Biascorrected estimator for intraclass correlation coefficient in the balanced oneway random effects model
 Eshetu G Atenafu†^{1},
 Jemila S Hamid†^{2, 4},
 Teresa To^{3, 4, 5},
 Andrew R Willan^{3, 4},
 Brian M Feldman^{3, 4, 5} and
 Joseph Beyene^{2, 3, 4, 5}Email author
DOI: 10.1186/1471228812126
© Atenafu et al.; licensee BioMed Central Ltd. 2012
Received: 15 August 2011
Accepted: 18 July 2012
Published: 20 August 2012
Abstract
Background
Intraclass correlation coefficients (ICCs) are used in a wide range of applications. However, most commonly used estimators for the ICC are known to be subject to bias.
Methods
Using second order Taylor series expansion, we propose a new biascorrected estimator for one type of intraclass correlation coefficient, for the ICC that arises in the context of the balanced oneway random effects model. A simulation study is performed to assess the performance of the proposed estimator. Data have been generated under normal as well as nonnormal scenarios.
Results
Our simulation results show that the new estimator has reduced bias compared to the least square estimator which is often referred to as the conventional or analytical estimator. The results also show marked bias reduction both in normal and nonnormal data scenarios. In particular, our estimator outperforms the analytical estimator in a nonnormal setting producing estimates that are very close to the true ICC values.
Conclusions
The proposed biascorrected estimator for the ICC from a oneway random effects analysis of variance model appears to perform well in the scenarios we considered in this paper and can be used as a motivation to construct biascorrected estimators for other types of ICCs that arise in more complex scenarios. It would also be interesting to investigate the biasvariance tradeoff.
Background
The intraclass correlation coefficient (ICC), often denoted by ρ, was first introduced by Fisher [1] to study the familial resemblance between siblings. Since then it has obtained a wide range of applications in many areas such as psychology, epidemiology, genetics and genomics. See Donner [2] for an extensive review of inference procedures. In psychology, it plays a fundamental role in studying interrater reliability [3, 4]. It is used as a measure of heritability in classical genetic linkage studies to quantify the proportion of variance in traits of interest explained by genetic factors [5]. Intraclass correlation obtained from genomewide association data has recently been used to provide a better estimate of heritability [6] . Sensitivity analysis is another application where ρ may be used as a means of investigating the effectiveness of an experimental treatment [7]. The intraclass correlation has also found some interesting application in genomics where it has been used to assess methodological and biological variations in DNA microarray analysis [8].
The intraclass correlation coefficient also plays a key role in study design such as design of cluster randomized trials where it is traditionally used to quantify the degree of similarity between individuals within clusters [9, 10].
Over the last decade, ICCs have received more attention in the literature and there has been an increasing awareness and appreciation of methodological issues related to these indices [11–13].
The most fundamental interpretation of ICCs is as a measure of the proportion of variance of a given outcome variable explained by a factor of interest in an analysis of variance model where it measures the relative homogeneity within groups [14, 15]. The first and essential step, therefore, is to specify an appropriate analysis of variance (ANOVA) model that best describes the study. The choice of the model is dictated by the specific situation defined by the experimental design and conceptual intent of the study [15]. Moreover, various forms of ICCs arise depending on the chosen model and the nature of the study [16, 17].
For reasons mentioned above, inference procedures for ρ are closely related to the more general statistical problem of variance components [14, 18]. It is well known that estimation and hypothesis testing procedures for ICCs are, in general, sensitive to the assumption of normality and are subject to unstable variance [1, 19]. One, therefore, needs to consider normalizing and variancestabilizing transformations on the basis of the rate of convergence to normality when constructing confidence intervals for the ICC. One of the well known and most commonly used normalization technique is Fisher’s Z transformation [1]. Other types of transformations have also been considered for the intraclass correlation coefficient [19, 20].
Another important issue concerning ICCs is bias [21, 22]. The two most commonly used estimators, maximum likelihood and least square estimators, are known to be negatively biased. Although a Minimum Variance Unbiased (MVU) estimator for the intraclass correlation coefficient under two normal distributions is derived by [23], use of this estimator has been hindered because of absence of a closed form. Consequently, the MVU estimator is less widely recognized while the least square and maximum likelihood estimators are wellknown. A computationally intensive FORTRAN subroutine is provided by Donoghue and Collins (1990).
The purpose of this paper is, therefore, to provide a biascorrected estimator for the intraclass correlation coefficient which is much simpler to compute and hence useful in practice. We consider a particular type of ICC in which we consider the estimation problem for ICC resulting from a oneway random effects analysis of variance model. We approximate the bias using a secondorder Taylor series expansion and adjust the estimator to reduce the bias.
