Hardigan et al.

BMC Medical Informatics and Decision Making 2013, 13:60

http://www.biomedcentral.com/1472-6947/13/60

RESEARCH ARTICLE Open Access

Using latent class analysis to model prescription

medications in the measurement of falling
among a community elderly population
Patrick C Hardigan1*, David C Schwartz2 and William D Hardigan3

Abstract
Background: Falls among the elderly are a major public health concern. Therefore, the possibility of a modeling
technique which could better estimate fall probability is both timely and needed. Using biomedical,
pharmacological and demographic variables as predictors, latent class analysis (LCA) is demonstrated as a tool for
the prediction of falls among community dwelling elderly.
Methods: Using a retrospective data-set a two-step LCA modeling approach was employed. First, we looked for
the optimal number of latent classes for the seven medical indicators, along with the patients prescription
medication and three covariates (age, gender, and number of medications). Second, the appropriate latent class
structure, with the covariates, were modeled on the distal outcome (fall/no fall). The default estimator was
maximum likelihood with robust standard errors. The Pearson chi-square, likelihood ratio chi-square, BIC, Lo-
Mendell-Rubin Adjusted Likelihood Ratio test and the bootstrap likelihood ratio test were used for model
comparisons.
Results: A review of the model fit indices with covariates shows that a six-class solution was preferred. The
predictive probability for latent classes ranged from 84% to 97%. Entropy, a measure of classification accuracy, was
good at 90%. Specific prescription medications were found to strongly influence group membership.
Conclusions: In conclusion the LCA method was effective at finding relevant subgroups within a heterogenous at-
risk population for falling. This study demonstrated that LCA offers researchers a valuable tool to model medical
data.

Background model assumptions [1-4]. In this paper, we demonstrate

Latent Class Analysis (LCA) is a statistical method for the utility of LCA for the prediction of falls among
finding subtypes of related cases (latent classes) from community dwelling elderly.
multivariate categorical data [1]. The most common use Falls among the elderly are a major public health con-
of LCA is to discover case subtypes (or confirm hypoth- cern. Research on falls and fall-related behavior among
esized subtypes) based on multivariate categorical data the elderly has found that falls are the leading cause of
[1-4]. LCA is well suited to many health applications injury deaths among individuals who are over 65 years
where one wishes to identify disease subtypes or diag- of age [5-11]. Research has shown that sixty percent of
nostic subcategories [1-4]. LCA models do not rely on fall-related deaths occur among individuals who are
traditional modeling assumptions (normal distribution, 75 years of age or older [5-11]. Demography research
linear relationship, homogeneity) and are therefore, less estimates that by 2030, the population of individuals
subject to biases associated with data not conforming to who are 65 years of age or older will double and by 2050
the population of individuals who are 85 years of age or
* Correspondence: [email protected] older will quadruple [5-11].

Equal contributors Predicting elderly falling can be complex and often

1
Department of Public Health, Nova Southeastern University, 3200 South involves heterogeneous markers. Therefore, the identifi-
University Dr., Health Professions Division, Ft. Lauderdale, FL 33328, USA
Full list of author information is available at the end of the article cation of more homogeneous subgroups of individuals

2013 Hardigan et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
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and the refinement of the measurement criteria are typ- or no fall) and second what covariates increase or decrease
ically inter-related research goals. Appropriate statistical the likelihood of this occurrence. The four specific aims of
applications, such as latent class analysis, have become the study are to identify items that indicate classes,
available for researchers to model the complex hetero- estimate class probabilities, relate the class probabilities to
genous measurements. covariates, and predict a distal outcome (fall/no-fall) based
Latent class models are used to cluster participants. on class membership. We model this process through the
This type of model is adequate if the sample consists of application of latent class analysis (Figure 1).
different subtypes and it is not known before-hand
which participant belongs to which of the subtypes [2].
The latent categorical variable is used to model hetero- Methods
geneity. In the classic form of the latent class model, A convenient retrospective database consisting of a ran-
observed variables within each latent class are assumed dom sample of 3,293 elderly patients was used to develop
to be independent, and no structure for the covariances a model to predict the likelihood of falling among individ-
of observed variables is specified [2]. uals aged 65 years or older. Due to the retrospective
LCA is one of the most widely used latent structure nature of this study, this study was granted an exemption
models for categorical data [12]. LCA differs from more in writing by the Nova Southeastern Universitys IRB.
well-known methods such as K-means clustering which This is a poof-of-concept analysis so it should be noted
apply arbitrary distance metrics to group individuals that this data set was not designed for an LCA, therefore,
based on their similarity [13-15]. LCA derives clusters additional medical variables which may predict falling
based on conditional independence assumptions applied were not available. For this study an elderly person was
to multivariate categorical data distributed as binomial defined as someone aged 65 years or older. Descriptive
or multinomial variables [16,17]. Using statistical distri- data were as follows (Table 1): The average age of patients
butions rather than distance metrics to define clusters was 77 years old; 32 percent of the subjects had fallen in
helps in evaluating whether a model with a particular the last 30 days; falling patients were taking an average of
number of clusters is able to fit the data, since tests can five prescription medications while non-fallers were con-
be performed to observed (ni) versus model expected suming two; and 75 percent of the subjects were female.
values (mi), using exact methods as recommended [18,19]. Research demonstrates that about 22% of community-
This comparison gives rise to a 2 test of global model fit, dwelling elderly persons fall each year; 10% of these
in which significant values indicate lack of fit [20]. Here "fallers" have multiple episodes [21]. This research was ap-
lack of fit means deviation of (model) predicted (m) proved by Nova Southeastern University's Institutional
frequencies from observed frequencies (n) [16]. Review Board for human subjects research.
Latent class analysis assumes that each observation is a
member of one and only one latent class (unobservable)
and that the indicator (manifest) variables are mutually in-
dependent of each other [20]. The models are expressed
in probabilities of belonging to each latent class. For
example, seven manifest variables can be expressed as:
AjX BjX CjX DjX EjX FjX GjX
ijklmnot Xt it jt kt lt mt nt ot

