prior to intervention (VAGWCT1).

Figure 2. Frequency of protected vaginal sex (VCD)

The ZIP model consisted of two components; the logistic model for the inflated zero component for VCD:

and the component of Poisson loglinear model for the at-risk subgroup:

The Vuong test statistic was 4.858 (p-value ＜0.00001),which indicates that the ZIP model is better than the Poisson regression model.

Based on the estimates of the parameters in the count component (Table 1), both the baseline sexual behavior and HIV knowledge are highly associated with VCD. Subjects with higher baseline sexual behavior and higher HIV knowledge tend to have high VCD in the 3-month follow-up. Depression (CESD) is not significantly associated with VCD. Based on the estimates of the parameters in the zero inflation component (Table 2),only the baseline sexual behavior is associated with being a structural zero in VCD. That is, subjects with higher baseline sexual behavior tend to be less likely to be a structural zero in VCD in the 3-month follow-up.

Table 1. Analysis of maximum likelihood parameter estimates for count component of VCD

Table 2. Analysis of maximum likelihood zero inflation parameter estimates for inflated zero component of VCD

In this example, application of zero-inflated models enables us to ascertain the exact effect of the educational intervention. HIV knowledge is associated with VCD, but mainly through its effect on the count for the at-risk subgroup.

4. Statistical Software

The ZIP and ZINB regression models have been implemented in some popular statistical software packages, including SAS and Stata. However, they are not yet available in SPSS. In SAS, one may use either PROC GENMOD or PROC COUNTREG for ZIP and ZINB models. Here are the sample codes for the example described above using PROC GENMOD:

In this sample code, text in italic can be modified to specify the data source and models, while the text not in italics are SAS key words and must be entered exactly as they appear. The Poisson component for the count response is specified in the statement ‘MODEL’,following the common format for generalized linear models (‘response = ＜effects＞’). The option ‘d=zip’is used to indicate a ZIP model as desired. One may replace this with ‘d=zinb’ to fit a ZINB model.

The structural zero component is specified by the‘ZEROMODEL’ statement. In the sample codes above,the logit link is used, yielding the logistic regression.However, as in modeling binary outcomes, other commonly used link functions such as probit and complementary log-log may also be used, which are both available in SAS.

In SAS, one may also use the COUNTREG procedure to fit a ZIP or ZINB model. Below is the sample codes for using this procedure. Although the statements are quite similar to PROC GENMOD, it is important to note the difference in specifying the “ZEROMODEL” statement.In particular, the extra ‘VCD～’ statement is required to indicate the count variable whose structural zeros are modeled by the logistic regression.

Like PROC GENMOD, one may also use the COUNTREG procedure to fit the ZINB as well as use different link functions.

Vuong’s test is not available from PROC GENMOD,but a SAS macro program is available and can be downloaded from http://support.sas.com/kb/42/514.html. In addition to testing whether the ZIP is a better fit to the data at hand than the Poisson, the test may also be used to compare the ZIP and ZINB to see which one fits the data better.

In Stata, one may use the ‘zip’ or ‘zinb’ commands to fit ZIP or ZINB models. For example, we may apply the following Command for the ZIP analysis for the example in the previous section:

The first variable after the command ‘zip’ is the count response, followed by all the predictors for the count component in italics until the comma. The predictors for the zero component are specified in the parenthesis after the ‘inflate’ statement. The optional‘vuong’ statement is specified to use the Vuong test to compare the ZIP and Poisson models. One may change the Command from zip to zinb to fit the ZINB regression model.

5. Discussion

This article discusses structural zeros in count outcomes and how to use zero-inflated models to address this issue. Zero-inflated models are the natural approach when the status of structural zeros are unknown, that is, when structural zeros cannot be distinguished from random zeros. In cases where this distinction is known,we may take advantage of the additional information and apply hurdle models.[20]Like the ZIP, hurdle models have two components, one for the count response and the other for the structural zeros. Again, the Poisson and NB may be used for modeling the count response,and logistic regression may be applied for the structural zeros. However, since the status of structural zero is known, no mixture distribution is needed and the Poisson (or NB) and logistic regression of the hurdle model are essentially two separate models. Thus, no new software is needed for fitting the hurdle model.

As illustrated by the real data example presented,zero-inflated models have both conceptual and analytics advantages when there are excessive zeros. The zeroinflated models not only correct the overdispersion arising from the existence of structural zeros, but also allow for the distinction of different risk groups,providing better understanding of the data.

We limited ourselves to parametric models and cross-sectional data analysis because of the availability in common software packages. However, parametric approaches are prone to distribution misspecification,potentially yielding bias in estimates. For example, if the count response for the at-risk subgroup in a study data does not follow the NB distribution, assuming and fitting a ZINB model may yield biased estimates.Another problem is that cross-sectional models cannot be applied to investigate temporal changes from repeated assessments in longitudinal studies. Some new methods have been developed to address both of these limitations,[22,23]but they have not yet been included in popular statistical software packages such as SAS and Stata.