The paper is organized as follows. We provide a brief background about the oneway random effects model and define the particular ICC of interest in Section “Methods”. In Section “Biascorrected estimator for the intraclass correlation coefficient”, we propose a technique for approximating the bias resulting from the conventional estimator of ρ and we derive a new biascorrected estimator for the parameter. We present simulation results in Section “Simulation Study” and provide a brief discussion in Section “Discussion”. Finally an Appendix consisting of some technical results is given at the end of the paper.
Methods
where it is assumed that ${a}_{i}\sim N(0,{\sigma}_{T}^{2}),\phantom{\rule{2.77695pt}{0ex}}\phantom{\rule{2.77695pt}{0ex}}\phantom{\rule{2.77695pt}{0ex}}{e}_{\mathit{\text{ij}}}\sim N(0,{\sigma}_{e}^{2})$.
Analysis of variance table for oneway random effects model
Source of Variation  df  SS  MS=SS/df  Expected MS 

Between Targets  n1  SSB  BMS  $k{\sigma}_{T}^{2}+{\sigma}_{e}^{2}$ 
Within Targets  n(k1)  SSE  EMS  ${\sigma}_{e}^{2}$ 
Note that,

EMS is an unbiased estimator of ${\sigma}_{e}^{2}$

(BMSEMS)/k is an unbiased estimator of ${\sigma}_{T}^{2}$
Although the estimator in (4) is a ratio of unbiased estimators, it need not necessarily be unbiased itself. We consider the bias resulting from this estimator in the next section and provide a new biascorrected estimator for the intraclass correlation coefficient.
Biascorrected estimator for the intraclass correlation coefficient
An unbiased estimator for F is provided in the following theorem, which is useful in approximating the bias for estimating intraclass correlation coefficient. The variance of is also given in the theorem. The theorem has been considered by [25] in a different context.
Theorem 1
A proof of the theorem is provided in the Appendix.
As mentioned earlier, the estimator, $\stackrel{~}{\rho}$, in (6) need not be unbiased although it is a function of unbiased estimators. In fact, the bias is always negative and depends on the degree of correlation and the design size and balance [21].
It can be shown using our approximation that the bias in general decreases as the degree of correlation moves away from 0.5. That is, the bias is small for both weak and strong correlations. Our simulation results confirm that the bias resulting from the analytical estimator is indeed small when the true value of ρis small (weak correlation) or large (strong correlation) (see Section “Discussion” for more details). As a result, we expect the performance of the conventional estimator to improve in such cases. In fact, previous simulation results have also showed that the analytical estimator, $\widehat{\rho}$, performs well for small values of ρ both for normal and nonnormal data (e.g., producing confidence intervals close to the nominal level [10]. Our simulation results show that the estimators we proposed in this paper provide a considerable bias reduction even under such circumstances (see Section “Discussion” for details).
Simulation Study
We carried out extensive simulations to evaluate the performance of our biascorrected estimator $\left({\stackrel{~}{\rho}}_{\mathit{\text{bc}}}\right)$. The bias resulting from our estimator is compared with bias from the conventional (analytical) estimator using normal as well as nonnormal data. It is to be recalled that we based the Taylor expansion around $\stackrel{~}{\rho}$ which a variant of the conventional estimator. We have, therefore, provided the bias resulting from this estimator for comparison purposes.
Simulation Design
Data were simulated as in [10], with slight modifications to the number of configurations that were allowed to vary. We used 3x8x2 design instead of their 3x4x2 configuration. That is, we considered 3 cluster sizes (10,30,50); 8 intraclass correlation coefficients (0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9) instead of only 4 true ICC values used in [10]; and two types of data distributions (normal versus nonnormal), for a total of 48 simulation configurations.
For normal outcome, data were simulated according to the framework of the oneway random effects model described in Section “Methods”. They were generated as the sum of two independent random variables ${a}_{i}\sim N(0,{\sigma}_{T}^{2})$ and ${e}_{\mathit{\text{ij}}}\sim N(0,{\sigma}_{e}^{2})$. When simulating nonnormal outcome, the e _{ ij } alone were generated from a normal distribution with the a _{ i }generated from a Gamma distribution with shape parameter α = 1.67 and scale parameter $\beta =\frac{\sqrt{\mathit{\text{Var}}}}{\alpha}$ so that skewness of the distribution will be $\frac{2}{\alpha}=1.2$ and a kurtosis coefficient of $\frac{6}{\alpha}=4$. The skewness and kurtosis coefficients represent marked deviation from normality. The skewness and kurtosis coefficients for a normally distributed random variable are 0 and 3, respectively.
