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Analysis of multiple informant/ multiple source data in Stata Nicholas J. Horton Department of Mathematics Smith College, Northampton MA Garrett M. Fitzmaurice.

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Presentation on theme: "Analysis of multiple informant/ multiple source data in Stata Nicholas J. Horton Department of Mathematics Smith College, Northampton MA Garrett M. Fitzmaurice."— Presentation transcript:

1 Analysis of multiple informant/ multiple source data in Stata Nicholas J. Horton Department of Mathematics Smith College, Northampton MA Garrett M. Fitzmaurice Harvard University nhorton at email.smith.edu http://www.biostat.harvard.edu/multinform

2 Acknowledgements Joint research project with Nan Laird and colleagues, Harvard School of Public Health Jane Murphy and the Stirling County Study for use of their example dataset (see Horton et al AJE, 2001 for more details) Supported by NIH grant RO1-MH54693

3 Outline Motivation for multiple source data Examples of multiple sources/informants Models for correlated multiple source data Accounting for complex survey design Accounting for incomplete/missing data Example (Stirling County Study) Conclusions

4 Why multiple source data? to provide better measures of some underlying construct that is difficult to measure or likely to be missing also known as multiple informant reports, proxy reports, co-informants, etc. discordance is expected, otherwise there is no need to collect multiple reports Statistical framework developed in (Horton and Fitzmaurice SIM tutorial, 2004)

5 Definition of multiple source data data obtained from multiple informants or raters (e.g., self-reports, family members, health care providers, teachers) or via different/parallel instruments or methods (e.g., symptom rating scales, standardized diagnostic interviews, or clinical diagnoses) None of the reports is a “gold’’ standard We consider multiple source data that are commensurate (multiple measures of the same underlying variable on a similar scale)

6 Examples of multiple source data child psychopathology (ask parents, teachers and children about underlying psychological state) service utilization studies (collect information from subjects and databases) medical comorbidity (query providers and charts to assess medical problems)

7 Examples of multiple source data (cont.) adherence studies (collect self-report of adherence, electronic pill caps [MEMS] plus pharmacy records) nutritional epidemiology (utilize multiple dietary instruments such as food frequency questionnaires, 24-hour recalls, food diaries)

8 Incomplete/missing reports Multiple source reports are commonly incomplete since, by definition, they are collected from sources other than the primary subject of the study This missingness may be by design or happenstance (or both!)

9 Example: missing source reports Consider service utilization studies that collect information from subjects and databases Subjects may be lost to follow-up (or only contacted periodically) Databases may be incomplete (lack of consent, lack of appropriate coverage)

10 Analytic approach Multiple sources can provide information on outcomes or predictors (risk factors) Multiple source outcome: what is the prevalence of child psychopathology? (measured using parallel parent and teacher reports) Fitzmaurice et al (AJE, 1995), Horton et al (HSOR, 2002), Horton and Fitzmaurice (SIM tutorial, 2004)

11 Analytic approach (cont.) Multiple source predictor: what are the odds of developing depression in adulthood, conditional on parallel reports of anxiety (collected from a child and a parent)? Examples: Horton et al (AJE, 2001), Lash et al (AJE, 2003), Liddicoat et al (JGIM, 2004), Horton and Fitzmaurice (SIM tutorial, 2004) We will focus on an example using multiple source predictors

12 Notation Let Y denote a univariate outcome for a given subject Let denote the l’ th multiple source predictor Let Z denote a vector of other covariates for the subject To simplify exposition, we consider two sources with dichotomous reports (L=2)

13 Questions to consider Are the sources reporting on the same underlying construct (are they commensurate or interchangeable?) Is it possible to combine the reports in some fashion? How to handle missing reports?

14 Analytic approaches Reviewed in Horton, Laird and Zahner (IJMPR, 1999) Use only one source Fit separate models

15 Analytic approaches (cont.) Combine (pool) the reports in some fashion Include both reports in the model

16 Analytic approaches (cont.) We considered simultaneous estimation of the marginal models: Non-standard application of GEE Method independently suggested by Pepe et al (SIM, 1999)

17 Advantages of new approach can be used to test for source differences in association with the outcome can test if the effects of other risk factors on the outcome differ by source

18 Advantages of new approach different source effects where necessary a pooled model can be fit if no significant source effects (potentially more efficient) can be fit using general purpose statistical software (Stata and others)

19 Accounting for survey design Many health services or epidemiologic studies arise from complex survey samples Need to address stratification, multi-stage clustering and unequal sampling weights Failing to properly account for survey design may lead to bias and incorrect estimation of variability

20 Accounting for survey design (cont.) Estimation proceeds using the approximate (quasi) log-likelihood (weighted version of the usual score equations for a GLM, accounting for the multi-stage clustering, including multiple source reports) Can be fit using general purpose statistical software (elegant and powerful implementation in Stata)

21 Accounting for incomplete source reports Missing source reports are missing predictors Use weighted estimating equation methodology of Robins et al (JASA, 1994) and Xie and Paik (Biometrics, 1997), applied by Horton et al, (AJE, 2001) Adds an additional “missingness weight” Complications to variance estimation

22 Example: Stirling County Study Outcome: time to event (death) over 16 year follow-up period (1952-1968) (n=1079) multiple source predictors: partially observed dichotomous physician report or self report of psychiatric disorder (dpax) other predictors: age (3 categories), gender statistical model: piecewise exponential survival with 4 intervals each of 4 years duration (subjects contribute time at risk in each interval)

23 Stirling County survey design Strata 1 Stratum 1 Stratum K Stratum k PSU 1PSU J PSU j self- report phys.- report

24 Implementation in Stata Specify probability sampling unit (subject), probability sampling weights (weight) and stratification variable (district): svyset id [pweight=weight], strata(district) Describe the sampling design: svydes