where Xt denotes the probability of being in a latent class

AjX
(t = 1,2,,T) of latent variable X; it denotes the condi-
tional probability of obtaining the ith response from item
BjX CjX DjX
A, from members of class t, i = 1,2,,I; and jt kt lt
EjX FjX GjX
mt nt ot , j = 1,2,,j k = 1,2,,k l = 1,2,,l m = 1,2,,m
n = 1,2,,n O = 1,2,,O are the corresponding conditional
probabilities for items B,C,D,E,F, and G respectively.
We are testing the hypothesis that a two-class distal Figure 1 Proposed fall model for the latent class analysis. Yi are
relationship (fall/no fall) can explain the relationship the observed categorical medical indicators on the latent classes C.
among the biomedical, pharmacological and demographic Drug Measure is the correspondence analysis derived drug score for
variables. Proper analysis of this data requires the under- each subject. Age is the age of patient. # Rx is the number of
prescriptions taken by each subject. Gender is the subjects reported
standing of two interdependent outcomes.2 First, the
gender. Falling is the distal outcome.
binary outcome is whether or not the event occurred (fall
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Table 1 Descriptive statistics cerebral ischemia. Data from both principal and
Variable Statistic No-Fall Fall secondary diagnosis fields within a patient record.
N = 1906 N = 908
Age Mean SD 77.47 6.91 77.98 7.41 Pharmacological variables
Number of Medications Mean SD 2.30 5.57 5.10 10.10
 Type of prescription medicationtype of
Gender Male 27% 22%
prescription medication was taken from patient
Female 73% 78% records.
 Number of prescription medicationswas taken
The data set was taken from the State of Floridas Elder from patient records.
Affairs Office. All variables were physician diagnosed and
recorded in an electronic dataset using appropriate ICD-9 Demographic variables
codes. Variables included in the database were:
 Agewas taken from patient records.
Biomedical  GenderSelf reported male or female taken from
patients record.
 Arthritisdefined as a person diagnosed with
osteoarthritis (OA) and/or rheumatoid arthritis Outcome
(RA). Presence or absence of arthritis was based on
responses to questions on the basis of ICD-9 714.0,  Fallingwas defined as an event which results in
715. -716., from both principal and secondary the person coming to rest inadvertently on the
diagnosis fields within a patient record. ground or other lower level, and other than as a
 High Blood Pressure (HBP)defined as a person consequence of sustaining a violent blow. Falling
diagnosed with hypertension. HBP was identified on was taken from both principal and secondary
the basis of ICD-9 codes 401405, from both diagnosis fields within a patient record.
principal and secondary diagnosis fields within a
patient record. A two-step modeling approach was employed. First, it
 Diabetesdefined as a person diagnosed with was necessary to reduce the number of different medica-
diabetes mellitus. Diabetes was identified on the tions (N = 121). Initially, a licensed geriatric pharmacist
basis of ICD-9 codes of 250.0250.5 and 250.7 (PharmD) reviewed the medication list for accuracy and
250.9 from both principal and secondary diagnosis to remove medications that have not been shown to im-
fields within a patient record. pact the probability of falling. Using correspondence
 Heart Disease (HD)defined as a person diagnosed analysis (CA) the medications were converted to con-
with coronary artery disease. HD was identified on tinuous scores. CA is an exploratory technique related
the basis of ICD-9 codes 414.0x, from both principal to principal components analysis which finds a multidi-
and secondary diagnosis fields within a patient mensional representation of the association between the
record. row and column categories of a multi-way contingency
 Foot Disorders (FD)defined as a person diagnosed table [22]. This technique finds scores for the row and
with peripheral neuropathy, foot wounds, peripheral column categories on a small number of dimensions
vascular disease, or Charcot arthropa. FD was which account for the greatest proportion of the chi2 for
identified on the basis of ICD-9 codes 356.9, 892.0- association between the row and column categories, just
892.2, 443.9, and 713.5 from both principal and as principal components account for maximum variance
secondary diagnosis fields within a patient record. [22]. These scores were then used in the latent class ana-
 Parkinsons Disease (PD)defined as a person lysis. Similar to other data reduction techniques, CA can
diagnosed with Parkinsons Disease. PD was be used to transform data [23].
identified on the basis of ICD-9 code 332.0 from Second, we looked for the optimal number of latent clas-
both principal and secondary diagnosis fields within ses for the seven binary indicators: (1) arthritis, (2) high
a patient record. blood pressure, (3) diabetes, (4) heart disease, (5) foot disor-
 Strokedefined as a person diagnosed with ders, (6) Parkinsons disease, and (7) stroke; along with the
occlusion and stenosis of precerebral arteries patients medication score and three covariates (age, gen-
including basilar artery, carotid artery, and vertebral der, and number of medications). The appropriate latent
artery, etc.; occlusion of cerebral arteries including class structure, with the covariates, were modeled on the
cerebral thrombosis and Cerebral embolism; distal outcome (fall/no fall). The default estimator was max-
unspecified cerebral artery occlusion; and transient imum likelihood with robust standard errors. The Pearson
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Table 2 List of medications and correspondence scores Results

