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Croy C, Novins D. Methods for Addressing Missing Data in Psychiatric and Developmental Research. J Am Acad Child Adolesc Psychiatry

RESOURCE APPENDIX

Reference Materials – General

For an introduction to methods for handling missing data, we recommend the book

Missing Data by Paul Allison (2002). For a more detailed treatment see “Missing Data:

Our View of the State of the Art” by Schafer and Graham (2002). Readers wanting a comprehensive review should consult Statistical Analysis with Missing Data (2nd ed.) by

Little and Rubin (2002).

Software

Calculation of Means and Covariance Matrix Using EM

S-Plus 6.0 http://www.insightful.com/products/splus/default.asp

SPSS For Windows 11.5 and higher, MVA Package

http://www.spss.com/missing_value/

SAS/STAT For Windows 8.2 and higher, Proc MI http://support.sas.com/rnd/app/da/new/dami.html

EM-based Imputation and Conditional Mean Substitution SPSS For Windows 11.5 and higher, MVA Package

http://www.spss.com/missing_value/

SAS/STAT 9.1 and higher, Proc MI

http://support.sas.com/91doc/docMainpage.jsp

(click refresh button on browser if contents of navigation window doesn’t appear)

1 Estimation of Linear Models Using Direct (Full Information) Maximum Likelihood

SAS (stand alone commercial software)

www.sas.com/technologies/analytics/statistics/stat/index.html

(look for SAS/STAT product, Proc Mixed Procedure)

SPSS (stand alone commercial software)

www.spss.com/advanced_models/brochures.htm

(download PDF spec sheet, look for Linear Mixed Models Procedure)

Amos (stand alone or module for SPSS) www.spss.com/amos/index.htm

Mplus (stand alone commercial software) www.statmodel.com

LISREL (stand alone commercial software)

http://www.ssicentral.com/lisrel/mainlis.htm

Mx (free stand-alone software for matrix algebra and numerical optimization)

http://www.vcu.edu/mx/

Multiple Imputation

Two Internet sites provide a lot of easy-to-digest explanations, citations for further reading, some source text available via links, and free software:

2 http://www.stat.psu.edu/~jls/misoftwa.html

(the link for Frequently Asked Questions is especially helpful)

http://www.multiple-imputation.com/

(the link for Literature is especially helpful)

Horton and Lipsitz (2001) provide a detailed review of the following software for multiple imputation:

SOLAS 3.0 www.statsol.ie/solas/solas.htm

(note that the propensity score method in SOLAS is invalid for many applications.

See Allison, (2000) or Schafer and Graham (2002))

SAS Version 8.2 (Procs MI and MI Analyze)

http://support.sas.com/rnd/app/da/new/dami.html

Missing Data Library for S-Plus 6.0 www.insightful.com

MICE www.multiple-imputation.com (free software)

Additional free software for multiple imputation:

At http://www.stat.psu.edu/~jls/misoftwa.html

NORM (S-Plus library or stand-alone Windows version for continuous normal

data)

CAT (S-Plus library for categorical data under log linear model)

MIX (S-Plus library for mixed continuous and categorical data)

PAN (S-Plus library for panel or clustered data)

3 At http://gking.harvard.edu/stats.shtml

Amelia (stand-alone program based on King et al.’s (2001) alternative algorithm)

At http://www.isr.umich.edu/src/smp/ive/

IVEware (stand-alone and SAS programs for imputing data of diverse types and calculating descriptive statistics including model coefficients. Uses sequential regression (Raghunathan et al., 2001)).

Stata users can download user-written package st0067_1 for multiple imputation. Royston (2005) describes this software and provides examples of usage. To download this software Stata users should open Stata, open the Help menu, click SJ and User-written Programs, then click Search, and enter the word

“imputation”. Click on Package st0067_1 in the results from the search to display a link to install the software.

4 TECHNICAL APPENDIX

Issues Relating to Whether Missing Data are Missing at Random and Informative Drop- outs in Longitudinal Studies

Psychiatric and developmental researchers may contemplate using imputation algorithms where the missing values for each study participant are predicted from the observed values for that person (from our perspective, most of the algorithms in imputation software that are both easy for psychiatric and developmental researchers to access and use and that are the focus of recent statistical research are of this type).