We simulated 5000 replications of data for each of the 48 scenarios. Different seeds were used for the random number generator at each replication while keeping it the same across different methods.
Results
Simulation results for the nonnormal data
Estimate  % Bias  

Clusters  ICC  $\widehat{\mathit{\rho}}$  $\stackrel{\mathbf{~}}{\mathit{\rho}}$  ${\stackrel{\mathbf{~}}{\mathit{\rho}}}_{\mathit{bc}}$  $\widehat{\mathit{\rho}}$  $\stackrel{\mathbf{~}}{\mathit{\rho}}$  ${\stackrel{\mathbf{~}}{\mathit{\rho}}}_{\mathit{bc}}$ 
10  0.1  0.0927  0.0891  0.0941  7.3  11.0  5.9 
0.2  0.1813  0.1768  0.1911  9.4  12.0  4.5  
0.3  0.2678  0.2627  0.2890  11.0  12.0  3.7  
0.4  0.3543  0.3488  0.3865  11.0  13.0  3.4  
0.5  0.4423  0.4367  0.4830  12.0  13.0  3.4  
0.6  0.5337  0.5282  0.5785  11.0  12.0  3.6  
0.7  0.6306  0.6256  0.6744  9.9  11.0  3.7  
0.8  0.7360  0.7319  0.7743  8.0  8.5  3.2  
0.9  0.8552  0.8526  0.8809  5.0  5.3  2.1  
30  0.1  0.0977  0.0964  0.0977  2.3  3.6  2.3 
0.2  0.1935  0.1919  0.1954  3.3  4.1  2.3  
0.3  0.2883  0.2865  0.2954  3.9  4.5  1.5  
0.4  0.3830  0.3810  0.3951  4.3  4.8  1.2  
0.5  0.4783  0.4763  0.4929  4.3  4.7  1.4  
0.6  0.5751  0.5733  0.5899  4.2  4.4  1.7  
0.7  0.6745  0.6728  0.6880  3.6  3.9  1.7  
0.8  0.7773  0.7760  0.7883  2.8  3 .0  1.5  
0.9  0.8851  0.8844  0.8919  1.7  1.7  0.9  
50  0.1  0.0984  0.0977  0.0984  1.6  2.3  1.6 
0.2  0.1957  0.1947  0.1965  2.1  2.6  1.8  
0.3  0.2924  0.2912  0.2966  2.5  2.9  1.1  
0.4  0.3890  0.3878  0.3968  2.8  3.1  0.8  
0.5  0.4862  0.4850  0.4951  2.8  3.0  1.0  
0.6  0.5844  0.5832  0.5931  2.6  2.8  1.2  
0.7  0.6842  0.6832  0.6921  2.3  2.4  1.1  
0.8  0.7861  0.7854  0.7925  1.7  1.8  0.9  
0.9  0.8911  0.8907  0.8949  1.0  1.0  0.6 
Simulation results for the normal data
Estimate  % Bias  

Clusters  ICC  $\widehat{\mathit{\rho}}$  $\stackrel{\mathbf{~}}{\mathit{\rho}}$  ${\stackrel{\mathbf{~}}{\mathit{\rho}}}_{\mathit{bc}}$  $\widehat{\mathit{\rho}}$  $\stackrel{\mathbf{~}}{\mathit{\rho}}$  ${\stackrel{\mathbf{~}}{\mathit{\rho}}}_{\mathit{bc}}$ 
10  0.1  0.0969  0.0932  0.0979  3.2  6.8  2.1 
0.2  0.1905  0.1858  0.2001  4.8  7.1  0.1  
0.3  0.2832  0.2778  0.3071  5.6  7.4  2.4  
0.4  0.3759  0.3701  0.4140  6.0  7.5  3.5  
0.5  0.4696  0.4637  0.5158  6.1  7.3  3.2  
0.6  0.5652  0.5596  0.6135  5.8  6.7  2.3  
0.7  0.6641  0.6591  0.7094  5.1  5.8  1.3  
0.8  0.7677  0.7638  0.8049  4.0  4.5  0.6  
0.9  0.8784  0.8760  0.9016  2.4  2.7  0.2  
30  0.1  0.0995  0.0983  0.0995  0.5  1.7  0.5 
0.2  0.1976  0.1960  0.1989  1.2  2.0  0.6  
0.3  0.2953  0.2934  0.3029  1.6  2.2  1.0  
0.4  0.3929  0.3909  0.4067  1.8  2.3  1.7  
0.5  0.4910  0.4889  0.5063  1.8  2.2  1.3  
0.6  0.5897  0.5878  0.6047  1.7  2.0  0.8  
0.7  0.6895  0.6878  0.7030  1.5  1.7  0.4  
0.8  0.7908  0.7895  0.8015  1.2  1.3  0.2  
0.9  0.8941  0.8934  0.9005  0.7  0.7  0.1  
50  0.1  0.0990  0.0983  0.0990  1.0  1.7  1.0 
0.2  0.1978  0.1969  0.1984  1.1  1.6  0.8  
0.3  0.2965  0.2954  0.3009  1.2  1.5  0.3  
0.4  0.3952  0.3940  0.4037  1.2  1.5  0.9  
0.5  0.4942  0.4929  0.5033  1.2  1.4  0.7  
0.6  0.5935  0.5924  0.6024  1.1  1.3  0.4  
0.7  0.6936  0.6926  0.7015  0.9  1.1  0.2  
0.8  0.7945  0.7938  0.8008  0.7  0.8  0.1  
0.9  0.8966  0.8961  0.9002  0.4  0.4  0.0 