Level Number Score Data reduction
PHENOBARBITAL 8 0.690 Based on patient charts forty-one different medications
CLOMIPRAMINE 8 0.690
were used in the latent class analysis (Table 2). To
reduce this to a manageable number, correspondence
METHADONE 7 0.690
analysis (CA) was employed and the CA values were
IMIPRAMINE 17 0.423 saved for use in the latent class analysis. Due to missing
MORPHINE 36 0.423 data this reduced the number of subjects in the final
PRIMIDONE 43 0.405 model to 2,814. The higher the CA score the more likely
HYDROCODONE 46 0.262 the medication will induce a fall. CA scores are given by
DIAZEPAM 128 0.234
the following formula
CHLORDIAZEPOXIDE 45 0.225
RBAMAZEPINE 37 0.187

D0:5
r Prc2 Dc0:5
OXAZEPAM 23 0.155
MIRTAZAPINE 86 0.124
AMITRIPTYLINE 180 0.095
where:
ALPRAZOLAM 1297 0.094
CLONAZEPAM 368 0.077  P is the matrix of counts divided by the total
BUSPIRONE 124 0.072 frequency
OXYCODONE 206 0.054  r and c are row and column sums of P
GABAPENTIN 210 0.051
 the Ds are diagonal matrices of the values of r and c

DIGOXIN 272 0.038

A plot of the values indicates that an elderly person with
MEPROBAMATE 44 0.010 a score of 0.40 has a 50% chance of falling (Figure 2).
LORAZEPAM 572 0.009 For this manuscript CA values are averaged for each
DISOPYRAMIDE 9 0.023 person and referred to as the drug falling measure
NEFAZODONE 6 0.023 (singular value = 25%, inertia = 6% chi-square = 164.63).
PHENYTOIN 35 0.023
For example, a person may be using three different
medications with CA values of -0.30, 0.20, and 1.20; so
TEMAZEPAM 1470 0.030
their drug falling measure is 0.37. A higher drug falling
ESTAZOLAM 179 0.045 measure is associated with a higher probability of falling
PAROXETINE 338 0.049 (r = .19, p < 0.00).
CHLORPROMAZINE 11 0.165
TRIAZOLAM 16 0.227
FLUOXETINE 310 0.241
BACLOFEN 25 0.379
DESIPRAMINE 6 0.379
HYDROMORPHONE 7 0.379
HALOPERIDOL 11 0.379
CITALOPRAM 60 0.414
TRAZODONE 234 0.455
BUPROPION 20 0.498
DOXEPIN 83 0.580
PERPHENAZINE 19 0.593
AMOXAPINE 7 1.449
THIORIDAZINE 8 1.449

chi-square, likelihood ratio chi-square, (BIC), Lo-Mendell- Figure 2 Proposed fall model for the latent class analysis. This
is a plot of the probability of falling by correspondence analysis
Rubin Adjusted Likelihood Ratio test and the bootstrap
derived drug score.
likelihood ratio test were used for model comparisons.
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Table 3 Basic latent class structure