These algorithms are based on the assumption that the data are Missing at Random.

Indeed “MAR [Missing at Random] is the formal assumption that allows us to first estimate the relationships among variables from the observed data, and then use these relationships to obtain unbiased predictions of the missing values from the observed values” (Schafer and Olsen, 1998, p. 552). Some researchers have gone so far as to say that “when the assumption of ignorable missing data is not met [i.e. when the data are not Missing at Random], imputation is usually not appropriate” (McCleary, 2002, p.

340), citing Rubin (1987)). Whether this advice is warranted or is an overgeneralization depends on the specific algorithms being considered.

Other researchers may be more comfortable estimating replacement values for a person from his/her observed data though they know the true values are related to data they have not collected. When such researchers impute using algorithms that are based on the Missing at Random assumption, they cannot take advantage of information that may be critical to obtaining accurate estimated values. Consequently any derived statistics may be biased by an unknown amount. Therefore, researchers

5 concerned that their missing data may not be Missing at Random should note the following points.

1. Whether imputation with algorithms that assume data are Missing at

Random is acceptable when the assumption may be violated to a minor degree is controversial. Schafer and Olsen (1998) report that “In the vast majority of studies, principled methods that assume MAR [Missing at Random] will tend to perform better than ad hoc procedures such as listwise deletion or imputation of means” (p. 553).

Collins et al. (2001) demonstrate that erroneous assumptions of Missing at Random may have only minor impact on estimates and standard errors. Additionally, Schafer and Graham (2002) suggest that standard maximum likelihood approaches may be useful because “in many psychological research settings the departures from MAR

[Missing at Random] are probably not serious” (p. 154). Schafer and Graham (2002) also note that when the missing data were never intended to be collected (e.g. cohort- sequential designs for longitudinal studies and use of multiple questionnaire forms containing different subsets of items) the missing values are either Missing Completely at Random or Missing at Random.

2. Having informative drop-out in longitudinal (repeated measures) studies is a special case of when data are likely to violate the Missing at Random assumption. Advanced methods for dealing with missing data that are not Missing at

Random are as appropriate for this situation as they are for cross-sectional studies.

Most of these methods are either selection models or pattern mixture models

(Fairclough, 2004; Little and Rubin, 2002; Schafer and Graham, 2002). In selection models one first specifies a frequency distribution for the complete data, and then one

6 models how the probability of drop-out depends on the data (Schafer and Graham,

2002). In pattern mixture models, the distribution of a variable’s values is estimated as a mixture of its distributions in sets of observations grouped according to their missing data pattern (Fairclough, 2004). Verbeke and Molenberghs (2000) and Little (1995) have reviewed both selection models and pattern mixture models for longitudinal studies with drop-out. The following references may also be of interest: Diggle and

Kenward (1994), Fitzmaurice et al. (1995), Follmann and Wu (1995), Hogan et al.

(2004), Jansen et al. (2003), Lin et al. (2004), Streiner (2002), Stubbendick and Ibrahim

(2003), Ten Have et al. (1998), and Wu and Bailey (1989).

Issues Relating to Imputed Values from SPSS MVA Package Using EM

von Hippel (2004) has pointed out that the imputed values from the SPSS

Missing Value Analysis package (MVA, 2004) using EM do not show sufficient variation because the regression equations used with the SPSS EM algorithm do not add random variance to the predicted variables. The SPSS EM algorithm compensates for this reduced variance of predicted values when calculating the final printed covariance matrix. However, since the special compensation adjustments are not built into SPSS

Base software or other analysis software, von Hippel concludes that “it is inadvisable to use the EM-imputed data outside the EM module” (p.163).

7 Using Multiple Imputation Methods For Continuous Data When Data are Not Normal or

Continuous

Many researchers may need to impute continuous data, and some research suggests that software intended for multivariate normal data will often work fine even if the continuous data have a substantially nonnormal distribution (Graham and Schafer,

1999). Allison (2002) notes : “… multiple imputation under the multivariate normal model is reasonably straightforward under a wide variety of data types and missing data patterns. As a routine method for handling missing data, it is probably the best that is currently available” (pp. 55-56).