25 Survey: Describing stage 1 sampling units pweight: weight VCE: linearized Strata 1: district SU 1: id FPC 1: #Obs per Unit ---------------------------- Stratum #Units #Obs min mean max -------- -------- -------- 1 93 654 2 7.0 8 2 37 284 4 7.7 8 3 51 346 2 6.8 8 4 202 1488 2 7.4 8 5 291 2104 2 7.2 8 6 128 946 2 7.4 8 7 50 374 4 7.5 8 8 98 706 2 7.2 8 9 129 968 2 7.5 8 -------- -------- -------- 9 1079 7870 2 7.3 8

26 Implementation in Stata (cont.) xi: svy: poisson event dpax int1 int2 int3 female ageind1 ageind2 diag i.diag*ageind1 i.diag*ageind2 i.dpax*female i.dpax*ageind1 i.dpax*ageind2 i.dpax*diag, exposure(atrisk)

27 Implementation in Stata (cont.) Can then test for significant informant effects (any term with dpax [self-report] in the model): test dpax=0 test _IdpaXfemal_1, accumulate test _IdpaXagein_1, accumulate test _IdpaXageina1, accumulate test _IdpaXdiag_1, accumulate

28 Results (separate parameters) Initially fit model with separate parameters No evidence for source interactions Implies that the association between risk factors and mortality did not differ by source Dropped these terms from the model, yielding parsimonious shared parameter model with smaller standard errors

29 Implementation (shared parameter) xi: svy: poisson event int1 int2 int3 female ageind1 ageind2 diag i.diag*ageind1 i.diag*ageind2, exposure(atrisk)

30 Results (shared parameter) Survey: Poisson regression Number of strata = 9 Number of obs = 7420 Number of PSUs = 1079 Population size = 64723.522 Design df = 1070 F( 9, 1062) = 21.94 Prob > F = 0.0000 ------------------------------------------------------------------------------ | Linearized event | Coef. Std. Err. t P>|t| [95% Conf. Interval] -------------+---------------------------------------------------------------- int1 | -.9594993.2058191 -4.66 0.000 -1.363354 -.5556444 int2 | -.5680445.1936756 -2.93 0.003 -.9480716 -.1880174 int3 | -.360743.2002561 -1.80 0.072 -.7536821.0321962 female | -.1298938.1493215 -0.87 0.385 -.42289.1631024 ageind1 | 2.484883.2820244 8.81 0.000 1.931499 3.038266 ageind2 | 3.530875.2894511 12.20 0.000 2.962919 4.098831 diag | 1.62166.3256041 4.98 0.000.982765 2.260555 _IdiaXage~_1 | -1.351475.379926 -3.56 0.000 -2.09696 -.6059908 _IdiaXage~a1 | -1.313849.4554167 -2.88 0.004 -2.20746 -.4202376 _cons | -5.577167.2941931 -18.96 0.000 -6.154428 -4.999906 atrisk | (exposure) ------------------------------------------------------------------------------

31 Results (shared parameters) Parameter (log MRR) Estimate (SE) female-0.13 (0.15) mid-age 2.48 (0.28) older-age 3.53 (0.33) diagnosis 1.62 (0.33) diagnosis*mid-age-1.35 (0.38) diagnosis*older-age-1.31 (0.46)

32 Interpretation of results (annual mortality rate) Age < 50 Age >= 70 Diagnosis=00.0010.056 Diagnosis=10.0070.093

33 Results (2 df test of interaction of age and diagnosis). test _IdiaXagein_1=0 Adjusted Wald test ( 1) [event]_IdiaXagein_1 = 0 F( 1, 1070) = 12.65 Prob > F = 0.0004. test _IdiaXageina1, accumulate Adjusted Wald test ( 1) [event]_IdiaXagein_1 = 0 ( 2) [event]_IdiaXageina1 = 0 F( 2, 1069) = 6.67 Prob > F = 0.0013

34 Results (calculation of MRR and 95% CI). lincom diag, eform ( 1) [event]diag = ------------------------------------------------------------------ event | exp(b) Std.Err. t P>|t| [95% Conf. Interval] ------+----------------------------------------------------------- (1) | 5.0615 1.6480 4.98 0.000 2.6718 9.5884 ------------------------------------------------------------------. lincom diag + _IdiaXagein_1, eform ( 1) [event]diag + [event]_IdiaXagein_1 = 0 ------------------------------------------------------------------ event | exp(b) Std.Err. t P>|t| [95% Conf. Interval] ------+----------------------------------------------------------- (1) | 1.3102.25297 1.40 0.162.89703 1.9137 ------------------------------------------------------------------

35 Conclusions new methods of analysis of multiple source data are available can be implemented using existing software methods allow the assessment of the relative association of each source each source yielded similar conclusions: association between psychiatric disorder and mortality is stronger for younger subjects unified model has less variability, pools information after testing for systematic differences

36 Conclusions (cont.) methods account for complex survey designs methods incorporate partially observed subjects to contribute, under MAR (Little and Rubin book) assumptions multiple source reports arise in many settings (not just for children anymore!)

37 Future work Maximum-likelihood estimation instead of GEE approach –May yield efficiency gains –Particularly useful for missing reports Non-commensurate reports –Different scales –Different underlying constructs –Consider latent variable models (e.g. work of Normand and colleagues) –See also gllamm and forthcoming Stata book by Rabe-Hesketh and Skrondal)

38 Analysis of multiple informant/ multiple source data in Stata Nicholas Horton Department of Mathematics Smith College, Northampton MA nhorton at email.smith.edu http://www.biostat.harvard.edu/multinform


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