Four class solution Five class solution Six class solution Seven class solution
Pearson 2 2519 2196 2173 2172
LR 2
1171 1156 1143 1107
2 df 478 469 462 454
Loglikelihood 12922 12012 11672 11509
Number of parameters 48 61 74 87
BIC 24226 23893 23718 23710
LMR (p value) .000 .029 .758 .626
BLRT (p value) .000 .028 .758 .626
Entropy .854 .883 .893 .839

Latent class analysis Group I. Seventeen percent of the sample is

For the latent class analysis, a review of the model fit in- classified into latent class one (Table 4). The
dices shows that a six-class solution was preferred classification accuracy is 95%; the misclassified
(Table 3). The six-class solution provided a lower Bayesian elderly were all placed into class four (Table 4).
Information Criteria--BIC (lower is better), much smaller Subjects in class one have a 47% chance of falling.
chi-square values, and as indicated by the procedures The odds ratio indicate that a person in class one is
(Lo-Mendell-Rubin likelihood ratio test--LMR and 4.41 times more likely to fall than a person in class
bootstrap likelihood ratio test--BLRT), non-significant six: Healthy Group II (Tables 5 and 6).
p-values. Age, number of medications, and gender were  Class two is also affected by all measured medical
shown to have a significant impact on falling. Females, conditions (Figure 3). The average age of this class is
older patients, and the more prescription drugs an elderly 76.89 7.02, the average number of medications is
person takes, the greater the probability that they will fall. 7.5, and the drug falling measure is 0.017. This is
Table 2 provides a comparison of fit indices for four-class, defined as the Poorest-Health Group II. Twenty-
five-class, six-class and seven-class solutions. The six class eight percent of the sample is placed into latent
structure, with covariates is interpreted as follows: class two (Table 4). The classification accuracy is
89% (Table 4); misclassified elderly were placed into
 Class one is most likely to be affected by all medical class three. Subjects in class two have a 46% chance
conditions (Figure 3). The average age of this class is of falling. The odds ratio indicate that a person in
77.78 7.01, the average number of medications is class two is about 4.67 times more likely to fall than a
4.7, and the average drug falling measure is 0.016. person in class six: Healthy Group II (Tables 5 and 6).
Latent class one is defined as the Poorest-Health  Class three is generally unaffected by all medical
markers (Figure 3). The average age of this class is
78.83 6.63, the average number of medications is
7.8, and the drug falling measure is 0.006. We define
1

this as the Healthy Group I. Seventeen percent of

.8

the sample is classified class three (Table 4). The

Probability
.6

classification accuracy for latent class three is 84%

(Table 4). Misclassified elderly were placed into class
.4

two, indicating some overlap between the two latent

.2

classes. Subjects in class three have a 16% chance of

falling. There is no significant difference in the
0

likelihood of falling between class three and class

is

FD

BP

PD

ke
D
rit

ro
H
th

St
Ar

Medical Condition six: Healthy Group II (Tables 5 and 6).

Latent Class 1 Latent Class 2  Class four is primarily affected by arthritis;
Latent Class 3 Latent Class 4
Latent Class 5 Latent Class 6 therefore, this is defined as the arthritis group
(Figure 3). Twenty-percent of the sample fell into
Figure 3 Overlay plot of latent classes by medical condition. latent class four (Table 4). The average age of this
Arthritis = Arthritis. HBP = High Blood Pressure. DB = Diabetes. class is 78.69 7.32, the average number of
HD = Heart Disease. FD = Foot Disorders. PD = Parkinsons
medications is 2.6, and the drug falling measure is
Disease. Stroke = Stroke.
-0.003. The classification accuracy is 96% (Table 4).
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Table 4 Most likely latent class membership

Count Proportion Class 1 Class 2 Class 3 Class 4 Class 5 Class 6
Class 1 477 17% 0.95 0.00 0.00 0.04 0.00 0.00
Class 2 792 28% 0.00 0.89 0.11 0.00 0.00 0.00
Class 3 486 17% 0.00 0.16 0.84 0.00 0.00 0.00
Class 4 553 20% 0.04 0.00 0.00 0.96 0.00 0.00
Class 5 222 8% 0.01 0.00 0.00 0.00 0.95 0.04
Class 6 284 10% 0.00 0.00 0.00 0.00 0.03 0.97
Total 2,814 100%