We have only discussed the structural zero issue when zero-inflated count variables are used as the response. The issue is also present when such variables serve as predictors in regression analyses. Indeed, using such variables as predictors and failing to distinguish structural and random zeros results in biased inference and makes it quite difficult to interpret estimates.[25]However, these issues have not yet been addressed in popular statistical software packages.

Conflict of interest

The authors decalre no conflict of interest.

Funding

This research was supported in part by NIH grant R33 DA027521 and a Novel Biostatistical and Epidemiologic Methods grants from the University of Rochester Medical Center Clinical and Translational Science Institute Pilot Awards Program.

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Dr. He is an Assistant Professor of Biostatistics in the Department of Biostatistics and Department of Psychiatry at the University of Rochester, as well as a researcher at the Center of Excellence for Suicide Prevention in Canandaigua, New York. Her research interests are in ROC analysis, semi-parametric and non-parametric inference, missing data modeling, causal inference, social network analysis,count data analysis and applications of statistical methods to psychosocial research. Dr. He received her PhD in Statistics from the Department of Biostatistics and Computational Biology at University of Rochester in 2007.

結(jié)構(gòu)性零和零膨脹模型

賀華, Wan TANG, Wenjuan WANG, Paul CRITS-CHRISTOPH

計(jì)數(shù)反應(yīng)，結(jié)構(gòu)性零，隨機(jī)零，零膨脹模型

Summary:In psychosocial and behavioral studies count outcomes recording the frequencies of the occurrence of some health or behavior outcomes (such as the number of unprotected sexual behaviors during a period of time) often contain a preponderance of zeroes because of the presence of ‘structural zeroes’ that occur when some subjects are not at risk for the behavior of interest. Unlike random zeroes(responses that can be greater than zero, but are zero due to sampling variability), structural zeroes are usually very different, both statistically and clinically. False interpretations of results and study findings may result if differences in the two types of zeroes are ignored. However, in practice, the status of the structural zeroes is often not observed and this latent nature complicates the data analysis. In this article, we focus on one model, the zero-inflated Poisson (ZIP) regression model that is commonly used to address zero-inflated data. We first give a brief overview of the issues of structural zeroes and the ZIP model. We then given an illustration of ZIP with data from a study on HIV-risk sexual behaviors among adolescent girls. Sample codes in SAS and Stata are also included to help perform and explain ZIP analyses.

[Shanghai Arch Psychiatry. 2014; 26(4): 236-242.

http://dx.doi.org/10.3969/j.issn.1002-0829.2014.04.008]

1Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY, USA

2Veterans Integrated Service Network, Center of Excellence for Suicide Prevention, Canandaigua VA Medical Center, Canandaigua, NY, USA3Department of Psychiatry, University of Rochester Medical Center, Rochester, NY, USA

4Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA

* correspondence: hua_he@urmc.rochester.edu

A full-text Chinese translation will be available at www.saponline.org on September 25, 2014.

概述：在社會(huì)心理學(xué)和行為學(xué)的研究中，記錄某些健康或行為結(jié)果發(fā)生頻率的計(jì)數(shù)中（如在一段時(shí)間內(nèi)無防護(hù)措施的性行為的次數(shù)）往往含有大量的零，這是因?yàn)楫?dāng)某些對(duì)象對(duì)于某種研究行為沒有危險(xiǎn)時(shí)就會(huì)產(chǎn)生“結(jié)構(gòu)性零”。不像隨機(jī)零（結(jié)果可以是大于零，但是也可能由于樣本變異性而成為零），結(jié)構(gòu)性零在統(tǒng)計(jì)和臨床上通常是非常不同的。如果兩種類型零的差異被忽略，就可能會(huì)導(dǎo)致對(duì)結(jié)果和研究發(fā)現(xiàn)的錯(cuò)誤解釋。然而在實(shí)踐中，結(jié)構(gòu)性零經(jīng)常會(huì)沒有被觀察到而這種潛在性使數(shù)據(jù)分析復(fù)雜化了。在這篇文章中，我們專注于一種模式，即通常用于解決零膨脹數(shù)據(jù)的零膨脹泊松（Zero-inflated Poisson，ZIP）回歸模型。首先，我們對(duì)結(jié)構(gòu)性零和ZIP模型做一個(gè)簡(jiǎn)要概述。然后我們以一項(xiàng)青春期少女艾滋病高危性行為的研究數(shù)據(jù)來闡述ZIP模型。文中還附有SAS和Stata的示例代碼，以幫助運(yùn)行和解釋ZIP分析。

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