Should software for imputing multivariate normal data ever be used to impute unordered (nominal) categorical data? This is a topic of active discussion and evolution of opinion. Sinharay et al. (2001, p. 321) cites Schafer (1997) as providing evidence that “the multivariate normal model gives quite acceptable results even when the variables are binary or categorical…and the imputed values [are] rounded off to the nearest category.” Similarly, Allison (2002) says that methods for multiply imputing categorical data and mixtures of categorical and continuous data are “typically much more difficult to use and often break down completely” (p. 39) and that “many users will do just as well by applying the normal methods [i.e. methods assuming a normal distribution] with some minor alterations” (p. 39). He then shows ways to round the results from multiple imputation under the normal model to impute dichotomous variables and variables with multiple categories coded as dummy (0/1) variables.

Schafer and Graham (2002) take a markedly different view, indicating “there are situations in which the normal model should be avoided – to impute variables that are

8 nominal (unordered categories), for example” (p. 168). Horton et al. (2003) show that rounding values imputed under the normal model to achieve discrete values can yield biased estimates and recommend against such rounding.

Before deciding to impute categorical data with algorithms intended for continuous data, researchers should examine the software available at these sites: http://www.stat.psu.edu/~jls/misoftwa.html and http://www.isr.umich.edu/src/smp/ive/ .

Methods For Preserving Interactions in Multiple Imputation

Special steps can be taken to impute in a way that takes interactions into account. However, the researcher must know prior to imputation which interactions will be tested later in models. When the effect of a variable on a dependent variable is thought to vary across the levels of a second variable (e.g. gender), Allison (2002) and

Schafer and Graham (2002) recommend splitting the data into groups corresponding to the levels of the second variable. The researcher then runs separate imputations on the groups (e.g. impute the missing data on the male and female cases separately and then combine the male and female cases back into a single dataset). A less preferred method is to create an interaction indicator variable by multiplying the variables with an interaction and imputing the missing values for this interaction variable along with the other variables (Allison, 2002). Allison (2002) likewise recommends creating variables that are squares or other powers of variables and imputing them with the other data rather than merely squaring values prior to analysis.

9 Which Variables Should Be Used in Multiple Imputation?

Researchers should include a variety of variables in the imputation process. The imputation process should include all the variables that will be used in later models.

When variables are used in models but not used in imputation, the model parameters for those variables will be biased (Allison, 2002; Sinharay et al., 2001). Furthermore, the imputation process should include variables that predict whether the values of other variables may be missing, as well as variables that are correlated with the variables having the most missing data. This will increase the chances that the data are Missing at Random (an assumption for many multiple imputation procedures) and help reduce standard errors, thereby increasing statistical power (Collins et al., 2001; Sinharay et al.,

2001).

How Many Imputations Should be Used in Multiple Imputation?

Rubin (1996) says “as few as five multiple imputations (or even three in some cases) is adequate under each model for nonresponse” (p. 480). Allison (2003) says that five imputed data sets is widely regarded as sufficient for small to moderate amounts of missing data, but says “achieving optimal confidence intervals and hypothesis tests may require substantially more imputations” (p. 553). Schafer and

Olsen (1998) show that with 30% missing information, using 3 imputations yields standard errors that are 91% efficient, 5 imputations gives standard errors that are 94% efficient, and 10 imputations yield standard errors that are 97% efficient. A statistic that is 100% efficient has a sampling variance that is at least as small as that of any other estimator (Allison, 2003).

10 REFERENCES

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strategies in modern missing data procedures. Psychol Methods 6: 330-351

Diggle P, Kenward MG (1994), Informative drop-out in longitudinal data analysis. Appl

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Fairclough DL (2004), Patient reported outcomes as endpoints in medical research.

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Fitzmaurice GM, Molenberghs G, Lipsitz SR (1995), Regression models for longitudinal

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14

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