Misclassified elderly were placed into class one. Discussion

Subjects in class three have a 26% chance of falling. This paper demonstrated the utility of LCA in the meas-
The odds ratio indicate that a person in class four urement of falling among community-dwelling elderly.
is approximately 2.07 times more likely to fall than The basic idea underlying LCA is that variables differ
a person in class six: Healthy Group II (Tables 5 across previously unrecognized subgroups [24]. These
and 6). subgroups form the categories of a categorical latent
 Class five is primarily affected by high blood variable. Given the potential for confounding among the
pressure,diabetes, heart disease and foot disorders study variables, latent class analysis holds great promise.
(Figure 3). This group is defined as the diabetes- The six-class solution was statistically sound and pro-
heart disease group. Eight percent of the sample fell vided a relatively straightforward interpretable number
into latent class five (Table 4). The average age of of classes. The interpretation of a LCA relies on both
this class is 77.53 7.04, the average number of the statistical indices and the practical interpretation of
medications is 3.1, and the drug falling measure is -0 the classes. In our example, the statistical indices
.009. The classification accuracy is 95% (Table 4). strongly point toward a six factor model. The classifica-
Misclassified elderly were placed into either class tion accuracy for the model was very good. Furthermore,
one (Unhealthy Group I) or six (Healthy Group I). we were able to define each latent class, which provides
Subjects in class five have a 29% chance of falling. researchers and practitioners practical implications of
The odds ratio indicates that a person in class five is the analysis.
2.24 times more likely to fall than a person in class Medication usage helped differentiate the latent clas-
six: Healthy Group II (Tables 5 and 6). ses. Subjects in latent class one have higher probabilities
 Class six is least affected by the medical conditions of possessing the seven medical conditions than subjects
and is defined as healthy group II (Figure 3). Ten in latent class two; yet, subjects in latent class two pos-
percent of the sample fell into latent class six sess similar rates of falling. This may be explained by the
(Table 4). The average age of this class is 78.87 number of medications that class two is taking (7.5 vs.
7.48, the average number of medications is 4.3, and 4.7). Similarly latent class three and six are both defined
the drug falling measure is -0.012. The classification as the healthy groups. Differentiating the two groups is
accuracy is 97% (Table 4). Subjects in class three the number of medications taken by subjects in latent
have a 15% chance of falling. Misclassified elderly class three vs. latent class six (7.8 vs. 4.3).
were placed into class five: the diabetes-heart disease It also true that the type of medications subjects are tak-
group (Tables 5 and 6). ing is impacting their probability of falling. This can be
demonstrated for latent class one. Holding age and

Table 5 Most likely latent class membership Table 6 Odds ratios

Class 1 Class 2 Class 3 Class 4 Class 5 Class 6 Class Class Odds ratio P-Value Lower Upper
95% CI 95% CI
Class 1 .95 .00 .00 .04 .00 .00
6 Vs 1 4.41 0.000 3.07 6.46
Class 2 .00 .89 .11 .00 .00 .00
6 Vs 2 4.67 0.000 3.32 6.72
Class 3 .00 .16 .84 .00 .00 .00
6 Vs 3 1.12 0.574 0.75 1.69
Class 4 .04 .00 .00 .96 .00 .00
6 Vs 4 2.07 0.000 1.43 3.04
Class 5 .01 .00 .00 .00 .95 .04
6 Vs 5 2.24 0.000 1.45 3.49
Class 6 .00 .00 .00 .00 .03 .97
Note: Base or comparison group is class six or the healthy group II group.
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Competing interests
The authors declare that they have no competing interests.
doi:10.1186/1472-6947-13-60
Cite this article as: Hardigan et al.: Using latent class analysis to model
Authors contributions prescription medications in the measurement of falling among a
PH, DS and WH participated in the design, coordination, project planning community elderly population. BMC Medical Informatics and Decision
and data collection. PH performed the statistical analysis and drafted the Making 2013 13:60.
manuscript. All authors read and approved the final manuscript.

Author details
1
Department of Public Health, Nova Southeastern University, 3200 South
University Dr., Health Professions Division, Ft. Lauderdale, FL 33328, USA. 2The
ElderCare Companies, Inc, 2517 State Rt. 35, Bldg. J Ste. 203, Manasquan, NJ
08736, USA. 3College of Pharmacy, Nova Southeastern University, 3200 South
University Dr., Health Professions Division, Ft. Lauderdale, FL 33328, USA. Submit your next manuscript to BioMed Central
and take full advantage of:
Received: 8 August 2012 Accepted: 13 May 2013
Published: 25 May 2013
Convenient online submission

References Thorough peer review

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