In general, a considerable bias reduction has been obtained by using our biascorrected estimator. This is true for all values of ρand all cluster sizes although the improvement is much larger for moderate correlations (see Figure 1). Moreover, the improvement obtained for the nonnormal sample is relatively larger than that obtained for the normal sample. For the nonnormal sample, for instance, using the conventional estimator resulted in 12% bias whereas only 3.4% bias was obtained from our estimator for cluster size 10 and moderate correlations. For the normal sample and the same scenario, biases resulting from the conventional estimator and the biascorrected estimator are 6% and 3%, respectively. Improvements are also obtained for small or large ρ values, that is, in situations where the bias from the conventional estimator is small. For instance, for cluster size 10 from the nonnormal sample with ρ = 0.2, 9.4% and 12% biases were obtained using $\widehat{\rho}$ and $\stackrel{~}{\rho}$, respectively, whereas only 4.5% bias was observed for our estimator. For the normal sample with the same cluster size and correlation, $\widehat{\rho}$ and $\stackrel{~}{\rho}$ resulted in 4.8% and 7.1% biases. In this situation, the bias reduced to 0.05% when using our bias corrected estimator. Similar statements can be made for large ICC values.
Discussion
The intraclass correlation coefficient (ICC) has widespread applications from measuring heritability in genetic studies to measuring reliability, consistency and agreement of measurements in a host of clinical, biomedical and psychosocial areas. The ICC has important role in study design and sample size calculations as well. For instance, designs of familybased genetic studies can be greatly impacted by the estimated ICC (often referred to as the coefficient of heritability in the genetics literature). Similarly, trials involving clustering of some degree (e.g., longitudinal study design, multilevel models, cluster randomized trials, etc.) will be influenced to various extent by the magnitude of the intraclass correlation coefficient. Because ICC estimates have great implications to design considerations, statistical analysis as well as interpretation of study findings, it is critical to use an estimator with minimal bias.
In this paper, we proposed a new biascorrected estimator for one type of intraclass correlation coefficient. We used a variant of the conventional estimator (ANOVA estimator) and applied Taylor series expansion to approximate the bias. The approximate bias was then used and a new adjusted estimator is proposed. The biascorrected estimator proposed in this paper is much simpler to compute than the minimum variance unbiased (MVU) estimator of Olkin and Pratt [23]. Moreover, our simulation study shows that our estimator outperforms the conventional estimator by providing a substantial decrease in the bias. For small cluster sizes from normal data, however, a positive bias was introduced although the percentage bias resulted from our estimator is still smaller than that of the ANOVA estimator. This might be improved by using second order Taylor series expansion instead of using only the first order adopted in this paper.
Conclusion
We considered a particular type of intraclass correlation coefficient that arises from a oneway random effects analysis of variance model, although the method can be extended to provide biascorrected estimators for other types of ICCs. Furthermore, the current paper is focused on bias reduction in a balanced data setting, and we plan to investigate other optimality measures as well as the performance of the biascorrected method for unbalanced data when the number of observations differ from cluster to cluster. Finally, we would like to highlight that ICCs are subject to different interpretations, so the user should apply the various ICCs with caution [17, 26–28].
Appendix
Which implies that $E\left[\frac{1}{\mathit{\text{SSE}}}\right]=\frac{1}{{\sigma}_{e}^{2}\left[n(k1)2\right]}$.
which proves the first part of the theorem.
Notes
Declarations
Acknowledgements
We would like to gratefully acknowledge a seed grant support provided by the Research Institute of the Hospital for Sick Children, Toronto, Ontario, Canada.
Authors’ Affiliations
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